Intravenous fosfomycin for the treatment of patients with bone and joint infections: a review

ABSTRACT

Introduction

Fosfomycin is a wide spectrum bactericidal antibiotic with a unique mode of action, low toxicity, and good penetration in tissues with deep-seated infections, including bone and joint infections.

Areas covered

Data were extracted from 19 published articles. Three hundred and sixty-five patients, with broad age range, received intravenous fosfomycin for the treatment of bone and joint infections (including arthritis, acute and chronic osteomyelitis, discitis, periprosthetic joint infection). Fosfomycin was given as part of a combination antimicrobial therapy in the majority of patients (93.7%). The dosage of fosfomycin ranged from 4 g/day (in one case) to 24 g/day. The dosage of fosfomycin, in some cases, mostly pediatric, was calculated based on body weight, ranging from 50 mg/kg/day to 250 mg/kg/day. The duration of fosfomycin treatment ranged from a couple of days up to 3 months. The most common isolated pathogen was Staphylococcus aureus (38.9%). Three hundred patients (82.2%) were successfully treated. Fosfomycin was well tolerated, as few patients developed mild adverse events, mostly gastrointestinal discomfort, hypernatremia, skin rash, and neutropenia.

Expert opinion

The available data suggests that intravenous fosfomycin may be beneficial for the treatment of patients with bone and joint infections, especially when used as part of a combination antibiotic regimen.

KEYWORDS:

• Fosfomycin
• bone and joint infections
• osteomyelitis
• arthritis
• discitis
• combination

Article highlights

• Fosfomycin has strong antimicrobial activity against many bacterial pathogens and is considered for various types of infections including staphylococcal, enterococcal and ESBL-producing E. coli biofilms, particularly in combination with other antibacterials

• The use of intravenous fosfomycin has been recently revised, because the antibiotic has favorable pharmacokinetic characteristics, low toxicity and high tissue penetration, even in deep-seated infections, like bone and joint infections.

• A critical evaluation of the availale evidence showed that 300 of 365 patients (82.2%) who received intravenous fosfomycin, alone or in combination with another antibiotic, for the treatment of bone and joint infections were succesfully treated.

• Intravenous fosfomycin may be beneficial for empiric and targeted first-line treatment of patients with bone and joint infections. Also, it is a therapeutic option in patients with bone and joint infections when there is failure of initial antibiotic therapy or concurrent presence of difficult-to-treat pathogens.

Abbreviations

ALT: alanine aminotransferase

AUC: area under the curve

EMA: European medicines agency

ESBL: extended-spectrum beta-lactamase-producing

MDR: multidrug resistant

MRSA: methicillin-resistant Staphylococcus aureus

PAE: postantibiotic effect

SPC: summary of product characteristics

XDR: extensively drug resistant

Notes on contribution

All authors have substantially contributed to the production of the article and agreed with its final version.

Declaration of interest

ME Falagas participated in advisory boards of AstraZeneca, Infectopharm, Tetraphase, Shionogi, and Xellia; received lecture honoraria from Cipla, Merck, and Pfizer; and received research support from Shionogi, Tetraphase, Helperby and Xellia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by InfectoPharm.