Inpatient antibiotic resistance: Everyone’s problem

Health care-associated methicillin-resistant Staphylococcus aureus

S. aureus is a common culprit of hospital-acquired infections, including central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and nosocomial skin and soft tissue infections. In fact, nearly half of all isolates from these infections are reported to be methicillin-resistant S. aureus (MRSA).³

Nearly half of all Staphylococcus aureus isolates from hospital-acquired infections are reported to be methicillin-resistant.

Patients at greatest risk for MRSA infections include those who have been recently hospitalized, those receiving recent antibiotic therapy or surgery, long-term care residents, intravenous drug abusers, immunocompromised patients, hemodialysis patients, military personnel, and athletes who play contact sports.^4,5 Patients with these infections often require the use of an anti-MRSA agent (eg, vancomycin, linezolid) in empiric antibiotic regimens.^6,7 The focus of this discussion is on MRSA in hospital and long-term care settings; a discussion of community-acquired MRSA is addressed elsewhere. (See “Antibiotic stewardship: The FP’s role,” J Fam Pract. 2016;65:876-885.⁸)

Efforts are working, but problems remain. MRSA accounts for almost 60% of S. aureus isolates in ICUs.⁹ Thankfully, rates of health care-associated MRSA are now either static or declining nationwide, as a result of major initiatives targeted toward preventing health care-associated infection in recent years.¹⁰

Methicillin resistance in S. aureus results from expression of PBP2a, an altered penicillin-binding protein with reduced binding affinity for beta-lactam antibiotics. As a result, MRSA isolates are resistant to most beta-lactams.⁹ Resistance to macrolides, azithromycin, aminoglycosides, fluoroquinolones, and clindamycin is also common in health care-associated MRSA.⁹

The first case of true vancomycin-resistant S. aureus (VRSA) in the United States was reported in 2002.¹¹ Fortunately, both VRSA and vancomycin-intermediate S. aureus (VISA) have remained rare throughout the United States and abroad.^9,11 Heterogeneous VISA (hVISA), which is characterized by a few resistant subpopulations within a fully susceptible population of S. aureus, is more common than VRSA or VISA. Unfortunately, hVISA is difficult to detect using commercially available susceptibility tests. This can result in treatment failure with vancomycin, even though the MRSA isolate may appear fully susceptible and the patient has received clinically appropriate doses of the drug.¹²

Treatment. Vancomycin is the mainstay of therapy for many systemic health care-associated MRSA infections. Alternative therapies (daptomycin or linezolid) should be considered for isolates with a vancomycin minimum inhibitory concentration (MIC) >2 mcg/mL or in the setting of a poor clinical response.⁴ Combination therapy may be warranted in the setting of treatment failure. Because comparative efficacy data for alternative therapies is lacking, agent selection should be tailored to the site of infection and patient-specific factors such as allergies, drug interactions, and the risk for adverse events (TABLE 1^13-17).

Ceftaroline, the only beta-lactam with activity against MRSA, is approved by the US Food and Drug Administration (FDA) for use with acute bacterial skin and skin structure infections (ABSSIs) and community-acquired bacterial pneumonia.¹⁸ Tedizolid, a new oxazolidinone similar to linezolid, as well as oritavancin and dalbavancin—2 long-acting glycopeptides—were also recently approved for use with ABSSIs.^13,14,19

Oritavancin and dalbavancin both have dosing regimens that may allow for earlier hospital discharge or treatment in an outpatient setting.^13,14 Telavancin, quinupristin/dalfopristin, and tigecycline are typically reserved for salvage therapy due to adverse event profiles and/or limited efficacy data.¹⁵