Combination therapy with daptomycin, vancomycin, and rifampin for recurrent, severe bone and prosthetic joint infections involving methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) infections are commonly treated with vancomycin (VAN) or another glycopeptide antibiotic. However, when vancomycin fails or infections recur, there are few other therapeutic options. Presented here are 2 cases where a novel combination of daptomycin, vancomycin, and rifampin resolved recurrent MRSA bone and prosthetic joint functions.     

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.     

Intraleukocytic sequestration as a cause of persistent Staphylococcus aureus peritonitis in continuous ambulatory peritoneal dialysis

Peritonitis caused by Staphylococcus aureus in four patients undergoing continuous ambulatory peritoneal dialysis failed to respond to, or relapsed immediately after cessation of, intraperitoneal antibiotic therapy with vancomycin or cephalothin and tobramycin. Sequestration of viable staphylococci within polymorphonuclear leukocytes in the peritoneal fluid was suspected for two reasons: (1) staphylococci could still be grown after treatment of the dialysate cell fraction with lysostaphin, a procedure that kills only extracellular staphylococci, and (2) diminished polymorphonuclear leukocyte bactericidal activity was demonstrated in peritoneal dialysis effluent. Addition of rifampin, which readily penetrates polymorphonuclear leukocytes, to the treatment regimen of all patients led to prompt resolution of peritonitis without relapse.     

Rates of killing of methicillin-resistant Staphylococcus aureus by ceftaroline, daptomycin, and telavancin compared to that of vancomycin

Treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) remains an important concern. In order to investigate new MRSA treatment modalities, we used standard time-kill assays to determine the in vitro killing rate of 22 strains of MRSA by vancomycin, telavancin, daptomycin, and ceftaroline. Studies were carried out with 7-10-times the minimum bactericidal concentrations of each antibiotic in broth culture for 24 h, with subculture at 4, 8, and 24 h. We found that killing by ceftaroline closely paralleled that of vancomycin. Telavancin killed bacteria significantly more slowly, whereas daptomycin killed significantly more rapidly.     

Efficacy of intravenous vancomycin in the treatment of gram-positive peritonitis in long-term peritoneal dialysis

Peritonitis is the major complication of long-term peritoneal dialysis. Gram-positive bacteria are responsible for two thirds of the total number of peritonitis episodes. Conventional therapy consists of daily administration of antibiotics, either parenterally or intraperitoneally. Vancomycin, an antibiotic with a prolonged half-life in renal failure, has a wide spectrum of activity against gram-positive bacteria and diffuses readily across the peritoneal membrane. In the present study, 82 percent of gram-positive peritonitis episodes were cured following the intravenous administration of vancomycin at weekly intervals. This cure rate compares favorably with that obtained following conventional therapy of peritonitis. It is concluded that intravenous vancomycin is an effective treatment for gram-positive peritonitis in patients undergoing long-term peritoneal dialysis. This form of therapy is convenient, reduces hospitalization, minimizes cost, and avoids possible contamination of the peritoneal dialysate used during the intraperitoneal administration of antibiotics.     

Tratamiento con daptomicina en pacientes diabéticos

In diabetic patients, there is a high prevalence of skin or nasal carriage of Staphylococcus aureus, which is associated with an increased risk of local or systemic infections and consequently with greater morbidity and mortality. The microorganisms causing most infections in diabetic ulcers and diabetic foot are S. aureus and Streptococcus pyogenes, although chronic diabetic foot infections are generally polymicrobial, including Pseudomonas aeruginosa and enterobacteria. The present article describes experience with daptomycin in the treatment of the most frequent infectious complications in diabetic patients. The Cubicin Outcomes Registry and Experience (CORE) registry contains information on 60 patients with skin and soft tissue infections treated with daptomycin, with a success rate of 83%. Other recent studies comparing daptomycin with vancomycin or semi-synthetic penicillins have also shown the efficacy and safety of daptomycin with cure rates of between 70% and 80%. In the European version of the CORE registry, the EUROCORE, diabetic patients who developed bacteremia or endocarditis due to Gram-positive pathogens and who received daptomycin showed success rates of 76.8% and 72%, respectively. No significant differences were found in a study comparing daptomycin or standard therapy with vancomycin in methicillin-resistant S. aureus (MRSA) or antistaphylococcal penicillin in methicillin-susceptible S. aureus (MSSA) in diabetic patients with bacteremia or endocarditis. Because of its rapid bactericidal action and scarce adverse effects, daptomycin is an attractive antimicrobial agent in the treatment of Gram-positive infections in diabetic patients, whether in monotherapy or in association with other agents.     

腹膜透析相关感染性腹膜炎病原菌及耐药性分析

目的:观察腹膜透析(PD)相关感染性腹膜炎病原菌分布及耐药性变化. 方法:同顾分析61例次PD相关感染性腹膜炎病例,比较其PD时间、透液液白细胞数、血白细胞数、血白蛋白、血肌酐、细菌培养及药敏试验、疗效及转归等. 结果:(1)61例次病原菌培养阳性33例次(54.1%),其中革兰阳性(G~+)菌17例次(51.5%),革兰阴性(G~-)菌7例次(21.2%),真菌9例次(27.3%).(2)G~+菌对头孢唑啉的耐药率高达50%,对万古霉素、左旋氧氟沙星、利福平等的耐药率低.G~-菌对阿米卡星及左旋氧氟沙星敏感,而对庆大霉素、头孢他定、氨曲南的耐药率上升.(3)真菌性腹膜炎病例PD时间明显长于G~+及G~-菌性腹膜炎病例(P<0.05),血白蛋白均明显低于两种细菌性腹膜炎病例(P<0.05).2例真菌病例死亡,7例拔管病例中4例为真菌者.真菌性腹膜炎死亡及退出率明显高于G~+与G~-细菌性腹膜炎(P均<0.05). 结论:G~+菌仍是PD相关感染性腹膜炎的主要致病菌,但对头孢哗林的耐药率高达50%.真菌感染率大幅上升,是导致病例死亡及退出的主要致病菌.     

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.     

Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis

OBJECTIVE: To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. DESIGN: Cohort analysis of a randomized study. SETTING: University medical center. PATIENTS: Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days. MEASUREMENTS: Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia. MAIN RESULTS: The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy. CONCLUSIONS: Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia.     

Intraperitoneal administration of daptomycin in recurrent peritonitis with suspected biofilm

Forms of peritonitis are the most problematic infections in patients undergoing peritoneal dialysis since they can jeopardise the technique. Current treatment includes administering vancomycin, cephalosporins and aminoglycosides empirically until the cause of the infection is known. However, the current situation with regard to emerging bacterial resistances makes it necessary to include new drugs in the therapeutic array for complicated forms of peritonitis that may become recurrent and compromise dialyser efficacy. Daptomycin is a lipopeptide antibiotic used to treat gram-positive bacterial infections. It has not yet been approved for treatment of infections of this type, but it is starting to be used in this area due to being highly effective against methicillin-resistant bacteria with intermediate sensitivity to vancomycin, particularly when the bacteria are associated with biofilm formation.     

A retrospective analysis of practice patterns in the treatment of methicillin-resistant Staphylococcus aureus skin and soft tissue infections at three Canadian tertiary care centres

BACKGROUND:

Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly being encountered and pose an increasing burden to the health care system in Canada.

OBJECTIVE:

To elucidate and characterize the factors influencing the current MRSA treatment patterns in patients with skin and soft tissue infections (SSTIs) before linezolid became available on the Canadian market.

METHODS:

A retrospective study collected demographic, treatment and resource use data on patients hospitalized at one of three geographically distinct tertiary care facilities, where MRSA SSTI treatment was initiated with intravenous (IV) vancomycin. Analysis of opportunities for IV-to-oral switch therapy was based on eligibility criteria.

RESULTS:

Of 89 patients identified over a 43-month period, the mean (±SD) durations of anti-infective treatment and hospitalization were 22.4±21 days and 28.9±20.8 days, respectively. An infected surgical wound was most common, representing 62.9% of infections. The mean duration of vancomycin treatment was 19.5 days and the mean number of 1 g doses received was 29.0±32.9. The majority of patients (55.1%) initiated vancomycin therapy a mean of 5.4±8.9 days after confirmation of MRSA. Of the 70% of patients meeting criteria for IV-to-oral switch therapy, only 10% received oral treatment. The most common reason cited for not switching was lack of an effective oral alternative. Analysis of switch therapy criteria found that IV treatment continued for a mean of 13 days despite the appropriateness of the oral route.

CONCLUSIONS:

Considerable variation exists in treatment patterns for MRSA infections. Improvements in the initiation of therapy and the use of IV-to-oral switch therapy may improve care and reduce the duration of hospitalization for MRSA SSTIs.Key Words: Methicillin-resistant Staphylococcus aureus, Switch therapy, Treatment patterns, VancomycinAntibiotic resistance is of growing importance to health care systems worldwide, and Canada is no exception (1). Due to the serious nature of emerging antibiotic-resistant pathogens and the limited therapeutic options available to treat them, infections caused by these organisms may be associated with increased morbidity and mortality (2-4) compared with those caused by drug-sensitive organisms, and pose an increasing economic burden to health care systems (5). Among the resistant organisms, methicillin-resistant Staphylococcus aureus (MRSA) is increasingly being encountered in Canadian health care facilities (1). Although the first report of an MRSA isolate in Canada was in 1981 (6), only occasional reports followed. In 1995, the Canadian Nosocomial Infection Surveillance Program (CNISP) began following the incidence of MRSA prospectively and reported an increase from 1% of all S aureus isolates in 1995 to 8.1% in 2000 in the health care facilities participating in the CNISP (7). The majority of the increase in MRSA cases has occurred in Ontario and Quebec, followed by British Columbia (7). Although MRSA was initially a hospital-acquired pathogen, it has also recently been recognized as a community-acquired organism (8-11) in Canada, particularly among First Nations peoples.Because MRSA is often resistant to multiple antibiotics, treatment options may be limited. The usual treatment for serious infections caused by MRSA is vancomycin (12). This antibiotic is available only in the intravenous (IV) form for treatment of these types of infections, and it has the potential for greater toxicity and may be less effective than conventional therapy for infections caused by susceptible staphylococci (5). Furthermore, certain organisms have exhibited increasing rates of resistance to vancomycin, which may limit its usefulness. A Passive Reporting Network established within the CNISP identified 1315 cases of vancomycin-resistant enterococci throughout Canada between 1994 and 1998 (13). In addition, cases of vancomycin-intermediate strains of S aureus have been reported recently in Japan, Europe, Hong Kong and the United States (14-16), although no cases have yet been confirmed in Canada.Other than intravenous vancomycin, several oral MRSA treatment alternatives are available including trimethoprim-sulfamethoxazole, alone or in combination with rifampin; doxycycline; fusidic acid in combination with rifampin; or fluoroquinolones alone or in combination with rifampin, dependent on the susceptibility of the strain. Five years of MRSA surveillance in several hospitals across Canada found resistance rates to ciprofloxacin, trimethoprim-sulfamethoxazole, rifampin and fusidic acid to be 89%, 56%, 3% and 3%, respectively (17). Linezolid, an antibacterial agent available in both IV and oral forms, was approved for use in Canada following the completion of the present study and represents a new option for the treatment of Gram-positive infections, including those caused by MRSA.Although vancomycin IV has been identified as the current drug of choice for the treatment of MRSA infections, very little is known regarding the real-life practice patterns of treating physicians across Canada. In an effort to gain an understanding of how MRSA infections are currently being treated, we undertook a retrospective study of vancomycin treatment patterns for MRSA infections in geographically distinct regions across Canada, focusing on infections of the skin and soft tissue (SSTIs). Emphasis was placed on determining MRSA treatment characteristics including antimicrobial use, duration of therapy, length of hospital stay (LOS) and use of home IV care services. In addition, an analysis of IV-to-oral switch therapy patterns was conducted to understand the current level of acceptance of the practice, its potential benefits and the barriers to switch therapy in MRSA SSTIs.     

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.     

Infecciones causadas por bacterias grampositivas multirresistentes (Staphylococcus aureus y Enterococcus spp.)

Methicillin -resistant Staphylocccus aureus (MRSA) and multirresistant entorococci are still problematic in nosocomial infections and new challenges have emerged for their containment. MRSA has increased the multiresistant profile; it has been described vancomycin and linezolid resistant isolates and isolates with decreased daptomycin susceptibility. Moreover, new clones (ST398) have emerged, initially associated with piggeries, and new mec variants (mecC) with livestock origin that escape to the detection with current molecular methods based on mecA gene have been detected. In enterococci, linzeolid resistant isolates and isolates with deceased susceptibility to daptomycin have been described. Moreover, ampicillin resistant Enterococcus faecium due to β-lactamase production has been recently found in Europe. Control of MRSA isolates and multiresistant enteroccocci should combined antibiotic stewardship strategies and epidemiological measures, including detection of colonized patients in order to reduce colonization pressure and their transmission.     

万古霉素等十种抗生素对耐苯唑西林葡萄球菌的体外活性比较

为了比较万古霉素等１０种抗生素对１９９５年分离的９５株耐苯唑西林的金黄色葡萄球菌和７２株凝固酶阴性葡萄球菌的体外活性，用ＮＣＣＬＳ颁布的琼脂稀释法测ＭＩＣ。结果受检的１０种抗生素中万古霉素的活性最好，其ＭＩＣ５０及ＭＩＣ９０分别为１ｍｇ／Ｌ及２ｍｇ／Ｌ，平均值为１２４ｍｇ／Ｌ；耐药率为０％。其次为壁霉素，其ＭＩＣ５０及ＭＩＣ９０分别为２ｍｇ／Ｌ及８ｍｇ／Ｌ，平均值为２５１ｍｇ／Ｌ；耐药率为２％。利福平ＭＩＣ５０及ＭＩＣ９０分别为０１２５ｍｇ／Ｌ及３２ｍｇ／Ｌ，平均值为０２２ｍｇ／Ｌ；耐药率为１４％。其它依ＭＩＣ９０的大小排序，为氧氟沙星，甲氧苄啶，红霉素，庆大霉素，磷霉素，磺胺甲恶唑等。用柱状图显示了前三种药的ＭＩＣ值的分离，万古霉素具有良好的分散性，全部落在敏感区，且为单峰。结果表明万古霉素对ＭＲＳＡ和ＭＲＳＣｏＮ有良好的抗菌活性。     

Daptomycin and vancomycin non-susceptible methicillin-resistant Staphylococcus aureus clonal lineages from bloodstream infection in a Brazilian teaching hospital

IntroductionThis study aimed to characterize Staphylococcus aureus isolates from bloodstream infections in patients attending a teaching hospital, between 2011 and 2015.MethodsThe minimum inhibitory concentration for daptomycin, linezolid, oxacillin, teicoplanin, vancomycin, and trimethoprim/sulfamethoxazole was accessed by broth microdilution. SCCmec type and clonal profile were determined by molecular tests. Vancomycin heteroresistance was evaluated using screening tests and by population analysis profile/area under the curve.ResultsAmong 200 S. aureus isolates, 55 (27.5%) were MRSA, carrying SCCmec II (45.5%) or IV (54.5%). The most frequent MRSA lineages were USA100 (ST5-II) (45.5%) and USA800 (ST5-IV) (30.9%). Six isolates were confirmed as vancomycin heteroresistant, showing area under the curve ratio 1.1, 1.2 or 1.3 (four USA100, one USA800 and one USA1100 isolates).ConclusionsDaptomycin and vancomycin non-susceptible MRSA clonal lineages were found in bloodstream infections over five years, highlighting the importance of continuous surveillance of multiresistant bacteria in hospitals.     

Tratamiento con daptomicina en pacientes con bacteriemia

Community-acquired bacteremias assciated with healthcare and, especially, those of nosocomial origin, are mainly caused by Gram-positive microorganisms. Notable among this group are Staphylococcus spp, with an incidence of methicillin resistance of approximately 30% in S. aureus and of 70% in coagulase-negative staphylococcus, which is higher in patients admitted to intensive care units. Vancomycin has been the most widely used antibiotic in these situations but its toxicity, especially in the kidney, and reports of failure when used for the treatment of methicillin-resistant S. aureus (MRSA) and with a vancomycin MIC > 1 mg/L have led to the search for other treatments.Daptomycin is a new lipopeptide antibiotic that has been shown to be not inferior to vancomycin in a pivotal clinical trial in patients with bacteremia and right endocarditis due to S. aureus. Recent guidelines and consensus documents place daptomycin as an ideal alternative in these situations, indicating its use in MRSA bacteremia with a vancomycin MIC > 1 mg/L, as well as in patients whose renal dysfunction excludes the use of vancomycin therapy. Evidence of worse prognosis in MRSA bacteremia when empirical treatment is inappropriate has led to the recommendation of daptomycin as the first-choice drug in critically ill patients with suspected Gram-positive bacteremic infection and renal dysfunction and/or in hospitals where there is a high prevalence of MRSA with a MIC > 1 mg/L. The recommended dose in severely ill patients should be higher than 6 mg/kg/day.     

Positive Dialysate Gram Stain Predicts Outcome of Empirical Antibiotic Therapy for Peritoneal Dialysis-associated Peritonitis

Empirical antibiotic treatment with a first-generation cephalosporin plus gentamicin for peritoneal dialysis (PD)-associated peritonitis before culture results are available is still wildly used due to concerns regarding the economic burden and antibiotic-resistant bacterial infections. The aim of this study is to define the factors that predict the outcome of empirical antibiotic therapy for PD peritonitis. This is a retrospective study of patients with PD peritonitis over the last 10 years. Patients who had been treated empirically with intermittent intraperitoneal first-generation cephalosporin and gentamicin were enrolled. Eighty-three patients had 192 episodes of PD peritonitis. In total, 159 peritonitis episodes were treated with intraperitoneal antibiotics combined with first-generation cephalosporin and gentamicin empirically. Twenty-five peritonitis episodes had no pathogens identified by dialysate culture. In total, 122 (122/159, 76.7%) PD peritonitis episodes were caused by bacteria, 9 (9/159, 5.7%) were fungal, and 3 (3/159, 1.9%) were Mycobacterium tuberculosis peritonitis. Sixty-four (64/159, 40.3%) peritonitis episodes were successfully cured by empirical intraperitoneal antibiotic therapy. Empirical antibiotic treatment failed in 95 episodes (95/159, 59.7%). The positive rates of dialysate Gram stain in the empirical treatment success and failure groups were 15.6% and 40.0%, respectively (P = 0.001). The odds ratio of empirical treatment failure with a positive bacteria Gram stain was 3.60 (95% CI: 1.65–7.82). The dialysate Gram staining result was a significant predictor of empirical antibiotics treatment outcome for PD-associated peritonitis. Therefore, using an empirical antibiotic regimen for patients with an initial positive bacterial Gram stain of the dialysate should be introduced cautiously.     

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.     

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.     

Daptomycin for the treatment of vancomycin resistant Enterococcus faecium bacteremia

The best therapeutic options for serious infections due to vancomyci resistant Enterococcus (VRE) remain unclear. We describe the successful treatment of vancomycin resistant Enterococcus faecium bacteremia in 2 patients using daptomycin. We also briefly review the literature on antibiotic options for VRE infection including the use of daptomycin.