Role Of Vancomycin

PATHCHAT NO 11: The role of vancomycin in the treatment of Staphylococcus aureusinfections: 2008 Update

Dr Maria Botha MBChB(UP), FCPath(SA) Microbiology, MMed(UP) Microbiology

Staphylococcus aureus is an important cause of community-associated skin and soft tissue infections and a leading cause of nosocomial infections, especially bloodstream infections (often catheter-related), pneumonia and surgical site infections. This is not an organism to be trifled with, as crude mortality rates from 18% for nosocomial bloodstream infections to more than 50% in ventilator-associated pneumonia have been reported.

Since the advent of the first methicillin resistance in S. aureus in 1961, these MRSA strains have become endemic and even epidemic in many hospitals, long-term care facilities and communities. Contrary to popular belief, community-associated MRSA (CA-MRSA) strains are now spreading into the health-care system in the US rather than the other way around.

Infections due to drug-resistant pathogens generally result in poorer clinical and economic outcomes as opposed to those due to sensitive strains. This also holds true for MRSA vs. MSSA (methicillin sensitive S. aureus) infections. The reason for this is not necessarily greater virulence of the resistant organism (with the exception of community-associated MRSA possessing unique virulence factors) but other confounding factors, such as severity of illness and adequacy of empirical treatment.

The ever increasing rates of these strains in our health care facilities and the emergence of CA-MRSA necessitates a closer look at the antimicrobial treatment options available, not only for known MRSA infections but also for empirical use.

Vancomycin efficacy: the story thus far

Initially developed and approved for the treatment of penicillin-resistant S. aureus in 1958, vancomycin soon became the drug of choice for the treatment of MRSA infections, partly due to the limited other therapeutic options that had been available in the past. However, in recent years the increasing prevalence of MRSA has been a catalyst for the development of new antimicrobials. With alternatives suddenly available, the efficacy of vancomycin has come under close scrutiny.

Fearing Armageddon, the medical world has been awaiting the arrival of vancomycin resistance in MRSA with trepidation. However, this did not happen with a “bang”, but has instead slowly crept up on us in the last decade.

The terminology used to describe Staphylococcus aureuswith reduced susceptibility to glycopeptides (i.e. vancomycin and teicoplanin) remains complex and often confusing.

Glycopeptide -resistant Staphylococcus aureus (GRSA) refer to isolates with MIC's (minimum inhibitory concentrations i.e. the minimum concentration of the antibiotic that inhibits growth of the organism) that fall within the resistant range for vancomycin (≥16 mg/l) and/or teicoplanin (≥32 mg/l). Only 6 cases of GRSA have been reported in the literature so far.

Glycopeptide-intermediate S. aureus (GISA) isolates have MIC's (for vancomycin and/or teicoplanin that fall within the intermediately susceptible range (4-8 mg/l for vancomycin and 16mg/l for teicoplanin). Heteroresistant GISA (hGISA) isolates contain only a subpopulation of organisms that exhibit reduced killing with vancomycin. The MIC's of these phenotypes, as detected in the routine clinical laboratory, are within the susceptible range but most frequently on the higher side (1-2 mg/l). Identification of hGISA requires further testing in the laboratory.

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Role Of Vancomycin