Microbiologic treatment failure following clinical cure was found to be independently associated with recurrent pneumonia or death among patients with bacterial pneumonia. According to these results, published in Clinical Infectious Diseases, microbiologic cure as a metric to guide therapeutic intervention warrants further study.
To better understand the clinical significance of microbiologic cure, a common outcome in clinical trials, investigators from the University of Michigan in Ann Arbor, conducted a retrospective cohort study of adult patients hospitalized with bacterial pneumonia who achieved clinical cure. The rates of recurrent pneumonia and death between 204 patients with persistent growth of the index pathogen at the time of clinical cure (microbiologic failure) and 237 patients with pathogen eradication (microbiologic cure) were compared.
The prevalence of comorbidities, ventilator-dependence, and severity of acute illness were similar between groups. After controlling for these factors and for appropriateness of empiric antibiotics, placement in the intensive care unit, tracheostomy-dependence and immunocompromised status, results demonstrated that patients with microbiologic failure experienced significantly higher rates of recurrent pneumonia or death after clinical cure compared with those with microbiologic cure (90-day multivariable adjusted odds ratio [OR], 1.56; 95% CI, 1.04-2.35). This association was found among patients with pneumonias caused by Staphylococcus aureus (90-day multivariable adjusted OR, 3.69; 95% CI, 1.73-7.90), and a trend was observed among pneumonias caused by nonfermenting gram-negative bacilli. No association was found in relation to Enterobacteriaceae or other pathogens.
The investigators noted several important study limitations. They reported concern regarding the results’ generalizability to less severely ill patients because the majority recruited for this study were critically ill. Investigators also acknowledged that the requirement for follow-up respiratory cultures in this population created a potential for selection bias and limits generalizability to patients who would not normally have cultures performed at the end of therapy. Patient readmission data were also only available for patients readmitted to the study hospital, meaning that any participant readmitted to another facility was not captured. Finally, the study did not require that participants have quantitative respiratory cultures or distal sampling of the lungs. The study did employ rigorous and blinded clinician review for diagnostic case validity to reduce the likelihood of including patients with respiratory colonization.
Investigators concluded that, “this study demonstrated that in patients with bacterial pneumonia who achieved clinical cure, microbiologic failure was associated with recurrent pneumonia and death, a finding driven by pneumonia caused by Staphylococcus aureus and nonfermenting gram-negative bacilli.” The results also highlight the need for further study into the relevance of microbiologic treatment failure to clinical practice and the design of clinical trials within the setting of clinical cure of bacterial pneumonia.
Albin OR, Henig O, Patel TS, et al. Clinical implications of microbiologic treatment failure in the setting of clinical cure of bacterial Pneumonia [published online December 13 2019]. Clin Infect Dis. doi:10.1093/cid/ciz1187