Rifampin resistance. Development during the therapy of methicillin-resistant Staphylococcus aureus infection

The incidence of methicillin-resistant staphylococcal infections, for which vancomycin hydrochloride remains the only active cell-wall antibiotic therapy, is rising. Some physicians have been combining other antibiotics with vancomycin in hopes of obtaining a more effective regimen for the therapy of these infections. Rifampin has been advocated as a concurrent second antibiotic because of its extraordinary potent bactericidal activity for Staphylococcus aureus. When rifampin is used in combination with a cell-wall antibiotic, suppression of the development of rifampin resistance has been thought possible. We report a case of infection caused by a methicillin-resistant S aureus in which the rifampin resistance occurred during therapy with vancomycin and rifampin. The rifampin resistance was stable and was present after ten serial broth and agar passages. Physicians are cautioned against the indiscriminant or routine use of rifampin as a second antibiotic in combination with vancomycin for the therapy of infections caused by S aureus.     

Rifampin in the treatment of serious staphylococcal infections

Eight patients with serious staphylococcal infections such as endocarditis, meningitis, epidural abscess, shunt and graft infections were treated with nafcillin, cephalothin or vancomycin in combination with rifampin. In vitro antibiotic sensitivities demonstrated that the Staphylococcus aureus and Staphylococcus epidermidis were highly sensitive to rifampin with minimum inhibitory and bactericidal levels of .0078-.25 micrograms/ml. In all patients reviewed and reported, when serum bactericidal levels were measured before and after the addition of rifampin, there was a positive correlation between microbiological and clinical outcome. Thus, in selected patients with life-threatening infections caused by S. aureus and S. epidermidis rifampin should be considered an adjunctive therapy.     

Approaches to serious methicillin-resistant Staphylococcus aureus infections with decreased susceptibility to vancomycin: clinical significance and options for management

PURPOSE OF REVIEW: This review addresses therapeutic approaches to Staphylococcus aureus infections with diminished susceptibility to vancomycin, focusing on recently published data in English language medical literature between June 2006 and July 2007. RECENT FINDINGS: Knowledge regarding the potential limitations of vancomycin therapy for S. aureus infections continues to emerge. Recent changes include alteration of the Clinical Laboratory and Standards Institute vancomycin breakpoint for S. aureus and questions regarding the utility of the lower breakpoint of 2.0 mg/l. Interest continues in the accessory gene regulator (agr) locus and its impact on the activity of vancomycin. Newer options for drug therapy progress, with strengths and limitations becoming more apparent for each. SUMMARY: Newer antimicrobial agents active against methicillin-resistant S. aureus such as daptomycin and linezolid continue to show value. Older antimicrobial agents may play an important therapeutic role and warrant further examination. Work is needed to evaluate current agents against methicillin-resistant S. aureus in the setting of elevated vancomycin minimum inhibitory concentrations or clinical failure. Antimicrobial selection for methicillin-resistant S. aureus infections with reduced susceptibility to vancomycin should be governed by disease severity, susceptibility patterns, knowledge of the limitations of current susceptibility testing, and strengths and weaknesses of the agents being considered.     

Clinical outcome with oral linezolid and rifampin following recurrent methicillin-resistant Staphylococcus aureus bacteremia despite prolonged vancomycin treatment

Drug-resistant Gram-positive bacteria, especially Staphylococcus aureus, are emerging as the predominant organisms involved in both nosocomial and community-acquired infections. Since the 1980s, vancomycin has been the first-line antibiotic used to treat methicillin- resistant S aureus. However, allergy and intolerance to vancomycin, the increasing number of vancomycin clinical failures and the existence of vancomycin intermediate-susceptible isolates of S aureus suggest that new antibiotics are needed. This paper reports the only known case of a successful clinical outcome with long term oral linezolid and rifampin therapy in the management of recurrent and persistent methicillin-resistant S aureus bacteremia with metastatic infections despite prolonged vancomycin use. More than two years since the initiation of linezolid and rifampin, the study patient has been clinically well with no evidence of adverse drug reactions including cytopenia and hepatic toxicities. Physicians must be aware of the novel developments in antibiotic therapy to treat drug-resistant bacterial infections.Key Words: Linezolid, MRSA bacteremia, Osteomyelitis, VancomycinAccording to the National Nosocomial Infection Surveillance System, Gram-positive pathogens, especially Staphylococcus aureus, are emerging as the predominant organisms involved in both nosocomial and community-acquired infections (1). S aureus is spread via contact and is a common cause of numerous infections including soft tissue infections (cellulitis and impetigo), wound infections, bacteremia with metastatic infections (osteomyelitis, septic arthritis and acute infective endocarditis) and toxic shock syndrome (2-4).Since the introduction of antibiotics in the 1940s, S aureus has been most effective in its ability to develop resistance to antimicrobial agents, thus evoking significant concern in both the public and the health care communities. For example, one year following the introduction of methicillin for the treatment of penicillin-resistant S aureus, the first strain of methicillin-resistant S aureus (MRSA) was identified (5).Over the past two decades, MRSA rates have increased dramatically in both the community and hospital settings, to the point that this pathogen is now endemic in many American centres (5). Methicillin resistance is associated with significant morbidity and mortality. Bacteremia due to MRSA, when compared with methicillin-susceptible S aureus, has a two- to threefold increase in mortality (6-7).Vancomycin was initially introduced in the middle 1960s but gained significant recognition in the early 1980s as the treatment of choice for MRSA (8). While this antibiotic is principally used for the treatment of MRSA infections today, it has a relatively high clinical failure rate (9,10). Various reasons for the decreased clinical efficacy of vancomycin despite the in vitro sensitivity of MRSA to the antibiotic have been suggested. First, vancomycin has decreased bactericidal activity against S aureus (11). Second, its low tissue concentration prevents effective eradication of virulent Gram-positive pathogens (12,13).In July 2002, the first case of infection due to vancomycin-resistant S aureus (VRSA, minimum inhibitory concentration [MIC] greater than 128 µg/mL) related to catheter exit site infection in a Michigan patient was reported (14). There have also been several worldwide reports of glycopeptide-intermediate S aureus (GISA), defined as an MIC of 8 to 16 µg/mL. The first case of GISA was reported in Japan in 1996 (5). Since then, strains of GISA, also resistant to methicillin, were reported from Italy, the United Kingdom, France and the United States (2,15-21). Prolonged intermittent vancomycin use has been associated with the development of GISA and VRSA strains (14,16).Current antimicrobial agents routinely used to treat antibioticresistant Gram-positive organisms, especially MRSA, have limitations in terms of their efficacy. With the emergence of the aforementioned resistant strains, newer antimicrobial agents must be considered.This paper reports the only known case of a successful clinical outcome and no adverse drug reactions with long term linezolid and rifampin therapy in the management of recurrent and persistent MRSA bacteremia with metastatic infections despite prolonged vancomycin use.     

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.     

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.     

Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance

Vancomycin has been the most reliable therapeutic agent against infections caused by meticillin-resistant Staphylococcus aureus (MRSA). However, in 1996 the first MRSA to acquire resistance to vancomycin, was isolated from a Japanese patient. The patient had contracted a post-operative wound infection that was refractory to long-term vancomycin therapy. Subsequent isolation of several vancomycin resistant S. aureus (VRSA) strains from USA, France, Korea, South Africa, and Brazil has confirmed that emergence of vancomycin resistance in S aureus is a global issue. A certain group of S. aureus, designated hetero-VRSA, frequently generate VRSA upon exposure to vancomycin, and are associated with infections that are potentially refractory to vancomycin therapy. Presence of hetero-VRSA may be an important indicator of the insidious decline of the clinical effectiveness of vancomycin in the hospitals. Vancomycin resistance is acquired by mutation and thickening of cell wall due to accumulation of excess amounts of peptidoglycan. This seems to be a common resistance mechanism for all VRSA strains isolated in the world so far.     

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.     

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.     

Diagnosis and management of Staphylococcus aureus infections of the skin and soft tissue

Infections involving the skin and soft tissue are common and range from superficial, localized and sometimes self-limiting infections to deep, rapidly spreading and potentially life-threatening infections. Skin infections caused by Staphylococcus aureus include primary pyodermas, while those involving the soft tissues include cellulitis and pyomyositis. Surgical site infections and infections in intravenous drug users are also commonly caused by S. aureus. The severity of the infection determines the choice of treatment. There are few studies that have critically appraised the use of antibiotics in skin and soft tissue infections, and most guidelines are based on expert opinion. The beta-lactam group of antibiotics are the mainstay of treatment for methicillin-susceptible S. aureus infections. For methicillin-resistant S. aureus (MRSA) infections, both with community-acquired and hospital-acquired strains--which are becoming an increasing problem--the antibiotic choice is determined by local susceptibility patterns. Macrolides, clindamycin and cotrimoxazole are options for community-acquired MRSA, while vancomycin is reserved for treatment of infections caused by multiresistant MRSA strains and for patients with suspected endocarditis or severe sepsis. Although a number of the newer antibiotics such as linezolid and quinopristin/dalfopristin have been shown to have good activity against MRSA, these agents should only be used with specialist advice.     

Cavernous sinus thrombosis and meningitis from community-acquired methicillin-resistant Staphylococcus aureus infection

Septic cavernous sinus thrombosis is an uncommon clinical syndrome with a high morbidity and mortality. The commonest bacterial pathogen is Staphylococcus aureus. We describe the study of a patient with cavernous sinus thrombosis and meningitis caused by community-acquired methicillin-resistant S. aureus (CA-MRSA) infection. The isolate was genotyped as the ST93 (Queensland) clone of CA-MRSA and carried the Panton-Valentine leucocidin genes. Cure was obtained following prolonged antimicrobial therapy with vancomycin, rifampicin, cotrimoxazole and linezolid. Given the high morbidity and mortality of cavernous sinus thrombosis and the worldwide recent emergence of CA-MRSA, clinicians treating patients with this infection should consider early empirical coverage for CA-MRSA with an antimicrobial agent, such as vancomycin or linezolid, particularly in the presence of suspected facial staphylococcal skin infections. If vancomycin is used, we emphasize that high doses may be required to achieve even low levels in the cerebrospinal fluid.     

Efficacy of linezolid in the treatment of mediastinitis due to methicillin-resistant Staphylococcus aureus: an experimental study.

INTRODUCTION: The treatment of postoperative mediastinitis is very important because of its high morbidity, mortality, and increased hospital stay and hospital costs. The aims of our research were to investigate whether linezolid alone can be an effective treatment agent for methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis, and to determine whether linezolid can provide synergistic activity when given in combination with rifampin. METHODS: A partial upper median sternotomy was performed on 70 rats. The animals were divided into seven groups: an uncontaminated control group; an untreated contaminated group; three contaminated groups that received antibiotic therapy with either 25 or 50 mg/kg linezolid twice a day, or rifampin 5 mg/kg twice a day; and two contaminated groups that received a combination therapy consisting of 25 or 50 mg/kg linezolid and rifampin 5 mg/kg twice a day. The antibiotic treatment lasted 7 days. Tissue samples from the upper ends of the sternum and swab specimens of the upper mediastinum were obtained and evaluated microbiologically. RESULTS: The 25-mg/kg dose of linezolid, either alone or combined with rifampin, was not effective in reducing the bacterial counts in mediastinum and sternum. Quantitative bacterial cultures of mediastinum and sternum were significantly lower in the groups receiving 50 mg/kg linezolid alone or in combination with rifampin compared with the control. Adding of rifampin to linezolid therapy did not result in a significant change in bacterial counts versus linezolid alone. CONCLUSION: A high dose of linezolid should be considered as a possible therapeutic agent for the treatment of post-sternotomy infection caused by MRSA.     

Methicillin-Resistant S. aureus Ventilator-Associated Pneumonia: Strategies to Prevent and Treat

Ventilator-associated pneumonias (VAPs) due to methicillin-resistant Staphylococcus aureus (MRSA) are rising in incidence and pose unique challenges in their prevention and treatment. Risk factors for the development of MRSA VAP include nasal carriage, prior antibiotic therapy, prolonged mechanical ventilation, poor infection control practices, head trauma/coma, and viral infection. Measures to prevent the development of MRSA VAP include general VAP prevention strategies and reduction of S. aureus nasal carriage. S. aureus possesses a variety of transferable genetic elements that encode proteins conferring resistance to several antibiotics, including beta-lactams and glycopeptides. Successful treatment of MRSA VAP with currently available antibiotics has been poor. Current management guidelines recommend glycopeptides as initial therapy for MRSA VAP. However vancomycin success rates are low, ranging from only 35 to 57%. This may be due to the poor penetration of vancomycin into the lung, and alternate dosing regimens to increase tissue levels need to be further studied. Treatment with linezolid, which penetrates well into the lung, is associated with higher cure and survival rates. Further data are needed to evaluate the efficacy of new antibiotics in MRSA VAP.     

Treatment of Resistant Enterococcal Urinary Tract Infections

Enterococcus spp have emerged as important pathogens in urinary tract infection (UTI), especially in hospitalized patients. Resistance to multiple antibiotics, including vancomycin, has become common, particularly in infections involving Enterococcus faecium. The management of UTIs caused by Enterococcus spp has become challenging given the presence of underlying comorbidities in these patients and the limited therapeutic options available to treat multidrug-resistant (MDR) Enterococcus. Routine therapy for asymptomatic bacteriuria with MDR-Enterococcus is not recommended. Removal of indwelling urinary catheters should be considered. Appropriate antibiotic therapy selection should be guided by urine culture and susceptibility results. Data are limited on the treatment of UTIs caused by MDR-Enterococcus. Potential oral agents active against MDR-Enterococcus that may be considered for acute uncomplicated UTI include nitrofurantoin, fosfomycin, and fluoroquinolones. Potential parenteral agents for the treatment of pyelonephritis and complicated UTIs caused by MDR-Enterococcus include daptomycin, linezolid, and quinipristin-dalfopristin. Aminoglycosides or rifampin may be considered as adjunctive therapy in serious infections.     

The costs and consequences of methicillin-resistant Staphylococcus aureus infection treatments in Canada.

BACKGROUND: A multinational randomized controlled trial has shown a trend toward early discharge of patients taking oral linezolid versus intravenous vancomycin (IV) in the treatment of methicillinresistant Staphylococcus aureus (MRSA) infections. Infection treatments resulting in shorter hospitalization durations are associated with cost savings from the hospital perspective. OBJECTIVE: To determine whether similar economic advantages are associated with oral linezolid, the costs and consequences of linezolid use following vancomycin IV versus the existing practice in the treatment of infections caused by MRSA were compared. METHODS: The charts of all patients admitted to one of three tertiary care teaching hospitals between January 1, 1997 and August 31, 2000 and treated with vancomycin IV for an active MRSA infection (skin and soft tissue only) were reviewed. Based on the vancomycin IV chart review data set and a simulated linezolid data set, the clinical consequences and the associated costs of MRSA treatment with vancomycin IV, and oral and IV forms of linezolid were quantified and compared within the framework of a cost-consequence analysis. RESULTS: Patients treated with oral and IV forms of linezolid compared with the existing practice had a shorter length of stay and required fewer home IV care services, which resulted in a cost savings of $750 (2001 values) to the Canadian health care perspective. CONCLUSIONS: The estimated cost savings associated with linezolid use not only offset the higher acquisition cost of the anti-infective, but may be substantial to health care systems across Canada, especially as the incidence of MRSA continues to rise.     

Treatment of community-acquired methicillin-resistant Staphylococcus aureus in children

PURPOSE OF REVIEW: The concept of methicillin-resistant Staphylococcus aureus (MRSA) associated with broad resistance, nosocomial acquisition, and known risk factors has recently been expanded. A new type of MRSA that is resistant to fewer antibiotics has emerged in pediatric practice since the mid-1990s. These isolates are community acquired and have been reported from diverse geographic regions. Awareness of these organisms is important for appropriate treatment of S. aureus infections in children. RECENT FINDINGS: Community-acquired MRSA (CA-MRSA) isolates are similar in many respects to community-acquired methicillin-susceptible S. aureus (CA-MSSA). There are usually no differences in risk factors between children with CA-MRSA infections and those with CA-MSSA infections or their household contacts. In one study, however, multivariate analysis showed that age greater than 1 year and health care contact in the preceding month were significant risk factors for CA-MRSA. Skin and soft tissue infections are the most common manifestations, although serious invasive infections and death may occur. Pneumonia has been reported more often in children with CA-MRSA than in those with CA-MSSA. Clindamycin is an effective therapy for CA-MRSA, but there is a risk for development of clindamycin resistance during treatment of a CA-MRSA that is clindamycin susceptible and inducibly erythromycin resistant. Trimethoprim-sulfamethoxazole is likely to be effective, and linezolid is a new option for treatment. SUMMARY: The appearance of CA-MRSA has important implications for therapy of infections caused by S. aureus in children. Three specific issues are the development of resistance during clindamycin therapy, insufficient data on the use of trimethoprim-sulfamethoxazole in serious CA-MRSA infections, and the appropriate role for newer antibiotics such as linezolid.     

Vancomycin-resistant Staphylococcus aureus: a real and present danger?

The glycopeptide antibiotic, vancomycin and teicoplanin, are the mainstay of therapy for infections involving strains of Staphylococcus aureus that are resistant to methicillin and gentamicin. During the last 5 years, clinical isolates of S. aureus showing reduced susceptibility to glycopeptides have been reported from many countries around the world, often associated with prolonged glycopeptide therapy. Detection and monitoring of such strains has been hindered by the fact that vancomycin (or glycopeptide)-intermediate S. aureus (VISA) isolates may be missed on conventional disk sensitivity tests. Effective control measures are required to prevent the increasing occurrence and spread of such strains in both the hospital and community settings. An important aspect of control is promoting the judicious use of glycopeptides. The recent introduction of the alternative antibiotics quinupristin/dalfopristin and linezolid, which are active against S. aureus strains resistant to many other classes of agent, should facilitate this process. Received: November 14, 2001 · Revision accepted: February 16, 2001     

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.     

Vancomycin-intermediate and -resistant Staphylococcus aureus: what the infectious disease specialist needs to know.

Ever since the first strain of Staphylococcus aureus with reduced susceptibility to vancomycin and teicoplanin was reported from Japan, there has been a lot of confusion regarding the laboratory and clinical approach to patients with infections due to S. aureus with reduced susceptibility to vancomycin. To date, 6 clinical infections with vancomycin-intermediate S. aureus (VISA) have been reported in the United States. Intermediate resistance appears to develop from preexisting strains of methicillin-resistant S. aureus in the presence of vancomycin, and all but 1 infection occurred in patients with exposure to dialysis for renal insufficiency. Detection of VISA is difficult in the laboratory, and special inquiries about susceptibility testing methods may be needed. These VISA-infected patients had underlying illnesses, and their infections did not appear to respond well to conventional treatment. Prevention strategies have been outlined. Without continued vigilance in enforcing infection-control measures, improved use of antimicrobials, and coordination of efforts among public health authorities, increasing levels of vancomycin resistance in S. aureus are likely to be encountered.     

Optimizing therapy for MRSA pneumonia

With its remarkable armamentarium of resistance and virulence factors, Staphylococcus aureus has emerged as a dominant pathogen causing pneumonia of all classifications. Rates of methicillin resistance are increasing as clinicians struggle to find ways to prevent the acquisition of methicillin-resistant Staphylococcus aureus (MRSA) and to effectively treat MRSA pneumonia. Community-associated MRSA has been identified as an important subset of MRSA with unique characteristics. Vancomycin remains a recommended first-line therapy for MRSA pneumonia, but resistance and therapeutic failures with vancomycin are being increasingly reported. Factors associated with vancomycin success or failure have been identified, including the genetics of the MRSA isolate, vancomycin lung penetration, minimum inhibitory concentration, and pharmacokinetic and pharmacodynamic variables. Retrospective analyses suggest that linezolid may provide improved outcomes compared with vancomycin for MRSA pneumonia, but validation in a prospective trial is currently lacking. Other treatment options are limited, but new prospects are being investigated. This paper reviews the epidemiology and pharmacotherapy of MRSA pneumonia.