Intravenous fosfomycin—back to the future. Systematic review and meta-analysis of the clinical literature

Grabein, B.; Graninger, Wolfgang; Rodríguez-Baño, Jesús; Dinh, Aurélien; Liesenfeld, David B.

doi:10.1016/j.cmi.2016.12.005

Cited by 137 publications

(132 citation statements)

References 42 publications

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“…However, aminopenicillins cannot be administered in case of allergy to β-lactams, and gentamicin has a poor intracellular penetration, does not cross the BBB efficiently, and is nephrotoxic or ototoxic [10, 69, 70]. Due to its bactericidal activity and synergistic action with many antimicrobials including β-lactams, aminoglycosides, meropenem, linezolid, daptomycin and vancomycin, the “old” antibiotic fosfomycin [14] is currently resurging as a therapeutic option for the treatment of critically ill patients with invasive or systemic bacterial infections [12, 13, 71]. Rapid, effective bactericidal action is paramount in neuromeningeal, bacteremic or materno-fetal listeriosis to limit disease severity, relapses and fatal outcomes [2, 9, 70, 72, 73].…”

Section: Discussionmentioning

confidence: 99%

Epistatic control of intrinsic resistance by virulence genes in Listeria

et al. 2018

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Elucidating the relationships between antimicrobial resistance and virulence is key to understanding the evolution and population dynamics of resistant pathogens. Here, we show that the susceptibility of the gram-positive bacterium Listeria monocytogenes to the antibiotic fosfomycin is a complex trait involving interactions between resistance and virulence genes and the environment. We found that a FosX enzyme encoded in the listerial core genome confers intrinsic fosfomycin resistance to both pathogenic and non-pathogenic Listeria spp. However, in the genomic context of the pathogenic L. monocytogenes, FosX-mediated resistance is epistatically suppressed by two members of the PrfA virulence regulon, hpt and prfA, which upon activation by host signals induce increased fosfomycin influx into the bacterial cell. Consequently, in infection conditions, most L. monocytogenes isolates become susceptible to fosfomycin despite possessing a gene that confers high-level resistance to the drug. Our study establishes the molecular basis of an epistatic interaction between virulence and resistance genes controlling bacterial susceptibility to an antibiotic. The reported findings provide the rationale for the introduction of fosfomycin in the treatment of Listeria infections even though these bacteria are intrinsically resistant to the antibiotic in vitro.

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Section: Discussionmentioning

confidence: 99%

Epistatic control of intrinsic resistance by virulence genes in Listeria

et al. 2018

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“…However, less activity against P. aeruginosa and A. baumannii with fosfomycin monotherapy has been observed, with resistance emerging rapidly [44]. Although not currently available in the U.S., intravenous fosfomycin penetrates the lung well, and limited data suggest it may be efficacious in this setting [45]. …”

Section: Contemporary Treatment Strategies For Gram-negative Vapmentioning

confidence: 99%

Resistance Trends and Treatment Options in Gram-Negative Ventilator-Associated Pneumonia

Rhodes

Cruce

O’Donnell

et al. 2018

Curr Infect Dis Rep

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Rapid identification technologies and phenotypic methods, new therapeutic strategies, and novel treatment paradigms have evolved in an attempt to improve treatment outcomes for VAP; however, clinical data supporting alternative treatment strategies and adjunctive therapies remain sparse. Importantly, new classes of antimicrobials, novel virulence factor inhibitors, and beta-lactam/beta-lactamase inhibitor combinations are currently in development. Conscientious stewardship of new and emerging therapeutic agents will be needed to ensure they remain effective well into the future.

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“…Fosfomycin as monotherapy for the treatment of multidrug-resistant organism (MDRO)-associated invasive infections is limited by the emergence of drug resistance to fosfomycin during treatment 39 . A more recently published meta-analysis conducted by Grabein et al tried to summarize the current clinical evidence of intravenous fosfomycin in 128 studies 43 . According to their results, the drug showed comparable clinical or microbiological efficacy compared with other antibiotics when used for sepsis/bacteremia, urinary tract, respiratory tract, bone and joint, and central nervous system infections 43 .…”

Section: Decision Making On Esbl-pe Antimicrobial Treatmentmentioning

confidence: 99%

“…A more recently published meta-analysis conducted by Grabein et al tried to summarize the current clinical evidence of intravenous fosfomycin in 128 studies 43 . According to their results, the drug showed comparable clinical or microbiological efficacy compared with other antibiotics when used for sepsis/bacteremia, urinary tract, respiratory tract, bone and joint, and central nervous system infections 43 . The pooled estimate for resistance development during fosfomycin monotherapy was 3.4% (95% CI 1.8%–5.1%).…”

Section: Decision Making On Esbl-pe Antimicrobial Treatmentmentioning

confidence: 99%

Treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLs) infections: what have we learned until now?

Pana

Zaoutis

2018

F1000Res

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The spread of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) has dramatically increased worldwide, and this “evolving crisis” is currently regarded as one of the most important public health threats. The growing problem of ESBL-PE antimicrobial resistance seems to have a dual face between “Scylla and Charybdis”: on one hand the potential for rapid spread and dissemination of resistance mechanisms and on the other hand the injudicious overuse of antimicrobial agents and the inadequate infection control measures, especially in the health-care setting. Given the World Health Organization’s warning against a “post antibiotic era”, health-care providers are at a critical standpoint to find a “balance” between safe and effective ESBL-PE treatment and avoidance of inducing further resistance mechanisms. The aim of the review is to summarize the updated published knowledge in an attempt to answer basic everyday clinical questions on how to proceed to effective and the best ESBL-PE treatment options based on the existing published data.

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Intravenous fosfomycin—back to the future. Systematic review and meta-analysis of the clinical literature

Abstract: Intravenous fosfomycin can play a vital role in the antibiotic armamentarium, given its long history of effective and safe use. However, well-designed randomized controlled trials are still desired.

Cited by 137 publications

References 42 publications

Epistatic control of intrinsic resistance by virulence genes in Listeria

Epistatic control of intrinsic resistance by virulence genes in Listeria

Resistance Trends and Treatment Options in Gram-Negative Ventilator-Associated Pneumonia

Treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLs) infections: what have we learned until now?

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