Staphylococcus aureus: The new adventures of a legendary pathogen
ABSTRACTNosocomial infections with strains of methicillin-resistant Staphylococcus aureus (MRSA) began to emerge in the 1960s, are increasing in frequency, and tend to have worse outcomes than infections due to methicillin-susceptible S aureus. Community-associated MRSA infections emerged in the 1990s. Community-associated MRSA strains have up to now been epidemiologically and bacteriologically distinct from hospital-associated MRSA strains, but in a new twist, MRSA strains that have so far been only community-associated are invading the hospital. Another worrisome trend is increasing resistance to vancomycin (Vancocin).
KEY POINTS
- Community-associated MRSA infections tend to affect patients younger than those who traditionally get hospital-associated MRSA infections. Most of these infections are of the skin and soft tissues, but this pathogen can also affect deeper tissues, and bacteremia and necrotizing pneumonia have been reported.
- For patients with skin and soft-tissue infections due to MRSA, incision and drainage rather than antibiotic therapy is often the key intervention.
- Vancomycin has been our stalwart for treating MRSA infections for more than 40 years, but it is not working as well as it used to, at least in certain situations. Vancomycin should not be used to treat infections due to methicillin-susceptible S aureus.
- Needed are better understanding of the factors that influence persistent S aureus bacteremia, well-controlled, prospective studies, and continued antibiotic development.
NEW ANTIBIOTICS
Several new antibiotics are active against gram-positive cocci.41–44 However, the majority of them have not been prospectively studied for treating bacteremia or endocarditis.
Quinupristin/dalfopristin (Synercid) has not been formally studied for treatment of MRSA bacteremia or endocarditis. There are a few case reports of its use in these conditions.45 Quinupristin/dalfopristin is bacteriostatic, and its use may be associated with phlebitis, myalgias, and arthralgias.46
Linezolid (Zyvox) is approved for treatment of complicated skin and soft-tissue infections and for hospital-acquired pneumonia. There have been no specific studies of linezolid in the treatment of S aureus bacteremia or endocarditis. However, Shorr et al47 retrospectively looked at the bacteremic patients in five previous studies of linezolid vs vancomycin and found 144 cases of S aureus bacteremia, half of which were due to MRSA. Of 53 assessable patients with MRSA bacteremia, the primary infection was cured in 14 (56%) of the linezolid patients and 13 (46%) of the vancomycin patients.
The oral form is 100% bioavailable. One should avoid concomitant use of serotonin-reuptake inhibitors because of the risk of serotonin syndrome. Adverse effects include altered taste sensation and peripheral neuropathy. There are other potential toxicities, including hematologic changes (thrombocytopenia, leukopenia) and metabolic effects (lactic acidosis), so clinical and laboratory monitoring is important.48 The role of linezolid in the treatment of patients with S aureus bacteremia or endocarditis remains to be defined.
Daptomycin is indicated for complicated skin and soft-tissue infections, bacteremia, and right-sided endocarditis due to S aureus. Fowler et al20 found that daptomycin was not inferior to beta-lactam antibiotics for treatment of MSSA bacteremia and right-sided endocarditis, and for MRSA infections it outperformed vancomycin, but the difference was not statistically significant.
The dosing interval should be increased from once every 24 hours to every 48 hours if the creatinine clearance is 30 mL/minute or less. Adverse effects include myalgia, rhabdomyolysis (rare), and elevations in creatine phosphokinase. Reports of rising MICs during daptomycin therapy, in some cases associated with persistent infection,49 suggest that careful attention be paid to dosing and clinical monitoring.
Tigecycline (Tygacil) is indicated for complicated skin and soft-tissue infections and complicated intra-abdominal infections due to susceptible organisms. It is active against both MSSA and MRSA, but clinical experience with its use in invasive infections is somewhat limited.50 The dose of tigecycline should be reduced in advanced cirrhosis. Adverse effects include nausea and vomiting.
Telavancin, dalbavancin, and oritavancin, investigational parenteral antibiotics that are derivatives of vancomycin, are in clinical trials. The pharmacokinetic activity of these agents is of interest: telavancin is being studied with a once-daily dosing interval and dalbavancin’s half-life allows once-weekly dosing. In a limited trial, dalbavancin was found to be safe and effective in the treatment of catheter-related bloodstream infections.51 None of the antibiotics in this group has been studied for treatment of S aureus endocarditis. Telavancin therapy has been associated with rash, hypokalemia, QT prolongation, and creatinine elevations. Gastrointestinal symptoms have been reported with the use of dalbavancin.
Ceftobiprole, another investigational agent, is the only cephalosporin antibiotic that is active against MRSA. It is given every 12 hours. Adverse effects include nausea and taste disturbance.
Iclaprim is a novel diaminopyrimidine and a dihydrofolate reductase inhibitor. In vitro, it is active against gram-positive bacteria, including MRSA, VISA, and VRSA; clinical investigations at this point are limited to the treatment of skin and soft-tissue infections.
