Nosocomial outbreak by Proteus mirabilis producing extended-spectrum beta-lactamase VEB-1 in a Korean university hospital.
OBJECTIVE
To examine the molecular mechanisms involved in the beta-lactam resistance of multidrug-resistant Proteus mirabilis isolates that showed an unusual synergy between imipenem and ceftazidime in a Korean hospital.


METHODS
Over an 11 month period, a total of 12 P. mirabilis isolates showing resistance to ampicillin, gentamicin, ceftazidime, cefotaxime, cefuroxime, cefalothin, cefepime, piperacillin, trimethoprim/sulfamethoxazole and ciprofloxacin, were recovered from the sputum and urine specimens of nine patients who were hospitalized in the neurosurgery ward. The extended-spectrum beta-lactamases were screened with a double disc synergy test using ceftazidime, cefotaxime, aztreonam, cefepime and clavulanate. The ESBL types were determined by PCR using specific primers for bla(TEM-1), bla(SHV-1), bla(CTX-M-1), bla(CTX-M-2), bla(CTX-M-8), bla(CTX-M-9), bla(PER-1), bla(GES-1), bla(VEB-1), bla(OXA-10) and bla(OXA-13) followed by sequencing. All the isolates underwent molecular typing by PFGE. The transferability was examined by conjugation.


CONCLUSIONS
All the isolates showed a marked synergy between the extended-spectrum cephalosporins and clavulanate together with an unusual synergy between cefoxitin and the cephalosporins (cefalothin, cefuroxime, ceftazidime, cefotaxime) and between imipenem, and ceftazidime and cefotaxime. Isoelectric focusing of the crude bacterial extracts showed a beta-lactamase band with a pI value of 5.4, which was inhibited by clavulanate. PCR and sequencing identified the gene to be bla(VEB-1). In addition, the aadB gene was detected, conferring aminoglycoside resistance. The resistance was not transferred by conjugation. The outbreak was of a clonal origin as shown by PFGE demonstrating an identical banding pattern. This is the first report of VEB-1-producing Enterobacteriaceae in Korea.
Kim
Ja-Young
JY
Department of Clinical Pathology, College of Medicine, The Catholic University of Korea, Kangnam St Mary's Hospital, 505 Banpo-dong, Seocho-ku, Seoul 137-701, Korea.
Park
Yeon-Joon
YJ
Kim
Sang-Il
SI
Kang
Moon Won
MW
Lee
Seung-Ok
SO
Lee
Kyo-Young
KY
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D029968:Escherichia coli Proteins; D006785:Hospitals, University; D006801:Humans; D007723:Korea / Q000453:epidemiology; D011512:Proteus Infections / Q000453:epidemiology / Q000382:microbiology; D011513:Proteus mirabilis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; C119424:beta-lactamase VEB-1, E coli; D001618:beta-Lactamases