European perspective and update on the management of complicated skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid (original) (raw)
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Core Evidence, 2012
Methicillin-resistant Staphylococcus aureus (MRSA), including community-associated and hospital-associated strains, is a major cause of human morbidity and mortality. Treatment options have become limited due to the emergence of MRSA strains with decreased sensitivity to vancomycin, which has long been the first-line therapy for serious infections. This has prompted the search for novel antibiotics that are efficacious against MRSA. Linezolid, an oxazolidinone class of antibiotic, was approved by the Food and Drug Administration in 2000 for treatment of MRSA infections. Since then, there have been a multitude of clinical trials and research studies evaluating the effectiveness of linezolid against serious infections, including pneumonia (both community-and hospital-acquired), skin and soft-tissue infections such as diabetic foot ulcers, endocarditis, osteomyelitis, prosthetic devices, and others. The primary aim of this review is to provide an up-to-date evaluation of the clinical evidence for using linezolid to treat MRSA infections, with a focus on recently published studies, including those on nosocomial pneumonia. Other objectives are to analyze the cost-effectiveness of linezolid compared to other agents, and to review the pharmokinetics and pharmacodynamics of linezolid, emphasizing the most current concepts.
The American Journal of Surgery, 2010
BACKGROUND: This open-label study compared oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections (cSSTIs) caused by methicillinresistant Staphylococcus aureus (MRSA). METHODS: Patients with proven MRSA cSSTI were randomized to receive linezolid or vancomycin. Clinical and microbiologic outcomes, duration of antimicrobial therapy, length of hospital stay, and safety were assessed. RESULTS: In the per-protocol population, the rate of clinical success was similar in linezolid-and vancomycin-treated patients (P ϭ .249). The rate of success was significantly higher in linezolid-treated patients in the modified intent-to-treat population (P ϭ .048). The microbiologic success rate was higher for linezolid at the end of treatment (P Ͻ .001) and was similar at the end of the study (P ϭ .127). Patients receiving linezolid had a significantly shorter length of stay and duration of intravenous therapy than patients receiving vancomycin. Both agents were well tolerated. Adverse events were similar to each drug's established safety profile. CONCLUSIONS: Linezolid is an effective alternative to vancomycin for the treatment of cSSTI caused by MRSA.
Objectives: To evaluate the in-vitro activities of linezolid, vancomycin, ciprofloxacin, gentamicin, amikacin, trimethoprim and fusidic acid, against methicillin resistant isolates. Materials and Methods: Three hundred and twenty two non-duplicate archived Staphylococcal isolates recovered from routine cultures performed in the microbiology laboratory from wounds, and abscesses swabs, urine, blood, pus, derived from both in-and out patients were tested. Results: A total of 274 S. aureus and 76 CNS clinical isolates were included in the study, 46.7% were MRSA and 21% methicillin resistant CNS (MRCNS). None of the strains was found to be resistant to linezolid and vancomycin. The resistance rates of MRSA isolates to antibiotics were as follows: 86% to gentamicin, 84.3% to fusidic acid, 80% to trimethoprim, 78.2% to ciprofloxacin and 76.5% to amikacin. Similar trend were also obtained for MRCNS isolates. The majority (70%) of MRSA isolates were resistant to all used classes of antibiotics in the study, while only 4.3% were sensitive to such antimicrobial agents. Conclusion: Due to the high prevalence of multi-drug resistant MRSA, this study has provided valuable baseline information to clinicians regarding the benefit of linezolid, suggesting that it can be used as an alternative drug in such severe life threatening infections caused by MRSA, especially if the side effect of vancomycin was observed.
Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections
Antimicrobial Agents and Chemotherapy, 2005
Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P ؍ 0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P < 0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.
Colonization is an important step in the pathogenesis of methicillin-resistant Staphylococcus aureus (MRSA) infection. Both patients and healthcare workers (HCWs) colonized by MRSA playing important role in MRSA transmission. Linezolid is the first antibiotic of the oxazolidinones class approved for clinical use by the FDA as a response to the rising incidence of MRSA. Investigation of the clinical (in vivo) and microbiological laboratory (in vitro) effect of linezolid on nasal and throat colonization with MRSA. A prospective cohort, opened, controlled and randomized study was conducted, where nasal and throat swabs were obtained from the healthcare workers (HCWs) in different hospital departments to investigate for methicillin-resistant Staphylococcus aureus (MRSA) carriers. Eligible personnel colonized with MRSA were randomized into linezolid group received (linezolid) 600 mg every 12 hours in form of oral tablet for 10 days. The quantitative assay for minimum inhibitory concentrations (MICs) of linezolid against MRSA was determined by using the Epsilon test (E-test) strips. Overall 134 healthcare workers screened, 43 (32%) were found to be MRSA carriers; 41 (95%) were nasal carriers and 2(5%) were nasal plus throat carriers. The MRSA carriages were found as following; (35.7%) between doctors, (32%) between nursing staff and (27.8%) between cleaning workers. From 30 HCWs received linezolid oral tablet 19 (63.3%) cleared from MRSA colonization while no one in the control group who did not receive linezolid was able to clear MRSA with (P = 0.002). Out of 28 nasal carriers 17 (60.7%) cleared from MRSA colonization and all 2 (100%) nasal plus throat carriers cleared from MRSA without significant difference between both carriers. Linezolid was responsible for nausea (P = 0.04) which was observed only in the first day of starting the treatment and bad taste (P = 0.01). Linezolid showed excellent (100%) in vitro activity against MRSA strains before and after treatment and the minimum inhibitory concentrations (MICs) range of linezolid for MRSA isolates obtained from HCWs before treatment was (0.38-2 µg/ml). The decolonization rate of linezolid E-test strips was (100%) compared to (63.3%) for the oral tablet of linezolid, therapy failure was not likely to be due to linezolid resistance, all the HCWs that showed therapy failure 11 (36.7%) were still susceptible for linezolid. The use of linezolid is considered to be promising regarding MRSA eradication. Linezolid is effective in eradication of both nasal and nasal plus throat colonization. Linezolid was well tolerated from HCWs.
International Journal of Infectious Diseases, 2010
Background: Staphylococcus aureus is a facultatively anaerobic, Gram-positive coccus. It is a major pathogen associated with serious community and hospitalacquired infections. By designation methicillin resistant Staphylococcus aureus (MRSA) is a strain of Staphylococcus aureus that is resistant to all beta-lactams, including penicillins, cephalosporins and carbapenems. Vancomycin has a narrow spectrum of activity, restricted to most Gram-positive bacteria, and is the drug of choice for the treatment of methicillin resistant Staphylococcus aureus. This agent, however, requires intravenous administration, and occasionally patients experience unacceptable side effects. Linezolid, a member of the new oxazolidinone class of antibiotics, has shown very good activity against methicillin resistant Staphylococcus aureus, has excellent oral bioavailability and is inexpensive as compared to vancomycin. Aims and Objectives: Comparison of in vitro activities of vancomycin and linezolid against methicillin resistant Staphylococcus aureus. Materials and Method: The study was conducted over a period of 6 months. Fifty Methicillin resistant Staphylococcus aureus isolated from the clinical isolates of Military hospital Rawalpindi were subjected to the determination of Minimum inhibitory concentrations of linezolid and vancomycin using E-strips. Minimum inhibitory concentrations 50 and minimum inhibitory concentrations 90 were calculated. Results: All the isolated organisms were uniformly susceptible to both the antibiotics. Vancomycin showed higher minimum inhibitory concentrations (MICs) as compared to linezolid MICs. Conclusion: This study suggests that linezolid and vancomycin have similar in vitro efficacy for methicillin resistant Staphylococcus aureus infections. Linezolid's oral dosing option can allow earlier discharge of hospitalized patients and its low cost reduces health care expenses.
Journal of Antimicrobial Chemotherapy, 2007
Linezolid soft tissue penetration and serum antimicrobial activity were analysed in six patients with peripheral vascular disease and severe diabetic foot infections requiring surgical intervention. Methods: Blood draws (1, 3, 6, 9 and 12 h after initiation of a 1 h infusion) and a viable soft tissue sample at the site of infection were obtained in patients receiving linezolid (600 mg every 12 h) on the day of surgery. Concentrations of linezolid were determined by HPLC in both tissue (pre-treated with tissue lysis buffer) and serum. In addition, serum inhibitory and bactericidal activity (dilution titres 1:2-1:32) of linezolid was determined in these patients against strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (vancomycin MICs 5 2, 4, 8, 256 and >256 mg/L). Results: Linezolid concentrations in tissue were found to be 51% (range, 18% to 78%) of simultaneous serum concentrations. Rapid (1 h) and prolonged (12 h) inhibitory activity (titres 1:2) was observed for linezolid against each of the study isolates. Furthermore, bactericidal activity (titres 1:2) was observed for at least 6 h (50% of the dosing interval) against four of these five strains. Conclusions: These findings suggest that linezolid could be effective in the treatment of multidrugresistant MRSA even when concentrations at the infection site are diminished due to impaired blood flow.
International Journal of Infectious Diseases, 2010
Background: Staphylococcus aureus is a facultatively anaerobic, Gram-positive coccus. It is a major pathogen associated with serious community and hospitalacquired infections. By designation methicillin resistant Staphylococcus aureus (MRSA) is a strain of Staphylococcus aureus that is resistant to all beta-lactams, including penicillins, cephalosporins and carbapenems. Vancomycin has a narrow spectrum of activity, restricted to most Gram-positive bacteria, and is the drug of choice for the treatment of methicillin resistant Staphylococcus aureus. This agent, however, requires intravenous administration, and occasionally patients experience unacceptable side effects. Linezolid, a member of the new oxazolidinone class of antibiotics, has shown very good activity against methicillin resistant Staphylococcus aureus, has excellent oral bioavailability and is inexpensive as compared to vancomycin. Aims and Objectives: Comparison of in vitro activities of vancomycin and linezolid against methicillin resistant Staphylococcus aureus. Materials and Method: The study was conducted over a period of 6 months. Fifty Methicillin resistant Staphylococcus aureus isolated from the clinical isolates of Military hospital Rawalpindi were subjected to the determination of Minimum inhibitory concentrations of linezolid and vancomycin using E-strips. Minimum inhibitory concentrations 50 and minimum inhibitory concentrations 90 were calculated. Results: All the isolated organisms were uniformly susceptible to both the antibiotics. Vancomycin showed higher minimum inhibitory concentrations (MICs) as compared to linezolid MICs. Conclusion: This study suggests that linezolid and vancomycin have similar in vitro efficacy for methicillin resistant Staphylococcus aureus infections. Linezolid's oral dosing option can allow earlier discharge of hospitalized patients and its low cost reduces health care expenses.
Microbiology Research, 2011
Linezolid is approved for complicated and uncomplicated skin and soft tissue infections. We have evaluated the efficacy of this drug in murine as well as in rat skin and soft tissue infection models using Staphylococcus aureus ATCC and clinical strains. In thigh infection model the dose of linezolid required for more than 1 log 10 kill from baseline inoculum in neutropenic mice and rats was 100 mg/kg and 50 mg/kg, b.i.d/day, respectively, which was 5 and 4 folds more than that in immunocompetent animals, respectively. Dose required to achieve 1 log 10 killing was similar against different strains of S. aureus in immunocompetent mouse thigh infection model. However, in murine groin abscess infection model, a dose of 100 mg/kg, b.i.d/day of linezolid produce static effect in 2 days, but revealed to be superior in 4 days treatment and showed approximately 1 log 10 killing from base line inoculums. Based upon pharmacokinetic profile, a 24-h AUC/MIC required for linezolid efficacy in murine groin abscess model was 91.5 for the strain used in this study. As linezolid is taken as a gold standard drug in the evaluation of new chemical entity, this data could be useful for comparing the preclinical efficacy of new anti-MRSA agents.