Chemo-Immunotherapy Regimes for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Network Meta-Analysis and Cost-Effectiveness Analysis.
Frontiers in pharmacology
In 2021, two phase III clinical trials confirmed that toripalimab or camrelizumab combined with gemcitabine and cisplatin (TGP or CGP) provide more benefits in the first-line treatment of R/M NPC than GP. Fortunately, TGP and CGP were recently approved as first-line treatments for cases experiencing R/M NPC by the China National Medical Products Administration in 2021. However, due to the high cost and variety of treatment options, the promotion of chemo-immunotherapeutics in the treatment of R/M NPC remains controversial. Therefore, we performed a cost-effectiveness assessment of the two newly approved treatment strategies to assess which treatments provide the greatest clinical benefits at a reasonable cost. A cost-effectiveness analysis and network meta-analysis network meta-analysis was conducted based on the JUPITER-02 and CAPTAIN-first Phase 3 randomized clinical trials. A Markov model was expanded for the evaluation of the effectiveness and cost of TGP, CGP, and GP chemotherapy with a 10-years horizon and measured the health achievements in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and life-years (LYs). We constructed a treatment strategy and other parameters based on two clinical trials and performed one-way and probabilistic sensitivity experiments for the evaluation of the uncertainty in the model. For the model of patients with treatment-R/M NPC, TGP was associated with a total cost of $48,525 and 2.778 QALYs (4.991 LYs), leading to an ICER of $15,103 per QALY ($10,321 per LY) compared to CGP. On comparing the GP chemotherapy, we found TGP and CGP incurred substantial health costs, resulting in ICERs of $19,726 per QALY and $20,438 per QALY, respectively. The risk of adverse events (AEs) and the price of the drugs had significant impacts on the ICER. At the assumed willingness-to-pay (WTP) threshold of $35,673 per QALY, there were approximately 75.8 and 68.5% simulations in which cost-effectiveness was achieved for TGP and CGP, respectively. From the Chinese payer's perspective, TGP is more possible to be a cost-effective regimen compared with CGP and GP for first-line treatment of patients with R/M NPC at a WTP threshold of $35,673 per QALY.
Immune Checkpoint Inhibitors Plus an Anti-VEGF Antibody as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis and Cost-Effectiveness Analysis.
Frontiers in pharmacology
Sintilimab + a bevacizumab biosimilar (IBI305) (SB) and atezolizumab + bevacizumab (AB) have been approved for the treatment of unresectable hepatocellular carcinoma (HCC). At present, oncologists and their patients remain indecisive on their preferred treatment regime. Therefore, assessing their efficacy a network meta-analysis and determining their comparative cost-effectiveness is necessary. To evaluate the cost-effectiveness of SB and AB compared with sorafenib alone for the treatment of unresectable HCC. The data used in our analysis were obtained from patients in ORIENT-32 and IMbrave150 phase III randomized clinical trials. A Bayesian network meta-analysis and cost-effectiveness analysis that included 1,072 patients were performed in this study. A partitioned survival model was applied to the patients with unresectable HCC. The model was designed with a 15-year time horizon, 1-month cycle, and 5% discount rate for costs and outcomes. In China, an incremental cost-effectiveness ratio (ICER) value of less than $33,500 (three times the GDP per capita in 2020) per quality-adjusted life-year (QALY) is considered cost-effective. The influence of parameter uncertainty on the results was verified by one-way deterministic sensitivity analysis and probability sensitivity analysis. Furthermore, scenario analyses of the patient assistance program (PAP) were conducted to explore the cost-effectiveness of SB and AB. For the model of 1,072 patients, treatment with SB produced an additional 0.617 QALYs compared with sorafenib, resulting in an ICER of $39,766.86/QALY. Similarly, treatment with AB produced an additional 0.596 QALYs compared with sorafenib, resulting in an ICER of $103,037.66/QALY. The probability sensitivity analysis showed that when the willingness-to-pay (WTP) threshold was $33,500/QALY, the cost-effectiveness of SB and AB was 15.4 and 0.4%, respectively. However, in the scenario analyses, the probability of SB and AB regimens being cost-effective was 65.4 and 15.8%, respectively, at a WTP of $33,500/QALY. The findings from our study showed that sintilimab + a bevacizumab biosimilar is a cost-effective regimen compared with sorafenib as the first-line therapy for unresectable HCC in China at a $33,500 WTP threshold if sintilimab PAP is considered. However, the atezolizumab + bevacizumab regimen is not cost-effective whether atezolizumab PAP is considered or not.
Evaluation of Plazomicin, Tigecycline, and Meropenem Pharmacodynamic Exposure against Carbapenem-Resistant Enterobacteriaceae in Patients with Bloodstream Infection or Hospital-Acquired/Ventilator-Associated Pneumonia from the CARE Study (ACHN-490-007).
Kuti Joseph L,Kim Aryun,Cloutier Daniel J,Nicolau David P
Infectious diseases and therapy
INTRODUCTION:CARE was a Phase 3, randomized study evaluating the efficacy and safety of plazomicin-based combination therapy compared with colistin-based combination therapy for the treatment of patients with bloodstream infections or hospital-acquired/ventilator-associated pneumonia due to carbapenem-resistant Enterobacteriaceae (CRE). Adjunctive therapies included either tigecycline or meropenem. We sought to understand the contribution of tigecycline and meropenem to plazomicin-treated-patient outcomes by determining their observed pharmacodynamic exposures against baseline pathogens. METHODS:Blood samples collected for plazomicin therapeutic monitoring were assayed for tigecycline and meropenem concentrations. Population pharmacokinetic models were constructed for each antibiotic. Using the individual Bayesian posterior or a covariate-based model, concentration time profiles were simulated to estimate the pharmacodynamic exposures for each patient. Pharmacodynamic thresholds for plazomicin, tigecycline, and meropenem were a total area under the curve to minimum inhibitory concentration ratio (AUC/MIC) ≥ 85, free (f) AUC/MIC ≥ 0.9, and free time above the MIC (fT > MIC) of ≥ 40%, respectively. RESULTS:Fifteen plazomicin-treated patients were included (12 received tigecycline, 4 received meropenem, 1 received both). Microbiological response was observed in 13 (86.7%) and clinical efficacy was achieved in 11 (73.3%). Plazomicin achieved its pharmacodynamic target in all 15 patients. Meropenem fT > MIC was 0% in all 4 patients, and tigecycline fAUC/MIC was ≥ 0.9 in 9 (75%) patients. Overall, 6 (40%) of 15 patients had a tigecycline or meropenem exposure below the requisite thresholds. Microbiological response and clinical efficacy were observed in 100% (6/6) and 83.3% (5/6) of patients with low threshold attainment by tigecycline and meropenem dosing regimens, respectively. CONCLUSIONS:Plazomicin successfully achieved its requisite pharmacodynamic exposure, and these data suggest that optimization of tigecycline and meropenem therapy was not required for the combination to achieve microbiological response and clinical efficacy against serious CRE infections. TRIAL REGISTRATION:ClinicalTrials.gov number, NCT01970371. FUNDING:Achaogen, Inc.
Cost-Effectiveness of Linaclotide Compared to Osmotic Laxatives in the Treatment of Irritable Bowel Syndrome with Constipation in China.
Advances in therapy
INTRODUCTION:Linaclotide, a selective agonist of guanylate cyclase C, was highly recommended for the treatment of irritable bowel syndrome with constipation (IBS-C). However, the cost-effectiveness of linaclotide in Chinese is not known, and this study aimed to assess the cost-effectiveness of linaclotide for patients with IBS-C. METHODS:An economic evaluation was conducted with a Markov model from a societal perspective. The Markov model was structured to simulate the discontinuation and continuation of medication in IBS-C patients in clinical practice, as well as the revisit and non-visit of non-responding patients. The cycle of the model was 4 weeks, and the time horizon was 1 year. The efficacy data in the model was from the risk ratios obtained by the meta-analysis and the calculation of the response rate of the three medications. The utility, discontinuation rate of the medication, and revisit rate data were from published literature, while the cost data were obtained from experts' opinions and published literature. A series of sensitivity analyses was performed on parameters potentially having impact on the model outputs. RESULTS:The QALYs (quality-adjusted life years) gained for 1-year treatment with linaclotide, polyethylene glycol, and lactulose were 0.821, 0.795, and 0.781, respectively. The corresponding total costs were CNY 7,721 (USD 1,120), CNY 8,797 (USD 1,276) and CNY 9,481 (USD 1,375). In both comparisons, linaclotide was dominant. Compared with polyethylene glycol and lactulose, the likelihood of linaclotide being cost-effective was 100% for both, using 1 times per capita GDP per QALY as willingness-to-pay threshold. CONCLUSIONS:IBS-C seriously affects the quality of life of patients with IBS-C, and linaclotide can improve symptoms and quality of life at less cost.
Trends and patterns of antibiotic consumption in China's tertiary hospitals: Based on a 5 year surveillance with sales records, 2011-2015.
Wushouer Haishaerjiang,Tian Ye,Guan Xiao-Dong,Han Sheng,Shi Lu-Wen
The consumption of antibiotics is a major driver in the development of antimicrobial resistance. This study aims to identify the trends and patterns of the total antibiotic consumption in China's tertiary hospitals from 2011 to 2015 by retrospectively analyzing aggregated monthly surveillance data on antibiotic sales made to 468 hospitals from 28 provinces. Antibiotic consumption was expressed in DDD per 1,000 inhabitants per day (DID). We compared population weighted antibiotic consumption patterns in China with European countries using indicators from the European Surveillance of Antimicrobial Consumption (ESAC). Total antibiotic consumption, including all the specific antibiotic class except for aminoglycoside antibacterials, were significantly increased during the study period from an average of 7.97 DID in 2011 to 10.08 DID in 2015. In 2015, the eastern regions of China consumed the most antibiotics using population denominator while the western regions consumed the most using inpatient denominator. Cephalosporins accounted for 28.6% of total DID, followed by beta-lactam-beta-lactamase inhibitor combinations (20.0%), macrolides (17.4%), and fluoroquinolones (10.5%). Antibiotic in parenteral form accounted for nearly half of all antibiotics. Although over the past few years major efforts had been made to reduce the risks of excessive antibiotic use through antibiotic stewardship, total antibiotic consumption showed a significant upward trend during the study period. A consistent preference for cephalosporins, macrolides, beta-lactam-beta-lactamase inhibitor combinations, as well as parenteral preparations was observed.
Cost-Effectiveness of Alectinib for Patients with Untreated ALK-Positive Non-Small Cell Lung Cancer in China.
Guan Haijing,Sheng Yanan,Guo Wanjie,Han Sheng,Shi Luwen
Advances in therapy
INTRODUCTION:To assess the cost-effectiveness of alectinib versus crizotinib as first-line treatments for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients from the perspective of China's healthcare system. METHODS:A Markov model was developed to assess the clinical outcomes and costs of alectinib and crizotinib, which included five health states: progression-free (PF) without central nervous system (CNS) progression, PF with CNS progression, post-progression (PP) without CNS progression, PP with CNS progression, and death. Clinical data for transition probabilities were obtained from the ALEX trial at the updated data cutoff. Healthcare resource utilization and costs were derived from clinical expert opinions and published literature. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the uncertainty of the results. Scenario analyses were conducted including using clinical data from the ALESIA trial in Asian patients, using utilities from the ALEX trial, and choosing different parametric survival models. RESULTS:In base case analysis, alectinib yielded an additional 1.04 quality-adjusted life years (QALYs) with incremental costs of $54,827, resulting in an incremental cost-effectiveness ratio (ICER) of $52,869/QALY. In scenario analysis, the ICER was $56,787/QALY using clinical data from the ALESIA trial. In probabilistic sensitivity analysis, the probabilities of alectinib being cost-effective were 0.4% and 43.7% when the willingness-to-pay (WTP) thresholds were $28,109/QALY and $50,000/QALY, respectively. CONCLUSION:Alectinib could prolong the mean time of PF and delay the time to CNS progression. However, because of its high drug cost, alectinib was unlikely to be cost-effective for untreated ALK-positive NSCLC patients in China.
Cost-Effectiveness Analysis of Xiyanping Injection (Andrographolide Sulfonate) for Treatment of Adult Community Acquired Pneumonia: A Retrospective, Propensity Score-Matched Cohort Study.
Shi Honghao,Guo Wanjie,Zhu He,Li Meng,Ung Carolina Oi Lam,Hu Hao,Han Sheng
Evidence-based complementary and alternative medicine : eCAM
Xiyanping injection (andrographolide sulfonate) has shown clinical effects on community acquired pneumonia. However, there is little known about the effectiveness and costs of combining Xiyanping injection with conventional treatment on adult community acquired pneumonia in daily practice. The aim of this study was to evaluate the cost-effectiveness of combining Xiyanping injection with conventional treatment for treatment of adult community acquired pneumonia by comparing with conventional treatment from a societal perspective. Using retrospective cohort method, this study demonstrates that Xiyanping injection combined with conventional treatment is superior to conventional treatment for patients using cephalosporins and antibiotics under the effectiveness index of length of hospital stay and is more cost-effective.
Cost-Effectiveness of Donafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma in China.
Advances in therapy
INTRODUCTION:This study aimed to evaluate the cost-effectiveness of donafenib compared to sorafenib and lenvatinib as first-line treatments for patients with advanced hepatocellular carcinoma (HCC) in China. METHODS:A partitioned survival model was developed to estimate the clinical and economic outcomes of donafenib, sorafenib, and lenvatinib for advanced HCC. The key clinical data of these targeted therapies were assessed through a network meta-analysis. The cost and health utilities were mainly collected from the literature. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICER) were the primary outcomes. Model uncertainty was tested with one-way sensitivity analyses, scenario analyses, and probabilistic sensitivity analyses (PSA). RESULTS:For health outcomes, donafenib gained the highest QALYs among the three treatments, followed by lenvatinib and sorafenib (1.106, 0.999, and 0.915 QALYs, respectively). For cost, donafenib was the cheapest option, followed by sorafenib and lenvatinib ($42,116, $43,193, and $44,261). The PSA indicated that the probability of being cost-effective for donafenib was 86.98% and 93.56% when the willingness-to-pay thresholds were one and three times the gross domestic product per capita in China, respectively. The one-way sensitivity analyses and scenario analyses also found the results to be robust. CONCLUSION:Compared to sorafenib and lenvatinib, donafenib was likely to be a cost-effective treatment with the highest QALYs and the lowest cost for patients with advanced HCC in China.
Cost-effectiveness analysis of vaborem for the treatment of carbapenem-resistant Enterobacteriaceae-Klebsiella pneumoniae carbapenemase (CRE-KPC) infections in the UK.
The European journal of health economics : HEPAC : health economics in prevention and care
OBJECTIVE:The study objective of this analysis was to determine the cost-effectiveness of vaborem (meropenem-vaborbactam) compared to the best available therapy (BAT) in adult patients with carbapenem-resistant Enterobacteriaceae-Klebsiella pneumoniae carbapenemase (CRE-KPC) infections from the perspective of the UK National Health Service (NHS) and Personal Social Services (PSS). METHODS:A decision tree model was developed to conduct a cost-effectiveness analysis for Vaborem compared to BAT in CRE-KPC patients over a 5 year time horizon. The model structure for Vaborem simulated the clinical pathway of patients with a confirmed CRE-KPC infection. Model inputs for clinical effectiveness were sourced from the TANGO II trial, and published literature. Costs, resource use and utility values associated with CRE-KPC infections in the UK were sourced from the British National Formulary, NHS reference costs and published sources. RESULTS:Over a 5 year time horizon, Vaborem use increased total costs by £5165 and increased quality-adjusted life years (QALYs) by 0.366, resulting in an incremental cost-effectiveness ratio (ICER) of £14,113 per QALY gained. The ICER was most sensitive to the probability of discharge to long-term care (LTC), the annual cost of LTC and the utility of discharge to home. At thresholds of £20,000/QALY and £30,000/QALY, the probability of Vaborem being cost-effective compared to BAT was 79.85% and 94.93%, respectively. CONCLUSION:Due to a limited cost impact and increase in patient quality of life, vaborem can be considered as a cost-effective treatment option compared to BAT for adult patients with CRE-KPC infections in the UK.
Cost-effectiveness analysis of linezolid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus: complicated skin and skin structure infection using Bayesian methods for evidence synthesis.
Bounthavong Mark,Zargarzadeh Amir,Hsu Donald I,Vanness David J
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research
BACKGROUND:Methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and skin structure infection (cSSSI) is a prominent infection encountered in hospital and outpatient settings that is associated with high resource use for the health-care system. OBJECTIVE:A decision analytic (DA) model was developed to evaluate the cost-effectiveness analysis (CEA) of linezolid, daptomycin, and vancomycin in MRSA cSSSI. METHODS:Bayesian methods for evidence synthesis were used to generate efficacy and safety parameters for a DA model using published clinical trials. CEA was done from the US health-care perspective. Efficacy was defined as a successfully treated patient at the test of cure without any adverse reaction. Primary outcome was the incremental cost-effectiveness ratio between linezolid and vancomycin, daptomycin and vancomycin, and linezolid and daptomycin in MRSA cSSSI. Univariate and probabilistic sensitivity analyses were performed to test the robustness of the model. RESULTS:The total direct costs of linezolid, daptomycin, and vancomycin were $18,057, $20,698, and $23,671, respectively. The cost-effectiveness ratios for linezolid, daptomycin, and vancomycin were $37,604, $44,086, and $52,663 per successfully treated patient, respectively. Linezolid and daptomycin were dominant strategies compared to vancomycin. However, linezolid was dominant when compared to daptomycin. The model was sensitive to the duration of daptomycin and linezolid treatment. CONCLUSION:Linezolid and daptomycin are potentially cost-effective based on the assumptions of the DA model; however, linezolid appears to be more cost-effective compared to daptomycin and vancomycin for MRSA cSSSIs.
Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of methicillin-resistant Staphylococcus aureus infection: a healthcare system perspective.
von Dach E,Morel C M,Murthy A,Pagani L,Macedo-Vinas M,Olearo F,Harbarth S
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
OBJECTIVE:Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection. METHODS:We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity. RESULTS:Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin. CONCLUSIONS:Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection.
Clinical Efficacy and Cost-Effectiveness of β-Lactam/β-Lactamase Inhibitor Combinations and Carbapenems in Liver Cirrhosis Patients with Gram-Negative Bacteria Bloodstream Infection.
Infection and drug resistance
BACKGROUND:Gram-negative bacteria bloodstream infection (GNB-BSI) results in considerable mortality and hospitality costs in cirrhotic patients. β-lactam/β-lactamase inhibitor combinations (BLBLIs) and carbapenems (CARs) are widely recommended for treating GNB-BSI in cirrhotic patients, while the efficacy and cost-effectiveness of two strategies have never been evaluated. Therefore, we conducted a retrospective cohort study to evaluate the efficacy and the cost-effectiveness of BLBLIs and CARs. PATIENTS AND METHODS:Cirrhotic patients with GNB-BSI treated by BLBLIs or CARs were included. A propensity score-matching analysis was performed to compare the efficacy between BLBLIs and CARs. A decision tree was used to estimate the clinical outcomes and direct costs of treating BSI using two strategies from the patients' perspective. RESULTS:No statistically significant difference was found between the BLBLIs (n = 41) group and the CARs (n = 43) group regarding the time to defervescence (2.4 ± 0.2 vs 2.5 ± 0.3, = 0.94). Thirty-seven patients from each group were matched in propensity-score-matched cohort, and there was no significant difference between two groups in terms of the time to defervescence (2.4 ± 0.3 vs 2.4 ± 0.3, = 0.75) and success rate (86.5% vs 78.4%; OR = 0.57; = 0.36). Based on the drug and hospital costs in China, cefoperazone/sulbactam was cost-effective in the present analysis under the willingness-to-pay threshold (¥64,644). CONCLUSION:The efficacy of BLBLIs is similar to CARs. Cefoperazone/sulbactam could be a cost-effective therapy in cirrhotic patients with GNB-BSI. Carbapenems-sparing regimens should be encouraged in regions with a low prevalence of MDR bacteria.
Ceftazidime-avibactam in the treatment of infections from carbapenem-resistant Klebsiella pneumoniae: Ceftazidime-avibactam against CR-KP infections.
Gu Jie,Xu Jie,Zuo Ting-Ting,Chen Yan-Bin
Journal of global antimicrobial resistance
OBJECTIVES:Clinical experience with ceftazidime-avibactam (CAZ-AVI) for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections is not well evaluated. The aim of this study was to assess its efficacy in a single-centre cohort of patients infected with CR-KP. METHODS:We conducted a retrospective observational study of consecutive patients treated for >72 h with CAZ-AVI or other active antibiotics (OAAs) for CR-KP infections. The primary outcome was 30-d mortality. The secondary outcomes were 14-d clinical failure and 14-d microbiological failure. Multivariate regression and propensity score matching were used to evaluate the relationship between CAZ-AVI treatment and outcomes. RESULTS:Ninety infections caused by CR-KP were documented in our study. Forty-two patients were treated with CAZ-AVI and 48 with OAAs. The crude 30-d mortality (8/42 vs. 22/48, P=0.007), 14-d clinical failure (14/42 vs. 24/48, P=0.046) and 14-d microbiological failure (11/42 vs. 15/48, P=0.034) were significantly lower in patients with CAZ-AVI treatment. The Kaplan-Meier survival curves of 30-d mortality confirmed the findings (logrank=0.004). In the multivariable models, the odds ratio (OR) of 30-d mortality (OR 0.23 95% CI 0.10-0.51, P<0.000), 14-d clinical failure (OR 0.37, 95% CI 0.14-0.95, P=0.039) and 14-d microbiological failure (OR 0.17, 95% CI 0.08-0.93, P=0.038) remain consistently significant. In the subgroup analysis, CAZ-AVI was associated with decreased 30-d mortality in the positive blood culture (OR 0.23, 95% CI 0.08-0.63, P=0.004), septic shock (OR 0.23, 95% CI 0.07-0.78, P=0.019), SOFA score (>5, OR 0.13, 95% CI 0.04-0.36, P<0.000), mechanical ventilation (OR 0.13, 95% CI 0.04-0.36, p<0.000) and Charlson comorbidity index (>3, OR 0.15, 95% CI 0.04-0.55, P=0.004). After propensity score matching, 29 cases from each group were well matched. The 30-d mortality remained significantly lower in the CAZ-AVI group (6/29 vs. 13/29, P=0.05). CONCLUSION:CAZ-AVI may be a more valuable therapeutic option for severe CR-KP infections than for mild cases and further randomized controlled trials are needed to evaluate the efficacy.
The Monte Carlo Simulation of Three Antimicrobials for Empiric Treatment of Adult Bloodstream Infections With Carbapenem-Resistant Enterobacterales in China.
Zou Dongna,Yao Guangyue,Shen Chengwu,Ji Jinru,Ying Chaoqun,Wang Peipei,Liu Zhiying,Wang Jun,Jin Yan,Xiao Yonghong
Frontiers in microbiology
The aim of this study was to predict and evaluate three antimicrobials for treatment of adult bloodstream infections (BSI) with carbapenem-resistant Enterobacterales (CRE) in China, so as to optimize the clinical dosing regimen further. Antimicrobial susceptibility data of blood isolates were obtained from the Blood Bacterial Resistance Investigation Collaborative Systems in China. Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) of tigecycline, polymyxin B, and ceftazidime/avibactam against CRE. For the results of PTAs, tigecycline following administration of 50 mg every 12 h, 75 mg every 12 h, and 100 mg every 12 h achieved > 90% PTAs when minimum inhibitory concentration (MIC) was 0.25, 0.5, and 0.5 μg/mL, respectively; polymyxin B following administration of all tested regimens achieved > 90% PTAs when MIC was 1 μg/mL with CRE; ceftazidime/avibactam following administration of 1.25 g every 8 h, 2.5 g every 8 h achieved > 90% PTAs when MIC was 4 μg/mL, 8 μg/mL with CRE, respectively. As for CFR values of three antimicrobials, ceftazidime/avibactam achieved the lowest CFR values. The highest CFR value of ceftazidime/avibactam was 77.42%. For tigecycline and ceftazidime/avibactam, with simulated regimens daily dosing increase, the CFR values were both increased; the highest CFR of tigecycline values was 91.88%. For polymyxin B, the most aggressive dosage of 1.5 mg/kg every 12 h could provide the highest CFR values (82.69%) against CRE. This study suggested that measurement of MICs and individualized therapy should be considered together to achieve the optimal drug exposure. In particular, pharmacokinetic and pharmacodynamic modeling based on local antimicrobial resistance data can provide valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.
Antibiotic strategies and clinical outcomes for patients with carbapenem-resistant Gram-negative bacterial bloodstream infection.
Qu Junyan,Feng Chunlu,Li Huan,Lv Xiaoju
International journal of antimicrobial agents
Carbapenem-resistant Gram-negative bacterial bloodstream infection (CRGNB-BSI) has become a rapidly growing global threat with limited antibiotic options and significant mortality. The aim of this study was to explore the antibiotic strategies and clinical outcomes of patients with CRGNB-BSI in Western China. We retrospectively investigated the demographic, microbiological and clinical characteristics of 355 patients with CRGNB-BSI from 2012-2017. Treatment failure and 28-day in-hospital mortality rates were 49.3% (175/355) and 23.7% (84/355), respectively. The most frequently isolated micro-organism was Acinetobacter baumannii (58.6%; 208/355). Patients with treatment failure had higher procalcitonin and interleukin-6 levels (P < 0.05). High-dosage tigecycline therapy (200 mg loading dose followed by 100 mg every 12 h) was not superior to standard tigecycline dosing (P > 0.05). Multivariable analysis revealed that multiple organ dysfunction syndrome (MODS) (OR = 2.226, 95% CI 1.376-3.602; P = 0.001) and intensive care unit (ICU) admission (OR = 3.116, 95% CI 1.905-5.097; P = 0.000) were independent risk factors for treatment failure, whereas monotherapy (OR = 0.386, 95% CI 0.203-0.735; P = 0.004) had a protective effect. Survival analysis revealed that inappropriate therapy, MODS and ICU admission were associated with a higher 28-day in-hospital mortality rate (P < 0.001). Combination antimicrobial therapy was not superior to monotherapy (P = 0.387). This study demonstrates that appropriate therapy is significantly associated with lower treatment failure and 28-day in-hospital mortality rates. Tigecycline might not be a suitable option for CRGBN-BSI. Patients with MODS and admitted to the ICU had poor clinical outcomes.
Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae.
van Duin David,Lok Judith J,Earley Michelle,Cober Eric,Richter Sandra S,Perez Federico,Salata Robert A,Kalayjian Robert C,Watkins Richard R,Doi Yohei,Kaye Keith S,Fowler Vance G,Paterson David L,Bonomo Robert A,Evans Scott,
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Background:The efficacy of ceftazidime-avibactam-a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown. Methods:Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results:Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin. Conclusions:Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.
Treatment options and clinical outcomes for carbapenem-resistant Enterobacteriaceae bloodstream infection in a Chinese university hospital.
Li Chen,Li Yi,Zhao Zhichang,Liu Qing,Li Bin
Journal of infection and public health
BACKGROUND:Carbapenem resistant Enterobacteriaceae (CRE) has become a serious public health problem. Limited information is available about the treatment options that physicians used to fight CRE infections and related clinical outcomes in China. The aim of the present study was to explore the treatment options and clinical outcomes of patients with CRE bloodstream infection (BSI) in a Chinese teaching hospital. METHODS:A retrospective study was conducted during 2011 to 2015 in one Chinese teaching hospital. Demographic, microbiological and clinical characteristics of enrolled subjects were collected from medical records. Data were analyzed by Kaplan-Meier graphs, log-rank test, and Cox regression. RESULTS:A total of 98 inpatients with CRE BSI were enrolled in this study. For empirical therapy, 26 patients (26.5%) received at least one active drug within 48h after the onset of bacteremia. For definitive treatment, 59.2% (49/82) patients received at least one active drug and 40.2% (33/82) patients received therapy with no active drug. The overall 30-day mortality was 53.1% (52/98). Adverse outcome appeared to be more likely among patients with previous carbapenem exposure, neutropenia, severity of septic and time to initiation of BSIs. There was no significant difference in the mortality between the two groups of patients with combination therapy versus monotherapy (p=0.105). Severity of sepsis and neutropenia were identified as independent predictors of mortality. CONCLUSIONS:Our study demonstrated a high mortality associated with CRE BSI and a high percentage of inappropriate empirical treatment for CRE BSI patients in a Chinese teaching hospital. Particular attention should be given to the patients with CRE BSI.
Retrospective Observational Study from a Chinese Network of the Impact of Combination Therapy versus Monotherapy on Mortality from Carbapenem-Resistant Bacteremia.
Wang Xiaojuan,Wang Qi,Cao Bin,Sun Shijun,Zhang Yawei,Gu Bing,Li Binbin,Liao Kang,Zhao Feng,Jin Liang,Jin Chunmei,Yang Chunxia,Pei Fengyan,Zhang Zhijie,Wang Hui
Antimicrobial agents and chemotherapy
Data for a total of 164 bloodstream infection cases due to carbapenem-resistant (CRE) from 2013 to 2017 were retrospectively collected from 36 tertiary hospitals in 19 provinces in China to evaluate the outcomes and risk factors for mortality by univariable and multivariable analysis. The most frequent infecting species was (69.5%, 114/164). The overall in-hospital and 14-day mortality rates were 32.9% (54/164) and 31.1% (42/135), respectively. Multivariable analysis revealed that septic shock (adjusted odds ratio [aOR], 6.339; 95% confidence interval [CI], 1.586 to 25.332; = 0.009), the Pitt bacteremia score (aOR, 1.300; 95% CI, 1.009 to 1.676; = 0.042), and the Charlson comorbidity index (aOR, 1.392; 95% CI, 1.104 to 1.755; = 0.005) were independently associated with a hazard effect on mortality. Combination therapy, especially tigecycline-based combination therapy, resulted in relatively low rates of in-hospital mortality and failure in clearance of CRE infection. Survival analysis revealed that appropriate therapy was associated with a lower 14-day mortality rate than inappropriate therapy (including nonactive therapy; = 0.022), that combination therapy was superior to monotherapy ( = 0.036), that metallo-β-lactamase producers were associated with a lower 14-day mortality than strains without carbapenemases or KPC-2 producers ( = 0.009), and that strains with MICs of >8 mg/liter for meropenem were associated with a higher 14-day mortality rate than those with MICs of ≤8 mg/liter ( = 0.037). Collectively, the severity of illness, meropenem MICs of >8 mg/liter, and carbapenemase-producing types were associated with the clinical outcome. Early detection of the carbapenemase type and initiation of appropriate combination therapy within 96 h might be helpful for improving survival.
Tigecycline Treatment for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review and Meta-Analysis.
Ni Wentao,Han Yuliang,Liu Jie,Wei Chuanqi,Zhao Jin,Cui Junchang,Wang Rui,Liu Youning
Carbapenem-resistant Enterobacteriaceae (CRE) infections are prevalent worldwide; they have few effective treatments and this jeopardizes public health. Clinicians often use tigecycline to combat CRE, but its clinical efficacy remains controversial. Therefore, to compare the efficacy and safety of tigecycline in treating CRE infections compared with that of other antimicrobial agents, and to evaluate whether combination therapy and high-dose regimens are beneficial, we performed a systematic review and meta-analysis. PubMed and Embase were searched for controlled trials or cohort studies reporting the efficacy and/or safety of tigecycline-based regimens to treat CRE infections. Statistical analyses were performed using the Comprehensive Meta-Analysis V2.2. All meta-analyses were performed based on fixed- or random-effects model, and the I method was used to assess heterogeneity. Twenty-one controlled studies and 5 single-arm studies were included in this systematic review. With regard to the controlled studies, the tigecycline groups did not differ significantly from the control groups in terms of overall mortality (Odds ratio (OR) = 0.96 [95% confidence interval (CI) = 0.75-1.22; P = 0.73]), clinical response rate (OR = 0.58 [95% CI = 0.31-1.09; P = 0.09]), or microbiological response rate (OR = 0.46 [95% CI = 0.15-1.44; P = 0.18]). Subgroup analyses showed that 30-day mortality was significantly lower in patients who received tigecycline combination therapy than in those who received monotherapy (OR = 1.83 [95% CI = 1.07-3.12; P = 0.03]) and other antibiotic regimens (OR = 0.59 [95% CI = 0.39-0.88; P = 0.01]), respectively. In addition, high-dose tigecycline regimens differed significantly from standard dose schedules in terms of ICU mortality (OR = 12.48 [95% CI = 2.06-75.43; P = 0.006]). The results of the 5 single-arm studies corroborated the findings of the controlled studies. Our results indicated that the efficacy of tigecycline in treating CRE infections is similar to that of other antibiotics. Tigecycline combination therapy and high-dose regimens may be more effective than monotherapy and standard-dose regimens, respectively. Nonetheless, considering that the current available evidence is limited, well-designed randomized controlled trials are urgently needed to clarify the comparative efficacy of tigecycline in treating CRE infections.
Ceftazidime/Avibactam versus Polymyxin B in the Challenge of Carbapenem-Resistant Infection.
Infection and drug resistance
PURPOSE:Ceftazidime/avibactam (CAZ/AVI) monotherapy and polymyxin B-based combination therapy are currently two treatment options for patients with carbapenem-resistant (CRPA) infection; however, few studies have contrasted the relative efficacy of the two antibiotic regimens. The purpose of this study was to compare the effectiveness of CAZ/AVI and polymyxin B against CRPA infection and analyze the independent predictors of 30-day mortality or survival. PATIENTS AND METHODS:This single-center retrospective observational study included patients with CRPA infection treated with CAZ/AVI or polymyxin B between January 2018 and December 2020. The primary outcomes were the 14-day and 30-day mortality. The secondary outcomes were in-hospital mortality and bacterial clearance. Baseline characteristics and outcomes were compared between the two groups, and COX regression analysis was used to identify predictors of 30-day mortality. RESULTS:A total of 136 patients with CRPA infection were enrolled, including 51 patients in the CAZ/AVI group and 85 patients in the polymyxin B group. The 14-day mortality (5.9% vs 27.1%, p=0.002), 30-day mortality (13.7% vs 47.1%, p<0.001) and in-hospital mortality (29.4% vs 60.0%, p=0.001) in the CAZ/AVI group were significantly lower than the polymyxin B group. The bacterial clearance rate (45.1% vs 12.9%, p<0.001) in the CAZ/AVI group were higher than in the polymyxin B group. After adjustment by propensity score matching, the CAV/AVI group still had lower 30-day mortality (14.3% vs 42.9%, p=0.018) and higher bacterial clearance rate (42.9% vs 14.3%, p=0.018) than the polymyxin B group. The multivariate COX analysis showed that the age was identified as independent predictor of 30-day mortality while CAZ/AVI therapy and central venous catheterization emerged as independent predictors of 30-day survival. CONCLUSION:CAZ/AVI therapy was superior to polymyxin B therapy for patients with CRPA infection, and provided significant survival benefits, but further larger studies were needed to substantiate our findings.
Efficacy of Ceftazidime-Avibactam Versus Polymyxin B and Risk Factors Affecting Clinical Outcomes in Patients With Carbapenem-Resistant Infections a Retrospective Study.
Fang Jie,Li Hui,Zhang Min,Shi Guochao,Liu Mengying,Wang Yujie,Bian Xiaolan
Frontiers in pharmacology
The worldwide outbreak of carbapenem-resistant (CRKP) has become an urgent public health problem. High mortality and lack of effective treatments further pose new challenges to control this infection. However, studies about the evaluation of available antibiotics for CRKP infection are limited. The present study aimed to compare the efficacy of polymyxin B versus ceftazidime-avibactam (CAZ/AVI) in Chinese patients with CRKP infections and to identify risk factors affecting 7-day bacterial eradication and 28-day all-cause mortality. From January 8, 2018, to July 6, 2020, a total of 115 adult CRKP infected patients from two tertiary teaching hospitals in Shanghai, China were enrolled based on the inclusion and exclusion criteria. By reviewing electronic medical records of these patients, demographic and clinical data were extracted. The selected patients were divided into polymyxin B and CAZ/AVI groups according to primary antibiotic exposure to compare therapeutic effects. Binary logistic and cox's regression analysis were performed to identify risk factors for 7-day bacterial eradication and all-cause mortality. One hundred and five patients were treated with polymyxin B (67.8%) or CAZ/AVI (32.2%). Patients in the CAZ/AVI group had significantly lower rates of 28-day mortality (8.1 vs 29.5%, = 0.013), higher microbiological eradication and 28-day clinical success. Multivariate analysis showed that Charlson comorbidity index (≥3) and prior antibiotic use within 90 days were independent risk factors for poor microbiological eradication. Cox's regression analysis indicated that the length of hospitalization after CRKP infection and baseline creatinine clearance negatively affected 28-day mortality. CAZ/AVI was more effective than polymyxin B and appeared to be a promising drug for CRKP infection, especially for critically ill patients.
Cost-effectiveness of de-escalation from micafungin versus escalation from fluconazole for invasive candidiasis in China.
Chen Dechang,Wan Xianyao,Kruger Eliza,Chen Can,Yue Xiaomeng,Wang Liang,Wu Jiuhong
Journal of medical economics
AIMS:Guidelines on treating invasive candidiasis recommend initial treatment with a broad-spectrum echinocandin (e.g. micafungin), then switching to fluconazole if isolates prove sensitive (de-escalation strategy). This study aimed to evaluate the cost-effectiveness of de-escalation from micafungin vs escalation from fluconazole from a Chinese public payers perspective. MATERIALS AND METHODS:Cost-effectiveness was estimated using a decision analytic model, in which patients begin treatment with fluconazole 400 mg/day (escalation) or micafungin 100 mg/day (de-escalation). From Day 3, when susceptibility results are available, patients are treated with either fluconazole (if isolates are fluconazole-sensitive/dose-dependent) or micafungin (if isolates are resistant). The total duration of (appropriate) treatment is 14 days. Model inputs are early (Day 3) and end-of-treatment mortality rates, treatment success rates, and health resource utilization. Model outputs are costs of health resource utilization over 42 days, incremental cost per life-year, and incremental cost per quality-adjusted life-year (QALY) over a lifetime horizon. RESULTS:In the base-case analysis, the de-escalation strategy was associated with longer survival and higher treatment success rates compared with escalation, at a lower overall cost (-¥1,154; -175 United States Dollars). Life-years and QALYs were also better with de-escalation. Thus, this strategy dominated the escalation strategy for all outcomes. In a probabilistic sensitivity analysis, 99% of 10,000 simulations were below the very cost-effective threshold (1 × gross domestic product). LIMITATIONS:The main limitation of the study was the lack of real-world input data for clinical outcomes on treatment with micafungin in China; data from other countries were included in the model. CONCLUSION:A de-escalation strategy is cost-saving from the Chinese public health payer perspective compared with escalation. It improves outcomes and reduces costs to the health system by reducing hospitalization, due to an increase in the proportion of patients receiving appropriate treatment.
Ceftolozane/Tazobactam and Ceftazidime/Avibactam for Multidrug-Resistant Gram-Negative Infections in Immunocompetent Patients: A Single-Center Retrospective Study.
Cultrera Rosario,Libanore Marco,Barozzi Agostino,d'Anchera Erica,Romanini Letizia,Fabbian Fabio,De Motoli Francesco,Quarta Brunella,Stefanati Armando,Bolognesi Niccolò,Gabutti Giovanni
Antibiotics (Basel, Switzerland)
Complicated infections from multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a serious problem presenting many challenges. Resistance to many classes of antibiotics reduces the probability of an adequate empirical treatment, with unfavorable consequences, increasing morbidity and mortality. Readily available patient medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. There are few literature data that report real-life experiences in the use of ceftolozane/tazobactam and ceftazidime/avibactam, with particular reference to microbiological cure. Some studies reported experiences for the treatment of MDR-GNB infections in patients with hematological malignancies or specifically in infections. We report our clinical single-center experience regarding the real-life use of ceftolozane/tazobactam and ceftazidime/avibactam to treat serious and complicated infections due to MDR-GNB and carbapenem-resistant (CRE), with particular regard given to intra-abdominal and urinary tract infections and sepsis.
Clinical Benefits and Cost-Effectiveness of Moxifloxacin as Initial Treatment for Community-Acquired Pneumonia: A Meta-Analysis and Economic Evaluation.
Du Xiwen,Han Yi,Jian Yifei,Chen Liping,Xuan Jianwei
PURPOSE:Moxifloxacin and levofloxacin are currently recommended as empirical initial treatment options for community-acquired pneumonia (CAP) in China according to guidelines. Most studies that evaluated the efficacy and safety of moxifloxacin and levofloxacin in treating CAP as initial empirical treatment were single-centered trials assessing different clinical end points. In addition, there is limited research investigating moxifloxacin's clinical benefits in the context of health care resource utilization and reimbursement from the payer's perspective in China. Hence, this study was aimed at comparing the clinical efficacy of moxifloxacin and levofloxacin by conducting a meta-analysis and assessing their economic value from the China payer's perspective through a cost-utility analysis model. METHODS:For the meta-analysis, 6 bibliographic databases were searched for relevant publications from January 2000 to August 2020, and studies were assessed for eligibility under predetermined criteria. Meta-analysis was performed by using a random effects model when analyses included >2 trials. For the economic evaluation, a decision-tree model was constructed to investigate the cost-utility of moxifloxacin versus levofloxacin as initial regimens in the treatment of CAP inpatients. Parameter values were derived from meta-analysis, published literature, and clinician survey. The outcome was reported in the form of an incremental cost-effectiveness ratio. One-way sensitivity analysis and probabilistic sensitivity analysis were undertaken to assess the robustness of the model. FINDINGS:Twenty-seven randomized controlled trials were included in the meta-analysis. Results indicated that the clinical response rate at the test-of-cure visit with initial treatment of moxifloxacin was significantly higher than that of levofloxacin (3441 patients; random effects model; I = 49%; odds ratio, 3.35; 95% CI, 2.35-4.77; P < 0.001). In terms of the safety profile, total adverse events were not significantly different between the 2 groups (2770 patients; random effects model; I = 40%; odds ratio, 0.77; 95% CI, 0.56-1.06; P = 0.11). Output of the cost-utility model showed that under the willingness-to-pay threshold of one-time China gross domestic product per capita, moxifloxacin is dominant over levofloxacin, being less costly and more efficacious (0.002 quality-adjusted life year gained, CNY 844 [US$131] saved in total cost, negative incremental cost-effectiveness ratio). Sensitivity analyses indicated the robustness of the model as moxifloxacin remained dominant when model parameter values fluctuated. IMPLICATIONS:Moxifloxacin is more efficacious than levofloxacin as the initial empirical treatment for CAP. In addition, treatment of CAP with moxifloxacin instead of levofloxacin is expected to be cost-saving from the perspective of payers in China. However, for the cost-utility analysis, in the absence of a national representative database on costs for hospitalization in China, inputs in the cost-utility model could be underestimated or overestimated due to estimating errors applied to both treatment arms.
Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs.
Shen Fengcai,Han Qianpeng,Xie Di,Fang Ming,Zeng Hongke,Deng Yiyu
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
OBJECTIVES:To assess the efficacy and safety of tigecycline in comparison with other antimicrobial treatments for infectious diseases. DESIGN:Databases of PubMed, Embase and the Cochrane Library were searched through Feb. 2015. The reference lists of the initially identified articles and systemic review articles were manually searched. Randomized controlled trials assessing tigecycline and other antibiotics for infectious diseases in adult patients were included. RESULTS:Fifteen RCTs including 7689 cases were identified. We found that tigecycline was not as effective as the comparator agents for clinical treatment success (for the clinically evaluable population, odds ratio [OR] = 0.83, 95% confidence interval [CI] = (0.73, 0.96), P=0.01; for the clinically modified intent-to-treat (mITT) population, OR = 0.81, 95% CI = (0.72, 0.92), P=0.001). There was no significant difference in microbiological treatment success with lower eradication rate in tigecycline versus comparators (for the microbiologically evaluable population, OR = 0.94, 95% CI = (0.77, 1.16), P=0.56; for the microbiological mITT populations, OR = 0.91, 95% CI = (0.74, 1.11), P=0.35). Adverse events and all-cause mortality were more common in the tigecycline group. CONCLUSIONS:Tigecycline is not as effective as other antibiotics with relatively more frequency of adverse events and higher mortality rate.
Effectiveness of tigecycline in the treatment of infections caused by carbapenem-resistant gram-negative bacteria in pediatric liver transplant recipients: A retrospective study.
Chen Fang,Shen Chuan,Pang Xiaoyun,Zhang Zaili,Deng Yuxiao,Han Longzhi,Chen Xiaosong,Zhang Jianjun,Xia Qiang,Qian Yongbing
Transplant infectious disease : an official journal of the Transplantation Society
INTRODUCTION:Tigecycline (TGC) is effective for the infections caused by carbapenem-resistant gram-negative bacteria (CRGNB) in adults, but it is not investigated systematically in children because of concern about adverse effects. This study aimed to analyze the effectiveness of TGC in treating CRGNB infections in children after receiving liver transplant. METHODS:The subjects in this retrospective study were pediatric liver transplant recipients treated with TGC for at least 3 days to fight microbiologically verified CRGNB infection after initial antibiotic failure during the period from January 2014 to May 2018. Clinical and microbiological outcomes were reviewed to evaluate the efficacy and safety of TGC. RESULTS:Of the 1177 pediatric liver transplant recipients, 13 patients were eligible for inclusion in this analysis. All the patients received TGC at dose of 2 mg/kg every 12 hours for a duration of 10.1 ± 5.1 days on average to treat CRGNB infections, including complicated intra-abdominal infection, ventilator-associated pneumonia, and bloodstream infection. The isolates included Klebsiella pneumoniae (69.2%, 9/13) and Acinetobacter baumannii (30.8%, 4/13). Clinical efficacy was achieved in 84.6% (11/13) and pathogen eradicated in 69.2% (9/13) of the patients. The overall mortality rate was 15.4% (2/13). No TGC-related serious adverse event was reported. CONCLUSION:Tigecycline can be considered in combination antimicrobial regimen for treating CRGNB-related infections in pediatric liver transplant recipients.
Antibiotic management of complicated intra-abdominal infections in adults: The Asian perspective.
Kurup Asok,Liau Kui-Hin,Ren Jianan,Lu Min-Chi,Navarro Narciso S,Farooka Muhammad Waris,Usman Nurhayat,Destura Raul V,Sirichindakul Boonchoo,Tantawichien Terapong,Lee Christopher K C,Solomkin Joseph S
Annals of medicine and surgery (2012)
Regional epidemiological data and resistance profiles are essential for selecting appropriate antibiotic therapy for intra-abdominal infections (IAIs). However, such information may not be readily available in many areas of Asia and current international guidelines on antibiotic therapy for IAIs are for Western countries, with the most recent guidance for the Asian region dating from 2007. Therefore, the Asian Consensus Taskforce on Complicated Intra-Abdominal Infections (ACT-cIAI) was convened to develop updated recommendations for antibiotic management of complicated IAIs (cIAIs) in Asia. This review article is based on a thorough literature review of Asian and international publications related to clinical management, epidemiology, microbiology, and bacterial resistance patterns in cIAIs, combined with the expert consensus of the Taskforce members. The microbiological profiles of IAIs in the Asian region are outlined and compared with Western data, and the latest available data on antimicrobial resistance in key pathogens causing IAIs in Asia is presented. From this information, antimicrobial therapies suitable for treating cIAIs in patients in Asian settings are proposed in the hope that guidance relevant to Asian practices will prove beneficial to local physicians managing IAIs.
Carbapenems vs β-Lactam Monotherapy or Combination Therapy for the Treatment of Complicated Intra-abdominal Infections: Systematic Review and Meta-analysis of Randomized Controlled Trials.
Open forum infectious diseases
BACKGROUND:Complicated intra-abdominal infections (cIAIs) result in significant morbidity, mortality, and cost. Carbapenem-resistant sepsis has increased dramatically in the last decade, resulting in infections that are difficult to treat and associated with high mortality rates. To prevent further antibacterial resistance, it is necessary to use carbapenem selectively. The objective of this study was to compare the effectiveness and safety of carbapenems vs alternative β-lactam monotherapy or combination therapy for the treatment of cIAIs. METHODS:The PubMed, Embase, Medline (via Ovid SP), and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing carbapenems vs alternative β-lactam monotherapy or combination therapy for the treatment of cIAIs. RESULTS:Twenty-two studies involving 7720 participants were included in the analysis. There were no differences in clinical treatment success (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.71-1.05; = 35%), microbiological treatment success (OR, 0.88; 95% CI, 0.71-1.09; = 25%), adverse events (OR, 0.98; 95% CI, 0.87-1.09; = 17%), or mortality (OR, 0.96; 95% CI, 0.68-1.35; = 7%). Patients. treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative β-lactam monotherapy or combination therapy. CONCLUSIONS:No differences in clinical outcomes were observed between carbapenems and noncarbapenem β-lactams in cIAIs. Patients treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative β-lactam monotherapy or combination therapy.
[Interpretation of domestic and foreign guidelines on diagnosis and treatment of abdominal infection].
Wu X W,Ren J A
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
In recent years, both international and domestic societies have published several guidelines on diagnosis and management of intra-abdominal infection. Due to the different evidence and the different methods adopted in the actual formulation of the guidelines, the recommendations of each version of the guidelines are different. Three international guidelines with great impacts were reviewed, including published in 2010, published in 2017, and by . The above guidelines were used to compare with the which was published in early 2020. Recommendations on the disease severity classification, source control, and antimicrobial therapy are further explained in order to provide guidelines for clinicians.
The Attributable Direct Medical Cost of Healthcare Associated Infection Caused by Multidrug Resistance Organisms in 68 Hospitals of China.
Jia Huixue,Li Weiguang,Hou Tieying,Ma Hongqiu,Yang Yun,Wu Anhua,Liu Yunxi,Wen Jianguo,Yang Huai,Luo Xiaoli,Xing Yawei,Zhang Weihong,Wu Yinghong,Ding Lili,Liu Weiping,Lin Ling,Li Ying,Chen Meilian,Li Liuyi
BioMed research international
Healthcare associated infection (HAI) is known to increase the economic burden of patients while the medical cost due to MDRO HAI is even higher. Three hundred eighty-one multidrug resistance organisms (MDROs) healthcare associated infection (HAI) case-patients and three hundred eighty-one matched control-patients were identified between January and December in 2015. The average total hospitalization medical cost of the case group was $6127.65 and that of the control group was $2274.02. The difference between the case group and the control group was statistically significant (t = 21.07; P < 0.01). The attributable cost of MDRO HAI was $3853.63. The direct medical costs due to different MDRO infections were different. The increased medical costs of CR-AB, CR-KP, and CR-PA were significantly higher than that of MRSA, MRSE, ESBL E. coli, and ESBL Kp (P < 0. 05). Among the subitem expenses, the drug cost increased the most (the average cost was $1457.72), followed by the treatment fee and test fee; the differences were statistically significant (P < 0.01).
Clinical and economic outcomes associated with community-acquired intra-abdominal infections caused by extended spectrum beta-lactamase (ESBL) producing bacteria in China.
Hu Bijie,Ye Huifeng,Xu Yingchun,Ni Yuxing,Hu Yunjian,Yu Yunsong,Huang Zhenfei,Ma Larry
Current medical research and opinion
BACKGROUND:To compare clinical and economic outcomes in patients with community-acquired intra-abdominal infection (IAI) due to extended spectrum beta-lactamase (ESBL) producing (ESBL-positive) bacteria versus non-ESBL-producing (ESBL-negative) bacteria in China. METHODS:This was a retrospective chart review study of patients hospitalized with community-acquired IAI due to ESBL-positive or ESBL-negative infections caused by Escherichia coli or Klebsiella spp. Data were collected from six hospitals in China that participated in the Study for Monitoring Antibiotic Resistance Trends (SMART) during 2006-2007. Outcomes included clinical response at discharge and following first-line antibiotic, number of antibiotic agents and classes, duration of hospitalization, and overall hospitalization and intravenous antibiotic costs. RESULTS:Of the 85 patients included in the study, 32 (37.6%) had ESBL-positive and 53 (62.4%) had ESBL-negative infections; E. coli was responsible for 77.6% of infections. Infection resolved at discharge in 30 (93.8%) ESBL-positive and 48 (90.6%) ESBL-negative patients (P = NS). Fewer ESBL-positive patients achieved complete response following first-line antibiotics (56.3% versus 83.0%; P = 0.01). ESBL-positive patients required longer antibiotic treatment, more antibiotics, longer hospitalization (24.3 versus 14.6 days; 1.67-fold ratio; P = 0.001), and incurred higher hospitalization costs ( yen24,604 vs. yen13,788; $3604 vs. $2020; 1.78-fold ratio; P < 0.001). CONCLUSIONS:Patients with ESBL-positive infection had similar resolution rates at discharge compared to those with ESBL-negative infection, despite poorer first-line antibiotic response. However, ESBL-positive infection led to significantly greater hospitalization cost and intravenous antibiotic cost, and longer hospital stay.
A systematic review and meta-analysis of disease burden of healthcare-associated infections in China: an economic burden perspective from general hospitals.
The Journal of hospital infection
Healthcare-associated infections (HAIs) are a global public health issue. However, the economic burden attributable to HAIs at a national level is unknown in China. The aim of this systematic review was to estimate the direct economic burden caused by HAIs in China. Medline, EMBASE and Chinese Journals Online databases were searched, including studies published from 2009 to 2019. The pooled estimates with 95% confidence interval were calculated with quantile estimation. The random effects model of the DerSimonian-Laird method was used. The statistical significance was set as P<0.05. A total of 2756 publications were identified; six studies were included in a meta-analysis to calculate the pooled estimates of direct economic burden, while five were included in the pooled estimates of the additional economic burden. The pooled median estimates of the total medical expenditure, the medicine expenditure and hospitalization days per inpatient of patients with HAIs were ¥34,415.62, ¥20,065.21 and 34.01 days, respectively (P<0.0001). The pooled median estimates of the differences of the total medical expenditure, the medicine expenditure and hospitalization days per inpatient between patients with HAIs and patients without HAIs were ¥24,881.37, ¥9,438.46 and 13.89 days, respectively (P<0.01). In conclusion, the cost of care for patients with HAIs was significantly higher than that for those without HAIs. This excess economic burden is likely to impact on patients and their families as well as health service providers and the healthcare system as a whole. Effective surveillance systems and cost-effective interventions are needed to control HAIs.
A New Scoring System to Predict Blood Stream Infections in Patients with Complicated Intra-Abdominal Infections: Experience from a Tertiary Referral Hospital in China.
Huang Jinjian,Ren Jianan,Brakert Luise,Jiao Jiao,Liu Qinjie,Wang Gefei,Wu Xiuwen,Damink Steven W M Olde
BACKGROUND:This purpose of this study was to investigate the effects of blood stream infections (BSIs) on the prognosis of patients with complicated intra-abdominal infections (IAIs) and to make predictions based on patients' characteristics on admission. PATIENTS AND METHODS:One hundred eighty-seven patients with complicated IAI in 2014 and 2015 were included in our retrospective analysis, except for those diagnosed with central line-associated blood stream infections (CLABSIs). Patients with BSIs were compared with patients without BSIs. Multivariable logistic regression was applied to identify factors associated with BSIs and also the subtypes of BSIs. The predictive score systems were established further. RESULTS:Seventy-four patients (39.6%) with complicated IAIs developed BSIs after admission. Four factors evaluated on admission were associated independently with BSIs including alanine aminotransferase (ALT) ≥66 U/L (two scores), insensitivity to initial empirical antibiotic agents (IIEA; three scores), Sepsis-Related Organ Failure Assessment (SOFA) score of two or more (three scores), and generalized peritonitis (four scores). A total score of five or more was regarded as the critical value in the combined test to predict BSIs, with a sensitivity of 0.78 and a specificity of 0.73. Blood stream infections were further divided as secondary BSIs and non-secondary BSIs. The risk factors of secondary BSIs included IIEA (three scores), SOFA score of two or more (five scores), and generalized peritonitis (eight scores), where a total score of nine or more was regarded as the critical value in the combined test, with a sensitivity of 0.68 and a specificity of 0.87, whereas the risk factors of non-secondary BSIs included IIEA (three scores), SOFA score of two or more (three scores) and procalcitonin (PCT) ≥0.43 mcg/L (three scores), where a total score of six or more was regarded as the critical value in the combined test, with a sensitivity of 0.75 and a specificity of 0.70. Moreover, BSIs were linked with the worse clinical outcomes in organ functions, hospitalization costs, and mortality. CONCLUSIONS:Our new scoring methods may have potential advantages on the early prediction and recognition of BSIs in patients with complicated IAIs.
Novel Multiparametric Nomogram for Overall Survival Prediction in Complicated Intra-Abdominal Infection: A Multicenter Study in China.
Huang Sisi,Chen Limin,Liu Jiao,Zhang Sheng,Zhang Lidi,Wen Zhenliang,Chen Yizhu,Chen Dechang
Frontiers in medicine
Complicated intra-abdominal infections (cIAIs) in the abdominal cavity or within an abdominal organ are numerous and frequent dangerous entities in the treatment of critically ill patients. Early clinical evaluation is necessary. This retrospective multicenter study included patients from 10 intensive care units (ICUs). Risk factors for the overall survival (OS) of patients with cIAI were selected using least absolute shrinkage and selection operator regression, and a nomogram was constructed subsequently. Calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the calibration and discriminative ability. In total, 544 patients diagnosed with cIAI were enrolled and divided into the study ( = 276) and validation ( = 268) sets. Sex, acute gastrointestinal injury, acute kidney injury, rare bacterium infection, Charlson score, and APACHE II score were identified as independent risk factors and were constructed for the nomogram. The nomogram showed marked calibration capability with a concordance index (C-index) of 0.909 and 0.831 in the study and validation set, respectively. Compared with the common clinical prognostic scoring system, the nomogram achieved the highest discrimination ability with an area under the curve (AUC) value of 0.91 and 0.83 in the study set and validation set, respectively. Our newly constructed nomogram provides a useful tool for risk stratification and prognosis evaluation of cIAI.
Multicentre study of ceftazidime/avibactam for Gram-negative bacteria infections in critically ill patients.
Balandín Bárbara,Ballesteros Daniel,Pintado Vicente,Soriano-Cuesta Cruz,Cid-Tovar Irene,Sancho-González Milagros,Pérez-Pedrero María José,Chicot Marta,Asensio-Martín María José,Silva José Alberto,de Luna Rafael Ruiz,Gesso Cristina Martín-Dal,Rodríguez-Serrano Diego Aníbal,Martínez-Sagasti Fernando,Royuela Ana
International journal of antimicrobial agents
This study aimed to assess the efficacy of ceftazidime/avibactam (C/A) in the treatment of infections due to Gram-negative bacteria (GNB) in critically ill patients. A multicentre, retrospective, observational study was conducted in critically ill patients receiving C/A for GNB infections. We evaluated demographic data, localisation and severity of infection, clinical and microbiological outcomes, and mortality. A total of 68 patients received C/A for serious GNB infections. The main infections were respiratory (33.8%), intra-abdominal (22.1%) and urinary tract infections (10.3%); bacteraemia was found in 22 cases (32.4%). Most infections were complicated by septic shock (58.8%) or sepsis (36.8%) and most of them required life-supporting therapies. Enterobacterales (79.4%) and Pseudomonas aeruginosa (19.1%) were the most frequently isolated bacteria; 84.2% of isolates were carbapenem-resistant. Thirty-four patients (50.0%) received C/A in combination with other antimicrobials. Fifty patients (73.5%) presented a favourable clinical response. Microbiological eradication was documented in 25 cases (36.8%). No significant differences were found in clinical response between patients treated with monotherapy or combined therapy (79.4% vs. 67.6%; P = 0.27). Overall intensive care unit (ICU) mortality was 41.2%. Univariate analysis showed that 30-day all-cause mortality was significantly (P < 0.05) associated with bacteraemia, previous corticosteroid use and the need of life-supporting therapies. C/A appears to be an effective therapy for severe infections due to GNB, including carbapenem-resistant isolates, in critically ill patients. C/A combination therapy was not associated with a higher clinical response. Mortality correlated significantly with the presence of bacteraemia, previous corticosteroid use and the need for life-supporting therapies.
Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study.
The Journal of antimicrobial chemotherapy
OBJECTIVES:To investigate pharmacokinetics (PK) and safety (primary objectives) and efficacy (secondary objective) of the investigational monobactam/β-lactamase inhibitor combination aztreonam/avibactam in patients with complicated intra-abdominal infection (cIAI). METHODS:This Phase 2a open-label, multicentre study (NCT02655419; EudraCT 2015-002726-39) enrolled adults with cIAI into sequential cohorts for 5-14 days treatment. Cohort 1 patients received an aztreonam/avibactam loading dose of 500/137 mg (30 min infusion), followed by maintenance doses of 1500/410 mg (3 h infusions) q6h; Cohort 2 received 500/167 mg (30 min infusion), followed by 1500/500 mg (3 h infusions) q6h. Cohort 3 was an extension of exposure at the higher dose regimen. Doses were adjusted for creatinine clearance of 31-50 mL/min (Cohorts 2 + 3). All patients received IV metronidazole 500 mg q8h. PK, safety and efficacy were assessed. RESULTS:Thirty-four patients (Cohort 1, n = 16; Cohorts 2 + 3, n = 18) comprised the modified ITT (MITT) population. Mean exposures of aztreonam and avibactam in Cohorts 2 + 3 were consistent with those predicted to achieve joint PK/pharmacodynamic target attainment in >90% patients. Adverse events (AEs) were similar between cohorts. The most common AEs were hepatic enzyme increases [n = 9 (26.5%)] and diarrhoea [n = 5 (14.7%)]. Clinical cure rates at the test-of-cure visit overall were 20/34 (58.8%) (MITT) and 14/23 (60.9%) (microbiological-MITT population). CONCLUSIONS:Observed AEs were consistent with the known safety profile of aztreonam monotherapy, with no new safety concerns identified. These data support selection of the aztreonam/avibactam 500/167 mg (30 min infusion) loading dose and 1500/500 mg (3 h infusions) maintenance dose q6h regimen, in patients with creatinine clearance >50 mL/min, for the Phase 3 development programme.
Optimal Treatment for Complicated Intra-abdominal Infections in the Era of Antibiotic Resistance: A Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Therapy With Metronidazole.
Mikamo Hiroshige,Yuasa Akira,Wada Keiko,Crawford Bruce,Sugimoto Naomi
Open forum infectious diseases
Carbapenem-resistant has increased dramatically in the last decade, resulting in infections that are difficult to treat and associated with high mortality rates. To prevent further antibacterial resistance, it is necessary to use carbapenem selectively. A combination of metronidazole with an antimicrobial agent active against aerobes is an alternative effective treatment for patients with complicated intra-abdominal infections (cIAIs). This study aimed to compare efficacy and safety of metronidazole combination therapies and carbapenem and to provide clinical evidence regarding the optimal treatment of cIAI. A systematic review and a meta-analysis of randomized clinical trials in the treatment of cIAI were conducted. The systematic review with PubMed, Embase, and the Cochrane Database of Systematic Reviews followed the Cochrane Handbook's recommended methodology, and the meta-analysis used a Mantel-Haenszel random-effects model with RevMan, version 5.3. Primary endpoints were clinical success and bacteriological eradication, and secondary endpoints were all-cause mortality and drug-related adverse events. Eight studies comparing metronidazole combination therapies and carbapenem were included in the meta-analysis. No difference was found between combined therapy with metronidazole and carbapenem regarding clinical success (odds ratio [OR] = 1.31; 95% confidence interval [CI], .75-2.31), bacteriological eradication (OR = 1.27; 95% CI, .84-1.91), all-cause mortality (OR = 0.61; 95% CI, .37-1.00), or drug-related adverse events (OR = 0.58; 95% CI, .18-1.88). Sensitivity analyses found similar results. Combined therapy with metronidazole is as effective and safe as carbapenem in treatment of cIAI. Therefore, combined therapy with metronidazole offers an effective alternative to carbapenem with low risk of drug resistance.
Risk factors for acute kidney injury in critically ill patients with complicated intra-abdominal infection.
Suarez-de-la-Rica Alejandro,Anillo Víctor,Montero Ana,Hernandez-Gancedo Carmen,Lopez-Tofiño Araceli,Gilsanz Fernando,Maseda Emilio
Journal of critical care
PURPOSE:The aim was to determine the factors related to acute kidney injury (AKI) in surgical septic patients with complicated intra-abdominal infection (CIAI) and mortality associated to AKI. METHODS:An observational study was performed in patients with CIAI requiring surgery and ICU admission (June 2011-June 2013). Factors at admission associated with developing of AKI and renal replacement therapy (RRT) and association between mortality and AKI and RRT were studied. RESULTS:A total of 114 patients were included. Developing of AKI was independently associated with the sequential organ failure assessment (SOFA) score (odds ratio [OR], 1.570; 95% confidence interval [CI], 1.286-2.016) and creatinine at admission (OR for 0.1 units, 1.560; 95% CI, 1.296-1.990). Renal replacement therapy was independently associated with arterial hypertension (OR, 4.896; 95% CI, 1.501-15.971) and SOFA (OR, 1.713; 95% CI, 1.377-2.132). In another model with more predictive capacity, the number of previous medications that may alter renal function (OR, 3.732; 95% CI, 1.923-8.383) and SOFA (OR, 1.860; 95% CI, 1.469-2.541) were related to RRT. Both AKI and RRT were related to intensive care unit (P=.014 and P<.001, respectively) and 28-day mortality (P=.045 and P<.001, respectively). CONCLUSIONS:Acute kidney injury in patients with CIAI is clearly associated with SOFA and creatinine at admission. Severe AKI with RRT need is highly associated with both previous arterial hypertension and the number of previous medications potentially affecting renal function.
Ceftazidime/avibactam: a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections.
Hidalgo Jose A,Vinluan Celeste M,Antony Nishaal
Drug design, development and therapy
There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P. aeruginosa and avibactam is a novel nonbeta-lactam beta-lactamase inhibitor. Avycaz(®), the trade name for this new combination antibiotic, restores the activity of ceftazidime against some of the previously resistant pathogens. Avycaz was approved in 2015 for the treatment of complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections with the addition of metronidazole in patients with little to no other treatment options. This review article assesses the clinical trials and data that led to the approval of this antibiotic, in addition to its spectrum of activity and limitations.
The impact of initial antibiotic treatment failure: real-world insights in patients with complicated, health care-associated intra-abdominal infection.
Peeters Pascale,Ryan Kellie,Karve Sudeep,Potter Danielle,Baelen Elisa,Rojas-Farreras Sonia,Rodríguez-Baño Jesús
Infection and drug resistance
PURPOSE:The RECOMMEND study (NCT02364284; D4280R00005) assessed the clinical management patterns and treatment outcomes associated with initial antibiotic therapy (IAT; antibiotics administered ≤48 hours post-initiation of antibiotic therapy) for health care-associated infections across five countries. PATIENTS AND METHODS:Data were collected from a retrospective chart review of patients aged ≥18 years with health care-associated complicated intra-abdominal infection (cIAI). Potential risk factors for IAT failure were identified using logistic regression analyses. RESULTS:Of 385 patients with complete IAT data, bacterial pathogens were identified in 270 (70.1%), including Gram-negative isolates in 221 (81.9%) and Gram-positive isolates in 92 (34.1%). Multidrug-resistant (MDR) pathogens were identified in 112 patients (41.5% of patients with a pathogen identified). IAT failure rate was 68.3% and in-hospital mortality rate was 40.8%. Multivariate regression analysis demonstrated three factors to be significantly associated with IAT failure: patients admitted/transferred to the intensive care unit during index hospitalization, isolation of an MDR pathogen and previous treatment with β-lactam antibiotics. CONCLUSION:We reveal the real-world insights into the high rates of IAT failure and mortality observed among patients with cIAI. These data highlight the challenges associated with choosing IAT, the impact of MDR pathogens on IAT outcomes and the importance of tailoring IAT selection to account for local epidemiology and patient history.
Clinical and Microbiological Characteristics of Patients with Complicated Intra-abdominal Infections in Intensive Care Unit.
Xiong Yang-Mei,Rao Xin
Current medical science
In order to investigate the clinical and microbiological characteristics of patients with complicated intra-abdominal infections (cIAIs) in intensive care unit (ICU), the clinical data of 612 cIAIs patients from January 2016 to December 2018 were retrospectively collected. Clinical characteristics, distribution of pathogens and drug resistance were statistically analyzed. It was found that patients with community-acquired intra-abdominal infections (CA-IAIs) made up a majority of cIAIs patients. The positive rate of abdominal drainage fluid culture was 55.56%. Gramnegative bacteria accounted for the majority, the most commonly isolated bacteria of which were Escherichia coli (20.96%), Klebsiella pneumoniae (10.20%) and Pseudomonas aeruginosa (5.57%). The most commonly isolated gram-positive bacteria were Enterococcus (16.88%) and Methicillin-resistant staphylococcus aureus (MRSA, 3.90%). Enterobacter isolates showed high resistance rate to most cephalosporins and low resistance rate to piperacillin/tazobactam and carbapenems. Extended spectrum beta-lactamase (ESBL) screen positive isolates from CA-IAIs patients showed an increasing trend in past three years. Enterococcus and MRSA showed high resistance rate to clindamycin, quinolone, erythromycin and tetracycline, while they showed high sensitivity rate to linezolid, tegacycline, teicoplanin and vancomycin. Our results indicate that isolated bacteria from abdominal drainage fluid show high resistance rates to commonly used antibiotics in ICU patients with cIAIs. The curative effects on diseases should be monitored continuously when antibiotics are used. Meanwhile, we should always keep eyes on drug-resistant bacteria, especially when the treatment efficacy is not good.
Risk Factors and Molecular Epidemiology of Complicated Intra-Abdominal Infections With Carbapenem-Resistant Enterobacteriaceae: A Multicenter Study in China.
Liu Jiao,Zhang Lidi,Pan Jingye,Huang Man,Li Yingchuan,Zhang Hongjin,Wang Ruilan,Zhao Mingyan,Li Bin,Liu Long,Gong Ye,Bian Jinjun,Li Xiang,Tang Yan,Lei Ming,Chen Dechang
The Journal of infectious diseases
BACKGROUND:Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with poor patient outcomes. Data on risk factors and molecular epidemiology of CRE in complicated intra-abdominal infections (cIAI) in China are limited. This study examined the risk factors of cIAI with CRE and the associated mortality based on carbapenem resistance mechanisms. METHODS:In this retrospective analysis, we identified 1024 cIAI patients hospitalized from January 1, 2013 to October 31, 2018 in 14 intensive care units in China. Thirty CRE isolates were genotyped to identify β-lactamase-encoding genes. RESULTS:Escherichia coli (34.5%) and Klebsiella pneumoniae (21.2%) were the leading pathogens. Patients with hospital-acquired cIAI had a lower rate of E coli (26.0% vs 49.1%; P < .001) and higher rate of carbapenem-resistant Gram-negative bacteria (31.7% vs 18.8%; P = .002) than those with community-acquired cIAI. Of the isolates, 16.0% and 23.4% of Enterobacteriaceae and K pneumoniae, respectively, were resistant to carbapenem. Most carbapenemase-producing (CP)-CRE isolates carried blaKPC (80.9%), followed by blaNMD (19.1%). The 28-day mortality was 31.1% and 9.0% in patients with CRE vs non-CRE (P < .001). In-hospital mortality was 4.7-fold higher for CP-CRE vs non-CP-CRE infection (P = .049). Carbapenem-containing combinations did not significantly influence in-hospital mortality of CP and non-CP-CRE. The risk factors for 28-day mortality in CRE-cIAI included septic shock, antibiotic exposure during the preceding 30 days, and comorbidities. CONCLUSIONS:Klebsiella pneumoniae had the highest prevalence in CRE. Infection with CRE, especially CP-CRE, was associated with increased mortality in cIAI.
Risk factors for mortality and cost implications of complicated intra-abdominal infections in critically ill patients.
De Pascale Gennaro,Carelli Simone,Vallecoccia Maria Sole,Cutuli Salvatore Lucio,Taccheri Temistocle,Montini Luca,Bello Giuseppe,Spanu Teresa,Tumbarello Mario,Cicchetti Americo,Urbina Irene,Oradei Marco,Marchetti Marco,Antonelli Massimo
Journal of critical care
PURPOSE:To assess risk factors for 28-day mortality and cost implications in intensive care unit (ICU) patients with complicated intra-abdominal infections (cIAIs). METHODS:Single-center retrospective cohort study of prospectively collected data analysing ICU patients with a microbiologically confirmed complicated intra-abdominal infections. RESULTS:137 complicated intra-abdominal infections were included and stratified according to the adequacy of antimicrobial therapy (initial inadequate antimicrobial therapy [IIAT], n = 44; initial adequate antimicrobial therapy [IAAT], n = 93). The empirical use of enterococci/methicillin-resistant Staphylococcus aureus active agents and of carbapenems was associated with a higher rate of therapeutic adequacy (p = 0.016 and p = 0.01, respectively) while empirical double gram-negative and antifungal therapy did not. IAAT showed significantly lower mortality at 28 and 90 days and increased clinical cure and microbiological eradication (p < 0.01). In the logistic and Cox-regression models, IIAT and inadequate source control were the unique predictors of 28-day mortality. No costs differences were related to the adequacy of empirical therapy and source control. The empirical double gram-negative and antifungal therapy (p = 0.03, p = 0.04) as well as the isolation of multidrug-resistant (MDR) bacteria and the microbiological failure after targeted therapy were drivers of increased costs (p = 0.004, p = 0.04). CONCLUSIONS:IIAT and inadequate source control are confirmed predictors of mortality in ICU patients with complicated intra-abdominal infections. Empirical antimicrobial strategies and MDR may drive hospital costs.
Predictors of efficacy and health resource utilization in treatment of complicated intra-abdominal infections: evidence for pooled clinical studies comparing tigecycline with imipenem-cilastatin.
Mallick Rajiv,Sun Steven,Schell Scott R
BACKGROUND:Duration of intravenous (IV) treatment, surgical/radiologic interventions for infection control, and hospital length of stay (LOS) are important cost considerations in complicated intra-abdominal infections (cIAIs). METHODS:Data were pooled from two multinational, double-blind studies conducted in hospitalized adults with cIAIs who were randomized (1:1) to receive tigecycline (100 mg IV initial dose then 50 mg IV every 12 h) or imipenem-cilastatin (500 mg IV every 6 h) for 5 to 14 days in order to assess tigecycline safety and efficacy. This report focuses on developing predictors of cure and health care resource utilization, including the need for repeat surgical/radiologic interventions, duration of IV antibiotic therapy, and hospital LOS. Multiple regression models were applied for each of the above outcomes, incorporating both baseline and on-treatment potential covariates. Logistic modeling was used for categorical outcomes (cure; repeat surgical/radiologic interventions) and least squares modeling for continuous outcomes (duration of IV antibiotic therapy; LOS). Stepwise selection was used to retain only those predictors found to be significant (p < 0.05) independent risk factors. RESULTS:The most common causative pathogen was Escherichia coli (63.0%), with 63.3% of the patients exhibiting polymicrobial infections. The most common cIAI diagnosis was complicated appendicitis (51.9%). Lack of clinical cure (+ 6.1 days; p < 0.0001), perforation of the intestine (+3.7 days; p < 0.0001), an Acute Physiology and Chronic Health Evaluation (APACHE) score >15 (+3.1 days; p=0.039), abnormal plasma sodium concentration (+3.7 days; p=0.026), and repeat surgical/radiologic intervention (+2.2 days; p=0.0097) were identified as key risk factors for longer LOS. Inadequate source control was associated with reduced odds of cure, longer IV treatment duration (+1.5 days; p=0.007), and longer LOS. The treatment groups did not differ in terms of LOS, IV treatment duration, or clinical cure. CONCLUSION:Tigecycline was similar to imipenem-cilastatin in terms of both efficacy and health resource utilization. Risk factors identified in this study for both outcome measures are offered as support for guiding clinical practice.
Clinical characteristics and antimicrobial patterns in complicated intra-abdominal infections: a 6-year epidemiological study in southern China.
Ouyang Wenwei,Xue Huiling,Chen Yunqin,Gao Weiguo,Li Xiaoyan,Wei Jia,Wen Zehuai
International journal of antimicrobial agents
Complicated intra-abdominal infection (cIAIs) are a common and important cause of morbidity worldwide. In this study, the clinical features, microbiological profiles, antimicrobial patterns and treatments of 3233 cIAI patients (mean age, 47.6 years; 54.7% male) with 3531 hospitalisations from 2008-2013 were retrospectively investigated. The most commonly isolated bacteria were Escherichia coli (47.6%), Klebsiella pneumoniae (16.9%), Enterococcus faecalis (10.4%) and Pseudomonas aeruginosa (8.8%). Ciprofloxacin, aminoglycoside (gentamicin), piperacillin/tazobactam and carbapenems exhibited activity against 53%, 76%, 88% and 100% of extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae isolates, respectively. Pseudomonas aeruginosa isolates exhibited 100%, 95%, 88%, 71% and 76% susceptibility to aminoglycoside (gentamicin), ciprofloxacin, meropenem, imipenem and ceftazidime, respectively, and Enterococcus remained 100% susceptible to vancomycin and linezolid. β-Lactam antibacterials other than penicillin (specifically third-generation cephalosporins) and imidazole derivatives (ornidazole and metronidazole) were the most common first-line treatments. Patients subjected to regimen change after initial antibiotic treatment had predisposing conditions (e.g. older age, more severe co-morbidities) and a higher incidence of P. aeruginosa infection; in addition, these patients encountered a higher average cost of care and worse clinical outcomes compared with those without medication modification. Taken together, these findings indicate the importance of appropriate initial empirical therapy and suggest the use of combination therapy comprising cephalosporins and metronidazole.
Epidemiologic analysis and control strategy of infection in intensive care units in a teaching hospital of People's Republic of China.
Wang Chunrui,Yuan Zhe,Huang Wenxiang,Yan Li,Tang Jun,Liu Cheng-Wei
Infection and drug resistance
BACKGROUND: (KP) is the most common pathogen isolated in intensive care units (ICUs) and the most frequently encountered carbapenemase-producing Enterobacteriaceae. Increasing antimicrobial drug resistance, especially in carbapenem-resistant KP (CRKP), can limit the choice of antibiotics used for the treatment of infectious diseases and further poses a negative impact on patient outcome. However, the reason behind this increasing resistance is not well known. PATIENTS AND METHODS:A retrospective analysis of laboratory records and clinical cases of KP infection in the ICUs of a hospital from January 2013 to December 2017 was conducted. The disk diffusion method and double-paper synergy test were used to test drug sensitivity for extended-spectrum β-lactamase (ESBL) detection. WHONET5.6 and SPSS 21.0 software were used for statistical analysis. RESULTS:A total of 64.8% (570/847) of patients with KP infection were older than 60 years. The lower respiratory tract was the main infection site, accounting for 70.84% (600/847); the highest rate of ICU admission was for neurosurgery, accounting for 28.69% (243/847). Some 444 multidrug-resistant KP strains were detected, including 69 CRKP and 299 ESBL-producing strains. In the past 5 years, the resistance rate of detected strains to common antibiotics increased to various degrees, particularly carbapenem-resistant strains which increased from 4.76% (9/189) in 2013 to 16.00% (28/175) in 2017. All carbapenem-resistant isolates were resistant to β-lactam antibiotics, and no isolates were resistant to tigecycline. CONCLUSION:CRKP and ESBLKP prevalence and resistance rates gradually increased in our ICUs in the past 5 years. The reasons for this are manifold. Regular surveillance of resistance, rational use of antibiotics, and other effective infection control measures need to be strengthened to slow down the production of multidrug-resistant bacteria and prevent their spread in ICU settings.
Tigecycline Therapy for Infections Caused by Extended-Spectrum β-Lactamase-Producing in Critically Ill Patients.
Yu Wen-Liang,Lee Nan-Yao,Wang Jann-Tay,Ko Wen-Chien,Ho Chung-Han,Chuang Yin-Ching
Antibiotics (Basel, Switzerland)
We aimed to evaluate tigecycline on the clinical effectiveness in treating complicated skin and soft tissue infections (cSSTI), complicated intra-abdominal infections (cIAI), and pneumonia, caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, as data are limited. From three medical centers in Taiwan, we retrospectively studied the cSSTI, cIAI, and/or pneumonia caused by ESBL-producing Enterobacteriaceae. Among the 71 patients, including 39 patients infected with , 30 infected with and others, the clinical success rate of tigecycline-based therapy was 80%-90% for pneumonia and cSSTI caused by and 50%-60% for cIAI caused by and . Microbiological and clinical outcome of pneumonia caused by carbapenem-resistant was poor. Univariate Cox analysis showed that dyspnea, SOFA score, septic shock, thrombocytopenia, prolonged prothrombin time, and lesser microbiological eradication were significant factors associated with 30-day mortality after the end of therapy. Cox regression proportional hazards model revealed dyspnea and a SOFA score > 8 to be independently associated with time to death. For ESBL producers, tigecycline showed good effects for cSSTI and pneumonia by , ordinary for cIAI, but ineffective for pneumonia by . Dyspnea and a high SOFA score predict a poor outcome.
[Hospital management of patients with complicated intra-abdominal infections: pharmacoeconomic evaluations].
Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive
Due to their high incidence and large resource consumption, complicated intra-abdominal infections (cIAIs) represent a heavy burden for the Italian National Health System (NHS) and the Italian society, with estimated annual costs of 1,5 and 3 billions Euro, respectively. The different strategies, monotherapy or antibiotic combinations, indicated for treating cIAIs induce significantly different acquisition and administration costs but substantially equivalent therapeutic results, with average clinical effectiveness rates of 70-80%. This apparent equivalence among different antibiotic protocols presumably depends on the widespread trend to individualize the therapeutic strategy according to the clinical severity and the community or nosocomial origin of cIAIs, as well as on some degree of non-appropriateness when empirically choosing a first-line antibiotic. The average cost for the nosocomial management of cIAI patients depends on several factors: posology and antibiotic drug acquisition and administration costs, days of antibiotic therapy, mix of antibiotic schedules, rates of the therapeutic failures that induce further drug consumption, prolong hospitalization and often require re-intervention and ICU utilization. The introduction in the therapeutic arsenal of a new antibiotic like tigecycline leads to a mild increase of the average antibiotic acquisition and treatment costs per patient: this increase is proportional to the percentage of patients treated with the new antibiotic. According to a decisional model, implemented on international outcome data and Italian costs, the mean cost for first-line antibiotic acquisition and the mean cost for first- and second-line antibiotic treatment represent respectively only 2% and 8% of the mean overall hospitalization cost. The mean hospitalization cost estimated by the model is noticeably higher than the mean value of DRG tariffs presumably reimbursed by the Italian NHS to hospitals for cIAI-related hospitalizations. Greater overall efficiency levels in the nosocomial management of cIAI patients are achievable mainly through the reduction of non-appropriateness rates in first line antibiotic choices and better treatment individualization, possible if the physician is offered the choice of as many valid therapeutic options as possible, in order to guarantee the best cure chances to each patient.
Hospital management of complicated intra-abdominal infections: pharmacoeconomic evaluation.
Journal of chemotherapy (Florence, Italy)
Complicated intra-abdominal infections (cIAIs) represent a heavy burden for the italian National Health System (NHS) and the italian society, with estimated annual costs of 1.5 and 3 billion euros, respectively. Both monotherapy and antibiotic combinations induce significantly different acquisition and administration costs but substantially equivalent therapeutic results, with average clinical effectiveness rates of 70-80%. this apparent equivalence presumably depends on the widespread trend to individualize the therapeutic strategy according to the clinical severity and the community or nosocomial origin of cIAIs, as well as to the degree of non-appropriateness when empirically choosing a first-line antibiotic.The average cost of nosocomial management of cIAI patients depends on several factors: posology, antibiotic drug acquisition, administration costs, duration of therapy, mix of antibiotic schedules, rates of the therapeutic failures, prolonged hospitalization. The introduction of a new antibiotic like tigecycline to the therapeutic arsenal leads to a small increase in average antibiotic acquisition and treatment costs per patient: this increase is proportional to the percentage of patients treated with the new antibiotic. According to a decisional model, implemented on international outcome data and italian costs, the mean cost for first-line antibiotic acquisition and the mean cost for first- and second-line antibiotic treatment represent respectively only 2% and 8% of the mean overall hospitalization cost. the mean hospitalization cost estimated by the model is noticeably higher than the mean value of Diagnosis Related Group (DRG) tariffs presumably reimbursed by the italian NHS to hospitals for ciAi-related hospitalizations. Greater overall efficiency levels in the nosocomial management of cIAI patients are achievable mainly through the reduction of non-appropriateness rates in first-line antibiotic choices and better treatment individualization, possible if the physician is offered the choice of as many valid therapeutic options as possible, in order to guarantee the best possibility of cure for each patient.
Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial.
Chen Zhangjing,Wu Jufang,Zhang Yingyuan,Wei Junming,Leng Xisheng,Bi Jianwei,Li Rong,Yan Lunan,Quan Zhiwei,Chen Xiaoping,Yu Yunsong,Wu Zhiyong,Liu Dawei,Ma Xiaochun,Maroko Robert,Cooper Angel
BMC infectious diseases
BACKGROUND:Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs. METHODS:In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for </=2 weeks. The primary efficacy endpoints were clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat and microbiologically evaluable populations. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin, no formal statistical analysis was performed. Two-sided 95% confidence intervals (CIs) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purposes. RESULTS:One hundred ninety-nine patients received >/=1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (P < 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; P < 0.001) and vomiting (12.4% vs. 2.0%; P = 0.005). CONCLUSIONS:Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed. TRIAL REGISTRATION:ClinicalTrials.gov NCT00136201.
A multicenter, double-blind, randomized, comparison study of the efficacy and safety of tigecycline to imipenem/cilastatin to treat complicated intra-abdominal infections in hospitalized subjects in China.
Chen Yijian,Zhu Demei,Zhang Yingyuan,Zhao Yongjie,Chen Gang,Li Ping,Xu Lihong,Yan Ping,Hickman M Anne,Xu Xiajun,Tawadrous Margaret,Wible Michele
Therapeutics and clinical risk management
PURPOSE:To assess the efficacy and safety of tigecycline in treating complicated intra-abdominal infections (cIAIs) in hospitalized patients in China. PATIENTS AND METHODS:A Phase IV, multicenter, randomized, double-blinded, active-controlled, non-inferiority study was conducted. Hospitalized cIAI patients ≥18 years of age were randomized (1:1) to receive intravenous tigecycline (initial dose 100 mg, then 50 mg q12h) or imipenem/cilastatin (500 mg/500 mg or adjusted for renal dysfunction, q6h) for 5-14 days. The primary end point was clinical response for clinically evaluable (CE) subjects at test-of-cure (TOC) assessment. RESULTS:Four hundred and seventy subjects were randomized; 232 in the tigecycline and 231 in the imipenem/cilastatin group were treated. Tigecycline was non-inferior to imipenem/cilastatin with respect to clinical response at TOC for all CE subjects, ie, the lower bound of the two-sided 95% CI (-12.0%, -1.4%) for the treatment difference in cure rate, tigecycline (89.9%) minus imipenem/cilastatin (96.6%), was >-15%. As non-inferiority was concluded in the CE population, superiority of tigecycline over imipenem/cilastatin and superiority of imipenem/cilastatin over tigecycline were tested on the CE and the modified intent-to-treat (mITT) populations according to pre-specified statistical criteria, and neither could be demonstrated (the cure rate was 82.8% vs 88.7%, difference -6.0% [-12.8%, 0.8%], for the mITT population). The subject-level microbiological response rate at TOC for the microbiologically evaluable population was 88.0% (110/125) vs 95.3% (102/107, difference -7.3% [-15.2%, 0.5%]). Nausea, drug ineffectiveness, postoperative wound infection, vomiting, and pyrexia were the most common adverse events in tigecycline-treated subjects; pyrexia, nausea, vomiting, and increased alanine aminotransferase and aspartate aminotransferase levels were most common in imipenem/cilastatin-treated subjects; none were unanticipated. CONCLUSION:Tigecycline was non-inferior to imipenem/cilastatin in treating hospitalized adult patients with cIAI. Superiority of tigecycline over imipenem/cilastatin or imipenem/cilastatin over tigecycline could not be demonstrated. Safety was consistent with the known profile for tigecycline. CLINICALTRIALSGOV IDENTIFIER:NCT01721408.
Carbapenems vs tigecycline for the treatment of complicated intra-abdominal infections: A Bayesian network meta-analysis of randomized clinical trials.
Chen Lingyuan,Liang Xueyan,Jiang Junsong,Li Xianshu,Li Yan
BACKGROUND:Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality. Carbapenems and tigecycline (TGC) are recommended for antimicrobial therapies for cIAIs. OBJECTIVE:To compare the effectiveness and safety of different carbapenems vs TGC for the treatment of cIAIs. METHODS:PubMed, Embase, Medline (via Ovid SP) and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing different carbapenems vs TGC for the treatment of cIAIs. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. We estimated summary ORs using pairwise and network meta-analysis with random effects. RESULTS:Fifteen studies involving 6745 participants were included in the analysis. Five different carbapenems and TGC were ultimately evaluated in this study. Although, the efficacy of carbapenems and TGC by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that clinical treatment success from best to worst was doripenem (DOPM), meropenem (MEPM), imipenem/cilastatin (IC), biapenem (BAPM), TGC and imipenem/cilastatin/relebactam (ICRB); microbiological treatment success from best to worst was DOPM, MEPM, IC, BAPM, ICRB and TGC. As for the risk of adverse events (AEs), TGC showed higher risk of AEs compared with IC (OR = 1.53, 95% CrI = 1.02-2.41), the remain antibiotic agents from lower to higher was MEPM, IC, BAPM, DOPM, ICRB and TGC. The risk of mortality from lower to higher was BAPM, DOPM, MEPM, IC, TGC and ICRB. CONCLUSION:No differences in clinical and microbiological outcomes were observed between different carbapenems and TGC. Balancing the evidence for drug efficacy and side effects, DOPM appears to be the best available treatment for cIAIs. Therefore, it is reasonable to consider that DOPM is one of the best carbapenem monotherapy for cIAIs. MEPM and IC was also associated with higher rates of clinical and microbiological treatment success following DOPM. Empiric antimicrobial treatment of patients with cIAIs should be selected in light of the local bacterial epidemiology and patterns of resistance.
An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by in Critically Ill Adult Patients.
Gatti Milo,Viaggi Bruno,Rossolini Gian Maria,Pea Federico,Viale Pierluigi
Infection and drug resistance
Prompt implementation of appropriate targeted antibiotic therapy represents a valuable approach in improving clinical and ecological outcome in critically septic patients. This multidisciplinary opinion article focused at developing evidence-based algorithms for targeted antibiotic therapy of bloodstream (BSIs), complicated urinary tract (cUTIs), and complicated intrabdominal infections (cIAIs) caused by . The aim was to provide a guidance for intensive care physicians either in appropriately placing novel antibiotics or in considering strategies for sparing the broadest-spectrum antibiotics. A multidisciplinary team of experts (one intensive care physician, one infectious disease consultant, one clinical microbiologist and one MD clinical pharmacologist), performed several rounds of assessment to reach agreement in developing six different algorithms according to the susceptibility pattern (one each for multi-susceptible, extended-spectrum beta-lactamase-producing, AmpC beta-lactamase-producing, carbapenemase (KPC)-producing, OXA-48-producing, and Metallo-beta-lactamase (MBL)-producing ). Whenever multiple therapeutic options were feasible, a hierarchical scale was established. Recommendations on antibiotic dosing optimization were also provided. In order to retrieve evidence-based support for the therapeutic choices proposed in the algorithms, a comprehensive literature search was performed by a researcher on PubMed-MEDLINE from inception until March 2021. Quality and strength of evidence was established according to a hierarchical scale of the study design. Only articles published in English were included. It is expected that these algorithms, by allowing prompt revision of antibiotic regimens whenever feasible, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens, may be helpful either in improving clinical outcome or in containing the spread of antimicrobial resistance.
Pharmacoeconomics of ciprofloxacin plus metronidazole vs. piperacillin-tazobactam for complicated intra-abdominal infections.
Paladino Joseph A,Gilliland-Johnson Kristin K,Adelman Martin H,Cohn Stephen M
BACKGROUND:A series of 459 hospitalized adults with complicated intra-abdominal infections participated in a randomized, double-blind, multicenter clinical trial. The present study was conducted to add a pharmacoeconomic analysis to the results. METHODS:A cost-effectiveness analysis from the perspective of the hospital provider was carried out. Decision analysis was used to illustrate outcomes and to provide a basis on which to conduct a sensitivity analysis. Cost-effectiveness ratios, representing the cost per expected successfully treated patient, were calculated to determine the most cost-effective alternative. RESULTS:Among 244 economically evaluable patients, enrolled from 34 centers in the U.S. and Canada, 131 patients received ciprofloxacin-metronidazole (75% clinical success rate), and 113 received piperacillin-tazobactam (65% clinical success rate; p = 0.06). Switch to oral antibiotics was possible for 81 patients who received ciprofloxacin-metronidazole (85% clinical success rate) and 67 piperacillin-tazobactam patients (70% clinical success rate; p = 0.027). The mean hospital cost was US$10,662 +/- 7,793 for patients in the ciprofloxacin-metronidazole group and $10,009 +/- 7,023 for patients in the piperacillin-tazobactam group (p = 0.492). Significantly lower costs were documented for patients who could be switched to oral antibiotics than for those continued on intravenous antibiotic orders ($8,684 +/- 4,120 vs. $12,945 +/- 10,204, respectively; p < 0.001). Patients with appendicitis had lower mean hospital costs than those with other infections ($7,169 +/- 3,705 vs. $12,097 +/- 8,342, respectively; p < 0.001). The cost-effectiveness ratios were $14,216:1 for patients in the ciprofloxacin-metronidazole group and $15,398:1 for patients in the piperacillin-tazobactam group. CONCLUSIONS:The mean hospital costs associated with ciprofloxacin-metronidazole were similar to those of piperacillin-tazobactam for the treatment of adults with complicated intra-abdominal infections. Lower costs were documented for patients able to be switched to oral antibiotics and for patients with appendicitis.
Cost efficacy of tazobactam/piperacillin versus imipenem/cilastatin in the treatment of intra-abdominal infection.
Dietrich E S,Schubert B,Ebner W,Daschner F
OBJECTIVE:To compare the cost, efficacy and cost efficacy of tazobactam/piperacillin and imipenem/cilastatin in the treatment of intra-abdominal infection. DESIGN:The analysis was retrospective and based on a decision tree. Effectiveness data were obtained from 19 published clinical trials. Direct costs were quantified per patient from the time the decision was made to administer the antibacterial to the end of the first course of treatment or the end of a subsequent course of treatment, if required. The primary end-point was the cost per successfully treated patient. The cost per life saved was also analysed. Various follow-up times were taken into account. PERSPECTIVE:German National Health Insurance funds. STUDY POPULATION:1744 patients with intra-abdominal infection. INTERVENTIONS:Tazobactam/piperacillin (total daily dosage of 13.5 g/day) and imipenem/cilastatin (total daily dosage of 1.5 to 4 g/day). The mean duration of treatment varied from 5.5 to 8.2 days for tazobactam/piperacillin and 5 to 9.4 days for imipenem/cilastatin. MAIN OUTCOME MEASURE AND RESULTS:Compared with imipenem/cilastatin, treatment with tazobactam/piperacillin was more effective and the overall treatment costs were lower. In the base-case analysis, the cost-efficacy ratio (cost per successfully treated patient) was 7881 German deutschmarks (DM) for tazobactam/piperacillin and DM11,390 for imipenem/cilastatin. The incremental cost-efficacy ratio (per life saved) varied between -DM72,567 and -DM350,738 for tazobactam/piperacillin. Sensitivity analyses revealed that the results were robust against various assumptions on cost parameters, clinical outcomes and length of treatment. All costs reflect 1998 values; $US1 = DM1.85. CONCLUSIONS:This study suggests that compared with imipenem/cilastatin, tazobactam/piperacillin is more cost efficacious in the treatment of intra-abdominal infections and that it offers a cost advantage through fewer relapses and lower daily therapeutic costs.
The cost-effectiveness of cefepime plus metronidazole versus imipenem/cilastatin in the treatment of complicated intra-abdominal infection.
Barie Philip S,Rotstein Ori D,Dellinger E Patchen,Grasela Thaddeus H,Walawander Cynthia A
BACKGROUND:Our objective was to compare the economic benefits of cefepime plus metronidazole with those of imipenem/cilastatin in the treatment of complicated intra-abdominal infections. METHODS:We used a retrospective analysis of clinical outcomes and health resource utilization data collected during a randomized, double-blind, multi-center clinical trial. Seventeen university-affiliated hospitals in the United States and Canada participated, as did 323 patients with complicated intra-abdominal infections. Decision analysis was conducted using a decision node of cefepime vs. imipenem, and chance nodes that included an Acute Physiology and Chronic Health Evaluation (APACHE) II score of #15 versus .15; a need for posttreatment surgical procedures; and clinical outcomes. Effectiveness of treatment was measured by differences in the length and cost of hospital stays, the number and cost of surgical procedures after treatment, cure rates, and the cost of antibiotics. Also evalulated were the incremental costs of cure (i.e., the costs of additional cures). RESULTS:Comparing cefepime plus metronidazole with imipenem/cilastatin, the expected cost of patient care was $8,218 versus $10,414, respectively, and the cost-effectiveness ratio per cure was $10,058 versus $13,685. For severely ill patients (APACHE II score .15), the expected cost was $12,962 versus $23,153, and the cost-effectiveness ratio per cure was $15,321 versus $64,313. CONCLUSIONS:Cefepime plus metronidazole was more cost-effective than imipenem/cilastatin in the treatment of complicated intra-abdominal infections, primarily because of fewer post-treatment surgical procedures and shorter hospital stays. The primary advantage accrued to severely ill patients who had an APACHE II score .15.
Cost-effectiveness of Treatment Regimens for Clostridioides difficile Infection: An Evaluation of the 2018 Infectious Diseases Society of America Guidelines.
Rajasingham Radha,Enns Eva A,Khoruts Alexander,Vaughn Byron P
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:In 2018, the Infectious Diseases Society of America (IDSA) published guidelines for diagnosis and treatment of Clostridioides (formerly Clostridium) difficile infection (CDI). However, there is little guidance regarding which treatments are cost-effective. METHODS:We used a Markov model to simulate a cohort of patients presenting with an initial CDI diagnosis. We used the model to estimate the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the recently published 2018 IDSA guidelines. The model includes stratification by the severity of the initial infection, and subsequent likelihood of cure, recurrence, mortality, and outcomes of subsequent recurrences. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS:Use of fidaxomicin for nonsevere initial CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and fecal microbiota transplantation (FMT) for subsequent recurrence (strategy 44) cost an additional $478 for 0.009 QALYs gained per CDI patient, resulting in an ICER of $31 751 per QALY, below the willingness-to-pay threshold of $100 000/QALY. This is the optimal, cost-effective CDI treatment strategy. CONCLUSIONS:Metronidazole is suboptimal for nonsevere CDI as it is less beneficial than alternative strategies. The preferred treatment regimen is fidaxomicin for nonsevere CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and FMT for subsequent recurrence. The most effective treatments, with highest cure rates, are also cost-effective due to averted mortality, utility loss, and costs of rehospitalization and/or further treatments for recurrent CDI.
Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia, Including Ventilator-associated Pneumonia, in Italy.
Tichy Eszter,Torres Antoni,Bassetti Matteo,Kongnakorn Thitima,Di Virgilio Roberto,Irani Paurus,Charbonneau Claudie
PURPOSE:Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose combination antibiotic approved in Europe and the United States for patients with hospital-acquired pneumonia, including ventilator-associated pneumonia (HAP/VAP). The economic benefits of a new drug such as CAZ-AVI are required to be assessed against those of available comparators, from the perspective of health care providers and payers, through cost-effectiveness and cost-utility analyses. The objective of this analysis was to compare the cost-effectiveness of CAZ-AVI versus meropenem in the empirical treatment of appropriate hospitalized patients with HAP/VAP caused by gram-negative pathogens, from the perspective of publicly funded health care in Italy (third-party perspective, based on the data from the REPROVE (Ceftazidime-Avibactam Versus Meropenem In Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia) clinical study; ClinicalTrials.gov NCT01808092). METHODS:A patient-level, sequential simulation model of the HAP/VAP clinical course was developed using spreadsheet software. The analysis focused on direct medical costs. The time horizon of the model selected was 5 years, with an annual discount rate of 3% on costs and quality-adjusted life-years (QALYs). Clinical inputs for treatment comparisons were mainly obtained from the REPROVE clinical study data. In addition to clinical outcomes observed in the trial, the model incorporated impact of resistance pathogens, based on data from published studies and expert opinion. Certain assumptions were made for some model parameters due to a lack of data. FINDINGS:The analysis demonstrated that the intervention sequence (CAZ-AVI followed by colistin + high-dose meropenem) versus the comparator sequence (meropenem followed by colistin + high-dose meropenem) provided a better clinical cure rate (+13.52%), which led to a shorter hospital stay (-0.40 days per patient), and gains in the number of life-years (+0.195) and QALYs (+0.350) per patient. The intervention sequence had an estimated net incremental total cost of €1254 ($1401) per patient, and the estimated incremental cost-effectiveness ratio was €3581 ($4000) per QALY gained, well below the willingness-to-pay threshold of €30,000 ($33,507) per QALY in Italy. IMPLICATIONS:The model results showed that CAZ-AVI is expected to provide clinical benefits in hospitalized patients with HAP/VAP in Italy at an acceptable cost compared to meropenem.
[Cost-effectiveness of ceftazidime/avibactam versus colistin + meropenem for treatment of carbapenemic-resistant enterobacteria infections in Chile].
Gutiérrez A Magda,Fandiño Cecil
Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia
BACKGROUND:Ceftazidime-avibactam (C/A), has shown reduction in mortality rates and risk of nephrotoxicity, compared to colistin, conventional therapy. AIM:To estimate the cost-effectiveness of C/A versus colistin + meropenem in the treatment of infections due to carbapenem-resistant Enterobacteriaceae (CRE) in Chile. METHODS:An economic decision tree type model was adapted. The perspective of the public payer was used with a time horizon of 30 days and extrapolation to life expectancy. The clinical information was derived from an observational study. Medication and care costs correspond to local reports. The results are expressed as incremental cost-effectiveness ratio (ICER) per life year gained (LYG) and per quality adjusted life year (QALY) in Chilean pesos and US dollars (US$ 1.00 = $792.2218). RESULTS:8.65 and 6.48 LYGs and 6.44 and 4.27 QALYs were obtained, for C/A and colistin + meropenem, respectively. The estimated ICER for C/A was $940,488 (US$1,187.2) per AVG and $938,715 (US$1,184.9) per QALY. DISCUSSION:Given the lack of publications or evidence, the model is based on an observational study. C/A would reduce the death rate and increase LYGs and QALYs, resulting in a cost-effective alternative vs. colistin + meropenem for CRE.
Cost-effectiveness of ceftazidime-avibactam for treatment of carbapenem-resistant bacteremia and pneumonia.
Simon Matthew S,Sfeir Maroun M,Calfee David P,Satlin Michael J
Antimicrobial agents and chemotherapy
Ceftazidime/avibactam (CAZ-AVI) may improve outcomes among patients with carbapenem-resistant (CRE) infections compared to conventional therapies. However, CAZ-AVI's cost-effectiveness is unknown. We used a decision analytic model to estimate the health and economic consequences of CAZ-AVI-based therapy compared to colistin-based therapy (COL) for a hypothetical cohort of patients with CRE pneumonia or bacteremia over a 5-year horizon. Model inputs were from published sources and included CRE mortality with COL (41%), CAZ-AVI's absolute risk reduction in CRE mortality (23%), daily cost of CAZ-AVI ($926), risk of nephrotoxicity with COL (42%) and probability of discharge to long-term care (LTC) following CRE infection (56%). Outcomes included quality adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER; $/QALY). 1-way and probabilistic sensitivity analyses were performed and ICERs were compared to willingness to pay standards of $100,000/QALY and $150,000/QALY. In the base case, CAZ-AVI had an ICER of $95,000/QALY. At a $100,000/QALY threshold, results were sensitive to a number of variables including: the probability and cost of LTC, quality of life following CRE infection, CAZ-AVI's absolute risk reduction in mortality, all-cause mortality, daily cost of CAZ-AVI, and healthcare costs after CRE infection. The ICER did not exceed $150,000/QALY after varying all model inputs across a wide range of plausible values. In probabilistic sensitivity analysis, CAZ-AVI was the optimal strategy in 59% and 99% of simulations at $100,000/QALY and $150,000/QALY threshold, respectively. CAZ-AVI is a cost-effective treatment for CRE bacteremia and pneumonia based on accepted willingness to pay standards in the US.
Comparing ceftolozane/tazobactam versus piperacillin/tazobactam as empiric therapy for complicated urinary tract infection in Taiwan: A cost-utility model focusing on gram-negative bacteria.
Chen Guan-Jhou,Pan Sung-Ching,Foo Jason,Morel Chaienna,Chen Wei-Ting,Wang Jann-Tay
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
BACKGROUND:Complicated urinary tract infection (cUTI) is often associated with drug-resistant pathogens and requires therapy with broad-spectrum antibiotics. Choice of empiric therapy should be based on an evaluation of clinical efficacy and medical costs. We used a cost-utility model to compare the empiric use of a new antibiotic, ceftolozane/tazobactam with piperacillin/tazobactam in patients with cUTI. METHODS:The analysis was conducted using a decision tree and patient-level simulation approach. Patients in the model received empiric antibiotic treatment with ceftolozane/tazobactam or piperacillin/tazobactam. Outcomes included mortality, medical costs and quality-adjusted life years (QALYs). Parameters related to pathogen distribution, length of hospital stay and medical costs, were estimated based on a cohort of patients with cUTI admitted during July 1st, 2015 to August 31st, 2016 to the National Taiwan University Hospital, a teaching hospital in Taiwan. Isolates used for the patient-level simulation to determine susceptibility to either drug were taken from the Study for Monitoring Antimicrobial Resistance Trend database. RESULTS:The analysis was performed on a simulation of 1000 patients. Empiric use of ceftolozane/tazobactam leads to higher total medical costs (USD 4199.01 per patient versus USD 3594.76, respectively) but also more discounted QALYs (4.80 versus 4.78, respectively). The additional cost per discounted QALY gained associated with empiric ceftolozane/tazobactam was 32,521.08 USD (956,282 NTD). CONCLUSIONS:Our results suggest that empiric use of ceftolozane/tazobactam for the treatment of cUTI could be a cost-effective choice in Taiwan.