title: Carbapenem-resistant-only Pseudomonas aeruginosa infection in patients formerly infected by carbapenem-susceptible strains.
abstract: Pseudomonas aeruginosa isolates that were initially carbapenem-susceptible and later became selective carbapenem-resistant following antimicrobial therapy were identified from individual cases during the same hospitalisation. Cross-resistance to other β-lactams was not found and their susceptibilities remained identical in consecutive isolates. Real-time quantitative reverse transcription PCR was performed to investigate the role of OprD, an outer membrane protein regulating the entry of carbapenems, in the appearance of carbapenem-resistant-only P. aeruginosa (CROPA). Fifteen paired isolates of carbapenem-susceptible P. aeruginosa (CS-PA) and CROPA were identified. All of the cases had carbapenem exposure history within 1 month before the appearance of CROPA (mean 10 days). Reduced OprD expression was found in 93% (14/15) of the isolates, suggesting that oprD inactivation was the major contributor to selective carbapenem resistance. Of the 14 cases with CROPA due to oprD mutation, 71% (10/14) were persistent infection, as genotype analysis revealed that their paired strains were isogenic; 29% (4/14) represented re-infections as they were heterogenic, suggesting that oprD-deficient CROPA existed in the hospital and that carbapenem selective pressure promoted its spread to patients. We conclude that CROPA may occur soon after the use of carbapenems to treat CS-PA infections and that oprD mutation is the major mechanism of resistance in CROPA. Restriction of empirical use of carbapenems by antibiotic stewardship is important to halt the occurrence of CROPA.
authors.affiliation: Department of Pediatrics, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Tsu-Lan
authors.initials: TL
authors.lastname: Wu
authors.affiliation: Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Su
authors.affiliation: Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Lo
authors.affiliation: Chang Gung University College of Medicine, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chyi-Liang
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Liang
authors.affiliation: Chang Gung University College of Medicine, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan. Electronic address: chchiu@adm.cgmh.org.tw.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Chiu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018272:Porins / Q000235:genetics*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa
keywords: Carbapenem resistance; Pseudomonas aeruginosa; oprD