treatment of legionella pneumonia include macrolide and fluoroquinolone

The preferred agent for treatment of Legionnaires disease would be either a respiratory fluoroquinolone or a macrolide, with both antibiotic classes having equal efficacy. Fluoroquinolones and macrolides achieve high intracellular concentrations, penetrate lung tissue, and are active against all Legionella species that cause human infection. Levofloxacin, moxifloxacin, and ciprofloxacin are all good respiratory fluoroquinolones, with levofloxacin being commonly used in clinical practice. Among the macrolides the preferred choice is azithromycin, with similar results to clarithromycin, erythromycin, or roxithromycin. Tetracyclines (eg, doxycycline) also have intracellular activity and are used in patients with abnormal QT prolongation; however, Legionella longbeachae can be resistant to tetracyclines.

This patient has a microbiologically confirmed Legionella pneumonia secondary to Legionella pneumophila serogroup 1, as identified by Legionella urinary antigen test. There are no randomized controlled trials directly evaluating the efficacy and adverse events of anti-Legionella antibiotics. One observational study suggested that fluoroquinolones may be superior to macrolides and should be the preferred choice. Additionally, a randomized controlled trial of patients with pneumonia patients suggested benefit of a fluoroquinolone such as levofloxacin at higher doses (750 mg daily), based on a faster symptom resolution when compared with lower doses (500 mg daily). However, a systematic review and meta-analysis of nonrandomized controlled trials failed to show differences in mortality when comparing fluoroquinolones with macrolides (choices C and D are incorrect). Twenty-one publications with 3,525 patients had a mortality rate of 6.9% for patients treated with a fluoroquinolone vs 7.4% among those treated with a macrolide.

Additionally, patients treated with a fluoroquinolone vs a macrolide had no differences in clinical cure, time to apyrexia, length of hospital stay, and occurrence of complications. In post hoc analyses, there were no differences when comparing type of macrolide (azithromycin or clarithromycin) or fluoroquinolone used (levofloxacin or moxifloxacin), presence or absence of immunosuppression, or disease severity (defined as ICU admission vs nonadmission). Combination therapy using both a fluoroquinolone and a macrolide does not appear to improve outcomes (choice A is incorrect).

Pneumonia is the most commonly described manifestation of Legionella infection and is termed “Legionnaires disease.” Legionella is an aerobic, nutritionally fastidious, Gram-negative bacillus, and a facultative intracellular pathogen. The bacterial family of Legionellacea consists of >60 species and >70 serogroups. L pneumophila is the most common cause of human disease and is divided into >15 serogroups, with serogroup 1 recognized as the most prevalent in North America. The transmission of Legionella species is typically via inhalation of aerosols derived from water or soil. Legionnaires disease can be acquired sporadically, as was most likely in this patient, or during outbreaks or travel. Outbreaks are usually associated with water-supply contamination as can occur in large facilities, such as hospitals, hotels, or apartment buildings. Legionella infection is associated with host risk factors such as older age, immunocompromised status, current or past smoking, chronic respiratory disease, cardiovascular disease, and end-stage renal disease. Clinical and radiographic characteristics of Legionella pneumonia are similar to other forms of pneumonia. However, there are certain clinical features that may suggest the diagnosis, such as the presence of GI symptoms (eg, nausea, vomiting, and diarrhea), hyponatremia, increased liver function tests, and failure to respond to treatment for pneumonia with a beta-lactam monotherapy. This patient presentation is consistent with failure of a beta-lactam monotherapy with oral amoxicillin as it has no activity against Legionella species.

The severity of this patient’s condition at presentation merits admission to a highly monitored unit as several minor criteria for severe community-acquired pneumonia from the American Thoracic Society and the 2019 Infectious Diseases Society of America guidelines are met—namely, tachypnea (respiratory rate ≥30/min), hypoxemia, uremia (BUN of ≥20mg/dL [≥7.14 mmol/L]), and thrombocytopenia (platelet count <100 × 103/μL (<100.0 × 109/L).

The preferred method to confirm presence of Legionella pneumonia is polymerase chain reaction (PCR) obtained from a lower respiratory tract sample (eg, sputum or BAL specimen) owing to high accuracy and ability to detect all Legionella species and serogroups. Rapid testing for pneumonia is likely to be more readily available in the future. If rapid testing platforms are not available or if the sputum sample cannot be obtained (as in this case), the use of Legionella urinary antigen test can reveal the diagnosis. Legionella urinary antigen can identify L pneumophila serogroup 1, which is highly prevalent in the United States. Culture on special media (buffered charcoal yeast extract agar) is considered the gold standard for diagnosing Legionella infections, and it can be performed on any sample, with results usually available in 3 to 5 days. Negative test result for Legionella urinary antigen does not completely exclude the presence of Legionella species, so results need to be considered in context using other available diagnostic methods and in terms of geographic variability and patient risk factors. Other methods such as direct fluorescent antibody staining and serology are available but not generally used in clinical practice