Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Jan 2008
Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa by South Florida plant extracts.
Quorum sensing (QS) is a key regulator of virulence and biofilm formation in Pseudomonas aeruginosa and other medically relevant bacteria. Aqueous extracts of six plants, Conocarpus erectus, Chamaesyce hypericifolia, Callistemon viminalis, Bucida buceras, Tetrazygia bicolor, and Quercus virginiana, were examined in this study for their effects on P. aeruginosa virulence factors and the QS system. ⋯ Additionally, each plant presented a distinct effect profile on the las and rhl QS genes and their respective signaling molecules, suggesting that different mechanisms are responsible for efficacy. Extracts of all plants caused the inhibition of QS genes and QS-controlled factors, with marginal effects on bacterial growth, suggesting that the quorum-quenching mechanisms are unrelated to static or cidal effects.
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Antimicrob. Agents Chemother. · Dec 2007
Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa isolates from Spanish hospitals.
All (236) Pseudomonas aeruginosa isolates resistant to imipenem and/or meropenem collected during a multicenter (127-hospital) study in Spain were analyzed. Carbapenem-resistant isolates were found to be more frequently resistant to all beta-lactams and non-beta-lactam antibiotics than carbapenem-susceptible isolates (P < 0.001), and up to 46% of the carbapenem-resistant isolates met the criteria used to define multidrug resistance (MDR). Pulsed-field gel electrophoresis revealed remarkable clonal diversity (165 different clones were identified), and with few exceptions, the levels of intra- and interhospital dissemination of clones were found to be low. ⋯ The class 1 integron harboring bla(VIM-2) was characterized as well, and two interesting features were revealed: intI1 was found to be disrupted by a 1.1-kb insertion sequence, and a previously undescribed aminoglycoside acetyltransferase-encoding gene [designated aac(6')-32] preceded bla(VIM-2). AAC(6')-32 showed 80% identity to AAC(6')-Ib' and the recently described AAC(6')-31, and when aac(6')-32 was cloned into Escherichia coli, it conferred resistance to tobramycin and reduced susceptibility to gentamicin and amikacin. Despite the currently low prevalence of epidemic clones with MDR, active surveillance is needed to detect and prevent the dissemination of these clones, particularly those producing integron- and plasmid-encoded MBLs, given their additional capacity for the intra- and interspecies spread of MDR.
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Antimicrob. Agents Chemother. · Nov 2007
Randomized Controlled TrialRandomized, double-blind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection.
Empirical use of beta-lactam antibiotics, the preferred agents for treating uncomplicated skin and soft tissue infections, may no longer be appropriate for these infections because of the increasing prevalence of community strains of methicillin-resistant Staphylococcus aureus (MRSA). Retrospective studies, however, suggest that outcomes are good even when beta-lactams are used. We conducted a randomized, double-blind trial of 166 outpatient subjects comparing placebo to cephalexin at 500 mg orally four times for 7 days after incision and drainage of skin and soft tissue abscesses. ⋯ Of the isolates tested 87.8% were MRSA, 93% of which were positive for Panton-Valentine leucocidin genes. Clinical cure rates were 90.5% (95% confidence interval, 0.82 to 0.96) in the 84 placebo recipients and 84.1% (95% confidence interval, 0.74 to 0.91) in the 82 cephalexin recipients (difference in the two proportions, 0.0006; 95% confidence interval, -0.0461 to 0.0472; P = 0.25). The 90.5% cure rate observed in the placebo arm and 84.1% cure rate observed in the cephalexin arm provide strong evidence that antibiotics may be unnecessary after surgical drainage of uncomplicated skin and soft tissue abscesses caused by community strains of MRSA.
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Antimicrob. Agents Chemother. · Nov 2007
Comparative StudyComparison of beta-lactam and macrolide combination therapy versus fluoroquinolone monotherapy in hospitalized Veterans Affairs patients with community-acquired pneumonia.
Data comparing the treatment outcomes of the two most frequently recommended empirical antibiotic regimens for community-acquired pneumonia (CAP)--combination therapy with an extended-spectrum beta-lactam and a macrolide (BL+M) or fluoroquinolone (F) monotherapy--for patients with severe CAP are sparse. The purpose of this study was to compare empirical BL+M combination therapy with F monotherapy for Veterans Affairs (VA) patients with severe CAP. This retrospective study included patients with CAP who received empirical therapy with BL+M or F between October 1999 and May 2003 in the Upstate New York VA Network. ⋯ The overall median LOS was significantly longer for the BL+M combination group than for the F monotherapy group (6.0 days versus 5.0 days, respectively [P = 0.01]), but no difference in LOS was noted among PSI class V patients. Our study showed that improved outcomes may be realized with BL+M in cases of severe CAP. A randomized clinical study is warranted based on these results.
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Antimicrob. Agents Chemother. · Oct 2007
Randomized Controlled TrialSteady-state pharmacokinetic and safety profiles of voriconazole and ritonavir in healthy male subjects.
Since there is a likelihood of coadministration of voriconazole and ritonavir, two studies were conducted to evaluate the potential of drug interaction. Study A was a randomized, placebo-controlled, two-period, parallel-group trial (n = 34). Study B had the same design without the placebo group (n = 17). ⋯ Voriconazole had no apparent effect on the exposure of high-dose ritonavir but slightly decreased the exposure of low-dose ritonavir (AUC(0-12), -14%; C(max), -24%). The safety profile of combination therapy was not notably different from that of voriconazole or ritonavir alone. Due to the significant effect of ritonavir on voriconazole exposure, coadministration of voriconazole with 400 mg BID ritonavir is contraindicated; coadministration with 100 mg BID ritonavir should be avoided, unless an assessment of the benefit/risk to the patient justifies the use.