The use of fluoroquinolones in the treatment of community-acquired pneumonia and their cardiotoxic effects | CMAC

The use of fluoroquinolones in the treatment of community-acquired pneumonia and their cardiotoxic effects

Clinical Microbiology and Antimicrobial Chemotherapy. 2024; 26(4):452-461

​ Gamayunov D.Yu., Kalyagin A.N., Orlova G.M., Balabina N.M., Sinkova G.M., Sinkov A.V.
10.36488/cmac.2024.4.452-461
community-acquired pneumonia fluoroquinolones cardiotoxicity QT prolongation torsade de pointes sudden cardiac death
Section
Antimicrobials
Type
Review
Publication
Clinical Microbiology and Antimicrobial Chemotherapy. 2024; 26(4):452-461

Abstract

Fluoroquinolones (FQ) are widely used in the treatment of community-acquired pneumonia (CAP) in certain cases specified in Russian clinical guidelines. However, FQ are known to have cardiotoxic effects. There have been reports on proarrhythmogenic effect of this drug class, which is more often presented as QT prolongation and may lead to the development of “torsade de pointes” and ventricular fibrillation. Adverse effects of FQ on aortic wall leading to the formation of aneurysm are also reported. Given the above, treatment of CAP in patients with chronic heart failure is challenging. This paper provides a review of clinical pharmacology of FQ, their role in the treatment of CAP, general issues related to cardiotoxicity as well as possible cardiotoxic manifestations of this antibiotic class.

Danil Yu. Gamayunov

Irkutsk State Medical University, Irkutsk, Russia

Kalyagin A.N.

Irkutsk State Medical University, Irkutsk, Russia
Irkutsk City Clinical Hospital No. 1, Irkutsk, Russia

Orlova G.M.

Irkutsk State Medical University, Irkutsk, Russia

Balabina N.M.

Irkutsk State Medical University, Irkutsk, Russia

Sinkova G.M.

Irkutsk State Medical University, Irkutsk, Russia

Sinkov A.V.

Irkutsk State Medical University, Irkutsk, Russia

  • 1. Patel N., Hatley O., Berg A., Romero K., Wisniowska B., Hanna D., et al. Towards bridging translational gap in cardiotoxicity prediction: an application of progressive cardiac risk assessment strategy in TdP risk assessment of moxifloxacin. AAPS J. 2018;20(3):47. DOI: 10.1208/s12248-018-0199-4
  • 2. Molchan N.V., Smirnova Ju.A., Vel’c N.Ju., Darmostukova M.A., Kazakov A.S., Polivanov V.A. Fluoroquinolone antibiotics: safety of use by the example of ciprofloxacin. Safety and risk of pharmacotherapy. 2019;7(2):72-83. Russian. DOI: 10.30895/2312-7821-2019-7-2-72-83
  • 3. Pena R.C.F., Hofmann Bowman M.A., Ahmad M., Pham J., Kline-Rogers E., Case M.J., et al. Aortic Dissection Collaborative. An assessment of the current medical management of thoracic aortic disease: a patient-centered scoping literature review. Semin Vasc Surg. 2022;35(1):16-34. DOI: 10.1053/j.semvascsurg.2022.02.007
  • 4. Tamargo J., Agewall S. Fluoroquinolone use and valvular heart disease: is the jury still out? Eur Heart J. 2021;42(30):2909-2911. DOI: 10.1093/eurheartj/ehab426
  • 5. Hussen N.H.A., Qadir S.H., Rahman H.S., Hamalaw Y.Y., Kareem P.S.S., Hamza B.A. Long-term toxicity of fluoroquinolones: a comprehensive review. Drug Chem Toxicol. 2023:1-12. DOI: 10.1080/01480545.2023.2240036
  • 6. Kuula L.S.M., Backman J.T., Blom M.L. Healthcare costs and mortality associated with serious fluoroquinolonerelated adverse reactions. Pharmacol Res Perspect. 2022;10(2):e00931. DOI: 10.1002/prp2.931
  • 7. Kukes V.G., Sychev D.A. Clinical pharmacology: textbook. 5nd ed. M.: GJeOTAR-Media 2017. 1024 p. Russian.
  • 8. Sauer A., Peukert K., Putensen C., Bode C. Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment. Eur Respir Rev. 2021;30:210093. DOI: 10.1183/16000617.0093-2021
  • 9. Yudhawati R., Wicaksono N.F. Immunomodulatory effects of fluoroquinolones in community-acquired pneumonia-associated acute respiratory distress syndrome. Biomedicines. 2024;12(4):761. DOI: 10.3390/biomedicines12040761
  • 10. Tsai Y.F., Chen C.Y., Yang S.C., Syu Y.T., Hwang T.L. Apremilast ameliorates acute respiratory distress syndrome by inhibiting neutrophil-induced oxidative stress. Biomed J. 2023;46:100560. DOI: 10.1016/j.bj.2022.09.001
  • 11. Muanda F.T., Sood M.M., Weir M.A., Sontrop J.M., Ahmadi F., Yoo E., et al. Association of higher-dose fluoroquinolone therapy with serious adverse events in older adults with advanced chronic kidney disease. JAMA Netw Open. 2022;5(8):e2224892. DOI: 10.1001/jamanetworkopen.2022.24892
  • 12. Bertino J.S. Jr., Fish D. The safety profile of the fluoroquinolones. Clin Ther. 2000;22(7):798-817. DOI: 10.1016/S0149-2918(00)80053-3
  • 13. Eyler R.F., Shvets K. Clinical pharmacology of antibiotics. Clin J Am Soc Nephrol. 2019;14(7):1080-1090. DOI: 10.2215/CJN.08140718
  • 14. Avdeev S.N., Dekhnich A.V., Zajcev A.A., Kozlov R.S., Rachina S.A., Rudnov V.A., et al. Federal guidelines on diagnosis and treatment of community-acquired pneumonia. Pulmonologiya. 2022;32(3):295-355. Russian. DOI: 10.18093/0869-0189-2022-32-3-295-355
  • 15. Avdeev S.N., Beloborodov V.B., Belocerkovskij B.Z., Grican A.I., Dekhnich A.V., Zajcev A.A., et al. Severe community-acquired pneumonia in adults. Clinical recommendations from Russian Federation of Anaesthesiologists and Reanimatologists. Russian journal of anesthesiology and reanimatology. 2022;(1):6-35. Russian. DOI: 10.17116/anaesthesiology20220116
  • 16. Xu L.Y., Wang C.C., Peng X.X., Jiao Y., Zhao C.Z., Zhang L., et al. Empirical antibiotic treatment strategies for community-acquired pneumonia: a network meta-analysis. J Glob Antimicrob Resist. 2022;30:1-9. DOI: 10.1016/j.jgar.2022.05.009
  • 17. Han X., Chen L., Wang Y., Li H., Wang H., Xing X., et al., CAP-China Network. Cost effectiveness of different initial antimicrobial regimens for elderly community-acquired pneumonia patients in general ward. Infect Drug Resist. 2021;14:1845-1853. DOI: 10.2147/IDR.S302852
  • 18. Li J., Peng Y., Li X. Meta-analysis of the effects of combination therapies of β-lactams and fluoroquinolones or macrolides in the treatment of community-acquired pneumonia. Am J Transl Res. 2021;13(4):2439-2446. PMID: 34017402.
  • 19. Horcajada J.P., Salata R.A., Álvarez-Sala R., Nitu F.M., Lawrence L., Quintas M., et al., DEFINE-CABP Study Group. A phase 3 study to compare delafloxacin with moxifloxacin for the treatment of adults with communityacquired bacterial pneumonia (DEFINE-CABP). Open Forum Infect Dis. 2019;7(1):ofz514. DOI: 10.1093/ofid/ofz514
  • 20. Zhang Y., Wang X., Cheng Y., Wang X., Zhang Y. A typical presentation of moxifloxacin-induced DRESS syndrome with pulmonary involvement: a case report and review of the literature. BMC Pulm Med. 2022;22(1):279. DOI: 10.1186/s12890-022-02064-1
  • 21. Kuz’mina T.P., Davydkin I.L., Tereshina O.V., Danilova O.E., Shpigel’ A.S., Betaneli T.Sh., et al. Cardiotoxicity and methods of its diagnosis in hematology patients (review). Sibirskij nauchnyj medicinskij zhurnal. 2019;39(1):34-42. Russian. DOI: 10.15372/SSMJ20190105
  • 22. Kogonija L.M., Rusanov M.O., Shikina V.E. Cardiotoxicity of anticancer drugs and radiotherapy in patients with hematologic malignancies and solid tumors. Oncohematology. 2022;17(3):127-136. Russian. DOI: 10.17650/1818-8346-2022-17-3-127-136
  • 23. Lyon A.R., López-Fernández T., Couch L.S., Asteggiano R., Aznar M.C., Bergler-Klein J., et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43:4229-4361. DOI: 10.1093/eurheartj/ehac244
  • 24. Tlegenova Zh.Sh., Zholdin B.K., Gendlin G.E., Balmagambetova S.K., Kurmanalina G.L., Talipova I.Zh. The troponin prognostic capability in diagnosing cardiotoxicity during chemotherapy with anthracyclines and monoclonal antibodies in breast cancer patients. Nauka i zdravookhranenie. 2021;23(5):132-148. Russian. DOI: 10.34689/SH.2021.23.5.016
  • 25. Seliverstova D.V., Evsina O.V. Cardiotoxicity of chemotherapy. Russian heart journal. 2016;15(1):50-57. Russian. DOI: 10.18087/rhj.2016.1.2115
  • 26. Kaljuta T.Ju., Kiselev A.R., Bazarbaeva A.H. Medication cardiotoxicity: potential of prevention and correction (review). Saratov journal of medical scientific research. 2020;16(3):736-743. Russian.
  • 27. Jesaulenko A.N., Moiseeva A.Ju., Ivannikov A.A., Bratishhev I.V., Alidzhanova H.G. Cardiotoxicity with antihypertensive drugs (literature review). Part 1. Calcium channel blockers and beta-blockers. Medical alphabet. 2021;(25):12-19. Russian. DOI: 10.33667/2078-5631-2021-25-12-19
  • 28. Moiseeva A.Ju., Jesaulenko Je.N., Ivannikov A.A., Bratishhev I.V., Alidzhanova H.G. Cardiotoxicity with antihypertensive drugs (literature review). Part II. Angiotensin converting enzyme inhibitors and multi-drug intoxication. Medical alphabet. 2021;(42):8-14. Russian. DOI: 10.33667/2078-5631-2021-42-8-14
  • 29. Chang H.M., Moudgil R., Scarabelli T., Okwuosa T.M., Yeh E.T.H. Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: part 1. J Am Coll Cardiol. 2018;71(5):587. DOI: 10.1016/j.jacc.2017.12.041
  • 30. Assimon M.M., Pun P.H., Wang L.C., Al-Khatib S.M., Brookhart M.A., Weber D.J., et al. Analysis of respiratory fluoroquinolones and the risk of sudden cardiac death among patients receiving hemodialysis. JAMA Cardiol. 2022;7(1):75-83. DOI: 10.1001/jamacardio.2021.4234
  • 31. Mozhokina G.N., Samojlova A.G. Cardiac toxicity of fluoroquinolones and bedaquiline. Tuberculosis and lung diseases. 2019;97(4):56-62. Russian. DOI: 10.21292/2075-1230-2019-97-4-56-62
  • 32. Stahlmann R. Clinical toxicological aspects of fluoroquinolones. Toxicol Lett. 2002;127(1-3):269-277. DOI: 10.1016/s0378-4274(01)00509-4
  • 33. Tisdale J.E., Chung M.K., Campbell K.B., Hammadah M., Joglar J.A., Leclerc J., et al. American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing. Drug-induced arrhythmias: a scientific statement from the American Heart Association. Circulation. 2020;142(15):e214-e233. DOI: 10.1161/CIR.0000000000000905
  • 34. Zünkler B.J., Claassen S., Wos-Maganga M., Rustenbeck I., Holzgrabe U. Effects of fluoroquinolones on HERG channels and on pancreatic beta-cell ATP-sensitive K+ channels. Toxicology. 2006;228(2-3):239-248. DOI: 10.1016/j.tox.2006.09.002
  • 35. Lenz K.D., Klosterman K.E., Mukundan H., KubicekSutherland J.Z. Macrolides: from toxins to therapeutics. Toxins. 2021;13:347. DOI: 10.3390/toxins13050347
  • 36. Täubel J., Prasad K., Rosano G., Ferber G., Wibberley H., Cole S.T., et al. Effects of the fluoroquinolones moxifloxacin and levofloxacin on the QT subintervals: sex differences in ventricular repolarization. J Clin Pharmacol. 2020;60(3):400-408. DOI: 10.1002/jcph.1534
  • 37. Shojaei L., Ruzbahani M., Khajavian S., Shahsavari S., Tamasoki N., Rajabian M., et al. Analysis of QTc interval during levofloxacin prescription in cardiac patients with pneumonia. Curr Drug Saf. 2020;15(2):111-116. DOI: 10.2174/1574886315666200213112702
  • 38. Täubel J., Ferber G., Fernandes S., Camm A.J. Diurnal profile of the QTc interval following moxifloxacin administration. J Clin Pharmacol. 2019;59(1):35-44. DOI: 10.1002/jcph.1283
  • 39. Khan F., Ismail M., Khan Q., Ali Z. Moxifloxacin-induced QT interval prolongation and torsades de pointes: a narrative review. Expert Opin Drug Saf. 2018;17(10):1029-1039. DOI: 10.1080/14740338.2018.1520837
  • 40. Berger F.A., Monadian N., de Groot N.M.S., Santbergen B., van der Sijs H., Becker M.L., et al. QTc prolongation during ciprofloxacin and fluconazole combination therapy: prevalence and associated risk factors. Br J Clin Pharmacol. 2018;84(2):369-378. DOI: 10.1111/bcp.13457
  • 41. Postma D.F., Spitoni C., van Werkhoven C.H., van Elden L.J.R., Oosterheert J.J., Bonten M.J.M. Cardiac events after macrolides or fluoroquinolones in patients hospitalized for community-acquired pneumonia: posthoc analysis of a cluster-randomized trial. BMC Infect Dis. 2019;19(1):17. DOI: 10.1186/s12879-018-3630-7
  • 42. Aspinall S.L., Sylvain N.P., Zhao X., Zhang R., Dong D., Echevarria K., et al. Serious cardiovascular adverse events with fluoroquinolones versus other antibiotics: a selfcontrolled case series analysis. Pharmacol Res Perspect. 2020;8(6):e00664. DOI: 10.1002/prp2.664
  • 43. Yang P.C., DeMarco K.R., Aghasafari P., Jeng M.T., Dawson J.R.D., Bekker S., et al. A computational pipeline to predict cardiotoxicity: from the atom to the rhythm. Circ Res. 2020;126(8):947-964. DOI: 10.1161/CIRCRESAHA.119.316404
  • 44. Blinova K., Schocken D., Patel D., Daluwatte C., Vicente J., Wu J.C., et al. Clinical trial in a dish: personalized stem cell-derived cardiomyocyte assay compared with clinical trial results for two QT-prolonging drugs. Clin Transl Sci. 2019;12(6):687-697. DOI: 10.1111/cts.12674
  • 45. Smith A.S., Macadangdang J., Leung W., Laflamme M.A., Kim D.H. Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening. Biotechnol Adv. 2017;35(1):77-94. DOI: 10.1016/j.biotechadv.2016.12.002
  • 46. Cho Y., Park H.S. Association of oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin with the risk of serious ventricular arrhythmia: a nationwide cohort study in Korea. BMJ Open. 2018;8(9):e020974. DOI: 10.1136/bmjopen-2017-020974
  • 47. Assimon M.M., Pun P.H., Wang L., Al-Khatib S.M., Brookhart M.A., Weber D.J., et al. Azithromycin use increases the risk of sudden cardiac death in patients with hemodialysisdependent kidney failure. Kidney Int. 2022;102(4):894-903. DOI: 10.1016/j.kint.2022.05.024
  • 48. Taubel J., Pimenta D., Cole S.T., Graff C., Kanters J.K., Camm A.J. Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes. Clin Res Cardiol. 2022;111(10):1147-1160. DOI: 10.1007/s00392-022-02037-8
  • 49. Ellenardóttir V., Coronel R., Folke F., Halili A., Arulmurugananthavadivel A., Parveen S., et al. Fluoroquinolones do not provide added risk of out-of-hospital cardiac arrest: a nationwide study. Open Heart. 2024;11(1):e002520. DOI: 10.1136/openhrt-2023-002520
  • 50. Mennander A.A. The dark side of fluoroquinolones. J Thorac Cardiovasc Surg. 2019;157(1):122-123. DOI: 10.1016/j.jtcvs.2018.09.021
  • 51. Wee I., Chin B., Syn N., Lee K.S., Ng J.J., Choong A.M.T.L. The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis. Sci Rep. 2021;11(1):11073. DOI: 10.1038/s41598-021-90692-8
  • 52. Frankel W.C., Trautner B.W., Spiegelman A., Grigoryan L., LeMaire S.A. Patients at risk for aortic rupture often exposed to fluoroquinolones during hospitalization. Antimicrob Agents Chemother. 2019;63(2):e01712-18. DOI: 10.1128/AAC.01712-18
  • 53. Chen Y.Y., Yang S.F., Yeh H.W., Yeh Y.T., Huang J.Y., Tsao S.L., et al. Association between aortic aneurysm and aortic dissection with fluoroquinolones use in patients with urinary tract infections: a population-based cohort study. J Am Heart Assoc. 2022;11(6):e023267. DOI: 10.1161/JAHA.121.023267
  • 54. Strange J.E., Holt A., Blanche P., Gislason G., TorpPedersen C., Christensen D.M., et al. Oral fluoroquinolones and risk of aortic or mitral regurgitation: a nationwide nested case-control study. Eur Heart J. 2021;42(30):2899-2908. DOI: 10.1093/eurheartj/ehab374
  • 55. Chen S.W., Chan Y.H., Chien-Chia Wu.V., Cheng Y.T., Chen D.Y., Lin C.P., et al. Effects of fluoroquinolones on outcomes of patients with aortic dissection or aneurysm. J Am Coll Cardiol. 2021;77(15):1875-1887. DOI: 10.1016/j.jacc.2021.02.047
  • 56. DeGette R.L., Grant R.W., Mph M.D. Observational study design challenges-the case of fluoroquinolones and aortic disease. JAMA Intern Med. 2020;180(12):1605-1606. DOI: 10.1001/jamainternmed.2020.4191
  • 57. Lai C.C., Wang Y.H., Chen K.H., Chen C.H., Wang C.Y. The association between the risk of aortic aneurysm/aortic dissection and the use of fluroquinolones: a systematic review and meta-analysis. Antibiotics (Basel). 2021;10(6):697. DOI: 10.3390/antibiotics10060697
  • 58. Newton E.R., Akerman A.W., Strassle P.D., Kibbe M.R. Association of fluoroquinolone use with shortterm risk of development of aortic aneurysm. JAMA Surg. 2021;156(3):264-272. DOI: 10.1001/jamasurg.2020.6165
  • 59. Lawaetz Kristensen K., Hallas J., Sanddal Lindholt J. Fluoroquinolones as a trigger for rupture of abdominal aortic aneurysm: a case-crossover analysis. Basic Clin Pharmacol Toxicol. 2021;129(1):44-51. DOI: 10.1111/bcpt.13591
  • 60. Sim S., Wong N.K. Nanotechnology and its use in imaging and drug delivery (review) Biomed. Rep. 2021;14:42. DOI: 10.3892/br.2021.1418
  • 61. Kucukoglu V., Uzuner H., Kenar H., Karadenizli A. In vitro antibacterial activity of ciprofloxacin loaded chitosan microparticles and their effects on human lung epithelial cells. Int. J. Pharm. 2019;569:118578. DOI: 10.1016/j.ijpharm.2019.118578
  • 62. Iervolino A., Spadafora L., Spadaccio C., Iervolino V., Biondi Zoccai G., Andreotti F. Myocardial cell preservation from potential cardiotoxic drugs: the role of nanotechnologies. Pharmaceutics. 2022;15(1):87. DOI: 10.3390/pharmaceutics15010087
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