Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Apr 2017
Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Bacteria Isolated from Patients Hospitalized with Pneumonia in U.S. Medical Centers, 2011 to 2015.
Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated pneumonia (VAP), from 76 U. S. medical centers in 2011 to 2015. The Gram-negative organisms (n = 11,185, including 1,097 from VAP) were tested for susceptibility to ceftazidime-avibactam and comparators by the broth microdilution method. β-Lactamase-encoding genes were screened using a microarray-based assay on selected isolates. ⋯ The most common β-lactamases detected among Klebsiella pneumoniae and E. coli isolates were K. pneumoniae carbapenemase (KPC)-like and CTX-M-15, respectively. Only 8 of 6,209 Enterobacteriaceae isolates (0.1%) were ceftazidime-avibactam nonsusceptible, three NDM-1-producing strains with ceftazidime-avibactam MIC values of >32 μg/ml and five isolates with ceftazidime-avibactam MIC values of 16 μg/ml and negative results for all β-lactamases tested. Susceptibility rates among isolates from VAP were generally similar or slightly higher than those from all PHP.
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Antimicrob. Agents Chemother. · Apr 2017
Nasal Methicillin-Resistant Staphylococcus aureus (MRSA) PCR Testing Reduces the Duration of MRSA-Targeted Therapy in Patients with Suspected MRSA Pneumonia.
The objective of this study was to evaluate the impact of pharmacist-ordered methicillin-resistant Staphylococcus aureus (MRSA) PCR testing on the duration of empirical MRSA-targeted antibiotic therapy in patients with suspected pneumonia. This is a retrospective analysis of patients who received vancomycin or linezolid for suspected pneumonia before and after the implementation of a pharmacist-driven protocol for nasal MRSA PCR testing. Patients were included if they were adults of >18 years of age and initiated on vancomycin or linezolid for suspected MRSA pneumonia. ⋯ Fewer patients in the post-PCR group required vancomycin serum levels and dose adjustment (48.1% versus 16.7%; P = 0.02). There were no significant differences between the pre- and post-PCR groups regarding days to clinical improvement (1.78 ± 2.52 versus 2.27 ± 3.34; P = 0.54), length of hospital stay (11.04 ± 9.5 versus 8.2 ± 7.8; P = 0.22), or hospital mortality (14.8% versus 6.7%; P = 0.41). The use of nasal MRSA PCR testing in patients with suspected MRSA pneumonia reduced the duration of empirical MRSA-targeted therapy by approximately 2 days without increasing adverse clinical outcomes.
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Antimicrob. Agents Chemother. · Apr 2017
Inhibition of Pseudomonas aeruginosa by Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers.
Pseudomonas aeruginosa is a highly virulent, multidrug-resistant pathogen that causes significant morbidity and mortality in hospitalized patients and is particularly devastating in patients with cystic fibrosis. Increasing antibiotic resistance coupled with decreasing numbers of antibiotics in the developmental pipeline demands novel antibacterial approaches. Here, we tested peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs), which inhibit translation of complementary mRNA from specific, essential genes in P. aeruginosa PPMOs targeted to acpP, lpxC, and rpsJ, inhibited P. aeruginosa growth in many clinical strains and activity of PPMOs could be enhanced 2- to 8-fold by the addition of polymyxin B nonapeptide at subinhibitory concentrations. ⋯ Importantly, treatment with various combinations of a PPMO and a traditional antibiotic demonstrated synergistic growth inhibition, the most effective of which was the PPMO targeting rpsJ with tobramycin. Furthermore, treatment of P. aeruginosa PA103-infected mice with PPMOs targeting acpP, lpxC, or rpsJ significantly reduced the bacterial burden in the lungs at 24 h by almost 3 logs. Altogether, this study demonstrates that PPMOs targeting the essential genes acpP, lpxC, or rpsJ in P. aeruginosa are highly effective at inhibiting growth in vitro and in vivo These data suggest that PPMOs alone or in combination with antibiotics represent a novel approach to addressing the problems associated with rapidly increasing antibiotic resistance in P. aeruginosa.