Emergence of antibiotic resistance during therapy for infections caused by Enterobacteriaceae producing AmpC beta-lactamase: implications for antibiotic use.
Enterobacter spp., Serratia marcescens, Citrobacter freundii, and Morganella morganii are characterized by chromosomally encoded AmpC beta-lactamases and possess the ability to develop resistance upon exposure to broad-spectrum cephalosporins. To determine the incidences of the emergence of resistance during antimicrobial therapy for infections caused by these organisms and the effect of the emergence of resistance on patient outcomes, all patients who were admitted to the Asan Medical Center (Seoul, Republic of Korea) from January 2005 to June 2006 and whose clinical specimens yielded Enterobacter spp., S. marcescens, C. freundii, or M. morganii were monitored prospectively. The main end point was the emergence of resistance during antimicrobial therapy. A total of 732 patients with infections were included for analysis. The overall incidence of the emergence of antimicrobial resistance during antimicrobial therapy was 1.9% (14/732). Resistance to broad-spectrum cephalosporins, cefepime, extended-spectrum penicillin, carbapenem, fluoroquinolones, and aminoglycosides emerged during treatment in 5.0% (11/218), 0% (0/20), 2.0% (2/100), 0% (0/226), 0% (0/153), and 1.1% (1/89) of patients, respectively. The emergence of resistance to broad-spectrum cephalosporins occurred more often in Enterobacter spp. (8.3%, 10/121) than in C. freundii (2.6%, 1/39), S. marcescens (0%, 0/37), or M. morganii (0%, 0/21). Biliary tract infection associated with malignant bile duct invasion was significantly associated with the emergence of resistance to broad-spectrum cephalosporins (P = 0.024 at a significance level of 0.042, by use of the Bonferroni correction). Only 1 of the 14 patients whose isolates developed resistance during antimicrobial therapy died. The emergence of resistance was more frequently associated with broad-spectrum cephalosporins than with the other antimicrobial agents tested, especially in Enterobacter spp. However, the emergence of resistance was associated with a low risk of mortality.
Choi
Sang-Ho
SH
Division of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Lee
Jung Eun
JE
Park
Su Jin
SJ
Choi
Seong-Ho
SH
Lee
Sang-Oh
SO
Jeong
Jin-Yong
JY
Kim
Mi-Na
MN
Woo
Jun Hee
JH
Kim
Yang Soo
YS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004359:Drug Therapy, Combination; D016521:Electrophoresis, Gel, Pulsed-Field; D004755:Enterobacteriaceae / Q000145:classification / Q000187:drug effects* / Q000201:enzymology; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000453:epidemiology* / Q000382:microbiology; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C048795:AmpC beta-lactamases; D001618:beta-Lactamases