In this episode, I’ll discuss whether critically ill patients with Legionella pneumonia should receive double antibiotic coverage.
Before we begin, I’d like to share a pearl from my book, A Pharmacist’s Guide to Inpatient Medical Emergencies:
“Causes of low O2 sat: PE, shunting, airway obstruction (functional or mechanical)” #pharmacists https://t.co/w0tP1mmQW7
— Pharmacy Joe (@PharmacyJoe) September 11, 2016
Legionnaires’ Disease
Legionella is one of the three “atypical” pathogens that must be covered during empiric treatment of community-acquired pneumonia. The other two are Mycoplasma pnemoniae and Chlamydia pnemoniae. This group of pathogens is called “atypical” because they do not grow on traditional laboratory culture media, and cannot be detected on the gram stain.
Legionella is a rare cause of pneumonia, but it should be suspected in patients with severe disease. IDSA CAP guidelines from 2007 state that all patients with CAP who are admitted to the ICU should receive a urine antigen screen for Legionella.
Older data described pneumonia from Legionella as having a case fatality rate of up to 25%. Newer data from 2005 puts the case fatality rate at 5%. In a study of 139 consecutive patients with Legionella pnemonia, almost 50% had a Pneumonia Severity Index score indicating “high-risk.”
Combination therapy
Because of the severity of disease associated with Legionella pneumonia, combination therapy is sometimes considered. Combination therapy for Legionella consists of two or more antibiotics from the following classes: Quinolones, Macrolides, Rifampin. In the remainder of this episode, I’ll review recommendations and evidence for combination therapy for Legionella pneumonia.
Johns Hopkins Antibiotic Guide
Johns Hopkins Antibiotic Guide states:
Benefit of combination therapy is unclear, used mainly w/ severe illness
Hopkins’ suggested combination regimens are for rifampin plus either levofloxacin, moxifloxacin, or azithromycin.
Guidelines
The 2007 IDSA CAP guidelines do not make a recommendation for or against combination therapy for Legionella pneumonia. These guidelines are scheduled to be updated in the Summer of 2017.
Recent articles
A 2013 study looked at all patients with Legionella pneumonia admitted to 33 ICUs in Spain over a two year period. Patients with Legionella pneumonia who presented in shock and received combination antibiotic therapy had a statistically significant lower mortality rate compared with monotherapy.
The most frequently used combinations were:
Rifampicin plus clarithromycin
and
Rifampicin plus clarithromycin plus ciprofloxacin or levofloxacin
Despite this seemingly positive study, combination therapy appears to be rarely used. In a 2015 study of over 3000 patients hospitalized with Legionella pneumonia in the US, only 1.8% received combination therapy.
In 2013 a case report was published describing the successful treatment of Legionella pneumonia using a combination of levofloxacin, rifampin, and ECMO.
Summary
Although the evidence to support combination therapy for Legionella pneumonia is weak, I support using it for patients who present to the ICU in shock from Legionella. The combination I have usually seen is rifampin plus levofloxacin. However, after reading the 2013 study conducted in Spain, I think that triple combination therapy with rifampin, azithromycin, and a quinolone is worth considering.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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