IV Fosfomycin is an ideal combination partner

  • Difficult-to-treat infections in patients with or without life-threatening conditions, especially caused by multidrug-resistant organisms, are very often treated with combination chemotherapy1
  • IV Fosfomycin can be combined with all other antibiotics, such as β-lactams and β-lactam/β-lactam inhibitors, aminoglycosides, glycopeptides, polymyxins,  oxazolidinones or rifamycins for treatment of Gram-positive and Gram-negative pathogens2, 3, 4
  • Mostly additive and synergistic action5, 6
  • Synergistic effects with other, later-stage, cell wall synthesis-inhibiting antibiotics (β-lactams) is explained by its early stage action in bacterial cell wall synthesis
  • IV Fosfomycin increases bacterial cell wall permeability and hence facilitates the antimicrobial activity of other antibiotics

Synergistic activity of IV Fosfomycin with a selection of commonly used antibiotics 7, 8, 9, 10

Synergistic activity of IV Fosfomycin

1 Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Paño-Pardo JR, Venditti M, Tumbarello M, Daikos G, Cantón R, Doi Y, Tuon FF, Karaiskos I, Pérez-Nadales E, Schwaber MJ, Azap ÖK, Souli M, Roilides E, Pournaras S, Akova M, Pérez F, Bermejo J, Oliver A, Almela M, Lowman W, Almirante B, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodríguez-Baño J; REIPI/ESGBIS/INCREMENT Investigators. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis. 2017 Jul;17(7):726-734
2 Dinh A, Salomon J, Bru JP, Bernard L. Fosfomycin: efficacy against infections caused by multidrug-resistant bacteria. Scand J Infect Dis. 2012 Mar;44(3):182-9
3 Pontikis K, Karaiskos I, Bastani S, Dimopoulos G, Kalogirou M, Katsiari M, Oikonomou A, Poulakou G, Roilides E, Giamarellou H. 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 Jan;43(1):52-9.
4 Putensen C, Ellger B, Sakka SG, Weyland A, Schmidt K, Zoller M, Weiler N, Kindgen-Milles D, Jaschinski U, Weile J, Lindau S, Kieninger M, Faltlhauser A, Jung N, Teschendorf P, Adamzik M, Gründling M, Wahlers T, Gerlach H, Litty FA. Current clinical use of intravenous fosfomycin in ICU patients in two European countries. Infection. 2019 Oct;47(5):827-836
5 Falagas ME, Vouloumanou EK, Samonis G, Vardakasa KZ. Fosfomycin. Clin Microbiol Rev 2016; 29: 321–347
6 Flamm RK, Rhomberg PR, Lindley JM, Sweeney K, Ellis-Grosse EJ, Shortridge D. Evaluation of the Bactericidal Activity of Fosfomycin in Combination with Selected Antimicrobial Comparison Agents Tested against Gram-Negative Bacterial Strains by Using Time-Kill Curves. Antimicrob Agents Chemother. 2019;63(5):e02549-18. Published 2019 Apr 25. doi:10.1128/AAC.02549-18
7 Popovic M, Steinort D, Pillai S, Joukhadar C. Fosfomycin: an old, new friend? Eur J Clin Microbiol Infect Dis. 2010 Feb;29(2):127-42
8 Albiero J, Mazucheli J, Barros JPDR, Szczerepa MMDA, Nishiyama SAB, Carrara-Marroni FE, Sy S, Fidler M, Sy SKB, Tognim MCB. Pharmacodynamic Attainment of the Synergism of Meropenem and Fosfomycin Combination against Pseudomonas aeruginosa Producing Metallo-β-Lactamase. Antimicrob Agents Chemother. 2019 May 24;63(6). pii: e00126-19. doi: 10.1128/AAC.00126-19
9 Ojdana D, Gutowska A, Sacha P, Majewski P, Wieczorek P, Tryniszewska E. Activity of Ceftazidime-Avibactam Alone and in Combination with Ertapenem, Fosfomycin, and Tigecycline Against Carbapenemase-Producing Klebsiella pneumoniae. Microb Drug Resist. 2019 Jul 11. doi: 10.1089/mdr.2018.0234.
10 Antonello RM, Principe L, Maraolo AE, Viaggi V, Pol R, Fabbiani M, Montagnani F, Lovecchio A, Luzzati R, Di Bella S. Fosfomycin as Partner Drug for Systemic Infection Management. A Systematic Review of Its Synergistic Properties from In Vitro and In Vivo Studies. Antibiotics (Basel). 2020 Aug 10;9(8):500