Antibiotic Treatment Strategies for Community Acquired Pneumonia in Adults

May Le, Mercer University College of Pharmacy 2015

Based on mortality surveillance results from 122 United States cities, the Centers for Disease Control and Prevention reported that six point five percent of deaths from March 29 to April 4, 2015 were due to pneumonia and influenza.1  According to Infectious Diseases Society of America/ American Thoracic Society (IDSA/ATS) consensus guidelines, patients with community-acquired pneumonia (CAP) are managed as outpatients, non-intensive care unit (ICU) inpatients, or ICU patients depending on the severity level of the disease.  Bacteria commonly found in these patients are Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Haemophilus influenzae, and Legionella species.  For these patients, the consensus guidelines recommend a respiratory fluoroquinolone (moxifloxacin, levofloxacin, or gemifloxacin) or a beta-lactam plus macrolide as the empiric antibiotic treatment of choice.  The IDSA/ATS suggests that antibiotic therapy should last for at least five days until the patients are afebrile for 48 to 72 hours and have at most one sign of clinical instability.2

A recently published study compared the use of beta-lactam monotherapy versus beta-lactam plus macrolide or fluoroquinolone as preferred empiric therapy for CAP.3

Title:  Antibiotic Treatment Strategies for Community Acquired Pneumonia in Adults3
Design Cluster-randomized, crossover trial, seven hospitals in the Netherlands, (N= 2283)
Objective To assess whether a strategy of preferred empirical treatment with beta-lactam monotherapy is noninferior to either preferred beta-lactam–macrolide combination therapy or preferred fluoroquinolone monotherapy, with regard to 90-day all-cause mortality among adults with clinically suspected CAP who are admitted to non-ICU wards
Study Groups Beta-lactam group: n= 656

Beta-lactam-macrolide group: n= 739

Fluoroquinolone group: n= 888

Methods Computer-generated randomization of antibiotic strategy was conducted for the hospitals.  The three antibiotic strategies were beta-lactam monotherapy (amoxicillin, amoxicillin-clavulanate, or a third-generation cephalosporin), beta-lactam-macrolide combination therapy (penicillin, amoxicillin, amoxicillin-clavulanate, or a third-generation cephalosporin with azithromycin, erythromycin, or clarithromycin), and fluoroquinolone monotherapy (moxifloxacin or levofloxacin).  Cross over of the hospitals to one of the three strategies occurred every four months.  When a specific organism was identified, empiric therapy was deescalated.  Non-inferiority margin of three percentage points was used in the analysis.
Duration February 2011 through August 2013
Primary Outcome Measure All-cause mortality within 90 days after admission
Baseline Characteristics Median age 70 years

Microbial causes of CAP: Streptococcus pneumoniae 15.9%, Haemophilus influenzae 6.8%, atypical pathogens 2.1%

Results Mortality within 90 days

Beta-lactam: 9%

Beta-lactam–macrolide: 11.1%

Fluoroquinolone: 8.8%

No p value provided for the primary outcome

Adverse Events Common Adverse Events: not reported
Serious Adverse Events:

Beta-lactam group: In-hospital mortality 3.2%, respiratory insufficiency 2.7%, ICU admission 2.7%, organ failure 0.8%, septic shock 0.6%

Beta-lactam-macrolide group: In-hospital mortality 3.8%, respiratory insufficiency 1.5%, ICU admission 1.6%, organ failure 0.3%, septic shock 0.4%

Fluoroquinolone group: In-hospital mortality 2.9%, respiratory insufficiency 2%, ICU admission 1.6%, organ failure 1%, septic shock 0.3%

Percentage that Discontinued due to Adverse Events: not reported
Study Author Conclusions Among patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with a beta-lactam–macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality.

The authors of this study conclude that beta-lactam monotherapy is noninferior to beta-lactam plus macrolide or fluoroquinolone monotherapy as the empiric treatment of choice for inpatient non-ICU CAP.  However, successful treatment of CAP also depends on the selection of antibiotic for deescalation therapy, which may vary depending on the hospital site, making the validity of this conclusion questionable.  Moreover, the prevalence of the bacterial cause of CAP at a hospital may influence the effectiveness of beta-lactam monotherapy since it may not cover atypical pathogens.3

References:

  1. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/flu/weekly/#S2. Accessed April 14, 2015.
  2. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72.
  3. Postma DF, Van werkhoven CH, Van elden LJ, et al. Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults. N Engl J Med. 2015;372(14):1312-1323.
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