Outbreak of meropenem-resistant Serratia marcescens comediated by chromosomal AmpC beta-lactamase overproduction and outer membrane protein loss.
The aim of this study was to investigate the mechanisms involved in the meropenem resistance of Serratia marcescens clinical isolates. Meropenem-resistant (MIC range, 16 to 32 μg/ml) S. marcescens isolates were recovered from nine patients in a tertiary hospital in Seoul, South Korea, from June to November 2005. All the isolates shared identical or similar (>85% similarity) SpeI macrorestriction patterns, indicating clonal spread. PCR experiments did not detect any carbapenemase in those isolates. They carried the bla(CTX-M-22) gene located on a 150-kbp plasmid of the incompatibility group L/M; however, the addition of clavulanic acid exhibited few effects on meropenem MICs. Although meropenem MICs were reduced 4- to 16-fold with the addition of boronic acid, no plasmid-borne AmpC β-lactamase gene was detected in PCR experiments. Real-time quantitative PCR experiments showed that expression levels of the chromosomal ampC gene in those isolates were 87.06 to 155.76 times higher than that of the reference strain ATCC 8100. SDS-PAGE showed a lack of the 42-kDa outer membrane protein (OmpF). In combination with the overproduction of the chromosomal AmpC enzyme, the loss of OmpF may have played a role in the acquisition of meropenem resistance in our isolates.
Suh
Borum
B
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 120-752, 134 Shinchon-dong, Seodaemun-gu, Seoul, Republic of Korea.
Bae
Il Kwon
IK
Kim
Juwon
J
Jeong
Seok Hoon
SH
Yong
Dongeun
D
Lee
Kyungwon
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015139:Blotting, Southern; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018272:Porins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016868:Serratia Infections / Q000188:drug therapy / Q000382:microbiology*; D012706:Serratia marcescens / Q000187:drug effects* / Q000235:genetics; D013845:Thienamycins / Q000494:pharmacology; D055815:Young Adult; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C109237:OmpF protein; D018272:Porins; D013845:Thienamycins; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D000077731:Meropenem