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Critical Care (London, England) 2011Several reports have shown marked heterogeneity of antibiotic pharmacokinetics (PK) in patients admitted to ICUs, which might potentially affect outcomes. Therefore, the... (Review)
Review
INTRODUCTION
Several reports have shown marked heterogeneity of antibiotic pharmacokinetics (PK) in patients admitted to ICUs, which might potentially affect outcomes. Therefore, the pharmacodynamic (PD) parameter of the efficacy of β-lactam antibiotics, that is, the time that its concentration is above the bacteria minimal inhibitory concentration (T > MIC), cannot be safely extrapolated from data derived from the PK of healthy volunteers.
METHODS
We performed a full review of published studies addressing the PK of intravenous β-lactam antibiotics given to infected ICU patients. Study selection comprised a comprehensive bibliographic search of the PubMed database and bibliographic references in relevant reviews from January 1966 to December 2010. We selected only English-language articles reporting studies addressing β-lactam antibiotics that had been described in at least five previously published studies. Studies of the PK of patients undergoing renal replacement therapy were excluded.
RESULTS
A total of 57 studies addressing six different β-lactam antibiotics (meropenem, imipenem, piperacillin, cefpirome, cefepime and ceftazidime) were selected. Significant PK heterogeneity was noted, with a broad, more than twofold variation both of volume of distribution and of drug clearance (Cl). The correlation of antibiotic Cl with creatinine clearance was usually reported. Consequently, in ICU patients, β-lactam antibiotic half-life and T > MIC were virtually unpredictable, especially in those patients with normal renal function. A better PD profile was usually obtained by prolonged or even continuous infusion. Tissue penetration was also found to be compromised in critically ill patients with septic shock.
CONCLUSIONS
The PK of β-lactam antibiotics are heterogeneous and largely unpredictable in ICU patients. Consequently, the dosing of antibiotics should be supported by PK concepts, including data derived from studies of the PK of ICU patients and therapeutic drug monitoring.
Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Critical Illness; Humans; Imipenem; Infections; Meropenem; Piperacillin; Thienamycins; beta-Lactams; Cefpirome
PubMed: 21914174
DOI: 10.1186/cc10441 -
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 -
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