Sitafloxacin in the treatment of patients with infections caused by vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus

Sitafloxacin is a new quinolone active against multi-resistant Gram-positive pathogens. An open study was conducted in patients with serious systemic infections with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococcus (VRE). Patients with MRSA were recruited if treatment with glycopeptides had failed. Of 11 patients with MRSA infection, four were cured, six failed treatment and one was indeterminate. Of nine patients with VRE infection (one patient had both pathogens), five were cured and four failed. Fifteen adverse events in 12 patients were potentially related to the study drug. Sitafloxacin was effective in VRE and some recalcitrant MRSA infections.     

Efficacy of linezolid alone or in combination with vancomycin for treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus

The levels of effectiveness of linezolid, vancomycin, and the combination of linezolid and vancomycin were compared in the rabbit model of endocarditis caused by a clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate. Vancomycin alone was more effective than either linezolid alone or the combination of linezolid and vancomycin for the treatment of endocarditis due to MRSA.     

In vitro activity of linezolid against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.

We report the activity of the new oxazolidinone antimicrobial agent linezolid against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 20 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci were inhibited by < or = 4 ug/ml of linezolid. All isolates of methicillin-resistant S. aureus were inhibited by < or = 8 ug/ml of linezolid. All isolates of penicillin-resistant S. pneumoniae were inhibited by < or = 2 ug/ml of linezolid. Linezolid inhibits strains of multidrug resistant Gram-positive cocci in vitro at concentrations < or = 8 ug/ml.     

Cost-effectiveness analysis of linezolid compared with vancomycin for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus

OBJECTIVE: This study compared the cost-effectiveness of linezolid and vancomycin in the treatment of patients with nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS: A retrospective decision-analytic model was applied to pooled data from 2 prospective, randomized, controlled, double-blind studies, and claims data from a large health plan (3.3 million members) located in the Mid-Atlantic region. Using hospital claims for patients in the health plan with suspected NP, we then determined their daily billed (submitted) hospital charges for 4 mutually exclusive potential health outcomes of linezolid or vancomycin treatment: survival with bacteremia, survival without bacteremia, nonsurvival with bacteremia, and nonsurvival without bacteremia. To generate the expected total daily billed hospital charge for each drug-treatment group, we weighted the determined daily billed hospital charges by the probabilities of each outcome developing in each treatment arm, as derived from the clinical-trial data. Drug acquisition costs were then incorporated, and the difference in expected total costs relative to the difference in rates of survival between the linezolid and vancomycin arms was used to calculate the incremental cost-effectiveness ratio (ICER) for linezolid. RESULTS: Costs were higher for nonsurviving patients compared with surviving patients. Estimated median daily billed treatment charges were $2888 for linezolid and $2993 for vancomycin. Based on Monte Carlo simulations, the respective 95% CIs were $2671 to $3106 and $2615 to $3372. Using mean treatment durations of 11.3 and 10.7 days, respectively, we obtained expected total hospitalization charges of $32,636 for linezolid treatment (95% CI, $30,182-$35,098), compared with $32,024 for vancomycin treatment (95% CI, $27,978-$36,078). The ICER for linezolid per life saved was $3600. CONCLUSIONS: The higher acquisition cost of linezolid was almost completely offset by improved survival and a reduction in health care costs associated with improved survival. As a result, linezolid was almost cost-neutral compared with vancomycin in the treatment of NP caused by MRSA.     

Antimicrobial therapy of multidrug-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus

Antibiotic resistance among pneumococci, enterococci, and staphylococci has become increasingly important in recent decades. Clinicians should be familiar with the nuances of antibiotic susceptibility testing and interpretation in selecting antibiotics for these infections. The clinical significance of penicillin-resistant Streptococcus pneumoniae, macrolide-resistant S pneumoniae, and multidrug-resistant S pneumoniae is discussed. The clinical spectrum and therapeutic approach to Enterococcus faecalis (i.e., vancomycin-sensitive enterococci) and E faecium (i.e., vancomycin-resistant enterococci) are discussed. Differences in therapeutic approach between methicillin-sensitive Staphylococcus aureus and methicillin-resistant S aureus (MRSA) infections are reviewed. Differences between in vitro susceptibility testing and in vivo effectiveness of antibiotics for hospital-acquired MRSA (HA-MRSA) are described. Finally, the clinical features of infection and therapy of HA-MRSA and community-acquired MRSA (CA-MRSA) infections are compared.     

利奈唑胺和万古霉素治疗甲氧西林耐药金黄色葡萄球菌感染的疗效比较

甲氧西林耐药金葡菌(MRSA)感染可选择的治疗药物有限,多年来万古霉素是治疗的金标准。对万古霉素敏感性下降菌株的出现,增加了对新型抗感染药物的需求,噁唑烷酮类药物利奈唑胺是治疗MRSA感染的新药。然而,评价该药临床疗效的研究较少。本文比较利奈唑胺与万古霉素治     

Enoxacin compared with vancomycin for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis.

Enoxacin administered orally was compared with vancomycin administered intravenously for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis. The MICs and MBCs of both enoxacin and vancomycin for an inoculum of 5.0 X 10(5) CFU of the methicillin-resistant S. aureus strain per ml were 1.56 microgram/ml. With an inoculum of 10(8) CFU/ml, enoxacin at 6 micrograms/ml and vancomycin at 180 micrograms/ml resulted in similar decreases in numbers of methicillin-resistant S. aureus in broth. Methicillin-resistant S. aureus endocarditis in rabbits was treated with enoxacin at 100 mg/kg orally every 12 h or vancomycin at 30 mg/kg intravenously every 12 h for 3 or 5 days. Enoxacin treatment for 3 or 5 days and vancomycin treatment for 5 days significantly reduced bacterial counts of vegetations compared with those in untreated control rabbits after 1 day of infection. Bacterial counts of vegetations after vancomycin treatment for 3 days did not differ significantly from those of untreated controls. Bacterial counts of vegetations in the four therapeutic groups did not differ significantly from one another. In uninfected rabbits single doses of vancomycin at 30 mg/kg administered intravenously achieved much higher concentrations in serum than did single doses of enoxacin at 100 mg/kg administered orally. Enoxacin had an elimination half-life in serum that was approximately 1.5 times longer than that of vancomycin. This study demonstrated that enoxacin administered orally is as effective as vancomycin administered intravenously for the treatment of experimental methicillin-resistant S. aureus endocarditis.     

Efficacy of linezolid against methicillin-resistant or vancomycin-insensitive Staphylococcus aureus in a model of hematogenous pulmonary infection

We investigated the activities of linezolid, vancomycin, and teicoplanin in a murine model of hematogenous pulmonary infection with Staphylococcus aureus. Our results demonstrate that linezolid clearly reduced bacterial numbers in the methicillin-resistant S. aureus hematogenous infection model and significantly improved the survival rate of immunocompromised mice infected with vancomycin-insensitive S. aureus compared with vancomycin and teicoplanin. The pharmacokinetic profiles also reflected the effectiveness of linezolid.     

Nisin,alone and combined with peptidoglycan-modulating antibiotics: activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci

OBJECTIVE: We have sought ways to circumvent resistance, by combining nisin with other antibiotics known to target bacterial cell wall biosynthesis. METHODS: Twenty strains each of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) were tested in vitro by standardized methods against nisin alone and combined with bacitracin, ramoplanin and chloramphenicol. RESULTS: Ramoplanin was the most potent compound, and bacitracin had the least activity. Two-way synergy was observed with nisin and ramoplanin. However, chloramphenicol was clearly antagonistic to the activity of nisin. CONCLUSIONS: Observations of synergy between nisin and ramoplanin against MRSA and VRE offer a promising approach to the concept of combining nisin with inhibitors of cell wall peptidoglycan. Further investigations are needed in order to develop this approach as a clinical possibility.     

Prospective, randomized study comparing quinupristin-dalfopristin with linezolid in the treatment of vancomycin-resistant Enterococcus faecium infections

OBJECTIVES: Quinupristin-dalfopristin and linezolid have been shown to be efficacious in the treatment of vancomycin-resistant Enterococcus faecium (VREF) infections. However, the two antibiotics have not been compared in terms of safety and efficacy in a prospective randomized study. The objective of this study was to compare the safety and efficacy of the two drugs in the treatment of VREF infections in cancer patients. PATIENTS AND METHODS: Forty cancer patients with VREF infection were randomized to receive linezolid 600 mg every 12 h or quinupristin-dalfopristin 7.5 mg/kg every 8 h. All patients were followed up for 30 days after discontinuation of study drugs. RESULTS: Linezolid and quinupristin-dalfopristin had comparable clinical responses (58% and 43%, respectively, P = 0.6). Myalgias and/or arthralgias occurred at a frequency of 33% in patients who received quinupristin-dalfopristin, but were not observed in the linezolid group (P = 0.03). In contrast, drug-related thrombocytopenia occurred in 11% of patients who received linezolid, but was not observed in the quinupristin-dalfopristin group (P = 0.2). CONCLUSION: In cancer patients, quinupristin-dalfopristin treatment is associated with a relatively high frequency of myalgias/arthralgias; however, profound thrombocytopenia might limit the choice of linezolid in a subpopulation of cancer patients.     

Activities of ceftobiprole, linezolid, vancomycin, and daptomycin against community-associated and hospital-associated methicillin-resistant Staphylococcus aureus

We evaluated the activity of ceftobiprole against 100 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and 100 hospital-associated MRSA (HA-MRSA) isolates. Eight isolates were evaluated by time-kill studies for kill rate and potential for synergy with tobramycin. Ceftobiprole MIC₅₀ and MIC₉₀ values were 1 and 2 μg/ml, respectively, against CA-MRSA and HA-MRSA. In time-kill analysis, ceftobiprole was bactericidal at all concentrations tested.     

In vitro activities of ceftobiprole, dalbavancin, daptomycin, linezolid, and tigecycline against methicillin-resistant Staphylococcus aureus blood isolates: stratified analysis by vancomycin MIC

The in vitro activities of newer agents against 569 methicillin-resistant Staphylococcus aureus (MRSA) blood isolates stratified by vancomycin MIC values (≤1 versus >1 μg/mL) were evaluated using broth microdilution methods. All agents had good in vitro activities against MRSA regardless of vancomycin MIC values. Some significant correlations between vancomycin and newer agents' MIC values were observed.