Introduction

Antimicrobial resistance is a huge barrier to the effective prevention and treatment of infectious diseases worldwide.11Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 2022; 399: 629–55. 10.1016/S0140-6736(21)02724-0 [Europe PMC free article] Over time, infectious agents such as bacteria, viruses and fungi acquire resistance to anti-infectives, which is associated with disease progression, increased numbers of treatment cycles and hospital stays, negative impacts on health-related quality of life, and higher patient mortality.22Naylor NR, Atun R, Zhu Net al. . Estimating the burden of antimicrobial resistance: a systematic literature review. Antimicrob Resist Infect Control 2018; 7: 58. 10.1186/s13756-018-0336-y

ESBL remains a major healthcare challenge

Previous research has demonstrated that community-onset infections with ESBL-producing bacteria are a challenge facing treatment protocols in clinical practice.33Mushtaq S, Hope R, Warner M, et al. Activity of faropenem against cephalosporin-resistant Enterobacteriaceae. J Antimicrob Chemother. 2007;59(5):1025–1030.
Studies from India suggest that with a high prevalence of >62% in E. coli and Klebsiella, ESBL remains a major healthcare challenge. The prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) in India has been reported at 41% in a multicenter study.4 Alarmingly, the resistance of MRSA isolates to co-trimoxazole was 55.6%, to erythromycin was 70.8% and to ciprofloxacin was 79.3%.44Indian Network for Surveillance of Antimicrobial Resistance (INSAR) group, India. Methicillin-resistant Staphylococcus aureus (MRSA) in India: Prevalence & susceptibility pattern. Indian J Med Res. 2013;137(2):363–369
In various studies, ESBL-producing isolates were consistently susceptible only to carbapenems.55Manoharan A, Premalatha K, Chatterjee S, et al . Correlation of TEM, SHV and CTX-M extended-spectrum beta-lactamases among Enterobacteriaceae with theirin vitro antimicrobial susceptibility. Indian J Med Microbiol. 2011;29(2):161–164.

Therapeutic options for treating severe and resistant bacterial infections

Several hundred β-lactam antibiotics exist, but the carbapenems have the broadest spectrum of activity and greatest potency against Gram-positive and Gram-negative bacterial species.66Papp-Wallace KM, Endimiani A, Taracila MAet al. . Carbapenems: past, present, and future. Antimicrob Agents Chemother 2011; 55: 4943–60. 10.1128/AAC.00296-11
For this reason, when treatment with other antibiotics fails, carbapenems are used as the last-line antibiotics for treating severe and resistant bacterial infections that often are associated with high morbidity and mortality. Carbapenems as IV formulations are available in most countries for the treatment of severe, complicated and resistant bacterial infections, including those affecting the respiratory, abdominal and urinary tracts, and the skin. While faropenem demonstrates high oral bioavailability (around 70%–80% in its ester prodrug form), carbapenems must be administered parenterally. Efforts to improve the oral bioavailability of carbapenems are ongoing.77Veeraraghavan B, Bakthavatchalam YD, Sahni RD. Oral antibiotics in clinical development for community-acquired urinary tract infections. Infect Dis Ther 2021; 10: 1815–35. 10.1007/s40121-021-00509-4
An oral penem, faropenem, is available in Japan and India for the treatment of urinary tract infections (UTIs), respiratory tract infections, skin and skin structure infections and gynaecological infections.88Gandra S, Klein EY, Pant Set al. . Faropenem consumption is increasing in India. Clin Infect Dis 2016; 62: 1050–2. 10.1093/cid/ciw055,99Hatakeyama S, Ohama Y, Okazaki Met al. . Antimicrobial susceptibility testing of rapidly growing mycobacteria isolated in Japan. BMC Infect Dis 2017; 17: 197. 10.1186/s12879-017-2298-8
This narrative review aims to profile the only available oral penem that addresses the challenge of resistant infectious diseases.