Daptomycin

Atlanta -- The strongest predictors of poor outcome in patients with Staphylococcus aureus wound infection are patient-dependent factors, such as the presence of diabetes mellitus, according to Lisa Tibor, M.D., an orthopedics resident at the University of Michigan Hospitals. At the annual meeting of the Wound Healing Society here, Dr. Tibor presented results of a study she conducted as a Fulbright fellow and third-year medical student at the Microbial Genetics Laboratory, University of Tubingen and the Wound Healing Laboratory, UCSF Medical School.

Staphylococcus aureus is the most common bacterium cultured from infected wounds. Some studies have suggested that methicillin resistant S. aureus (MRSA) strains are associated with increased virulence, although conflicting results have been obtained with other studies.

Dr. Tibor and colleagues at UCSF and the University of Tubingen hypothesized that infection by S. aureus strains with methicillin resistance would be a strong bacterial predictor of poor clinical outcome. They also hypothesized that presence of diabetes mellitus and/or peripheral arterial disease would be a strong patient predictor of poor clinical outcome. Poor clinical outcome was defined as sepsis, amputation or death.

Dr. Tibor and colleagues selected 38 strains isolated from clinical wound cultures of patients treated at the University of Tubingen from September to November, 2001. The selection criteria were:

* The infection occurred in a wound;

* The pathogen was S. aureus.

The clinic where the patient received treatment and the location of the wound were not considered in strain selection.

From chart review they collected patient data on wound type, wound location, co-morbidities and the antibiotic resistance profile of the bacterial strain at the time of isolation. To the extent that it could be determined, they also collected information on the ultimate clinical outcome of the infected wound. Of the 38 patients, 12 had diabetic arterial ulcers, nine had arterial ulcers and eight had venous ulcers. Each of the remaining nine patients had a unique wound, such as infected hematoma, pressure ulcer, purpuric vasculitis and others.

The S. aureus chromosome contains a G/C-rich Staphylococcus repeat element, or STAR element, which varies in length and copy number among different S. aureus strains. Molecular analysis of specific chromosomal loci with STAR elements provides a way of characterizing and defining different S. aureus strains.

"STAR element analysis has potential as a quick, easy, PCR-based method of strain typing and may ultimately be useful for predicting a strain's antibiotic resistance pattern," Dr. Tibor says.

STAR patterns at two chromosomal loci were analyzed by PCR. Strains were tested for resistance to methicillin and eight other antibiotics using antibiotic-impregnated BM agar. Antibiotic concentration was 5 mcg/ml. Strains were considered resistant if bacteria grew on the plates after overnight incubation at 37[degrees]C.

"One of the main concerns we had during the study was that all of these strains might be the same strain, because they were generally collected during the same time period from the same hospital," Dr. Tibor says. "The STAR analysis was one way for us to type them epidemiologically and ascertain that the strains were different."

Analysis of STAR patterns in the 38 clinical strains showed seven distinct groups, each with three or more strains. Twelve of the 38 strains had a unique pattern. Many of the strains in STAR group II/I and all strains in STAR group III/IV were MRSA strains.

There was a trend towards association of MRSA strain and poor clinical outcome. Approximately 40 percent of patients with MRSA strains had poor clinical outcomes, compared to 20 percent of patients with strains resistant to other antibiotics. However, with the small sample size, the difference did not show statistical significance.

Severe outcomes occurred in a higher proportion of patients with diabetic ulcers than in non-diabetic patients with other types of wounds. "Nearly 60 percent of diabetic patients had severe outcomes," Dr. Tibor says. "By comparison, no non-diabetic patient with peripheral arterial disease had a poor outcome. This was a statistically significant result."

The study was supported by the Deutsche Forschungsgemeinschaft and by a Fulbright fellowship to Dr. Tibor. The antibiotics daptomycin and linezolid were provided by Cubist Pharmaceuticals (Lexington, MA) and Pharmacia (Erlangen, Germany), respectively.

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