Abstract
The emergence of extreme drug resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii represent a major problem in health care settings. Colistin is the only therapeutic option available for treatment of infections caused by such pathogens. Worryingly, colistin resistance recently emerged which may lead to the return to the pre antibiotic era. The aim of the present study was to assess for the first time the bactericidal activity of four novel triple antibiotic combinations, including imipenem (IMP), amikacin (AK), cefepime (CEF) and tigecycline (TIG) against four XDR P. aeruginosa and A. baumannii clinical pathogens. Antibiotic combinations were evaluated by time-kill assay at the breakpoints. Three combinations (IMP/TIG/AK, TIG/AK/CEF and IMP/TIG/CEF) showed significant bactericidal activity against XDR A. baumannii isolates. Only two combinations (IMP/AK/CEF and IMP/TIG/AK) displayed remarkable killing against XDR P. aeruginosa isolates. These finding revealed that these triple antibiotic combinations are attractive therapeutic options for treatment of infections caused by XDR pathogens and could be utilized as an alternative to colistin. Further studies are warranted to assess the clinical outcomes of such combinations. Key words: Extreme drug resistant (XDR), Pseudomonas aeruginosa, Acinetobacter baumannii, antibiotic combinations, bactericidal activity.
Highlights
Antimicrobial resistance represents a global health threat and has reached crisis points in different areas around the world (Lee et al, 2011)
Two combinations (IMP/AK/CEF and IMP/TIG/AK) displayed remarkable killing against XDR P. aeruginosa isolates. These finding revealed that these triple antibiotic combinations are attractive therapeutic options for treatment of infections caused by XDR pathogens and could be utilized as an alternative to colistin
VITEK 2 compact automated system was used for identification of four non-duplicate XDR A. baumannii and P. aeruginosa pathogens and for determination of their resistance pattern against twenty different antimicrobial agents
Summary
Antimicrobial resistance represents a global health threat and has reached crisis points in different areas around the world (Lee et al, 2011). Many extreme drug resistant (XDR) pathogens were isolated. These pathogens showed resistance to most available antimicrobial agents. Infections with such pathogens are associated with high rate of morbidity and mortality (Papp-Wallace et al, 2011). A bacterial isolate of A. baumannii or P. aeruginosa is considered as XDR when it remains susceptible to only one or two antimicrobial categories (aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, penicillins plus β-lactamase inhibitors, polymyxins, etc) (Magiorakos et al, 2012). In addition to its intrinsic resistance, P. aeruginosa has acquired resistance through production of β-lactamases and carbapenemases, overexpression of efflux pumps and reduction in porin channels while A. baumannii have developed resistance to several antimicrobial agents via production of aminoglycoside-modifying enzymes, ESBLs, and carbapenemases, in addition to target-site alteration such as changes in outer membrane proteins, penicillin binding proteins and topoisomerases (Slama, 2008)
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