Arbekacin activity against contemporary clinical bacteria isolated from patients hospitalized with pneumonia
Helio S Sader1, Paul R Rhomberg2, David J Farrell2
1JMI Laboratories, North Liberty, Iowa, USA helio-sader@jmilabs.com.
Abstract:
Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States. We evaluated the occurrence of organisms isolated from pneumonias in U.S. hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and the in vitro activity of arbekacin. Organism frequency was evaluated from a collection of 2,203 bacterial isolates (339 from VAP) consecutively collected from 25 medical centers in 2012 through the SENTRY Antimicrobial Surveillance Program. Arbekacin activity was tested against 904 isolates from PHP collected in 2012 from 62 U.S. medical centers and 303 multidrug-resistant (MDR) organisms collected worldwide in 2009 and 2010 from various infection types. Susceptibility to arbekacin and comparator agents was evaluated by the reference broth microdilution method. The four most common organisms from PHP were Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella spp., and Enterobacter spp. The highest arbekacin MIC among S. aureus isolates from PHP (43% methicillin-resistant S. aureus [MRSA]) was 4 μg/ml. Among P. aeruginosa isolates from PHP, only one had an arbekacin MIC of >16 μg/ml (MIC50 and MIC90, 1 and 4 μg/ml), and susceptibility rates for gentamicin, tobramycin, and amikacin were 88.0, 90.0, and 98.0%, respectively. Arbekacin (MIC50, 2 μg/ml) and tobramycin (MIC50, 4 μg/ml) were the most potent aminoglycosides tested against Acinetobacter baumannii. Against Enterobacteriaceae from PHP, arbekacin and gentamicin (MIC50 and MIC90, 0.25 to 1 and 1 to 8 μg/ml for both compounds) were generally more potent than tobramycin (MIC50 and MIC90, 0.25 to 2 and 1 to 32 μg/ml) and amikacin (MIC50 and MIC90, 1 to 2 and 2 to 32 μg/ml). Arbekacin also demonstrated potent in vitro activity against a worldwide collection of well-characterized MDR Gram-negative and MRSA strains.
Insights
Arbekacin shows strong in vitro activity against common pneumonia pathogens in U.S. hospitals, including MRSA and MDR Gram-negative bacteria. This broad-spectrum aminoglycoside demonstrates potent efficacy, supporting its potential use in treating serious bacterial infections.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Arbekacin is a broad-spectrum aminoglycoside with established systemic use in Japan.
- It is currently under clinical development in the United States as an inhalation solution.
- Evaluating arbekacin's activity against contemporary U.S. pneumonia isolates is crucial.
Purpose of the Study:
- To assess the prevalence of bacterial organisms causing pneumonia in U.S. hospitalized patients (PHP), including ventilator-associated pneumonia (VAP).
- To determine the in vitro antimicrobial activity of arbekacin against these prevalent pathogens.
- To compare arbekacin's activity with other commonly used antibiotics.
Main Methods:
- Bacterial isolates (n=2,203) from PHP and VAP were collected from 25 U.S. medical centers (2012) via the SENTRY Antimicrobial Surveillance Program.
- Arbekacin susceptibility was tested against 904 PHP isolates and 303 multidrug-resistant (MDR) organisms using broth microdilution.
- Prevalent pathogens included Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella spp., and Enterobacter spp.
Main Results:
- Arbekacin demonstrated potent activity against Staphylococcus aureus (MIC ≤4 μg/ml), including 43% methicillin-resistant S. aureus (MRSA).
- Against Pseudomonas aeruginosa, arbekacin showed high potency (MIC50/MIC90, 1/4 μg/ml), with susceptibility rates higher than other aminoglycosides.
- Arbekacin was more potent than other tested aminoglycosides against Acinetobacter baumannii and Enterobacteriaceae, including MDR strains.
Conclusions:
- Arbekacin exhibits significant in vitro activity against key pathogens responsible for hospital-acquired pneumonia in the U.S.
- Its potent efficacy against MRSA and MDR Gram-negative bacteria warrants further clinical investigation for pneumonia treatment.
- Arbekacin represents a promising therapeutic option for managing challenging bacterial respiratory infections.
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