Antibiotics are the foundation of therapy for respiratory tract infections. The approach to use varies with the type of pneumonia, age of the affected patient, presence of various comorbid illnesses, risk factors for infection by specific pathogens, and severity of the acute illness. For most patients, initial therapy is empiric, aimed at a broad spectrum of potential pathogens. Once culture data become available, therapy can be pathogen-specific making it possible to de-escalate to fewer drugs with a narrower antimicrobial spectrum.1 In some cases, initial empiric therapy must be continued because no etiologic pathogen is identified.
The transformation of modern medicine over the last century can be attributed in part to the discovery and development of antibiotics. However, with widespread use of antibiotics, antimicrobial resistance in bacterial pathogens has become rampant, and once easily treatable conditions, such as pneumococcal pneumonia, are becoming deadly again.2 The Presidential Executive Order 13676 for Combating Antibiotic-Resistant Bacteria (CARB) released in 2014 recognizes the importance of curbing antimicrobial resistance and sets forward a set of principles to help tackle this emerging issue.1
When a pathogen is defined, the term “appropriate” refers to the use of at least one antimicrobial agent that is active in vitro against the etiologic pathogen. The term “adequate” includes not only appropriate therapy, but also the use of that agent in the correct dose, via the right route, given in a timely fashion, and with penetration to the site of infection. Timely and appropriate antibiotic therapy can improve survival in patients with community-acquired pneumonia (CAP) and nosocomial pneumonia or hospital-acquired pneumonia (HAP), and the benefits are most evident in patients who are not otherwise terminally ill.3,4 Ventilator-associated pneumonia (VAP) is nosocomial pneumonia that develops after at least 48 h of preceding mechanical ventilation, and thus some ventilated HAP patients may not have VAP, since they do not satisfy this definition of prolonged preceding mechanical ventilation.
In the setting of CAP, effective initial antibiotic therapy is associated with a marked improvement in survival, compared with ineffective therapy, particularly in patients with severe illness.3,5 In several studies, identification of the pathogens causing severe CAP did not lead to an improved survival rate, while the use of a broad-spectrum, empiric regimen directed at likely pathogens reduced mortality. Further, patients with CAP have reduced mortality if initial antibiotic therapy is provided within 4 h of arrival to the hospital. In the treatment of VAP, data show that appropriate therapy should be given as soon as the infection is clinically identified, and lower respiratory tract samples have been collected for culture. Delay of even 24 h in starting therapy is an important mortality risk factor in VAP.4 In general, with severe illness, those receiving antibiotics earlier in their course have a lower mortality than those receiving delayed therapy, with the risk of death rising 7% to 8% for each ...