Vancomycin in high doses for the treatment of MRSA infections
The high prevalence of methicillin-resistant Staphylococcus aureus clinical isolates with a high BMC value of vancomycin requires an aggressive empirical dosage of the drug to reach target concentrations of more than 15 μg / ml.
The ineffectiveness of vancomycin in the treatment of infections caused by drug-sensitive strains of methicillin-resistant Staphylococcus aureus (MRSA) with high minimum inhibitory concentration (MIC) values has led to recommendations for increasing the dose of the drug in such clinical situations in order to reach target concentrations 15-20 mcg / ml.
The objective of a prospective cohort study by L.K. Hidayat et al. (United States) for the period August 2004 to June 2005, this involved determining the MPC range of vancomycin for MRSA and treatment outcomes for adult patients with infections caused by this micro- organism when using the drug in doses that reach concentrations exceeding the CPI of four. and many times. The selection of patients to be included in the study was made using the computer database of the microbiology laboratory. The main evaluation indicators were clinical efficacy, mortality and nephrotoxicity. All patients were divided into subgroups based on the extent to which target drug concentrations were achieved, as well as the BMC level of vancomycin for the strain that caused the infection (high over 2 μg / ml vs low less than 2 μg / ml) to analyze the effectiveness of the therapy and the level of drug concentration (greater than 15 μg / ml vs low less than 15 μg / ml ) for the analysis of nephrotoxicity.
In 51 (54%) of the 95 patients included in the study, strains of MRSA with high BMD were isolated. Staph infections in these patients were mainly represented by pneumonia (77%) and / or bacteremia. According to the results, the initial positive dynamics in response to antibiotic therapy were observed in 74% of patients when the target drug concentrations were reached, regardless of BMD. However, despite reaching the target drug concentrations, patients infected with MRSA strains with a high BMD showed a lower frequency of effectiveness of the treatment at the time of its discontinuation and a higher mortality from infectious diseases than those from the group of patients infected with weak BMD strains. (24/39, 62% vs 34/40, 85%; p = 0.02 and 11/51, 24% vs 4/44, 10%; p = 0.16, respectively).
According to the results of a multivariate analysis, the high MPC values of vancomycin for the strain of microorganism which caused the infection (p = 0.03) and the total score on the APACHE II scale (p = 0.009) were independent predictors of treatment failure. Nephrotoxicity was observed only in the group of patients receiving high doses of vancomycin (11/63, 12%), and the concomitant use of nephrotoxic drugs was an important prognostic factor in the development of this adverse drug reaction.
Based on the results obtained, the authors conclude that the high prevalence of clinical MRSA isolates with high BMC values of vancomycin (2 μg / ml) requires empirical administration of the drug at higher doses to achieve BMD values. targets greater than 15 μg / ml. For invasive infections caused by these strains, the use of other antibacterial drugs or combination therapy can be considered an alternative.