Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Oct 2018
APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method.
APX001A is the active moiety of the first-in-class drug candidate APX001. So far, most susceptibility testing studies have examined ≤30 isolates/species, and only one used the EUCAST method. Here, we investigated the in vitro activity of APX001A and five comparators against 540 candidemia and 122 C. auris isolates. ⋯ APX001A was equally or more active in vitro than the comparators against all species except C. krusei and C. norvegensis Four isolates were APX001A non-WT; all were fluconazole resistant. A correlation was observed between APX001A and fluconazole MICs across all species except Candida guilliermondii and C. auris, and when comparing high and low fluconazole MIC isolates of C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, and C. auris APX001A showed promising in vitro activity against most Candida and other yeast species, including C. auris, compared to five comparators. WT-UL were suggested for the common species, and a new and unexplained correlation to fluconazole susceptibility was observed.
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Antimicrob. Agents Chemother. · Sep 2018
β-Lactam Dosage Regimens in Septic Patients with Augmented Renal Clearance.
Augmented renal clearance is commonly observed in septic patients and may result in insufficient β-lactam serum concentrations. The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of β-lactam antibiotics and measured creatinine clearance and to quantify the need for drug dosage adjustments in septic patients with different levels of augmented renal clearance. We reviewed 256 antibiotic measurements (512 drug concentrations) from a cohort of 215 critically ill patients who had a measured creatinine clearance of ≥120 ml/min and who received therapeutic drug monitoring of meropenem, cefepime, ceftazidime, or piperacillin from October 2009 until December 2014 at Erasme Hospital. ⋯ Measured creatinine clearance adequately explained changes in drug concentrations in population pharmacokinetic models for cefepime, ceftazidime, and meropenem but not for piperacillin. Therefore, specific PK modeling can predict certain β-lactam concentrations based on renal function but not on absolute values of measured creatinine clearance, easily available for clinicians. Currently, routine therapeutic drug monitoring is required to adjust daily regimens in critically ill patients receiving standard dosing regimens.
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Antimicrob. Agents Chemother. · Sep 2018
Randomized Controlled TrialMolecular Characterization of Nasal Methicillin-Resistant Staphylococcus aureus Isolates Showing Increasing Prevalence of Mupirocin Resistance and Associated Multidrug Resistance following Attempted Decolonization.
Sequential methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients following attempted mupirocin nasal decolonization showed an increase in mupirocin resistance (MR) from 6.6% to 20%. MR isolates from patients who failed decolonization yielded indistinguishable spa types and carried multiple antimicrobial and antiseptic resistance genes, which may guide infection control and prevention.
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Antimicrob. Agents Chemother. · Sep 2018
Pharmacodynamic Target Attainment for Cefepime, Meropenem, and Piperacillin-Tazobactam Using a Pharmacokinetic/Pharmacodynamic-Based Dosing Calculator in Critically Ill Patients.
This was a prospective study to determine if pharmacokinetic/pharmacodynamic (PK/PD)-based antibiotic dosing software aids in achieving concentration targets in critically ill patients receiving cefepime (n = 10), meropenem (n = 20), or piperacillin-tazobactam (n = 19). Antibiotic calculator doses targeting a >90% probability of target attainment (PTA) differed from package insert doses for 22.4% (11/49) of patients. Target attainment was achieved for 98% of patients (48/49). A PK/PD-based antibiotic dosing calculator provides beta-lactam doses with a high PTA in critically ill patients.
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Antimicrob. Agents Chemother. · Aug 2018
Meta AnalysisIncidences of Pseudomonas aeruginosa-Associated Ventilator-Associated Pneumonia within Studies of Respiratory Tract Applications of Polymyxin: Testing the Stoutenbeek Concurrency Postulates.
Regimens containing topical polymyxin appear highly effective at preventing ventilator-associated pneumonia (VAP) overall and, more so, VAP caused by Gram-negative bacteria. However, Stoutenbeek's postulates that VAP incidences within studies of topical antibiotics depend on the context of whether the component (control and intervention) groups of each study were concurrent versus nonconcurrent remain untested. The literature was searched for concurrent control (CC) versus nonconcurrent control (NCC) designed studies of respiratory tract applications of topical polymyxin to mechanically ventilated (MV) patients that reported incidences of Pseudomonas-associated ventilator-associated pneumonia (PsVAP). ⋯ The mean PsVAP within CC polymyxin control groups (9.9%; CI, 7.6 to 12.8%) is higher than that of all other component group categories. The PsVAP incidences of control and intervention groups of studies of respiratory tract applications of polymyxin are dependent on whether the groups were within a concurrent versus nonconcurrent study. Stoutenbeek's concurrency postulates are validated.