ABSTRACT
BACKGROUND: Additional antibiotic options are needed to treat bone and joint infections caused by penicillin-resistant Gram-positive pathogens. OBJECTIVE: This subanalysis of the Telavancin Observational Use Registry (TOUR™) aimed to record real-world telavancin usage patterns in patients with bone and joint infections treated with telavancin. METHODS: TOUR was a multicenter observational-use registry study conducted at 45 US sites between January 2015 and March 2017. Patient characteristics, infection type, infecting pathogen(s), previous treatment, telavancin dosing and duration, clinical response, and adverse event data were collected by retrospective medical chart reviews. As such, inclusion/exclusion criteria were limited, and any patient receiving at least one dose of telavancin at the discretion of the treating physician was eligible. Patients were assessed as either positive clinical response, failed treatment, or indeterminate outcome. RESULTS: Of the 1063 patients enrolled in TOUR, 27.4% (291/1063) were patients with bone and joint infections including osteomyelitis (with or without prosthetic material), acute septic arthritis, and prosthetic joint infections. Most of these patients had osteomyelitis without prosthetic material (191/291; 66.0%). Among patients assessed at the end of treatment, 211/268 (78.7%) achieved a positive clinical response, 26/268 (9.7%) failed treatment, and 31/268 (11.6%) had an indeterminate outcome. The most frequent pathogen was methicillin-resistant Staphylococcus aureus (110/291; 37.8%). The median (interquartile range [IQR as Q1, Q3]) telavancin dose was 750.0 mg (IQR, 750, 750 mg) or 8.2 mg/kg (IQR, 6.8, 9.7 mg/kg) administered for a median of 26 days (IQR, 12, 42 days). These assessments were recorded in the registry ≥ 30 days after the last dose of telavancin was administered. CONCLUSIONS: Real-world data from the TOUR study show that clinicians are using once-daily telavancin with positive clinical outcomes for the treatment of bone and joint infections caused by Gram-positive pathogens. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02288234) on 11 November, 2014.
ABSTRACT
STUDY OBJECTIVE: Telavancin and vancomycin are both approved for treatment of hospital-acquired and ventilator-associated bacterial pneumonias caused by Staphylococcus aureus, and both agents can cause renal dysfunction. The objective of this study was to assess renal function changes by performing renal shift table analyses of telavancin- and vancomycin-treated patients in phase III trials. DESIGN: Retrospective, descriptive analysis of data from the safety population from the Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) trials. PATIENTS: A total of 1503 adults with hospital-acquired or ventilator-associated bacterial pneumonia primarily caused by gram-positive pathogens and who received telavancin (n = 751) or vancomycin (n = 752). MEASUREMENTS AND MAIN RESULTS: Decline or improvement in creatinine clearance (CrCl) across seven defined categories (≤30, >30-40, >40-50, >50-60, >60-70, >70-80, and >80 ml/min) was classified as negative or positive shifts, respectively. The number of categories crossed (either positive or negative) determined the grade of shift (of a potential grades 1-6, with crossing from one category to the next adjacent category defined as a grade 1 shift) at specific time points compared with baseline: day 4, day 7, and end of therapy (EOT). Approximately 77%-91.6% of patients had either no change or improvement of CrCl across all time points for both treatments. Negative shifts were consistent for telavancin (day 4, 19.3%; day 7, 19.0%; EOT, 23.0%) but increased over time for vancomycin (day 4, 8.4%; day 7, 12.3%; EOT, 19.3%). A significantly lower proportion of patients receiving vancomycin showed renal function decline on day 4 and day 7. At EOT, negative shift rates were similar between treatments (treatment difference 3.6% [95% CI -0.7 to 7.9]). At day 7 and EOT, a higher percentage of vancomycin-treated patients experienced high-grade negative shifts relative to telavancin (day 7, vancomycin 2.8% vs telavancin 1.9%; EOT, vancomycin 4.7% vs telavancin 4.1%), though differences were not statistically significant. CONCLUSION: Use of shift tables revealed differences in timing of renal function changes in patients receiving telavancin and vancomycin. Telavancin-related declines in renal function were similar at day 4 and day 7, with a slight increase by EOT. This differed from vancomycin, which caused a steady increase in the percentage of patients with renal function decline over time. A significant difference in negative renal shifts between treatments occurred at day 4 and day 7 and favored vancomycin; however, the difference was minimal and not significant at EOT.
Subject(s)
Aminoglycosides/administration & dosage , Anti-Bacterial Agents/administration & dosage , Lipoglycopeptides/administration & dosage , Vancomycin/administration & dosage , Adult , Aged , Aminoglycosides/adverse effects , Anti-Bacterial Agents/adverse effects , Clinical Trials, Phase III as Topic , Creatinine/metabolism , Female , Healthcare-Associated Pneumonia/drug therapy , Humans , Kidney Function Tests , Lipoglycopeptides/adverse effects , Male , Middle Aged , Pneumonia, Staphylococcal/drug therapy , Pneumonia, Ventilator-Associated/drug therapy , Randomized Controlled Trials as Topic , Retrospective Studies , Time Factors , Vancomycin/adverse effectsABSTRACT
BACKGROUND: When hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is caused by gram-positive and gram-negative pathogens or both (mixed infections), the adequacy of gram-negative coverage (GNC) can confound the assessment of a gram-positive agent under study. This analysis examines the influence of gram-negative infections and the adequacy of GNC on clinical efficacy and all-cause mortality in the telavancin HABP/VABP phase 3 ATTAIN trials (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia). METHODS: This post hoc analysis evaluated 3 patient groups from ATTAIN: (1) gram-positive-only infections, (2) gram-positive-only and mixed infections-adequate GNC, and (3) gram-negative-only infections and mixed infections with inadequate GNC. For each, clinical efficacy at test of cure and all-cause mortality at day 28 were compared for telavancin and vancomycin. RESULTS/CONCLUSIONS: In the ATTAIN safety population there were 16 more deaths in the telavancin arms than in the vancomycin arms. Of these, 13 were in patients with gram-negative-only infections (n = 9) or with mixed infections and inadequate GNC (n = 4) and all had estimated baseline creatinine clearances of <30ml/min. Based on this analysis, clinical response and all-cause mortality could be confounded because there were more patients with gram-negative pathogens at baseline and more patients received inadequate treatment of these gram-negative infections in the telavancin groups.
Subject(s)
Aminoglycosides/therapeutic use , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Gram-Positive Bacterial Infections/drug therapy , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/therapy , Adult , Aminoglycosides/administration & dosage , Aminoglycosides/adverse effects , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Coinfection/drug therapy , Coinfection/mortality , Cross Infection/microbiology , Cross Infection/mortality , Double-Blind Method , Female , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/mortality , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/mortality , Hospital Mortality , Humans , Lipoglycopeptides , Male , Middle Aged , Pneumonia, Ventilator-Associated/microbiology , Pneumonia, Ventilator-Associated/mortality , Time Factors , Treatment Outcome , Vancomycin/therapeutic use , Young AdultSubject(s)
Community-Acquired Infections/drug therapy , Doxycycline/therapeutic use , Methicillin Resistance , Staphylococcal Infections/drug therapy , Staphylococcus aureus , Adult , Aged , Community-Acquired Infections/epidemiology , Female , Humans , Male , Retrospective Studies , Skin Diseases, Infectious/drug therapy , Skin Diseases, Infectious/epidemiology , Soft Tissue Infections/drug therapy , Soft Tissue Infections/epidemiology , Staphylococcal Infections/epidemiologyABSTRACT
Lack of standardization in antibiogram (ABGM) preparation (the overall profile of antimicrobial susceptibility results of a microbial species to a battery of antimicrobial agents) has not been addressed until recently. The objective of this study was to analyze current antibiograms using the recently published NCCLS M39-A guidelines for preparation of antibiograms to identify areas for improvement in the reporting of antibiogram susceptibility data. Antibiograms from across the United States were obtained by various methods, including direct mailings, Internet searches, and professional contacts. Each ABGM collected was analyzed using prospectively defined elements from the M39-A guidelines. Additionally, seven quality indicators were also evaluated to look for the reporting of any atypical or inappropriate susceptibility data. The 209 antibiograms collected from 149 institutions showed at least 85% compliance to 5 of the 10 M39-A elements analyzed. Clinically relevant elements not met included annual analysis, duplicate isolate notation, and the exclusion of organisms with fewer than 10 isolates. As for the quality indicators evaluated, unexpected results included the 7% of antibiograms that reported <100% vancomycin susceptibility for Staphylococcus aureus, 24% that had inconsistent beta-lactam susceptibility for Staphylococcus aureus, 20% that reported <100% imipenem susceptibility for Escherichia coli, and 37% that reported >0% ampicillin susceptibility for Klebsiella pneumoniae. These findings suggest that antibiograms should be reviewed thoroughly by infectious disease specialists (physicians and pharmacists), clinical microbiologists, and infection control personnel for identification of abnormal findings prior to distribution.
Subject(s)
Anti-Bacterial Agents/pharmacology , Laboratories, Hospital , Microbial Sensitivity Tests/standards , Practice Guidelines as Topic/standards , Gram-Negative Bacteria/drug effects , Gram-Positive Cocci/drug effects , Humans , Microbial Sensitivity Tests/methods , Microbial Sensitivity Tests/statistics & numerical data , Quality Control , United StatesABSTRACT
Duplicate Staphylococcus aureus isolates were analyzed to determine the impact of multiple isolates from the same patient on annual antibiogram data. During a 6-year period (1996 to 2001), 3,227 patients with 4,844 S. aureus isolates were evaluated. A total of 39% of patients with methicillin-resistant S. aureus (MRSA) (n = 860) and 23% of patients with methicillin-susceptible S. aureus (MSSA) (n = 2,367) infections had duplicate isolates. Cumulative data show that 91% of the patients during this 6-year period with duplicate isolates (2 to 13 duplicates/year) did not switch between MSSA and MRSA but retained the original S. aureus strain whether it was MSSA or MRSA. Rates of MRSA were calculated for each year by using all isolates and then eliminating duplicates. The impact of duplicate MRSA and MSSA isolates was evaluated by using the ratio of isolates per patient such that ratios of >1.0 indicate >1 isolate per patient. The 6-year ratio for MRSA was 1.90 isolates/patient, and the ratio for MSSA was 1.35. A significant difference (P < 0.05) was noted in the MRSA rates in 4 of 6 years when duplicate isolates were removed. Common phenotypic antibiogram patterns were compared for all MRSA isolates during the 6-year period, and 64% were of a single antibiogram phenotype. Eighty-eight percent of patients with duplicate MRSA isolates had phenotypically identical multiple isolates. The rate of MRSA differs when duplicate isolates are removed from the antibiogram data.