Is there any rationale for treatment of Staphylococcus aureus infections with antimicrobials that are determined to be ineffective in vitro?

Antimicrobial drug resistance remains a leading problem in modern healthcare, 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 of whether clinical improvement is likely if treatment of Staphylococcus aureus infections is attempted with 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) strains have become the most common multidrug-resistant healthcare-related infection-causing bacteria in Europe. As intention-to-treat studies with an 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 caused by MRSA might tempt physicians to use 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, lower toxicity and better bioavailability in specific compartments, and/or the assumption of 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 than would be obtained with 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, either as a single administration or in combination therapy.