BACKGROUND: Prostate cancer is the most common malignant solid tumour in men aged >70 years and is the second most common cause of death from oncological circumstances. AIM: To evaluate the effect of different short-term prophylactic antibiotic regimens in transrectal prostate biopsy (PB) on the incidence of infectious complications. METHODS: Patients who underwent transrectal ultrasound-guided PB between January 2021 and December 2022 were included in the prospective randomized study. According to the regimen of prophylaxis, patients were randomized into three groups: (1) fosfomycin trometamol 3 g, 3 h before the procedure + ciprofloxacin 500 mg, 2 h before the procedure; (2) fosfomycin trometamol 3 g, 3 h before and 24 h after the procedure; (3) ciprofloxacin 500 mg 12, 2 h before the procedure, and 12 h after the procedure. A rectal swab was performed 1-2 weeks before PB to evaluate the culture findings. Complications were evaluated during follow-up visits within one month after PB. FINDINGS: In the monitored period, 605 PBs were performed, and 544 patients met the inclusion criteria (184, 161, and 199 in groups 1, 2, and 3). Infectious complications occurred in 10 cases (1.83%), namely 3, 4, and 3 according to patient groups. There was no statistically significant difference between the individual groups. None of the patients required hospitalization and all were free of symptoms of sepsis. CONCLUSION: Short-term antibiotic prophylaxis in PB using fosfomycin trometamol, ciprofloxacin, or their combination appears to be effective. Fosfomycin trometamol is a suitable alternative to fluoroquinolone antibiotics.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- antibiotická profylaxe metody MeSH
- biopsie škodlivé účinky metody MeSH
- ciprofloxacin terapeutické užití MeSH
- fosfomycin * terapeutické užití MeSH
- lidé MeSH
- prospektivní studie MeSH
- prostata * diagnostické zobrazování patologie MeSH
- rektum MeSH
- tromethamin MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Antimicrobial resistance is well-known to be a global health and development threat. Due to the decrease of effective antimicrobials, re-evaluation in clinical practice of old antibiotics, as fosfomycin (FOS), have been necessary. FOS is a phosphonic acid derivate that regained interest in clinical practice for the treatment of complicated infection by multi-drug resistant (MDR) bacteria. Globally, FOS resistant Gram-negative pathogens are raising, affecting the public health, and compromising the use of the antibiotic. In particular, the increased prevalence of FOS resistance (FOSR) profiles among Enterobacterales family is concerning. Decrease in FOS effectiveness can be caused by i) alteration of FOS influx inside bacterial cell or ii) acquiring antimicrobial resistance genes. In this review, we investigate the main components implicated in FOS flow and report specific mutations that affect FOS influx inside bacterial cell and, thus, its effectiveness. FosA enzymes were identified in 1980 from Serratia marcescens but only in recent years the scientific community has started studying their spread. We summarize the global epidemiology of FosA/C2/L1-2 enzymes among Enterobacterales family. To date, 11 different variants of FosA have been reported globally. Among acquired mechanisms, FosA3 is the most spread variant in Enterobacterales, followed by FosA7 and FosA5. Based on recently published studies, we clarify and represent the molecular and genetic composition of fosA/C2 genes enviroment, analyzing the mechanisms by which such genes are slowly transmitting in emerging and high-risk clones, such as E. coli ST69 and ST131, and K. pneumoniae ST11. FOS is indicated as first line option against uncomplicated urinary tract infections and shows remarkable qualities in combination with other antibiotics. A rapid and accurate identification of FOSR type in Enterobacterales is difficult to achieve due to the lack of commercial phenotypic susceptibility tests and of rapid systems for MIC detection.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální léková rezistence genetika MeSH
- Escherichia coli genetika MeSH
- fosfomycin * farmakologie MeSH
- Klebsiella pneumoniae genetika MeSH
- proteiny z Escherichia coli * genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Fosfomycin (FOS) has been recently reintroduced into clinical practice, but its effectiveness against multidrug-resistant (MDR) Enterobacterales is reduced due to the emergence of FOS resistance. The copresence of carbapenemases and FOS resistance could drastically limit antibiotic treatment. The aims of this study were (i) to investigate fosfomycin susceptibility profiles among carbapenem-resistant Enterobacterales (CRE) in the Czech Republic, (ii) to characterize the genetic environment of fosA genes among the collection, and (iii) to evaluate the presence of amino acid mutations in proteins involved in FOS resistance mechanisms. During the period from December 2018 to February 2022, 293 CRE isolates were collected from different hospitals in the Czech Republic. FOS MICs were assessed by the agar dilution method (ADM), FosA and FosC2 production was detected by the sodium phosphonoformate (PPF) test, and the presence of fosA-like genes was confirmed by PCR. Whole-genome sequencing was conducted with an Illumina NovaSeq 6000 system on selected strains, and the effect of point mutations in the FOS pathway was predicted using PROVEAN. Of these strains, 29% showed low susceptibility to fosfomycin (MIC, ≥16 μg/mL) by ADM. An NDM-producing Escherichia coli sequence type 648 (ST648) strain harbored a fosA10 gene on an IncK plasmid, while a VIM-producing Citrobacter freundii ST673 strain harbored a new fosA7 variant, designated fosA7.9. Analysis of mutations in the FOS pathway revealed several deleterious mutations occurring in GlpT, UhpT, UhpC, CyaA, and GlpR. Results regarding single substitutions in amino acid sequences highlighted a relationship between ST and specific mutations and an enhanced predisposition for certain STs to develop resistance. This study highlights the occurrence of several FOS resistance mechanisms in different clones spreading in the Czech Republic. IMPORTANCE Antimicrobial resistance (AMR) currently represents a concern for human health, and the reintroduction of antibiotics such as fosfomycin into clinical practice can provide further option in treatment of multidrug-resistant (MDR) bacterial infections. However, there is a global increase of fosfomycin-resistant bacteria, reducing its effectiveness. Considering this increase, it is crucial to monitor the spread of fosfomycin resistance in MDR bacteria in clinical settings and to investigate the resistance mechanism at the molecular level. Our study reports a large variety of fosfomycin resistance mechanisms among carbapenemase-producing Enterobacterales (CRE) in the Czech Republic. Our study summarizes the main achievements of our research on the use of molecular technologies, such as next-generation sequencing (NGS), to describe the heterogeneous mechanisms that reduce fosfomycin effectiveness in CRE. The results suggest that a program for widespread monitoring of fosfomycin resistance and epidemiology fosfomycin-resistant organisms can aide timely implementation of countermeasures to maintain the effectiveness of fosfomycin.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální léková rezistence genetika MeSH
- beta-laktamasy genetika MeSH
- Escherichia coli MeSH
- fosfomycin * farmakologie MeSH
- karbapenemy farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- aminoglykosidy aplikace a dávkování farmakologie MeSH
- bakteriální léková rezistence MeSH
- cystitida epidemiologie farmakoterapie MeSH
- fluorochinolony aplikace a dávkování farmakologie škodlivé účinky MeSH
- fosfomycin aplikace a dávkování farmakologie MeSH
- infekce močového ústrojí * epidemiologie mikrobiologie MeSH
- infekce získané v komunitě * epidemiologie mikrobiologie MeSH
- infekční komplikace v těhotenství farmakoterapie mikrobiologie MeSH
- lidé MeSH
- mužské urogenitální nemoci farmakoterapie mikrobiologie MeSH
- nitrofurantoin aplikace a dávkování farmakologie škodlivé účinky MeSH
- postmenopauza MeSH
- pyelonefritida farmakoterapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- analýza moči MeSH
- antibakteriální látky MeSH
- antiinfekční látky močové MeSH
- bakteriurie farmakoterapie MeSH
- cystitida farmakoterapie MeSH
- dospělí * MeSH
- fluorochinolony terapeutické užití MeSH
- fosfomycin terapeutické užití MeSH
- infekce močového ústrojí * diagnóza klasifikace terapie MeSH
- lidé MeSH
- nitrofurantoin terapeutické užití MeSH
- Check Tag
- dospělí * MeSH
- lidé MeSH
- MeSH
- antibakteriální látky terapeutické užití MeSH
- antibiotická profylaxe MeSH
- dlouhodobá péče MeSH
- Escherichia coli účinky léků MeSH
- fosfomycin * terapeutické užití MeSH
- infekce močového ústrojí * farmakoterapie MeSH
- infekce vyvolané Escherichia coli farmakoterapie MeSH
- lidé MeSH
- recidiva MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Klíčová slova
- Urifos 3g,
- MeSH
- antiinfekční látky močové terapeutické užití MeSH
- fosfomycin terapeutické užití MeSH
- infekce močového ústrojí farmakoterapie mikrobiologie MeSH
- nitrofurantoin terapeutické užití MeSH
- Publikační typ
- novinové články MeSH
BACKGROUND: Against a background of rapid increase of β-lactamase-producing or multi-resistant pathogenic bacteria and the resulting lack of effective antibiotic treatment, some older antibiotics have been tested for new therapeutic uses. One of these is fosfomycin, to which according to studies these resistant bacteria are very sensitive. Our study was designed because there is no data on the fosfomycin susceptibility rate in the Czech Republic. METHOD: In this study from January 2013 to June 2014 3295 unique isolates of Gram-negative bacteria which had caused urinary tract infections were examined. The antibiotic susceptibility was measured by disk diffusion test. Both EUCAST and CLSI guidelines criteria (for fosfomycin only) were used for the antibiotic susceptibility evaluation. RESULTS: The most frequently tested bacterial isolates were Escherichia coli (51.3%, n = 1703), Klebsiella pneumoniae (19.4%, n = 643) and Proteus spp. (11.8%, n = 392). Among all isolates 29.0% (n = 963) were resistant to fluoroquinolones, 11.3% (n = 374) produced extended spectrum β-lactamase and 4.2% (n = 141) produced AmpC β-lactamase. The overall in vitro susceptibility was significantly higher for fosfomycin compared to the other tested per-oral antibiotics (nitrofurantoin, ampicillin, co-trimoxazole, ciprofloxacin and cefuroxime) against all tested Gram-negative rod isolates (excluding Morganella morgani and Acinetobacter spp. isolates). Fosfomycin also remained highly active against those isolates with extended spectrum β-lactamase (ESBL) production (95.8% in Escherichia coli isolates and 85.3% in Klebsiella pneumoniae isolates), unlike other tested per-oral antibiotics, which showed significant (p < 0.0001) susceptibility decrease. CONCLUSION: We have confirmed in the Czech Republic the very high susceptibility to fosfomycin trometamol of urinary tract infection pathogens, particularly Gram-negative rods including those producing β-lactamase.
- MeSH
- antibakteriální látky farmakologie MeSH
- beta-laktamasy MeSH
- fosfomycin farmakologie MeSH
- gramnegativní bakterie účinky léků izolace a purifikace MeSH
- infekce močového ústrojí mikrobiologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
