Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Dec 2013
Impact of Bolus dosing versus continuous infusion of Piperacillin and Tazobactam on the development of antimicrobial resistance in Pseudomonas aeruginosa.
Management of nosocomial pneumonia is frequently complicated by bacterial resistance. Extended infusions of beta-lactams are increasingly being used to improve clinical outcomes. However, the impact of this strategy on the emergence of antimicrobial resistance is not known. ⋯ A stratified approach, according to bacterial density, is required to treat patients with nosocomial pneumonia. Antimicrobial monotherapy may be sufficient for some patients. However, for patients with a high bacterial burden, alternative therapeutic strategies are required to maximize bacterial killing and prevent antimicrobial resistance.
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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
Antimicrobial activity of ceftolozane-tazobactam tested against Enterobacteriaceae and Pseudomonas aeruginosa with various resistance patterns isolated in U.S. Hospitals (2011-2012).
Ceftolozane/tazobactam, a novel antimicrobial agent with activity against Pseudomonas aeruginosa (including drug-resistant strains) and other common Gram-negative pathogens (including most extended-spectrum-β-lactamase [ESBL]-producing Enterobacteriaceae strains), and comparator agents were susceptibility tested by a reference broth microdilution method against 7,071 Enterobacteriaceae and 1,971 P. aeruginosa isolates. Isolates were collected consecutively from patients in 32 medical centers across the United States during 2011 to 2012. Overall, 15.7% and 8.9% of P. aeruginosa isolates were classified as multidrug resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% of Enterobacteriaceae were classified as MDR and XDR. ⋯ In summary, ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporary Enterobacteriaceae and P. aeruginosa isolates collected in U. S. medical centers. Importantly, ceftolozane/tazobactam retained potency against many MDR and XDR strains.
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Antimicrob. Agents Chemother. · Dec 2013
Optimizing empiric antibiotic therapy in patients with severe β-lactam allergy.
Antibiotic selection is challenging in patients with severe β-lactam allergy due to declining reliability of alternate antibiotics. Organisms isolated from these patients may exhibit unique resistance phenotypes. The objective of this study was to determine which alternate antibiotics or combinations provide adequate empirical therapy for patients with β-lactam allergy who develop Gram-negative infections at our institution. ⋯ Single alternate agents were adequate less frequently than β-lactams and combination regimens. Only in cases without risk factors for resistance did single-agent regimens demonstrate acceptable adequacy rates; each factor conferred a doubling of risk for resistance. Resistance risk factors should be considered in selecting empirical antibiotics for Gram-negative pathogens in patients unable to take β-lactams due to severe allergy.
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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.