Procalcitonin for Antibiotic Prescription in Chronic Obstructive Pulmonary Disease Exacerbations: Systematic Review, Meta-Analysis, and Clinical Perspective.

The 2020 Global Initiative for Obstructive Lung Disease report indicates that the blood biomarker procalcitonin (PCT) may assist in decision-making regarding the initiation of antibiotics for chronic obstructive pulmonary disease (COPD) exacerbations. PCT is an acute-phase reactant that increases in response to inflammation and infection, and has been studied in various bacterial infections for initiation and de-escalation of antibacterials. The purpose of this systematic review and meta-analysis was to evaluate the strength of the data on the use of PCT to guide antibiotic prescription in COPD exacerbations. Among the randomized clinical trials included in our meta-analysis, almost all of which were conducted exclusively in the hospital setting. PCT was found to decrease overall antibiotic exposure in COPD exacerbations by 2.01 days (p = 0.04), while no apparent effects were found on clinical outcomes (length of hospital stay, p = 0.88; treatment failure p = 0.51; all-cause mortality p = 0.28). However, the majority of blood PCT levels in COPD exacerbations were below the manufacturer-recommended cutoff for antibiotics, and the use of this marker was associated with worse outcomes in the intensive care setting. Further, based on additional sensitivity analysis excluding studies with high risk of bias or with converted outcome value, the effect of PCT on antibiotic duration in RCTs was no longer significant (MD = -1.88 days, 95% CI [-3.95, 0.19] days, p = 0.08, and MD = -1.72 days, 95% CI [-4.28, 0.83] days, p = 0.19, respectively). Our review and analysis does not support the use of PCT to guide antibiotic prescription in COPD exacerbations.

A Systematic Review and Meta-Analysis of Sputum Purulence to Predict Bacterial Infection in COPD Exacerbations.

The 2020 Global Initiative for Obstructive Lung Disease (GOLD) Report highlights the importance of sputum purulence in the decision to prescribe antibiotics for acute exacerbations. The purpose of this systematic review and meta-analysis was to evaluate the strength of literature supporting inclusion of sputum purulence in criteria utilized to evaluate if antimicrobials are indicated in acute COPD exacerbation. A total of 6 observational studies met inclusion criteria for this meta-analysis. Sputum purulence was defined by visual assessment of color, either subjectively by providers and/or patients or by a colored chart, where green or yellow sputum was considered purulent. Four of the studies were primarily conducted in hospitalized patients, one in the emergency department, and one in the primary care setting. Five studies relied upon expectorated sputum and one used bronchoscopy to obtain sputum samples for bacterial cultures. Compared with mucoid sputum, purulent sputum had a significantly higher probability of positive bacterial culture results (RR = 2.14, 95%CI [1.25, 3.67], p = 0.006, moderate quality). For sensitivity analysis, after removal of studies losing 2 or more points from the New Castle-Ottawa scale, the effect value remained statistically significant. This systematic review and meta-analysis showed a moderate level of evidence that purulent sputum during COPD exacerbation, as defined by yellow or green color, is associated with a significantly higher probability of potentially pathogenic bacteria, supporting GOLD report and NICE recommendations.

A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects.

A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (+/- standard error) Acute Physiology and Chronic Health Evaluation II score (16.8+/-0.6 vs. 15.0+/-0.7; P=.039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P=.08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P=.043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P=.02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.