Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Narrative Review

Vol. 19 No. 1 (2021)

Mechanisms of action by antimicrobial agents: A review

DOI
https://doi.org/10.26443/mjm.v19i1.217
Submitted
August 5, 2020
Published
2021-01-04

Abstract

Microorganisms and associated conditions make up some of the world’s leading causes of death and have the potential to cause a significant societal effect during pandemic states. Despite such significance in the healthcare field, attention and funding directed towards microbiological research lags its cohorts in cancer and cardiovascular disease. In the current SAR-CoV-2 pandemic, the importance of practicing clinicians and providers to remain knowledgeable on antimicrobial therapy for their patients is higher than ever before. The scope of this review is to provide clinicians a semi-comprehensive, up-to-date understanding of the mechanisms of action among antimicrobial agents as well as key distinctions in clinical manifestations of pathogens.

References

  1. Levison WE. Review of Medical Microbiology and Immunology. MCGRAW-HILL EDUCATION. 2016. 14th edition.
  2. Scheffers DJ, Pinho MG. Bacterial cell wall synthesis: new insights from localization studies. Microbiol Mol Biol Rev. 2005;69(4):585–607.
  3. Soares, Geisla Mary Silva et al. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs. Journal of applied oral science. 2012. 20(3);295-309.
  4. Yocum RR, Rasmussen JR, Strominger JL. The mechanism of action of penicillin. Penicillin acylates the active site of Bacillus stearothermophilus D-alanine carboxypeptidase. J Biol Chem. 1980. 255(9);3977-86.
  5. Hélène Barreteau, Andreja Kovač, Audrey Boniface, Matej Sova, Stanislav Gobec, Didier Blanot, Cytoplasmic steps of peptidoglycan biosynthesis, FEMS Microbiology Reviews. 2008. 32(2);168–207.
  6. Lahiri SD, Johnstone MR, Ross PL, McLaughlin RE, Olivier NB, Alm RA. Avibactam and Class C β-Lactamases: Mechanism of Inhibition, Conservation of the Binding Pocket, and Implications for Resistance. Antimicrobial Agents and Chemotherapy. 2014. 58(10);5704-5713.
  7. Lambert MP, Neuhaus FC. Mechanism of D-cycloserine action: alanine racemase from Escherichia coli W. J Bacteriol. 1972. 110(3);978-87.
  8. Nguyen R, Sun Y. Bacitracin Topical. [Updated 2019 Sep 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019.
  9. Free SJ. Fungal cell wall organization and biosynthesis. Adv Genet. 2013;81:33-82.
  10. Gow NAR, Latge JP, Munro CA. The Fungal Cell Wall: Structure, Biosynthesis, and Function. Microbiol Spectr. 2017. May;5(3).
  11. Letscher-Bru V, Herbrecht R. Caspofungin: the first representative of a new antifungal class, Journal of Antimicrobial Chemotherapy. 2003. 51(3);513–521.
  12. Datry A, Bart-Delabesse E. Caspofungin: mode of action and therapeutic applications. Rev Med Interne. 2006. 27(1):32-93.
  13. Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: An Overview. Cold Spring Harb Perspect Med. 2016. 6(6):a027029.
  14. Rougier F, Claude D, Maurin M, Sedoglavic A, Ducher M, Corvaisier S, Jelliffe R, Maire P. Aminoglycoside nephrotoxicity: modeling, simulation, and control. Antimicrob Agents Chemother. 2003. 47(3);1010-6.
  15. Adeyemo AA, Oluwatosin O, Omotade OO. Study of streptomycin-induced ototoxicity: protocol for a longitudinal study. Springerplus. 2016. 15(1):758.
  16. Luzzatto L, Apirion D, Schlessinger D. Mechanism of action of streptomycin in E. coli: interruption of the ribosome cycle at the initiation of protein synthesis. Proc Natl Acad Sci U S A. 1968. 60(3):873-80.
  17. Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001. 65(2):232-60.
  18. Allison JL, Hartman RE, Hartman RS, Wolfe AD, Ciak J, Hahn FE. Mode of action of chloramphenicol. VII. Growth and multiplication of Escherichia coli in the presence of chloramphenicol. J Bacteriol. 1962. 83(3):609-15.
  19. Kanoh S, Rubin BK. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin Microbiol Rev. 2010. 23(3):590-615.
  20. Murphy PB, Le JK. Clindamycin. [Updated 2019 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019.
  21. Bozdogan B, Appelbaum PC. Oxazolidinones: activity, mode of action, and mechanism of resistance. Int J Antimicrob Agents. 2004 Feb;23(2):113-9.
  22. Henry RJ. THE MODE OF ACTION OF SULFONAMIDES. Bacteriol Rev. 1943. 7(4):175-262.
  23. Cudmore J, Seftel M, Sisler J, Zarychanski R. Methotrexate and trimethoprim-sulfamethoxazole: toxicity from this combination continues to occur. Can Fam Physician. 2014. 60(1):53-6.
  24. Kurien G, Jamil RT, Preuss CV. Dapsone. [Updated 2019 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019.
  25. Wozel G, Blasum C. Dapsone in dermatology and beyond. Arch Dermatol Res. 2014. 306(2):103-24.
  27. Hooper DC. Mechanisms of action of antimicrobials: focus on fluoroquinolones. Clin Infect Dis. 2001, 15;32 Suppl 1:S9-S15.
  28. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry. 2014. 18;53(10):1565-74.
  29. Loyse A, Dromer F, Day J, Lortholary O, Harrison TS. Flucytosine and cryptococcosis: time to urgently address the worldwide accessibility of a 50-year-old antifungal. J Antimicrob Chemother. 2013. 68(11):2435-44.
  30. Vermes A, Guchelaar HJ, Dankert J. Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother. 2000. 46(2):171-9.
  31. Saito K, Warrier T, Somersan-Karakaya S, Kaminski L, Mi J, Jiang X, Park S, Shigyo K, Gold B, Roberts J, Weber E, Jacobs WR Jr, Nathan CF. Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations. Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4832-E4840.
  32. Wehrli W. Rifampin: mechanisms of action and resistance. Rev Infect Dis. 1983. 5 Suppl 3:S407-11.
  33. Velkov T, Roberts KD, Nation RL, Thompson PE, Li J. Pharmacology of polymyxins: new insights into an 'old' class of antibiotics. Future Microbiol. 2013. 8(6):711-24.
  34. Bolard J, Joly V, Yeni P. Mechanism of Action of Amphotericin B at the Cellular Level. Its Modulation by Delivery Systems, Journal of Liposome Research. 2003. 3:3, 409-427.
  35. Noor A, Preuss CV. Antifungal Membrane Function Inhibitors (Amphotericin B). StatPearl. Treasure Island (FL): StatPearls Publishing; 2019.
  36. Quinn M, Fannin JT, Sciasci J, Bragg A, Campbell PK, Carias D, Crews KR, Gregornik D, Jeha S, Maron G, Pauley JL, Swanson HD, Wolf J, Greene W. Pentamidine for Prophylaxis against Pneumocystis jirovecii Pneumonia in Pediatric Oncology Patients Receiving Immunosuppressive Chemotherapy. Antimicrobial Agents and Chemotherapy. 2018. 62 (8) e00173-18.
  37. Olson JM, Shah NA. Microtubule Assembly Inhibitors (Griseofulvin) [Updated 2019 Aug 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019.
  38. Zhu JD, Meng W, Wang XJ, Wang HC. Broad-spectrum antiviral agents. Front Microbiol. 2015. 22; 6:517.
  39. Razonable RR. Antiviral drugs for viruses other than human immunodeficiency virus. Mayo Clin Proc. 2011 Oct;86(10):1009-26.
  40. Davies BE. Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations. J Antimicrob Chemother. 2010. 65 Suppl 2(Suppl 2):ii5-ii10.
  41. Patick AK, Potts KE. Protease inhibitors as antiviral agents. Clin Microbiol Rev. 1998. 11(4):614-27.
  42. Anderson J, Schiffer C, Lee SK, Swanstrom R. Viral protease inhibitors. Handb Exp Pharmacol. 2009;(189):85-110.
  43. Kimberlin DW, Whitley RJ. Antiviral therapy of HSV-1 and -2. In: Arvin A, Campadelli-Fiume G, Mocarski E, et al., editors. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007. Chapter 64.
  44. Andrei G, Topalis D, De Schutter T, Snoeck R. Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia. Antiviral Res. 2015. 114:21-46.
  45. Gitto S, Gamal N, Andreone P. NS5A inhibitors for the treatment of hepatitis C infection. J Viral Hepat. 2017. 24(3):180-186.
  46. Perry CM, Balfour JA. Fomivirsen. Drugs. 1999 Mar;57(3):375-80; discussion 381.
  47. Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, Waggoner J, Goodman Z, Banks SM, Hoofnagle JH. Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med. 1989. 30;321(22):1506-10.
  48. Hare S, Vos AM, Clayton RF, Thuring JW, Cummings MD, Cherepanov P. Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc Natl Acad Sci U S A. 2010. 107(46):20057-62.
  49. Powers JH. Antimicrobial drug development — the past, the present, and the future. Clin Microbiol Infect. 2004;10(Suppl 4): 23–31.elect
  50. Packer S, Berman SA. Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid. Am J Psychiatry. 2007. 164(2):346-7.
  51. Grinde B. Herpesviruses: latency and reactivation - viral strategies and host response. J Oral Microbiol. 2013. 5:10.3402/jom.v5i0.22766.
  52. Sehrawat S, Kumar D, Rouse BT. Herpesviruses: Harmonious Pathogens but Relevant Cofactors in Other Diseases? Front Cell Infect Microbiol. 2018. 25;8:177. PMID: 29888215.
  53. Karnsakul W, Schwarz KB. Hepatitis B and C. Pediatr Clin North Am. 2017 Jun;64(3):641-658.
  54. Hønge B, Jespersen S, Medina C, Té D, da Silva Z, Ostergaard L, Laursen A, Wejse C, Krarup H, Erikstrup C. Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients. HIV Med. 2014 Oct;15(9):571-6.
  55. Bouvier NM, Palese P. The biology of influenza viruses. Vaccine. 2008 Sep 12;26 Suppl 4(Suppl 4):D49-53.
  56. Singh S, Casubhoy I, Frankow J, Chronwall B. (2018). Influenza: How to Prevent the Next Pandemic. 10.13140/RG.2.2.20847.79522.
  57. Naif HM. Pathogenesis of HIV Infection. Infect Dis Rep. 2013 Jun 6;5(Suppl 1):e6. PMID: 24470970.
  58. Burke DS. Recombination in HIV: an important viral evolutionary strategy. Emerg Infect Dis. 1997 Jul-Sep;3(3):253-9.
  59. Singh S, Day A, Ganesan V, Shah S, Kim G, Moon J, Feldman K, Goldman J. (2019). Seroprevalence and Risk Factors of the Herpes Simplex Virus family: A Nationwide Sample Study. doi: 10.13140/RG.2.2.17492.35203.
  60. Zhanel GG, Karlowsky JA, Rubinstein E, Hoban DJ. Tigecycline: a novel glycylcycline antibiotic. Expert Rev Anti Infect Ther. 2006 Feb;4(1):9-25. doi: 10.1586/14787210.4.1.9
  61. Fredrick K, Ibba M. Protein synthesis: Errors rectified in retrospect. Nature. 2009 Jan 8;457(7226):157-8.
  62. Duke T, Michael A, Mokela D, et al. Chloramphenicol or ceftriaxone, or both, as treatment for meningitis in developing countries? Archives of Disease in Childhood 2003;88:536-539.
  63. Kapoor G, Saigal S, Elongavan A. Action and resistance mechanisms of antibiotics: A guide for clinicians. J Anaesthesiol Clin Pharmacol. 2017 Jul-Sep;33(3):300-305
  64. Le T, Bhushan V, Sochat M, Chavda Y, Zureick A, Kalani M, Kallianos, K.First Aid for USMLE STEP 1 2019. MCGRAW-HILL EDUCATION. 2018.
  65. Coronavirus disease 2019 (COVID-19) in the U.S. Atlanta: Centers for Disease Control and Prevention, February 26, 2020 (https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html).
  66. Munita JM, Arias CA. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016 Apr;4(2):10.1128/microbiolspec.VMBF-0016-2015. doi: 10.1128/microbiolspec.VMBF-0016-2015.
  67. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. Published online April 13, 2020. doi:10.1001/jama.2020.6019.
  68. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 Mar 4:105932. doi: 10.1016/j.ijantimicag.2020.105932.
  69. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052.
  70. Chen CT, Ng KJ, Lin Y, Kao MC. Red man syndrome following the use of vancomycin-loaded bone cement in the primary total knee replacement: A case report. Medicine (Baltimore). 2018 Dec;97(51):e13371.
  71. Park H, Youk J, Shin DY, Hong J, Kim I, Kim NJ, Lee JO, Bang SM, Yoon SS, Park WB, Koh Y. Micafungin prophylaxis for acute leukemia patients undergoing induction chemotherapy. BMC Cancer. 2019 Apr 16;19(1):358. doi: 10.1186/s12885-019-5557-9. PMID: 30991992; PMCID: PMC6469030.
  72. Craft AW, Brocklebank JT, Hey EN, Jackson RH. The 'grey toddler'. Chloramphenicol toxicity. Arch Dis Child. 1974 Mar;49(3):235-7. doi: 10.1136/adc.49.3.235.
  73. Hilgenfeldt EG, Schlachterman A, Firpi RJ. Hepatitis C: Treatment of difficult to treat patients. World J Hepatol. 2015 Jul 28;7(15):1953-63. doi: 10.4254/wjh.v7.i15.1953. PMID: 26244069; PMCID: PMC4517154.
  74. Santos KB, Souza RS, Atalla A, Hallack-Neto AE. Herpes zoster after autologous hematopoietic stem cell transplantation. Rev Bras Hematol Hemoter. 2016 Oct-Dec;38(4):298-301. doi: 10.1016/j.bjhh.2016.05.015. Epub 2016 Jul 12. PMID: 27863756; PMCID: PMC5119674.
  75. Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018;379(10):913‐923.

Downloads

Download data is not yet available.