From the Guidelines
Methicillin-resistant (mec) organisms in blood cultures require prompt treatment with vancomycin as the first-line treatment, at a dose of 15-20 mg/kg IV every 8-12 hours, with target trough levels of 15-20 μg/mL for serious infections, as recommended by recent guidelines 1. The treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia involves the use of alternative antibiotics that target different bacterial structures or functions to effectively eliminate the infection.
- The mec genes encode penicillin-binding protein 2a (PBP2a), which has low affinity for beta-lactam antibiotics, rendering methicillin and other beta-lactams ineffective 1.
- Vancomycin is the first-line treatment for MRSA bacteremia, with a recommended dose of 15-20 mg/kg IV every 8-12 hours, and target trough levels of 15-20 μg/mL for serious infections 1.
- Alternatives to vancomycin include daptomycin (6-10 mg/kg IV daily) or linezolid (600 mg IV/PO twice daily) 1.
- Treatment duration is typically 2 weeks for uncomplicated bacteremia and 4-6 weeks for complicated cases involving endocarditis, osteomyelitis, or persistent bacteremia.
- Source control through removal of infected catheters or drainage of abscesses is essential, and blood cultures should be repeated every 24-48 hours until clearance is documented 1.
- The probability of survival in MRSA bacteremia is greater if the vancomycin concentration over time divided by the vancomycin MIC for the bacterium is high (AUC24h /MIC ratio > 400) 1.
- It is also important to consider the risk of multidrug-resistant bacteria, particularly in patients with a history of antibiotic therapy within the last 6 months, as this risk is approximately doubled 1.
From the FDA Drug Label
Baseline bacteremia in the tedizolid arm with relevant pathogens included two subjects with MRSA, four subjects with MSSA, two subjects with S. pyogenes, one subject with S. agalactiae, and one subject with S. constellatus. Methicillin-resistant S. aureus112/141 (79.4)113/146 (77.4)114/141 (80.9)111/146 (76.0) Methicillin-susceptible S. aureus164/188 (87.2)167/198 (84.3)166/188 (88.3)167/198 (84.3)
The mec (methicillin) resistances in blood culture are:
- Methicillin-resistant S. aureus (MRSA): 112/141 (79.4%) and 113/146 (77.4%)
- Methicillin-susceptible S. aureus (MSSA): 164/188 (87.2%) and 167/198 (84.3%) 2
From the Research
Methicillin Resistance in Blood Culture
- Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in the hospital setting, causing substantial morbidity and mortality each year 3.
- MRSA bacteremia is a serious clinical infection associated with a high risk of mortality, and dual therapy is often used in patients with persistent bacteremia 4.
Treatment of MRSA Bacteremia
- Vancomycin has remained a first-line treatment for many different types of MRSA infections, but it has limitations, such as nephrotoxicity and rapid target attainment 3.
- Newer anti-MRSA antibiotics, including linezolid, daptomycin, and ceftaroline, have been approved and are now recommended as co-first-line options in clinical practice guidelines 3.
- Studies have compared the outcomes of vancomycin or daptomycin monotherapy with those of dual therapy with ceftaroline in high-grade or persistent MRSA bacteremia, showing similar 30-day mortality rates between the monotherapy and dual therapy groups 4.
- The combination of vancomycin and cefazolin lipid nanoparticles has been shown to overcome antibiotic resistance of MRSA, with liposomal vancomycin reducing minimum inhibitory concentration (MIC) values 2-fold compared to commercial vancomycin 5.
Comparison of Antibiotic Regimens
- A cost-effectiveness analysis compared the cost-effectiveness of vancomycin and other antibiotic regimens against MRSA bloodstream infections, finding that intravenous linezolid was the least expensive regimen at 4 and 6 weeks 6.
- Daptomycin was more expensive and more effective than linezolid, with an incremental cost-effectiveness ratio (ICER) of ~$13,000 (4 weeks) per composite failure avoided 6.
- Vancomycin and ceftaroline/daptomycin were dominated strategies at both 4 and 6 weeks, and vancomycin was favored when its microbiological failure risk was less than 20.1% 6.