Risk of emergence of Pseudomonas aeruginosa resistance to beta-lactam antibiotics in intensive care units.
OBJECTIVE
The emergence of Pseudomonas aeruginosa resistance to antimicrobial drugs is frequent in intensive care units and may be correlated with the use of some specific drugs. The purpose of our study was to identify a relationship between the use of various beta-lactam antibiotics and the emergence of resistance and to characterize the mechanism of resistance involved.


METHODS
We conducted an open prospective study over a 3-yr period by including all patients in whom P. aeruginosa had been isolated from one or more specimens: bronchial aspiration, blood cultures, catheters, and urinary cultures.


METHODS
General intensive care unit.


METHODS
One hundred and thirty-two intensive care unit patients.


METHODS
The antibiotics studied were amoxiclav, piperacillin-tazobactam, cefotaxime, ceftazidime, cefepim, and imipenem. The mechanisms of resistance studied were production of penicillinase or cephalosporinase, nonenzymatic mechanisms, and loss of porin OprD2. Analysis was performed using Cox proportional-hazard regression with time-dependant variables.


RESULTS
Forty-two strains became resistant, 30 to one antibiotic, nine to two, and three to three, leading to the study of 57 resistant strains. Imipenem (hazard ratio 7.8; 95% confidence interval, 3.4-18.1), piperacillin-tazobactam (hazard ratio 3.9; 95% confidence interval, 1.3-11.9), and cefotaxim (hazard ratio 9.3; 95% confidence interval, 2.9-30.2) were strongly linked to the emergence of resistance. The use of imipenem (p<.0001) was associated with the loss of porin OprD2. Thirty-six strains from nine patients, assayed by pulsed-field gel electrophoresis, showed that for any one patient, all the strains were genetically related.


CONCLUSIONS
Our results show that there is a high risk of the emergence of drug resistance during treatment with cefotaxime, imipenem, and piperacillin-tazobactam. This has to be taken into account in the therapeutic choice and in the patient's surveillance.
Georges
Bernard
B
Anesthésie Réanimation Polyvalente, CHU Rangueil, Toulouse, France.
Conil
Jean-Marie
JM
Dubouix
Anne
A
Archambaud
Maryse
M
Bonnet
Eric
E
Saivin
Sylvie
S
Lauwers-Cancès
Valérie
V
Cristini
Christelle
C
Cougot
Pierre
P
Decun
Jean-François
JF
Mathe
Olivier
O
Chabanon
Gérard
G
Marty
Nicole
N
Seguin
Thierry
T
Houin
Georges
G
D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D012307:Risk Factors; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams