INTRODUCTION — Issues related to the treatment of bacteremia (in the absence of endocarditis) in adults caused by methicillin-resistant Staphylococcus aureus (MRSA) will be reviewed here.
General issues related to the clinical approach to patients with S. aureus bacteremia are discussed further separately. (See "Clinical approach to Staphylococcus aureus bacteremia in adults".)
Issues related to treatment of MRSA endocarditis are discussed separately. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Methicillin resistant' and "Antimicrobial therapy of prosthetic valve endocarditis", section on 'Staphylococci'.)
Other issues related to MRSA are discussed further separately:
●(See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Epidemiology".)
●(See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control".)
●(See "Methicillin-resistant Staphylococcus aureus (MRSA): Microbiology".)
●(See "Virulence determinants of community-acquired methicillin-resistant Staphylococcus aureus".)
Issues related to treatment of S. aureus bacteremia caused by vancomycin-intermediate and vancomycin-resistant isolates (vancomycin minimum inhibitory concentration ≥4) is discussed separately. (See "Staphylococcus aureus bacteremia with reduced susceptibility to vancomycin", section on 'Infection due to VISA or VRSA'.)
CLINICAL APPROACH — General issues related to the clinical approach to the treatment of MRSA bacteremia, including history and physical examination, infectious disease consultation, echocardiography, imaging, and source control, are discussed separately. (See "Clinical approach to Staphylococcus aureus bacteremia in adults", section on 'Clinical approach'.)
INTERPRETING ANTIBIOTIC SUSCEPTIBILITY DATA
MIC breakpoints — Methicillin resistance in S. aureus is defined as an oxacillin minimum inhibitory concentration (MIC) of ≥4 mcg/mL [1].
Vancomycin breakpoints for S. aureus (preferably determined by E-tests) set by the United States Clinical and Laboratory Standards Institute (CLSI) are as follows [1]:
●Susceptible = MIC ≤2 mcg/mL
●Intermediate = MIC 4 to 8 mcg/mL
●Resistant = MIC ≥16 mcg/mL
Vancomycin breakpoints for S. aureus set by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:
●Susceptible = MIC ≤2 mg/L
●Resistant = MIC >2 mg/L
Outcome data — Data regarding the impact of antibiotic susceptibility on response to treatment are conflicting, and other factors (apart from MIC) may influence clinical outcome. For these reasons, clinical factors (including symptomatic improvement and timeframe for clearance of bacteremia) are the most important indicators of response to antimicrobial therapy.
●Outcome data based on MIC are conflicting − Some studies suggest a worse clinical outcome associated with vancomycin therapy for infection due to MRSA with vancomycin MIC ≥2 mcg/mL [2-8], while others do not [9-12].
•A 2012 meta-analysis including 22 studies noted increased mortality among patients with MRSA bacteremia (vancomycin MIC ≥2 mcg/mL by E-test) treated with vancomycin (odds ratio [OR] 1.7, 95% CI 1.3-2.2); increased mortality was not observed in cases with vancomycin MIC ≤1.5 mcg/mL [6].
Similarly, in a 2016 retrospective study including 170 patients with MRSA bacteremia (vancomycin MICs 1.5 to 2 mcg/mL), treatment with vancomycin was associated with a higher rate of treatment failure (24 versus 11 percent) and a higher rate of renal complications (23 versus 9 percent) than daptomycin [13].
•However, a 2014 meta-analysis including 38 studies and more than 8200 episodes of S. aureus bacteremia found no difference in mortality between patients whose isolate had high vancomycin MIC (≥1.5 mg/L) and those whose isolate had low vancomycin MIC (<1.5 mg/L) [9].
Similarly, a 2016 prospective study including 429 patients with S. aureus bacteremia noted that there was no association between vancomycin MIC and 30- or 90-day mortality [12].
●Other factors (apart from MIC) may influence clinical outcome – There may be other factors (apart from vancomycin MIC) that contribute to clinical outcome; in one study including 532 patients with S. aureus bacteremia, those with infection due to strains with vancomycin MIC >1.5 mcg/mL (by E-test) had poorer outcomes than those infected with strains with vancomycin MIC ≤1.5 mcg/mL [7]; the outcome was independent of the methicillin susceptibility and whether the patients were treated with vancomycin or a beta-lactam.
In addition, clinical failure has been observed in patients without evidence of vancomycin resistance [14]; some of these failures have occurred in patients with heteroresistant infection (in which subpopulations of organisms have higher vancomycin MICs), although it is uncertain whether heteroresistance is a cause of vancomycin treatment failure [15]. (See "Overview of antibacterial susceptibility testing", section on 'Heteroresistance'.)
ANTIMICROBIAL THERAPY — Treatment of MRSA bacteremia consists of prompt source control (such as removal of infected vascular catheters and/or drainage of purulent collections if present) as well as initiation of appropriate antimicrobial therapy.
Initial treatment — Initial treatment of MRSA bacteremia consists of monotherapy with vancomycin; daptomycin is an acceptable alternative agent. Ceftobiprole is also a potential alternative agent; thus far it is not available in the United States. (See 'Treatment regimens' below and 'Agents warranting further study' below.)
Issues related to empiric treatment of S. aureus bacteremia (prior to availability of susceptibility data) are discussed separately. (See "Clinical approach to Staphylococcus aureus bacteremia in adults", section on 'Empiric antibiotic therapy'.)
Tailor treatment to clinical circumstances — Following initiation of antibiotic treatment for MRSA bacteremia, blood cultures should be repeated to document clearance of bacteremia. Persistent bacteremia (ie, 48 to 72 hours after initiation of treatment) has been associated with increased morbidity and mortality [16-18]. Failure to clear bacteremia within 48 to 72 hours after initiation of therapy should prompt further evaluation. (See 'Unfavorable response to initial treatment' below.)
Favorable response to initial treatment — A favorable clinical response to initial treatment includes clearance of bacteremia within 48 to 72 hours, resolution of fever and improvement in clinical manifestations.
The optimal approach to treatment of patients with a favorable clinical response is uncertain; thus far, monotherapy (with vancomycin or daptomycin) remains standard of care [19]. However, further study of combination therapy is needed; some investigators have proposed combination therapy for patients with no clear source of bacteremia and risk factors for poor outcome (including critical illness, age >65 years, renal disease, vertebral spine infection, injection drug use, and/or prior vancomycin therapy) [20].
●Monotherapy − For patients with MRSA bacteremia who respond clinically to initial treatment with vancomycin, we continue treatment with vancomycin; daptomycin is an acceptable alternative regimen (table 1) [19]. Ceftobiprole is also a potential alternative agent; thus far it is not available in the United States. (See 'Vancomycin' below and 'Daptomycin' below and 'Agents warranting further study' below.)
In areas where teicoplanin is available, some use it as the drug of choice for initial therapy of S. aureus bacteremia, while others favor its use for patients intolerant to vancomycin [21]. (See 'Teicoplanin (in areas where available)' below.)
●Combination therapy – Data on use of combination therapy are discussed further below. (See 'Combination therapy' below.)
Unfavorable response to initial treatment — Patients with unfavorable clinical response to initial treatment (persistent bacteremia beyond 48 to 72 hours, persistent fever, and lack of improvement in clinical manifestations) warrant further evaluation and antibiotic adjustment as follows:
●Clinical evaluation
•Patients should undergo evaluation for occult focus of infection that may require drainage. The approach to imaging should be tailored to findings on history and physical examination. Persistent foci of infection (such as a deep-seated bone infection, abscess, retained prosthetic device, or endovascular source of infection) should be eliminated if feasible [22]. (See "Clinical approach to Staphylococcus aureus bacteremia in adults", section on 'Diagnostic evaluation'.)
•Antibiotic susceptibility results (on the original isolate as well as the breakthrough isolate) should be reviewed carefully for susceptibility to vancomycin as well as alternative agents. Repeated isolation of S. aureus from normally sterile sites despite seemingly appropriate antibiotic therapy should prompt suspicion for emergence of an S. aureus isolate with reduced vancomycin susceptibility, even if the MIC of the original isolate was within the susceptible range [2,23-25].
●Antibiotic adjustment − For patients with persistent bacteremia (beyond 48 to 72 hours) in the absence of a removable focus of infection, antibiotic failure should be suspected and antibiotic adjustment is warranted [16,19,26-28].
The optimal antibiotic approach is uncertain; options include switching from vancomycin to daptomycin monotherapy or switching to combination therapy:
•Switch from vancomycin to daptomycin monotherapy – For patients with a clear source of bacteremia (such as skin/soft tissue infection) in the absence of the above risk factors, we favor switching to daptomycin monotherapy [19]. (See 'Daptomycin' below.)
Caution is required when treating S. aureus infection with daptomycin in the setting of vancomycin failure; infrequently, S. aureus nonsusceptibility to daptomycin has been observed when bacteremia has persisted in spite of vancomycin therapy [29]. In addition, breakthrough staphylococcal bacteremia in patients treated with daptomycin may reflect emergence of daptomycin nonsusceptibility; this possibility should be evaluated by performing susceptibility studies on breakthrough isolates.
For patients with bacteremia attributable to a pneumonia source, daptomycin should not be used; the approach to treatment of MRSA pneumonia is discussed separately. (See "Treatment of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Methicillin-resistant S. aureus'.)
•Switch from monotherapy to combination therapy
-For patients with a clear source of bacteremia (such as skin/soft tissue infection) in the absence of the above risk factors who were initially treated with daptomycin (in the setting of vancomycin intolerance), we favor switching to combination therapy. Cultures should be repeated; if a new isolate is identified, daptomycin susceptibility should be re-evaluated.
-For patients with no clear source of bacteremia and increased risk for poor outcome (including critical illness, age >65 years, renal disease, vertebral spine infection, injection drug use, and/or prior vancomycin therapy) [18,20,30], we favor switching from vancomycin monotherapy to combination therapy [20]. (See 'Combination therapy' below.)
Among the combination regimens, we favor daptomycin plus ceftaroline, if supported by susceptibility data. In such cases, we administer combination therapy until bacteremia has cleared with resolution of fever and clinical improvement, then complete treatment with monotherapy (daptomycin or ceftaroline, depending on clinical circumstances). (See 'Combination therapy' below.)
Duration of treatment — The duration of treatment for S. aureus bacteremia is discussed separately. (See "Clinical approach to Staphylococcus aureus bacteremia in adults", section on 'Completing antibiotic therapy'.)
TREATMENT REGIMENS
Monotherapy
Preferred agents
Vancomycin — Vancomycin is a bactericidal glycopeptide antibiotic that inhibits cell wall synthesis; in vitro, it kills staphylococci more slowly than beta-lactam antibiotics and is inferior to beta-lactams for treatment of methicillin-susceptible S. aureus bacteremia [4,31-35].
Vancomycin is the antibiotic agent for which there is the greatest cumulative clinical experience for treatment of MRSA bacteremia [19]. The mortality rate associated with vancomycin monotherapy for treatment of S. aureus bacteremia is 20 to 25 percent [30].
Dosing is discussed separately; monitoring is necessary due to risk of nephrotoxicity. (See "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)
Daptomycin — Daptomycin is a bactericidal cyclic lipopeptide antibiotic with concentration-dependent activity [36,37]. (See "Daptomycin: An overview".)
Dosing for treatment of bacteremia (as approved by the US Food and Drug Administration [FDA]) consists of 6 mg/kg intravenously (IV) once daily; however, we favor higher dosing of 8 to 10 mg/kg IV once daily since daptomycin exhibits concentration-dependent killing [38,39].
The daptomycin minimum inhibitory concentration may increase during therapy and may be influenced by prior exposure to vancomycin [40]. Therefore, daptomycin susceptibility testing must be performed prior to therapy and repeated in the event of positive cultures obtained during therapy, particularly if prolonged therapy is administered and/or there is microbiologic evidence of persistent infection during therapy [19].
Adverse effects associated with daptomycin include myopathy, peripheral neuropathy, and eosinophilic pneumonia [41]. Serial measurements of serum creatine kinase should be monitored at least weekly, and daptomycin should be discontinued in patients with symptomatic myopathy and creatine phosphokinase (CPK) ≥5 times the upper limit of normal (ULN) or in asymptomatic patients with CPK ≥10 times the ULN. (See "Daptomycin: An overview".)
Efficacy data for daptomycin include:
●A 2006 randomized trial including 246 patients with S. aureus bacteremia (89 patients with MRSA bacteremia) in which daptomycin was demonstrated to be noninferior to an antistaphylococcal penicillin or vancomycin plus low-dose gentamicin for treatment of S. aureus bacteremia [40]. At the time of the trial, the comparator regimen was standard of care; however, synergistic aminoglycosides are no longer routinely used for treatment of S. aureus infection given their association with renal dysfunction. A successful outcome was observed for 44 percent of patients who received daptomycin and 42 percent of patients who received antistaphylococcal penicillin or vancomycin plus low-dose gentamicin (absolute difference 2.4 percent, 95% CI -10.2 to 15.1 percent).
●A 2016 retrospective cohort study including 262 cases of MRSA bacteremia between 2010 to 2015 in which those who received daptomycin had a lower mortality rate (6.1 versus 15.3 percent) and a lower clinical failure rate (composite endpoint including mortality, bacteremia ≥7 days, or a change in antibiotic regimen due to persistent or worsening signs or symptoms; 29 versus 45 percent) than those who received vancomycin [42].
●A 2021 retrospective study including more than 7400 patients with MRSA bacteremia in which 30-day survival was superior among patients switched from vancomycin to daptomycin within three days of treatment onset (hazard ratio 0.48, 95% CI 0.25-0.92); the survival advantage did not persist beyond this early window [43].
Daptomycin should not be used for treatment of MRSA bacteremia associated with pneumonia. (See "Treatment of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Methicillin-resistant S. aureus'.)
Teicoplanin (in areas where available) — Teicoplanin is a bacteriostatic glycopeptide with similar spectrum of activity and efficacy as vancomycin [44,45]. It has a longer half-life than vancomycin and can be administered once daily with more rapid infusion rates than vancomycin. It can also be given intramuscularly.
Teicoplanin tends to be better tolerated than vancomycin. In one meta-analysis including 1276 patients, the efficacy of teicoplanin and vancomycin was similar, but there were fewer episodes of vancomycin infusion reaction and other adverse events in patients treated with teicoplanin (14 versus 21 percent) [44]. Another meta-analysis including 24 studies and 2610 patients noted a lower risk of nephrotoxicity with teicoplanin than with vancomycin (risk ratio 0.51, 95% CI 0.30-0.88) [21].
Teicoplanin is not available in the United States. In areas where it is available, some favor its use for patients with intolerance to vancomycin, while others use it as the drug of choice for initial therapy of gram-positive pathogens [46].
Agents warranting further study — Antimicrobial agents warranting further investigation for treatment of MRSA bacteremia are summarized below. Antibiotic susceptibility should be determined prior to use. Agents that are not appropriate for monotherapy of MRSA bacteremia include fluoroquinolones, trimethoprim-sulfamethoxazole (TMP-SMX), tigecycline, and quinupristin-dalfopristin [47-51].
●Cephalosporins
•Ceftaroline – Ceftaroline is a bactericidal fifth-generation cephalosporin; it is administered as a prodrug whose active metabolite has activity against MRSA and vancomycin-intermediate S. aureus (VISA) as well as some gram-negative pathogens [52]. Ceftaroline has in vitro activity against staphylococci with reduced susceptibility to vancomycin, daptomycin, or linezolid [53].
Thus far ceftaroline is approved by the FDA for community-acquired bacterial pneumonia with concurrent bacteremia but not for bacteremia in other contexts.
Data supporting use of ceftaroline for treatment of MRSA bacteremia are limited [54-57]. In one retrospective study including 270 patients with MRSA bacteremia treated with daptomycin or ceftaroline, no difference in 30-day mortality was observed [58].
For treatment of bacteremia, we favor administration of ceftaroline every eight hours (table 1), which is more frequent than dosing for other indications such as pneumonia or skin and skin structure infections [57,59].
Prolonged use of ceftaroline has been associated with neutropenia; monitoring of hematologic parameters is warranted for patients taking ceftaroline >7 days [60]. In addition, ceftaroline has been associated with encephalopathy in patients with severe kidney impairment [61].
•Ceftobiprole – Ceftobiprole is a bactericidal fifth-generation cephalosporin with activity against MRSA and MSSA; it is available outside the United States, including in Canada and the European Union.
Among patients with complicated S. aureus bacteremia, ceftobiprole has been observed to be noninferior to daptomycin. In a trial including 387 patients with S. aureus bacteremia (of whom 75 percent had methicillin-susceptible infection), patients were randomly assigned to treatment with ceftobiprole or daptomycin [62]. The most common conditions were soft tissue infection (237 patients) and osteoarticular infection (67 patients); the median treatment duration was 21 days (range 21 to 24 days). The rate of treatment success (survival, symptom improvement, S. aureus bloodstream clearance, absence of new bacteremia-related complications, and no use of other potentially effective antibiotics) was comparable between the groups (69.8 versus 68.7 percent; adjusted difference, 2.0 percentage points; 95% CI −7.1 to 11.1), as was the frequency of serious adverse events (18.8 versus 22.7 percent, respectively). However, the trial was not powered for subgroup evaluation; further study of ceftobiprole in patients with MRSA bacteremia is needed.
●Lipoglycopeptides
•Telavancin − Telavancin is a bactericidal semisynthetic lipoglycopeptide that inhibits cell wall synthesis and disrupts cell membrane permeability [63-67]. It has a half-life of seven to nine hours, permitting once-daily dosing. Telavancin should be avoided in patients at risk for nephrotoxicity. Telavancin has a higher rate of toxicity than vancomycin (including taste disturbance, nausea, vomiting, and renal dysfunction) and has been associated with teratogenicity.
Data on telavancin for treatment of bacteremia are limited [68].
•Dalbavancin and oritavancin − Dalbavancin and oritavancin are long-acting lipoglycopeptides; data on these agents for treatment of MRSA bacteremia are limited [69]. Two studies reported success using dalbavancin as follow-up treatment for serious staphylococcal infections among people who inject drugs and for patients with bacteremia [70,71].
●Linezolid and tedizolid – Linezolid and tedizolid are bacteriostatic oxazolidinones that inhibit initiation of protein synthesis at the 50S ribosome [72,73]. This drug class may have enhanced efficacy against strains producing toxins such as Panton-Valentine leukocidin, alpha-hemolysin, and toxic shock syndrome toxin 1 [74-76].
Linezolid has excellent tissue distribution and may be administered parenterally or orally (table 1). In a randomized trial including 95 adults with MRSA bacteremia, linezolid and vancomycin had equivalent clinical cure rates (56 and 50 percent, respectively) [77].
Linezolid resistance has been observed among MRSA isolates; the mechanism appears to be via the bacterial cfr gene, which resides in a potentially mobile genetic element [78]. Clinical outbreaks of linezolid-resistant S. aureus have been described; reduction of linezolid use and infection control measures were associated with termination of the outbreaks [79,80].
Safety concerns limit the extended use of linezolid. Adverse effects include thrombocytopenia, anemia, lactic acidosis, peripheral neuropathy, serotonin toxicity, and ocular toxicity [81-83]. (See "Linezolid and tedizolid (oxazolidinones): An overview".)
Linezolid can reversibly inhibit monoamine oxidase; when administered with serotonergic agents (particularly selective serotonin reuptake inhibitors), it can induce the serotonin syndrome [84,85]. (See "Serotonin syndrome (serotonin toxicity)".)
●Investigational agents − Bacteriophages and endolysins are being studied for the treatment of serious MRSA infections [86]. In one proof of concept study, including 43 patients with MRSA bacteremia/endocarditis, patients were randomly assigned to receive standard of care (SOC) or SOC plus a single infusion of exebacase (an antistaphylococcal lysin), the 14-day clinical response rate was higher in the exebacase group (74 versus 31 percent) [87].
Combination therapy — The optimal approach to use of combination antibiotic therapy for treatment of MRSA bacteremia is uncertain; potential circumstances in which such treatment may be appropriate are discussed above [20]. (See 'Unfavorable response to initial treatment' above.)
Daptomycin and ceftaroline — Combination therapy with daptomycin plus ceftaroline may be a useful regimen for treatment of MRSA bacteremia; further study is needed.
●In a retrospective study including 58 patients treated with daptomycin (mean dose 8.2 mg/kg IV every 24 hours) plus ceftaroline (600 mg IV every 8 hours) and 113 matched controls (treated with vancomycin), those treated with combination therapy had a lower 30-day mortality (8.3 versus 14.2 percent) [88]. In addition, among 63 patients who received initial vancomycin treatment but required salvage therapy in the setting of endovascular infection, there was a trend toward improved survival among those who switched within 72 hours of the index culture.
●In a randomized open-label trial including 40 patients treated with either daptomycin (6 to 8 mg/kg IV every 24 hours) plus ceftaroline (600 mg IV every 8 hours) or vancomycin, the in-hospital mortality rates were 0 versus 26 percent, respectively, leading to early study termination for ethics [89].
For combination therapy regimens, we administer daptomycin dosed at 8 to 10 mg/kg (rather than 6 mg/kg) intravenously daily.
Other regimens — Combination regimens warranting further investigation for treatment of MRSA bacteremia are summarized below.
●Daptomycin plus a beta-lactam – Combination therapy with daptomycin plus a beta-lactam may be a useful regimen for treatment of MRSA bacteremia if administered early in the course of bacteremia; further study is needed.
In a retrospective study including 229 patients treated with daptomycin with or without beta-lactam (including cephalosporins, piperacillin-tazobactam, ampicillin-sulbactam), those treated with combination therapy had a reduced odds of clinical failure (adjusted odds ratio 0.39, 95% CI 0.18-0.85) [90].
●Vancomycin plus a hydrophilic beta-lactam – Combination therapy with vancomycin plus a hydrophilic beta-lactam (cefazolin, ceftaroline) may be a useful regimen for treatment of MRSA bacteremia [91-93]; further study is needed. However, available data suggest that combination therapy with vancomycin plus a hydrophobic beta-lactam (such as oxacillin, flucloxacillin, or cloxacillin) is precluded by increased risk of nephrotoxicity [20,94].
In a randomized trial including more than 300 patients with MRSA bacteremia, addition of a beta-lactam (flucloxacillin, cloxacillin, or cefazolin; most received flucloxacillin or cloxacillin) to standard antibiotic therapy (intravenous vancomycin or daptomycin; most received vancomycin) was not associated with improvement in the primary composite end point of 90-day mortality, persistent bacteremia at day 5, relapse, or treatment failure (absolute difference -4.2 percent, 95% CI -14.3 to 6.0 percent) [94]. However, the all-cause mortality in the vancomycin arm was 11 percent (lower than the mortality rate of 20 to 25 percent generally accepted in the literature); in addition, only 4.3 percent had confirmed endocarditis but 38 percent had skin or catheter sources of bacteremia, suggesting that the study population represented a lower risk group without need for combination therapy [20].
Nephrotoxicity occurred more frequently among patients treated with combination therapy (23 versus 6 percent), primarily in those receiving flucloxacillin or cloxacillin, leading to early termination of the trial [94]. This finding is in keeping with other studies describing increased nephrotoxicity risk in the setting of coadministration of vancomycin with hydrophobic beta-lactams (including piperacillin); the potential for nephrotoxicity appears to be lower with hydrophilic beta-lactams (ampicillin, most cephalosporins) [20]. (See "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults", section on 'Acute kidney injury'.)
●Additional regimens – Potential combination regimens for which data are limited include:
•Daptomycin plus fosfomycin [95]
•Daptomycin plus TMP-SMX [96]
•Ceftaroline plus TMP-SMX [97]
●Regimens associated with adverse effects – Combination regimens associated with adverse effects include:
•Vancomycin plus gentamicin – Associated with an increased risk of nephrotoxicity [98]
•Vancomycin plus rifampin – Associated with hepatotoxicity, drug interactions, and emergence of rifampin resistance [99,100].
•Vancomycin plus a hydrophobic beta-lactam (such as oxacillin, flucloxacillin, or cloxacillin) [20,94]
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of Staphylococcus aureus infection".)
SUMMARY AND RECOMMENDATIONS
●Antibiotic susceptibility data − Data regarding the impact of antibiotic susceptibility on clinical response to treatment are conflicting, and other factors (apart from minimum inhibitory concentration) may influence clinical outcome. For these reasons, clinical factors (including symptomatic improvement and timeframe for clearance of bacteremia) are the most important indicators of response to antimicrobial therapy. (See 'Interpreting antibiotic susceptibility data' above.)
●Initial treatment − Initial treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia consists of monotherapy with vancomycin; daptomycin is an acceptable alternative agent. (See 'Initial treatment' above.)
●Tailored treatment − Following initiation of antibiotic treatment for MRSA bacteremia, blood cultures should be repeated to document clearance of bacteremia. Failure to clear bacteremia within 48 to 72 hours after initiation of therapy should prompt further evaluation. (See 'Tailor treatment to clinical circumstances' above.)
•Favorable initial response − For patients with favorable clinical response to initial treatment (clearance of bacteremia within 48 to 72 hours), we continue treatment with vancomycin monotherapy (table 1). (See 'Favorable response to initial treatment' above.)
•Unfavorable initial response − Patients with unfavorable clinical response to initial treatment (persistent bacteremia beyond 48 to 72 hours, persistent fever and lack of clinical improvement) warrant further evaluation for occult focus of infection that may require drainage, guided by clinical history and physical examination. In addition, antibiotic susceptibility results (on the original isolate as well as the breakthrough isolate) should be reviewed carefully for susceptibility to vancomycin as well as alternative agents. (See 'Unfavorable response to initial treatment' above.)
For patients with persistent bacteremia (beyond 48 to 72 hours) in the absence of a removable focus of infection, we modify the antibiotic regimen:
-For patients with no clear source of bacteremia and increased risk for poor outcome (including critical illness, age >65 years, renal disease, vertebral spine infection, injection drug use, and/or prior vancomycin therapy), we suggest switching to combination therapy with daptomycin plus ceftaroline (Grade 2C), if supported by susceptibility data. We continue combination therapy until bacteremia has cleared with resolution of fever and clinical improvement, then complete treatment with daptomycin monotherapy.
-For patients with a clear source of bacteremia (such as skin/soft tissue infection) in the absence of the above risk factors, we suggest switching from vancomycin to daptomycin monotherapy (Grade 2C). However, daptomycin should not be used for patients with bacteremia attributable to a pneumonia source; this is discussed separately. (See "Treatment of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Methicillin-resistant S. aureus'.)
●Duration of treatment − The duration of treatment is discussed separately. (See "Clinical approach to Staphylococcus aureus bacteremia in adults", section on 'Completing antibiotic therapy'.)
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