Community-acquired pneumonia: identification and evaluation of nonresponders

Abstract

Community acquired pneumonia (CAP) is a relevant public health problem, constituting an important cause of morbidity and mortality. It accounts for a significant number of adult hospital admissions and a large number of those patients ultimately die, especially the population who needed mechanical ventilation or vasopressor support.Thus, early identification of CAP patients and its rapid and appropriate treatment are important features with impact on hospital resource consumption and overall mortality. Although CAP diagnosis may sometimes be straightforward, the diagnostic criteria commonly used are highly sensitive but largely unspecific. Biomarkers and microbiological documentation may be useful but have important limitations.Evaluation of clinical response is also critical especially to identify patients who fail to respond to initial treatment since these patients have a high risk of in-hospital death. However, the criteria of definition of non-response in CAP are largely empirical and frequently markedly diverse between different studies. In this review, we aim to identify criteria defining nonresponse in CAP and the pitfalls associated with this diagnosis. We also aim to overview the main causes of treatment failure especially in severe CAP and the possible strategies to identify and reassess non-responders trying to change the dismal prognosis associated with this condition.

The Modern Diagnostic Approach to Community-Acquired Pneumonia in Adults

“…Nevertheless, as a result of this and other studies, it is important to question the diagnosis of CAP, particularly when X-ray is equivocal, and to reevaluate the accuracy of the diagnosis if patients do not respond to treatment as expected. 39 Lung ultrasound has been proposed as an alternative, and is attractive because ultrasound has become a routine skill for respiratory physicians in the management of pleural disease. [40][41][42] A systematic review of the use of lung ultrasound for diagnosis of CAP in adults concluded it has a sensitivity of 95% and specificity of 90%, and that based on a final discharge diagnosis of CAP, it therefore had a superior sensitivity and similar specificity to chest X-ray.…”

Factors associated with early treatment failure in adult hospitalized patients with community-acquired pneumonia

“…While the majority of hospitalized patients with CAP achieve an adequate clinical response to initial empiric antibiotic and supportive therapy, some of them experience an early treatment failure (ETF) within 72 hours after initiation of the treatment, developing progression of underlying infection [9][10][11][12][13][14][15] . ETF inevitably leads to the more extensive use of microbiological and diagnostic tests, change in antimicrobial treatment and use of invasive therapeutic procedures, followed by prolonged hospitalization and much higher treatment costs 9,11,13,14 .…”

“…ETF inevitably leads to the more extensive use of microbiological and diagnostic tests, change in antimicrobial treatment and use of invasive therapeutic procedures, followed by prolonged hospitalization and much higher treatment costs 9,11,13,14 . Moreover, there is a piece of evidence supporting a strong association between ETF and increased mortality 9,10,[12][13][14][15][16] . As a consequence of considerable diversity in criteria used to define early CAP non-responders in hospitalized patients, there is a marked heterogeneity in reported prevalence of ETF with an average rate of 10-15% 9-13, 15, 16 .…”

“…As a consequence of considerable diversity in criteria used to define early CAP non-responders in hospitalized patients, there is a marked heterogeneity in reported prevalence of ETF with an average rate of 10-15% 9-13, 15, 16 . These criteria were mainly based on the deterioration of nonspecific clinical and radiological parameters previously used to diagnose CAP or the necessity to change antibiotic(s) [9][10][11][12][13][14][15][16] . However, previous studies showed that risk of death was significantly higher, up to five times, in patients experiencing ETF in comparison to satisfactory responders, regardless of criteria that were used to distinguish these two populations of inpatients with CAP 9, 10, 12, 13, 15-17 . Pursuant to the foregoing, adequate response to initial therapy is being regarded as essential for successful treatment of severe CAP.…”

When antibiotic treatment fails

“…If microbiological results show that an antibiotic regimen (that is now defined "targeted") is appropriate or if they are inconclusive, several other causes of therapy failure must be considered, namely: wrong diagnosis (non-infectious disease), development of infectious complication, persistence of inflammation, inadequate source control, antibiotic pharmacokinetic and pharmacodynamic (PK/ PD) issues and host immunosuppression [12]. Failure to respond to antibiotics includes also the emergence of resistant organisms, superinfections and drug interactions.…”