Invasive Disease

Invasive disease includes bacteraemia, endocarditis, bone and joint infection and deep-site abscesses. One or more investigations may be required to delineate the extent of disease. Collections of pus should be drained where technically possible. Infected joints should be washed out by an orthopaedic surgeon in theatre to reduce joint damage and concomitant poor function. Temporary prosthetic material such as intravenous devices should be removed without delay.

Infection caused by methicillin-susceptible strains should be treated with a P-lactamase-resistant penicillin such as flucloxacillin. The current parenteral treatment of choice for methicillin-resistant strains is vancomycin. The choice of antibiotic for empiric treatment of suspected S. aureus, or for culture-proven disease before susceptibility test results becoming available, will depend on the rate of MRSA endemicity within a given unit and/or recent significant exposure to another patient either carrying or infected with MRSA. Strains with reduced susceptibility to vancomycin are currently rare in clinical practice, and treatment of such patients should be guided by a team including clinicians, microbiologists and the hospital infection control officer.

The broad range of clinical manifestations of S. aureus disease makes it impossible to present a suitable treatment regimen and duration in all cases. The optimal duration of treatment for patients with bacteraemia but no evidence of seeding to distant sites or heart valves is unclear. A meta-analysis of 11 studies in which patients were treated with 2 weeks of therapy reported an average late complication rate of 6.1% (Jernigan and Farr 1993). This study has been used to support the use of 2 weeks of intravenous antibiotics for uncomplicated S. aureus bacteraemia. Many centres are keen to treat for shorter periods or to change from intravenous to oral treatment after signs and symptoms have resolved. A switch to oral therapy for patients considered to be at low risk of complicated bacteraemia would reduce the potential problems associated with an extended hospital stay and the risk of (further) intravenous device-related infection. However, efficacy of shorter treatment has not been validated by clinical trial. It is recommended that management follow published guidelines and existing recommendations (Mermel etal. 2001).

Guidelines have been published for the treatment of native or prosthetic valve S. aureus endocarditis (Wilson etal. 1995; Working Party of the British Society for Antimicrobial Chemotherapy 1998; Horstkotte etal. 2004). An overview is given below.

Native Valve Endocarditis

Left-sided native valve S. aureus endocarditis requires 4 weeks of parenteral antibiotic therapy. MSSA infection is treated with a P-lactamase-resistant penicillin such as flucloxacillin. Vancomycin is the treatment of choice for patients with MRSA native valve endocarditis or for those with an anaphylactic penicillin allergy, although this is associated with a higher rate of treatment failure (Small and Chambers 1990; Levine, Fromm and Reddy 1991). Evidence for the benefit of combination therapy with gentamicin is limited. One study demonstrated that patients receiving nafcillin plus gentamicin had a more rapid rate of bacteraemia clearance, a higher rate of nephrotoxicity but no difference in mortality compared with those treated with nafcillin alone (Korzeniowski and Sande 1982). Gentamicin is currently added for the first 3-5 or 7 days (the duration of gentamicin differing between US and UK guidelines, respectively). The benefit of adding rifampicin to a penicillinase-resistant penicillin or vancomycin is also uncertain. Individuals with right-sided native valve endocarditis caused by MSSA (usually intravenous drug users) may be suitable for a shorter course of therapy (as little as 2 weeks) (Korzeniowski and Sande 1982; Chambers, Miller and Newman 1988; DiNubile 1994; Ribera etal. 1996).

Prosthetic Valve Endocarditis

Treatment requires a combined medical and surgical approach. Recommended antimicrobial therapy is 6 weeks of a penicillinase-resistant penicillin (or vancomycin if methicillin resistant) plus rifampicin and gentamicin for the first 2 weeks. Surgery is often required, and timely valve replacement surgery may be life saving. Mortality is high at 40% (Petti and Fowler 2003).

The decision to undertake valve replacement during the management of patients with both native and prosthetic valve S. aureus endocarditis should be taken on an individual patient basis. Clinical indications for surgery include uncontrolled infection, congestive cardiac failure, paravalvular abscess or haemodynamically significant valvular dysfunction (Petti and Fowler 2003). The American Heart Association Committee on infective endocarditis has identified echocardiographic features associated with a potential need for surgery (Bayer etal. 1998).

Other Invasive Disease

Infection of other deep sites often requires 4-6 weeks or more of treatment, depending on the nature and extent of infection, and treatment should be guided by experienced medical staff. Microbiologists in many hospitals in the United Kingdom provide bedside consultations and advice, while some hospitals have a more extensive consult service of microbiologists and virologists and general and infectious disease physicians.

There is a lack of consensus about the management of S. aureus meningitis (Norgaard etal. 2003). The rare community-acquired cases may be treated with high-dose P-lactamase-resistant penicillin assuming that the isolate is methicillin susceptible (Roos and Scheld 1997). Empiric treatment for community-acquired meningitis before culture results often includes the use of ceftriazone, which is a suitable alternative for MSSA. Community-acquired meningitis caused by MRSA is most unusual given the current low rate of MRSA carriage in the community and usually occurs as a complication of neurosur-gery, often in the presence of a ventricular shunt. Entry of vancomycin into the CSF is poor in the absence of meningeal inflammation, and penetration in the presence of inflammation is not well documented in human infection. Vancomycin is used for this infection, but intrathecal instillation may be used in the presence of a shunt or drain, and a second antibiotic is usually added (Pintado etal. 2002). This highly specialized area is best managed by experienced medical staff.

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