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The Cochrane Database of Systematic... Jan 2014Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy.
OBJECTIVES
Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics.
SEARCH METHODS
In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004.
SELECTION CRITERIA
We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis.
DATA COLLECTION AND ANALYSIS
The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible.
MAIN RESULTS
We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons.We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies.
AUTHORS' CONCLUSIONS
The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.
Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cause of Death; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Randomized Controlled Trials as Topic; beta-Lactams
PubMed: 24395715
DOI: 10.1002/14651858.CD003344.pub3 -
Acta Gastro-enterologica Belgica Jun 2013Hydatidosis is not uncommon in Western Europe, mainly due to the presence of immigrants from endemic countries, and hepato-gastroenterologist must then be able to manage... (Review)
Review
Hydatidosis is not uncommon in Western Europe, mainly due to the presence of immigrants from endemic countries, and hepato-gastroenterologist must then be able to manage this infectious disease. The hepatic hydatidosis is due to development in the liver of the larvae of Echinococcus granulosus that causes liver cysts. It can grow in size throughout the years and can give rise to complications, mainly pain, super-infection or cyst rupture. Recent progresses in imaging modalities play an important role in diagnosis, classification and evaluation of response to treatment of the cysts. Imaging techniques led to both Gharbi's and WHO's classifications. Those can provide markers of cyst activity and can help to determine the best therapeutic strategy. By combining two immunodiagnostic techniques, the diagnostic accuracy of laboratory tests is excellent. During the last decade, treatment has improved : the main therapeutic modality in the past was surgery, until the discovery of PAIR procedure (Puncture, Aspiration, Injection, Re-aspiration). Albendazole also plays an important role in the treatment of hydatid cysts either alone or as a pre-procedure or post procedure prophylaxis. This review will cover the major aspects of the disease emphasizing the recent diagnostic and therapeutic advances.
Topics: Animals; Diagnosis, Differential; Disease Management; Echinococcosis, Hepatic; Echinococcus; Gastroenterology; Global Health; Humans; Incidence; Liver; Practice Guidelines as Topic
PubMed: 23898558
DOI: No ID Found -
The Cochrane Database of Systematic... Jun 2013Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum beta-lactams have been introduced as single treatment, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum beta-lactams have been introduced as single treatment, and classically, a combination of a beta-lactam with an aminoglycoside has been used.
OBJECTIVES
To compare beta-lactam monotherapy versus beta-lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia.
SEARCH METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing any beta-lactam antibiotic monotherapy with any combination of a beta-lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed.
DATA COLLECTION AND ANALYSIS
Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors.
MAIN RESULTS
Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same beta-lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different beta-lactams-usually a broad-spectrum beta-lactam compared with a narrower-spectrum beta-lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same beta-lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different beta-lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials.
AUTHORS' CONCLUSIONS
Beta-lactam monotherapy is advantageous compared with beta-lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.
Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Cause of Death; Child; Combined Modality Therapy; Humans; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic; beta-Lactams
PubMed: 23813455
DOI: 10.1002/14651858.CD003038.pub2 -
The Cochrane Database of Systematic... Mar 2013Intravenous broad-spectrum antibiotics are indicated for the treatment of severe infections. However, the emergence of infections caused by multi-drug resistant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intravenous broad-spectrum antibiotics are indicated for the treatment of severe infections. However, the emergence of infections caused by multi-drug resistant organisms in conjunction with a lack of novel antibiotics has prompted the investigation of alternative dosing strategies to improve clinical efficacy and tolerability. To optimise pharmacokinetic and pharmacodynamic antibiotic parameters, continuous antibiotic infusions have been compared to traditional intermittent antibiotic infusions.
OBJECTIVES
To compare the clinical efficacy and safety of continuous intravenous administration of concentration-dependent and time-dependent antibiotics to traditional intermittent intravenous administration in adults with severe acute bacterial infections.
SEARCH METHODS
The following electronic databases were searched in September 2012: The Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S). The reference lists of all relevant material, the Internet and the trials registry www.clinicaltrials.gov for completed and ongoing trials were also searched.
SELECTION CRITERIA
Randomized controlled trials in adults with a bacterial infection requiring intravenous antibiotic therapy comparing continuous versus intermittent infusions of antibiotics were included. Both time-dependent and concentration-dependent antibiotics were considered.
DATA COLLECTION AND ANALYSIS
Three independent authors performed data extraction for the included studies. All data was cross-checked and disagreements resolved by consensus. An intention to treat analysis was conducted using a random-effects model.
MAIN RESULTS
Twenty-nine studies met inclusion criteria with a combined total of over 1,600 patients. The majority of included studies were judged to be at unclear or high risk of bias with regard to randomisation sequence generation, allocation concealment, blinding, management of incomplete outcome data, selective outcome reporting, and other potential threats to validity. No studies were judged to be at low risk of bias for all methodological quality items assessed. There were no differences in all-cause mortality (n=1241, RR 0.89, 95% CI 0.67 - 1.20, p=0.45), infection recurrence (n=398, RR 1.22, 95% CI 0.35 - 4.19, p=0.76), clinical cure (n=975, RR 1.00, 95% CI 0.93 - 1.08, p=0.98), and superinfection post-therapy (n=813, RR 1.08, 95% CI 0.60 - 1.94, p=0.79). There were no differences in safety outcomes including adverse events (n=575, RR 1.02, 95% CI 0.94 - 1.12, p=0.63), serious adverse events (n=871, RR 1.36, 95% CI 0.80 - 2.30, p=0.26), and withdrawal due to adverse events (n=871, RR 2.03, 95% CI 0.52 - 7.95, p=0.31). A difference was observed in the subgroup analyses of clinical cure in septic versus non-septic patients, where intermittent antibiotic infusions were favoured for clinical cure in septic patients. However, this effect was not consistent between random-effects and fixed-effects analyses. No differences were found in sensitivity analyses conducted.
AUTHORS' CONCLUSIONS
There were no differences in mortality, infection recurrence, clinical cure, superinfection post-therapy, and safety outcomes when comparing continuous infusions of intravenous antibiotics to traditional intermittent infusions of antibiotics. However, the wide confidence intervals suggest that beneficial or harmful effects cannot be ruled out for all outcomes. Therefore, the current evidence is insufficient to recommend the widespread adoption of continuous infusion antibiotics in the place of intermittent infusions of antibiotics. Further large prospective randomised trials, with consistent and complete reporting of clinical outcome measures, conducted with concurrent pharmacokinetic and pharmacodynamic studies in special populations are required to determine whether adoption of continuous antibiotic infusions is warranted in specific circumstances.
Topics: Acute Disease; Adult; Anti-Bacterial Agents; Bacterial Infections; Humans; Infusions, Intravenous; Randomized Controlled Trials as Topic; Recurrence
PubMed: 23543565
DOI: 10.1002/14651858.CD008481.pub2 -
The Cochrane Database of Systematic... Nov 2010Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia.
OBJECTIVES
To compare the effectiveness of different anti-pseudomonal beta-lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta-lactams.
SEARCH STRATEGY
We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to another antipseudomonal beta-lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients.
DATA COLLECTION AND ANALYSIS
Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all-cause mortality. Risk of bias was assessed using a domain-based evaluation and its effect of results was assessed through sensitivity analyses.
MAIN RESULTS
Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile.
AUTHORS' CONCLUSIONS
Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.
Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Fever; Humans; Imipenem; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Thienamycins; beta-Lactams
PubMed: 21069685
DOI: 10.1002/14651858.CD005197.pub3 -
The Cochrane Database of Systematic... May 2010Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of prophylactic antibiotics raises concerns about antibiotic resistance and fungal infection.
OBJECTIVES
To determine the efficacy and safety of prophylactic antibiotics in acute pancreatitis complicated by CT proven pancreatic necrosis.
SEARCH STRATEGY
Searches were updated in November 2008, in The Cochrane Library (Issue 2, 2008), MEDLINE, EMBASE, and CINAHL. Conference proceedings and references from found articles were also searched.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis.
DATA COLLECTION AND ANALYSIS
Primary outcomes were mortality and pancreatic infection rates. Secondary end-points included non pancreatic infection, all sites infection, operative rates, fungal infections, and antibiotic resistance. Subgroup analyses were performed for antibiotic regimen (beta-lactam, quinolone, and imipenem).
MAIN RESULTS
Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance.With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84).
AUTHORS' CONCLUSIONS
No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.
Topics: Acute Disease; Antibiotic Prophylaxis; Bacterial Infections; Humans; Necrosis; Pancreas; Pancreatitis; Pancreatitis, Acute Necrotizing; Randomized Controlled Trials as Topic; Superinfection
PubMed: 20464721
DOI: 10.1002/14651858.CD002941.pub3 -
Revista Espanola de Quimioterapia :... Mar 2005The aim of this study was to analyze the effect of using different antibiotics on the risk of acquiring a bacterial or fungal superinfection in hospital-acquired... (Comparative Study)
Comparative Study Review
The aim of this study was to analyze the effect of using different antibiotics on the risk of acquiring a bacterial or fungal superinfection in hospital-acquired infections. A systematic review of the literature using the PubMed (Medline) database from January 1990 to December 2003 was performed. We selected only those studies with at least 25 patients in each arm in which the clinical efficacy of several antibiotics (third generation cephalosporins, fluorquinolones, piperacillin-tazobactam and carbapenems) were evaluated for the treatment of severe infections, and which specifically reported the rate of superinfection. The microorganisms most frequently implicated in the development of superinfection were: Candida spp. (42.3%), Enterococcus spp. (18.8%), enterobacteria (13.8%), Staphylococcus spp. (9.5%), Pseudomonas aeruginosa (6.6%), and Clostridium difficile (4.1%). The antibiotic most frequently related to superinfection was ciprofloxacin (38.1%), followed by cefotaxime (23.3%), imipenem (12%), meropenem (10.2%), and cefepime (6.1%). The lowest percentage of superinfection was observed with the use of piperacillin-tazobactam (5.4%).
Topics: Anti-Bacterial Agents; Humans; Risk Factors; Superinfection
PubMed: 15915231
DOI: No ID Found -
BMJ (Clinical Research Ed.) May 2003To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia.
DATA SOURCES
Medline, Embase, Lilacs, the Cochrane Library, and conference proceedings to 2002. References of included studies and contact with authors. No restrictions on language, year of publication, or publication status.
STUDY SELECTION
All randomised trials of beta lactam monotherapy compared with beta lactam-minoglycoside combination therapy as empirical treatment for patients with fever and neutropenia.
DATA SELECTION
Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. An intention to treat approach was used. Relative risks were pooled with the random effect model.
MAIN OUTCOME MEASURE
All cause fatality.
RESULTS
Forty seven trials with 7807 patients met inclusion criteria. Nine trials compared the same beta lactam. There was no significant difference in all cause fatality (relative risk 0.85, 95% confidence interval 0.72 to 1.02). For success of treatment there was a significant advantage with monotherapy (0.92, 0.85 to 0.99), though there was considerable heterogeneity among trials. There was no significant difference between monotherapy and combination treatment in trials that compared the same beta lactam, whereas there was major advantage with monotherapy in trials that compared different beta lactams (0.87, 0.80 to 0.93). Rates of superinfection were similar. Adverse events, including those associated with severe morbidity, were significantly more common in the combination treatment group. Detected flaws in methods did not affect results.
CONCLUSIONS
For patients with fever and neutropenia there is no clinical advantage in treatment with beta lactam-aminoglycoside combination therapy. Broad spectrum beta lactams as monotherapy should be regarded as the standard of care for such patients.
Topics: Aminoglycosides; Anti-Bacterial Agents; Cause of Death; Drug Therapy, Combination; Fever; Humans; Neutropenia; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Superinfection; Treatment Failure; beta-Lactams
PubMed: 12763980
DOI: 10.1136/bmj.326.7399.1111