Efficacy and Safety of Oral Solithromycin versus Oral Moxifloxacin for Treatment of Community-acquired Bacterial Pneumonia: a Global, Double-blind, Multicenter, Randomized, Active-controlled, Non-inferiority Trial (SOLITAIRE-ORAL)

Sol Ahn, Mercer University College of Pharmacy

Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality in adults. The overall annual incidence of CAP ranges from five to 11 per 1,000 persons, with more cases occurring in the winter months. [1]

In a systemic review article of seven clinical studies, it is stated that the rapid increase in the prevalence of S. pneumoniae isolates resistant to multiple antibiotics has cast doubt on the efficacy of macrolide antibiotics for serious pneumococcal infections. [2]

The American Thoracic Society and the Infectious Disease Society of America (ATS-IDSA) treatment guidelines for community-acquired bacterial pneumonia (CABP) recommend empirical outpatient treatment with a respiratory fluoroquinolone or a beta-lactam plus a macrolide if the local rate of macrolide resistance is greater than 25%. [3]

Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicenter, randomized, active-controlled, non-inferiority trial (SOLITAIRE-ORAL) [4]
Design Randomized, double-blind, active-controlled, non-inferiority trial; N= 860
Objective To compare the efficacy and safety of solithromycin with moxifloxacin for treatment of community-acquired bacterial pneumonia (CABP)
Study Groups Solithromycin (n= 426); moxifloxacin (n= 434)
Methods A total of 860 patients with clinically and radiographically confirmed pneumonia of Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV were randomly assigned to receive either oral solithromycin (800 mg on day one, 400 mg on days two to five, placebo on days six and seven) or oral moxifloxacin (400 mg on days one to seven).
Duration Jan 3, 2013 to Sep 24, 2014
Primary Outcome Measure Early clinical response, defined as an improvement in at least two of four symptoms (cough, chest pain, sputum production, dyspnea)
Baseline Characteristics Solithromycin group (n= 426) Moxifloxacin group (n= 434)
Male, n (%) 227 (53%) 229 (53%)
Mean Age (years) 58.5 56.7
White, n (%) 347 (81%) 367 (85%)
African American, n (%) 46 (11%) 40 (9%)
Asian, n (%) 4 (1%) 4 (1%)
Other, n (%) 29 (7%) 23 (5%)
Mean PORT score 71.1 71.2
Port risk class I, n (%) 1 (< 1%) 0
Port risk class II, n (%) 209 (49%) 223 (51%)
Port risk class III, n (%) 168 (39%) 173 (40%)
Port risk class IV, n (%) 48 (11%) 38 (9%)
Patients with any baseline pathogen, n (%) 233 (55%) 226 (52%)
Results Solithromycin group (n= 426) Moxifloxacin group (n= 434) Difference (95% CI)
Early clinical response, n (%) 333 (78.2%) 338 (77.9%) 0.29% (-5.5 to 6.1)
Adverse Events Common Adverse Events: diarrhea (5.3%), nausea (3.7%), headache (3.4%), vomiting (2.3) and dizziness (1.9%)
Serious Adverse Events: C. difficile colitis (0.2%), eye disorder (0.2%, eye irritation and black spots in vision), myocardial infarction (0.1%), respiratory failure (0.3%), cerebral vascular accidents (0.2%), bronchospasm (0.1%), septic shock (0.1%), hepatorenal failure following thrombosis of an abdominal aortic aneurysm (0.1%), pulmonary embolism (0.1%), congestive heart failure (0.1%), and a combined cardiac and pulmonary failure (0.1%)
Percentage that Discontinued due to Adverse Events: 3.3%
Study Author Conclusions Oral solithromycin was non-inferior to oral moxifloxacin for treatment of patients with CABP, showing the potential to restore macrolide monotherapy for this indication.

Oral solithromycin, a fourth generation macrolide with activity against macrolide-resistant CABP pathogens, was non-inferior to moxifloxacin for the treatment of CABP in adult patients in terms of the rates of early clinical response. The study result showed the potential to restore macrolide monotherapy for CABP management, especially when the local rate of macrolide-resistant of common CABP pathogens is greater than 25%. However, when considering the effect of CABP on long-term morbidity and mortality, a 30-day follow-up period can be a limitation of the study.

References

  1. Watkins RR, Lemonovich TL. Diagnosis and Management of Community-Acquired Pneumonia in Adults. Am Fam Physician. 2011 Jun 1;83(11):1299-1306.
  1. Kahn JB, Wiesinger BA, Xiang J. Macrolide-Resistant Streptococcus pneumoniae in Community-Acquired Pneumonia: Clinical and Microbiological Outcomes for Patients Treated with Levofloxacin. Clin Infect Dis 2004;38;S24-33.
  1. Mandell LA et al. Infectious Disease Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Disease 2007;44:S27-72.
  1. Barrera CM, Mykietiuk A, Metev H, et al. Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL). Lancet Infect Dis. 2016;
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