Short-course nafithromycin noninferior to 7-day moxifloxacin regimen for pneumonia

A 3-day course of oral nafithromycin is equally efficacious as the 7-day course of oral moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP) in adults, as shown in a phase III study.

The primary endpoint of early clinical response at day 4 in the modified-intent-to-treat population (MITT) was documented in 91.3 percent of nafithromycin-treated patients and 89 percent of those who received moxifloxacin (difference, 2.3 percent, 95 percent confidence interval [CI], −3.1 to 7.8), establishing the noninferiority of the short-course antibiotic regimen. [Lancet Reg Health Southeast Asia 2025;doi:10.1016/j.lansea.2025.100666]

Nafithromycin efficacy was consistent across subgroups defined by age, sex, PORT risk class, BMI, extent of pulmonary involvement, systemic inflammatory response, renal function, and baseline pathogens relevant for CABP such as H. influenzae, H. parainfluenzae, M. catarrhalis, C. pneumoniae, L. pneumophila, and M. pneumoniae. 

Investigator-determined clinical cure rates (IDCCRs) within 11–21 days of randomization (test of cure visit) were 97.7 percent with nafithromycin and 97 percent with moxifloxacin for all atypical pathogens and 95.5 percent and 88.9 percent, respectively, for gram-negative fastidious pathogens. Overall, IDCCR at test of cure was similar between the treatment arms, regardless of whether the patient had a monomicrobial or polymicrobial infection.

Both drugs were safe and well tolerated, with no new safety signals emerging and no deaths/severe treatment-emergent adverse event (TEAE) occurring. The overall incidence of TEAEs was 20.1 percent with nafithromycin and 15.3 percent with moxifloxacin.

The most common TEAEs were abdominal pain, diarrhoea, headache, and nausea, which were all mild in severity. Two patients in the moxifloxacin arm discontinued treatment due to vomiting, pruritus, and rash. No TEAE-related discontinuations were reported among patients in the nafithromycin arm.

“These data provide strong evidence for the therapeutic utility of nafithromycin in CABP as a safe and efficacious monotherapy option, particularly in the setting of increased macrolide resistance,” according to the authors.

“While antibiotics are generally considered safe, reducing the overall exposure is associated with many benefits, particularly as it relates to antimicrobial resistance rates, cost, and development of C. difficile infections or intestinal dysbiosis,” they added.

The study was conducted at 31 sites across India and included 488 patients (mean age 41.6 years, 80.9 percent male, mean BMI 23.75 kg/m²) with CABP (PORT risk class II, III, IV). These patients were randomly assigned to receive treatment with oral nafithromycin 800 mg once daily for 3 days (n=244) or oral moxifloxacin 400 mg once daily for 7 days (n=244). The MITT population comprised 477 patients, of which 40 percent had PORT risk class III/IV.