Risk factors associated with extended-spectrum beta-lactamase-producing organisms at a tertiary care hospital.
BACKGROUND
In 1995, beta-lactam inhibitor combinations replaced third-generation cephalosporins as empirical therapy in an effort to manage extended-spectrum beta-lactamase (ESBL) resistance. This study investigated the relationship between antibiotic usage and ESBL organisms from 1994 through 2002 using epidemiological and molecular analysis.


METHODS
A case-control study of 119 patients with ESBL organisms and 132 patients with non-ESBL organisms was conducted. Demographics, co-morbidities, device utilization and antibiotic use were analysed for all patients and infected patients only (cases = 75, controls = 83). Both exposure and degree of exposure (in grams) to antibiotics were included. A dot blot hybridization technique was used to identify genes in plasmid extracts from the ESBL organisms.


RESULTS
Ventilator days OR 1.1 (1.06, 1.15) P < 0.001, adult respiratory distress syndrome (ARDS) OR 3.1 (1.0, 9.7) P = 0.05, prior aminoglycoside use OR 2.7 (1.2, 6.1) P = 0.02, prior third-generation cephalosporin use OR 7.2 (2.6, 20) P < 0.001, and prior trimethoprim/sulfamethoxazole use OR 8.8 (3.1, 26) P < 0.001 were significantly associated with ESBL organisms by multivariate analysis. All models were concordant with a significant association of ventilator days, third-generation cephalosporins and trimethoprim/sulfamethoxazole with ESBL organisms. beta-Lactamase inhibitor combinations were not associated with ESBL organisms. Hybridization of plasmid extracts demonstrated that 95% of the ESBL organisms carried intI1, a mobile DNA element with a sulphonamide-resistance (R) gene and a frequent carrier of other R factors. Genes for specific types of trimethoprim-R and aminoglycoside-R were present in 26% and 40% of the extracts, respectively.


CONCLUSIONS
These data indicate that, besides patient risk factors and third-generation cephalosporins, other antibiotics may provide selective pressures in maintaining ESBL organisms due to multiple resistance genes on plasmids. beta-Lactamase inhibitor combinations appear to be an acceptable substitute to third-generation cephalosporins in strategies to control ESBL organisms.
Graffunder
Eileen M
EM
Department of Epidemiology MC-45, Albany Medical Center, NY 12208, USA. Graffue@mail.amc.edu
Preston
Karen E
KE
Evans
Ann M
AM
Venezia
Richard A
RA
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000209:etiology*; D016022:Case-Control Studies; D002511:Cephalosporins / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D012121:Respiration, Artificial / Q000009:adverse effects; D012307:Risk Factors; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases