Abstract
BackgroundMethicillin resistant Staphylococcus aureus (MRSA) is an increasingly common cause of nosocomial infections, causing severe morbidity and mortality worldwide, and accounting in some hospitals for more than 50% of all S. aureus diseases. Treatment of infections caused by resistant bacterial pathogens mainly relies on two therapeutic modalities: development of new antimicrobials and use of combinations of available antibiotics.Combinations of antibiotics used in the empiric treatment of infections with suspected methicillin resistant Staphylococcus aureus etiology were investigated.MethodsDouble (vancomycin or teicoplanin with either levofloxacin or cefotaxime) and triple (vancomycin or teicoplanin + levofloxacin + one among amikacin, ceftazidime, cefepime, imipenem, piperacillin/tazobactam) combinations were evaluated by means of checkerboard assay and time kill curves. Mutational rates of single and combined drugs at antimicrobial concentrations equal to the resistance breakpoints were also calculated.ResultsVancomycin or teicoplanin + levofloxacin showed synergy in 16/50 and in 9/50 strains respectively, while vancomycin or teicoplanin + cefotaxime resulted synergic for 43/50 and 23/50 strains, respectively. Triple combinations, involving teicoplanin, levofloxacin and ceftazidime or piperacillin/tazobactam gave synergy in 20/25 strains. Teicoplanin + levofloxacin gave synergy in triple combinations more frequently than vancomycin + levofloxacin.For single antibiotics, mutational frequencies ranged between 10-5 and <10-9 for levofloxacin, cefotaxime, amikacin and imipenem, and <10-9 for vancomycin and teicoplanin. When tested in combinations, mutational frequencies fell below 10-9 for all the combinations.ConclusionIn vitro evidence of synergy between glycopeptides, fluoroquinolones (levofloxacin) and β-lactams and of reduction of mutational frequencies by combinations are suggestive for a potential role in empirical therapy of severe pneumonia with suspected MRSA etiology.
Highlights
Methicillin resistant Staphylococcus aureus (MRSA) is an increasingly common cause of nosocomial infections, causing severe morbidity and mortality worldwide, and accounting in some hospitals for more than 50% of all S. aureus diseases
Mutational frequencies ranged between 10-5 and
In vitro evidence of synergy between glycopeptides, fluoroquinolones and β-lactams and of reduction of mutational frequencies by combinations are suggestive for a potential role in empirical therapy of severe pneumonia with suspected MRSA etiology
Summary
Methicillin resistant Staphylococcus aureus (MRSA) is an increasingly common cause of nosocomial infections, causing severe morbidity and mortality worldwide, and accounting in some hospitals for more than 50% of all S. aureus diseases. Treatment of infections caused by resistant bacterial pathogens mainly relies on two therapeutic modalities: development of new antimicrobials and use of combinations of available antibiotics. Prevalence of bacterial pathogens resistant to the available antibiotics has been increasing over the past several decades This feature represents a major challenge for developing innovative therapeutic modalities, for treatment of Gram-positive infections. Methicillin resistant Staphylococcus aureus (MRSA) is an increasing common cause of nosocomial infections, causing severe morbidity and mortality worldwide, and accounting in some hospitals for more than 50% of all S. aureus diseases [1,2,3,4]. Of particular concern is that methicillin resistance, in nosocomial strains, is often associated with resistance to other antibiotics such as macrolides and fluoroquinolones, so that glycopeptides and the oxazolidinones constitute the only available therapeutic options, once an MRSA infection has been diagnosed
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