Heteroresistance to Fosfomycin Is Predominant in Streptococcus pneumoniae and Depends on the
            <i>murA1</i>
            Gene

Engel, H. W. B.; Gutiérrez-Fernández, Javier; Flückiger, Christine; Martı́nez-Ripoll, M.; Mühlemann, Kathrin; Hermoso, J.A.; Hilty, Markus; Hathaway, Lucy J.

doi:10.1128/aac.00223-13

Cited by 34 publications

(23 citation statements)

References 50 publications

(49 reference statements)

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“…When this gene was introduced into a heteroresistant strain, its heteroresistance phenotype was not changed. Thus, MurA is required for heteroresistance, but it is not the only factor involved (123). Heteroresistance was also described in MDR and non-MDR P. aeruginosa strains (124).…”

Section: Heteroresistancementioning

confidence: 93%

Fosfomycin

et al. 2016

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SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

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Section: Heteroresistancementioning

confidence: 93%

Fosfomycin

et al. 2016

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“…Heteroresistance to fosfomycin is predominant among S. pneumoniae isolates (44). The UDP-N-acetylglucosamine enolpyruvyltransferase MurA1, which catalyzes the first step of peptidoglycan synthesis, contributes to heteroresistance against fosfomycin; however, this is not the only factor involved, and such heteroresistance is potentially multifactorial (44).…”

Section: Heteroresistance To Fosfomycinmentioning

confidence: 99%

“…Counting of CFU by dropping smaller aliquots is as efficient as spread plate techniques (6,42). Turbidimetric PAP assays are also performed using 2-fold antibiotic increments (6,43) and antibiotic increments of Ͼ2-fold (2,44).…”

Section: Population Analysis Profilingmentioning

confidence: 99%

Antimicrobial Heteroresistance: an Emerging Field in Need of Clarity

2015

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SUMMARY “Heteroresistance” describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic. Unfortunately, a lack of standard methods to determine heteroresistance has led to inappropriate use of this term. Heteroresistance has been recognized since at least 1947 and occurs in Gram-positive and Gram-negative bacteria. Its clinical relevance may be considerable, since more resistant subpopulations may be selected during antimicrobial therapy. However, the use of nonstandard methods to define heteroresistance, which are costly and involve considerable labor and resources, precludes evaluating the clinical magnitude and severity of this phenomenon. We review the available literature on antibiotic heteroresistance and propose recommendations for definitions and determination criteria for heteroresistant bacteria. This will help in assessing the global clinical impact of heteroresistance and developing uniform guidelines for improved therapeutic outcomes.

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“…Although not extensively described, fosfomycin heteroresistance has been observed in S. pneumoniae and P. aeruginosa isolates. These isolates possessed the MurA1 enzyme, and deletion of this gene removed heteroresistance …”

Section: Resistance To Fosfomycinmentioning

confidence: 99%

Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide

2019

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Fosfomycin was initially discovered in 1969 but has recently gained renewed interest for the treatment of multidrug‐resistant (MDR) bacterial infections, particularly in the United States. Its unique mechanism of action, bactericidal activity, broad spectrum of activity, and relatively safe and tolerable adverse effect profile make it a great addition to the dwindling antibiotic armamentarium. Fosfomycin contains a three‐membered epoxide ring with a direct carbon to phosphorous bond that bypasses the intermediate oxygen bond commonly present in other organophosphorous compounds; this structure makes the agent unique from other antibiotics. Despite nearly 50 years of parenteral fosfomycin use in Europe, fosfomycin has retained stable activity against most pathogens. Furthermore, fosfomycin demonstrated in vitro synergy in combination with other cell wall–active antibiotics (e.g., β‐lactams, daptomycin). These combinations may offer respite for severe infections due to MDR gram‐positive and gram‐negative bacteria. The intravenous (IV) formulation is currently under review in the United States, and apropos, this review collates more contemporary evidence (i.e., studies published between 2000 and early 2019) in anticipation of this development. The approval of IV fosfomycin provides another option for consideration in the management of MDR infections. Its unique structure will give rise to a promising epoxide epoch in the battle against MDR bacteria.

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Heteroresistance to Fosfomycin Is Predominant in Streptococcus pneumoniae and Depends on the murA1 Gene

Cited by 34 publications

References 50 publications

Fosfomycin

Fosfomycin

Antimicrobial Heteroresistance: an Emerging Field in Need of Clarity

Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide

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