Early and Late Treatment Failure in Community-Acquired Pneumonia

Early and Late Treatment Failure in Community-Acquired Pneumonia

Abstract and Introduction

Abstract

Treatment failure is a matter of great concern in the management of community-acquired pneumonia (CAP). Defined generally as lack of response or clinical deterioration, failure is considered early when it occurs within the first 72 hours and late when it occurs after 72 hours. The reported incidence of treatment failure among hospitalized patients with CAP ranges from 2.4 to 31% for early failure and from 3.9 to 11% for late failure. Most cases of early failure occur because of inadequate host-pathogen responses. Factors associated with treatment failure include high-risk pneumonia, liver disease, multilobar infiltrates, Legionella pneumonia, gram-negative pneumonia, pleural effusion, cavitation, leucopenia, and discordant antimicrobial therapy. Conversely, influenza vaccination, initial treatment with fluoroquinolones, and chronic obstructive pulmonary disease have been linked with a lower risk of failure. Treatment failure is associated with high morbidity and mortality rates. Its detection and management require careful clinical assessment. Certain serum biological markers may be helpful to identify patients with a higher risk of deterioration and poor prognosis. Because inadequate host-pathogen responses are responsible for a significant number of failures, strategies aimed at modulating the inflammatory response should be investigated. Discordant therapy can be prevented by rational application of the current antibiotic guidelines.

Introduction

Community-acquired pneumonia (CAP) continues to be one of the most common infectious diseases. Our understanding of CAP has improved substantially in recent years, and many new practices have been introduced. Several new microbial causes have been described, antibiotic resistance among respiratory pathogens has increased worldwide, and new antibiotic agents have been introduced as therapy for CAP. Although most hospitalized patients with CAP respond satisfactorily to treatment, some develop treatment failure and may experience rapidly progressive life-threatening pneumonia. Therefore, treatment failure is a matter of particular concern in the management of CAP. Treatment failure can be classified as early or late. Early failure is generally defined as lack of response or worsening of clinical status (i.e., hemodynamic instability, impairment of respiratory failure, need for mechanical ventilation, radiographic progression, or appearance of new metastatic infectious foci) within the first 72 hours of treatment and late failure when this occurs after 72 hours. The reported incidence among hospitalized patients with CAP ranges from 2.4 to 31% for early failure and from 3.9 to 11%, for late failure, depending on the population analyzed and the definitions used.

This article summarizes the latest evidence on early and late treatment failure in hospitalized patients with CAP. New data on its causes, etiology, risk factors, outcomes, and the usefulness of serum biological markers to predict failure are reviewed.