Dataset Information

Assessment of Minimum Inhibitory Concentrations of Telavancin by Revised Broth Microdilution Method in Phase 3 Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Clinical Isolates.

ABSTRACT:

Introduction

The broth microdilution method (BMD) for testing telavancin minimum inhibitory concentrations (MICs) was revised (rBMD) in 2014 to improve the accuracy, precision, and reproducibility of the testing method. The aim of this study was to determine the effect of the revised method on telavancin MIC values for Staphylococcus aureus (S. aureus) clinical isolates obtained from hospital-acquired pneumonia (HAP) patients.

Methods

Isolates from patients who participated in the phase 3 Assessment of Telavancin for Treatment of HAP Studies were retested using the rBMD method.

Results

Retesting of 647 isolates produced a range of telavancin MIC values from 0.015 µg/mL to 0.12 µg/mL with MIC_50/90 values of 0.06/0.06 µg/mL for the total pool of samples. For methicillin-resistant S. aureus (MRSA), MIC_50/90 values were 0.06/0.12 µg/mL. These values are up to 4-fold lower than MIC_50/90 values obtained using the original method. These results were used in part to justify lowering the telavancin breakpoints. All tested isolates remained susceptible to telavancin at the revised susceptibility breakpoint of ≤0.12 µg/mL. Overall, the clinical cure rate for microbiologically evaluable telavancin-treated patients was 78% for S. aureus, 76% for patients with MRSA, and 79% for patients with isolates with reduced susceptibility to vancomycin (MIC ≥1 µg/mL).

Conclusion

Results from the rBMD method support the in vitro potency of telavancin against S. aureus.

Trial registration

ATTAIN (NCT00107952 and NCT00124020).

Funding

Theravance Biopharma Antibiotics, Inc.

SUBMITTER: Smart JI

PROVIDER: S-EPMC5125136 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Hospital-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. METHODS:Data 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. RESULTS:A 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. CONCLUSION:This post hoc subgroup analysis of the ATTAIN studies demonstrated similar cure rates for telavancin and vancomycin for treatment of NV-HAP.

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Project description:ObjectivesVentilator-acquired pneumonia (VAP) is the leading cause of serious associated infections in Intensive Care Units (ICU) and is associated with significant morbidity. The use of hyperbaric oxygen therapy (HBOT) in patients on mechanical ventilation may increase exposure to certain risk factors such as hyperoxemia and the need for multiple transfers. The aim of our study was to assess the relationship between HBOT and VAP.MethodThis retrospective observational study was performed from March 2017 to March 2018 in a 10-bed ICU using HBOT. All patients receiving mechanical ventilation (MV) for more than 48 hours were eligible. VAP was defined using clinical and radiological criteria. Data collection was carried out via digital medical records. Risk factors for VAP were determined by univariate and multivariate analysis.ResultsForty-two (23%) of the 182 patients enrolled developed at least one episode of VAP. One hundred and twenty-four (68%) patients received HBOT. The incidence rate of VAP was 34 per 1000 ventilator days. The occurrence of VAP was significantly associated with immunosuppression (p<0.029), MV duration (5 [3-7] vs 8 [5-11.5] days, p<0.0001), length of stay (8 [5-13] vs 19.5 [13-32] days, p<0.0001), reintubation (p<0.0001), intra-hospital transport (p = 0.001), use of paralytic agents (p = 0.013), tracheotomy (p = 0.003) and prone position (p = 0.003). The use of HBOT was not associated with the occurrence of VAP. Multivariate analysis identified reintubation (OR: 8.3 [2.6-26.6]; p<0.0001), intra-hospital transport (OR: 3.5 [1.3-9.2]; p = 0.011) and the use of paralytic agents (OR: 3.3 [1.3-8.4]; p = 0.014) as independent risk factors for VAP.ConclusionKnown risk factors for VAP are to be found within our ICU population. HBOT, however, is not an extra risk factor for VAP within this group. Further experimental and clinical investigations are needed to understand the impact of HBOT on the occurrence of VAP and on physiological microbiome.