Comparative Effectiveness of Antibiotic Treatments for Methicillin-Susceptible Staphylococcus Aureus Infections
Summary
Methicillin-susceptible Staphylococcus aureus (MSSA) remains a leading cause of bloodstream and deep-seated infections worldwide. Treatment guidelines have historically favoured antistaphylococcal penicillins such as nafcillin or oxacillin and first-generation cephalosporins, notably cefazolin, based on superior bactericidal activity and lower toxicity compared with glycopeptides. Recent clinical studies have explored alternative β-lactams—such as dicloxacillin, cephalotin, ceftriaxone—and combination regimens including ertapenem plus cefazolin, to address drug shortages, outpatient parenteral therapy needs and persistent bacteraemia. Comparative data highlight that β-lactams confer lower mortality, fewer renal adverse events and reduced treatment failure than vancomycin when definitive culture results confirm MSSA. However, inoculum effects and regional antibiotic susceptibility patterns can influence outcomes, prompting renewed interest in penicillin susceptibility testing where penicillin-susceptible MSSA (PSSA) emerges. Optimisation of regimen selection requires balancing efficacy, safety and pharmacokinetic–pharmacodynamic parameters, with global stewardship efforts aimed at preserving first-line agents and expanding outpatient care options for MSSA infections.
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Comparative Effectiveness of Antibiotic Treatments for Methicillin-Susceptible Staphylococcus Aureus Infections publication trend
The graph below shows the total number of articles in comparative effectiveness of antibiotic treatments for methicillin-susceptible staphylococcus aureus infections across all publications each year (not limited to Nature Index journals).
Technical terms
Methicillin-susceptible Staphylococcus aureus (MSSA): A strain of Staphylococcus aureus lacking mecA-mediated resistance, indicating susceptibility to methicillin and related β-lactam antibiotics.
β-Lactam antibiotics: A class of antibiotics characterised by a β-lactam ring, including penicillins and cephalosporins, that inhibit bacterial cell-wall synthesis.
Antistaphylococcal penicillins: Narrow-spectrum β-lactams (e.g., nafcillin, oxacillin, dicloxacillin) engineered to resist inactivation by staphylococcal β-lactamases.
Inoculum effect: A phenomenon where higher bacterial load increases the minimum inhibitory concentration (MIC) of an antibiotic, potentially reducing clinical efficacy.
References
- Cephalotin Versus Dicloxacillin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteraemia: A Retrospective Cohort Study. Antibiotics (2024).
- Comparative Effectiveness of Beta-Lactams Versus Vancomycin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections Among 122 Hospitals. Clinical Infectious Diseases (2015).
- Efficacy and safety of cefazolin versus antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a systematic review and meta-analysis. BMC Infectious Diseases (2018).
- Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia. Antimicrobial Agents and Chemotherapy (2016).
- The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia. Open Forum Infectious Diseases (2018).
- Genomic epidemiology and characterisation of penicillin-sensitive Staphylococcus aureus isolates from invasive bloodstream infections in China: an increasing prevalence and higher diversity in genetic typing be revealed. Emerging Microbes & Infections (2022).
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