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.