Introduction

Tuberculosis (TB) remains a major global health burden despite the availability of standard 6‑month therapy. Long treatment duration can affect adherence and increase toxicity. Faropenem, an oral β-lactam antibiotic with demonstrated anti-tuberculosis activity in vitro, was evaluated as a replacement for ethambutol in patients with drug-susceptible pulmonary TB. 

Aim

• To evaluate whether replacing ethambutol with faropenem in the standard first-line anti-TB regimen is noninferior to standard therapy in newly diagnosed drug-susceptible pulmonary TB. 
• To compare treatment outcomes, microbiological response, and safety between treatment groups. 

Patient Profile

• Adults (≥18 years) with newly diagnosed, drug-susceptible pulmonary TB. 

Methods

Study Design

• Multicenter, randomized, open-label, noninferiority trial. 
• Conducted at 13 centers in China. 

Patient Population

• 227 eligible patients randomized 1:1 to faropenem or standard treatment.
• Randomized population: 227 patients 
  • Faropenem group: 114
  • Control group: 113
• mITT population: 217 patients 
  • Faropenem: 110
  • Control: 107 

Treatment

Control Arm

• 2 months HRZE (isoniazid + rifampicin + pyrazinamide + ethambutol)
• Followed by 4 months HR. 

Faropenem Arm

• Ethambutol replaced with faropenem 200 mg three times daily for 8 weeks (HRZF)
• Followed by 4 months HR. 

Study Endpoints

Primary Endpoint

• Treatment success rate after 6 months without relapse. 

Secondary Endpoints

• Xpert MTB/RIF negative conversion time.
• Culture conversion rates.
• Acid-fast bacilli (AFB) conversion rates.
• Cure rate.
• Safety and adverse events. 

Results

• Faropenem demonstrated noninferiority to standard therapy for treatment success. 
• mITT treatment success: 88.18% vs 85.98%. 
• PP treatment success: 96.04% vs 95.83%.

Table 1. Primary Treatment Outcomes

Outcome	Faropenem	Control
mITT Treatment Success	88.18%	85.98%
Difference	2.2%
PP Treatment Success	96.04%	95.83%
Difference	2.1%

mITT, modified intention-to-treat; PP, per-protocol; CI, confidence interval. Noninferiority margin = -10%. 

Figure 1. Treatment Success Rates

Microbiological Findings

• Median time to Xpert MTB/RIF negativity was comparable between groups (29 vs 30 days; P=0.14)
• No significant differences in culture conversion rates throughout treatment
• No significant differences in AFB smear conversion rates 
• Cure rates numerically favored faropenem but were not statistically significant (79.09% vs 71.03%; P=0.21)

Table 2. Microbiological Outcomes

Outcome	Faropenem	Control	P-value
Median Xpert conversion time	29 days	30 days	0.14
8-week Culture Conversion (mITT)	81.81%	78.50%	0.61
8-week AFB Conversion (mITT)	84.54%	83.18%	0.85
Cure Rate (mITT)	79.09%	71.03%	0.21

AFB, acid-fast bacilli; mITT, modified intention-to-treat population. 

Safety Findings

• Overall adverse events were significantly lower with faropenem (31.81% vs 49.53%; P<0.01). 
• No deaths or grade 4 adverse events were reported. 
• Visual impairment occurred only in the ethambutol-containing control arm (4.67% vs 0%; P=0.02). 
• Rates of hepatotoxicity were similar between groups (19.09% vs 21.50%; P=0.66). 

Table 3. Safety Outcomes

Adverse Event	Faropenem (%)	Control (%)	P-value
Any adverse event	31.81	49.53	<0.01
Grade 3 adverse event	2.72	4.55	0.49
Hepatotoxicity	19.09	21.50	0.66
Visual impairment	0.00	4.67	0.02

Conclusion

• Replacement of ethambutol with oral faropenem in the first-line regimen demonstrated noninferior treatment success compared with the standard regimen in patients with drug-susceptible pulmonary TB
• Faropenem was associated with significantly fewer adverse events (31.81% vs 49.53%; P<0.01) and eliminated ethambutol-associated visual impairment, suggesting an improved safety profile while maintaining comparable efficacy 

Reference 

Int. J. Infect. Dis. 132 (2023) 99–107