Treatment of infective endocarditis caused by methicillin-resistant Staphylococcus aureus: teicoplanin versus vancomycin in a retrospective study

Infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) is increasing. Vancomycin and teicoplanin are 2 intravenous glycopeptides appropriate for its treatment. There is no human study comparing teicoplanin and vancomycin for the treatment of MRSA endocarditis. Between 1996 and 2006, 51 MRSA endocarditis patients were treated at the authors' hospital. There were 29 patients with nosocomial infection; 15 were treated with teicoplanin. Teicoplanin was used as the first therapeutic agent in 3 patients because of renal insufficiency. Vancomycin was used as the first therapeutic agent in 12 patients. Treatment was changed to teicoplanin because of adverse reactions in 10 and persistent bacteremia in 2 patients. Early operation was performed in 2 patients because of persistent MRSA bacteremia. Overall, 7 patients died in hospital. There was no statistically significant difference in hospital mortality rate (42% vs 47%) and bacteriologic failure rate (34% vs 40%) between 36 patients treated with vancomycin and 15 patients treated with teicoplanin. Teicoplanin can be an alternative therapy of MRSA infective endocarditis.     

Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection.

OBJECTIVE: To compare trimethoprim-sulfamethoxazole (TMP-SMZ) and vancomycin regarding efficacy and safety in the therapy of serious Staphylococcus aureus infections. DESIGN: Randomized, double-blind comparative trial. SETTING: A tertiary-care hospital. PATIENTS: One hundred and one intravenous drug users hospitalized with S. aureus infection. MEASUREMENTS: Cure and failure rates; blood and wound cultures; minimum inhibitory and bactericidal concentrations; serum inhibitory and bactericidal titers; temperature; leukocyte count; durations of treatment and hospitalization; and toxicity. RESULTS: Of 228 intravenous drug users, 101 had S. aureus infection and were included in the efficacy analysis (43 received TMP-SMZ and 58 received vancomycin). Methicillin-resistant S. aureus (MRSA) accounted for 47% of S. aureus isolates, and 65% of patients were bacteremic. Infections were cured in 57 of 58 vancomycin recipients and in 37 of 43 TMP-SMZ recipients (P less than 0.02). Failure occurred mostly in patients with tricuspid valve endocarditis and only in those with infection caused by methicillin-sensitive S. aureus (MSSA). The mean duration of bacteremia was 6.7 days in TMP-SMZ recipients and 4.3 days in vancomycin recipients. Among 222 subjects hospitalized for at least 24 hours, toxicity rates were similar for TMP-SMZ (23%) and vancomycin (20%) recipients; nausea and vomiting were associated with TMP-SMZ and inflammation at the intravenous site was associated with vancomycin. Forty-four percent of TMP-SMZ recipients and 29% of vancomycin recipients experienced side effects in the efficacy cohort (P greater than 0.05). CONCLUSIONS: Vancomycin is superior to TMP-SMZ in efficacy and safety when treating intravenous drug users who have staphylococcal infections. However, all treatment failures occurred in patients with MSSA infection at any site. Therefore, TMP-SMZ may be considered as an alternative to vancomycin in selected cases of MRSA infection.     

Methicillin-resistant Staphylococcus aureus prosthetic aortic valve endocarditis with paravalvular abscess treated with daptomycin

Prosthetic valves have been used extensively for severe cardiac valvular dysfunction for the past 3 decades. Prosthetic cardiac valves may be infected with organisms causing bacteremia, particularly gram-positive cocci. Staphylococcus epidermidis (coagulase negative staphylococci) and Staphylococcus aureus , both methicillin-susceptible S. aureus and methicillin-resistant S. aureus (MRSA) strains, are the most frequent pathogens causing prosthetic valve endocarditis (PVE). Vancomycin has been the cornerstone of therapy for serious MRSA infections including bacteremia and endocarditis. Clinicians have noted that MRSA bacteremias treated with vancomycin often fail to clear even with prolonged therapy. Persistent or prolonged MRSA bacteremia unresponsive to vancomycin therapy has led to the treatment of these infections by other agents, that is, quinupristin, dalfopristin, linezolid, or daptomycin. These antibiotics have been found particularly useful in treating MRSA bacteremias unresponsive to vancomycin therapy. We report a case of a patient who presented with MRSA PVE complicated by perivalvular aortic abscess with persistent MRSA bacteremia unresponsive to vancomycin therapy. The patient's MRSA bacteremia was cleared with daptomycin therapy (6 mg/kg/d). Because the patient refused surgery, daptomycin therapy was continued in hopes of curing the endocarditis and sterilizing the perivalvular aortic abscess. Transesophageal echocardiogram revealed a decrease in abscess in the aortic perivalvular abscess after 1 week of daptomycin therapy. The patient made an uneventful recovery. The cure of PVE and perivalvular abscesses usually requires removal of the prosthetic device and abscess drainage. In this case, in which surgery was not an option, medical therapy of PVE and a decrease in size of the aortic perivalvular abscess were accomplished with daptomycin therapy. Daptomycin is an alternative to vancomycin therapy in patients with prolonged or persistent MRSA bacteremia secondary to endocarditis or abscess.     

Comparison of methicillin-resistant and methicillin-sensitive Staphylococcus aureus bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) has become endemic in Detroit, accounting for 50% of bacteremias in heroin abusers. To identify the salient epidemiologic and clinical features of MRSA bacteremia, case-control studies were performed comparing 28 cases of MRSA bacteremia to 28 cases of methicillin-sensitive S. aureus (MSSA) bacteremia in intravenous drug abusers. Infective endocarditis was diagnosed in 46.4% (13 of 28). In endocarditis and nonendocarditis bacteremia alike, the duration of fever, length of hospitalization, need for surgery, and mortality rates were similar. A history of recent antimicrobial therapy, especially cephalosporins, was more common in the MRSA group (p = 0.006). Complications including neurologic, renal, vascular, and musculoskeletal manifestations were more common in the MSSA endocarditis patients than MRSA endocarditis patients, although this difference was not significant. Complications related to antibiotic therapy were similar for both groups. The case-control studies indicate that MRSA and MSSA are similar in their virulence as measured by duration of hospitalization, duration of fever, complications, and mortality.     

Efficacy of vancomycin plus rifampin in experimental aortic-valve endocarditis due to methicillin-resistant Staphylococcus aureus: in vitro-in vivo correlations

Studies of in vitro and in vivo bactericidal interactions of vancomycin plus rifampin against Staphylococcus aureus have yielded conflicting results. In this study the efficacy of this drug combination in experimental endocarditis due to a methicillin-resistant strain of S. aureus was investigated. Left-sided endocarditis was induced in 84 rabbits by an infecting strain that had been found to be synergistically killed by vancomycin plus rifampin in vitro when tested by the timed-kill curve technique; in contrast, the checkerboard technique had indicated that the two drugs were antagonistic against this strain. Infected animals received no therapy, vancomycin alone (30 mg/kg per day), rifampin alone (20 mg/kg per day), or both drugs (in the same doses). The combination was significantly more effective than the single-drug regimens in terms of (1) reduction of mean methicillin-resistant S. aureus vegetation titers (P less than .05-.0005), (2) rate and incidence of sterilization of vegetations (P less than .0005), and (3) rate of "radical" cure of endocarditis (P less than .005). Vancomycin alone and vancomycin plus rifampin were equally effective in reducing mortality and sterilizing renal abscesses. The use of vancomycin prevented the in vivo development of resistance to rifampin. No evidence that rifampin exerted an antagonistic effect on the in vivo bactericidal activity of vancomycin was found.     

Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection

We performed a retrospective cohort study to measure the impact of vancomycin resistance on clinical outcome for 83 episodes of enterococcal bloodstream infection (BSI; 22 with vancomycin-resistant enterococci [VRE] and 61 with vancomycin-susceptible enterococci [VSE]) in 77 patients with neutropenia. Cox proportional hazards models showed that vancomycin resistance was an independent predictor of mortality, after controlling for severity of illness, enterococcal species, gram-negative copathogens, sex, race, duration of neutropenia before bacteremia, and early administration of active antibiotics. This effect was evident only > or =10 days after the onset of bacteremia (P=.0263; hazard ratio [HR], 4.969) but not after adjustment for duration of bacteremia. The median duration of bacteremia was 4.5 days for VRE BSI and <1 day for VSE BSI (P=.0001). The only independent predictor of bacteremia duration was vancomycin resistance (P=.0284; HR, 3.863). Vancomycin resistance is associated with increased mortality in patients with neutropenia, possibly because of prolonged duration of bacteremia.     

A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance

Our objectives were to determine the incidence of endocarditis in patients whose Staphylococcus aureus bacteremia was community-acquired, related to hemodialysis, or hospital-acquired; to assess clinical factors that would reliably distinguished between S. aureus bacteremia and S. aureus endocarditis; to assess the emergence of methicillin-resistant S. aureus (MRSA) as a cause of endocarditis; and to examine risk factors for mortality in patients with S. aureus endocarditis.We conducted a prospective observational study in 6 university teaching hospitals; we evaluated 505 consecutive patients with Staphylococcus aureus bacteremia. Thirteen percent of patients with S. aureus bacteremia were found to have endocarditis, including 21% with community-acquired S. aureus bacteremia, 5% with hospital-acquired bacteremia, and 12% on hemodialysis. Infection was due to MRSA in 31%.Factors predictive of endocarditis included underlying valvular heart disease, history of prior endocarditis, intravenous drug use, community acquisition of bacteremia, and an unrecognized source. Twelve patients with bacteremia had a prosthetic valve; 17% developed endocarditis. Unexpectedly, nonwhite race proved to be an independent risk factor for endocarditis by both univariate and multivariate analyses. Persistent bacteremia (positive blood cultures at day 3 of appropriate therapy) was identified as an independent risk factor for both endocarditis and mortality, a unique observation not reported in other prospective studies of S. aureus bacteremia.Patients with endocarditis due to MRSA were significantly more likely to have complicating renal insufficiency and to experience persistent bacteremia than those with endocarditis due to MSSA. The 30-day mortality was 31% among patients with endocarditis compared to 21% in patients who had bacteremia without endocarditis (p = 0.055). Risk factors for death due to endocarditis included severity of illness at onset of bacteremia (as measured by Apache III and Pitt bacteremia score), MRSA infection, and presence of atrioventricular block on electrocardiogram.Patients with S. aureus bacteremia who have community acquisition of infection, underlying valvular heart disease, intravenous drug use, unknown portal of entry, history of prior endocarditis, and possibly, nonwhite race should undergo echocardiography to screen for the presence of endocarditis. We recommend that blood cultures be repeated 3 days following initiation of antistaphylococcal antibiotic therapy in all patients with S. aureus bacteremia. Positive blood cultures at 3 days may prove to be a useful marker in promoting more aggressive management, including more potent antibiotic therapy and surgical resection of the valve in endocarditis cases. MRSA as the infecting organism should be added to the list of risk factors for consideration of valvular resection in cases of endocarditis.     

Predicting methicillin resistance and the effect of inadequate empiric therapy on survival in patients with Staphylococcus aureus bacteremia

BACKGROUND: The restriction of vancomycin hydrochloride use is recommended as a measure to decrease the emergence of vancomycin resistance in gram-positive organisms; however, vancomycin also is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections. If vancomycin use is restricted to patients with documented infections due to methicillin-resistant organisms, then patients with MRSA infections may not initially receive vancomycin. This study was performed to determine factors that predict MRSA bacteremia and if ineffective empiric antibiotic therapy increased the risk of death in patients with S aureus bacteremia. METHODS: We conducted a retrospective cohort study of all patients with clinically significant S aureus bacteremia (132 episodes in 128 patients) diagnosed between October 1, 1995, and January 1, 1998, at an urban acute care Veterans Affairs medical center (approximately 200 acute care beds) in Baltimore, Md. During the study period, vancomycin was a restricted antibiotic. Empiric use had to be approved by an attending physician specializing in infectious diseases. RESULTS: Compared with patients who had methicillin-sensitive S aureus bacteremia, patients with MRSA bacteremia were significantly older (70 vs 58 years; P<.01), more likely to have a history of MRSA (47% vs 6%; P<.01) and a nosocomial infection (76% vs 50%; P<.01), and less likely to use injection drugs (8% vs 32%; P<.01). In addition, compared with patients who had methicillin-sensitive S aureus bacteremia, patients with MRSA bacteremia were significantly less likely (45% vs 98%; P<.01) to receive effective antibiotic therapy during the first 48 hours of hospitalization. However, the risk of death due to ineffective empiric therapy was less than 1 (relative risk, 0.82; 95% confidence interval, 0.36-1.88) and did not change significantly when adjusted for age, occurrence of sepsis, or nosocomial infection. CONCLUSIONS: The results of this study support the safety of the restriction of vancomycin use in patients with clinically significant S aureus bacteremia. However, patients with a history of MRSA are more likely to have future MRSA infections and should receive empiric therapy using vancomycin for possible S aureus infections, particularly for nosocomial infections.     

High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity

BACKGROUND: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL. METHODS: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs <2 microg/mL) for efficacy and high vs low trough (>/=15 vs <15 microg/mL) for nephrotoxicity analyses. RESULTS: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. CONCLUSIONS: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.     

Enterococcal meningitis: Combined vancomycin and rifampin therapy

Intrathecal vancomycin and oral rifampin have been used together to successfully treat a patient with enterococcal meningitis who was allergic to penicillin and who had failed a course of treatment with chloramphenicol. This therapy was tolerated very well and represents an alternate mode of therapy which should be considered in penicillin allergic patients with enterococcal meningitis.     

Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia.

BACKGROUND: Vancomycin treatment failure in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not uncommon, even when MRSA is susceptible to vancomycin. The aim of our study was to evaluate whether vancomycin minimum inhibitory concentration has any influence on the mortality associated with MRSA bacteremia. METHODS: A total of 414 episodes of MRSA bacteremia were prospectively followed-up from 1991 through 2005. MIC of vancomycin for the first isolate was determined by E-test. Clinical variables recorded were age, comorbidity, prior administration of vancomycin, use of corticosteroids, prognosis of underlying disease, source of bacteremia, the need for mechanical ventilation, shock, and mortality. A "treatment group" variable was created and defined as follows: (1) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1 microg/mL (38 episodes), (2) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1.5 microg/mL (90 episodes), (3) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (40 episodes), and (4) receipt of inappropriate empirical therapy (246 episodes). Univariate and multivariate analyses were performed. RESULTS: Episodes caused by strains with a vancomycin MIC of 2 microg/mL were independently associated with a lower risk of shock (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.15-0.75). Multivariate analysis selected receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (OR, 6.39; 95% CI, 1.68-24.3), receipt of inappropriate empirical therapy (OR, 3.62; 95% CI, 1.20-10.9), increasing age (OR, 1.02; 95% CI, 1.00-1.04), use of corticosteroids (OR, 1.85; 95% CI, 1.04-3.29), an ultimately (OR, 10.2; 95% CI, 2.85-36.8) or rapidly (OR, 1.81; 95% CI, 1.06-3.10) fatal underlying disease, high-risk (OR, 3.60; 95% CI, 1.89-6.88) and intermediate-risk (OR, 2.18; 95% CI, 1.17-4.04) sources of bacteremia, and shock (OR, 7.38; 95% CI, 4.11-13.3) as the best predictors of mortality. CONCLUSIONS: Mortality associated with MRSA bacteremia was significantly higher when the empirical antibiotic was inappropriate and when vancomycin was empirically used for treatment of infection with strains with a high vancomycin MIC (>1 microg/mL).     

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study

BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.     

Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study

Staphylococcus aureus bacteremia is associated with substantial morbidity. Recurrence is common, but incidence and risk factors for recurrence are uncertain. The emergence of methicillin resistance and the ease of administering vancomycin, especially in patients who have renal insufficiency, have led to reliance on this drug with the assumption that it is as effective as beta-lactam antibiotics, an assumption that remains open to debate.We initiated a multicenter, prospective observational study in 6 university hospitals and enrolled 505 consecutive patients with S. aureus bacteremia. All patients were monitored for 6 months and patients with endocarditis were followed for 3 years. Recurrence was defined as return of S. aureus bacteremia after documentation of negative blood cultures and/or clinical improvement after completing a course of antistaphylococcal antibiotic therapy. All blood isolates taken from patients with recurrent bacteremia underwent pulsed-field gel electrophoresis testing. Recurrence was subclassified as reinfection (different pulsed-field gel electrophoresis patterns) or relapse (same pulsed-field gel electrophoresis pattern).Forty-two patients experienced 56 episodes of recurrence (79% were relapses and 21% were reinfection). Relapse occurred earlier than reinfection (median, 36 versus 99 d, p < 0.06). Risk factors for relapse of S. aureus bacteremia included valvular heart disease, cirrhosis of the liver, and deep-seated infection (including endocarditis). Nafcillin was superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for methicillin-susceptible S. aureus (MSSA) bacteremia. Failure to remove infected intravascular devices/catheters and vancomycin therapy were common factors in patients experiencing multiple (greater than 2) relapses. However, by multivariate analysis, only endocarditis and therapy with vancomycin (versus nafcillin) were significantly associated with relapse.Recurrences occurred in 9.4% of S. aureus bacteremias following antistaphylococcal therapy, and most were relapses. Duration of antistaphylococcal therapy was not associated with relapse, but type of antibiotic therapy was. Nafcillin was superior to vancomycin in efficacy in patients with MSSA bacteremia.     

Successful treatment of disseminated cerebritis complicating methicillin-resistant Staphylococcus aureus Endocarditis unresponsive to vancomycin therapy with linezolid

A unique case of community acquired methicillin resistant Staphylococcus aureus (MRSA) sepsis, with endocardial and cerebral metastatic seeding, caused by a strain representative of the Italian clone, is described. The patient was a 47-y-old man without apparent risk factors for endocarditis and for MRSA infection who developed coma with multiple cerebritis lesions under vancomycin plus amikacin therapy. He was eventually cured with the addition of linezolid to the initial antimicrobial regimen. This observation seems to confirm previous reports of the efficacy of linezolid for the treatment of central nervous system infections caused by multidrug resistant Gram-positive bacteria. To our knowledge, this is the first report of MRSA disseminated cerebritis, a nearly always fatal disease, cured with this oxazolidinone drug. The increase in community acquired MRSA may have some impact on empirical treatment of serious infections caused by this organism.     

Methicillin-resistant staphylococci and their treatment in the intensive care unit

Methicillin resistance in Staphylococcus aureus (MRSA) and the coagulase-negative staphylococci (MRCNS) is widespread and continues to increase in prevalence, particularly in the health care setting. The clinical significance of methicillin resistance for patients with staphylococcal infections is not clear: studies in patients with bacteremia, pneumonia, and mediastinitis show a higher mortality with MRSA infection compared to methicillin-sensitive Staphylococcus aureus (MSSA) infection, though this may be due to underlying patient, pharmacodynamic, or microbiological differences. For serious methicillin-resistant staphylococcal infections, vancomycin-based regimens are preferred. Treatment alternatives for patients with severe methicillin-resistant infections who are unable to tolerate vancomycin include linezolid and quinupristin/dalfopristin; these agents should be considered second-line options, given the relative lack of clinical experience and the nonsignificant but consistent trends toward worse outcomes in bacteremia and pneumonia with these agents compared to vancomycin. For less severe infections, treatment options also include trimethoprim-sulfamethoxazole, or fluoroquinolones in combination with rifampin.     

New agents for Staphylococcus aureus endocarditis

PURPOSE OF REVIEW: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) as well as newly discovered S. aureus strains with reduced susceptibility to vancomycin mandates development of new antistaphylococcal agents. This review summarizes currently available and forthcoming antimicrobials for treatment of S. aureus endocarditis. RECENT FINDINGS: No new antimicrobial has been proven superior to antistaphylococcal penicillins for treatment of methicillin-sensitive S. aureus (MSSA) endocarditis. Vancomycin has become standard treatment for MRSA but poor outcomes have been reported, both with susceptible and intermediately resistant S. aureus strains (VISA). Linezolid has successfully treated individual cases of MRSA endocarditis, but limitations include long-term safety. Daptomycin has recently been proven effective and well tolerated for MSSA and MRSA bacteremia, including right-sided endocarditis. New glycopeptides, including dalbavancin and telavancin, as well as the new cephalosporin ceftobiprole, have not yet been studied for treatment of endocarditis but appear active against MRSA and potentially VISA. SUMMARY: Antistaphylococcal penicillins remain the treatment of choice for MSSA. Of the currently available newer agents, daptomycin appears to have the most rapid bactericidal activity and provides a much-needed alternative to vancomycin for treatment of MRSA or MSSA bacteremia and right-sided endocarditis.     

Incidence and outcome of vancomycin-resistant enterococcal bacteremia following autologous peripheral blood stem cell transplantation

A retrospective evaluation of 321 consecutive recipients of high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of vancomycin-resistant enterococcal (VRE) bacteremia. Ten patients developed VRE bacteremia at a median of 6 days following PBSCT. Nine isolates were Enterococcus faecium and one was E. faecalis. The median duration of bacteremia was 5 days. The central venous catheter was removed in seven individuals. Nine patients were treated with a variety of antimicrobial agents including quinupristin-dalfopristin, chloramphenicol, doxycycline, oral bacitracin, co-trimoxazole, and nitrofurantoin. Bacteremia resolved without adverse sequelae in seven patients. Two individuals who died of other causes had persistent or relapsed bacteremia at the time of death. An additional patient suffered multiple relapses of VRE bacteremia and died as a result of VRE endocarditis 605 days following PBSCT. Mortality as a direct result of VRE bacteremia was 10% in this series. The optimal type and duration of treatment of VRE bacteremia has not been clearly defined. Therefore, we perform weekly stool surveillance cultures for VRE in our hospitalized transplant population and apply strict barrier precautions in those individuals in whom stool colonization has been identified. Furthermore, the empiric use of vancomycin has been restricted. Bone Marrow Transplantation (2000) 25, 147-152.     

E. faecalis vancomycin-sensitive enterococcal bacteremia unresponsive to a vancomycin tolerant strain successfully treated with high-dose daptomycin

Enterococci are part of the normal flora of the gastrointestinal tract. Intra-abdominal and genitourinary enterococcal infections may be complicated by enterococcal bacteremia. Most strains of enterococci fecal flora in antibiotic-naive patients are E. faecalis. Because nearly all E. faecalis strains are sensitive to vancomycin, E. faecalis is synonymous with vancomycin-sensitive enterococci (VSE). E. faecium, which is nearly always vancomycin-resistant, is termed vancomycin-resistant enterococci (VRE). High-grade continuous enterococcal bacteremias may result in endocarditis. Persistent VSE and VRE bacteremias may be related to device-associated infections; intra-abdominal, pelvic, and/or renal abscesses; or enterococcal endocarditis. If these causes of persistent enterococcal bacteremia are eliminated, microbiologic and antimicrobial therapy-related causes for persistent bacteremia should be considered. We present a case of a male with a E. faecalis (VSE) bacteremia unresponsive to parenteral vancomycin therapy but sensitive to vancomycin in vitro (minimum inhibitory concentration [MIC] = 1 microg/mL). The patient was treated with high-dose daptomycin (12 mg/kg intravenously [IV] q 24 hours) empirically pending susceptibility testing. High-dose daptomycin therapy cleared the patient's E. faecalis bacteremia. Subsequently, it was determined that the strain of E. faecalis was "tolerant" of vancomycin (MIC = 1 microg/mL, MBC = >64 microg/mL). We believe this is the first case of enterococcal (VSE) bacteremia unresponsive to vancomycin tolerant strain of E. faecalis that responded to high-dose daptomycin (12 mg/kg IV q 24 hours) therapy.     

The impact of serum vancomycin levels and minimum inhibitory concentrations of methicillin-resistant Staphylococcus aureus on mortality in patients with nosocomial pneumonia

BACKGROUND:

Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure is not uncommon, even when the minimum inhibitory concentration (MIC) of the MRSA strain is within the susceptible range for vancomycin.

OBJECTIVE:

To describe the relationship between molecular markers such as the mecA and agrII genes, serum vancomycin levels and vancomycin MICs, and the 30-day mortality rate of patients with nosocomial MRSA pneumonia in an intensive care unit (ICU).

METHODS:

The present study was a prospective cohort study including all patients with MRSA hospital-acquired pneumonia or ventilator-associated pneumonia who were admitted to the ICU of a tertiary care hospital between June 2009 and December 2011. The MIC for vancomycin was determined using the E-test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the Acute Physiology and Chronic Health Evaluation II (APACHE) score and the presence of the agrII gene. The primary outcome was mortality at 30 days.

RESULTS:

Thirty-six (42.4%) patients died within 30 days of the index MRSA culture. A multiple regression analysis that included the variables of MIC (determined using the E-test or broth microdilution methods), APACHE II score, serum vancomycin level and the presence of agrII revealed that only the APACHE II score was related to the 30-day mortality rate (P=0.03). Seven patients (9.0%) with isolates exhibiting an MIC ≥1.5 μg/mL according to the E-test method died, and nine patients (11.6%) survived (P=0.76). Of the patients for whom MICs were determined using the broth microdilution method, 11 (14.1%) patients with MICs of 1.0 μg/mL died, and 16 (20.5%) survived (P=0.92). The median APACHE II score of survivors was 22.5, and the median score of nonsurvivors was 25.0 (P=0.03). The presence of the agrII gene was not related to the 30-day mortality rate.

CONCLUSIONS:

Patients with severe hospital-acquired pneumonia presented with MRSA isolates with low to intermediate vancomycin MICs in the ICU setting. At the Hospital de Clínicas de Porto Alegre (Porto Alegre, Brazil), the 30-day mortality rate was high, and was similar among patients with severe hospital-acquired pneumonia infected with MRSA isolates that exhibited MICs of ≤1.5 μg/mL determined using the E-test method and ≤1.0 μg/mL determined using the broth microdilution method in those who achieved optimal serum vancomycin levels. The APACHE II scores which provides an overall estimate of ICU mortality were independently associated with mortality in the present study, regardless of the MICs determined. Molecular markers, such as the agrII gene, were not associated with higher mortality in the present study.     

Enteral vancomycin to control methicillin-resistant Staphylococcus aureus outbreak in mechanically ventilated patients

BACKGROUND: Screening for and treating gut carriage of methicillin-resistant Staphylococcus aureus (MRSA) may control transmission and subsequent endemicity of MRSA. OBJECTIVE: Enteral vancomycin was evaluated as a measure to control an outbreak of MRSA infection in the intensive care unit (ICU). METHODS: During the 8-month study of sequential design, 176 patients were admitted, 65 (37%) of whom required a minimum of 3 days of ventilation. Forty-four patients were studied in the first 5 months, during which traditional measures were reinforced (control group). During the following 3 months, 13 of 21 patients developed MRSA carriage and received 2 g/day of enteral vancomycin, with high standards of hygiene maintained (treatment group). RESULTS: Thirty-three MRSA infections occurred in 22 patients (50%) in the control group, whereas 2 patients (9.5%) had 2 MRSA infections in the treatment group (P <.05 for carriage, infection rates, and episodes). Of the 33 MRSA infections in the control group, 27 were due to MRSA acquired in the ICU, whereas the 2 infections in the treatment group were primary endogenous (ie, caused by MRSA present in the patient's admission flora). The probability of developing an MRSA infection was reduced in patients receiving enteral vancomycin compared with patients in the control group (odds ratio, 0.37; 95% CI, 0.24-0.58). Enteral vancomycin significantly reduced the level of MRSA carriage; the mean carriage index was 1.01 in the control group versus 0.58 in the test group (P <.05). Neither vancomycin-resistant enterococci nor vancomycin-intermediate Staphylococcus aureus were isolated from either surveillance or diagnostic samples. CONCLUSIONS: The eradication of MRSA gut carriage by enteral vancomycin in a small subset of ICU patients was effective in the control of an MRSA outbreak.