Burden of methicillin-resistant Staphylococcus aureus: focus on clinical and economic outcomes

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major public concern. Hospital-acquired MRSA rates have steadily increased over the past 25 years, and the bacterial strain is making inroads to the community. The morbidity and mortality burden of MRSA infection is compounded by delayed or inappropriate antibiotic treatment, taking a toll on health care resources that are already stretched thin. Vancomycin has historically been the drug of choice for this pathogen because its broad spectrum can address the multidrug resistance of most MRSA infections. Despite its sustained in vitro microbiologic inhibitory activity, researchers are beginning to question the continued utility of vancomycin for MRSA infections. Evidence against vancomycin is most notable with regard to nosocomial pneumonia and skin and soft tissue infections. In addition, because vancomycin must be administered intravenously, patients typically require prolonged hospitalization, which further increases the cost of MRSA treatment and exposes patients to additional nosocomial infections. Recent studies have shown that antibiotics with good bioavailability, such as linezolid, can be given orally to facilitate early hospital discharge, thus alleviating the economic burden of MRSA infections. Several agents have been developed over the past decade that have excellent in vitro activity against MRSA. Further studies are needed to determine if these drugs can better eradicate MRSA than vancomycin and remedy the adverse outcomes frequently observed with this organism.     

Synthesis and in vitro evaluation of substituted phenyl-piperazinyl-phenyl oxazolidinones against Gram-positive bacteria

With the incidence of linezolid-resistant Enterococcus faecalis, E. faecium and Staphylococcus aureus, modification of linezolid at the 5- and/or 3-positions led to the development of a series of 3-(methoxyl-phenyl)-piperazinyl-phenyl oxazolidinone analogues. These compounds were tested in vitro against six gram-positive standard organisms (S. aureus, S. epidermidis, S. pneumoniae, S. albus, Streptococcus enteridis and S. nonhemolyticus). 5-acetylaminomethyl oxazolidinones bearing fluorine at 3'-position of phenyl ring showed activities against several gram-positive bacteria (MIC: 3.13-6.25 mug/mL). The position of methoxyl group on the phenyl ring of piperazine group affected antibacterial spectrum. 3-(4'- (para-methoxyl-phenyl)-piperazinyl)-(3'-fluoro)-phenyl-5-acetylaminomethyl oxazolidinone was found active against 5 gram-positive organisms except S. nonhemolyticus, whereas 3-(4'-(ortho-methoxyl-phenyl)-piperazinyl)-(3'-fluoro)-phenyl-5-acetylaminomethyl oxazolidinone was found active only against 2 gram-positive organisms, namely S. albus, S. enteridis.     

Bacterial meningitis: new therapeutic approaches

Bacterial meningitis remains a disease with high mortality and long-term morbidity. Outcome critically depends on the rapid initiation of effective antibiotic therapy. Since a further increase of the incidence of pathogens resistant to antibacterials can be expected both in community-acquired and nosocomial bacterial meningitis, the choice of an optimum initial empirical antibiotic regimen will gain significance. In this context, the use of antibiotics which are bactericidal but do not lyse bacteria, may emerge as a therapeutic option. Conversely, the role of corticosteroids, which decrease the entry of hydrophilic antibacterials into the cerebrospinal fluid, as adjunctive therapy will probably decline as a consequence of the increasing antibiotic resistance of bacteria causing meningitis. Consequent vaccination of all children at present is the most efficient manner to reduce disease burden.     

A comparison of linezolid with glycopeptides in severe MRSA pneumonia

Evaluation of: Luna CM, Bruno DA, García-Morato J et al. Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in piglets. Chest 135(6), 1564–1571 (2009).

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen in nosocomial infections and accounts for a large proportion of nosocomial pneumonia. However, there are limited antibiotics available for the treatment of this serious and potentially lethal infection. Until recently, the only effective antibiotic was vancomycin, but the oxazolidinones, such as linezolid, have been shown to be a valuable addition to the arsenal of antimicrobial agents that can be used for MRSA pneumonia. Clinical trials have been conducted to compare vancomycin and linezolid head-to-head in pneumonia and, in post hoc subgroup analyses, showed that linezolid use was associated with improved survival. The ensuing debate over these results was dominated by two opinions; there were those who speculated on the mechanism by which linezolid achieved this benefit, namely attributing it to pharmacodynamics and pharmacokinetics, and others who criticized the methodology of the studies and questioned the validity of the results altogether. This study by Luna and colleagues was designed with several goals in mind. The first was to attempt to generate an animal model of MRSA pneumonia in piglets by duplicating techniques used in animal models of Gram-negative pneumonia. Then they studied the effect of three antibiotics (vancomycin, linezolid and teicoplanin) on outcomes in the same model, while simultaneously measuring antibiotic levels in the serum, bronchoalveolar lavage fluid and lung tissue, in an attempt to attribute differences in survival to pharmacological properties of the drugs used. Their results showed a survival benefit only for linezolid, despite the fact that all three antibiotics had levels above MIC in all the compartments sampled, leading them to speculate that linezolid may have improved outcomes by mechanisms not directly related to its antimicrobial actions.     

Morbidity,mortality, and management of methicillin-resistant S. aureus bacteremia in the USA: update on antibacterial choices and understanding

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with significant healthcare costs, morbidity, and mortality in the United States. Complications of MRSA bacteremia include infective endocarditis, osteomyelitis, and sepsis, all of which are difficult to treat. Time to effective therapy and antibacterial choice greatly affect patient outcomes. Vancomycin and daptomycin remain first-line therapies; however, reports of vancomycin-associated treatment failure and reduced daptomycin susceptibility highlight the need to define alternative strategies for MRSA bacteremia treatment. In addition, several patient- and pathogen-specific factors influence the outcomes of MRSA bacteremia. It is, therefore, critical to explore the interaction between host- and pathogen-specific factors and its effect on MRSA bacteremia pathogenesis and mortality. This review discusses the factors that drive the development of MRSA bacteremia and examines alternative treatment strategies.     

利奈唑胺治疗广泛耐药结核病的临床疗效评价

目的评价利奈唑胺治疗广泛耐药结核病的临床疗效。方法我院收治的24例广泛耐药结核病患者,随机分为两组,对照组12人采用常规化疗,试验组12人加用利奈唑胺,比较不良反应和疗效。结果试验组试验组症状改善、病灶吸收、空洞闭合、抗酸染色涂片阴性、痰结核分枝杆菌阴性、痰定量PCR阴性例数均明显高于对照组,试验组不良反应发生率高于对照组,差异均有统计学意义（P〈0.05）,经对症治疗后均痊愈。结论利奈唑胺治疗广泛耐药结核病疗效显著。     

A review of linezolid: the first oxazolidinone antibiotic

Resistance of Gram-positive bacterial pathogens, such as Staphylococcus aureus and Enterococcus faecium, to existing antibiotics continues to increase, and new antibiotics with activity against these pathogens are in demand. Linezolid (Zyvox^®, Pharmacia and Upjohn) is the first agent of a new class of antibiotics called the oxazolidinones. Linezolid possesses excellent microbial activity against a wide variety of Gram-positive pathogens including those resistant to methicillin and vancomycin (Vancocin^®, Eli Lilly). Linezolid is available for intravenous and oral administration and possesses excellent bioavailability. It exhibits good penetration into pulmonary, as well as skin and related structure tissues, and does not require dosage adjustment in hepatic or renal dysfunction. Linezolid is generally well-tolerated, with the predominant adverse effect manifesting as a duration dependent, reversible thrombocytopenia. Linezolid possesses monoamine oxidase inhibitor activity and caution is warranted with coadministration of adrenergic or seritonergic medications. Clinical trials conducted with linezolid in skin and structure infections, lower respiratory tract infections and vancomycin-resistant enterococcal infections demonstrate that linezolid is an effective therapy. Recent data suggest that linezolid may be superior to vancomycin for the treatment of infections caused by methicillin-resistant S. aureus. Linezolid is an excellent and promising new antibiotic for the treatment of resistant Gram-positive pathogens.     

Update on prevalence and treatment of methicillin-resistant Staphylococcus aureus infections

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is characterized by variations (sometimes extreme) by country and geographic region. The conventional association of MRSA with healthcare settings has been upset by the emergence of community-associated MRSA infections in many areas. With this surge in MRSA comes a renewed interest in alternative agents to vancomycin for treatment of MRSA infections, including older drugs, such as clindamycin, doxycycline and trimethoprim– sulfamethoxazole. Newer agents, such as linezolid and daptomycin, are aiming to improve on the poor cure rates found with vancomycin in serious MRSA infections, but definitive studies showing superiority of these drugs are not yet available. Finally, the drug-development pipeline contains a number of agents for the treatment of MRSA infections, including enhanced glycopeptides (dalbavancin, oritavancin and telavancin) and anti-MRSA cephalosporins (ceftobiprole). As MRSA becomes the ‘new normal’ in many areas, clinicians will have to sort out the proper role of a dozen or more anti-MRSA drugs.     

Current challenges in treating MRSA: what are the options?

This review looks at the challenges facing the worldwide community with the increasing problem of methicillin resistance in Staphylococcus aureus. The epidemiology and natural history of community-associated methicillin-resistant Staphylococcus aureus and the challenge of control is discussed. Options for treatment and review of key antimicrobial agents acting against methicillin-resistant S. aureus, both currently in use and in development, are addressed. There are a number of new agents, the place of which in therapeutic regimens is yet to emerge. The review attempts to inform the reader of the probable position of these agents.     

Successful treatment of vancomycin-resistant Enterococcus faecium endocarditis with linezolid in a renal transplant recipient with human immunodeficiency virus infection

Infections with vancomycin-resistant Enterococci cause significant morbidity and mortality in hospitalized patients, including transplant recipients. We report the successful use of oral linezolid to treat a case of vancomycin-resistant Enterococcus faecium endocarditis in a renal transplant recipient with human immunodeficiency virus infection.