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Pharmacological and patient-specific response determinants in patients with hospital-acquired pneumonia treated with tigecycline.

ABSTRACT: 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.

SUBMITTER: Bhavnani SM

PROVIDER: S-EPMC3264202 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Pharmacological and patient-specific response determinants in patients with hospital-acquired pneumonia treated with tigecycline.

Bhavnani Sujata M SM Rubino Christopher M CM Hammel Jeffrey P JP Forrest Alan A Dartois Nathalie N Cooper C Angel CA Korth-Bradley Joan J Ambrose Paul G PG

Antimicrobial agents and chemotherapy 20111205 2

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 fol ...[more]

PMID: 22143524

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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:IntroductionCommunity-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) are common complications in idiopathic inflammatory myopathy (IIM) patients, and are frequently associated with unfavorable outcome as well as prolonged antibiotic therapy. In this study, we intended to clarify whether clinical pulmonary infection score (CPIS) and multiple serum biomarkers are valuable in predicting unfavorable outcomes and prolonged antibiotic therapy in adult IIM patients complicated with CAP or HAP.MethodsData of IIM patients with CAP or HAP who were admitted to three tertiary centers from December 2010 to November 2019 were retrospectively collected. Cox proportional hazards regression analysis and logistic regression analysis were adopted to identify risk factors for unfavorable outcomes and prolonged antibiotic therapy in these patients. The predictive values of potential predictors were assessed using receiver operating characteristic analysis.ResultsThe mortality rate was 60.6% in 109 IIM patients complicated with CAP or HAP. Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT) score, CPIS and timely adjustment to antibiotics based on drug susceptibility test (DST-based antibiotic) were significantly associated with long-term outcome in these patients. With an optimal cutoff value of 6.5 and area under the curve (AUC) of 0.813, CPIS was a more satisfying predictor compared with MYOACT score. The peak C-reactive protein (CRP) level, DST-based antibiotics, and complication of interstitial lung disease (ILD) were also significantly correlated with prolonged antibiotic therapy.ConclusionsIIM patients complicated with CAP or HAP frequently suffer from unfavorable outcomes. Compared with IIM disease activity, CPIS worked as a better predictor of outcome in these patients. Also, the peak CRP level during hospitalization might be valuable in predicting prolonged antibiotic therapy. The existence of ILD might impede early discontinuation of antibiotics. Timely adjustment to antibiotics based on drug susceptibility testing would decrease the mortality rate and reduce the incidence of prolonged antibiotic therapy.

Project description:BackgroundHospital-acquired pneumonia (HAP) is defined as radiologically confirmed pneumonia occurring ?48h after hospitalization, in non-intubated patients. Empirical treatment regimens use broad-spectrum antimicrobials.AimTo evaluate the accuracy of the diagnosis of HAP and to describe the demographic and microbiological features of patients with HAP.MethodsMedical and surgical inpatients receiving intravenous antimicrobials for a clinical diagnosis of HAP at a UK tertiary care hospital between April 2013 and 2014 were identified. Demographic and clinical details were recorded.FindingsA total of 166 adult patients with a clinical diagnosis of HAP were identified. Broad-spectrum antimicrobials were prescribed, primarily piperacillin-tazobactam (57.2%) and co-amoxiclav (12.5%). Sputum from 24.7% of patients was obtained for culture. Sixty-five percent of patients had radiological evidence of new/progressive infiltrate at the time of HAP treatment, therefore meeting HAP diagnostic criteria (2005 American Thoracic Society/Infectious Diseases Society of America guidelines). Radiologically confirmed HAP was associated with higher levels of inflammatory markers and sputum culture positivity. Previous surgery and/or endotracheal intubation were associated with radiologically confirmed HAP. A bacterial pathogen was identified from 17/35 sputum samples from radiologically confirmed HAP patients. These were Gram-negative bacilli (N = 11) or Staphylococcus aureus (N = 6). Gram-negative bacteria tended to be resistant to co-amoxiclav, but susceptible to ciprofloxacin, piperacillin-tazobactam and meropenem. Five of the six S. aureus isolates were meticillin susceptible and all were susceptible to doxycycline.ConclusionIn ward-level hospital practice 'HAP' is an over-used diagnosis that may be inaccurate in 35% of cases when objective radiological criteria are applied. Radiologically confirmed HAP represents a distinct clinical and microbiological phenotype. Potential risk factors were identified that could represent targets for preventive interventions.

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Pharmacological and patient-specific response determinants in patients with hospital-acquired pneumonia treated with tigecycline.

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Pharmacological and patient-specific response determinants in patients with hospital-acquired pneumonia treated with tigecycline.

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