1. Int J Antimicrob Agents. 2010 Dec;36(6):513-22.

In vivo development of antimicrobial resistance in Pseudomonas aeruginosa strains
isolated from the lower respiratory tract of Intensive Care Unit patients with
nosocomial pneumonia and receiving antipseudomonal therapy.

Riou M, Carbonnelle S, Avrain L, Mesaros N, Pirnay JP, Bilocq F, De Vos D, Simon 
A, Piérard D, Jacobs F, Dediste A, Tulkens PM, Van Bambeke F, Glupczynski Y.

Unité de Pharmacologie Cellulaire et Moléculaire & Louvain Drug Research
Institute, Université Catholique de Louvain, Brussels, Belgium.

Pseudomonas aeruginosa causes severe nosocomial pneumonia in Intensive Care Unit 
(ICU) patients, with an increased prevalence of multiresistant strains. We
examined the impact of the use of antipseudomonal antibiotic(s) on the
susceptibility of P. aeruginosa isolated from ICU patients with clinically
suspected hospital-acquired pneumonia collected in five teaching hospitals (110
non-duplicate initial isolates; 62 clonal pairs of initial and last isolates
during treatment). Minimum inhibitory concentrations (MICs) were determined for
amikacin, ciprofloxacin, meropenem, piperacillin/tazobactam (TZP), cefepime and
ceftazidime (used in therapy) as well as five reporter antibiotics (aztreonam,
colistin, gentamicin, piperacillin and ticarcillin) using Clinical and Laboratory
Standards Institute (CLSI) methodology. Susceptibility was assessed according to 
European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI
breakpoints. Resistance rates prior to treatment exceeded 25% for cefepime,
ceftazidime, piperacillin, ticarcillin and aztreonam (EUCAST and CLSI) and for
gentamicin, TZP and colistin (EUCAST only). The highest rates of cross-resistance
were noted for ceftazidime and cefepime and the lowest rate for amikacin. Mean
MIC values were systematically higher in isolates from patients previously
exposed (1 month) to the corresponding antibiotic. For clonal pairs, a systematic
increase in MIC between initial and last isolates (significant for amikacin,
cefepime, meropenem and TZP) was noted. There was a significant correlation
between the use of antibiotics (adjusted for respective proportional use of each 
drug) and loss of susceptibility at the population level when using EUCAST
breakpoints. The high level of resistance of P. aeruginosa in ICU patients with
nosocomial pneumonia as well as its further increase during treatment severely
narrows the already limited therapeutic options. Further observational studies
and the development of early diagnosis for resistant isolates are warranted.

PMID: 20926262 [PubMed - in process]