Linezolid resistant Staphylococcus aureus (LRSA) emerging

by Kristina Fiore

The first known outbreak of linezolid and methicillin-resistant Staphylococcus aureus (LRSA) occurred during a 13-week period in 2008 in a hospital in Madrid, researchers say.

The LRSA outbreak, involving 12 patients in the hospital’s intensive care unit (ICU), was also the first with cfr gene-mediated linezolid resistance and was associated with nosocomial transmission and prior administration of linezolid, Miguel Sanchez Garcia, MD, PhD, of Hospital Clinico San Carlos in Madrid, and colleagues reported in the June 9 issue of the Journal of the American Medical Association.

“Although [these patients] developed potentially severe invasive infections, associated organ dysfunction was moderate, all infections improved, and we attributed only one death to LRSA infection,” they wrote.

Hospital Clínico San Carlos is a 1,000-bed tertiary care university teaching hospital in Madrid. Methicillin-resistant Staphylococcus aureus (MRSA) is endemic at the facility, the researchers said, with a mean cumulative incidence rate in the intensive care department of seven patients per 1,000 admissions.

Linezolid is widely used in critical care facilities because of its broad antimicrobial spectrum, favorable short-term safety profile, and its effectiveness, according to background provided in the paper. Linezolid is also one of the few therapeutic options for severe MRSA infections (e.g., in ventilator-associated pneumonia).

However, linezolid resistance is extremely rare in Staphylococcus aureus. The literature consists of only eight cases from the U.S., two from Germany, and one case each from the U.K., Brazil, and Colombia.

But between April 13 and June 26, 2008, the researchers identified a dozen patients with LRSA in the hospital’s ICU. They believe it was the first LRSA outbreak ever reported.

All patients were placed in isolation under strict contact precautions.

Patients’ LRSA infections were associated with moderate organ dysfunction. The disease caused ventilator-associated pneumonia in six patients and bacteremia in three. Six of the patients died, five of them in the ICU.

However, the researchers attributed just one death to LRSA infection because the patient in question had severe acute respiratory distress syndrome. Despite clinical and microbiological resolution after treatment with other antibiotics, the patient still developed this condition; therefore, the death was attributed to LRSA, the researchers said.

In assays, bacterial isolates were susceptible to trimethoprim-sulfamethoxazole, glycopeptides, tigecycline, and daptomycin, and antibiotic therapy was associated with a favorable clinical response in all cases, they added.

Genotyping identified one predominant clone and three other types of the bacteria, but cfr-mediated resistance was present in all isolates, the researchers said.

They said the “apparent risk factor is prior administration of linezolid.” Therefore, the use of linezolid in the ICU was decreased from 202 defined daily doses in April 2008 to 25 in July 2008, they wrote.