Gram-Negative Bacteria Antibiotic Susceptibility for Pneumonia in the ICU

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Investigators demonstrated that the 2 cephalosporin/b-lactamase inhibitor combinations recently approved by the FDA represent a valuable addition to the anti-P aeruginosa armamentarium.
Investigators demonstrated that the 2 cephalosporin/b-lactamase inhibitor combinations recently approved by the FDA represent a valuable addition to the anti-P aeruginosa armamentarium.

Antimicrobial agents ceftazidime/avibactam and amikacin provided the best overall coverage against Gram-negative organisms isolated from patients with pneumonia in the intensive care unit (ICU), according to a study published in the Journal of Antimicrobial Chemotherapy.

Pneumonia is the second most common infection in hospitalized patients and is associated with significant morbidity and mortality. The initial antimicrobial management of patients with pneumonia is determined mostly by the understanding of causative pathogens. However, there is little current information regarding the frequency and antimicrobial susceptibility of organisms causing healthcare-associated pneumonia. The choice of antimicrobial treatment for pneumonia is based on various factors, but the foundation for such treatment generally includes drugs from the β-lactam class.

However, there has been an increasing trend in microbial resistance in the ICU because of antimicrobial selection pressure limiting the clinical utility of β-lactams in recent years. Most of these organisms harbor various β-lactamase genes and resistance determinants for other antimicrobial classes. Although a variety of non- β-lactam agents are being developed, and numerous investigational approaches involving both established and new β-lactamase inhibitors in novel combinations are being researched, scarce data are available on the frequency and antimicrobial susceptibility of bacteria isolated from patients with pneumonia in the ICU. Thus, this study endeavored to fill this research gap. Further, the activity and spectrum of 2 recently US Food and Drug Administration (FDA)-approved β-lactamase inhibitor combinations, ceftazidime/avibactam and ceftolozane/tazobactam, and other antimicrobial agents currently used to treat pneumonia, were investigated.

A total of 6091 bacterial isolates were collected from 75 US medical centers from 2015 to 2017 as part of the International Network for Optimal Resistance Monitoring (INFORM) program and tested for susceptibility to multiple antimicrobial agents at a central laboratory via the reference broth microdilution method.

Gram-negative bacteria were isolated from 67.1% of patients; 32.9% were gram-positive. The most common organisms isolated from individuals hospitalized in the ICU with pneumonia were Staphylococcus aureus (30.0%), Psuedomonas aeruginosa (20.7%), Klebsiella spp. (11.8%), Enterobacter spp (8.3%), Escherichia coli (7.1%), Stenotrophomonas maltophilia (5.1%), Serratia marcescens (4.6%), Haemophilus influenzae (2.8%), Acinetobacter baumannii (2.8%), and Streptococcus pneumoniae (1.5%). P aeruginosa and Enterobacteriaceae represented >80% of these organisms.

Results showed that ceftazidime/avibactam and amikacin provided the best coverage against Gram-negative organisms overall. P aeruginosa was the most common gram-negative organism present and demonstrated low susceptibility rates to many antimicrobial agents, with 26% and 11.5% of isolates showing multi-drug resistance and extensive drug resistance phenotypes, respectively. Colistin (99.8% susceptible), ceftazidime/avibactam (96.8% susceptible in 2015 to 2017 and 96.2% in 2017), and ceftolozane/tazobactam (96.5% susceptible in 2017) were the most active compounds against P aeruginosa. Ceftazidime/avibactam (100.0% susceptible), amikacin (99.4% susceptible), and meropenem (97.6% susceptible) were the most active compounds against Enterobacteriaceae. S maltophilia and A baumannii exhibited high resistance to most antimicrobials tested, which is of great concern due to their increased prevalence.

Overall, the investigators concluded that, “Our results corroborate reports from other investigators by showing the predominance of Gram-negative bacteria and high occurrence of multi-drug resistant organisms …and also indicate that the two cephalosporin/b-lactamase inhibitor combinations recently approved by the FDA [US Food and Drug Administration], ceftazidime/avibactam and ceftolozane/tazobactam, represent a valuable addition to the anti-P aeruginosa armamentarium.”

Reference

Sader HS, Castanheira M, Mendes RE, Flamm RK. Frequency and antimicrobial susceptibility of Gram-negative bacteria isolated from patients with pneumonia hospitalized in ICUs of US medical centres [published online July 27, 2018] J Antimicrob Chemother. doi:10.1093/jac/dky279

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