Clinical Presentation: A Man With MRSA
The patient is a 48-year-old man with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. He was on dialysis and had rigors, fever, and hypotension.
Blood cultures were obtained and he was admitted to the hospital after a dose of vancomycin and ceftazidime. Within 18 hours his blood cultures were positive for what would be identified as MRSA.
History and Physical Examination
History. The patient has had insulin-dependent diabetes since he was a teenager, and currently his A1c is approximately 10 mmol/mol. He has neuropathy, retinopathy, and nephropathy. He has a dilated cardiomyopathy after myocardial infarctions and an ejection fraction of 22%.
Physical examination. On physical examination, the following were noted:
* The patient was febrile and tachycardic
* HEENT: no emboli; he is legally blind
* Heart: 3/6 systolic murmur
* Lungs: basilar crackles
* Abdomen: nontender
* Extremities: 2+ edema, no emboli
Labs and imaging. As expected, the patient's lab studies indicated that he was diabetic, had an infection, and was in renal failure.
Hospital course. The patient's fever gradually resolved over 7 days. His blood cultures were positive on day 3 (but not day 5) for MRSA with a minimum inhibitory concentration (MIC) to vancomycin of 1.0 µg/mL. The organism was resistant to all other antibiotics except linezolid and daptomycin. The dialysis catheter was removed, and a tip culture was negative. A transthoracic echocardiogram showed vegetation on the mitral valve. He was sent home on a 6-week course of vancomycin and he completed the course, the vancomycin trough levels never falling below 18 µg/mL.
One week after completion of antibiotics, the patient was again febrile and hypotensive on dialysis and his blood cultures grew the same MRSA, with a MIC of 1.0 µg/mL to vancomycin. His evaluation in the hospital was identical to that of his last admission.
Neither the thoracic surgeon nor the patient wished to proceed with valve replacement, the former because of worries about infecting the prosthetic valve, and the latter simply not wanting the intervention.
Questions answered incorrectly will be highlighted.
What treatment option would you choose for relapsed endocarditis?Discussion: Considering the Alternatives
There is no right answer. As is often the case, it is a matter of choosing the "least bad" therapeutic option when faced with inadequate clinical trial evidence to support the alternatives.
My belief is that all of the antibiotics we have to treat MRSA stink, at least compared with a beta-lactam. I will start with some fighting words, then discuss each option.
Although vancomycin is often considered "strong," "powerful," or a "big gun," these are marketing terms used to provide a sense of false security. What you want to give are appropriate antibiotics: Kill the organism in the infected space with the least cost and toxicity. In this case, what is appropriate? Let's consider the options:
1. Another 6-week course of vancomycin. It may be said that one definition of insanity is to repeat a failed process and expect different results. Part of the problem with this treatment may be the slightly higher MIC to vancomycin. S aureus is considered susceptible at MICs of 0.5, 1.0, 1.5, and 2.0 µg/mL, but as the MIC increases, the success rate falls. Vancomycin has an expected 31% failure rate in dialysis patients with methicillin-susceptible S aureus bacteremia compared with 13% for cefazolin.[1]
2. A 6-week course of linezolid. There are no clinical trials of linezolid in endocarditis, only case reports. A review[2] suggests that "a total of 63.6% (21/33) of patients with endocarditis were cured after linezolid administration. The overall and endocarditis-related mortality was 33.3% (11/33)." Not a confidence-inducing result.
3. A 6-week course of daptomycin. Only case series for daptomycin in left-sided endocarditis have been reported, and the results were dismal: "Fifty-three patients were included: 35 with right-sided endocarditis (RIE) and 18 with left-sided endocarditis (LIE). The success rates in patients with RIE were similar between daptomycin and the comparator (42% vs 44%)....In the LIE population, treatment success rates were poor in both arms (11% vs 22%)."[3]
4. A 6-week course of linezolid and a carbapenem. This is a synergistic combination of antibiotics against MRSA[4] and, although not studied specifically in endocarditis, this approach has been evaluated in patients with recurrent MRSA bacteremia (some of whom had endocarditis) and appears effective:
"Thirty-five patients with persistent MRSA bacteremia were studied. The early microbiological response (ie, negative results for follow-up blood culture within 72 hours) was significantly higher in the linezolid-based salvage therapy group than the comparison group (75% vs. 17%; P =.006). Adding aminoglycosides or rifampicin to vancomycin was not successful in treating any of the patients, whereas linezolid-based therapy gave an 88% salvage success rate (P =.001). The Staph aureus-related mortality rate was lower for patients treated with a linezolid salvage regimen than for patients continually treated with a vancomycin-based regimen (13% vs. 53%; P =.030)."[4]
5. Strongly encourage the patient and surgeon to proceed with replacing the mitral valve. Often, comorbidities and numerous reasons to avoid valve replacement are present. Infecting the new valve is rare; I can find rates from 0.5% to 4% documented in the literature.[5]
Outcome
The patient was treated with 6 weeks of linezolid and ertapenem and was cured. Another anecdote; do with it what you will.
