ABSTRACT
There is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa isolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severe A. baumannii or P. aeruginosa infections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lacking in vitro activity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P = 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P = 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64; P = 0.001). Creatinine clearance of ≥60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with ß-lactam or carbapenem was considered and in both subgroups of patients: those with A. baumannii infection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drug-resistant A. baumannii or P. aeruginosa infections.
Subject(s)
Acinetobacter baumannii/drug effects , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Polymyxin B/pharmacology , Polymyxin B/therapeutic use , Pseudomonas aeruginosa/drug effects , Acinetobacter Infections/drug therapy , Aged , Aged, 80 and over , Critical Illness , Drug Combinations , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Pseudomonas Infections/drug therapy , Retrospective StudiesSubject(s)
Carbapenems/pharmacology , Drug Resistance, Multiple , Enterobacteriaceae Infections/enzymology , Providencia/drug effects , Providencia/enzymology , beta-Lactamases/drug effects , Anti-Bacterial Agents/pharmacology , Disease Susceptibility , Ertapenem , Humans , Meropenem , Thienamycins/pharmacology , beta-Lactamases/biosynthesis , beta-Lactams/pharmacologySubject(s)
Anti-Infective Agents/pharmacology , Enterobacter/enzymology , Enterobacteriaceae Infections/microbiology , beta-Lactamases/genetics , Bacterial Proteins/genetics , Base Sequence , Brazil , Enterobacter/genetics , Enterobacter/isolation & purification , Humans , Plasmids/genetics , Sequence Analysis, DNAABSTRACT
OBJECTIVES: There are controversies regarding the association of cefepime therapy with increased mortality among patients with infections caused by Gram-negative bacteria (GNB). We evaluated the effect of cefepime on the mortality of patients with GNB bloodstream infections (BSIs). METHODS: A prospective cohort study was conducted in adult patients with creatinine ≤1.5 mg/dL who received empirical therapy with cefepime for at least 48 h for BSIs caused by GNB. The outcome was hospital mortality. Potential clinical predictors, including a high-dose regimen (2 g every 8 h), were assessed. RESULTS: One hundred and thirteen patients were included. Most (78.8%) isolates had low cefepime MICs (≤0.25 mg/L). The overall hospital mortality was 35.4% [25.6% (10/39) and 40.5% (30/74) in patients receiving high-dose and usual-dose cefepime, respectively (Pâ=â0.17)]. In a Cox regression model adjusted for cefepime MIC and propensity score, a high-dose regimen was independently associated with lower mortality rates [adjusted hazard ratio (aHR) 0.41; 95% CI 0.18-0.91; Pâ=â0.029] while presentation with severe sepsis or septic shock was independently associated with higher mortality rates (aHR 4.10; 95% CI 1.78-9.40; Pâ=â0.001). A trend to lower mortality rates was also found in the subgroup analysis of patients who had not switched antibiotic during therapy after adjustment for the latter variables. CONCLUSIONS: High-dose cefepime therapy was associated with lower mortality rates in patients with GNB BSIs, even for GNB with low cefepime MICs.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacteremia/drug therapy , Bacteremia/mortality , Cephalosporins/administration & dosage , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/mortality , Adult , Aged , Bacteremia/microbiology , Cefepime , Drug Resistance, Bacterial , Drug Substitution , Female , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/microbiology , Hospital Mortality , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Prospective Studies , Risk Factors , Treatment OutcomeABSTRACT
Rhizobium radiobacter is an uncommon agent of infection and has been associated with indwelling intravascular devices such as catheter in immunocompromised patients. Here, we report a case of R. radiobacter recovered from blood cultures in stem cell transplantation in a pediatric patient and present an extensive characterization of its antimicrobial susceptibility profile. The isolate presented low MICs to many antimicrobial agents, but high MICs to ceftazidime, piperacillin-tazobactam, aztreonam, and fosfomycin.
