MRSA treatment

As we are well aware here , methicillin-resistant staph (MRSA) infections are very common in the community. We have had very good success overall with trimethoprim/sulfa (TMP/SMX), though for deep-seated infections, I have prescribed linezolid (which is very expense, >$100/pill, and requires a prior approval). So, being strongly prior-approval averse, I was impressed with a Swedish trial showing non-inferiority between TMP/SMX plus rifampin and linezolid (see MRSA tmpsmx rifamp as good J Antimicrob Chemo 2014 in dropbox, or doi:10.1093/jac/dku352). Study publically-funded. Details:

--150 patients (ave age 69, 68% male, 93% hospitalized for infection but of those 31% were elective admission), most with significant comorbidities (63% cardiovasc,17% pulm, 20% renal, 25% cancer…) given either TMP/SMX DS tid plus rifampin 600 daily vs linezolid 600 bid
--all had had sensitivity testing and found to be susceptible to all of the meds prior to randomization
--most had deep-seated infections, though 30% had “skin and soft tissue infection”
--median duration of therapy 12 days
--on intention-to-treat analysis, no difference (75% in linezolid and 79% with TPM/SMX plus rifampin were cured on assessment at 6 weeks). For per-protocol analysis, also no difference (82% in linezolid and 88% with TPM/SMX plus rifampin were cured on assessment at 6 weeks). No difference by type/severity of infection, mortality.
--adverse reactions were common in both groups (66%), with serious adverse events in 15 pts with linezolid and 16 on combo regimen; also nonsignificant difference in adverse reactions directly attributable to linezolid (4) and combo (9)

So, potentially useful study. The vast majority of patients with MRSA seen as outpatients here respond well to TMP/SMX alone, and I would not change that. Though, before doing that in other areas, it would be useful to know community-based sensitivities of MRSA, since we do not know the patient’s bacterial sensitivities prior to starting therapy, and would only use TMP/SMX if low level of community resistance (I would guess reasonable cutoff would be around 15%, esp if the infection is not so severe). However, for patients who have more severe skin infections (and I have gone through the painful prior-approval process a couple of times for linezolid), it seems reasonable to me to try TMP/SMX plus rifampin (watching for drug-drug interactions, esp with rifampin) and follow the patient closely

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