Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Sep 2003
Effectiveness of combination antimicrobial therapy for Pseudomonas aeruginosa bacteremia.
It remains controversial whether combination therapy, given empirically or as definitive treatment, for Pseudomonas aeruginosa bacteremia is associated with a better outcome than monotherapy. The aim of the present study was to compare the rates of survival among patients who received either combination therapy or monotherapy for P. aeruginosa bacteremia. We assembled a historical cohort of 115 episodes of P. aeruginosa bacteremia treated with empirical antipseudomonal therapy between 1988 and 1998. ⋯ Compared to adequate definitive combination therapy, the risk of death at 30 days was also higher with inadequate definitive therapy (aHR, 2.6; 95% CI, 1.1 to 6.7) but not with adequate definitive monotherapy (aHR, 0.70; 95% CI, 0.30 to 1.7). In this retrospective analysis the use of adequate combination antimicrobial therapy as empirical treatment until receipt of the antibiogram was associated with a better rate of survival at 30 days than the use of monotherapy. However, adequate combination antimicrobial therapy given as definitive treatment for P. aeruginosa bacteremia did not improve the rate of survival compared to that from the provision of adequate definitive monotherapy.
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Antimicrob. Agents Chemother. · Aug 2003
Polymyxin B nephrotoxicity and efficacy against nosocomial infections caused by multiresistant gram-negative bacteria.
Reported rates of nephrotoxicity associated with the systemic use of polymyxins have varied widely. The emergence of infections due to multiresistant gram-negative bacteria has necessitated the use of systemic polymyxin B once again for the treatment of such infections. We retrospectively investigated the rate of nephrotoxicity in patients receiving polymyxin B parenterally for the treatment of infections caused by multiresistant gram-negative bacteria from October 1999 to September 2000. ⋯ The overall mortality was 20%, but it increased to 57% in those who developed renal failure. The organism was cleared in 88% of the patients from whom repeat specimens were obtained. The use of polymyxin B to treat multiresistant gram-negative infections was highly effective and associated with a lower rate of nephrotoxicity than previously described.
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Antimicrob. Agents Chemother. · May 2003
Efficacy of daptomycin in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus is becoming increasingly prevalent as both a nosocomial and a community-acquired pathogen. Daptomycin, a lipopeptide antibiotic now in phase III clinical trials, is rapidly bactericidal in vitro against a range of gram-positive organisms, including methicillin-resistant S. aureus (MRSA). In this study, we compared the efficacy of daptomycin with that of vancomycin, each with or without rifampin, in a model of experimental aortic valve endocarditis due to MRSA. ⋯ In the study of combination therapy, vegetation bacterial counts were as follows: daptomycin at 40 mg/kg, 4.6 +/- 1.6; rifampin, 3.6 +/- 1.3; vancomycin plus rifampin, 3.3 +/- 1.1; daptomycin plus rifampin, 2.9 +/- 0.8. The difference between daptomycin and daptomycin plus rifampin was statistically significant (P = 0.006). These results support the continued evaluation of daptomycin for serious MRSA infections, including infective endocarditis.
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Antimicrob. Agents Chemother. · Mar 2003
Low-level resistance to rifampin in Streptococcus pneumoniae.
Rifampin is recommended for combination therapy of meningitis due to beta-lactam-resistant Streptococcus pneumoniae. High-level rifampin resistance (MIC, > or =4 mg/liter) has been mapped to point mutations in clusters I and III of rpoB of the pneumococcus. The molecular basis of low-level resistance (MICs, > or =0.5 and <4 mg/liter) was analyzed. ⋯ Therefore, a resistance-mediating mutation located outside clusters I, II, and III has been described for the first time in the pneumococcus. In vitro low-level rifampin resistance in S. pneumoniae could be mapped to cluster II of rpoB. Mutants of pneumococcus with low-level resistance may be selected in vivo during therapy in tissue compartments with low antibiotic concentrations and play a role in the development of resistance.