Professor Lionel A. Mandell

20 June, 2018

Community-acquired pneumonia (or CAP) has a significant impact on both patients and society. It is the sixth leading cause of death overall in the US and the most common cause of death from infection, with 3-4 million cases occurring annually. It results in 10 million physician visits, 64 million days of restricted activity, 600,000 hospitalizations, and 45,000 deaths.Effective management of CAP is compromised by limitations of current diagnostic methods, the issue of multiple pathogens and the development of resistance.

Eliciting the agent responsible for CAP is difficult, as it is not a homogeneous disease. Therefore, the etiology of CAP should be considered according to:1.the site of care (whether outpatient, inpatient or nursing home) 2.the site of acquisition (community or nursing home) 3.the immune status of the patient4.the presence of comorbidity. The most important etiologic agent is S. pneumoniae, which accounts for two thirds of all cases.Atypical pathogens involved include Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella spp., with recent evidence demonstrating that these play a greater role in causing CAP than previously believed.

Antimicrobial resistance among respiratory pathogens has become a major concern, as several studies have found that it is associated with increased length of stay in the hospital, increased mortality…

…as well as with increased cost. The total estimated direct cost of resistance in the US is $4 billion dollars, or 0.5% of total US health care costs.

Approximately 80% of all CAP patients are treated as outpatients, and of the 20% requiring hospitalization, 90% are managed on a medical ward while 10% are admitted to ICU.

Therapy can be empiric or directed at an identified pathogen. While directed therapy is more desirable, in practical terms, the limitations of current diagnostic techniques mean that physicians generally do not have a confirmed pathogen and need to initiate rapid empiric therapy. The importance of this initial therapy is outlined by results from a five-year study of severe CAP which identified factors independently related to mortality. Of the factors identified, including underlying disease, shock, bacteremia and initial therapy, it was shown that ineffective initial therapy was the most important factor for predicting a worse outcome.

The importance of this initial therapy has led to the development of guidelines for the optimal treatment of CAP, three of which have recently been published in North America. The Canadian Infectious Diseases Society and Canadian Thoracic Society (or CIDS-CTS), the Infectious Diseases Society of America and the American Thoracic Society. These are similar and follow the same approach, dividing patients according to whether they are outpatients or hospitalized.

The general consensus for treatment of outpatients is to use a macrolide, doxycycline, -lactam, or a fluoroquinolone.

This is further clarified by the CIDS-CTS, which recommends agents depending on the presence or absence of modifying factors. In outpatients with chronic obstructive lung disease (or COLD) who have not received a recent antibiotic, a newer macrolide is recommended. However, if the patients recently received antibiotics, a fluoroquinolone was recommended as the first choice.

Recommended treatment for inpatients in a ward includes a b-lactam plus a macrolide or a fluoroquinolone as a single agent. Treatment for patients in the ICU includes a b-lactam/b-lactamase inhibitor plus either a fluoroquinolone or a macrolide.

Of the fluoroquinolones available, levofloxacin is one of the most commonly used for the treatment of CAP, with its efficacy having been confirmed in randomized clinical trials. In two pneumonia studies, levofloxacin was compared with ceftriaxone } cefuroxime axetil or ceftriaxone alone, and found to be equivalent or superior to the comparator in efficacy in treating CAP or hospitalized patients with pneumonia.

In another study, levofloxacin given once daily was found to be as effective as amoxicillin-clavulanic acid given three times a day in the treatment of CAP. In the bacteremia/sepsis study, levofloxacin was found to be equivalent to imipenem/cilastatin. A separate clinical trial assessed a critical pathway for the treatment of CAP and found that the use of levofloxacin was associated with a statistically significant reduction in the number of bed days per patient managed and an 18% decrease in admission of low risk patients. Thus, the use of levofloxacin has been shown to be superior or equally effective to comparators and associated with significant cost savings.