In this episode, I’ll discuss persistent MRSA bacteremia after vancomycin therapy.
The usual course of treatment for MRSA bacteremia is a minimum of 14 days, and the median time to bacterial clearance is about 7 days.
For this reason, IDSA guidelines recommend an assessment to determine whether a change in therapy is indicated if MRSA bacteremia persists at or around day 7 of vancomycin therapy.
The decision to change therapy is not automatic at day 7; rather IDSA recommends a series of 4 factors be considered:
(1) the patient’s overall clinical response;
(2) vancomycin trough serum concentrations;
(3) results of susceptibility testing; and
(4) the presence of and ability to remove other foci of infection.
It may be appropriate to change therapy before 7 days have ellapsed depending on the clinical condition of the patient. For example, if a patient’s condition is worsening before 7 days has elapsed AND adequate source control of the infection had already been achieved, it may be reasonable to change therapy.
The MIC of the MRSA to vancomycin can also play into the decision. For example, a patient who has a worsening condition and an MIC of 2 mcg/mL to vancomycin may warrant a therapy change. However a patient who is improving clinically, has a low MIC, but is still bacteremic at day 7 may simply need to continue vancomycin therapy with no changes.
When therapy needs to change, the IDSA guideline authors recommend that rather than adding a new antibiotic and continuing vancomycin, the vancomycin should be discontinued and the new antibiotic be used as monotherapy.
By the time a change in vancomycin therapy is decided upon, it is highly likely that sensitivity data of the organism will be available, and this can be used to guide the choice of treatment.
Daptomycin is a highly desirable choice as an anlternative treatment, especially because it is bacteriocidal. A high dose of 10 mg/kg/day is recommended by the IDSA guideline authors.
Should a strain of MRSA be non-susceptible to both vancomycin and daptomycin, there is little data to guide therapy. Other anti-MRSA agents or combination therapy may be used, but evidence is based only on case reports. Possible combinations are:
Ceftaroline + daptomycin
Ceftaroline + vancomycin
Ceftaroline + trimethoprim-sulfamethoxazole
Daptomycin + trimethoprim-sulfamethoxazole
The combination of ceftaroline and daptomycin is supported by a multi-center, 26 patient case series that showed a median time to bacterial clearance of 2 days. A single-center 11 patient case series also reported a 100% success rate with combining ceftaroline with either daptomycin (6 patients) or vancomycin (5 patients). It is possible that in vitro synergy between daptomycin and ceftaroline occurs in vivo as well and is responsible for high clearance rates in these case series.
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