Is there any rationale for treatment of Staphylococcus aureus infections with antimicrobials tested in vitro as ineffective?
Andreas Uekötter, Georg Peters, Karsten BeckerAbstract
Antimicrobial drug resistance remains a leading problem in modern health care, impacting on treatment options, mortality, infection control and economic issues. The introduction of new antimicrobial drugs has consistently been followed by the emergence of resistant bacteria. This review aims to answer the question whether clinical improvement is likely if treatment of Staphylococcus aureus infections is attempted using an antimicrobial drug against which resistance is expressed in vitro (RD). Over time, S. aureus has acquired a broad range of antimicrobial resistance mechanisms and methicillin-resistant S. aureus (MRSA) have become the most common multidrug-resistant healthcare-related infection-causing bacteria in Europe. Since intention-to-treat studies with a RD would be unethical, only observational studies to evaluate the impact of RD therapy have been performed. Most of these studies bolster the assumption that RD therapy offers no benefit to the patient, but some do not show a detrimental effect. Limited antimicrobial treatment options for severe, invasive infections due to MRSA might tempt physicians to treat with antimicrobials to which in vitro resistance is reported by the microbiological laboratory. Reasons for this non-evidence-based approach might include better pharmacokinetic/pharmacodynamic parameters, lesser toxicity and better bioavailability in specific compartments, and/or the assumption of an increased in vivo susceptibility of those microorganisms reported as resistant in vitro.
In vitro resistance of a bacterium to a drug implies that exposing this bacterium to that drug should result in a worse clinical outcome compared to the use of a drug to which resistance has not been observed (SD). As a counterpoint to in vitro resistance breakpoints, the concept of clinical breakpoints is therefore briefly revisited in this review. In a nutshell, no evidence has been published that S. aureus infections can be reliably treated with RDs, neither in single administration nor in combination therapy.
Clinical Microbiology and Infection, DOI: 10.1111/j.1469-0691.2011.03549.x
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