From the Guidelines
For methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia that is refractory to cefazolin, I recommend switching to intravenous nafcillin or oxacillin at 2 grams every 4 hours, or vancomycin with a target trough of 15-20 mg/L if beta-lactam allergies exist. Daptomycin at 8-10 mg/kg daily is another effective alternative, particularly for right-sided endocarditis or complicated bacteremia, as suggested by 1. Treatment failure with cefazolin may be due to the "cefazolin inoculum effect," where some MSSA strains produce beta-lactamases that can overwhelm cefazolin at high bacterial loads. Consider adding gentamicin 1 mg/kg every 8 hours for the first 3-5 days in severe cases or with endocarditis, although its use is controversial and should be weighed against the risk of nephrotoxicity, as noted in 1. Some key points to consider in the management of MSSA bacteremia include:
- Source control is essential - any infected devices should be removed, and abscesses drained, as emphasized in 1 and 1.
- Infectious disease consultation is strongly recommended.
- Monitor treatment response with daily blood cultures until negative for 48-72 hours, and continue therapy for at least 2 weeks for uncomplicated bacteremia or 4-6 weeks for endocarditis or complicated infections, as suggested by 1 and 1.
- Echocardiography should be performed to rule out endocarditis, and a thorough evaluation for metastatic foci of infection is necessary, as recommended in 1. The choice of antibiotic should be guided by susceptibility results and clinical response, with consideration of the potential for beta-lactamase production and the "cefazolin inoculum effect" 1. In cases where vancomycin is used, therapeutic drug monitoring is crucial to ensure adequate trough levels and minimize the risk of nephrotoxicity, as discussed in 1. Overall, the management of MSSA bacteremia requires a comprehensive approach that includes prompt antibiotic therapy, source control, and close monitoring for complications, as outlined in 1, 1, 1, 1, 1, and 1.
From the FDA Drug Label
The success rates by pathogen for microbiologically evaluable patients are presented in Table 16 Table 16: Clinical Success Rates by Infecting Pathogen in the cSSSI Trials in Adult Patients (Population: Microbiologically Evaluable) Pathogen Success Rate n/N (%) Daptomycin for Injection Comparator* Methicillin-susceptible Staphylococcus aureus (MSSA) † 170/198 (86%) 180/207 (87%)
The management of Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia that is refractory to cefazolin (Ancef) is not directly addressed in the provided drug label. However, based on the information provided, daptomycin has been shown to be effective against MSSA in the treatment of complicated skin and skin structure infections.
- Key points:
- Daptomycin has a high success rate against MSSA (86%) in the microbiologically evaluable population.
- The provided information does not specifically address the management of MSSA bacteremia that is refractory to cefazolin.
- Daptomycin may be considered as an alternative treatment option for MSSA infections, but its use in the specific context of MSSA bacteremia refractory to cefazolin is not explicitly supported by the provided drug label 2.
From the Research
Management of Methicillin-susceptible Staphylococcus aureus (MSSA) Bacteremia
- The management of MSSA bacteremia that is refractory to cefazolin (Ancef) involves considering alternative beta-lactam antibiotics, such as antistaphylococcal penicillins (ASPs) or ampicillin/sulbactam (SAM) 3.
- A study found that SAM can be an effective therapeutic option for bacteremia due to beta-lactamase-producing MSSA, with attention to adverse effects such as liver dysfunction 3.
- Another study suggested that cefazolin is not significantly different from cloxacillin in the treatment of MSSA bacteremia, while treatment with other beta-lactams, including second and third generation cephalosporins, might be associated with higher mortality 4.
- A systematic review and meta-analysis found that cefazolin was associated with significant reduction in mortality and clinical failure compared to ASPs, without increasing the recurrence of bacteremia 5.
- A comparative review of cefazolin versus ASPs for the treatment of MSSA bacteremia highlighted the utility of cefazolin, with similar clinical efficacy but better tolerability, and lower rates of discontinuation due to adverse drug reactions 6.
Alternative Treatment Options
- Antistaphylococcal penicillins (ASPs) are considered first-line treatment for MSSA bacteremia, but cefazolin can be used as an alternative for patients with non-severe penicillin allergies 6.
- Ampicillin/sulbactam (SAM) can be considered as a therapeutic option for MSSA bacteremia that is refractory to cefazolin, especially in cases of beta-lactamase-producing MSSA 3.
- Cloxacillin is another option that has been shown to be effective in the treatment of MSSA bacteremia, with similar efficacy to cefazolin 4.
Considerations for Treatment
- The choice of antibiotic should be based on the patient's allergy history, renal function, and the presence of any underlying conditions that may affect the pharmacokinetics of the antibiotic 6.
- Adequate source control, such as intravascular catheter removal, debridement, or drainage, is crucial for the effective treatment of MSSA bacteremia 6.
- Aggressive dosing of cefazolin may help mitigate the role of inoculum effect and improve clinical outcomes 6.