Antimicrobial Resistance Mechanisms in Pseudomonas aeruginosa

Extract

Pseudomonas aeruginosa is one of the leading causes of healthcare-associated infections (HAI). In the more severe infections such as bacteremia and pneumonia, mortality rates are high, and the infection is often difficult to treat because there are limited drugs with anti-pseudomonal activity. Infections caused by P. aeruginosa may be treated with antimicrobial agents from three major groups based on mechanism of action: aminoglycosides (interference with protein synthesis) such as tobramycin or amikacin; beta-lactams (inhibition of cell wall synthesis) such as piperacillin, ticarcillin, 3^rd and 4^th generation cephalosporins (ceftazidime and cefepime), and carbapenems like imipenem or meropenem; or fluoroquinolones (ciprofloxacin) (interference with nucleic acid replication). In 2005, the National Healthcare Safety Network (NHSN) began collecting, summarizing and reporting data on antimicrobial-resistant pathogens that cause HAI. As described in their 2008 report, HAI pose an “ongoing and increasing challenge to hospitals, both in the clinical treatment of patients and in the prevention of the cross-transmission of these problematic pathogens”.¹

As reported by the NHSN, increases in antimicrobial resistance have significantly limited the number of available treatment options.^2-4 Production of new classes of antibiotics has stalled in the last two decades, and novel agents with activity against P. aeruginosa will not be available in the foreseeable future, thus continuous surveillance of the development of resistance to current therapeutic agents is vital as is the appropriate utilization of antimicrobial agents to minimize the development of resistance.

To investigate the development of resistance to beta-lactam antibiotics, one group followed 132 intensive care unit (ICU) patients…

ABBREVIATIONS: NHSN = National Healthcare Safety Network; HAI = healthcare-associated infections; OprF = outer membrane protein F.