An old molecule, a new drug; the role of intravenous Fosfomycin in clinical use

Year 2022, , 95 - 100, 01.01.2022

Fatih Temoçin , Levent Şensoy , Tuba Kuruoğlu , Aynur Atilla , Esra Tanyel

https://doi.org/10.31362/patd.940929

Abstract

Purpose: Treatment of invasive infections caused by multidrug-resistant bacteria is getting more difficult. Problems in the development of new antibiotics have led to the use of fosfomycin, an old molecule that has a broad spectrum. In this study, it was aimed to discuss the real life data of intravenous fosfomycin in our clinical practice.
Materials and methods: Patients who were treated with IV fosfomycin in Ondokuz Mayıs University Medical Faculty Hospital were included in the study.
Results: A total of 36 patients, 18 (50%) male and 18 (50%) female, were included in the study. The mean age of the patients was 62.5±17.0 (18-90) years. 34.2% of the patients who used intravenous fosfomycin were in the intensive care unit. IV fosfomycin use indication, 30 patients (83.3%) upper urinary tract infection, three patients (8.3%) lower respiratory tract infection, two patients (5.5%) bone-joint infection and one patient (2%, 7) was found to be a bloodstream infection. Indication of iv fosfomycin use was found to be upper urinary tract infection in 30 patients (83.3%), lower respiratory tract infection in three patients (8.3%), bone-joint infection in two patients (5.5%), bloodstream infection in one patient (2%). The causative microorganism was Klebsiella pneumoniae 75%, Providencia retgerii 19.4%, and Escherichia coli 5.6%. Microbiological cure occurred in 72.7% of the patients. The mean duration use of IV fosfomycin was 8.6±4.1 days, and the average daily dose was 13.11±4.4 g. It was found that 16.7% of the patients developed hypernatremia. It was observed that fosfomycin was used in combination therapy in half of the study patients. In combination therapies, it is most frequently combined with a 33.3% carbapenem. When monotherapy and combination therapy were compared, no difference was found between the groups in terms of microbiological response, side effects and 14-day mortality.
Conclusion: Intravenous fosfomycin is used in many indications such as lower respiratory tract infections, osteomyelitis, bacterial meningitis, urinary tract infections, and sepsis. It is a new alternative especially used in the treatment of infections caused by multi-drug resistant microorganisms. As a result of this study, we think that intravenous fosfomycin is a good option among the treatment alternatives.

Keywords

Fosfomycin, intravenous, multi drug resistance

Eski bir molekül, yeni bir ilaç; intravenöz Fosfomisinin klinik kullanımdaki yeri

Abstract

Amaç: Çok ilaca dirençli bakterilerin sebep olduğu invaziv enfeksiyonların tedavisi zorlaşmaktadır. Yeni antibiyotik geliştirilmesindeki problemler, eski bir molekül olan ve geniş spektrumuna sahip olan fosfomisinin kullanımını gündeme getirmiştir. Bu çalışmada, intravenöz (İV) fosfomisinin klinik pratiğimizdeki gerçek yaşam verilerinin tartışılması amaçlanmıştır.
Gereç ve yöntem: Çalışmaya Ondokuz Mayıs Üniversitesi Tıp Fakültesi Hastanesi’nde, tedavisinde İV fosfomisin kullanılan hastalar dahil edilmiştir.
Bulgular: Çalışmaya 18 (%50)’i erkek, 18 (%50)’i kadın toplam 36 hasta dahil edilmiştir. Hastaların yaş ortalaması 62,5±17,0 (18-90) saptanmıştır. İntravenöz fosfomisin kullanılan hastaların %34,2'si yoğun bakımda yatıyordu. İV fosfomisin kullanım endikasyonunun, 30 hastada (%83,3) üst üriner sistem enfeksiyonu, üç hastada (%8,3) alt solunum yolu enfeksiyonu, iki hastada (%5,5) kemik-eklem enfeksiyonu ve bir hastada (%2,7) ise kan dolaşımı enfeksiyonu olduğu saptanmıştır. Etken mikroorganizma %75 oranında Klebsiella pneumoniae, %19,4 oranında Providencia retgerii ve %5,6 oranında Escherichia coli olmuştur. Hastaların %72,7’sinde mikrobiyolojik kür oldu. İV fosfomisinin ortalama kullanım süresi 8,6±4,1 gün, ortalama günlük dozu ise 13,11±4,4 gr bulunmuştur. Hastaların %16,7’sinde hipernatremi geliştiği saptanmıştır. Çalışma hastalarının yarısında fosfomisin kombinasyon tedavisinde kullanıldığı görülmüştür. Kombinasyon tedavilerinde en sık %33,3 oranında bir karbapenem ile kombine edilmiştir. Monoterapi ve kombineterapi karşılaştırıldığında mikrobiyolojik yanıt, yan etki ve 14 günlük mortalite açısından gruplar arasında bir fark saptanmamıştır.
Sonuç: İntravenöz fosfomisin, alt solunum yolu enfeksiyonları, osteomyelit, bakteriyel menenjit, üriner sistem enfeksiyonları ve sepsis gibi birçok endikasyonda kullanılmaktadır. Özellikle çok ilaca dirençli mikroorganizmaların neden olduğu enfeksiyonların tedavisinde kullanılan yeni bir alternatiftir. Bu çalışma sonucunda intravenöz fosfomisinin tedavi alternatifleri arasında iyi bir seçenek olduğunu düşünüyoruz.

Keywords

Fosfomisin, intravenöz, çok ilaca direnç

References

• 1.Livorsi DJ, Chorazy ML, Schweizer ML, Balkenende EC, Blevins AE, Nair R, et al. A systematic review of the epidemiology of carbapenem-resistant Enterobacteriaceae in the United States. Antimicrob Resist Infect Control 2018;7:55. https://doi.org/10.1186/s13756-018-0346-9
• 2.Logan LK, Weinstein RA. The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. T J Infect Dis 2017;215(suppl_1):S28-S36. https://doi.org/10.1093/infdis/jiw282
• 3.Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009;9(4):228-36. https://doi.org/10.1016/S1473-3099(09)70054-4
• 4.Monaco M, Giani T, Raffone M, Arena F, Garcia-Fernandez A, Pollini S, et al. Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy, November 2013 to April 2014. Euro Surveill 2014;19(42). https://doi.org/10.2807/1560-7917.es2014.19.42.20939
• 5.Falagas ME, Vouloumanou EK, Samonis G, Vardakas KZ. Fosfomycin. Clin Microbiol Rev 2016;29(2):321-47. https://doi.org/10.1128/CMR.00068-15
• 6.Grabein B, Graninger W, Rodriguez Bano J, Dinh A, Liesenfeld DB. Intravenous fosfomycin-back to the future. Systematic review and meta-analysis of the clinical literature. Clin Microbiol Infect 2017;23(6):363-72. https://doi.org/10.1016/j.cmi.2016.12.005
• 7.Livermore DM, Warner M, Jamrozy D, et al. In vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase. Antimicrob Agents Chemother 2015;59(9):5324-30. https://doi.org/10.1128/AAC.00678-15
• 8.Alm RA, Johnstone MR, Lahiri SD. Characterization of Escherichia coli NDM isolates with decreased susceptibility to aztreonam/avibactam: role of a novel insertion in PBP3. J Antimicrob Chemother2015;70(5):1420-8. https://doi.org/10.1093/jac/dku568
• 9.Falagas ME, Maraki S, Karageorgopoulos DE, et al. Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to fosfomycin. Int J Antimicrob Agents 2010;35(3):240-3. https://doi.org/10.1016/j.ijantimicag.2009.10.019
• 10.Schito GC. Why fosfomycin trometamol as first line therapy for uncomplicated UTI? Int J Antimicrob Agents 2003;22 Suppl 2:79-83. https://doi.org/10.1016/s0924-8579(03)00231-0
• 11.Pontikis K, Karaiskos I, Bastani S, et al. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria. Int J Antimicrob Agents 2014;43(1):52-9. https://doi.org/10.1016/j.ijantimicag.2013.09.010
• 12.Perdigao Neto LV, Oliveira MS, Martins RCR, et al. Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem. J Antimicrob Chemother 2019;74(1):177-81. https://doi.org/10.1093/jac/dky406
• 13.Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. Int J Infect Dis2011;15(11):e732-9. https://doi.org/10.1016/j.ijid.2011.07.00714.Iarikov D, Wassel R, Farley J, Nambiar S. Adverse Events Associated with Fosfomycin Use: Review of the Literature and Analyses of the FDA Adverse Event Reporting System Database. Infect Dis Ther 2015;4(4):433-58. . https://doi.org/10.1007/s40121-015-0092-8
• 15.Sirijatuphat R, Thamlikitkul V. Preliminary study of colistin versus colistin plus fosfomycin for treatment of carbapenem-resistant Acinetobacter baumannii infections. Antimicrob Agents Chemother 2014;58(9):5598-601. https://doi.org/10.1128/AAC.02435-13
• 16.Shorr AF, Pogue JM, Mohr JF. Intravenous fosfomycin for the treatment of hospitalized patients with serious infections. Expert Rev Anti Infect Ther 2017;15(10):935-45. https://doi.org/10.1080/14787210.2017.1379897
• 17.Reffert JL, Smith WJ. Fosfomycin for the treatment of resistant gram-negative bacterial infections. Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2014;34(8):845-57. https://doi.org/10.1002/phar.1434
• 18.Evren E, Azap OK, Colakoglu S, Arslan H. In vitro activity of fosfomycin in combination with imipenem, meropenem, colistin and tigecycline against OXA 48-positive Klebsiella pneumoniae strains. agn Microbiol Infect Dis 2013;76(3):335-8. https://doi.org/10.1016/j.diagmicrobio.2013.04.004
• 19.Kaye KS, Rice LB, Dane AL, et al. Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial. Clin Infect Dis. 2019;69(12):2045-56. https://doi.org/10.1093/cid/ciz181
• 20.Rosso-Fernandez C, Sojo-Dorado J, Barriga A, et al. Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial. BMJ open 2015;5(3):e007363. https://doi.org/10.1136/bmjopen-2014-007363
• 21.Neuner EA, Sekeres J, Hall GS, van Duin D. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother 2012;56(11):5744-8. https://doi.org/10.1128/AAC.00402-12
• 22. Burgos RM, Rodvold KA. ZTI-01 (fosfomycin for injection) in the treatment of hospitalized patients with complicated urinary tract infections. Future Microbiol 2019;14:461-75. https://doi.org/10.2217/fmb-2018-0303