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Telavancin for hospital-acquired pneumonia: clinical response and 28-day survival.

ABSTRACT: U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively). The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups. Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CLCR] of <50 ml/min). Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available.

SUBMITTER: Corey GR

PROVIDER: S-EPMC4023742 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Telavancin for hospital-acquired pneumonia: clinical response and 28-day survival.

Corey G Ralph GR Kollef Marin H MH Shorr Andrew F AF Rubinstein Ethan E Stryjewski Martin E ME Hopkins Alan A Barriere Steven L SL

Antimicrobial agents and chemotherapy 20140113 4

U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were app ...[more]

PMID: 24419353

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Project description:BackgroundHospital-acquired pneumonia (HAP) is the most common health care-associated infection contributing to death. Studies have indicated that there may be differences in the causative pathogens and outcomes of ventilator-associated pneumonia (VAP) and non-ventilator-associated pneumonia (NV-HAP). However, with limited NV-HAP-specific data available, treatment is generally based on data from studies of VAP. The Phase 3 Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) studies were two double-blind randomized controlled trials that demonstrated the non-inferiority of telavancin to vancomycin for treatment of Gram-positive HAP. We conducted a post hoc subgroup analysis of patients enrolled in the ATTAIN studies who had NV-HAP.MethodsData from the two ATTAIN studies were pooled, and patients with NV-HAP were analyzed. The all-treated (AT) population consisted of all randomized patients who received ≥1 dose of study medication, and the clinically evaluable (CE) population consisted of AT patients who were protocol-adherent or who died on or after study day 3, where death was attributable to the HAP episode under study. The primary endpoint was clinical response (cure, failure, or indeterminate) at the follow-up/test of cure visit, conducted 7-14 days after the end of therapy.ResultsA total of 1,076 patients (71.6% of overall ATTAIN AT population) had NV-HAP (533 and 543 patients in the telavancin and vancomycin treatment groups, respectively). Clinical cure rates in the CE population were similar for patients with NV-HAP treated with telavancin and vancomycin (83.1% [201/242] and 84.1% [233/277], respectively). In patients with methicillin-resistant Staphylococcus aureus isolated at baseline, cure rates in the CE population were 74.8% (77/103) for telavancin and 79.3% (96/121) for vancomycin. The incidence of adverse events, serious adverse events, and deaths in patients with NV-HAP was similar whether patients received telavancin or vancomycin.ConclusionThis post hoc subgroup analysis of the ATTAIN studies demonstrated similar cure rates for telavancin and vancomycin for treatment of NV-HAP.

Project description:BackgroundSocial and hospital environmental factors that may be associated with hospital-acquired pneumonia (HAP) have not been evaluated. Comprehensive risk assessment for the incidence of HAP including sociodemographic, clinical, and hospital environmental factors was conducted using national health insurance claims data.MethodsThis is a population-based retrospective cohort study of adult patients who were hospitalized for more than 3 days from the Health Insurance Review and Assessment Service-National Inpatient Sample data between January 1, 2016 and December 31, 2018 in South Korea. Multivariable logistic regression analyses were conducted to identify the factors associated with the incidence of HAP.ResultsAmong the 512,278 hospitalizations, we identified 25,369 (5.0%) HAP cases. In multivariable analysis, well-known risk factors associated with HAP such as older age (over 70 vs. 20-29; adjusted odds ratio [aOR], 3.66; 95% confidence interval [CI] 3.36-3.99), male sex (aOR, 1.35; 95% CI 1.32-1.39), pre-existing lung diseases (asthma [aOR, 1.73; 95% CI 1.66-1.80]; chronic obstructive pulmonary disease [aOR, 1.62; 95% CI 1.53-1.71]; chronic lower airway disease [aOR, 1.79; 95% CI 1.73-1.85]), tube feeding (aOR, 3.32; 95% CI 3.16-3.50), suctioning (aOR, 2.34; 95% CI 2.23-2.47), positioning (aOR, 1.63; 95% CI 1.55-1.72), use of mechanical ventilation (aOR, 2.31; 95% CI 2.15-2.47), and intensive care unit admission (aOR, 1.29; 95% CI 1.22-1.36) were associated with the incidence of HAP. In addition, poverty (aOR, 1.08; 95% CI 1.04-1.13), general hospitals (aOR, 1.54; 95% CI 1.39-1.70), higher bed-to-nurse ratio (Grade ≥ 5; aOR, 1.45; 95% CI 1.32-1.59), higher number of beds per hospital room (6 beds; aOR, 3.08; 95% CI 2.77-3.42), and ward with caregiver (aOR, 1.19; 95% CI 1.12-1.26) were related to the incidence of HAP.ConclusionsThe incidence of HAP was associated with various sociodemographic, clinical, and hospital environmental factors. Thus, taking a comprehensive approach to prevent and treat HAP is important.

Project description:IntroductionThe efficacy and safety of telavancin versus vancomycin in microbiologically evaluable patients with hospital-acquired or ventilator-associated pneumonia (HAP/VAP) caused by Staphylococcus aureus with vancomycin minimum inhibitory concentration (MIC) ≥ 1.0 µg/mL was analyzed using data derived from previously reported Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) trials.MethodsThis post hoc subgroup analysis of two randomized, double-blind, comparator-controlled, parallel-group phase 3 trials conducted at 274 sites in 38 countries included 194 microbiologically evaluable patients with HAP/VAP caused by monomicrobial S. aureus with vancomycin MIC ≥ 1.0 µg/mL. Patients received intravenous telavancin (10 mg/kg every 24 h) or intravenous vancomycin (1 g every 12 h with site-specific modifications) for 7-21 days. Efficacy was assessed by clinical cure, defined as improvement or non-progression of radiographic findings at end of treatment and resolution of pneumonia signs and symptoms at follow-up/test-of-cure visits, and survival 28 days post-randomization. Safety was assessed from categorical shifts in creatinine clearance during therapy and adverse events (AEs).ResultsClinical cure rates were numerically greater following telavancin versus vancomycin treatment overall (85.4% vs. 74.3%; treatment difference [95% confidence interval (CI)], 11.1% [- 0.002%, 22.2%]) and in patients aged ≥ 65 years (81.6% vs. 66.2%; treatment difference [95% CI], 15.5% [- 0.9%, 30.2%]) patients with VAP (92.3% vs. 47.6%; treatment difference [95% CI], 44.7% [18.1%, 64.9%]), and patients with baseline Acute Physiology And Chronic Health Evaluation II score ≥ 20 (71.4% vs. 55.6%; treatment difference [95% CI], 15.9% [- 11.7%, 40.5%]). Renal function declined in 7 (7.9%) patients receiving telavancin and 6 (5.7%) patients receiving vancomycin. Survival proportion was numerically higher (85.2% vs. 80.2%; treatment difference [95% CI], 5.0% [- 5.8%, 15.8%]) and AEs were comparable in patients treated with telavancin versus vancomycin.ConclusionTelavancin is an alternative to vancomycin for HAP/VAP caused by S. aureus with vancomycin MIC ≥ 1 µg/mL.FundingTheravance Biopharma R&D, Inc., South San Francisco, CA, USA.

Project description:BackgroundHospital-acquired pneumonia (HAP) is the most common hospital-acquired infection in China with substantial morbidity and mortality. But no specific risk assessment model has been well validated in patients with HAP. The aim of this study was to investigate the published risk assessment models that could potentially be used to predict 30-day mortality in HAP patients in non-surgical departments.MethodsThis study was a single-center, retrospective study. In total, 223 patients diagnosed with HAP from 2012 to 2017 were included in this study. Clinical and laboratory data during the initial 24 hours after HAP diagnosis were collected to calculate the pneumonia severity index (PSI); consciousness, urea nitrogen, respiratory rate, blood pressure, and age ≥65 years (CURB-65); Acute Physiology and Chronic Health Evaluation II (APACHE II); Sequential Organ Failure Assessment (SOFA); and Quick Sequential Organ Failure Assessment (qSOFA) scores. The discriminatory power was tested by constructing receiver operating characteristic (ROC) curves, and the areas under the curve (AUCs) were calculated.ResultsThe all-cause 30-day mortality rate was 18.4% (41/223). The PSI, CURB-65, SOFA, APACHE II, and qSOFA scores were significantly higher in non-survivors than in survivors (all P < 0.001). The discriminatory abilities of the APACHE II and SOFA scores were better than those of the CURB-65 and qSOFA scores (ROC AUC: APACHE II vs. CURB-65, 0.863 vs. 0.744, Z = 3.055, P = 0.002; APACHE II vs. qSOFA, 0.863 vs. 0.767, Z = 3.017, P = 0.003; SOFA vs. CURB-65, 0.856 vs. 0.744, Z = 2.589, P = 0.010; SOFA vs. qSOFA, 0.856 vs. 0.767, Z = 2.170, P = 0.030). The cut-off values we defined for the SOFA, APACHE II, and qSOFA scores were 4, 14, and 1.ConclusionsThese results suggest that the APACHE II and SOFA scores determined during the initial 24 h after HAP diagnosis may be useful for the prediction of 30-day mortality in HAP patients in non-surgical departments. The qSOFA score may be a simple tool that can be used to quickly identify severe infections.

Project description:Pharmacokinetic and clinical data from tigecycline-treated patients with hospital-acquired pneumonia (HAP) who were enrolled in a phase 3 clinical trial were integrated in order to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy. Univariable and multivariable analyses were conducted to identify factors associated with clinical and microbiological responses, based on data from 61 evaluable HAP patients who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and for whom there were adequate clinical, pharmacokinetic, and response data. The final multivariable logistic regression model for clinical response contained albumin and the ratio of the free-drug area under the concentration-time curve from 0 to 24 h (fAUC(0-24)) to the MIC (fAUC(0-24):MIC ratio). The odds of clinical success were 13.0 times higher for every 1-g/dl increase in albumin (P < 0.001) and 8.42 times higher for patients with fAUC(0-24):MIC ratios of ?0.9 compared to patients with fAUC(0-24):MIC ratios of <0.9 (P = 0.008). Average model-estimated probabilities of clinical success for the albumin/fAUC(0-24):MIC ratio combinations of <2.6/<0.9, <2.6/?0.9, ?2.6/<0.9, and ?2.6/?0.9 were 0.21, 0.57, 0.64, and 0.93, respectively. For microbiological response, the final model contained albumin and ventilator-associated pneumonia (VAP) status. The odds of microbiological success were 21.0 times higher for every 1-g/dl increase in albumin (P < 0.001) and 8.59 times higher for patients without VAP compared to those with VAP (P = 0.003). Among the remaining variables evaluated, the MIC had the greatest statistical significance, an observation which was not surprising given the differences in MIC distributions between VAP and non-VAP patients (MIC(50)and MIC(90) values of 0.5 and 0.25 mg/liter versus 16 and 1 mg/liter for VAP versus non-VAP patients, respectively; P = 0.006). These findings demonstrated the impact of pharmacological and patient-specific factors on the clinical and microbiological responses.

Dataset Information

Telavancin for hospital-acquired pneumonia: clinical response and 28-day survival.

Publications

Telavancin for hospital-acquired pneumonia: clinical response and 28-day survival.

Similar Datasets

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