Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Jan 2014
Activity of ceftolozane-tazobactam against a broad spectrum of recent clinical anaerobic isolates.
We evaluated in vitro activity of ceftolozane-tazobactam (TOL-TAZ), formerly CXA-201, against recent clinical anaerobic isolates with emphasis on the Bacteroides fragilis group. Ceftolozane-tazobactam showed good activity against B. fragilis species and intermediate to limited activity against other species of Bacteroides. Ceftolozane-tazobactam showed very good activity against Prevotella spp., Fusobacterium spp., and Propionibacterium spp., varying activities against Gram-positive cocci, and limited activity against Clostridium spp.
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Antimicrob. Agents Chemother. · Jan 2014
Single-dose pharmacokinetics of cidofovir in continuous venovenous hemofiltration.
Dosage recommendations for cidofovir are available for renally competent as well as impaired patients; however, there are no data for patients undergoing continuous renal replacement therapy. We determined the single-dose concentration-versus-time profile of cidofovir in a critically ill patient undergoing continuous venovenous hemofiltration (CVVH). One dose of 450 mg cidofovir (5 mg/kg) was administered intravenously due to a proven cytomegalovirus (CMV) infection and failure of first-line antiviral therapy. ⋯ Total removal of the drug was 30.99% after 24 h. Because of these data, which give us a rough idea of the concentration profile of cidofovir in patients undergoing CVVH, a toxic accumulation of the drug following repeated doses may be expected. Further trials have to be done to determine the right dosage of cidofovir in patients undergoing CVVH to avoid toxic accumulation of the drug.
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Antimicrob. Agents Chemother. · Jan 2014
Severe sepsis facilitates intestinal colonization by extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and transfer of the SHV-18 resistance gene to Escherichia coli during antimicrobial treatment.
Infections caused by multidrug-resistant pathogens are frequent and life threatening in critically ill patients. To investigate whether severe sepsis affects gut colonization by resistant pathogens and genetic exchange between opportunistic pathogens, we tested the intestinal-colonization ability of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain carrying the SHV-18 resistance gene and the transfer ability of the resistance gene to endogenous Escherichia coli under ceftriaxone treatment in rats with burn injury only or severe sepsis induced by burns plus endotoxin exposure. Without ceftriaxone treatment, the K. pneumoniae strain colonized the intestine in both septic and burned rats for a short time, with clearance occurring earlier in burn-only rats but never in sham burn rats. ⋯ Compared with burn-only injury, severe sepsis had a more significant effect on the change in antimicrobial resistance to ceftriaxone. Only in septic rats was the resistance gene successfully transferred from the challenge strain to endogenous E. coli during ceftriaxone treatment; the gene persisted for at least 4 weeks after ceftriaxone treatment. We concluded that severe sepsis can facilitate intestinal colonization by an exogenous resistant pathogen and the transfer of the resistance gene to a potential endogenous pathogen during antimicrobial treatment.
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Antimicrob. Agents Chemother. · Dec 2013
Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox).
Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917-918, 2003). ⋯ In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo-treated controls that survived infection. Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates, suggesting that it is reasonably likely to provide therapeutic benefit in smallpox-infected humans.
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Antimicrob. Agents Chemother. · Dec 2013
Observational StudyProtein binding of β-lactam antibiotics in critically ill patients: can we successfully predict unbound concentrations?
The use of therapeutic drug monitoring (TDM) to optimize beta-lactam dosing in critically ill patients is growing in popularity, although there are limited data describing the potential impact of altered protein binding on achievement of target concentrations. The aim of this study was to compare the measured unbound concentration to the unbound concentration predicted from published protein binding values for seven beta-lactams using data from blood samples obtained from critically ill patients. From 161 eligible patients, we obtained 228 and 220 plasma samples at the midpoint of the dosing interval and trough, respectively, for ceftriaxone, cefazolin, meropenem, piperacillin, ampicillin, benzylpenicillin, and flucloxacillin. ⋯ The percent protein binding of flucloxacillin and the plasma albumin concentration were also found to be linearly correlated (R(2) = 0.776; P < 0.01). In conclusion, significant differences between measured and predicted unbound drug concentrations were found only for the highly protein-bound beta-lactams ceftriaxone and flucloxacillin. However, direct measurement of unbound drug in research and clinical practice is suggested for selected beta-lactams.