Antibiotic regimens for secondary peritonitis of gastrointestinal origin in adults.
Wong P F,Gilliam A D,Kumar S,Shenfine J,O'Dair G N,Leaper D J
The Cochrane database of systematic reviews
BACKGROUND:Secondary peritonitis is associated with a high mortality rate and if not treated successfully leads to development of abscesses, severe sepsis and multi-organ failure. Source control and adjunctive antibiotics are the mainstay of treatment. However, no conclusive evidence suggest that one antibiotic regimen is better than any other but at the same time have a lower toxicity. OBJECTIVES:To ascertain the efficacy and adverse effects of different antibiotic regimens in treating intra-abdominal infections in adults. Outcomes were divided into primary (clinical success and effectiveness in reducing mortality) and secondary (microbiological success, preventing wound infection, intra-abdominal abscess, clinical sepsis, remote infection, superinfection, adverse reactions, duration of treatment required, effectiveness in reducing hospitalised stay, and time to defervescence). SEARCH STRATEGY:We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 4, 2004), MEDLINE (from 1966 to November 2004), EMBASE (from 1980 to November 2004) and Cochrane Colorectal Cancer Group specialised register SR-COLOCA. Bibliographies of identified studies were screened for further relevant trials. SELECTION CRITERIA:Randomised and quasi-randomised controlled trials comparing different antibiotic regimens in the treatment of secondary peritonitis in adults were selected. Trials reporting gynaecological or traumatic peritonitis were excluded from this review. Ambiguity regarding suitability of trials were discussed among the review team. DATA COLLECTION AND ANALYSIS:Six reviewers independently assessed trial quality and extracted data. Data collection was standardised using data collection form to ensure uniformity among reviewers. Statistical analyses were performed using the random effects model and the results expressed as odds ratio for dichotomous outcomes, or weight mean difference for continuous data with 95% confidence intervals. MAIN RESULTS:Fourty studies with 5094 patients met the inclusion criteria. Sixteen different comparative antibiotic regimens were reported. All antibiotics showed equivocal comparability in terms of clinical success. Mortality did not differ between the regimens. Despite the potential high toxicity profile of regimens using aminoglycosides, this was not demonstrated in this review. The reason for this could be the inherent bias within clinical trials in the form of patient selection and stringency in monitoring drug levels. AUTHORS' CONCLUSIONS:No specific recommendations can be made for the first line treatment of secondary peritonitis in adults with antibiotics, as all regimens showed equivocal efficacy. Other factors such as local guidelines and preferences, ease of administration, costs and availability must therefore be taken into consideration in deciding the antibiotic regimen of choice. Future trials should attempt to stratify patients and perform intention-to-treat analysis to allow better external validity.
Factors Associated with the Development of Tertiary Peritonitis in Critically Ill Patients.
Ballus Josep,Lopez-Delgado Juan C,Sabater-Riera Joan,Perez-Fernandez Xose L,Betbese Antoni J,Roncal Joan A
BACKGROUND:Critically ill surgical patients remain at a high risk of adverse outcomes as a result of secondary peritonitis (SP). The risk is even higher if tertiary peritonitis (TP) develops. Factors related to the development of TP, however, are scarce in the literature. The main aim of our study was to identify factors associated with the development of TP in patients with SP in the intensive care unit (ICU), and also to report differences in microbiologic patterns and antibiotic therapy in patients with the two conditions. PATIENTS AND METHODS:A prospective, observational study was conducted at our institution from 2010 to 2014. Baseline characteristics on admission, outcomes, microbiologic results, and antibiotic therapy were recorded for analysis. RESULTS:We included 343 patients with SP, of whom TP developed in 185 (53.9%). Almost two-thirds (64.4%) were male; mean age was 63.7 ± 14.3 years, and mean APACHE was 19.4 ± 7.8. In-hospital death was 42.6% (146). Multivariable analysis showed that longer ICU stay (odds ratio [OR]: 1.019; 95% confidence interval [CI]: 1.004-1.034; p = 0.010), urgent operation on hospital admission (OR: 3.247; 95% CI: 1.392-7.575; p = 0.006), total parenteral nutrition (TPN) (OR: 3.079; 95% CI: 1.535-6.177; p = 0.002) and stomach-duodenum as primary infection site (OR: 4.818; 95% CI: 1.429-16.247; p = 0.011) were factors associated with the development of TP, whereas patients with localized peritonitis were less prone to have TP develop (OR: 0.308; 95% CI: 0.152-0.624; p = 0.001). Higher incidences of Candida spp. (OR: 1.275; 95% CI: 1.096-1.789; p = 0.016), Enterococcus faecium (OR: 1.085; 95% CI: 1.018-1.400; p = 0.002), and Enterococcus spp. (OR: 1.370; 95% CI: 1.139-1.989; p = 0.047) were found in TP, and higher rates of cephalosporin use in SP (OR: 3.51; 95% CI: 1.139-10.817; p = 0.035). CONCLUSIONS:Complicated peritonitis remains a cause of a high numbers of deaths in the ICU. The need for TPN, urgent operation on hospital admission, and particularly surgical procedures in the proximal gastrointestinal tract were factors associated with development of TP and may potentially help to identify patients with SP at risk for development of TP. Physicians should be aware concerning multi-drug-resistant germs when treating these patients.
Initial microbial spectrum in severe secondary peritonitis and relevance for treatment.
van Ruler O,Kiewiet J J S,van Ketel R J,Boermeester M A,
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
This study aims to determine whether abdominal microbial profiles in early severe secondary peritonitis are associated with ongoing infection or death. The study is performed within a randomized study comparing two surgical treatment strategies in patients with severe secondary peritonitis (n = 229). The microbial profiles of cultures retrieved from initial emergency laparotomy were tested with logistic regression analysis for association with 'ongoing infection needing relaparotomy' and in-hospital death. No microbial profile or the presence of yeast or Pseudomonas spp. was related to the risk of ongoing infection needing relaparotomy. Resistance to empiric therapy for gram positive cocci and coliforms was moderately associated with ongoing abdominal infection (OR 3.43 95%CI 0.95-12.38 and OR 7.61, 95%CI 0.75-76.94). Presence of only gram positive cocci, predominantly Enterococcus spp, was borderline independently associated with in-hospital death (OR 3.69, 95%CI 0.99-13.80). In secondary peritonitis microbial profiles do not predict ongoing abdominal infection after initial emergency laparotomy. However, the moderate association of ongoing infection with resistance to the empiric therapy compels to more attention for resistance when selecting empiric antibiotic coverage.
Efficacy and safety of moxifloxacin in hospitalized patients with secondary peritonitis: pooled analysis of four randomized phase III trials.
De Waele Jan J,Tellado Jose M,Weiss Günter,Alder Jeffrey,Kruesmann Frank,Arvis Pierre,Hussain Tajamul,Solomkin Joseph S
BACKGROUND:Secondary peritonitis is an advanced form of complicated intra-abdominal infection (cIAI) requiring hospitalization, surgical source control, and empiric antibiotic therapy against causative aerobic and anaerobic bacteria. METHODS:This pooled analysis of four prospective, active-controlled randomized clinical trials compared the efficacy and safety of moxifloxacin with that of comparator antibiotics in patients with confirmed secondary peritonitis. The primary efficacy endpoint was clinical success rate at test-of-cure (TOC) between day 10 and 45 post-therapy in the per-protocol (PP) population. Safety and clinical efficacy were assessed also in the intent-to-treat population (ITT). Bacteriological success was assessed at TOC in the microbiologically-valid population as a secondary efficacy endpoint. RESULTS:Overall clinical success rates at TOC were 85.3% (431 of 505 patients) in the moxifloxacin and 88.4% (459 of 519 patients) in the comparator treatment groups (PP population, point estimate for the difference in success rates: -3.0%; 95% CI -7.06%, 1.05%), respectively. Similar clinical success rates between moxifloxacin and comparators were observed by anatomical site of infection, and ranged from 80.6% to 100% for moxifloxacin and from 71.4% to 96.6% for comparators, respectively. Bacteriologic success rates were similar with moxifloxacin (82.4%) and comparators (86.8%), respectively. The proportion of patients experiencing any treatment-emergent adverse events was slightly higher with moxifloxacin (67.3%) versus comparators (59.8%). Rates of drug-related adverse events (20.9% versus 20.0%) and deaths (4.3% versus 3.4%) were similar in moxifloxacin and comparator groups; none of the deaths were drug-related. CONCLUSIONS:The data suggests that once-daily IV (or IV/PO) moxifloxacin has a comparable efficacy and safety profile to antibiotic regimens approved previously in the subgroup of patients with secondary peritonitis of mild-to-moderate severity.
[Surgical therapy of peritonitis].
Strobel O,Werner J,Büchler M W
Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen
Despite significant progress the therapy of peritonitis remains challenging. With a mortality of up to 20% peritonitis is a predominant cause of death due to surgical infections. An early and efficient source control combined with effective antibiotic therapy and modern intensive care and sepsis therapy are definitive for the outcome and prognosis of secondary peritonitis. In approximately 90% of patients an effective source control can be achieved by one single operation with extensive peritoneal lavage. A reoperation is necessary in only about 10% of patients. The aggressive concepts of planned relaparotomy or open packing are associated with increased morbidity and are indicated only in rare cases. The gold standard is to attempt a definitive source control by one single operation. An operative revision should be performed only on demand. The antibiotic therapy should begin with a broadly calculated empirical therapy and should later be adapted to microbiological findings. The therapy of sepsis requires standardized and state of the art intensive care.
Comparison of on-demand vs planned relaparotomy strategy in patients with severe peritonitis: a randomized trial.
van Ruler Oddeke,Mahler Cecilia W,Boer Kimberly R,Reuland E Ascelijn,Gooszen Hein G,Opmeer Brent C,de Graaf Peter W,Lamme Bas,Gerhards Michael F,Steller E Philip,van Till J W Olivier,de Borgie Corianne J A M,Gouma Dirk J,Reitsma Johannes B,Boermeester Marja A,
CONTEXT:In patients with severe secondary peritonitis, there are 2 surgical treatment strategies following an initial emergency laparotomy: planned relaparotomy and relaparotomy only when the patient's condition demands it ("on-demand"). The on-demand strategy may reduce mortality, morbidity, health care utilization, and costs. However, randomized trials have not been performed. OBJECTIVE:To compare patient outcome, health care utilization, and costs of on-demand and planned relaparotomy. DESIGN, SETTING, AND PATIENTS:Randomized, nonblinded clinical trial at 2 academic and 5 regional teaching hospitals in the Netherlands from November 2001 through February 2005. Patients had severe secondary peritonitis and an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 11 or greater. INTERVENTION:Random allocation to on-demand or planned relaparotomy strategy. MAIN OUTCOME MEASURES:The primary end point was death and/or peritonitis-related morbidity within a 12-month follow-up period. Secondary end points included health care utilization and costs. RESULTS:A total of 232 patients (116 on-demand and 116 planned) were randomized. One patient in the on-demand group was excluded due to an operative diagnosis of pancreatitis and 3 in each group withdrew or were lost to follow-up. There was no significant difference in primary end point (57% on-demand [n = 64] vs 65% planned [n = 73]; P = .25) or in mortality alone (29% on-demand [n = 32] vs 36% planned [n = 41]; P = .22) or morbidity alone (40% on-demand [n = 32] vs 44% planned [n = 32]; P = .58). A total of 42% of the on-demand patients had a relaparotomy vs 94% of the planned relaparotomy group. A total of 31% of first relaparotomies were negative in the on-demand group vs 66% in the planned group (P <.001). Patients in the on-demand group had shorter median intensive care unit stays (7 vs 11 days; P = .001) and shorter median hospital stays (27 vs 35 days; P = .008). Direct medical costs per patient were reduced by 23% using the on-demand strategy. CONCLUSION:Patients in the on-demand relaparotomy group did not have a significantly lower rate of death or major peritonitis-related morbidity compared with the planned relaparotomy group but did have a substantial reduction in relaparotomies, health care utilization, and medical costs. TRIAL REGISTRATION:http://isrctn.org Identifier: ISRCTN51729393.
Surgical treatment of secondary peritonitis : A continuing problem.
van Ruler O,Boermeester M A
Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen
Secondary peritonitis remains associated with high mortality and morbidity rates. Treatment of secondary peritonitis is challenging even in modern medicine. Surgical intervention for source control remains the cornerstone of treatment, beside adequate antimicrobial therapy and resuscitation. A randomized clinical trial showed that relaparotomy on demand (ROD) after initial emergency surgery is the preferred treatment strategy, irrespective of the severity and extent of peritonitis. The effective and safe use of ROD requires intensive monitoring of the patient in a setting where diagnostic tests and decision making about relaparotomy are guaranteed round the clock. The lack of knowledge on timely and adequate patient selection, together with the lack of use of easy but reliable monitoring tools, seems to hamper full implementation of ROD. The accuracy of the relap decision tool is reasonable for prediction of ongoing peritonitis and selection for computer tomography (CT). The value of CT in an early postoperative phase is unclear. Future research and innovative technologies should focus on the additive value of CT in cases of operated secondary peritonitis and on the further optimization of bedside prediction tools to enhance adequate patient selection for intervention in a multidisciplinary setting.
Antibiotic sensitivity in correlation to the origin of secondary peritonitis: a single center analysis.
Grotelüschen Rainer,Heidelmann Lena M,Lütgehetmann Marc,Melling Nathaniel,Reeh Matthias,Ghadban Tarik,Dupree Anna,Izbicki Jakob R,Bachmann Kai A
Despite improvements in diagnosis, intensive-care medicine and surgical technique, the mortality of patients with secondary peritonitis is still high. Early and aggressive empiric antibiotic treatment has strong impact on the outcome. This retrospective study investigates bacterial and fungal pathogens and their antibiotic sensitivity in patients with secondary peritonitis. All patients that underwent emergency laparotomy due to secondary peritonitis at the Department of Surgery, University Medical Center Hamburg-Eppendorf between 2005 and 2015 were reviewed and overall 414 patients were included. We correlated the intra-abdominal localization of the organ perforation with intraoperative microbiological findings and corresponding sensitivities to relevant antibiotics. Overall, the most common findings were Escherichia coli (39%) and other Enterobacterica (24%). Depending on the location of the perforation, Cefuroxime/Metronidazole and Cefutaxime/Metronidazole were effective (based on in vitro susceptibility testing) in only 55-73% of the patients, while Meropenem/Vancomycin was able to control the peritonitis in more than 98% of the patients; independent of the location. Besides early source control, appropriate empiric treatment plays a pivotal role in treatment of secondary peritonitis. We are able to show that the frequently used combinations of second or third generation Cephalosporins with Metronidazole are not always sufficient, which is due to the biological resistance of the bacteria. Further clinical studies are needed to determine whether calculated use of broad-spectrum antibiotics with a sensitivity rate > 99%, such as Carbapenem plus Vancomycin, can improve overall survival rates in critically ill patients with secondary peritonitis.
[Septic peritonitis: etiology, pathophysiology, and diagnosis].
Ragetly G R,Bennett R A,Ragetly C A
Tierarztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
Septic peritonitis is an inflammatory condition of the peritoneum that occurs secondary to microbial contamination. This clinically important condition has a wide variety of clinical courses as well as high morbidity and mortality due to secondary multiorgan dysfunction. This article reviews the etiology and pathophysiology of this condition and its diagnosis in small animals; a companion article addresses treatment and prognosis.
Martín Luis García-Sancho
Anales de la Real Academia Nacional de Medicina
Tertiary peritonitis is an intraabdominal infection that arises in some patients with secondary peritonitis, despite receiving appropriate treatment. Recently described, it is a syndrome of late peritonitis and we are still lacking a precise and widely adopted definition. Diagnosis is difficult and treatment is complex. Among other therapeutic efforts, this entity requires early and repeated surgical treatment, either on demand or scheduled laparotomy, or even laparostomy. Prognosis is poor, and mortality can reach up to 60% of patients. We present the most interesting aspects of this disease.
[Relaparotomy in secondary peritonitis Planned relaparotomy or relaparotomy on demand?].
Lamme B,Mahler C W,van Till J W O,van Ruler O,Gouma D J,Boermeester M A
Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen
Secondary peritonitis is associated with serious morbidity and a persistent high mortality in recent decades, this despite improvement in antibiotic, intensive care and surgical treatment. The available literature regarding the surgical treatment of secondary peritonitis was searched through Pubmed (1966- January 2005) as well as a hand search of references of retrieved articles. Definitions, pathophysiology and classification of secondary peritonitis are discussed, as well as the scientific rationale for the surgical treatment in secondary peritonitis. The historical development and the scientific foundation of present-day relaparotomy strategies in secondary peritonitis are evaluated, with an emphasis on two frequently applied surgical treatment strategies: planned relaparotomy and relaparotomy on demand. Criteria for relaparotomy after the initial laparotomy and potential areas for further research to reduce both morbidity and mortality are discussed. Furthermore, the care of patients with secondary peritonitis is evolving from a surgical entity to a more multidisciplinary challenge uniting surgeons, intensivists, radiologists and microbiologists. Research needs to be expanded into novel fields to further decrease morbidity and mortality.
The innate immune response to secondary peritonitis.
van Till J W Olivier,van Veen Suzanne Q,van Ruler Oddeke,Lamme Bas,Gouma Dirk J,Boermeester Marja A
Shock (Augusta, Ga.)
Secondary peritonitis continues to cause high morbidity and mortality despite improvements in medical and surgical therapy. This review combines data from published literature, focusing on molecular patterns of inflammation in pathophysiology and prognosis during peritonitis. Orchestration of the innate immune response is essential. To clear the microbial infection, activation and attraction of leukocytes are essential and beneficial, just like the expression of inflammatory cytokines. Exaggeration of these inflammatory systems leads to tissue damage and organ failure. Nonsurvivors have increased proinflammation, complement activation, coagulation, and chemotaxis. In these patients, anti-inflammatory systems are decreased in blood and lungs, whereas the abdominal compartment shows decreased neutrophil activation and decreased or stationary chemokine and cytokine levels. A later down-regulation of proinflammatory mediators with concomitant overexpression of anti-inflammatory mediators leads to immunoparalysis and failure to clear residual bacterial load, resulting in the occurrence of superimposed infections. Thus, in patients with adverse outcome, the inflammatory reaction is no longer contained within the abdomen, and the inflammatory response has shifted to other compartments. For the understanding of the host response to secondary peritonitis, it is essential to realize that the defense systems presumably are expressed differently and, in part, autonomously in different compartments.
Organ dysfunction and long term outcome in secondary peritonitis.
Hynninen M,Wennervirta J,Leppäniemi A,Pettilä V
Langenbeck's archives of surgery
BACKGROUND AND AIMS:Secondary peritonitis is still associated with high mortality, especially when multiorgan dysfunction complicates the disease. Good prognostic tools to predict long term outcome in individual patients are lacking and therefore require further study. PATIENTS AND METHODS:163 consecutive patients with secondary peritonitis were included, except those with postoperative or traumatic peritonitis. In 58 patients treated in the intensive care unit (ICU), organ dysfunction was quantified using Sequential Organ Failure Assessment (SOFA) score in the first 4 days. Predictive factors for poor outcome were evaluated in all patients. Hospital and 1-year mortality was assessed. RESULTS:Hospital mortality was 19% and 1-year mortality 23%. Acute physiology and chronic health evaluation II (APACHE II), previous functional status, and sepsis category were predictive of fatal outcome in the total cohort (p = 0.034, p < 0.001, and p < 0.001). In patients treated in the ICU, advanced age and admission SOFA score were independent predictors of death (p = 0.014, p < 0.0001). The SOFA score showed the best discriminative ability for poor outcome (AuROC 0.78). CONCLUSION:Degree of organ dysfunction measured using SOFA score was the best predictor of hospital mortality in patients suffering from secondary peritonitis.
Secondary Peritonitis and Intra-Abdominal Sepsis: An Increasingly Global Disease in Search of Better Systemic Therapies.
Clements T W,Tolonen M,Ball C G,Kirkpatrick A W
Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society
Secondary peritonitis and intra-abdominal sepsis are a global health problem. The life-threatening systemic insult that results from intra-abdominal sepsis has been extensively studied and remains somewhat poorly understood. While local surgical therapy for perforation of the abdominal viscera is an age-old therapy, systemic therapies to control the subsequent systemic inflammatory response are scarce. Advancements in critical care have led to improved outcomes in secondary peritonitis. The understanding of the effect of secondary peritonitis on the human microbiome is an evolving field and has yielded potential therapeutic targets. This review of secondary peritonitis discusses the history, classification, pathophysiology, diagnosis, treatment, and future directions of the management of secondary peritonitis. Ongoing clinical studies in the treatment of secondary peritonitis and the open abdomen are discussed.