Barbara L. Jones

October 28, 2008

October 28, 2008 (Washington, DC) — Between mid-April and late-June, 2008, 12 critically ill patients in the intensive-care unit (ICU) of a Madrid hospital were identified by surveillance or diagnostic cultures as having linezolid-resistant (LR) methicillin-resistant Staphylococcus aureus (MRSA).

A late-breaking abstract describing the outbreak was presented here at the 48th Annual ICAAC/IDSA 46th Annual Meeting, a joint meeting of the American Society for Microbiology and the Infectious Diseases Society of America.

Swift contact isolation, cohorting of patients, use of environmental preventive strategies, and "drastic" reduction of linezolid use enabled the hospital to contain the outbreak. No LR-MRSA-attributed deaths occurred, and no new cases were identified from late June to October 23.

Coauthor Miguel Sanchez, MD, PhD, head of the Intensive Care Department at the Hospital Clinico San Carlos and Associate Professor of the Universidad Complutense, in Madrid, Spain, presented the study. He described the patients as male and female medical, surgical, and trauma patients with a mean age of 58.5 years. Each was "well into an ICU stay" (a mean of 34 days ) at the time of the positive index culture. All patients were intubated, had a central venous catheter, and received at least 5 days of broad-spectrum antibiotic therapy. Eleven patients had received intravenous linezolid for a median of 7.5 days. LR-MRSA was responsible for infection in 11 patients: 5 with ventilator-associated pneumonia, 5 with primary bacteremia, and 1 with catheter-related sepsis.

Laboratory findings showed that minimum inhibitory concentrations were above 8 mg/L for linelozid and less than 0.32 for tigecycline and daptomycin. Pulsed-field gel electrophoresis showed an identical pattern for all but 4 strains, which met the 80% criterion for 4 different clones (clone A predominated).

"Once the outbreak was identified, all patients were placed under strict contact isolation and cohorted, and barrier precautions were instituted hospital-wide," Dr. Sanchez said.

Environmental surfaces were swabbed and healthcare workers fingerprinted. Linezolid use was strictly limited to confirmed cases of MRSA-associated pneumonia. This mandate resulted in a sharp drop in linezolid use — from 202 defined daily doses in April, to 170 in May, to 20 in June, and 25 in July. LR-MRSA infections were thereafter treated only with vancomycin and/or tigecycline.

Fears of a coming increase in LR-MRSA infections are widespread worldwide. "It is a concerning issue and something we're worried about," said Robert Daum, MD, Professor of Pediatrics, Microbiology and Molecular Medicine at the University of Chicago, in Illinois.

But risk can vary by geography and standardized hospital practices. "In general, resistance has been very infrequent — actually quite rare — in the United States. We have not seen anything like this outbreak in [the United States]." Dr. Daum was not involved in the Madrid study, but he was a participant in the panel discussion entitled Update on Community-Associated Methicillin Resistance.

Dr. Daum described factors that might explain differing experiences with linezolid resistance, using his own institution as an example. "At our hospital, we have a very tight grip on linezolid use — you can't get it, you can't use it without calling infectious-disease people first. As a result, our use of it is very minimal in the inpatient setting."

The study did not receive commercial funding. The authors have disclosed no relevant financial relationships.

48th Annual ICAAC/IDSA 46th Annual Meeting: A Joint Meeting of the American Society for Microbiology and the Infectious Diseases Society of America: Abstract C2-1835a. Presented October 28, 2008.


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