Antimicrobial resistance in critically ill patients

 

This review focuses mainly on gram-negative bacteria. Although it approaches the problem in light of the covid-19 pandemic it has general applicability.

First a few definitions.

ESKAPE microorganisms : Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp

Enterobacterales: new term for enterobacteriaceae

MDR: resistant to at least one antibiotic in three or more categories

XDR (extensive drug-resistant): resistant to at least one antibiotic in all but two or fewer categories

PDR (pan drug-resistant): resistant to all antibiotics

Difficult to treat resistant pathogens: resistant to front line agents and requiring second-line agents of greater toxicity and often lower efficacy (eg aminoglycosides, colistin).

Rates of infections due to ESBL producing organisms and carbapenemase producing organisms are rising. K. pneumoniae carbapenemase (KPC) producing bacteria are the ones predominant in the United States. The New Delhi Metallo-beta-lactamase (NDM) and the OXA-48 carbapenemase are rising in importance.

Acinetobacter is a complex and rising concern. From the review:

Finally,A. baumannii complex frequently causes nosocomial infections, particularly in ICUs where the incidence has increased over time. The SENTRY program evaluated the frequency of cases and anti-microbial susceptibility profiles of the A. baumannii collection from medical centers registered in this program [13]. This study showed that these isolates were recovered mainly from patients with pneumonia and bloodstream infections and evidenced reduced susceptibility to most antimicrobials tested. In all regions, colistin was the most active agent followed by minocycline.

Despite this seemingly grim picture the pipeline seems to have kept up with these trends reasonably well. Newer agents include:

Ceftolozane and tazobactam (Zerbaxa) Enhanced pseudomonas activity; activity against ESBL organisms but significant resistance rates; no activity against carbapenemase producing bacteria. (If used for intra abdominal infections coadministration of metronidazole is required).

Ceftazidime–avibactam (Avycaz) and imipenem–relebactam (Recarbrio) are active against most carbapenemase producing bacteria.

Not mentioned were fosfomycin (not yet available in IV form in the US) and omadacycline (Nuzyra). Omadacycline, though expected to be bacteriostatic, has an impressive spectrum. From another paper:

Omadacycline maintains activity against difficult-to-treat pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterobacteriaceae that produce extended-spectrum β-lactamases (ESBLs) and carbapenemases, and multidrug-resistant (resistant to greater than or equal to 3 classes of agents) strains of Acinetobacter spp. and Stenotrophomonas maltophilia (2).