Clinical Efficacy of Oral Linezolid Compared With Intravenous Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus-Complicated Skin and Soft Tissue Infections: A Retrospective, Propensity Score-Matched, Case-Control Analysis
Linezolid is 100% bioavailable in oral and intravenous formulations. In a recent prospective, randomized, open-label, comparator-controlled, multicenter, phase 4 clinical trial in adults with complicated skin and soft tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA), linezolid achieved clinical and microbiologic success comparable to appropriately dosed intravenous vancomycin. Although patients were randomly assigned to receive linezolid or vancomycin, the protocol allowed patients to start therapy using oral or intravenous linezolid on the basis of investigator discretion and patient ability to tolerate oral medication.
The objective of this study was to assess the efficacy and tolerability of linezolid when administered orally in adults with cSSTI caused by MRSA. In this retrospective analysis, we examined data collected from the aforementioned trial to compare outcomes in patients who received either oral linezolid or intravenous vancomycin therapy.
This study analyzed outcomes in patients who received treatment for 7 to 14 days with either oral linezolid (600 mg q12h; n = 95) or intravenous vancomycin (15 mg/kg q12h, adjusted for creatinine clearance and trough concentration; n = 210). By design, these groups were not randomized. Propensity score matching on baseline variables was used to balance these groups by identifying a comparable group of patients who received vancomycin therapy and comparing them with patients who received oral linezolid therapy. Clinical and microbiologic success rates at the end of treatment and the end of the study (EOS) were then directly compared between the groups using matched-pair logistic regression. The tolerability of the 2 treatments (within this matched group) was also described.
Ninety-two patients with well-matched baseline characteristics were included in each treatment group. At EOS, the odds ratio for clinical success of oral linezolid therapy vs intravenous vancomycin therapy was 4.0 (95% CI, 1.3-12.0; P = 0.01), and the odds ratio for microbiologic success at EOS was 2.7 (95% CI, 1.2-5.7; P = 0.01). Overall rates of adverse events in each group were consistent with reported safety profiles for each drug.
A favorable clinical cure rate was achieved with oral linezolid therapy when compared with intravenous vancomycin therapy in propensity score-matched patients with cSSTI proved to be caused by MRSA. ClinicalTrials.gov Identifier: NCT00087490.
"The previous study demonstrated that a favorable clinical cure rate was achieved with oral linezolid therapy when compared with intravenous vancomycin therapy in propensity score-matched patients with complicated skin and soft tissue infections caused by MRSA isolates . However, a few data are available on which antibiotics can be used after intravenous glycopeptides in the management of patients with MRSA infections. "
[Show abstract][Hide abstract] ABSTRACT: Background:
Carefully switching from intravenous to oral antibiotic therapy has shown to reduce treatment costs and lengths of hospital stay as well as increase safety and comfort in patients with infections. The aim of this study was to compare the clinical efficacy and safety between the patients treated with glycopeptides (case group), and the patients given oral antibiotics, as the initial or step-down therapy (control group), in the treatment of patients with methicillin-resistant Staphylococcus aureus (MRSA) infection.
Materials and methods:
A multicenter observational study was retrospectively performed in 7 teaching hospitals in Korea from January to December 2012. The study included adult patients (≥ 18 years) with infection caused by MRSA isolates, susceptible to clindamycin, erythromycin, and ciprofloxacin. The primary end point was treatment outcome, including all-cause mortality and switching of antibiotics. Drug-related adverse events and the lengths of hospital stay were also compared between the two treatment groups.
During the study period, 107 patients (43 cases and 64 controls) with MRSA infections were enrolled from the participating hospitals. The most common sites of MRSA infection were skin and soft tissue (n = 28) and bone and joint (n = 26). The median Charlson comorbidity index (P = 0. 560), the frequency of severe sepsis (P = 0.682) or thrombocytopenia (P = 1.000), and median level of serum C-reactive protein (P = 0.157) at the onset of MRSA infections were not significantly different between the case and control groups. The oral antibiotics most frequently prescribed in the case group, were fluoroquinolones (n = 29) and clindamycin (n = 8). The median duration of antibiotic treatment (P = 0.090) and the occurrence of drug-related adverse events (P = 0.460) did not reach statistically significant difference between the two groups, whereas the total length of hospital stay after the onset of MRSA infection was significantly shorter in the case group than the control group [median (interquartile range), 23 days (8-41) vs. 32 days (15-54), P = 0.017]. In multivariate analyses, the type of antibiotic used was not an independent risk factor for treatment failure. The statistically significant factors associated with treatment failure included underlying hepatic diseases, prior receipt of antibiotics, and foreign body retention.
This study indicates that oral antibiotic therapy with active agents against MRSA isolates can be considered as the initial or step-down therapy for the treatment of MRSA infections and also reduce the length of hospital stay.
"Previous in vitro work supports daptomycin as the superior agent (Maraconescu et al. 2012). Multiple clinical studies, analyses and reviews, have suggested a possible advantage for linezolid (Menzin et al. 2010;Bounthavong et al. 2011;van Hal and Paterson 2011;Bounthavong and Hsu 2012;Logman et al. 2010;Itani et al. 2012;Barron et al. 2012;Watkins et al. 2012) or daptomycin (Itani et al. 2010;Quist et al. 2012;Falcone et al. 2012;Bliziotis et al. 2010;Davis et al. 2007) as compared to vancomycin in terms of time to clinical cure, hospital length of stay, or both. Despite the evidence favoring linezolid or daptomycin over vancomycin, some authors have been unconvinced of the clinical relevance of the purported superiority of the newer agents (Eckmann and Dryden 2010). "
[Show abstract][Hide abstract] ABSTRACT: Empiric therapy of inpatient skin and soft tissue infections (SSTIs) generally require methicillin resistant Staphylococcus aureus (MRSA) coverage. Limited data are available to directly compare the effect of initial antibiotic choice on treatment outcomes and length of stay (LOS).
To assess potential differences in length of hospital stay when inpatients with complex skin and soft tissue infections (SSTIs) were initially treated with either vancomycin, linezolid, or daptomycin.
A retrospective review of 219 patients diagnosed with inpatient SSTI who received linezolid, vancomycin, or daptomycin for >48 hours was performed. Data collected included demographics, comorbidities, microbiologic/laboratory data, additional management (surgical, non-study antibiotics), hospital LOS, treatment outcome and morbidity/mortality.
The three groups evaluated were linezolid (n = 45), vancomycin (n = 90) daptomycin (n = 84). There was no difference between the three groups with respect to gender, age, comorbidities, leukocytosis, fever, antibiotics prior to admission, site of infection culture results and surgical intervention. One death was recorded, not associated with diagnosis of SSTI. No significant difference in LOS was found (P = 0.525) between the 3 groups. The mean LOS in entire cohort was 4.5 days (SD ± 2.5); thirty patients had prolonged LOS for non-SSTI reasons; reanalyzing the data without these 30 patients did not produce any difference in the mean LOS between the 3 groups. Switching vancomycin just prior to discharge to facilitate outpatient therapy was common but did not impact LOS.
No difference was detected in hospital length of stay with respect to the initial choice of antibiotic (linezolid, vancomycin, or daptomycin) for SSTI. The three antibiotic regimens were equally effective in treating SSTIs as judged by LOS, irrespective of age, gender, comorbidities or baseline severity of SSTI. Given the large standard deviation in LOS, this result should be confirmed by larger studies.
"Both antibiotics were well tolerated. The same researchers then conducted a retrospective analysis of the safety and efficacy of oral linezolid for MRSA SSTIs compared to intravenous vancomycin.52 Patients received treatment for 7–14 days with either oral linezolid (600 mg/12 hours; n = 95) or intravenous vancomycin (15 mg/kg/12 hours, adjusted for creatinine clearance and trough concentration; n = 210). "
[Show abstract][Hide abstract] ABSTRACT: 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.
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