Orcun SOYSAL, İrfan ŞENCAN, Nesibe KORKMAZ

Hastanede yatan hastalarda antibiyotikle ilişkili advers olaylar ve risk faktörleri: prospektif kohort çalışması

Amaç: Bu çalışmanın amacı, hastanede yatan hastalarda antibiyotikle ilişkili advers olayları ve risk faktörlerini belirlemektir. Gereç ve Yöntem: Bu prospektif kohort çalışma, Ocak 2019 ile Aralık 2020 arasında antibiyotik tedavisi alan 776 yatan hastayı içermektedir. "kesin" veya "muhtemel" advers olay (AO) saptanan hastalar, Dünya Sağlık Örgütü-Uppsala İzleme Merkezi (DSÖ-UMC) kriterlerine göre incelenmiştir. Antibiyotikle ilişkili olumsuz olayların tanım ve ciddiyet kriterleri, Common Terminology Criteria for Adverse Events (CTCAE) kriterlerine göre belirlenmiştir. Bulgular: Antibiyotikle ilişkili AO’ın genel oranı 1000 hasta günü başına 7.9 (95% CI, 6.8-9.1) idi. Çalışmada, AO yaşayan 125 hastada toplam 152 advers olayı tespit edildi. Bu 152 advers olayın 63'ü (%41.4) ciddi ve 89'u (%58.6) hafif advers olaylardı. AO için bağımsız risk faktörleri, komorbiditelerin sayısı (4 kat daha yüksek artmış risk), kullanılan ilaçların sayısı ve antibiyotik tedavisinin süresini (12.3 kat daha yüksek ve her ek gün için %8 artmış risk) içeriyordu. En yaygın yan etkiler hematolojikti ve hematolojik sistemde 45 (%29.6) olgu bildirilmişti. Sonuç: Antibiyotik sürelerinin yönetimi, antibiyotikle ilişkili olumsuz olayların gelişiminde kontrol edilebilir bir faktör olduğu için kritiktir. Antibiyotiklerin rasyonel kullanımı, sadece direnç gelişimini önlemek açısından değil, aynı zamanda hayati risk taşıyabilecek olumsuz olayların sıklığını azaltmak açısından da önemlidir.

Anahtar Kelimeler:

Advers olaylar, antibiyotikler, risk faktörleri.

Antibiotic-related adverse events and risk factors in hospitalized patients: a prospective cohort study

Purpose: The objective of this study is to identify antibiotic-related adverse events and risk factors in hospitalized patients. Materials and Methods: This prospective cohort study included 776 inpatients who received antibiotic treatment between January 2019 and December 2020. Patients who experienced "definite" or "probable" adverse drug events (ADE) were examined using the World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria. The definition and severity criteria for antibiotic-related adverse events were determined according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: The overall rate of antibiotic-associated ADE was 7.9 (95%CI, 6.8-9.1) per 1000 person-days. The study identified a total of 152 adverse events in 125 patients who experienced ADE. Among the 152 adverse events, 63 (41.4%) were severe, and 89 (58.6%) were non-severe. Independent risk factors for ADE included the number of comorbidities (up to 4 times higher increased risk), number of drugs used, and duration of antibiotic administration (up to 12.3 times higher and 8% increased risk for each additional day). The most common side effects were hematological, with 45 (29.6%) cases reported in the hematological system advers events. Conclusion: The management of antibiotic durations, which is a controllable factor in the development of antibiotic-related adverse events, is crucial. Rational use of antibiotics is essential, not only in terms of preventing the development of resistance but also in terms of reducing the frequency of adverse events that may become life-threatening.

Keywords:

Adverse event, Risk factors, Antibiotics,

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Cunha BA, Antibiotic side effects. Med Clin North Am. 2001;85:149-85.
Magill SS, Edwards JR, Beldavs ZG, Dumyati G, Janelle SJ, Kainer MA et al.. Prevalence of antimicrobial use in US acute care hospitals, may- september 2011. JAMA 2014;312:1438-46.
D'arcy P, Griffin J, Thalidomide revisited. Adverse Drug React Toxicol Rev. 1994;13:65-76.
Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA. 2003;289:1107-16.
Kurnik D, Loebstein R, Farfel Z, Ezra D, Halkin H et al. Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland. Medicine (Baltimore). 2004;83:107-13.
Anderson BJ, Holford NH, Mechanism-based concepts of size and maturity in pharmacokinetics. Annu. Rev. Pharmacol. Toxicol, 2008;48:303-32.
Heuberger R, Polypharmacy and food–drug interactions among older persons: a review. J Nutr Gerontol Geriatr. 2012;31:325-403.
Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med. 2017;177:1308-15.
Pretorius, RW, Gataric, G, Swedlund SK, & Miller JR. Reducing the risk of adverse drug events in older adults. Am Fam Physician. 2013;87:331-6.
The use of the WHO-UMC system for standardized case causality assessment. World Health Organization (WHO) — Uppsala Monitoring Centre. http://www.who-umc.org/Graphics/24734.pdf. (accessed on 2022).
Common Terminology Criteria for Adverse Events (CTCAE). https://ctep.cancer.gov/protocoldevelopment. (accessed Sep 2022).
Guzmán MD, Galván Banqueri M, Otero MJ, Alfaro Lara ER, Casajus Lagranja P, Ramos B et al. Development of a trigger tool to identify adverse drug events in elderly patients with multimorbidity. J Patient Saf. 2021;17:e475-82.
Saedder EA, Lisby M, Nielsen LP, Bonnerup DK, Brock B. Number of drugs most frequently found to be independent risk factors for serious adverse reactions: a systematic literature review. Br J Clin Pharmacol. 2015;80:808-17.
Guzmán MD, Banqueri MG, Otero MJ, Fidalgo SS, Noguera IF, Guerrero, M et al. Validating a trigger tool for detecting adverse drug events in elderly patients with multimorbidity (TRIGGER-CHRON). J Patient Saf. 2021;17:e976-82.
Davies LE, Spiers G, Kingston A, Todd A, Adamson J & Hanratty B. Adverse outcomes of polypharmacy in older people: systematic review of reviews. J Am Med Dir Assoc. 2020;21:181-7.
Burt J, Elmore N, Campbell SM, Rodgers S, Avery AJ, Payne, R. Developing a measure of polypharmacy appropriateness in primary care: systematic review and expert consensus study. BMC Med. 2018;16:91.
Curran J, Lo J, Leung V, Brown K, Schwartz KL, Daneman, N et al. Estimating daily antibiotic harms: an umbrella review with individual study meta-analysis. Clin Microbiol Infect. 2022;28:479-90.
Lin RY, Nuruzzaman F, Shah SN. Incidence and impact of adverse effects to antibiotics in hospitalized adults with pneumonia. J Hosp Med. 2009;4:7-15.
Kim HS, Lee E, Cho YJ, Lee YJ, Rhie SJ. Linezolid-induced thrombocytopenia increases mortality risk in intensive care unit patients, a 10 year retrospective study. J Clin Pharm Ther. 2019;44:84-90.
Choi GW, Lee JY, Chang MJ, Kim YK, Cho Y, Yu, Y. M. et al. Risk factors for linezolid-induced thrombocytopenia in patients without haemato-oncologic diseases. Basic Clin Pharmacol Toxicol. 2019;124:228-34.
Benli A, Şimşek-Yavuz S, Başaran S, Çağatay A, Özsüt H, Eraksoy, H.. Hematologic adverse effects of prolonged piperacillin-tazobactam use in adults. Turk J Haematol. 2018;35:290-95.
Kouki I, Montagner C, Mauhin W, London J, Lazard T, Grimbert S et al. Coagulation disorders during treatment with cefazolin and rifampicin: rare but dangerous. J Bone Jt Infect. 2021;6:131-34.
Ngiam JN, Liong TS, Tham SM, Pramotedham T, AlAgha R, Yong J. et al. Deranged coagulation profile secondary to cefazolin use: case report. Infect Dis Rep. 2021;13:187-90.
Strazzulla A, Chakvetadze C, Picque M, Cassard B, Hernandez F, De Pontfarcy A. et al. Evolution of haemostatic parameters and risk of bleeding during treatment with cefazolin. Eur J Clin Microbiol Infect Dis. 2019;38:177-83.
Tanaka A, Takechi K, Watanabe S, Tanaka M, Suemaru K, Araki, H. Comparison of the prevalence of convulsions associated with the use of cefepime and meropenem. Int J Clin Pharm. 2013;35:683-7.
Courjon J, Pulcini C, Cua E, Risso K, Guillouet F, Bernard, E. et al. Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study. Eur J Clin Microbiol Infect Dis. 2013;32:1611-6.
Werner NL, Hecker MT, Sethi AK, Donskey CJ. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients. BMC Infect Dis. 2011;11:1-7