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Gram-Negative Bacteria in Pneumonia Patients Demands Targeted Therapies

Gram-negative organisms are showing up at higher rates in seriously ill pneumonia patients. What are the best antibiotics to prescribe, given the real risk of death and the need to avoid contributing to drug resistance?

Pneumonia is at or near the top of the list of most common infections in hospital patients. This lung condition kills tens of thousands in the United States annually; more than 53,000 died from pneumonia or influenza in American hospitals in 2013, according to the Centers for Disease Control and Prevention. Clearly, a problem this serious needs to be fought quickly and efficiently with appropriate antibiotics. Especially concerning to epidemiologists is that Gram-negative bacteria—which can be harder to combat—is showing up more and more in specimens collected from pneumonia patients.

Recognizing the risk posed by increasing numbers of infections caused by the Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae, as well as a host of other Gram-negative organisms, a team of scientists from JMI Laboratories in North Liberty, Iowa conducted a study on the effectiveness of a variety of antibiotics. The laboratory, which works with drug companies to develop new antimicrobial agents, investigated how well cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and polymyxins—among others—worked against microbial organisms. The trial was conducted using 6,091 bacterial samples that had been collected from pneumonia patients in intensive care units in 75 medical centers nationwide between 2015 and 2017.

Roughly two-thirds of all the specimens collected from patients contained Gram-negative bacteria, the most frequent of which was P. aeruginosa, which represented 20.7% of all samples overall (including both Gram-negative and Gram-positive bacteria). Klebsiella was the next most common Gram-negative bacteria, at 11.8% of all samples collected. Those were followed by Enterobacter (8.3%), E. coli (7.1%), Stenotrophomonas maltophilia (5.1%), Serratia marcescens (4.6%), H. influenzae (2.8%), Acinetobacter baumannii (2.8%), and Streptococcus pneumoniae (1.5%). Some of the bacteria samples were categorized by the investigators as either MDR or XDR. MDR meant they were not susceptible to 1 or more antimicrobials in 3 or more antimicrobial classes, and XDR meant they were not susceptible to 1 or more agents in all but 2 or fewer antimicrobial classes.

Against P. aeruginosa—the most common single Gram-negative bacteria in pneumonia patients in this study—colistin proved the most effective antimicrobial, with a susceptibility rate of 99.8%. Ceftolozane/tazobactam and ceftazidime/avibactam also yielded very high susceptibility rates. Against Enterobacteriaceae microbes, which were the most common family of bacteria isolated from patients in this study (and which includes Klebsiella), ceftazidime/avibactam was most effective with a 100% susceptibility rate. When looking at the best protection against Gram-negative bacteria overall, the investigators found that ceftazidime/avibactam and amikacin led the pack.

“Our results corroborate reports from other investigators by showing the predominance of Gram-negative bacteria and high occurrence of MDR organisms,” the investigators wrote in the discussion section of their report. “The results of the present study also indicate that the two cephalosporin/B-lactamase inhibitor combinations recently approved by the FDA, ceftazidime/avibactam and ceftolozane/tazobactam, represent a valuable addition to the anti-P. Aeruginosa armamentarium. Furthermore, ceftazidime/avibactam provided complete coverage against Enterobacteriaceae and may represent a valuable option for empirical therapy for patients hospitalized with pneumonia in U.S. medical centres.”

Because antibiotic resistance is a large and growing problem, scientists are under intense pressure to come up with new agents that are effective against microbes. Physicians also are under pressure to choose correctly when prescribing drugs already on the market, given influenza’s potentially serious complications.

Ms. Saloman is a health writer with more than 20 years of experience working for both consumer-and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.