Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Apr 2019
Cefepime Pharmacokinetics in Critically Ill Pediatric Patients Receiving Continuous Renal Replacement Therapy.
This retrospective study included pediatric intensive care unit patients receiving continuous veno-venous hemodiafiltration (CVVHDF) being treated with cefepime. The free drug concentration above one time the MIC (fT>1×MIC) and four times a presumed MIC (fT>4×MIC) of 8 μg/ml were calculated. ⋯ Three patients achieved 100% fT>1×MIC, with the fourth patient achieving 98% fT>1×MIC. Therapeutic drug monitoring should be considered for critically ill patients receiving cefepime on CVVHDF.
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Antimicrob. Agents Chemother. · Apr 2019
Antibacterial Activity of Lefamulin against Pathogens Most Commonly Causing Community-Acquired Bacterial Pneumonia: SENTRY Antimicrobial Surveillance Program (2015-2016).
Lefamulin, the first semisynthetic pleuromutilin antibacterial for intravenous and oral treatment of community-acquired bacterial pneumonia (CABP), and comparators were evaluated for in vitro activity against a global collection of pathogens commonly causing CABP (n = 8595) from the 2015 and 2016 SENTRY Antimicrobial Surveillance Program. Lefamulin was highly active against the pathogens Streptococcus pneumoniae, including multidrug-resistant and extensively drug-resistant strains (MIC50/90 for total and resistant subsets, 0.06/0.12 μg/ml; 100% inhibited at ≤1 μg/ml), Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA; both MIC50/90, 0.06/0.12 μg/ml; 99.8% and 99.6% inhibited at ≤1 μg/ml, respectively), Haemophilus influenzae (MIC50/90, 0.5/1 μg/ml; 93.8% inhibited at ≤1 μg/ml), and Moraxella catarrhalis (MIC50/90, 0.06/0.12 μg/ml; 100% inhibited at ≤0.25 μg/ml), and its activity was unaffected by resistance to other antibacterial classes.
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Antimicrob. Agents Chemother. · Apr 2019
In Vitro Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex.
Infections caused by the difficult-to-treat bacterium Mycobacterium abscessus are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active in vitro against M. abscessus, especially against clarithromycin-resistant strains. However, explorations for potential synergy between rifabutin and available antimicrobials are currently limited. ⋯ Significant synergism, classified by an FICI of ≤0.5, was demonstrated for the combinations of rifabutin and imipenem in 100% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates, and significant synergism for rifabutin and tigecycline was demonstrated in 77% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates. Among the 6 clarithromycin-resistant (MICs ≥ 8 mg/liter) M. abscessus subsp. abscessus isolates, the combination of rifabutin and clarithromycin was 100% synergistic. Rifabutin showed promising in vitro synergism with first-line anti-M. abscessus agents, especially for macrolide-resistant M. abscessus subsp. abscessus isolates.
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Antimicrob. Agents Chemother. · Mar 2019
In Vitro Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates.
Pulmonary disease due to infection with Mycobacterium abscessus complex (MABC) is notoriously difficult to treat, in large part due to the intrinsic resistance of MABC strains to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-β-lactam-based β-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC members to some β-lactams is increased in the presence of avibactam. ⋯ Our data demonstrate that both β-lactamase inhibitors significantly improved the anti-MABC activity of many carbapenems (including imipenem and meropenem) and cephalosporins (including cefepime, ceftaroline, and cefuroxime). As a meropenem-vaborbactam combination is now marketed and an imipenem-relebactam combination is currently in phase III trials, these fixed combinations may become the β-lactams of choice for the treatment of MABC infections. Furthermore, given the evolving interest in dual β-lactam regimens, our results identify select cephalosporins, such as cefuroxime, with superior activity in the presence of a β-lactamase inhibitor that are deserving of further evaluation in combination with these carbapenem-β-lactamase inhibitor products.
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Antimicrob. Agents Chemother. · Feb 2019
In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium abscessus Complex.
We performed bedaquiline broth microdilution susceptibility testing using Clinical and Laboratory Standards Institute (CLSI) guidelines on 104 nonduplicate isolates of Mycobacterium abscessus complex [M. abscessus subsp. abscessus (76); M. abscessus subsp. massiliense (10); M. abscessus subsp. bolletii (2); and M. abscessus subsp. abscessus-M. abscessus subsp. massiliense hybrid, i.e., M. abscessus subsp. abscessus by rpoB gene and M. abscessus subsp. massiliense by erm(41) gene (16)]. All isolates from patients not known to have been on bedaquiline prior had MIC values of ≤0.25 μg/ml. The bedaquiline MIC50 value for all 76 isolates of M. abscessus subsp. abscessus and 16 isolates of M. abscessus subsp. abscessus-M. abscessus subsp. massiliense hybrid was 0.06 μg/ml. ⋯ Only two isolates of M. abscessus subsp. bolletii were tested with bedaquiline MICs of 0.06 μg/ml. Our study suggests that oral bedaquiline may have potential use in the treatment of disease caused by the M. abscessus complex. Combination therapy with other agents (imipenem, cefoxitin, amikacin, and/or tigecycline) is recommended.