Pharmacodynamics of fosfomycin against ESBL- and/or carbapenemase-producing Enterobacteriaceae

Fransen, Fiona; Hermans, Kelly; Melchers, Maria J.; Lagarde, Claudia C M; Meletiadis, Joseph; Mouton, Johan W.

doi:10.1093/jac/dkx328

Cited by 26 publications

(28 citation statements)

References 23 publications

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“…Urinary tract infections (UTIs) are commonly seen and constitute a significant burden of hospitalizations and health-care cost. Increased antimicrobial resistance and limited treatment options in Gram-negative bacteria have increased the interest in 'old' antibiotic FT [11]. FT is a phosphonic acid derivative.…”

Section: Discussionmentioning

confidence: 99%

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Fosfomycin in the treatment of extended spectrum beta-lactamase-producing Enterobacteriaceae- related urinary tract infections

Tümtürk

Tonyalı

Tekçe

et al. 2019

J Infect Dev Ctries

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Introduction: We aimed to demonstrate if fosfomycin tromethamine (FT) treatment could be the treatment of choice in ESBL-producing Enterobacteriaceae strains as an alternative to carbapenem particularly in patients who we would like to treat on an outpatient basis. Methodology; We retrospectively analyzed the medical records of all patients who admitted to infectious disease outpatient clinic with complaints of dysuria and frequency and received FT for lower UTI between May 2016 and May 2017. Results: A total of 48 patients, 19 females (39.6%) and 29 males (60.4%), with a mean age of 62.5 (ranging from 27 to 85) years were included the study. 26 (76.4%) of patients with a history of urinary operation or intervention had also a history of antibiotic use within the past 3 months. The isolated pathogens included Escherichia Coli (n = 32), Klebsiella spp. (n = 12), Enterobacter spp. (n = 4). The overall microbiological response after treatment was 70.8% (34/48) and the clinical response was 75% (36/48). Clinical and microbiological response rates of patients with and without urinary operation/intervention, diabetes mellitus, history of antibiotic use and malignancy were found similar (p > 0.05). However, patients with a urinary stone disease history had significantly higher response rates than those without a urinary stone disease history (P = 0.042). Conclusion: Oral fosfomycin tromethamine might be the treatment of choice in ESBL-producing enterobactericea related UTIs especially caused by Escherichia Coli.

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Section: Discussionmentioning

confidence: 99%

“…Oral FT is well tolerated and has no serious side effects. Only 5% of patients are reported to have side effects, most commonly diarrhea [11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Fosfomycin in the treatment of extended spectrum beta-lactamase-producing Enterobacteriaceae- related urinary tract infections

Tümtürk

Tonyalı

Tekçe

et al. 2019

J Infect Dev Ctries

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“…Cells tolerated partial repression of these genes without exhibiting a fitness defect, perhaps due to transcriptional feedback and/or an excess of enzyme. If expression was sufficiently repressed, these strains lysed (Table S4) as has been described for murA, murG, and mraY inhibition in E. coli (29)(30)(31) and for murC, murD, and murG depletion in B. subtilis (8). However, the dearth of intermediate fitness outcomes upon repression of peptidoglycan precursor synthesis in both species is surprising.…”

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confidence: 82%

Modulated efficacy CRISPRi reveals evolutionary conservation of essential gene expression-fitness relationships in bacteria

et al. 2019

Preprint

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Essential genes are the central hubs of cellular networks. Despite their importance, the lack of high-throughput methods for titrating their expression has limited our understanding of the fitness landscapes against which essential gene expression levels are optimized. We developed a modified CRISPRi system leveraging the predictable reduction in efficacy of imperfectly matched sgRNAs to generate specific levels of CRISPRi activity and demonstrate its broad applicability in bacteria. Using libraries of mismatched sgRNAs, we characterized the expression-fitness relationships of essential genes in Escherichia coli and Bacillus subtilis. Remarkably, these relationships co-vary by pathway and are predominantly conserved between E. coli and B. subtilis despite ~ 2 billion years of evolutionary separation, suggesting that deeply conserved tradeoffs underlie bacterial homeostasis.One Sentence Summary: Bacterial essential genes have varying responses to CRISPRi knockdown that are largely conserved across ~2 billion years of evolution.

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“…Enterobacteriaceae üyelerindeki karbapenem direncinin büyük kısmından karbapenemaz enzimleri sorumlu tutulurken porin kaybının eşlik ettiği GSBL ve Amp C enzimi varlığı da karbapenem direnci veya karbapenemlere azalmış duyarlılığa yol açabilmektedir (20) . Gerek beta-laktam gerekse karba-penem dirençleri özellikle hastane enfeksiyonlarının tedavisini zorlaştırmakta, yeni tedavi arayışlarını gerekli kılmaktadır (10,12,16,17) .…”

Section: Discussionunclassified

“…Ülkemizde kullanıma girmesiyle birlikte özellikle E.coli nedenli üriner sistem enfeksiyonlarında fosfomisin trometamolün etkinliğiyle ilgili çok sayıda çalışma yapılmıştır (1,2,3,4,(11)(12)(13)14,(15)(16)(17)21) . (10,12,17) .…”

Section: Discussionunclassified

Fosfomycin Susceptibility of ESBL Positive and Negative Escherichia coli and Klebsiella spp. Resistant to at Least One Carbapenem

Atmaca¹,

Yakut²,

Özcan³

et al. 2018

Ankem Derg

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Enterobacterales üyelerinde genişlemiş spektrumlu beta laktamaz (GSBL) üretimi ve artan karbapenem direnci eski bir antibiyotik olan fosfomisine ilgiyi arttırmıştır. Çalışmada karbapenemlerden (ertapenem, imipenem, meropenem) en az birine dirençli GSBL pozitif ve GSBL negatif Escherichia coli ve Klebsiella spp. suşlarında fosfomisin duyarlılığı araştırılmıştır. Bir yıllık periyotta (Ocak-Aralık 2017) çeşitli klinik-yoğun bakım ve poliklinik hastalarından izole edilen karbapenemlerden en az birine dirençli E.coli ve Klebsiella izolatları çalışmaya dahil edilmiştir. Çalışmaya alınan 64 E.coli suşunda GSBL negatif suşlardaki fosfomisin duyarlılığının (41/43, % 95.3), GSBL pozitif suşlardaki fosfomisin duyarlılığından (17/21, % 80.9) daha yüksek olduğu görülmüştür. Ancak GSBL varlığı ile fosfomisin duyarlılığı arasında istatistiki olarak anlamlı bir ilişki saptanmamıştır(p>0.05) Klebsiella spp. suşlarında GSBL negatif suşlardaki fosfomisin duyarlılığı (42/53, % 79.2), GSBL pozitif suşlardaki fosfomisin duyarlılığından (16/29, % 55.1) yüksek bulunmuştur. Klebsiella spp. suşlarında GSBL varlığı ile fosfomisin direnci arasındaki ilişki istatistiki olarak anlamlı bulunmuştur (p<0.05). Çalışmada GSBL pozitif ve GSBL negatif olup çalışılan karbapenemlerden en az birine dirençli toplam E.coli suşlarındaki fosfomisin duyarlılığının (% 90.6), Klebsiella spp. izolatlarında elde edilen duyarlılığa göre (% 70.7) yüksekliği istatistiki olarak anlamlı bulunmamuştur (p>0.05). Karbapenem dirençli E.coli ve Klebsiella suşlarında yüksek fosfomisin duyarlılığı, ilacın idrar yolu dışındaki dirençli enfeksiyonlarda da kullanımını gündeme getirebilir.

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Pharmacodynamics of fosfomycin against ESBL- and/or carbapenemase-producing Enterobacteriaceae

Cited by 26 publications

References 23 publications

Fosfomycin in the treatment of extended spectrum beta-lactamase-producing Enterobacteriaceae- related urinary tract infections

Fosfomycin in the treatment of extended spectrum beta-lactamase-producing Enterobacteriaceae- related urinary tract infections

Modulated efficacy CRISPRi reveals evolutionary conservation of essential gene expression-fitness relationships in bacteria

Fosfomycin Susceptibility of ESBL Positive and Negative Escherichia coli and Klebsiella spp. Resistant to at Least One Carbapenem

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