title: Antimicrobial Effects of β-Lactams on Imipenem-Resistant Ceftazidime-Susceptible Pseudomonas aeruginosa.
abstract: We studied the resistance mechanism and antimicrobial effects of β-lactams on imipenem-resistantPseudomonas aeruginosaisolates that were susceptible to ceftazidime as detected by time-kill curve methods. Among 215P. aeruginosaisolates from hospitalized patients in eight hospitals in the Republic of Korea, 18 isolates (23.4% of 77 imipenem-resistant isolates) were imipenem resistant and ceftazidime susceptible. Multilocus sequence typing revealed diverse genotypes, which indicated independent emergence. These 18 isolates were negative for carbapenemase genes. All 18 imipenem-resistant ceftazidime-susceptible isolates showed decreased mRNA expression ofoprD, and overexpression ofmexBwas observed in 13 isolates. In contrast, overexpression ofampC,mexD,mexF, ormexYwas rarely found. Time-kill curve methods were applied to three selected imipenem-resistant ceftazidime-susceptible isolates at a standard inoculum (5 × 105CFU/ml) or at a high inoculum (5 × 107CFU/ml) to evaluate the antimicrobial effects of β-lactams. Inoculum effects were detected for all three β-lactam antibiotics, ceftazidime, cefepime, and piperacillin-tazobactam, against all three isolates. The antibiotics had significant killing effects in the standard inoculum, but no effects in the high inoculum were observed. Our results suggest that β-lactam antibiotics should be used with caution in patients with imipenem-resistant ceftazidime-susceptibleP. aeruginosainfection, especially in high-inoculum infections such as endocarditis and osteomyelitis.
authors.affiliation: Division of Infectious Diseases, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Wi
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Cheol-In
authors.initials: CI
authors.lastname: Kang
authors.affiliation: Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Asia Pacific Foundation of Infectious Diseases, Seoul, Republic of Korea.
authors.forename: Doo Ryeon
authors.initials: DR
authors.lastname: Chung
authors.affiliation: Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyong Ran
authors.initials: KR
authors.lastname: Peck
authors.affiliation: Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Asia Pacific Foundation of Infectious Diseases, Seoul, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Song
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea ksko@skku.edu.|Asia Pacific Foundation of Infectious Diseases, Seoul, Republic of Korea.
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Ko
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D000077723:Cefepime; D002442:Ceftazidime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D018272:Porins / Q000235:genetics; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002511:Cephalosporins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C118597:MexB protein, Pseudomonas aeruginosa; C121980:MexD protein, Pseudomonas aeruginosa; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; D000077725:Piperacillin, Tazobactam Drug Combination; D015378:Imipenem; D000077723:Cefepime; D010397:Penicillanic Acid; D002442:Ceftazidime; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; C063912:carbapenemase; D010878:Piperacillin
keywords: Pseudomonas aeruginosa; carbapenem resistance; ceftazidime susceptible; inoculum effect; time-kill assay