Resistencia A Los Antibióticos

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 2010, p. 1160–1164
0066-4804/10/$12.00 doi:10.1128/AAC.01446-09
Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Vol. 54, No. 3

Prevalence, Resistance Mechanisms, and Susceptibility of
Multidrug-Resistant Bloodstream Isolates of
Pseudomonas aeruginosa
Vincent H. Tam,1,2* Kai-Tai Chang,1 Kamilia Abdelraouf,1 CristinaG. Brioso,1 Magdalene Ameka,1
Laurie A. McCaskey,2 Jaye S. Weston,2 Juan-Pablo Caeiro,2 and Kevin W. Garey1,2
University of Houston College of Pharmacy1 and St. Luke’s Episcopal Hospital,2 Houston, Texas
Received 12 October 2009/Returned for modification 3 December 2009/Accepted 4 January 2010

Pseudomonas aeruginosa is an important pathogen commonly implicated in nosocomial infections. Theoccurrence of multidrug-resistant (MDR) P. aeruginosa strains is increasing worldwide and limiting our
therapeutic options. The MDR phenotype can be mediated by a variety of resistance mechanisms, and the
corresponding relative biofitness is not well established. We examined the prevalence, resistance mechanisms,
and susceptibility of MDR P. aeruginosa isolates (resistant to >3 classes ofantipseudomonal agents [penicillins/cephalosporins, carbapenems, quinolones, and aminoglycosides]) obtained from a large, university-affiliated hospital. Among 235 nonrepeat bloodstream isolates screened between 2005 and 2007, 33 isolates (from
20 unique patients) were found to be MDR (crude prevalence rate, 14%). All isolates were resistant to
carbapenems and quinolones, 91% were resistant topenicillins/cephalosporins, and 21% were resistant to the
aminoglycosides. By using the first available isolate for each bacteremia episode (n 18), 13 distinct clones
were revealed by repetitive-element-based PCR. Western blotting revealed eight isolates (44%) to have MexB
overexpression. Production of a carbapenemase (VIM-2) was found in one isolate, and mutations in gyrA
(T83I) and parC (S87L) werecommonly found. Growth rates of most MDR isolates were similar to that of the
wild type, and two isolates (11%) were found to be hypermutable. All available isolates were susceptible to
polymyxin B, and only one isolate was nonsusceptible to colistin (MIC, 3 mg/liter), but all isolates were
nonsusceptible to doripenem (MIC, >2 mg/liter). Understanding and continuous monitoring of the prevalenceand resistance mechanisms of MDR P. aeruginosa would enable us to formulate rational treatment strategies
to combat nosocomial infections.
toxicity concerns) may have to be used. The objectives of this
study were to examine (i) the prevalence of multidrug-resistant
P. aeruginosa, (ii) the mechanism and biofitness cost of multidrug resistance, and (iii) the susceptibilities of multidrug-resistantP. aeruginosa isolates to polymyxin antibiotics and a newer
carbapenem (doripenem). These investigations are expected to
provide a rationale for effective treatment strategies to combat
nosocomial infections.
(This study was presented in part at the 48th Interscience
Conference on Antimicrobial Agents and Chemotherapy-Infectious Diseases Society of America 46th Annual Meeting,
Washington,DC, 25 to 28 October 2008 [26].)

Pseudomonas aeruginosa is an important pathogen commonly
implicated in serious nosocomial infections such as pneumonia
and sepsis. The occurrence of multidrug-resistant P. aeruginosa
strains is increasing worldwide and limiting our therapeutic options. Resistance in P. aeruginosa may be mediated via several
distinct mechanisms (3, 13). In multidrug-resistantisolates, the
relative contributions of different molecular mechanisms toward
phenotypic multidrug resistance are not well established. While
there are multiple surveillance studies tracking the resistance of P.
aeruginosa to various antimicrobial agents over the years (6, 7),
studies reporting trends in concomitant resistance to multiple
agents over time are scarce.
A hypermutable state...