Clinical Implications of Microbiologic Treatment Failure in the Setting of Clinical Cure of Bacterial Pneumonia

Abstract

Background Microbiologic cure is a common outcome in pneumonia clinical trials, but its clinical significance is incompletely understood. Methods We conducted a retrospective cohort study of adult patients hospitalized with bacterial pneumonia who achieved clinical cure. Rates of recurrent pneumonia and death were compared between patients with persistent growth of the index pathogen at the time of clinical cure (microbiologic failure) and those with pathogen eradication (microbiologic cure). Results Among 441 patients, 237 experienced microbiologic cure and 204 experienced microbiologic failure. Prevalences of comorbidities, ventilator dependence, and severity of acute illness were similar between groups. Patients with microbiologic failure experienced significantly higher rates of recurrent pneumonia or death following clinical cure than patients with microbiologic cure, controlling for comorbid conditions, severity of acute illness, appropriateness of empiric antibiotics, intensive care unit placement, tracheostomy dependence, and immunocompromised status (90-day multivariable adjusted odds ratio [OR], 1.56; 95% confidence interval [CI], 1.04–2.35). This association was observed among patients with pneumonias caused by Staphylococcus aureus (90-day multivariable adjusted OR, 3.69; 95% CI, 1.73–7.90). A trend was observed among pneumonias caused by nonfermenting gram-negative bacilli, but not Enterobacteriaceae or other pathogens. Conclusions Microbiologic treatment failure was independently associated with recurrent pneumonia or death among patients with bacterial pneumonia following clinical cure. Microbiologic cure merits further study as a metric to guide therapeutic interventions for patients with bacterial pneumonia.

An Adjudication Protocol for Severe Bacterial and Viral Pneumonia

“…[11][12][13] For example, recurrent pneumonia was utilized as an endpoint in a study of microbiological treatment failure in bacterial pneumonia, but the adjudication process used to ascertain the endpoint was not outlined. 14 A large randomized controlled trial (RCT) of community-acquired pneumonia (CAP) employed an endpoint adjudication committee to determine the primary outcome, clinically indicated treatment with antibiotics, but did not detail the validity of the adjudication process. 15 Other literature focuses on diagnostic adjudication in pneumonia and does not address endpoint adjudication.…”

Utility of radiographic keyword abstraction for identification of misdiagnosed pneumonia

“…However, given the robust negative predicative value of keyword abstraction in ruling out pneumonia in this pneumonia-enriched cohort, application of this methodology to patients with a lower disease prevalence is expected to improve its negative predictive value. 6 These data support radiographic keyword abstraction as a viable method to identify patients with misdiagnosed pneumonia. a Keywords: "infection," "pneumonia," "consolidation," "opacity (ies)," "opacification," "infiltrate (s)," "airspace," assuming such words were not preceded by "no" or "no evidence of" in chest radiography interpretations within 48 hours of positive respiratory culture.…”

Outcomes in participants with failure of initial antibacterial therapy for hospital-acquired/ventilator-associated bacterial pneumonia prior to enrollment in the randomized, controlled phase 3 ASPECT-NP trial of ceftolozane/tazobactam versus meropenem

“…The ASPECT-NP study population included participants who were failing antibacterial therapy for vHABP/VABP at the time of enrollment, an important predefined subgroup that may have been at higher risk of mortality because of a refractory response to initial therapy [ 7 , 28 ]. Delay in initiation of effective antibacterial therapy for the treatment of serious bacterial infections (including nosocomial pneumonia) has consistently been associated with increased mortality [ 9 , 10 ]. Thus, a higher mortality rate is not unexpected in participants who had received > 48 h of ineffective therapy before receiving study drug than the rest of the study population, who received ≤ 24 h of standard of care antibacterial therapy prior to receiving study therapy.…”