Abstract :

In this review, we summarize the current “state of the art” of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the beta-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most beta-lactamases. Herein, we described the cost effectiveness, safety, and advantages of carbapenems as compared to other antibiotics. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges related to oral formulatuion of carbapenems and different strategies to overcome these challenges.

---

Keywords :

antibiotics, carbapenems, oral antibiotics

---

References :

1. Holmes KK, B.S., Bloom BR, et al, Major Infectious Diseases, Major Infectious Diseases: Key Messages from Disease Control Priorities. Third Edition.
2. Ritchie, M.R.a.H., Burden of Disease. 2020.
3. Larry M. Bush , M., FACP, Charles E. Schmidt, Manifestations of Infection. 2018, MERCK MANUAL Professional Version.
4. M, D., IV, Prevention, and Treatment. What You Need to Know About Infectious Disease, 2010.
5. Quante, M., I. Thate-Waschke, and M. Schofer, [What are the reasons for patient preference? A comparison between oral and subcutaneous administration]. Z Orthop Unfall, 2012. 150(4): p. 397-403.
6. Viswanathan, P., Y. Muralidaran, and G. Ragavan, Chapter 7 – Challenges in oral drug delivery: a nano-based strategy to overcome, in Nanostructures for Oral Medicine, E. Andronescu and A.M. Grumezescu, Editors. 2017, Elsevier. p. 173-201.
7. Popescu, M.A., Drug Delivery. 2011, Hauppauge, UNITED STATES: Nova Science Publishers, Incorporated.
8. Sevinç, F., et al., Early switch from intravenous to oral antibiotics: guidelines and implementation in a large teaching hospital. J Antimicrob Chemother, 1999. 43(4): p. 601-6.
9. Barlow, G.D. and D. Nathwani, Sequential antibiotic therapy. Current Opinion in Infectious Diseases, 2000. 13(6).
10. Slama, T.G., Clinical review: Balancing the therapeutic, safety, and economic issues underlying effective antipseudomonal carbapenem use. Critical Care, 2008. 12(5): p. 233.
11. Saito, T., Possible Factors Involved in Oral Inactivity of Meropenem, a Carbapenem Antibiotic. Pharmacology & Pharmacy, 2012. 03: p. 201-206.
12. Zhanel, G., et al., Comparative Review of the Carbapenems. Drugs, 2007. 67(7): p. 1027-1052.
13. Nguyen, C.P., et al., Clinical cure rate and cost-effectiveness of carbapenem-sparing beta-lactams vs. meropenem for Gram-negative infections: A systematic review, meta-analysis, and cost-effectiveness analysis. Int J Antimicrob Agents, 2019. 54(6): p. 790-797.
14. Australasian Society of, C., et al., Australian medicines handbook, in AMH online. 2000, Australian Medicines Handbook: Adelaide, S. Aust.
15. Liang, E.H., L.H. Chen, and E. Macy, Adverse Reactions Associated with Penicillins, Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study. The Journal of Allergy and Clinical Immunology: In Practice, 2020. 8(4): p. 1302-1313.e2.
16. Bartoletti, M., et al., Differences in the rate of carbapenem-resistant Enterobacteriaceae colonisation or Clostridium difficile infection following frontline treatment with tigecycline vs. meropenem for intra-abdominal infections. International Journal of Antimicrobial Agents, 2018. 51(3): p. 516-521.
17. Hawkey, P.M. and D.M. Livermore.
18. Miller, A.D., et al., Epileptogenic Potential of Carbapenem Agents: Mechanism of Action, Seizure Rates, and Clinical Considerations. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2011. 31(4): p. 408-423.
19. Alván, G. and C.E. Nord, Adverse effects of monobactams and carbapenems. Drug safety, 1995. 12(5): p. 305.
20. Frumin, J. and J.C. Gallagher, Allergic Cross-Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What are the Chances? Annals of Pharmacotherapy, 2009. 43(2): p. 304-315.
21. Pana, Z.D. and T. Zaoutis, Treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLs) infections: what have we learned until now? F1000Research, 2018. 7: p. F1000 Faculty Rev-1347.
22. , N.C.f.B., Imipenem, CID=104838, . PubChem Database, 2020.
23. Information, N.C.f.B., Meropenem, CID=441130. PubChem Database, 2020.
24. Information, N.C.f.B., Ertapenem, CID=150610. PubChem Database, 2020.
25. Information, N.C.f.B., Tebipenem pivoxil, CID=9892071. PubChem Database, 2020.
26. Information, N.C.f.B., Biapenem, CID=71339. PubChem Database, 2020.
27. Information, N.C.f.B., Panipenem, CID=72015. PubChem Database, 2020.
28. Information, N.C.f.B., Doripenem, CID=73303. PubChem Database, 2020.
29. Diseases, N.I.o.D.a.D.a.K., Imipenem-Cilastatin. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury 2012.
30. Nicolau, D.P., Carbapenems: a potent class of antibiotics. Expert Opinion on Pharmacotherapy, 2008. 9(1): p. 23-37.
31. Administration, U.F.a.D., FDA Drug Safety Communication: FDA approves label changes for antibacterial Doribax (doripenem) describing increased risk of death for ventilator patients with pneumonia. 2012.
32. Administration, U.S.F.a.D., DORIBAX® (doripenem for injection) Powder, For Solution for Intravenous use
33. Cheng, A. and W. Wuest, Signed, Sealed, Delivered: Conjugate and Prodrug Strategies as Targeted Delivery Vectors for Antibiotics. ACS Infect. Dis., 2019. 5(6): p. 816-828.
34. Jain, A., et al., Tebipenem, the first oral carbapenem antibiotic. Expert Review of Anti-infective Therapy, 2018. 16(7): p. 513-522.
35. Kato, K., et al., Intestinal Absorption Mechanism of Tebipenem Pivoxil, a Novel Oral Carbapenem: Involvement of Human OATP Family in Apical Membrane Transport. Molecular Pharmaceutics, 2010. 7(5): p. 1747-1756.
36. Rizvi, S.A.A. and A.M. Saleh, Applications of nanoparticle systems in drug delivery technology. Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 2018. 26(1): p. 64-70.
37. Patra, J.K., et al., Nano based drug delivery systems: recent developments and future prospects.(Report). Journal of Nanobiotechnology, 2018. 16(1).
38. Cao, S.-J., et al., Nanoparticles: Oral Delivery for Protein and Peptide Drugs. AAPS PharmSciTech, 2019. 20(5): p. 190-190.
39. Shaaban, M.I., M.A. Shaker, and F.M. Mady, Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates. Journal of Nanobiotechnology, 2017. 15(1): p. 29.
40. Shaker, M. and M. Shaaban, Formulation of Carbapenems Loaded Gold Nanoparticles to Combat Multi-antibiotic Bacterial Resistance: In vitro Antibacterial Study. International Journal of Pharmaceutics, 2017. 525.