High-Dose Antibiotics in Intensive Care: A Review of Their Role in Combatting and Contributing to Antimicrobial Resistance

Authors

  • Galo G. Farfán-Cano King Juan Carlos University, Spain; Society of Infectious Diseases of Guayas, Ecuador; Northern of Guayaquil “Los Ceibos” General Hospital, Ecuador 2University of Guayaquil, Ecuador https://orcid.org/0000-0001-8447-5764
  • Carlos R. Cedeño-Cevallos University of Guayaquil, Ecuador

DOI:

https://doi.org/10.54034/mic.e2250

Keywords:

antimicrobial resistance, high-dose antibiotics, randomized controlled trials, gram-negative infections

Abstract

Introduction. High-dose antibiotic regimens are commonly employed to improve outcomes in critically ill patients with severe infections; however, their direct impact on antimicrobial resistance (AMR) remains underexplored. Methods. This systematic review analyzed randomized controlled trials (RCTs) published between 2020 and 2024, focusing on high-dose regimens for gram-negative bacterial infections, cellulitis, and ventilated hospital-acquired bacterial pneumonia (vHABP). A comprehensive search was conducted using the Web of Science and PubMed databases, yielding four studies that met the inclusion criteria. Results. The results suggest that while high-dose regimens reduce treatment failure and improve clinical outcomes, they are associated with higher adverse effects and may contribute to antibiotic-resistant bacteria. Notably, none of the studies directly assessed the molecular or epidemiological mechanisms linking high-dose regimens to AMR, underscoring a significant gap in the current literature. Conclusion. Further research is required to elucidate these mechanisms and establish evidence-based guidelines that balance immediate clinical benefits with long-term public health concerns.

References

World Health Organization. Antimicrobial resistance. World Health Organization. https://www.who.int/es/news-room/fact-sheets/detail/antimicrobial-resistance [Accessed 14th August 2024].

Huemer M, Mairpady Shambat S, Brugger SD, Zinkernagel AS. Antibiotic resistance and persistence—Implications for human health and treatment perspectives. EMBO reports. 2020;21(12): e51034. https://doi.org/10.15252/embr.202051034.

Salam MdA, Al-Amin MdY, Salam MT, Pawar JS, Akhter N, Rabaan AA, et al. Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare. 2023;11(13): 1946. https://doi.org/10.3390/healthcare11131946.

Mississippi State Department of Health. About Antibiotic Resistance. Mississippi State Department of Health. https://msdh.ms.gov/page/14,23756,228.html [Accessed 18th August 2024].

Póvoa P, Moniz P, Pereira JG, Coelho L. Optimizing Antimicrobial Drug Dosing in Critically Ill Patients. Microorganisms. 2021;9(7): 1401. https://doi.org/10.3390/microorganisms9071401.

Martínez ML, Plata-Menchaca EP, Ruiz-Rodríguez JC, Ferrer R. An approach to antibiotic treatment in patients with sepsis. Journal of Thoracic Disease. 2020;12(3): 1007–1021. https://doi.org/10.21037/jtd.2020.01.47.

Vélez JW, Aragon DC, Donadi EA, Carlotti APCP. Risk factors for mortality from sepsis in an intensive care unit in Ecuador: A prospective study. Medicine. 2022;101(11). https://doi.org/10.1097/MD.0000000000029096.

Bruhn C. A, Pairumani M. R, Hernández P. G. Management of the patient in septic shock. Revista Médica Clínica Las Condes. 2011;22(3): 293–301. https://doi.org/10.1016/S0716-8640(11)70429-1.

Chinemerem Nwobodo D, Ugwu MC, Oliseloke Anie C, Al‐Ouqaili MTS, Chinedu Ikem J, Victor Chigozie U, et al. Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace. Journal of Clinical Laboratory Analysis. 2022;36(9): e24655. https://doi.org/10.1002/jcla.24655.

Uddin TM, Chakraborty AJ, Khusro A, Zidan BRM, Mitra S, Emran TB, et al. Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects. Journal of Infection and Public Health. 2021;14(12): 1750–1766. https://doi.org/10.1016/j.jiph.2021.10.020.

Cotta MO, Roberts JA, Lipman J. Antibiotic dose optimization in critically ill patients. Medicina Intensiva (English Edition). 2015;39(9): 563–572. https://doi.org/10.1016/j.medine.2015.07.001.

Muteeb G, Rehman MT, Shahwan M, Aatif M. Origin of Antibiotics and Antibiotic Resistance, and Their Impacts on Drug Development: A Narrative Review. Pharmaceuticals. 2023;16(11): 1615. https://doi.org/10.3390/ph16111615.

Martin-Loeches I, Timsit JF, Kollef MH, Wunderink RG, Shime N, Nováček M, et al. Clinical and microbiological outcomes, by causative pathogen, in the ASPECT-NP randomized, controlled, Phase 3 trial comparing ceftolozane/tazobactam and meropenem for treatment of hospital-acquired/ventilator-associated bacterial pneumonia. Journal of Antimicrobial Chemotherapy. 2022;77(4): 1166–1177. https://doi.org/10.1093/jac/dkab494.

Yadav K, Eagles D, Perry JJ, Taljaard M, Sandino-Gold G, Nemnom MJ, et al. High-dose cephalexin for cellulitis: a pilot randomized controlled trial. Canadian Journal of Emergency Medicine. 2023;25(1): 22–30. https://doi.org/10.1007/s43678-022-00433-7.

Timsit JF, Huntington JA, Wunderink RG, Shime N, Kollef MH, Kivistik Ü, et al. Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: subset analysis of the ASPECT-NP randomized, controlled phase 3 trial. Critical Care. 2021;25(1): 290. https://doi.org/10.1186/s13054-021-03694-3.

Tichy E, Torres A, Bassetti M, Kongnakorn T, Di Virgilio R, Irani P, et al. Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia, Including Ventilator-associated Pneumonia, in Italy. Clinical Therapeutics. 2020;42(5): 802–817. https://doi.org/10.1016/j.clinthera.2020.03.014.

Van Duijn PJ, Verbrugghe W, Jorens PG, Spöhr F, Schedler D, Deja M, et al. The effects of antibiotic cycling and mixing on acquisition of antibiotic resistant bacteria in the ICU: A post-hoc individual patient analysis of a prospective cluster-randomized crossover study. Yahav D (ed.) PLOS ONE. 2022;17(5): e0265720. https://doi.org/10.1371/journal.pone.0265720.

Bokhary H, Pangesti KNA, Rashid H, Abd El Ghany M, Hill-Cawthorne GA. Travel-Related Antimicrobial Resistance: A Systematic Review. Tropical Medicine and Infectious Disease. 2021;6(1): 11. https://doi.org/10.3390/tropicalmed6010011.

Gonçalves-Pereira J, Póvoa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams. Critical Care. 2011;15(5): R206. https://doi.org/10.1186/cc10441.

Ruiz-Ramos J, Escolà-Vergé L, Monje-López ÁE, Herrera-Mateo S, Rivera A. The Interventions and Challenges of Antimicrobial Stewardship in the Emergency Department. Antibiotics. 2023;12(10): 1522. https://doi.org/10.3390/antibiotics12101522.

Pasquau-Liaño J. Timing in antibiotic therapy: when and how to start, de-escalate and stop antibiotic therapy. Proposals from a stablished antimicrobial stewardship program. Revista Española de Quimioterapia. 2022; 35 (Suppl3): 102–107. https://doi.org/10.37201/req/s03.22.2022.

Ahmed SK, Hussein S, Qurbani K, Ibrahim RH, Fareeq A, Mahmood KA, et al. Antimicrobial resistance: Impacts, challenges, and future prospects. Journal of Medicine, Surgery, and Public Health. 2024;2: 100081. https://doi.org/10.1016/j.glmedi.2024.100081.

Cižman M, Plankar Srovin T. Antibiotic consumption and resistance of gram-negative pathogens (collateral damage). GMS Infectious Diseases; 6:Doc05. 2018; https://doi.org/10.3205/ID000040.

Cantón R, Morosini MI. Emergence and spread of antibiotic resistance following exposure to antibiotics. FEMS Microbiology Reviews. 2011;35(5): 977–991. https://doi.org/10.1111/j.1574-6976.2011.00295.x.

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Published

2024-12-03

How to Cite

1.
Farfán-Cano GG, Cedeño-Cevallos CR. High-Dose Antibiotics in Intensive Care: A Review of Their Role in Combatting and Contributing to Antimicrobial Resistance. Microbes Infect. Chemother. [Internet]. 2024 Dec. 3 [cited 2025 Feb. 18];4:e2250. Available from: https://revistas.unheval.edu.pe/index.php/mic/article/view/2250

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REVIEW ARTICLE