Vancomycin Area Under the Curve and Acute Kidney Injury: A Meta-analysis.
Aljefri Doaa M,Avedissian Sean N,Rhodes Nathaniel J,Postelnick Michael J,Nguyen Kevin,Scheetz Marc H
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:This study analyzed the relationship between vancomycin area under the concentration-time curve (AUC) and acute kidney injury (AKI) reported across recent studies. METHODS:A systematic review of PubMed, Medline, Scopus, and compiled references was conducted. We included randomized cohort and case-control studies that reported vancomycin AUCs and risk of AKI (from 1990 to 2018). The primary outcome was AKI, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on ≥2 consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Primary analyses compared the impact of AUC cutpoint (greater than ~650 mg × hour/L) and AKI. Additional analysis compared AUC vs trough-guided monitoring on AKI incidence. RESULTS:Eight observational studies met inclusion/exclusion criteria with data for 2491 patients. Five studies reported first-24-hour AUCs (AUC0-24) and AKI, 2 studies reported 24- to 48-hour AUCs (AUC24-48) and AKI, and 2 studies reported AKI associated with AUC- vs trough-guided monitoring. AUC less than approximately 650 mg × hour/L was associated with decreased AKI for AUC0-24 (OR, 0.36 [95% CI, .23-.56]) as well as AUC24-48 (OR, 0.45 [95% CI, .27-.75]). AKI associated with the AUC monitoring strategy was significantly lower than trough-guided monitoring (OR, 0.68 [95% CI, .46-.99]). CONCLUSIONS:AUCs measured in the first or second 24 hours and lower than approximately 650 mg × hour/L may result in a decreased risk of AKI. Vancomycin AUC monitoring strategy may result in less vancomycin-associated AKI. Additional investigations are warranted.
Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis.
Luther Megan K,Timbrook Tristan T,Caffrey Aisling R,Dosa David,Lodise Thomas P,LaPlante Kerry L
Critical care medicine
OBJECTIVES:The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy. DATA SOURCES:Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched. STUDY SELECTION:Articles not in English, pediatric studies, and case reports were excluded. DATA EXTRACTION:Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3. DATA SYNTHESIS:Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, -1.30; 95% CI, -3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57-4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83-3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97-3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48-20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83-2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86-2.11). CONCLUSIONS:The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed.
Optimal vancomycin dosing regimens for critically ill patients with acute kidney injury during continuous renal replacement therapy: A Monte Carlo simulation study.
Charoensareerat Taniya,Chaijamorn Weerachai,Boonpeng Apinya,Srisawat Nattachai,Pummangura Chalermsri,Pattharachayakul Sutthiporn
Journal of critical care
PURPOSE:This study aims to determine the optimal vancomycin dosing in critically ill patients with acute kidney injury receiving continuous renal replacement therapy (CRRT) using Monte Carlo simulation. METHODS:A one compartment pharmacokinetic model was conducted to define vancomycin deposition for the initial 48hours of therapy. Pharmacokinetic parameters were gathered from previously published studies. The AUC/MIC ratio of at least 400 and an average of AUC at > 700mgh/L were utilized to evaluate efficacy and nephrotoxicity, respectively. The doses achieved at least 90% of the probability of target attainment (PTA) with the lowest risk of nephrotoxicity defined as the optimal dose. RESULTS:The regimens of 1.75grams every 24hours and 1.5grams loading followed by 500mg every 8hours were recommended for empirical therapy of an MRSA infection with expected MIC ≤1mg/L, and definite therapy with actual MIC of 1mg/L. The probabilities of nephrotoxic results from these regimens were 35%. CONCLUSIONS:A higher dose of vancomycin than the current literature-based recommendation was needed in CRRT patients.
Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation.
Moise Pamela A,Culshaw Darren L,Wong-Beringer Annie,Bensman Joyce,Lamp Kenneth C,Smith Winter J,Bauer Karri,Goff Debra A,Adamson Robert,Leuthner Kimberly,Virata Michael D,McKinnell James A,Chaudhry Saira B,Eskandarian Romic,Lodise Thomas,Reyes Katherine,Zervos Marcus J
PURPOSE:Clinical studies comparing vancomycin with alternative therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are limited. The objective of this study was to compare outcomes of early daptomycin versus vancomycin treatment for MRSA bacteremia with high vancomycin MICs in a geographically diverse multicenter evaluation. METHODS:This nationwide, retrospective, multicenter (N = 11), matched, cohort study compared outcomes of early daptomycin with vancomycin for MRSA bloodstream infection (BSI) with vancomycin MICs 1.5 to 2 µg/mL. Matching variables, based on propensity regression analysis, included age, intensive care unit (ICU), and type of BSI. Outcomes were as follows: (1) composite failure (60-day all-cause mortality, 7-day clinical or microbiologic failure, 30-day BSI relapse, or end-of-treatment failure (EOT; discontinue/change daptomycin or vancomycin because of treatment failure or adverse event]); (2) nephrotoxicity; and (2) day 4 BSI clearance. FINDINGS:A total of 170 patients were included. The median (interquartile range) age was 60 years (50-74); the median (range) Acute Physiology and Chronic Health Evaluation II score was 15 (10-18); 31% were in an ICU; and 92% had an infectious disease consultation. BSI types included endocarditis/endovascular (39%), extravascular (55%), and central catheter (6%). The median daptomycin dose was 6 mg/kg, and the vancomycin trough level was 17 mg/L. Overall composite failure was 35% (59 of 170): 15% due to 60-day all-cause mortality, 14% for lack of clinical or microbiologic response by 7 days, and 17% due to failure at end of therapy (discontinue/change because of treatment failure or adverse event). Predictors of composite failure according to multivariate analysis were age >60 years (odds ratio, 3.7; P < 0.01) and ICU stay (odds ratio, 2.64; P = 0.03). Notable differences between treatment groups were seen with: (1) end of therapy failure rates (11% vs 24% for daptomycin vs vancomycin; P = 0.025); (2) acute kidney injury rates (9% vs 23% for daptomycin vs vancomycin; P = 0.043); and (3) day 4 bacteremia clearance rates for immunocompromised patients (n = 26) (94% vs 56% for daptomycin vs vancomycin; P = 0.035). IMPLICATIONS:Results from this multicenter study provide, for the first time, a geographically diverse evaluation of daptomycin versus vancomycin for patients with vancomycin-susceptible MRSA bacteremia with vancomycin MIC values >1 µg/mL. Although the overall composite failure rates did not differ between the vancomycin and daptomycin groups when intensively matched according to risks for failure, the rates of acute kidney injury were significantly lower in the daptomycin group. These findings suggest that daptomycin is a useful therapy for clinicians treating patients who have MRSA bacteremia. Prospective, randomized trials should be conducted to better assess the potential significance of elevated vancomycin MIC.
Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association.
Baddour Larry M,Wilson Walter R,Bayer Arnold S,Fowler Vance G,Tleyjeh Imad M,Rybak Michael J,Barsic Bruno,Lockhart Peter B,Gewitz Michael H,Levison Matthew E,Bolger Ann F,Steckelberg James M,Baltimore Robert S,Fink Anne M,O'Gara Patrick,Taubert Kathryn A,
BACKGROUND:Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances. METHODS AND RESULTS:This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations. CONCLUSIONS:Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.
Clinical and pharmacokinetic considerations for the use of daptomycin in patients with Staphylococcus aureus bacteraemia and severe renal impairment.
Chaves Ricardo L,Chakraborty Abhijit,Benziger David,Tannenbaum Stacey
The Journal of antimicrobial chemotherapy
OBJECTIVES:To support daptomycin dosing recommendations in patients with Staphylococcus aureus bacteraemia (SAB) and severe renal impairment using simulations from a population pharmacokinetic model for daptomycin. METHODS:A population pharmacokinetic model was developed using 4875 daptomycin plasma concentrations from 442 subjects. Daptomycin 24 h AUC and Cmax were then simulated for subjects with a CL(CR) < 30 mL/min [with or without haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD)] for different dosing frequencies (every 24 h, every 48 h and three times weekly) with doses of 4 mg/kg and 6 mg/kg. These results were compared with efficacy and safety exposure references based on daily dosing to understand the implications of less frequent dosing (for example, higher exposures on day 1 versus day 2) and to evaluate the 4 mg/kg versus 6 mg/kg regimens. RESULTS:Substantially more patients with SAB and severe renal impairment were underexposed (24 h AUCs compared with an efficacy reference of 6 mg/kg/day, CLCR ≥ 30 mL/min, pivotal trial population) at 4 mg/kg every 48 h compared with 6 mg/kg. Cmax results also favoured 6 mg/kg every 48 h over 4 mg/kg every 48 h. Both exposure metrics at 6 mg/kg every 48 h also stayed below the defined safety limits (based on 12 mg/kg/day, CL(CR) >80 mL/min, the highest dose in controlled clinical trials). CONCLUSIONS:For patients with SAB and CLCR <30 mL/min, or receiving HD or CAPD, the dose recommendation of 6 mg/kg every 48 h provides appropriate daptomycin exposure for this indication; this will not be the case for patients receiving 4 mg/kg every 48 h.
Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models.
Gomes Anna,van der Wijk Lars,Proost Johannes H,Sinha Bhanu,Touw Daan J
Gentamicin shows large variations in half-life and volume of distribution (Vd) within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1) creating an optimal model for endocarditis patients; and 2) assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE) and Median Absolute Prediction Error (MDAPE) were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients) with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358) renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076) L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68%) as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37%) and standard (MDPE -0.90%, MDAPE 4.82%) models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to avoid potential underdosing of gentamicin in endocarditis patients.
A comparison of different antibiotic regimens for the treatment of infective endocarditis.
Martí-Carvajal Arturo J,Dayer Mark,Conterno Lucieni O,Gonzalez Garay Alejandro G,Martí-Amarista Cristina Elena
The Cochrane database of systematic reviews
BACKGROUND:Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016. OBJECTIVES:To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. SELECTION CRITERIA:We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. DATA COLLECTION AND ANALYSIS:Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively. MAIN RESULTS:Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled. The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size. The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31). The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55). The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life. AUTHORS' CONCLUSIONS:This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.
Optimal teicoplanin dosage regimens for methicillin-resistant Staphylococcus aureus infections in endocarditis patients and renal failure patients.
Li Na,Zhu Liqin,Xu Gaoqi,Ge Tingyue,Qi Fang,Li Mengxue
Journal of chemotherapy (Florence, Italy)
This study aimed to assess whether traditional initial loading and maintenance doses of teicoplanin were appropriate in endocarditis and renal failure patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and to recommend optimal dosage regimens. Pharmacokinetic parameters and physicochemical properties of teicoplanin were performed to develop pharmacokinetic models using GastroPlus. Concentration-time curves of teicoplanin in endocarditis and renal failure patients with MRSA infections were simulated by changing clearance (CL) and volume of distribution of the central compartment (V). Different teicoplanin dosage regimens were assessed according to the target trough concentration, and optimal teicoplanin dosage regimens were recommended. Dosage regimen of four teicoplanin doses of 6 mg/kg q12 h followed by 6 mg/kg qd is recommended for renal failure patients infected by MRSA. And optimal dosage regimen is five teicoplanin doses of 15 mg/kg q12 h followed by doses of 12 mg/kg qd for endocarditis patients infected by MRSA.
Acute kidney injury during daptomycin versus vancomycin treatment in cardiovascular critically ill patients: a propensity score matched analysis.
Gaudard Philippe,Saour Marine,Morquin David,David Hélène,Eliet Jacob,Villiet Maxime,Daures Jean-Pierre,Colson Pascal
BMC infectious diseases
BACKGROUND:Gram-positive organisms are a leading cause of infection in cardiovascular surgery. Furthermore, these patients have a high risk of developing postoperative renal failure in intensive care unit (ICU). Some antibiotic drugs are known to impair renal function. The aim of the study was to evaluate whether patients treated for Gram-positive cardiovascular infection with daptomycin (DAP) experienced a lower incidence of acute kidney injury (AKI) when compared to patients treated with vancomycin (VAN), with comparable efficacy. METHODS:ICU patients who received either DAP or VAN, prior to or after cardiovascular surgery or mechanical circulatory support, from January 2010 to December 2012, were included in this observational retrospective cohort study. We excluded patients with end stage renal disease and antibiotic prophylaxis. The primary endpoint was the incidence of AKI within the first week of treatment. Secondary endpoints were the incidence of AKI within the first 14 days of treatment, the severity of AKI including renal replacement therapy (RRT), the rates of clinical failure (unsuccessful infection treatment) and of premature discontinuation and mortality. To minimize selection bias, we used a propensity score to compare the 2 groups. Univariate and multivariate analysis were performed to determine factors associated with AKI. RESULTS:Seventy two patients, treated for infective endocarditis, cardiovascular foreign body infection, or surgical site infection were included (DAP, n = 28 and VAN, n = 44). AKI at day 7 was observed in 28 (64%) versus 6 (21%) of the VAN and DAP patients, respectively (p = 0.001). In the multivariate analysis adjusted to the propensity score, vancomycin treatment was the only factor associated with AKI (Odds Ratio 4.42; 95% CI: 1.39-15.34; p = 0.014). RRT was required for 2 (7%) DAP patients and 13 (30%) VAN patients, p = 0.035. Premature discontinuation and clinical failure occurred more frequently in VAN group than in DAP group (25% versus 4%, p = 0.022 and 42% versus 12%, respectively, p = 0.027). CONCLUSIONS:Daptomycin appears to be safer than vancomycin in terms of AKI risk in ICU patients treated for cardiovascular procedure-related infection. Daptomycin could be considered as a first line treatment to prevent AKI in high-risk patients.
Successful treatment of acute renal failure secondary to complicated infective endocarditis by peritoneal dialysis: a case report.
Al-Osail Aisha M,Al-Zahrani Ibrahim M,Al-Abdulwahab Abdullah A,Alhajri Sarah M,Al-Osail Emad M,Al-Hwiesh Abdullah K,Al-Muhanna Fahad A
BMC research notes
BACKGROUND:Infective endocarditis is one of the most common infections among intravenous drug addicts. Its complications can affect many systems, and these can include acute renal failure. There is a scarcity of cases in the literature related to acute renal failure secondary to infective endocarditis treated with peritoneal dialysis. In this paper, the case of a 48-year-old Saudi male is reported, who presented with features suggestive of infective endocarditis and who developed acute kidney injury that was treated successfully with high tidal volume automated peritoneal dialysis. To our knowledge, this is the second report of such an association in the literature. CASE PRESENTATION:A 48-year-old Saudi gentleman diagnosed to have a glucose-6-phosphate dehydrogenase deficiency and hepatitis C infection for the last 9 years, presented to the emergency department with a history of fever of 2 days' duration. On examination: his temperature = 41 °C, there was clubbing of the fingers bilaterally and a pansystolic murmur in the left parasternal area. The results of the blood cultures and echocardiogram were supportive of the diagnosis of infective endocarditis, and the patient subsequently developed acute kidney injury, and his creatinine reached 5.2 mg/dl, a level for which dialysis is essential for the patient to survive. CONCLUSION:High tidal volume automated peritoneal dialysis is highly effective as a renal replacement therapy in acute renal failure secondary to infective endocarditis if no contraindication is present.
Update on endocarditis-associated glomerulonephritis.
Boils Christie L,Nasr Samih H,Walker Patrick D,Couser William G,Larsen Christopher P
Glomerulonephritis (GN) due to infective endocarditis (IE) is well documented, but most available data are based on old autopsy series. To update information, we now present the largest biopsy-based clinicopathologic series on IE-associated GN. The study group included 49 patients (male-to-female ratio of 3.5:1) with a mean age of 48 years. The most common presenting feature was acute kidney injury. Over half of the patients had no known prior cardiac abnormality. However, the most common comorbidities were cardiac valve disease (30%), intravenous drug use (29%), hepatitis C (20%), and diabetes (18%). The cardiac valve infected was tricuspid in 43%, mitral in 33%, and aortic in 29% of patients. The two most common infective bacteria were Staphylococcus (53%) and Streptococcus (23%). Hypocomplementemia was found in 56% of patients tested and ANCA antibody in 28%. The most common biopsy finding was necrotizing and crescentic GN (53%), followed by endocapillary proliferative GN (37%). C3 deposition was prominent in all cases, whereas IgG deposition was seen in <30% of cases. Most patients had immune deposits detectable by electron microscopy. Thus, IE-associated GN most commonly presents with AKI and complicates staphylococcal tricuspid valve infection. Contrary to infection-associated glomerulonephritis in general, the most common pattern of glomerular injury in IE-associated glomerulonephritis was necrotizing and crescentic glomerulonephritis.
Safety of treatment with high-dose daptomycin in 102 patients with infective endocarditis.
Durante-Mangoni Emanuele,Andini Roberto,Parrella Antonio,Mattucci Irene,Cavezza Giusi,Senese Alessandra,Trojaniello Claudia,Caprioli Roberta,Diana Maria Veronica,Utili Riccardo
International journal of antimicrobial agents
Daptomycin is commonly used at doses >6 mg/kg/day for various indications, including infective endocarditis (IE). A systematic assessment of skeletal muscle, renal, haematological, hepatic and pulmonary toxicity of high-dose daptomycin (HDD) in IE is lacking. A total of 102 IE patients treated with HDD were included in this non-comparative, observational, single-centre cohort study conducted from 2007 to 2014. The incidence, timing, severity and evolution of adverse events (AEs) were assessed. Patients had a median age of 61.5 years and a high prevalence of co-morbidities. Staphylococci were cultured in 87.2% of cases (62.2% meticillin-resistant). The median daptomycin dose was 8.2 mg/kg/day for a median of 20 days (range, 1-60 days). HDD was withdrawn due to AEs in 12 patients (11.8%). On-treatment death occurred in 4 cases (3.9%, none HDD-related). Muscle toxicity occurred in 15 patients in a median of 15 days after HDD starts, which was largely mild and reversible with ongoing HDD use. Mild renal toxicity was observed in 9 patients (8.8%) after a median of 12 days of HDD (RIFLE-Risk in 8, Injury in 1). A rise of peripheral blood eosinophils occurred in 16 patients (15.7%). There were three cases of eosinophilic interstitial pneumonia. Four patients (3.9%) had mild allergic or idiosyncratic reactions. No other hepatic or haematological AEs were observed. Our current experience with 102 patients suggests that HDD is safe in significantly ill IE patients with multiple co-morbidities. Muscle toxicity was clinically negligible. Most importantly, there was no significant renal toxicity. Eosinophils should be carefully monitored.
Outcome of dialysis-requiring acute kidney injury in patients with infective endocarditis: A nationwide study.
Petersen Jeppe Kofoed,Jensen Andreas Dalsgaard,Bruun Niels Eske,Kamper Anne-Lise,Butt Jawad Haider,Havers-Borgersen Eva,Chaudry Mavish S,Torp-Pedersen Christian,Køber Lars,Fosbøl Emil Loldrup,Østergaard Lauge
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:Infective endocarditis (IE) may be complicated by acute kidney injury, yet data on the use of dialysis and subsequent reversibility are sparse. METHODS:Using Danish nationwide registries, we identified patients with first-time IE from 2000 to 2017. Dialysis naïve patients were grouped into: those with and those without dialysis during admission with IE. Continuation of dialysis was followed one year post-discharge. Multivariable adjusted Cox proportional hazard analysis was used to examine one-year mortality for patients surviving IE according to use of dialysis. RESULTS:We included 7,307 patients with IE; 416 patients (5.7%) initiated dialysis treatment during admission with IE and these were younger, had more comorbidities and more often underwent cardiac valve surgery compared with non-dialysis patients (47.4% vs. 20.9%). In patients with both cardiac valve surgery and dialysis treatment (n=197), 153 (77.7%) initiated dialysis on- or after the date of surgery. The in-hospital mortality was 40.4% and 19.0% for patients with and without dialysis, respectively (p<0.0001). Of those who started dialysis and survived hospitalization, 21.6% continued dialysis treatment within one year after discharge. In multivariable adjusted analysis, dialysis during admission with IE was associated with an increased one-year mortality from IE discharge, HR=1.64 (95% CI: 1.21-2.23). CONCLUSION:In dialysis-naïve patients with IE, approximately 1 in 20 patients initiated dialysis treatment during admission with IE. Dialysis identified a high-risk group with an in-hospital mortality of 40% and an approximately 20% risk of continued dialysis. Those with dialysis during admission with IE showed worse long-term outcomes than those without.
Multicenter evaluation of the clinical outcomes of daptomycin with and without concomitant β-lactams in patients with Staphylococcus aureus bacteremia and mild to moderate renal impairment.
Moise Pamela A,Amodio-Groton Maria,Rashid Mohamad,Lamp Kenneth C,Hoffman-Roberts Holly L,Sakoulas George,Yoon Min J,Schweitzer Suzanne,Rastogi Anjay
Antimicrobial agents and chemotherapy
Patients with underlying renal disease may be vulnerable to vancomycin-mediated nephrotoxicity and Staphylococcus aureus bacteremia treatment failure. In light of recent data demonstrating the successful use of β-lactam plus daptomycin in very difficult cases of S. aureus bacteremia, we examined safety and clinical outcomes for patients who received daptomycin with or without concomitant β-lactams. We identified 106 patients who received daptomycin for S. aureus bacteremia, had mild or moderate renal insufficiency according to FDA criteria, and enrolled in the Cubicin Outcomes Registry and Experience (CORE), a multicenter registry, from 2005 to 2009. Daptomycin treatment success was 81%. Overall treatment efficacy was slightly enhanced with the addition of a β-lactam (87% versus 78%; P = 0.336), but this trend was most pronounced for bacteremia associated with endocarditis or bone/joint infection or bacteremia from an unknown source (90% versus 57%; P = 0.061). Factors associated with reduced daptomycin efficacy (by logistic regression) were an unknown source of bacteremia (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.55 to 37.2), moderate renal impairment (OR = 9.11; 95% CI = 1.46 to 56.8), and prior vancomycin failure (OR = 11.2; 95% CI = 1.95 to 64.5). Two patients experienced an increase in creatine phosphokinase (CPK) that resolved after stopping daptomycin. No patients developed worsening renal insufficiency related to daptomycin. In conclusion, daptomycin appeared to be effective and well tolerated in patients with S. aureus bacteremia and mild to moderate renal insufficiency. Daptomycin treatment efficacy might be enhanced with β-lactam combination therapy in primary endovascular and bone/joint infections. Additional studies will be necessary to confirm these findings.
Severity of gentamicin's nephrotoxic effect on patients with infective endocarditis: a prospective observational cohort study of 373 patients.
Buchholtz Kristine,Larsen Carsten T,Hassager Christian,Bruun Niels E
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:Gentamicin is often used to treat infective endocarditis (IE). Gentamicin is highly effective, but its applicability is reduced by its nephrotoxic effect. The aim of this study was to quantify the nephrotoxic effect of gentamicin and the association between the nephrotoxic effect and mortality in patients with IE. METHODS:A prospective observational cohort study was performed at 2 tertiary university hospitals in Copenhagen from October 2002 through October 2007; 373 consecutive patients with IE were included. A total of 287 (77%) of the patients received gentamicin treatment (median duration, 14 days); dosage was adjusted according to daily serum creatinine and trough serum gentamicin levels. Kidney function was determined by estimated endogenous creatinine clearance (EECC). Statistical correlation between gentamicin and EECC change was analyzed, and the association between mortality and nephrotoxicity was investigated. RESULTS:The primary bacteriological etiologies were as follows: Streptococcus species (37.1%), Staphylococcus aureus (18.2%), and Enterococcus species (16.1%). In the gentamicin group, the mean EECC change was an 8.6% decrease, but in the no-gentamicin group, the mean change was an increase of 2.3% (P = .05). The decrease in EECC was significantly correlated with the duration of gentamicin treatment: a 0.5% EECC decrease per day of gentamicin treatment (P = .002). The decrease in EECC during hospitalization was not related to postdischarge mortality. The mean duration of follow-up was 562 days. CONCLUSIONS:The nephrotoxic effect of gentamicin is directly related to treatment duration, with a decrease in EECC of 0.5% per day of gentamicin treatment. In patients treated with gentamicin, the in-hospital decrease in EECC was not related to postdischarge mortality. Consequently, this study does not support abolishment of gentamicin in treatment of IE.
[Clinical features and prognosis of infective endocarditis patients with acute kidney injury].
Zhang S Y,Li X H,Xiao F
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
OBJECTIVE:To investigate the clinical features and treatment of infective endocarditis (IE) patients with acute kidney injury (AKI), and to compare the adverse complications and outcome with IE patients without AKI. METHODS:Clinical data of 100 IE cases in Peking University First Hospital from January 2002 to June 2018 were retrospectively reviewed. The patients were divided into AKI group (n=21) and non-AKI group (n=79) based on the AKI network (AKIN) definition. The clinical data and prognosis were compared between the two groups. RESULTS:The incidence of AKI was 21%. The average age was (43.7±15.7) years, and the ratio of male to female was 3 ∶1. There was no significant difference in age and gender between the two groups. Compared with non-AKI group, the AKI group had more rash and lower limbs edema (P=0.017 and P=0.001), higher urine blood and protein positive rate (both P<0.001). Lower hemoglobin and serum albumin level (both P<0.001), worse clinical cardiac function (NYHA III-IV, P=0.033) were found in AKI group compared with non-AKI group. There was no significant difference in microbiologic positive rate and pathogenic bacteria sorts between the two groups. Nine patients refused surgery, and the other 91 cases underwent cardiac surgery with cardiopulmonary bypass under general anesthesia, including 19 cases of AKI group and 72 cases of non-AKI group. The ventilation time and intensive care unit (ICU) stay time were longer in AKI group than in non-AKI group (P=0.028 and P=0.003). AKI group needed more red blood cell transfusion (P=0.010). Using the last serum creatinine before surgery as basic level, there was more new-onset AKI cases in AKI group than in non-AKI group. During the median follow-up time 42 months, there was no significant difference in perioperative and follow-up mortality between the two groups (P=0.463 and P=0.581). CONCLUSION:More perioperation complications occurred in IE patients with AKI, but no significant difference in in-hospital and follow-up mortality between the AKI and non-AKI groups was observed.
2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM).
Habib Gilbert,Lancellotti Patrizio,Antunes Manuel J,Bongiorni Maria Grazia,Casalta Jean-Paul,Del Zotti Francesco,Dulgheru Raluca,El Khoury Gebrine,Erba Paola Anna,Iung Bernard,Miro Jose M,Mulder Barbara J,Plonska-Gosciniak Edyta,Price Susanna,Roos-Hesselink Jolien,Snygg-Martin Ulrika,Thuny Franck,Tornos Mas Pilar,Vilacosta Isidre,Zamorano Jose Luis,
European heart journal
Infective endocarditis: Clinical presentation, etiology, and early predictors of in-hospital case fatality.
Pilmis B,Mizrahi A,Laincer A,Couzigou C,El Helali N,Nguyen Van J-C,Abassade P,Cador R,Le Monnier A
Medecine et maladies infectieuses
OBJECTIVE:We aimed to assess the clinical presentation, microbial etiology and outcome of patients presenting with infective endocarditis (IE). PATIENTS AND METHODS:We conducted a four-year retrospective study including all patients presenting with IE. RESULTS:We included 121 patients in the study. The median age was 74.8years. Most patients had native valve IE (57%). Staphylococcus aureus accounted for 24.8% of all IE. Surgery was indicated for 70 patients (57.9%) but actually performed in only 55 (44.7%). Factors associated with surgery were younger age (P=0.002) and prosthetic valve IE (P=0.001). Risk factors associated with in-hospital mortality were diabetes mellitus (OR=3.17), chronic renal insufficiency (OR=6.62), and surgical indication (OR=3.49). Mortality of patients who underwent surgery was one sixth of that of patients with surgical indication who did not have the surgery (P<0.001).
Aetiology of renal failure in patients with infective endocarditis. The role of antibiotics.
Goenaga Sánchez Miguel Ángel,Kortajarena Urkola Xabier,Bouza Santiago Emilio,Muñoz García Patricia,Verde Moreno Eduardo,Fariñas Álvarez M Carmen,Teira Cobo Ramón,Pericás Pulido Juan Manuel,de Alarcón González Arístides,Sousa Regueiro Dolores,Ruiz Morales Josefa,Rodríguez-Álvarez Regino José,Antorrena Miranda Isabel,Iribarren Loyarte José Antonio,
BACKGROUND AND OBJECTIVES:The possible renal toxicity of certain antibiotics (AB) is well known. The objective of our work is to know the possible effect of AB treatments in the development of renal failure (RF) in patients with infective endocarditis (IE). MATERIAL AND METHOD:Collection from a national multi-centre registry of collection on renal function, both prior and its impairment, if any, during the treatment of IE and in relation to possible causative factors, including the use of AB. RESULTS:Between 2008 and 2012, 1,853 episodes of IE reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF. They developed new RF or impairment of renal function in 38.7% of the cases. In patients with prior RF, impairment was more frequent (64 vs. 31.7%, P<.001). Overall, patients with RF were older (70.6 vs. 67 years, P<.01), had more comorbidities (Charlson index 5 vs. 4, P<.01), and IE by Staphylococcus aureus (32.1 vs. 16.5%, P<.01). Potentially nephrotoxic AB use was only associated with RF in patients without prior RF (aminoglycosides: OR=1.47 [95% CI 1.096-1.988], P=.010; aminoglycosides with vancomycin: OR=1.49 [95% CI 1.069-2.09], P=.019). CONCLUSIONS:In patients without prior RF, the use of nephrotoxic AB is associated with impairment of renal function. In patients with RF prior to the IE episode, impairment of renal function was more frequent but appears to be more related to the severity of infection.
Long-term outcome of active infective endocarditis with renal insufficiency in cardiac surgery.
Tamura Kiyoshi,Arai Hirokuni,Yoshizaki Tomoya
Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia
BACKGROUND:The relation between infective endocarditis (IE) and renal insufficiency is uncertain. The aim of this study was to investigate active IE with renal insufficiency in cardiac surgery. PATIENTS AND METHODS:A retrospective record review was conducted of all cases with IE from January 1998 to July 2009. We identified 38 patients who had undergone surgical intervention (25 males and 13 females, mean age 57.3 ± 15.2 years, range 23-83 years) of IE as defined by the modified Duke criteria. Indications for surgical intervention included new, severe valvular regurgitation with heart failure, intracardiac abscesses, and recurrent embolic events. All patients were divided two groups; one group comprised patients without renal insufficiency (group N, n = 28), the other, those with renal insufficiency (group R, n = 10). RESULTS:Mean age of patients in group R was larger than that in of group N (66.3 ± 10.6 vs. 54.1 ± 15.4 years, p = 0.0268), and mean hemoglobin in group R than in group N (8.4 ± 0.9 vs. 10.3 ± 2.5 g/dl, p = 0.0215). In the early outcome, hospital death was greater in group R than in group N (20.0% vs. 0.0%, p = 0.0143). The 8-year survival was significantly worse in group R than in group N (50.0% vs. 96.4%, log rank test: p = 0.0042). Moreover, the 8-year actuarial freedom from cardiac events was significantly worse in group R than in group N (0.0% vs. 60.3%, log rank test: p = 0.0003), too. Renal insufficiency predicted an increase in long-term mortality (OR 12.104, 95%CI 1.349-108.641, p = 0.0259) and morbidity (OR 10.540, 95%CI 2.173-51.129, p = 0.0035). CONCLUSIONS:In IE, renal insufficiency may allow for risk stratification of patients undergoing surgical intervention.
Risk factors and short-term prognosis of preoperative renal insufficiency in infective endocarditis.
Liu Yang,Zhang Hang,Liu Yaoyang,Han Qingqi,Tang Yangfeng,Zhao Libo,Qiao Fan,Xu Zhiyun,Yu Min,Yuan Zhongxiang
Journal of thoracic disease
Background:The incidence of postoperative complications and the in-hospital mortality rate of infective endocarditis (IE) complicated with renal insufficiency are relatively high. This study aimed to analyze the clinical features, etiological characteristics, diagnosis and treatment, and prognosis of IE with renal insufficiency and to explore the risk factors for renal damage. Methods:IE patients undergoing valvular surgery between 2008 and 2017 in two cardiac centers were retrospectively analyzed. They were divided into renal insufficiency (RI) [endogenous creatinine clearance rate (Ccr) <60 mL/min/1.73 m] and normal renal function (NRF) (Ccr ≥60 mL/min/1.73 m) groups. The disease conditions at admission, etiology, treatment, and prognosis were compared between the two groups. Multivariate regression analysis was performed for the related factors. Results:A total of 8,055 cases of valvular surgery was performed during the study period. We analyzed 401 IE patients [average age 43.9±15 years; RI, n=56 (14%); NRF, n=345 (86%)], after the exclusion of 2 patients with primary glomerulonephritis. RI patients showed higher perioperative mortality (14.3% . 4.5%, P=0.042) and streptococcal infection (71.4% . 43.8%, P=0.001) rates. The RI group was also older and had worse heart function, greater decreases in hemoglobin and platelet levels, a higher rate of prosthetic valve involvement, more cases of postoperative dialysis, and worse prognosis (all P<0.05). Binary logistic multivariate regression analysis showed that the incidence of streptococcal infection [odds ratio (OR) =4.271, 95% confidence interval (CI), 1.846-9.884; P=0.001], age ≥51 years (OR =5.138, 95% CI, 2.258-11.694; P<0.001), and New York Heart Association (NYHA) functional class III-IV (OR =10.768, 95% CI, 2.417-47.972; P=0.002) were independent risk factors for preoperative renal insufficiency. Conclusions:IE patients with preoperative renal insufficiency had a high mortality rate and poor prognosis, with streptococcal infection predisposing to a higher risk of renal insufficiency. Moreover, older the age and worse heart function in IE resulted in a greater risk for renal insufficiency.
[Risk factors of acute kidney injury in hospitalized patients with infective endocarditis and their predictive values].
Zhang Wei,Xue Feng,Li Haina,Guan Chen,Xu Lingyu,Xu Yan
Zhonghua wei zhong bing ji jiu yi xue
OBJECTIVE:To analyze the risk factors of acute kidney injury (AKI) in hospitalized patients with infective endocarditis (IE), construct prediction model, and discuss its predictive value. METHODS:The clinical data of 402 adult inpatients diagnosed with IE admitted to the Affiliated Hospital of Qingdao University from January 2010 to January 2020 were retrospectively analyzed. The patients were divided into the AKI group and the non-AKI group. The clinical data, such as gender, age, presence of diabetes, basic estimated glomerular filtration rate (eGFR), laboratory indexes at admission, involvement of valves, presence of sepsis, medication during hospitalization, surgery and outcome of the two groups were compared. Multivariate Logistic regression analysis was used to screen the risk factors of AKI in IE inpatients. A predictive model was constructed, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of the model. RESULTS:A total of 290 patients with IE were enrolled, including 198 non-AKI patients and 92 AKI patients. The incidence of AKI was 31.7%. Among the 92 AKI patients, 46 patients were at AKI stage 1 (50.0%), while 46 patients were at AKI stage 2 and stage 3 (50.0%). Compared with the non-AKI group, patients in the AKI group were older [years old: 64 (55, 71) vs. 55 (46, 63)], and had lower basic eGFR (mL×min×1.73 m: 64.6±13.6 vs. 82.9±19.5), higher proportion of diabetic and incidence of sepsis (16.3% vs. 8.6%, 38.0% vs. 13.1%), more frequent use of angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists (ACEI/ARB), diuretics and non-steroidal anti-inflammatory drugs (NSAIDs; 25.0% vs. 15.2%, 82.6% vs. 63.1%, 58.7% vs. 24.2%), more abnormal urine test results (hematuria or proteinuria, 35.9% vs. 22.7%), higher pathogen culture negative rate (73.9% vs. 51.5%), lower Gram positive (G) cocci infection rate and surgery rate (22.8% vs. 40.4%, 60.9% vs. 81.8 %), with significant differences (all P < 0.05). There were no significant differences in the gender, number and location of involved valves, and laboratory indexes at admission between the two groups. Compared with the non-AKI group, the inpatient mortality rate of the AKI group was higher (30.4% vs. 8.6%, P < 0.01), and the inpatient mortality rate of patients with AKI stage 2 and stage 3 was significantly higher than that of patients with AKI stage 1 (43.5% vs. 17.4%, P < 0.01). In multivariate Logistic regression analysis, the lower basic eGFR [hazard ratio (HR) = 0.136, 95% confidence interval (95%CI) was 0.066-0.280], sepsis (HR = 6.100, 95%CI was 2.394-15.543), demand for NSAIDs (HR = 2.990, 95%CI was 1.184-7.546) and radiocontrast agent (HR = 3.153, 95%CI was 1.207-8.238) were independent risk factors for AKI in hospitalized patients with IE (all P < 0.05). A prediction model was constructed based on the above risk factors, and ROC curve analysis showed that the area under the ROC curve (AUC) of prediction model for AKI was 0.888 (95%CI was 0.833-0.943, P < 0.01) with sensitivity of 86.4% and specificity of 80.9%. CONCLUSIONS:In the IE-susceptible population, low basic eGFR, sepsis, the need for NSAIDs and contrast agent are independent risk factors to AKI. The predictive model constructed by the above risk factors has certain predictive value for the occurrence of AKI in the IE inpatients.
Acute kidney injury in infective endocarditis: A retrospective analysis.
Gagneux-Brunon A,Pouvaret A,Maillard N,Berthelot P,Lutz M F,Cazorla C,Tulane C,Fuzellier J F,Verhoeven P O,Frésard A,Duval X,Lucht F,Botelho-Nevers E
Medecine et maladies infectieuses
BACKGROUND:Acute kidney injury (AKI) is associated with high case fatality in infective endocarditis (IE), but epidemiological data on the frequency of AKI during IE is scarce. We aimed to describe the frequency and risk factors for AKI during the course of IE using Kidney Disease: Improving Global Outcomes consensual criteria. METHODS:Using the French hospital discharge database (French acronym PMSI), we retrospectively reviewed the charts of 112 patients presenting with a first episode of probable or definite IE between January 2010 and May 2015. RESULTS:Seventy-seven patients (68.8%) developed AKI. In univariate analysis, risk factors for AKI were cardiac surgery for IE (n=29, 37.7% vs. n=4, 1.4%, P<0.0005), cardiac failure (n=29, 36.7% vs. n=1, 2.9%, P<0.0005), diabetes mellitus (n=14, 18.2% vs. n=1, 0.9%, P=0.034), and prosthetic valve IEs (n=24, 31.2% vs. n=4, 11.4%). No differences were observed for gentamicin exposure (n=57, 64% vs. n=32, 86.5%, P=0.286). Prosthetic valve IE, cardiac failure, and vancomycin exposure were independently associated with AKI with respective odds ratio of 5.49 (95% CI 1.92-17.9), 4.37 (95% CI 4.37-465.7), and 1.084 (1.084-16.2). Mean length of hospital stay was significantly longer in patients presenting with AKI than in controls (respectively 52.4±22.1 days vs. 39.6±12.6, P<0.005). CONCLUSION:AKI is very frequent during IE, particularly in patients with prosthetic valve IE, cardiac failure, and those receiving vancomycin.