An Investigation on The Use of Colistin in Critically Ill Patients at A Teaching Hospital in Ho Chi Minh City
Abstract
Colistin is reintroduced into therapeutic protocols as one of the last resort antibiotics against multidrug-resistant (MDR) pathogens. In February 2019, the International Consensus Guidelines (ICG 2019) on optimizing the administration of colistin has for the first time stipulated an official recommendation for higher colistin dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) modeling data. This study aimed at assessing the current dosing of colistin at University Medical Center (UMC) of Ho Chi Minh City (HCMC) and to identify rates and risk factors of colistin-induced nephrotoxicity. A cross sectional study was conducted on patients admitted to Intensive Care Unit (ICU), being treated for severe infection with at least 5 days of colistin IV administration from April 2018 to April 2019. KDIGO criteria were used to evaluate nephrotoxicity during treatment. Colistin-resistance was detected in 4 cases during the study period. The majority (n=104, 87.4%) of patients was diagnosed with pneumonia due to mainly Acinetobacter baumannii. Rational dosing according to PK/PD approach, EMA, FDA was observed in 33 cases (27.8%), 39 cases (32,8%), and 44 cases (38,2%), respectively. 85 cases (71,4%) were evaluated as rational dosing in accordance with at least one of the three guidelines. Clinical efficacy was recorded in 59 infected patients (49.6%). Lower average maintenance dose was observed in patients with treatment failure (p = 0.002). KDIGO-defined acute kidney injury (AKI) developed in 70 patients (58,8%). Multivariate analysis showed that concomitant administration of vasopressors (OR = 16.52; 95% CI 5.3750.83; p = 0.001), furosemide (OR = 5.24; 95% CI 1.89–14.55; p = 0.001) and hypoalbuminemia (< 25 g/l) (OR = 6.24; 95% CI 2.17–17.93; p = 0.001) were significantly associated with nephrotoxicity. Consistent with previous studies, due to a very modest clinical cure rate with a high frequency of colistin-induced AKI and the development of colistin-resistant strains, alternative agents such as new beta-lactam/beta-lactamase inhibitor combinations with favourable safety data are strongly preferred for the treatment of carbapenem-resistant infection.
References
2. Bang T. C., Trang D. N. D. (2018), "Investigation on colistin use at the University Medical Center Hochiminh City", Pharmaceutical Sciences Asia, 42 (1), 37-44. https://doi.org/10.29090/psa.2018.01.037.
3. Binh N. G., Hayakawa K., Co D. X. et al. (2015), "The efficacy and nephrotoxicity associated with colistin use in an intensive care unit in Vietnam: Use of colistin in a population of lower body weight", Int J Infect Dis, 35, 18-23. https://doi.org/10.1016/j.ijid.2015.03.020.
4. The European Committee on Antimicrobial Susceptibility Testing, May 15, 2018. "Breakpoint tables for interpretation of MICs and zone diameters.", (Online). http://www.eucast.org, accessed: Dec. 18, 2018.
5. Cheah S. E., Wang J., Nguyen V. T. et al. (2015), "New pharmacokinetic/pharmacodynamic studies of systemically administered colistin against Pseudomonas aeruginosa and Acinetobacter baumannii in mouse thigh and lung infection models: smaller response in lung infection", J Antimicrob Chemother, 70 (12), 3291-3297. https://doi.org/10.1093/jac/dkv267.
6. Fiaccadori E., Antonucci E., Morabito S. et al. (2016), "Colistin Use in Patients With Reduced Kidney Function", Am J Kidney Dis, 68 (2), 296-306. https://doi.org/10.1053/j.ajkd.2016.03.421.
7. Giacobbe D. R., di Masi A., Leboffe L. et al. (2018), "Hypoalbuminemia as a predictor of acute kidney injury during colistin treatment", Sci Rep, 8 (1), 11968. https://doi.org/10.1038/s41598-018-30361-5.
8. Luo X., Jiang L., Du B. et al. (2014), "A comparison of different diagnostic criteria of acute kidney injury in critically ill patients", Critical care (London, England), 18 (4), R144-R144. https://doi.org/10.1186/cc13977.
9. Nation R. L., Garonzik S. M., Li J. et al. (2016), "Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform?", Clin Infect Dis, 62 (5), 552-558. https://doi.org/10.1093/cid/civ964.
10. Nation R. L., Garonzik S. M., Thamlikitkul V. et al. (2017), "Dosing guidance for intravenous colistin in critically-ill patients", Clin Infect Dis, 64 (5), 565-571. https://doi.org/10.1093/cid/ciw839.
11. Nation R. L., Rigatto M. H. P., Falci D. R. et al. (2019), "Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity", Antibiotics, 8 (1), 24. .
12. Omrani A. S., Alfahad W. A., Shoukri M. M. et al. (2015), "High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia", Ann Clin Microbiol Antimicrob, 14, 3. https://doi.org/10.1186/s12941-015-0062-8.
13. Clinical and Laboratory Standards Institute (CLSI) (2020), Performance Standards for Antimicrobial Susceptibility Testing, 30th, CLSI supplement M100, Wayne and PA: CLSI, ed, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087 USA, pp. 37-49.
14. Frédérique Schortgen, 2011, Prévention de l’insuffisance rénale aiguë ischémique chez le patient ventilé, UNIVERSITE PARIS EST - Sciences de la vie et de la santé -Faculté de médecine de Créteil - Institut Mondor de Recherche Biomédicale, .
15. Rhee C. (2016), " Using Procalcitonin to Guide Antibiotic Therapy", Open Forum Infectious Diseases, 4 (1), 249. .
16. Shields R. K., Anand R., Clarke L. G. et al. (2017), "Defining the incidence and risk factors of colistin-induced acute kidney injury by KDIGO criteria", PLoS One, 12 (3), e0173286. https://doi.org/10.1371/journal.pone.0173286.
17. Singer M., Deutschman C. S., Seymour C. W. et al. (2016), "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)", JAMA, 315 (8), 801-810. https://doi.org/10.1001/jama.2016.0287.
18. Sorli L., Luque S., Segura C. et al. (2017), "Impact of colistin plasma levels on the clinical outcome of patients with infections caused by extremely drug-resistant Pseudomonas aeruginosa", BMC Infect Dis, 17 (1), 11. https://doi.org/10.1186/s12879-016-2117-7.
19. Tamma P. D., Aitken S. L., Bonomo R. A. et al. (2021), "Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum beta-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)", Clin Infect Dis, 72 (7), 1109-1116. https://doi.org/10.1093/cid/ciab295.
20. Trifi A., Abdellatif S., Daly F. et al. (2016), "Efficacy and Toxicity of High-Dose Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections: A Comparative Study of a Matched Series", Chemotherapy, 61 (4), 190-196. https://doi.org/10.1159/000442786.
21. Tsuji B. T., Pogue J. M., Zavascki A. P. et al. (2019), "International Consensus Guidelines for the Optimal Use of the Polymyxins", Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 39 (1), 10-39. https://doi.org/10.1002/phar.2209.
22. Wangchinda W., Pati N., Maknakhon N. et al. (2018), "Collateral damage of using colistin in hospitalized patients on emergence of colistin-resistant Escherichia coli and Klebsiella pneumoniae colonization and infection", Antimicrob Resist Infect Control, 7, 84. https://doi.org/10.1186/s13756-018-0375-4.
23. Wiedermann C. J., Wiedermann W., Joannidis M. (2010), "Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies", Intensive Care Med, 36 (10), 1657-1665. https://doi.org/10.1007/s00134-010-1928-z.
24. Zarjou A., Agarwal A. (2011), "Sepsis and Acute Kidney Injury", Journal of the American Society of Nephrology, 22 (6), 999-1006. https://doi.org/10.1681/asn.2010050484.