fosfomycin and Escherichia-coli-Infections

Already used in various countries, trimethoprim (TMP) was withdrawn from the French market in 1990, but should be soon available again. This article reviews the experience of TMP use around the world and its current use in Europe. Label use and guidelines only recommend the use of TMP for the treatment of urinary tract infections (UTI). Compared with co-trimoxazole (Co-T), a combination of TMP and sulfamethoxazole (SMX), TMP has (a) a similar resistance rate among Escherichia coli strains (estimated between 10 and 20% in uncomplicated cystitis), (b) a similar clinical efficacy for cystitis prevention and treatment, (c) a lower toxicity (as severe toxicity adverse effects of Co-T come from its sulfonamide component), (d) limited data for the treatment of pyelonephritis and male UTIs, and (e) an important impact on the microbiota. TMP should thus be indicated in the third-line empirical treatment of acute uncomplicated cystitis (sparing fluoroquinolones and nitrofurantoin), in the prevention of recurrent acute cystitis when an antibiotic prophylaxis is required (possibly in first line), and in the treatment of documented acute cystitis at risk of complications. Updated data on the epidemiology of resistance to TMP per clinical pictures is now required. The bactericidal effect of TMP should also be confirmed on recent strains (although limited recent data suggests a bactericidia similar to that of Co-T) and its clinical efficacy should be evaluated in pyelonephritis and male UTI.

Topics: Anti-Bacterial Agents; Cystitis; Drug Resistance, Bacterial; Drug Utilization; Escherichia coli; Escherichia coli Infections; Fosfomycin; France; Humans; Practice Guidelines as Topic; Product Recalls and Withdrawals; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The continuously increasing problem of multidrug-resistant (extended-spectrum beta-lactamase and/or metallo-beta-lactamase producing) bacteria in recent years has created the need to re-evaluate antibiotic therapy for these infections. Fosfomycin is reconsidered to be an alternative treatment agent for such infections. Fosfomycin was first discovered in Spain in 1969 from cultures of Streptomyces species and originally called phosphonomycin. In the early years, fosfomycin was administered parenterally to the patients with many serious infections including meningitis. In some European countries, fosfomycin is occasionally administered for the initial empirical therapy of sepsis or soft-tissue infections. Although in most European countries fosfomycin has been used for many years, it has become available in clinical use only recently in Turkey. In USA, the Food and Drug Administration (FDA) has approved fosfomycin only for the treatment of patients with uncomplicated cystitis. The use of fosfomycin in the treatment of multidrug-resistant bacterial infections and in the treatment of pediatric cancer patients with fever and neutropenia in combination with other antibiotics, has withdrawn attention to this agent. Fosfomycin has a rapid bactericidal effect and a wide antibacterial spectrum, including methicillin-resistant Staphylococcus aureus, glycopeptide-susceptible or resistant enterococci and a large number of gram-negative pathogens. Since it has a long serum half-life and high concentrations are achieved in urine after oral administration; fosfomycin deserved further consideration for single-dose treatment of urinary tract infections caused by Escherichia coil and Enterococcus faecalis. In this review article the properties, mechanisms of action and resistance, antibacterial spectrum, clinical use, toxicity and adverse reactions of fosfomycin have been summarized.

Topics: Anti-Bacterial Agents; Enterococcus faecalis; Escherichia coli Infections; Fosfomycin; Gram-Positive Bacterial Infections; History, 20th Century; History, 21st Century; Humans; Urinary Tract Infections

Lower urinary tract infection remains frequent particularly in women, despite improvement in therapeutic means. It seems likely to revisit bacterial epidemiology and therapeutic available strategies. To analyze elements in presence i.e. infecting bacteria and antibiotics still active or identification of acquired resistance mechanisms should permit to establish the evolution during the last 10 years. The study shows that bacterial epidemiology in urinary tract infection has not changed significantly, despite antibiotic selective pressure expected from overused antibiotics. However few enterobacteriaceae more resistant than Escherichia coli have emerged, but the latter remains predominant. Development of resistance has concerned Negram, amoxicillin and Augmentin, but several active molecules such as ciprofloxacin, Monuril remain available. Duration of treatments are still discussed but there is a tend toward short durations and even mono-doses. The control of lower urinary tract infections remains relatively easy provided that a good therapeutic choice is based on well documented bacteriologic data (infecting species susceptible to the available antibiotics).

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Proteus Infections; Proteus mirabilis; Time Factors; Urinary Tract Infections

A review on the etiological profile of urinary tract infections in childhood and the sensitivity pattern of urinary pathogens in Spain is presented. Escherichia coli continues to be the main etiological agent of urinary tract infection in childhood. Consequently, its sensitivity pattern will usually determine the choice of empirical therapy. The predominance of E. coli is reduced in certain circumstances, in which the presence of other microorganisms is increased. However, the clinical information available at diagnosis does not allow accurate identification of the etiology; only staining and microscopic urine examination can help in treatment selection. In Spain, E. coli presents a high percentage of resistance to ampicillin and cotrimoxazole, whereas second- and third-generation cephalosporins, fosfomycin, aminoglycosides and amoxicillin-clavulanate maintain high sensitivity. In some areas, amoxicillin-clavulanate and first-generation cephalosporins show high levels of resistance, which can limit their empirical use.

Topics: Adult; Age Factors; Aminoglycosides; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Bacteria; Cephalosporins; Child; Child, Preschool; Clinical Trials as Topic; Consensus Development Conferences as Topic; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Evidence-Based Medicine; Fosfomycin; Hospitalization; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Risk Factors; Spain; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Dialysis; Electrolytes; Escherichia coli Infections; Escherichia coli O157; Fluid Therapy; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Prognosis; Shiga Toxins

Escherichia coli O157:H7 is a foodborne pathogen causing haemorrhagic colitis, which is sometimes complicated by haemolytic uraemic syndrome or thrombotic thrombocytopenic purpura.. To review the available evidence regarding the question of whether antibiotics are effective or harmful for the treatment of patients infected with E. coli O157:H7 infection.. We searched in the PubMed for relevant laboratory and clinical studies published between 1982 and 2005.. In vitro studies have shown that most E. coli O157:H7 isolates are susceptible to various antibiotics, although certain antibiotics, especially at sublethal concentrations, have been found to increase the release of Shiga-like toxins, which have been associated with the development of haemolytic uraemic syndrome/thrombotic thrombocytopenic purpura in humans. No clinical studies have indicated that antibiotics are effective in reducing the duration of E. coli O157:H7 infection or the duration of diarrhoea or bloody diarrhoea specifically, while a few studies have supported that some antibiotics, especially quinolones and fosfomycin, may prevent the development of haemolytic uraemic syndrome or thrombotic thrombocytopenic purpura. On the other hand, there are some clinical studies that associate antibiotics with a higher risk for haemolytic uraemic syndrome and/or longer duration of diarrhoea, even with high mortality.. More randomized controlled trials are necessary in order to elucidate whether antibiotics are effective in reducing the morbidity and mortality of E. coli O157:H7 infection, rather than having a detrimental effect.

Topics: Animals; Anti-Bacterial Agents; Diarrhea; Escherichia coli Infections; Escherichia coli O157; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Purpura, Thrombotic Thrombocytopenic; Quinolones; Shiga Toxins; Treatment Outcome

Verocytotoxin producing Escherichia coli(VTEC) causes gastrointestinal infections worldwide. In at most 8% of the children in Japan who are infected with VTEC, hemolytic-uremic syndrome(HUS) develops soon after the onset of diarrhea. Treatment with antibiotics does not ameliorate VTEC infections, and in some studies from western countries, it has been associated with worse clinical outcomes. It was recently indicated in Japan that early administration of fosfomycin to the patients with VTEC infection can decrease the risk of HUS. Moreover, early administration of Synsorb-Pk with high affinity to verocytotoxin to the patients with gastrointestinal VTEC infection was demonstrated to decrease the incidence of very mild and mild HUS, but it did not decrease the risk of moderate and severe HUS. In the developing stage of HUS, intravenous administration of fluid and electrolytes should be determined cautiously to prevent hyponatremia and systemic congestion.

Topics: Animals; Electrolytes; Escherichia coli Infections; Escherichia coli O157; Fluid Therapy; Fosfomycin; Gastroenteritis; Hemolytic-Uremic Syndrome; Humans; Hyponatremia; Organosilicon Compounds; Risk; Trisaccharides

Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec).. Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders.. Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen.. Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Recurrence; Tromethamine; Urinary Tract Infections

We aimed to determine the noninferiority of fosfomycin compared to ciprofloxacin as an oral step-down treatment for Escherichia coli febrile urinary tract infections (fUTIs) in women.. This was a double-blind, randomized, controlled trial in 15 Dutch hospitals. Adult women who were receiving 2-5 days of empirical intravenous antimicrobials for E. coli fUTI were assigned to step-down treatment with once-daily 3g fosfomycin or twice-daily 0.5g ciprofloxacin for 10 days of total antibiotic treatment. For the primary end point, clinical cure at days 6-10 post-end of treatment (PET), a noninferiority margin of 10% was chosen. The trial was registered on Trialregister.nl (NTR6449).. After enrollment of 97 patients between 2017 and 2020, the trial ended prematurely because of the coronavirus disease 2019 pandemic. The primary end point was met in 36 of 48 patients (75.0%) assigned to fosfomycin and 30 of 46 patients (65.2%) assigned to ciprofloxacin (risk difference [RD], 9.6%; 95% confidence interval [CI]: -8.8% to 28.0%). In patients assigned to fosfomycin and ciprofloxacin, microbiological cure at days 6-10 PET occurred in 29 of 37 (78.4%) and 33 of 35 (94.3%; RD, -16.2%; 95% CI: -32.7 to -0.0%). Any gastrointestinal adverse event was reported in 25 of 48 (52.1%) and 14 of 46 (30.4%) patients (RD, 20.8%; 95% CI: 1.6% to 40.0%), respectively.. Fosfomycin is noninferior to ciprofloxacin as oral step-down treatment for fUTI caused by E. coli in women. Fosfomycin use is associated with more gastrointestinal events.. Trial NL6275 (NTR6449).

Topics: Adult; Anti-Bacterial Agents; Ciprofloxacin; COVID-19; Double-Blind Method; Escherichia coli; Escherichia coli Infections; Female; Fever; Fosfomycin; Humans; Urinary Tract Infections

The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option.. To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli.. This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021.. Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days.. The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered.. Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01).. This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections.. ClinicalTrials.gov Identifier: NCT02142751.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Middle Aged; Spain

Transrectal prostate biopsies carry the risk of infection. By using non-selective culture plates, instead of commonly used ciprofloxacin (CIP)-containing plates, we analyzed the association between Escherichia coli CIP minimal inhibitory concentration (MIC) and post-biopsy infectious complications. A pre-biopsy rectal swab was taken from 207 consecutive men, scheduled for transrectal 12-core prostate biopsy with CIP 750 mg as the mostly used prophylaxis. CIP MIC of rectal Gram-negative bacilli was determined from a chromogenic agar. Rectal E. coli were categorized to resistant (R) and intermediate (I) isolates together (R + I, MIC > 0.25 mg/l) and to sensitive (S, MIC ≤ 0.25 mg/l) using EUCAST clinical breakpoints. In addition, epidemiological cutoff (ECOFF R, MIC > 0.064 mg/l) was used for categorization. Eighteen (8.7%) men showed CIP R + I E. coli by the EUCAST breakpoints and 41 (19.8%) using the ECOFF R criteria. During follow-up, 15 (7.2%) men had infectious symptoms, of which 9 (4.3%) were culture-confirmed infections. Only 4 (26.7%) of these 15 patients showed R + I E. coli in the rectal swab according to EUCAST, but 10 (66.7%) using the ECOFF cutoff. Rectal E. coli CIP R + I by the EUCAST clinical breakpoints associated with infectious complications with OR 5.7 (95% CI 1.5-21.8, P = 0.005) and ECOFF R E. coli by OR 10.7 (95% CI 3.0-37.6, P < 0.001). Men carrying rectal E. coli with moderately lowered CIP susceptibility (MIC > ECOFF 0.064 mg/l) were identified and, interestingly, they showed a high risk of developing infectious symptoms after the biopsy. This explains why some men develop infectious complications despite appropriate antibiotics before prostatic biopsies.. NCT02140502.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Image-Guided Biopsy; Male; Microbial Sensitivity Tests; Middle Aged; Prostate; Rectum

To describe the population pharmacokinetics of fosfomycin for patients with bacteraemic urinary tract infection (BUTI). The analysis identified optimal regimens on the basis of pharmacodynamic targets and assessed the adequacy of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility breakpoints for Escherichia coli.. Data of 16 patients with BUTI caused by multidrug-resistant E. coli (FOREST clinical trial) received intravenous fosfomycin (4 g every 6 hours) were analysed. A population pharmacokinetic analysis was performed, and Monte Carlo simulations were undertaken using 4 g every 6 hours and 8 g every 8 hours. The probability of pharmacodynamic target attainment was assessed using pharmacodynamic targets for E. coli for static effect, 1-log drop in bacterial burden and resistance suppression.. Sixty-four plasma samples were collected over a single dosing interval (day 2 or 3 after starting fosfomycin treatment). Fosfomycin concentrations were highly variable. Pharmacodynamic target attainment analysis showed mild improvement by increasing fosfomycin dosing (4 g every 6 hours vs. every 8 hours). These dosages showed success for decreasing 1-log bacterial burden in 89% to 96% (EUCAST breakpoints) and 33% to 54% (CLSI breakpoints) of patients, but they were unable to reach bacterial resistance suppression targets.. Fosfomycin concentrations are highly variable-a fact partially explained by renal impairment. The present work supports the use of 4 g every 6 hours as an effective regimen for the treatment of non-critically ill patients with BUTI caused by multidrug-resistant E. coli, as higher dosages might increase toxicity but may not significantly increase efficacy. The current information may suggest that fosfomycin susceptibility breakpoints need to be reappraised.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Computer Simulation; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Middle Aged; Models, Biological; Monte Carlo Method; Urinary Tract Infections; Uropathogenic Escherichia coli

Febrile Urinary Tract Infection (FUTI) is frequently treated initially with intravenous antibiotics, followed by oral antibiotics guided by clinical response and bacterial susceptibility patterns. Due to increasing infection rates with multiresistant Enterobacteriaceae, antibiotic options for stepdown treatment decline and patients more frequently require continued intravenous antibiotic treatment for FUTI. Fosfomycin is an antibiotic with high bactericidal activity against Escherichia coli and current resistance rates are low in most countries. Oral Fosfomycin-Trometamol 3000 mg (FT) reaches appropriate antibiotic concentrations in urine and blood and is considered safe. As such, it is a potential alternative for stepdown treatment.. The FORECAST study (Fosfomycin Randomized controlled trial for E.coli urinary tract infections as Alternative Stepdown Treatment) is a randomized, double-blind, double-dummy, non-inferiority trial in which 240 patients will be randomly allocated to a stepdown treatment with FT or ciprofloxacin (standard of care) for FUTI, caused by Escherichia coli with in vitro susceptibility to both antibiotics. The study population consists of consenting female patients (≥18 years) with community acquired E. coli FUTI. After intravenous antibiotic treatment during at least 48 (but less than 120) hours, and if eligibility criteria for iv-oral switch are met, patients receive either FT (3 g every 24 h) or ciprofloxacin (500 mg every 12 h) for a total antibiotic duration of 10 days. The primary endpoint is clinical cure (resolution of symptoms) 6-10 days post-treatment. Secondary endpoints are microbiological cure 6-10 days post-treatment, clinical cure, mortality, ICU admittance, relapse, reinfection, readmission, additional antibiotic use for UTI, early study discontinuation, adverse events, days of hospitalization and days of absenteeism within 30-35 days post-treatment. The sample size is based on achieving non-inferiority on the primary endpoint, applying a non-inferiority margin of 10%, a two-sided p-value of < 0.05 and a power of 80%.. The study aims to demonstrate non-inferiority of oral fosfomycin, compared to oral ciprofloxacin, in the stepdown treatment of E. coli FUTI.. Registered at the Nederlands trial register (Dutch trial register) on 4-10-2017.. NTR6449 . Secondary ID (national authority): NL60186.041.17.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ciprofloxacin; Double-Blind Method; Equivalence Trials as Topic; Escherichia coli; Escherichia coli Infections; Female; Fever; Fosfomycin; Humans; Middle Aged; Placebos; Urinary Tract Infections; Young Adult

Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future.. The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli.. Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals.. This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy.. NCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014.

Topics: Administration, Intravenous; Anti-Bacterial Agents; beta-Lactamases; Clinical Protocols; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Gastrointestinal Microbiome; Gram-Negative Bacteria; Humans; Intestines; Meropenem; Research Design; Thienamycins; Urinary Tract Infections

Fosfomycin calcium is a fosfomycin antimicrobial agent with a characteristic structure. After oral administration, the drug is absorbed and excreted via the kidneys in the unchanged form, without being metabolized in the body. It is, therefore, indicated for the treatment of urinary tract diseases, including cystitis and pyelonephritis. In the present study, the clinical usefulness of fosfomycin calcium (FOSMICIN® TABLETS 500) administered orally at the dosage of 1 g (two tablets) three times daily for 2 days was examined in female patients, who were at least 20 years of age, with acute uncomplicated cystitis of bacterial origin. Of the 48 patients enrolled between February 2008 and August 2008, 39 were evaluable for efficacy and safety. Overall evaluation of the cure revealed that microbiological eradication rate (microbiological outcome) and clinical efficacy rate (clinical outcome) at 5-9 days after drug administration (visit 2) were 94.9%. Determination of the microbiological and clinical outcomes for the evaluation of recurrence at 4-6 weeks after drug administration (visit 3) were 75.8 and 85.7%, respectively. Of the 48 patients, 40 (83.3%) returned to the clinic at visit 3. The causative bacterial species for cystitis was Escherichia coli in 31 (79.5%) of the 39 patients evaluable for efficacy and safety. Adverse drug reactions observed during the administration and follow-up periods included mild diarrhea and loose stools in 1 patient each, neither requiring any specific treatment. Evaluation of cure at visit 2 in patients in whom the causative bacterial species for the infection was E. coli revealed a microbiological outcome of 93.5%, and clinical outcome was 96.8%. Furthermore, evaluation for recurrence at visit 3 revealed a microbiological outcome of 74.1% and clinical outcome of 82.1%. When the patients were divided by age into an under 60 years of age group and an over 60 years of age group, the microbiological and clinical outcomes determined for evaluation of cure at visit 2 were 96.4 and 92.9%, respectively, and the corresponding rates determined for the evaluation of recurrence at visit 3 were 87.0 and 96.0%, respectively, in the under 60 years of age group. In the over 60 years of age group, the corresponding microbiological outcome and clinical outcome rates evaluated for cure were 90.9 and 100%, respectively, and those evaluated for recurrence were 50.0 and 60.0%, respectively. These results indicate the usefulness of fosfomycin calciu

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Cystitis; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Microbial Sensitivity Tests; Middle Aged; Treatment Outcome; Urinary Tract Infections

Uncomplicated lower urinary tract infections (UTIs) are the most frequent infections in females. Increased resistance rates against commonly used antibiotics have led to the use of novel antimicrobials. The aim of the present study was to evaluate the bacteriological and clinical effects of single-dose fosfomycin trometamol (FMT) and 5-day ciprofloxacin in females with uncomplicated UTIs. In this randomized comparative study, 260 female patients between 18 and 65 years of age enrolled, of whom 142 completed the study. The most frequently isolated bacterial pathogen in the urine cultures of patients were Escherichia coli (82.3%) and Enterobacter spp. (8.4%). FMT sensitivity was 94% and ciprofloxacin sensitivity was 59% in Escherichia coli; in comparison, FMT sensitivity was 75% and ciprofloxacin sensitivity was 50% in Enterobacter spp. The MIC90 for FMT was 4 μg/ml. Of the 142 patients, 77 were treated with FMT and 65 were treated with ciprofloxacin. The clinical remission rate was 83% in the FMT group and 81% in the ciprofloxacin group; the bacterial eradication rate was 83% in the FMT group and 78% in the ciprofloxacin group, and there was no significant difference between the two study groups. In conclusion, a single dose of FMT (at 3 g) was as effective as ciprofloxacin, at 500 mg twice a day for 5 days, in the treatment of uncomplicated lower UTIs. It was concluded that the use of FMT as a first-line treatment in the empirical treatment of uncomplicated UTIs might have a positive impact on the problem of resistance to other antibiotics.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Ciprofloxacin; Drug Administration Schedule; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Microbial Sensitivity Tests; Middle Aged; Treatment Outcome; Urinary Tract Infections; Urine; Young Adult

The objective of this study was to determine, in broilers, which modality of disodium fosfomycin (DF) administration and at what dose the best pharmacokinetic (PK) profile could be obtained, taking as reference a 110 field bacterial strains of Escherichia coli minimum inhibitory concentration survey. The DF was administered via drinking water either ad libitum or at a higher concentration having 1 h of water restriction to build up thirst in the birds (loading dose). Dosages tested were 10, 20, 40, and 80 mg/kg per administration, either once or twice daily. Birds included were 24-d-old Cornish broilers randomly assigned to 16 groups of 200 birds per group and 3 replicates per group. The PK of DF was determined after ad libitum administration of either a single- or double-loading dose or after an initial loading dose followed by ad libitum medication. Also, PK after i.v. administration was studied in separate groups. Serial blood samplings were performed in all groups. Serum obtained was analyzed for DF and a possible active metabolite by means of a microbiological agar diffusion assay. The DF showed a short elimination half-life (approximately 2 h after oral loading administration) with a rapid clearance (1.23 to 1.42 mL/kg per h). Apparent volume of distribution-area under the curve values were also low (10 and 80 mg/kg=0.25 L/kg and 0.22 L/kg, respectively). Considering a minimum inhibitory concentration level that inhibited 90% of total strains of 8 µg/mL for E. coli, it is concluded that single-loading administration at 10, 20, 40, and 80 mg/kg complies poorly with sustained serum concentrations over a dosing interval of 24 h. Doses of 10 and 20 mg/kg twice a day also were insufficient to attain therapeutic concentrations. Useful serum concentrations of DF to treat outbreaks of susceptible E. coli require an initial loading dose of 40 mg/kg, followed by an ad libitum medication of 40 mg/kg 8 h later (80 mg/kg per d).

Topics: Animals; Area Under Curve; Chickens; Dose-Response Relationship, Drug; Escherichia coli; Escherichia coli Infections; Fosfomycin; Half-Life; Microbial Sensitivity Tests; Poultry Diseases; Protein Binding; Time Factors

Untreated asymptomatic bacteriuria has been associated with acute pyelonephritis, which may have a role in many maternal and fetal complications. Acute pyelonephritis in pregnancy is related to anemia, septicemia, transient renal dysfunction, and pulmonary insufficiency. A randomized study was conducted to assess the clinical and microbiological efficacy of a single dose of fosfomycin trometamol for the treatment of asymptomatic bacteriuria in the second trimester of pregnancy compared with a 5-day regimen of cefuroxime axetyl. Forty-four women received fosfomycin trometamol and 40 women received cefuroxime axetyl. There were no statistically significant differences between both groups regarding the mean age and mean duration of pregnancy. Therapeutic success was achieved in 93.2% of the patients treated with fosfomycin trometamol vs 95% of those treated with cefuroxime axetyl. A single dose of fosfomycin trometamol is a safe and effective alternative in the treatment of asymptomatic urinary tract infections in the second trimester of pregnancy.

Topics: Adult; Age Factors; Anti-Bacterial Agents; Bacteriuria; Cefuroxime; Drug Administration Schedule; Escherichia coli Infections; Female; Fosfomycin; Humans; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Second; Safety; Single-Blind Method; Treatment Outcome

Two trials were made to assess the efficacy of including calcium fosfomycin in the drinking water or in the feed for four days to control the adverse effects of experimentally induced colibacillosis in broiler chickens. Trial 1 had five groups of 15 chicks each: one group of negative controls; an untreated infected control group and three groups treated with 50, 100 or 200 ppm of calcium fosfomycin in drinking water. Trial 2 had the same groups but the antibiotic was incorporated into the feed. The chickens were infected via their air sacs with 1.7 x 10(8) - 3.6 x 10(8) CFU/chick of Escherichia coli O78:K80. The morbidity and mortality, a score for the gross lesions, the relative weight of the liver and spleen, performance and re-isolation of the challenge bacteria were recorded. Calcium fosfomycin in the drinking water controlled the colibacillosis, particularly in the group treated with 200 ppm. However, no effect of the antibiotic was seen when calcium fosfomycin was incorporated into the feed, the mortality, score of lesions and re-isolation of E. coli from the organs in the three treated groups being similar to those for the infected unmedicated group. The amount of antibiotic ingested in trial I was three times more than in trial 2. These results suggest that calcium fosfomycin is best used in the drinking water for the treatment of colibacillosis.

Topics: Administration, Oral; Animal Feed; Animals; Anti-Bacterial Agents; Body Weight; Chickens; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Liver; Male; Myocardium; Poultry Diseases; Survival Rate; Water

To clarify the effect of early fosfomycin treatment, an antimicrobial agent in common use in Japan, on children with E. coli O157 with the aim of preventing hemolytic uremic syndrome (HUS).. Non-randomized prospective study for development of HUS among inpatients with E. coli O157.. The hospitals where the 292 inpatients were treated.. A total of 292 inpatients aged six to eleven years with E. coli O157 infection, 36 (12.3%) of whom were HUS cases.. Most of the HUS inpatients (91.7%) developed this complication between the sixth and ninth day of illness. We therefore analyzed the effects of antimicrobial therapy, especially that of fosfomycin, on prevention of HUS within the first five days of illness, because fosfomycin was the most frequently used (88.0%). To clarify the effect of fosfomycin alone on prevention of HUS, we carried out an analysis using the data for 130 inpatients who received fosfomycin alone or did not receive any antimicrobial agents, within the first five days of illness. multivariate analysis, controlled for age, gender and presence of fever, showed that all adjusted odds ratios for the development of HUS with the use of fosfomycin within the first three days of illness were less than 1.0, with the use of fosfomycin on the second day of illness achieving statistical significance (adjusted OR, 0.09; 95% CI, 0.01-0.79). Furthermore, inpatients who took fosfomycin within the first two days of illness developed HUS significantly less often than those who did not (adjusted OR, 0.15; 95% CI, 0.03-0.78). On the other hand, fosfomycin therapy on and after the third day of illness was not associated with the prevention of HUS.. The early use of fosfomycin within the first two days of illness might prevent the development of HUS.

Topics: Anti-Bacterial Agents; Child; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Male; Prospective Studies

This study is a comparison of the microbiological and clinical efficacy of single-dose fosfomycin trometamol therapy and a 5 day course of trimethoprim in the treatment of uncomplicated urinary tract infection in female patients. Urine dip-slide samples were obtained from 547 female patients aged 18-65 by 22 General Practitioners (GPs) participating in the study from 21 centres in the UK. All patients were diagnosed as having a urinary tract infection by their GP on the basis of history and clinical examination. Patients were randomised to receive either single dose fosfomycin trometamol or a 5 day course of trimethoprim in a 2:1 ratio. Patients who had significant bacteriuria (> or = 10(5) c.f.u/ml) at the first visit (300) were included in the microbiological analysis. The two commonest urinary pathogens isolated were Escherichia coli and Staphylococcus saprophyticus. Trimethoprim resistance was more frequent amongst E. coli isolates whereas fosfomycin trometamol resistance was more common amongst S. saprophyticus isolates. Microbiological cure was demonstrated in 83.3% of the trimethoprim treated group and 83% of the fosfomycin trometamol treated group. Persistence of the infecting bacteria was seen in 17% of each treatment arm.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Citrobacter; Drug Administration Schedule; Enterococcus faecalis; Escherichia coli; Escherichia coli Infections; Family Practice; Female; Fosfomycin; Humans; Klebsiella; Microbial Sensitivity Tests; Middle Aged; Proteus mirabilis; Staphylococcal Infections; Staphylococcus; Trimethoprim; United Kingdom; Urinary Tract Infections

Topics: Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Escherichia coli Infections; Female; Fosfomycin; Humans; Infant; Male; Netilmicin; Random Allocation; Urinary Tract Infections

Single-dose therapy of uncomplicated urinary tract infection (UTI) has been shown to be effective in many trials in adult women. The question which will be explored in this presentation is what properties constitute the ideal agent for the therapy of UTI. Important microbiological properties include spectrum of activity to include all common urinary pathogens, bactericidal action in urine and low prevalence of resistant bacteria. The vital feature of an antibacterial drug useful in the therapy of UTI is prolonged urinary concentrations. The agent must therefore be well absorbed and have slow renal excretion. Most beta-lactam drugs do not have these combined properties. Aminoglycosides are effective drugs but cannot be administered orally. Quinolones and the calcium salt of fosfomycin are useful but do not have an ideal pharmacokinetic profile. Cotrimoxazole, trimethoprim alone and the trometamol salt of fosfomycin all have good antibacterial activity combined with slow urinary excretion.

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Clinical Trials as Topic; Drug Combinations; Escherichia coli Infections; Fosfomycin; Humans; Kinetics; Lactams; Microbial Sensitivity Tests; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Forty-two infants, some premature, with enteropathogenic Esch. coli (EPEC) gastroenteritis were treated with an oral suspension of fosfomycin in a dose of 100 and 200 mg/kg per day. After the treatment there were 11 secondary clinical infections (6 reinfections and 5 relapses) which received a second treatment with fosfomycin. In total, 53 treatments were made with fosfomycin and in 92% of the cases there was both clinical and bacteriological cure. 93% of the EPEC strains were sensitive to fosfomycin in vitro, their minimum inhibitory concentrations being less than 64 mug/ml. The concentration of fosfomycin in blood and faeces was assayed by a diffusion plate microbiological method in a group of these children, showing that this antibiotic is partly absorbed and the rest eliminated in the faeces, where its concentration was found to be very high. Tolerance of the product was good, and there were neither toxic nor side effects.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Escherichia coli Infections; Feces; Female; Fosfomycin; Gastroenteritis; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Intestinal Absorption; Male; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

A rapid (<3 hours) and reliable multiplex PCR was developed for detecting simultaneously known plasmid-mediated fos genes conferring acquired resistance to fosfomycin. Our technique was tested on a collection of Escherichia coli isolates previously identified as bearing the fosA-, fosC- and fosL-like genes, showing a sensitivity and a specificity of 100%.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Multiplex Polymerase Chain Reaction; Plasmids

Fosfomycin is used to treat a variety of bacterial infections, including urinary tract infections caused by Escherichia coli. In recent years, quinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing bacteria have been increasing. Because fosfomycin is effective against many of these drug-resistant bacteria, the clinical importance of fosfomycin is increasing. Against this background, information on the mechanisms of resistance and the antimicrobial activity of this drug is desired to enhance the usefulness of fosfomycin therapy. In this study, we aimed to explore novel factors affecting the antimicrobial activity of fosfomycin. Here, we found that

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Urinary Tract Infections

There are few epidemiological or molecular data on Escherichia coli (E. coli) strains resistant to fosfomycin. In this study, we described the occurrence and characterization of fosfomycin-resistant uropathogenic E. coli (UPEC) isolated from children.. This study was carried out on 96 E. coli isolates obtained from children with urinary tract infections. Two methods were performed to detect fosfomycin resistance: The agar dilution method and the rapid fosfomycin test. The disc diffusion method was done to detect the antimicrobial susceptibility pattern of all isolates. The phylogenetic grouping of all isolates was done according to the modified Clermont method. Conventional PCR was performed to detect plasmid-mediated fosfomycin-resistant genes (fos genes) and the bla. Analyses of data were performed by SPSS software. A high percentage of fosfomycin resistance (37/96; 38.5%) was reported among UPEC isolates. The fosfomycin-resistant strains showed a higher resistance rate than fosfomycin-susceptible isolates to different antibiotics. E group (62.2%) was the most predominant phylogenetic group among the fosfomycin-resistant UPEC isolates, followed by Group B2 (21.6%) and group D (13.5%). The fos genes were detected in 21 isolates with the fosA3 gene as the most frequent, which was detected in 11 isolates followed by fosA (8), fosC2 (4), fosA4(1), and fosA5(1) genes.. This is the first report of a high prevalence of plasmid-mediated fosfomycin-resistant UPEC in Egypt. All of these isolates were multidrug-resistant to the tested antibiotics. Close monitoring of such strains is mandatory to prevent widespread dissemination of the genes code for antibiotic resistance.

Topics: Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Escherichia coli Infections; Fosfomycin; Humans; Incidence; Microbial Sensitivity Tests; Phylogeny; Urinary Tract Infections; Uropathogenic Escherichia coli

Escherichia coli ST131 clone was first reported in 2008 and defined as a 'high-risk pandemic clone'. This clone plays a critical role in the spread of antimicrobial resistance worldwide. It was reported in many studies that the E.coli ST131 clone is widespread worldwide and can carry virulence and antibiotic resistance genes. E.coli ST131 clone is associated with a fluoroquinolone and broad-spectrum cephalosporin resistance. The agents used in the treatment of infections caused by the E.coli ST131 clone are limited. For this reason, monitoring the resistance status of these limited agents is crucial. In this study, we aimed to investigate the prevalence of the O25b-ST131 clone, and the presence of carbapenem and fosfomycin resistance genes in fluoroquinolone-resistant E.coli isolates isolated from mid-stream urine samples. For the detection of the O25b-ST131 clone in fluoroquinolone-resistant E.coli isolates, amplification was performed with primers O25pabBspe-F and O25pabBspe-R. For the determination of resistance genes, carbapenem resistance genes blaNDM, blaVIM, blaKPC, blaIMP, and blaOXA-48 in carbapenem resistant isolates and plasmid-mediated fosfomycin resistance genes fosA3 and fosC2 in fosfomycin resistant isolates were investigated by multiplex PCR method. According to PCR results, the prevalence of E.coli O25b-ST131 isolates was 51.2%. Carbapenem resistance rate was 3.41%, and fosfomycin resistance rate was 3.41% in fluoroquinolone-resistant E.coli isolates. Carbapenem and fosfomycin resistance rates in E.coli O25bST131 isolates were determined as 0.83% and 2.5%, respectively. At least one of the carbapenem-resistance genes (blaNDM and/or blaOXA-48) was detected in six of the eight carbapenem-resistant isolates. Fosfomycin resistance gene fosA3 was seen in four of eight fosfomycin-resistant isolates. fosC2 gene was not detected in any of the isolates. In addition, the plasmid-mediated fosfomycin resistance gene fosA3 was detected in an E.coli O25b-ST131 isolate, and this result was confirmed by sequence analysis. To the best of our knowledge, this is the second report about fosA3 positivity in E.coli ST131 isolates from the world and the first reported from Europe and Türkiye. As a result, approximately half of the fluoroquinolone-resistant E.coli isolates were identified as E.coli ST131 clones. Despite the high rate of this clone, the carbapenem and fosfomycin resistance rates are still relatively low, which is pleasing for the future of treatm

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Clone Cells; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; Humans; Microbial Sensitivity Tests

To evaluate the occurrence of plasmid-mediated fos genes among fosfomycin-resistant Escherichia coli isolates collected from patients in Lisbon, Portugal, and characterize the fos-positive strains.. A total of 19 186 E. coli isolates were prospectively collected between April 2022 and January 2023 from inpatients and outpatients at a private laboratory in Lisbon. Fosfomycin resistance was initially assessed by semi-automated systems and further confirmed by the disc diffusion method. Resistant isolates were investigated for plasmid-mediated fos genes (fosA1-fosA10, fosC and fosL1-fosL2) and extended-spectrum beta-lactamases (ESBLs) by PCR and sequencing. Multilocus sequence typing was performed to evaluate the clonal relationship among fos-carrying isolates.. Out of the 19 186 E. coli isolates, 100 were fosfomycin-resistant (0.5%), out of which 15 carried a fosA-like gene (15%). The most prevalent fosfomycin-resistant determinant was fosA3 (n = 11), followed by fosA4 (n = 4). Among the 15 FosA-producing isolates, 10 co-produced an ESBL (67%), being either of CTX-M-15 (n = 8) or CTX-M-14 (n = 2) types. The fosA3 gene was carried on IncFIIA-, IncFIB-, and IncY-type plasmids, whereas fosA4 was always located on IncFIB-type plasmids. Most FosA4-producing isolates belonged to a single sequence type ST2161, whereas isolates carrying the fosA3 gene were distributed into nine distinct genetic backgrounds.. The prevalence of fosfomycin-resistant E. coli isolates is still low in Portugal. Notably, 15% of fosfomycin-resistant isolates harbour a transferable fosA gene, among which there is a high rate of ESBL producers, turning traditional empirical therapeutical options used in Portugal (fosfomycin and amoxicillin-clavulanic acid) ineffective.

Topics: Anti-Bacterial Agents; beta-Lactamases; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genes, fos; Humans; Plasmids; Portugal

Fosfomycin is a first-line treatment for uncomplicated urinary tract infections (UTIs) in several European countries, and it is increasingly becoming the treatment of choice globally. Resistance to fosfomycin in Escherichia coli can be exerted through several mechanisms, including the acquisition of fosfomycin-modifying enzymes, of which the FosA-type enzymes are the most common. This study analysed, both phenotypically and genotypically, an international collection of E. coli strains harbouring acquired fosA genes.. Thirty-one fosA-positive E. coli isolates were obtained from both clinical and environmental sources, from seven countries (Portugal (n = 12), Switzerland (n = 9), China (n = 3), France (n = 2), Nepal (n = 2), South Africa (n = 2), Kuwait (n = 1)). MICs were determined according to EUCAST guidelines. Whole genome sequencing (WGS) was performed on 23 isolates, and complete fosA plasmid sequences were determined for 12. Conjugation assays were performed on seven isolates.. All isolates exhibited high-level resistance to fosfomycin (64 to >256 mg/L). WGS of 23 isolates identified 17 sequence types (STs), and 16 harboured fosA3, four fosA4, two fosA8, and one fosA10. ESBLs, pAmpC, or carbapenemase genes were present in 15, four, and three isolates, respectively. The fosA plasmids of 12 isolates were determined and were diverse in size (∼67 kb to ∼235 kb), resistance gene carriage, and replicon types. Six fosA plasmids additionally carried ESBL or carbapenemase genes. Conjugation assays, performed on seven isolates harbouring diverse plasmids, identified that all were capable of being transmitted.. This study highlights the necessity of the surveillance and close monitoring of fosfomycin resistance in E. coli, essential to maintain the optimal use of this treatment option.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Plasmids

The aim of this study was to determine the in-vitro activity of fosfomycin against

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cross Infection; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Salvage Therapy; Urinary Tract Infections

The increasing number of globally established fosfomycin-resistant (Fos. Besides ten non-E. coli Enterobacterales, 29 E. coli were collected within this study. In silico-based subtyping revealed that E. coli isolates were assigned to six different serovars and 14 sequence types (ST), while O8:H21 and ST410 represented the major prevalent types, respectively. Fosfomycin resistance in the isolates was found to be mediated by the fosA4 (n = 18), fosA3 (n = 10) and fosA (n = 1), which are frequently associated with transmissible MGEs. Reconstruction of plasmid-associated fosA gene context revealed a linkage between the resistance cassette and IS6 (IS26 family) transposases, which might represent a major driver for the distribution of the genes and the generation of novel fosA-carrying plasmids.. The occurrence of plasmid-mediated, transmissible Fos

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Hospitals; Interspersed Repetitive Sequences; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Turkey; Wastewater

Urinary tract infections (UTIs) are prevalent worldwide, particularly among women. Their incidence increases with age, and treatment is increasingly challenging owing to antibiotic resistance and the lack of new agents. We investigated the susceptibility of current urinary isolates to fosfomycin and other antibiotics across Europe. This cross-sectional study collected consecutive urinary isolates from non-hospitalised women at 20 centres in Belgium, the UK, Italy, Spain and Russia. Bacteria were tested by disk diffusion with relevant antibiotics. As a quality control, a central laboratory re-tested, by agar dilution, (i) isolates found resistant to fosfomycin and (ii) every tenth isolate; all non-Russian sites were included. A total of 2848 isolates were analysed, principally Escherichia coli (2064; 72.5%), Klebsiella spp. (275; 9.7%) and Proteus spp. (103; 3.6%). For E. coli, agents active against >90% of isolates were nitrofurantoin (98.5%), fosfomycin (96.4%) and mecillinam (91.8%). Fosfomycin and nitrofurantoin remained active against >90% of cephalosporin-resistant E. coli. Among 143 E. coli recorded as susceptible locally by disk tests, 138 (96.5%) were confirmed susceptible by minimum inhibitory concentration (MIC) tests, however resistance was only confirmed in 29/58 (50.0%) of those reported resistant by local disk tests. Escherichia coli was found to be the most common uropathogen isolated and was highly susceptible to fosfomycin, nitrofurantoin and mecillinam, all used effectively for more than 30 years. Guidelines advocating fosfomycin for uncomplicated UTIs in women remain microbiologically valid.

Topics: Amdinocillin; Anti-Bacterial Agents; Cross-Sectional Studies; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Nitrofurantoin; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests

Plasmid-mediated colistin resistance genes, especially mcr-3 combined with the fosfomycin resistance gene fosA3, are a grave health concern. Our study was designed to determine the epidemiological characteristics of the combination of mcr-3 and fosA3 in Anhui province, China.. A total of 127 multi-drug-resistant (MDR) E. coli strains were assessed for antibiotic resistance/sensitivity to detect mcr-3 and fosA3 using polymerase chain reaction (PCR) and sequencing. The genes of interest were conjugated using EC600, and replicon and sequence types (STs) were identified by PCR-based replicon typing (PBRT) and multilocus sequence typing (MLST). Cluster similarity and genomic relatedness among the positive isolates were confirmed by Xbal PFGE.. The processed E. coli isolates were highly resistant to the tested antibiotics; the prevalence of mcr-3 was 0.78% in the transferable IncP-type plasmid in ST131, whereas fosA3 prevalence was 38.58% among different transferable plasmids, including IncFIIK, IncFII and IncA/C, and in various STs including ST69, ST1193, ST12, ST46, ST57, ST1196, ST38, ST95, ST131, ST7584 and ST10184. Both were successfully transferred to EC600. The Xbal PFGE cluster exposed similarities among the STs.. Our results show that to control the spread of colistin and fosfomycin resistance genes in human pathogens, the ban on colistin must be continued in animal feeding farms not only in China but around the world; additionally, awareness platforms on the use of colistin must be implemented and strict policies in poultry and pig farms must be maintained. Furthermore, fosfomycin misuse by patients and overuse by physicians must be strictly managed to stop the spread of fosfomycin resistance.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Colistin; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Swine

Topics: Anti-Bacterial Agents; beta-Lactamases; Biofilms; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Nitrofurantoin; Penicillins

BackgroundEvidence on the distribution of bacteria and therapy recommendations in male outpatients with urinary tract infections (UTI) remains insufficient.AimWe aimed to report frequency distributions and antimicrobial resistance (AMR) of bacteria causing UTI in men and to identify risk factors for resistance of

Topics: Adult; Aged, 80 and over; Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Laboratories; Male; Microbial Sensitivity Tests; Nitrofurantoin; Outpatients; Proteus mirabilis; Urinary Tract Infections

Antimicrobial resistance is a public health burden with worldwide impacts and was recently identified as one of the major causes of death in 2019. Fosfomycin is an antibiotic commonly used to treat urinary tract infections, and resistance to it in Enterobacteriaceae is mainly due to the metalloenzyme FosA3 encoded by the fosA3 gene. In this work, we adapted a CRISPR-Cas9 system named pRE-FOSA3 to restore the sensitivity of a fosA3+ Escherichia coli strain. The fosA3+ E. coli strain was generated by transforming synthetic fosA3 into a nonpathogenic E. coli TOP10. To mediate the fosA3 disruption, two guide RNAs (gRNAs) were selected that used conserved regions within the fosA3 sequence of more than 700 fosA3+ E. coli isolates, and the resensitization plasmid pRE-FOSA3 was assembled by cloning the gRNA into pCas9. gRNA_195 exhibited 100% efficiency in resensitizing the bacteria to fosfomycin. Additionally, the edited strain lost the ampicillin resistance encoded in the same plasmid containing the synthetic fosA3 gene, despite not being the CRISPR-Cas9 target, indicating plasmid clearance. The in vitro analysis presented here points to a path that can be explored to assist the development of effective alternative methods of treatment against fosA3+ bacteria.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Plasmids; RNA, Guide, Kinetoplastida

Endocarditis due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a rare but challenging condition. Its treatment relies on carbapenems alone or in combination, and no alternative has been described to date. The cephamycin cefoxitin has been used for treatment of mild ESBL-producing Enterobacteriaceae infections.. We report two patients with nosocomial endocarditis due to ESBL-producing Escherichia coli and Klebsiella pneumoniae who underwent clinical failure or adverse event, respectively, during treatment with imipenem-cilastatin. The first patient was subsequently treated with cefoxitin combined with ciprofloxacin with a favorable outcome. In the second patient, the endocarditis relapsed following a 6-week treatment with cefoxitin and fosfomycin. In time-kill assays, the cefoxitin/ciprofloxacin and cefoxitin/fosfomycin combinations showed synergistic effect.. These cases illustrate that cefoxitin is an interesting alternative to carbapenems, even in severe infections such as endocarditis. Pharmacokinetic optimization and combination with another synergistic antibiotic should be considered whenever possible.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefoxitin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Endocarditis; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

Fosfomycin has become a therapeutic option in urinary tract infections. Our objective was to evaluate the in vitro activity of fosfomycin against Escherichia coli isolated from urine samples in 2013, 2018 and 2021. We also determined a putative association between fosfomycin resistance and extended-spectrum β-lactamases (ESBL) production. Fosfomycin activity was evaluated against 7367, 8128 and 5072 Escherichia coli urinary isolates in 2013, 2018 and 2021, respectively. We compare the prevalence of fosfomycin-resistant strains among the ESBL- and non-ESBL-producing isolates. MICs of fosfomycin, cefotaxime, and cefotaxime-clavulanate were determined by a microdilution method. 302 ESBL-producers were selected to determine MICs of fosfomycin by agar dilution and genes encoding ESBLs were detected by PCR. Among the total of ESBL-producing strains, 14.3%, 20.8% and 20% were resistant to fosfomycin in 2013, 2018 and 2021, respectively, whereas fosfomycin resistance in non-ESBL producers was 3.5%, 4.05% and 5.53% for each year (P ≤ 0.001). In the 302 selected ESBL-producing isolates, CTX-M was the main ESBL (228 isolates), being 50.7% CTX-M-15. Resistance to fosfomycin among these ESBL-producing strains was associated (P = 0.049) with isolates that produced the CTX-M type. Our data show that fosfomycin resistance is increasing in Escherichia coli urinary isolates and it is related to ESBL-production. A follow-up of fosfomycin resistance is required.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

Urinary tract infection is among the greatest prevalent infections, and it is also one of the most challenging diseases to treat because there are germs that are resistant to several drugs. Antibiotics are typically provided as the treatment; however, there is a disparity in the type of antibiotic that was being prescribed, the amount of the dosage, and the length of time that patients were required to take antibiotics, which led to the creation of multidrug-resistant infections. The objective of this research is to prescribe Fosfomycin treatment for the infection brought by the Escherichia coli bacterium and to determine whether or not it is effective. Throughout the course of this research, the antimicrobial drugs fosfomycin were factored in the equation at various points. The patients who had exhibited symptoms of urinary tract infection provided their urine for the purpose of giving a sample for the studies, which were carried out on them. The results of these studies showed that there were Fosfomycin antimicrobials that were successful in disrupting the E. coli bacteria, and the least inhibitory concentration (MIC) required for the pathogen to be vulnerable was quite low. In addition, administration of fosfomycin intravenously considerably lowers both the bacterial load and the inflammatory infiltration in the kidney and bladder, which helps to preserve the structural integrity of the kidney.

Topics: Anti-Bacterial Agents; Apoptosis; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Necrosis; Urinary Tract Infections

Fosfomycin is an important broad-spectrum bactericidal antibiotic to treat multidrug-resistant bacteria infections. It is generally accepted that heteroresistant bacteria are an intermediate stage in the formation of drug resistance, but there are few studies on the formation mechanism underlying fosfomycin heteroresistance (FHR).. To reveal the characteristics and formation mechanisms of FHR in Escherichia coli isolates obtained from chickens.. We identified the FHR according to the population analysis profile (PAP) test and in vitro time-kill assay. Growth curves for FHR E. coli and their subpopulations were measured. Also, the subpopulations were repeatedly cultured in fosfomycin-free medium for 5-20 overnight incubation periods. The formation mechanisms of FHR in E. coli isolates were identified through accumulation assay, carbohydrate utilization testing, real-time relative quantitative PCR analysis, DNA sequencing, transcriptomic analysis, intracellular ATP and cAMP-level assessment.. Four of six E. coli strains were confirmed to show FHR, with a total of six subpopulations. The subpopulations restored phenotypic susceptibilities to fosfomycin within 5-20 overnight incubation sessions, but four of six subpopulations still maintained FHR characteristics. Differing from their parental isolates, the uptake of fosfomycin in the subpopulations through GlpT was reduced remarkably. Further studies identified that the low expression of glpT was due to the decrease of intracellular cAMP levels in the subpopulations, which was caused by the decreased ATP levels in cells.. Our findings revealed the formation mechanism of E. coli isolates showing FHR obtained from chicken in China and characterized the dynamic change traits in vitro of the subpopulations.

Topics: Adenosine Triphosphate; Animals; Anti-Bacterial Agents; Chickens; Cyclic AMP; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Microbial Sensitivity Tests

To reach their target site inside Gram-negative bacteria, almost all antibiotics need to cross the outer membrane. Computational modeling of such processes can be numerically demanding due to the size of the systems and especially due to the timescales involved. Recently, a hybrid Brownian and molecular dynamics approach, i.e., Brownian dynamics including explicit atoms (BRODEA), has been developed and evaluated for studying the transport of monoatomic ions through membrane channels. Later on, this numerically efficient scheme has been applied to determine the free energy surfaces of the ciprofloxacin and enrofloxacin translocation through the porin OmpC using temperature-accelerated simulations. To improve the usability and accuracy of the approach, schemes to approximate the position-dependent diffusion constant of the molecule while traversing the pore had to be established. To this end, we have studied the translocation of the charged phosphonic acid antibiotic fosfomycin through the porin OmpF from

Topics: Anti-Bacterial Agents; Cell Membrane Permeability; Diffusion; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Kinetics; Models, Molecular; Mutation; Porins; Protein Conformation; Thermodynamics

The aim of this this study was to describe the presence of different variants of the fosA gene in fosfomycin-resistant Escherichia coli strains in Madrid, Spain.. fos genes were searched for in 55 E. coli strains collected from seven representative hospitals located in Madrid. A phenotypic screening test was performed following the disk diffusion method with sodium phosphonoformate added as described by Nakamura et al. Additionally, a molecular study based on PCR was used to confirm the screening results. Positive strains for fos genes were further subjected to whole-genome sequencing (WGS).. Phenotypic screening was positive in 9/55 strains (16.4%), although genotypic detection was positive in only 3 (fosA3, fosA4 and fosA6). Thus, the prevalence of fos genes in Madrid was 5.5% (3/55). WGS data were not available for the fosA6-positive strain. One isolate with fosA3 (ST69) carried a bla. We detected the presence of different variants of plasmid-mediated fosA genes in fosfomycin-resistant E. coli strains in Madrid, Spain. Despite the few reports in Europe, it would be of interest to monitor the spread of these acquired resistance genes.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Europe; Fosfomycin; Humans; Prevalence; Spain

The plasmid-mediated

Topics: Animals; Anti-Bacterial Agents; Chickens; Colistin; Drug Resistance, Bacterial; Egypt; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Plasmids; Tigecycline

Topics: Anti-Bacterial Agents; Australia; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

This study evaluates whether the rapid fosfomycin resistance (fosfomycin NP) method can be used for detecting fosfomycin resistance in routine laboratory work. Results from the disk diffusion and rapid fosfomycin NP methods were compared with the reference agar dilution method for Escherichia coli and Klebsiella spp. strains isolated from urinary tract infections. The study included 57 E. coli and 48 Klebsiella spp. isolates from urinary tract infections. The reference agar dilution and disk diffusion methods were performed in accordance with EUCAST recommendations, and the results were evaluated according to EUCAST V.10.0. The method developed by Nordmann et al. was used for rapid detection of fosfomycin resistance (Nordmann, P., Poirel, L., Mueller, L., 2019. Rapid Detection of Fosfomycin Resistance in Escherichia coli. J Clin Microbiol. 57(1), e01531-18. doi:https://doi.org/10.1128/JCM.01531-18). The acceptable categorical agreement (CA ≥ 90%) and the rates of major error (ME <3%) and very major error (VME < 3%) of the two methods were compared with the reference method according to the criteria of ISO 20776-1. Fosfomycin resistance was detected in 15.8% of E. coli and 75% of Klebsiella spp. isolates using the reference method. Disk diffusion method showed CA 89.5%, ME 12.5% in E. coli isolates, and CA 75%, ME 100% in Klebsiella spp. isolates. No VME was detected in both methods. The rapid fosfomycin NP method resulted in CA 96.4%, ME 0.0%, VME 22.2% in E. coli isolates, and CA 77.3%, ME 81.8%, and VME 3% in Klebsiella spp. isolates. We believe the results from both of disk diffusion assay and rapid fosfomycin NP for the E. coli and Klebsiella spp. isolates are incompatible with the reference method and should not be used as an alternative to the agar dilution method.

Topics: Agar; Anti-Bacterial Agents; Diagnostic Tests, Routine; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Urinary Tract Infections

Among 162 isolates of extended-spectrum beta-lactamase-(ESBL)-producing Escherichia coli recovered from the urine of Canadian patients (2007-2017), five (3.1%) were not susceptible in vitro to fosfomycin (MIC ≥128 μg/mL). These isolates underwent whole genome sequencing to assess for the presence of fos genes. The fosA3 gene was detected in one isolate.

Topics: Anti-Bacterial Agents; beta-Lactamases; Canada; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genes, fos; Hospitals; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Urinary Tract Infections

The aim of this study was to report the epidemiological and genetic background of fosfomycin-resistant Escherichia coli isolates causing urinary tract infections (UTIs) in Spain.. A retrospective observational study of 39 randomly selected fosfomycin-resistant E. coli from urine samples collected during 2017 in Getafe (Spain) was performed. Medical records of 39 patients were reviewed. Phylogenetic groups were identified and the pandemic E. coli ST131 and clades thereof were sought by PCR and multilocus sequence typing (MLST). Screening and identification of fos genes and determination of their genetic environment (linkage to IS26) was performed by PCR.. Of the 39 E. coli strains, 49% were ESBL-producers. Most of the strains belonged to phylogenetic group B2 (23/39; 59%), and all of these belonged to ST131 but to different clades (20 to clade C and 3 to clade B). Two isolates from phylogenetic group A (both ST10) carried a plasmid-borne fosA3 gene flanked by IS26. Of the 39 patients, 31 were female (mean age 78 years) and 8 were male (mean age 71 years). Moreover, 27 patients (69%) were diagnosed with complicated UTIs and the remaining 12 (31%) had uncomplicated UTIs, and 33 patients (85%) had been previously treated with fosfomycin.. This study shows that fosfomycin-resistant E. coli strains are mainly isolated from elderly people with complicated UTIs and belong to the pandemic ST131 clone. To our knowledge, here we describe the fosA3 gene for the first time in Spain, which alerts for potential future dissemination that should be monitored.

Topics: Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Fosfomycin; Humans; Male; Multilocus Sequence Typing; Phylogeny; Spain; Urinary Tract Infections

Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC.. We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy.. Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum β-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P < 0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n = 24) or 93.3% (n = 14). The rate in patients with resistance to both antibiotics was 60.0% (n = 9), and the pathogens in the other 40.0% (n = 6) of patients with treatment failure were E. coli-ESBL.. Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

Topics: Adult; Aged; Aged, 80 and over; Amikacin; Ampicillin; Anti-Bacterial Agents; beta-Lactam Resistance; Cefaclor; Cefazolin; Cystitis; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Female; Fosfomycin; Humans; Klebsiella Infections; Levofloxacin; Microbial Sensitivity Tests; Middle Aged; Proteus Infections; Retrospective Studies; Staphylococcal Infections; Treatment Failure; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

Infections caused by Carbapenemase-producing Enterobacterales (CPE) are an important public health issue. Intravenous fosfomycin can be considered as an alternative for the treatment of serious infections caused by CPE. In this study, in vitro activity of fosfomycin was investigated among CPE isolates.. Overall, 158 clinically relevant isolates obtained from 18 hospitals of 13 cities in Turkey with predetermined carbapenemase types were evaluated in the study, including Escherichia coli (n = 19) and Klebsiella spp. (n = 139). In vitro activity of fosfomycin was determined with agar dilution method. Among Klebsiella spp., 104 harbored blaOXA-48, 15 isolates carried both blaOXA-48 and blaNDM; three had both blaOXA-48 and blaVIM and nine isolates had blaNDM alone. Four isolates carried only blaVIM and two isolates harbored blaIMP alone. One isolate co-harbored blaVIM and blaNDM. Among E. coli isolates, blaOXA-48 and blaNDM were carried by 18 and one isolates, respectively.. Resistance to fosfomycin was detected in 43.7% of the isolates. Among Klebsiella spp. and E. coli, these rates were 46.8% and 21.1%, respectively. In Klebsiella spp. resistance to fosfomycin was 49.5% in blaOXA-48 carriers; 26.7% in isolates co-harbouring blaOXA-48 and blaNDM and 66.7% in blaNDM carriers. In E. coli, fosfomycin resistance was detected among 16.7% of the blaOXA-48 carriers.. High level of fosfomycin resistance in these isolates may be attributable to the fact that these isolates are multidrug resistant. The genetic background of resistance should also be investigated in order to understand the co-occurrence and transfer of resistance among the CPE.

Topics: beta-Lactamases; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Turkey

Urinary tract infections (UTIs) caused by multidrug-resistant Escherichia coli have become a major medical concern. Old antibiotics such as fosfomycin have become an alternative therapeutic option due to their effectiveness and, as a result, fosfomycin is now used as a first-line drug for the treatment of UTIs in many countries. Despite low resistance rates, fosfomycin heteroresistance, defined as a phenomenon where subpopulations of bacteria are resistant to high antibiotic concentrations whereas most of the bacteria are susceptible, is an underestimated problem.. The frequency of heteroresistance in E. coli isolated from hospitalized patients in Brazil and its effect on susceptibility of E. coli in biofilms was studied and the isolates were molecularly characterized to reveal the mechanisms behind their fosfomycin heteroresistance using whole-genome sequencing.. A higher frequency of fosfomycin heteroresistance compared with other studies was found. In biofilms, most heteroresistant isolates were less sensitive to fosfomycin than control isolates and showed overexpression of metabolic genes thereby increasing their survival rate. Molecular characterization showed that some resistant subpopulations derived from heteroresistant isolates had a defect in their fosfomycin uptake system caused by mutations in transporter and regulatory genes, whereas others overexpressed the murA gene. None to minor effects on bacterial fitness were observed. Oxidative stress protection, virulence and metabolic genes were differentially expressed in resistant subpopulations and heteroresistant isolates.. Frequent detection of heteroresistance in UTIs may play a role in the failure of antibiotic treatments and should therefore be more carefully diagnosed.

Topics: beta-Lactamases; Brazil; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests

To explore the effect of combining defects in DNA repair systems with the presence of fosfomycin-resistant mechanisms to explain the mechanisms underlying fosfomycin heteroresistance phenotypes in Enterobacteriaceae.. We used 11 clinical Escherichia coli isolates together with isogenic single-gene deletion mutants in the E. coli DNA repair system or associated with fosfomycin resistance, combined with double-gene deletion mutants. Fosfomycin MICs were determined by gradient strip assay (GSA) and broth microdilution (BMD). Mutant frequencies for rifampicin (100 mg/L) and fosfomycin (50 and 200 mg/L) were determined. Using two starting inocula, in vitro fosfomycin activity was assessed over 24 h in growth (0.5-512 mg/L) and time-kill assays (64 and 307 mg/L).. Strong and weak mutator clinical isolates and single-gene deletion mutants, except for ΔuhpT and ΔdnaQ, were susceptible by GSA. By BMD, the percentage of resistant clinical isolates reached 36%. Single-gene deletion mutants showed BMD MICs similar to those for subpopulations by GSA. Strong mutators showed a higher probability of selecting fosfomycin mutants at higher concentrations. By combining the two mechanisms of mutation, MICs and ranges of resistant subpopulations increased, enabling strains to survive at higher fosfomycin concentrations in growth monitoring assays. In time-kill assays, high inocula increased survival by 37.5% at 64 mg/L fosfomycin, compared with low starting inocula.. The origin and variability of the fosfomycin heteroresistance phenotype can be partially explained by high mutation frequencies together with mechanisms of fosfomycin resistance. Subpopulations should be considered until clinical meaning is established.

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests

Escherichia coli ST131 clone and H30-R/H30-Rx subclones are the most common multidrug-resistant high-risk clones in UTIs. Antimicrobial susceptibility of fosfomycin was compared to five other agents in consecutively collected 299 urinary isolates using the agar dilution method. Prevalence of the ST131 clone and the occurrence of blaCTX-M were also investigated. Overall resistance to fosfomycin, cefuroxime, and ceftriaxone were 2.7%, 35.4%, and 30.1% respectively. fosA, fosA3, and fosC2 genes were not detected. In isolates resistant to ciprofloxacin (34.7%), the prevalence of ST131 clone was 31.7%, of which 81.8% belonged to H30-R and 66.7% to H30-Rx subclones. None of the isolates of the ST131 clone were resistant to fosfomycin. However, bla

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactamases; Ceftriaxone; Cefuroxime; Ciprofloxacin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Meropenem; Microbial Sensitivity Tests; Polymerase Chain Reaction; Prevalence; Urinary Tract Infections; Virulence Factors

Of 1033 Escherichia coli urinary tract infection isolates collected from females >12 years of age in Australia in 2019, only 2 isolates were resistant to fosfomycin with a minimum inhibitory concentration (MIC) of >256 mg/L. Despite having different multilocus sequence types, the two isolates harboured an identical plasmid-encoded fosA4 gene. The fosA4 gene has previously been identified in a single clinical E. coli isolate cultured in Japan in 2014. Each fosfomycin-resistant isolate harboured two conjugative plasmids that possessed an array of genes conferring resistance to aminoglycosides, β-lactams, macrolides, quinolones, sulfonamides and/or trimethoprim.

Topics: Anti-Bacterial Agents; Australia; Child; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Plasmids; Urinary Tract Infections; Whole Genome Sequencing

To investigate extended spectrum β-lactamase production and Fosfomycin resistance rates of Escherichia coli and Klebsiella species isolates from patients' urine culture.. Chromogenic agar was used to identify Escherichia coli and Klebsiella species strains. All antibiogram processing was carried out on a fully automated VITEK 2 identification and antibiogram system. The results obtained between January 2015 and December 2018 were retrospectively screened.. Escherichia coli and Klebsiella species were isolated from total 2868 urine cultures. Thus, 844 (34.9%) of 2418 Escherichia coli and 305 (67.8%) of 450 Klebsiella species producted ESBL. Sensitivity rate of ESBL producing Escherichia coli to Fosfomycin was 96.5%, and 98.8% for ESBL negative Escherichia coli. Sensitivity rate of ESBL producing Klebsiella pneumoniae to Fosfomycin was 70.5%, and 53.1% for ESBL negative Klebsiella pneumoniae. None of the three ESBL producing Klebsiella oxytoca strains were found to be resistant to Fosfomycin, though five of 15 ESBL negative strains were found to be resistant to Fosfomycin.. Taking into consideration the advantages of low resistant rate, it is concluded that Fosfomycin may be a good alternative for first step empirical treatment in urinary tract infections, especially in Escherichia coli positive cases. However, the rate of resistance identified in Klebsiella strains informs the onset of resistance problems in Fosfomycin.

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies

A protocol was started within a large health system to automatically test all confirmed extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli urine isolates for susceptibility to fosfomycin, an antibiotic not routinely included in such testing in most institutions. This study assessed the effectiveness of the protocol at reducing carbapenem use for the definitive treatment of ESBL E. coli urinary tract infection (UTI) through several endpoints.. Eighty and 99 patients were compared pre- and postintervention, respectively. The primary outcome was the proportion of patients who received definitive carbapenem therapy. Key secondary outcomes included median total carbapenem days of therapy (DOT), discharge on intravenous UTI antibiotics, and median total antibiotic DOT.. Preprotocol vs postprotocol definitive carbapenem use was seen in 59 of 80 patients (73.8%) and 71 of 99 patients (71.7%) (95% confidence interval [CI] for difference, -11.1% to 15.1%; P = 0.76). The rates of step-down to oral agents pre- and postintervention were 15 of 59 (25.4%) and 35 of 71 (49.3%) (P = 0.004). Median carbapenem DOT in those receiving carbapenems decreased from 8 to 4 days (95% CI, -5 to -1 days; P = 0.001). Median total DOT decreased from 10 to 8 days (95% CI, -3 to -1 days; P = 0.002).. Implementation of a laboratory policy to automatically test ESBL positive E. coli for fosfomycin susceptibility did not reduce the percentage of patients receiving at least 1 dose of carbapenem treatment. It did result in a larger percentage reduction in step-down use of intravenous antibiotics for UTI prior to discharge, reduction in carbapenem DOT, and reduction in total antibiotic DOT.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cohort Studies; Escherichia coli; Escherichia coli Infections; Female; Florida; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Pharmacy Service, Hospital; Retrospective Studies; Urinary Tract Infections

Escherichia coli is the most common cause of Gram-negative prosthetic joint infections (PJIs) and ciprofloxacin is the first-line antibiofilm antibiotic. Due to the emergence of fluoroquinolone resistance, management of E. coli PJIs has become challenging and is associated with high treatment failure rates. We evaluated the efficacy of a newly isolated bacteriophage ɸWL-3 as a therapeutic agent in combination with ciprofloxacin, fosfomycin, gentamicin, meropenem or ceftriaxone against biofilm of a ciprofloxacin/ceftriaxone-resistant E. coli strain and the ATCC 25922 reference strain. ɸWL-3 was first characterised in terms of virion morphology, absorption rate, burst size and killing kinetics against both E. coli strains. The tested antibiotics presented high inhibitory concentrations (ranging from 16 to >1024 μg/mL) when tested alone against biofilms. Co-administration of ɸWL-3 with antibiotics improved the antibiotic efficacy against biofilm, especially after staggered exposure, reducing the minimum biofilm bactericidal concentration (MBBC) up to 512 times. The in vivo antimicrobial activity of ɸWL-3/fosfomycin combination against both E. coli strains was assessed in a Galleria mellonella invertebrate infection model. Treatment of infected larvae after lethal doses of E. coli resulted in enhanced survival rates when combinatorial therapy with ɸWL-3/fosfomycin was applied on E. coli ATCC 25922-infected larvae compared with monotherapy, but not for EC1-infected larvae, which we speculated could be due to higher release of endotoxins in a shorter period in EC1-infected larvae exposed to ɸWL-3. Our study provides new insights into the use of bacteriophages and antibiotics in the treatment of biofilm-associated infections caused by antibiotic-resistant bacteria.

Topics: Animals; Anti-Bacterial Agents; Bacteriophages; Biofilms; Ceftriaxone; Ciprofloxacin; Combined Modality Therapy; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; Gentamicins; Meropenem; Microbial Sensitivity Tests; Moths; Phage Therapy; Prosthesis-Related Infections

Here, we characterize the

Topics: Anti-Bacterial Agents; beta-Lactamases; Canada; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Hospitals; Humans; Microbial Sensitivity Tests; Plasmids

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Gene Transfer, Horizontal; Humans; Microbial Sensitivity Tests; Symbiosis

With an increase in the numbers of bacterial isolates resistant to first-line antibiotics, there has been a revival in the use of older drugs including fosfomycin with novel mechanisms of action. We aimed to investigate the prevalence and genotypic nature of fosfomycin resistance in Escherichia coli from urinary tract infections (UTIs) using the various methods available in the clinical microbiology laboratory.. In total, 1000 culture-positive urine samples were assessed for the presence of E. coli and fosfomycin susceptibility was determined using the MAST Uri system, microbroth dilution, agar dilution and E-test strips.Results/Key findings. Initial investigation using breakpoint susceptibility testing on the MAST Uri system identified 62 of 657 (9.5 %) E. coli isolates as fosfomycin-resistant (MIC≥32 µg ml. Fosfomycin remains a viable option for the treatment of E. coli in uncomplicated UTIs; different susceptibility testing platforms can give very different results regarding the prevalence of fosfomycin resistance, with false positives being a potential problem that may unnecessarily limit the use of this agent.

Topics: Amino Acids; Anti-Bacterial Agents; Colony Count, Microbial; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections; Whole Genome Sequencing

Our aim was to evaluate the prevalence of fosfomycin-resistant strains among ESBL-producing Escherichia coli isolates recovered from community patients in Switzerland. A total of 1225 ESBL-producing E. coli isolates were collected between 2012 and 2013 from a private and community laboratory. Fosfomycin resistance was assessed by using the novel rapid fosfomycin/E. coli NP test and agar dilution method. Resistant isolates were further investigated for acquired resistance genes fosA1-7 by PCR and sequencing. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed to evaluate the clonal relationship among fosA3-carrying isolates. Out of the 1225 ESBL-producing E. coli isolates analyzed in this study, 1208 were fosfomycin susceptible while 17 were fosfomycin resistant. No discrepancy was observed between the rapid fosfomycin/E. coli NP test and the agar dilution method taken as the gold standard. Five out of the 17 resistant isolates carried a fosA-like gene. No clonal relationship was observed among those isolates. Here, the prevalence of fosfomycin resistance among ESBL-producing E. coli isolates in the community is reported for the first time in Switzerland, being ca. 1.4%. Among the five isolates carrying a fosA gene, four encoded the FosA3 enzyme, being the most prevalent fosfomycin-resistant determinant. An excellent correlation was observed between minimum inhibitory concentration-based susceptibility categorization and results of the rapid fosfomycin/E. coli NP test, further indicating the excellent sensitivity and specificity of this recently developed rapid test whose results are obtained in less than 2 h.

Topics: Anti-Bacterial Agents; beta-Lactamases; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Microbial Sensitivity Tests; Molecular Typing; Prevalence; Sequence Analysis, DNA; Switzerland

Antimicrobial resistance (AMR) is of increasing global concern, threatening to undermine recent progress in reducing child and neonatal mortality. Repurposing older antimicrobials is a prominent strategy to combat multidrug-resistant sepsis. A potential agent is fosfomycin, however, there is scarce data regarding its in vitro activity and pharmacokinetics in the paediatric population.. We analysed a contemporary, systematically collected archive of community-acquired (CA) and hospital-acquired (HA) paediatric Gram-negative bacteraemia isolates for their susceptibility to fosfomcyin. MICs were determined using agar serial dilution methods and validated by disk diffusion testing where breakpoints are available. Disk diffusion antimicrobial susceptibility testing was also conducted for current empirical therapies (ampicillin, gentamicin, ceftriaxone) and amikacin (proposed in the literature as a new combination empirical therapeutic option).. Fosfomycin was highly active against invasive Gram-negative isolates, including 90  % (202/224) of Enterobacteriaceae and 96  % (22/23) of Pseudomonas spp. Fosfomycin showed high sensitivity against both CA isolates (94 %, 142/151) and HA isolates (81 %, 78/96; P =0.0015). CA isolates were significantly more likely to be susceptible to fosfomycin than the current first-line empirical therapy (96  % vs 59  %, P <0.0001). Extended spectrum β-lactamases (ESBL) production was detected in 34  % (85/247) of isolates with no significant difference in fosfomycin susceptibility between ESBL-positive or -negative isolates [73/85 (86  %) vs 147/162 (91  %) respectively, P =0.245]. All isolates were susceptible to a fosfomycin-amikacin combination.. Gram-negative paediatric bacteraemia isolates are highly susceptible to fosfomycin, which could be combined with aminoglycosides as a new, carbapenem-sparing regimen to achieve excellent coverage to treat antimicrobial-resistant neonatal and paediatric sepsis.

Topics: Anti-Bacterial Agents; Bacteremia; Child, Preschool; Community-Acquired Infections; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Fosfomycin; Gram-Negative Bacteria; Humans; Infant; Infant, Newborn; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Pseudomonas; Sepsis

Fosfomycin tromethamine (FT), an old antibiotic revived as a new strategy to overcome antibiotic resistance, is an excellent option for the treatment of lower urinary tract infection (UTI). During UTI, Escherichia coli produces biofilms and could invade the bladder epithelial cells, developing intracellular bacterial communities (IBC). The present work aimed to evaluate the activity of FT on biofilms and IBC from clinical isolates of E. coli. A total of 38 E. coli clinical UTI isolates previously characterized as biofilm and IBC producers were studied. FT susceptibility was evaluated and its activity on 48 h biofilm was determined by microtiter plate-based biofilm assay comparing three different antibiotic concentrations. Two UPEC strains were selected to evaluate FT activity on IBC in vitro using T24 bladder cells. The survival percentage of intracellular bacteria after 24 h exposure to FT was calculated and compared to the percentage of intracellular bacteria without antibiotic. All the strains were susceptible to FT. FT produced a significant reduction of biofilms at the three concentrations tested, compared to the control. However, no statistically effect on IBC was observed after 24 h of fosfomycin exposure in cell culture. FT is a good option for bacterial biofilm reduction within UTI. However, it does not affect IBC.

Topics: Anti-Bacterial Agents; Biofilms; Cells, Cultured; Child; Child, Preschool; Epithelial Cells; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections; Uropathogenic Escherichia coli

The steps by which

Topics: Anti-Bacterial Agents; beta-Lactamases; Chromosomes, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Mutation; Urinary Tract; Urinary Tract Infections

Fosfomycin maintains activity against most

Topics: Anti-Bacterial Agents; Carbohydrate Metabolism; Culture Media; Disk Diffusion Antimicrobial Tests; DNA-Binding Proteins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Genome, Bacterial; Glucose-6-Phosphate; Monosaccharide Transport Proteins; Mutation; Mutation Rate; Reverse Transcriptase Polymerase Chain Reaction; Transcriptional Activation

Urinary tract infection (UTI) is a common type of infectious disease globally. The aim of this study was to detect the frequency of fosA3 and fosC2 genes in extended-spectrum β-lactamases (ESBL) and bla

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Child; Child, Preschool; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Fosfomycin; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Urinary Tract Infections; Young Adult

The emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cefoxitin; Cross Infection; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; Humans; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Pilot Projects; Prospective Studies; Prostatitis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

In this study, we assessed the therapeutic effects of fosfomycin tromethamine (FT) in a bacterial prostatitis (BP) rat model. The BP model was induced by Escherichia coli and was demonstrated after 7 days microbiologically and histologically. Then, 25 BP rats selected were randomly divided into five treatment groups: model group, positive group, FT-3 day group, FT-7 day group and FT-14 day group. Ventral lobes of prostate from all animals were removed, and the serum samples were collected at the end of the experiments. Microbiological cultures and histological findings of the prostate samples demonstrated reduced bacterial growth and improved inflammatory responses in FT-treatment groups compared with the model group, indicating that FT against prostatic infection induced by E. coli showed good antibacterial effects. Moreover, plasma pharmacokinetics and prostatic distribution of fosfomycin were studied and compared in BP and normal rats. The concentrations of fosfomycin in samples were analysed by liquid chromatography-tandem mass spectrometry. There were no differences in plasma pharmacokinetic parameters between two groups. But significantly higher penetration of fosfomycin into prostatic tissues was found in BP rats. We therefore suggested that FT had a good therapeutic effect on BP and it might be used in curing masculine reproductive system diseases.

Topics: Animals; Anti-Bacterial Agents; Escherichia coli Infections; Fosfomycin; Male; Models, Animal; Prostatitis; Rats; Rats, Sprague-Dawley; Tissue Distribution

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Gastrointestinal Tract; Hospitalization; Humans; Prospective Studies

Fosfomycin susceptibility testing is complicated and prone to error. Before using fosfomycin widely in patients with serious infections, acquisition of WT distribution data and reliable susceptibility testing methods are crucial. In this study, the performance of five methods for fosfomycin testing in the routine laboratory against the reference method was evaluated.. Ten laboratories collected up to 100 ESBL-producing isolates each (80 Escherichia coli and 20 Klebsiella pneumoniae). Isolates were tested using Etest, MIC test strip (MTS), Vitek2, Phoenix and disc diffusion. Agar dilution was performed as the reference method in a central laboratory. Epidemiological cut-off values (ECOFFs) were determined for each species and susceptibility and error rates were calculated.. In total, 775 E. coli and 201 K. pneumoniae isolates were tested by agar dilution. The ECOFF was 2 mg/L for E. coli and 64 mg/L for K. pneumoniae. Susceptibility rates based on the EUCAST breakpoint of ≤32 mg/L were 95.9% for E. coli and 87.6% for K. pneumoniae. Despite high categorical agreement rates for all methods, notably in E. coli, none of the alternative antimicrobial susceptibility testing methods performed satisfactorily. Due to poor detection of resistant isolates, very high error rates of 23.3% (Etest), 18.5% (MTS), 18.8% (Vitek2), 12.5% (Phoenix) and 12.9% (disc diffusion) for E. coli and 22.7% (Etest and MTS), 16.0% (Vitek2) and 12% (Phoenix) for K. pneumoniae were found. None of the methods adequately differentiated between WT and non-WT populations.. Overall, it was concluded that none of the test methods is suitable as an alternative to agar dilution in the routine laboratory.

Topics: Anti-Bacterial Agents; Diagnostic Errors; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Netherlands; Reproducibility of Results

Alternative therapeutic regimens are urgently needed against carbapenemase-producing Enterobacteriaceae. Fosfomycin often remains active against KPC and OXA-48 producers, but emergence of resistance is a major limitation. Our aim was to determine whether the association of temocillin with fosfomycin might be useful to treat KPC- or OXA-48-producing Escherichia coli infections.. Isogenic derivatives of E. coli CFT073 with blaKPC-3- or blaOXA-48-harbouring plasmids (named CFT073-KPC-3 and CFT073-OXA-48, respectively) were used. The addition of temocillin to fosfomycin was tested using the chequerboard method and time-kill curves as well as in a fatal peritonitis murine model. Mice were treated for 24 h with fosfomycin alone or in combination with temocillin. Bacterial loads, before and after treatment, were determined in the peritoneal fluid and fosfomycin-resistant mutants were detected.. Temocillin MICs were 8, 32 and 256 mg/L for CFT073 (WT), CFT073-KPC-3 and CFT073-OXA-48, respectively. Fosfomycin MIC was 0.5 mg/L for all strains. The chequerboard experiments demonstrated synergy for all three strains. In time-kill curves, combining temocillin with fosfomycin was synergistic, bactericidal and prevented emergence of resistance for CFT073-pTOPO and CFT073-KPC-3, but not CFT073-OXA-48. In vivo, for the three strains, bacterial counts were lower in peritoneal fluid with the combination compared with fosfomycin alone (P < 0.001) and inhibited growth of resistant mutants in all cases.. The combination of fosfomycin and temocillin demonstrated a benefit in vitro and in vivo against E. coli strains producing KPC-3 or OXA-48-type carbapenemases. This combination prevented the emergence of fosfomycin resistance and proved to be more bactericidal than fosfomycin alone.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bacterial Proteins; beta-Lactamases; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Fosfomycin; Mice; Microbial Sensitivity Tests; Penicillins; Peritonitis

The emergence of Enterobacteriaceae isolates resistant to the last-resort antibiotic fosfomycin outside of Asia is a public-health issue. Here we report the draft genome of an Escherichia coli isolate presenting both an extended-spectrum β-lactamase (ESBL) and the fosA3 gene in a healthy cow in Brazil.. Whole genomic DNA from E. coli E12 was extracted and 2×150-bp paired-end reads were generated using Illumina sequencing technology. De novo genome assembly was performed using SPAdes v.3.11 and the draft genome was annotated by the NCBI Prokaryotic Genome Annotation Pipeline. Further analyses were performed using the Center for Genomic Epidemiology databases.. Presence of the fosA3 gene on the same common plasmid as bla

Topics: Asia; Base Sequence; beta-Lactamases; Brazil; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Genome, Bacterial; Pandemics; Plasmids

Topics: Alkyl and Aryl Transferases; Anti-Bacterial Agents; Bacterial Proteins; Carrier Proteins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Membrane Proteins; Membrane Transport Proteins; Microbial Sensitivity Tests; Monosaccharide Transport Proteins; Phosphotransferases

We present the results of a multicenter retrospective study of 35 difficult-to-treat patients with urinary tract infections associated with indwelling urinary catheters (CAUTIs). All patients received oral administration of 3 g fosfomycin trometamol once a day for two days and then with a dose of 3 g every 48 h for two weeks. The most commonly isolated strains were: Escherichia coli (65.7%) and Enterococcus spp. (25.7%); prevalence of Extended-Spectrum Beta-Lactamase strains was 48.5%. Six patients (17.1%) had a clinical response after a single dose of fosfomycin trometamol, 12 (34.2%) after two doses and 13 (37.1%) patients had a clinical response after three or more doses. Four patients (11.6%) failed prolonged antibiotic treatment with fosfomycin trometamol. During the follow-up period, 30 out of 35 (85.7%) patients were without symptomatic infections. No significant side effects were reported. In conclusion, fosfomycin trometamol seems to be a valid treatment option in patients with CAUTIs.

Topics: Administration, Oral; Aged; Anti-Bacterial Agents; Catheter-Related Infections; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Enterococcus; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Retrospective Studies; Tromethamine; Urinary Tract Infections

Topics: Alkyl and Aryl Transferases; Anti-Bacterial Agents; Enzyme Inhibitors; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Molecular Docking Simulation; Quinazolinones; Structure-Activity Relationship

Fosfomycin in combination with various antibiotics represents an excellent clinically efficacious regimen for the treatment of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Underlying mechanisms of fosfomycin resistance remain largely uncharacterised. To investigate the antibacterial efficacy of fosfomycin against ESBL-producing E. coli, 356 non-repetitive ESBL-producing E. coli clinical isolates were collected from urine specimens from patients with UTI in Wenzhou, China, from January 2011 to December 2015. Antimicrobial sensitivity testing indicated that 6.7% (24/356) of the ESBL-producing E. coli strains were resistant to fosfomycin. The fosA3 gene encoding a fosfomycin-modifying enzyme was detected in 20 isolates by PCR and sequencing, alone or in combination with other ESBL determinants. Conjugation experiments and Southern blotting demonstrated that 70% (14/20) of the fosA3-positive isolates possessed transferable plasmids (ca. 54.2 kb) co-harbouring the ESBL resistance gene bla

Topics: Anti-Bacterial Agents; beta-Lactamases; Blotting, Southern; China; Conjugation, Genetic; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Gene Transfer, Horizontal; Humans; Microbial Sensitivity Tests; Plasmids; Polymerase Chain Reaction; Sequence Analysis, DNA; Urinary Tract Infections

Ciprofloxacin, meropenem, fosfomycin, and polymyxin B strongly increase production of outer membrane vesicles (OMVs) in

Topics: Anti-Bacterial Agents; Cell Membrane Structures; Ciprofloxacin; Escherichia coli Infections; Escherichia coli O104; Escherichia coli O157; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Meropenem; Microbial Sensitivity Tests; Polymyxin B; Shiga Toxin 2; Thienamycins

FosA, a glutathione S-transferase that inactivates fosfomycin, has been reported as the cause of enzymatic resistance to fosfomycin. We show that multiple lineages of FosA-producing extended spectrum β-lactamase Escherichia coli have circulated in France since 2012, potentially reducing the efficacy of fosfomycin in treating infections with antimicrobial drug-resistant gram-negative bacilli.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Foscarnet; Fosfomycin; France; Gene Expression; Humans; Isoenzymes; Microbial Sensitivity Tests; Plasmids; Prevalence

Prevalence of fosfomycin resistance in E. coli clinical isolates from UTIs remains very low. Our hypothesis was that fosfomycin resistance may be associated with a biological cost. Three groups of strains of E. coli belonging to the B2 phylogenetic group were used: clinical wild-type (WT) isolates, clinical multidrug-resistant isolates and in vitro fosfomycin-resistant derivatives from the uropathogen clinical strain E. coli CFT073. In each group fosfomycin-susceptible and -resistant isolates were compared. In vitro, we found a significantly decreased growth rate for fosfomycin-resistant strains as compared with susceptible strains in the WT group. In a murine model of ascending UTI, there was a significant reduction in infection rates with fosfomycin-resistant isolates as compared with susceptible ones, in all 3 study groups, ranging from 28 to 39% (P<0.03). All fosfomycin-susceptible clinical strains were virulent in vivo (13/13), while fosfomycin-resistant clinical strains were either virulent (2/7) or non-virulent (5/7) (P<0.002). This difference was not explained by the number of virulence factors or pathogenicity-associated islands. In conclusion, fosfomycin resistance appears to carry some biological cost in E. coli, which may explain in part the apparent paradox of the low prevalence of fosfomycin resistance despite a high rate of spontaneous mutants.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Genetic Fitness; Mice, Inbred CBA; Urinary Tract Infections; Virulence

The purpose of this study was to validate the mutant selection window (MSW) hypothesis in vitro and in vivo with Escherichia coli and Pseudomonas aeruginosa exposed to fosfomycin. Two standard strains of Gram-negative bacteria, those are E. coli ATCC 25922 and P. aeruginosa ATCC 27853, were exposed to fosfomycin at concentrations below MIC, between the MIC and the mutant prevention concentration (MPC), and above the MPC in Luria-Bertani broth and in a tissue-cage infection model, respectively. With the in vitro time-kill studies, there were bacterial re-growth and emergence of resistance thereafter for both strains at antibiotic concentrations of × 4, × 8 and × 16 MIC. In our animal model, the loss in susceptibility of P. aeruginosa at fosfomycin concentrations fluctuated between the lower and upper boundaries of the MSW. In contrast, the emergence of resistant mutants of E. coli was not observed in vivo, regardless of fosfomycin dosage. Interestingly, the in vitro-isolated resistant mutants of E. coli showed a decreased growth rate compared with the susceptible parental strains, whereas no fitness cost in P. aeruginosa was observed. The emergence of antibiotic resistance is shaped by several factors. MSW theory may not apply to all antimicrobial-pathogen combinations. Before it can be used as a framework for the design of antimicrobial therapy, the existence of the window must be demonstrated not only in vitro but also in vivo.

Topics: Animals; Anti-Bacterial Agents; Diffusion Chambers, Culture; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Microbial Sensitivity Tests; Mutation; Oxygen; Pseudomonas aeruginosa; Pseudomonas Infections; Selection, Genetic; Young Adult

Fosfomycin has become a therapeutic option in urinary tract infections. We identified 57 fosfomycin-resistant Escherichia coli from 465 urine-derived extended-spectrum β-lactamase (ESBL)-producing isolates from a Chinese hospital during 2010-2014. Of the 57 fosfomycin-resistant isolates, 51 (89·5%) carried fosA3, and one carried fosA1. Divergent pulsed-field gel electrophoresis profiles and multi-locus sequence typing results revealed high clonal diversity in the fosA3-positive isolates. Conjugation experiments showed that the fosA3 genes from 50 isolates were transferable, with IncFII or IncI1 being the most prevalent types of plasmids. The high prevalence of fosA3 was closely associated with that of bla CTX-M. Horizontal transfer, rather than clonal expansion, might play a central role in dissemination. Such strains may constitute an important reservoir of fosA3 and bla CTX-M, which may well be readily disseminated to other potential human pathogens. Since most ESBL-producing E. coli have acquired resistance to fluoroquinolones worldwide, further spread of fosA3 in such E. coli isolates should be monitored closely.

Topics: Anti-Bacterial Agents; beta-Lactamases; China; Conjugation, Genetic; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Gene Transfer, Horizontal; Genetic Variation; Genotype; Humans; Multilocus Sequence Typing; Plasmids; Prevalence; Tertiary Care Centers; Urinary Tract Infections; Urine

Topics: Anti-Bacterial Agents; Bacteriophage P1; Cephalosporins; China; Colistin; Conjugation, Genetic; DNA Transposable Elements; Drug Resistance, Bacterial; Enteropathogenic Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Lysogeny; Male; Plasmids; Sequence Analysis, DNA

Urinary tract infections (UTIs) are a common reason for empirical treatment with broad-spectrum antibiotics worldwide. However, population-based antimicrobial resistance (AMR) prevalence data to inform empirical treatment choice are lacking in many regions, because of limited surveillance capacity. We aimed to assess the prevalence of AMR to commonly used antimicrobial drugs in Escherichia coli and Klebsiella pneumoniae isolated from patients with community- or healthcare-associated UTIs on two islands of Indonesia.. We performed a cross-sectional patient-based study in public and private hospitals and clinics between April 2014 and May 2015. We screened patients for symptoms of UTIs and through urine dipstick analysis. Urine culture and susceptibility testing were supported by telemicrobiology and interactive virtual laboratory rounds. Surveillance data were entered in forms on mobile phones.. Of 3424 eligible patients, 3380 (98.7%) were included in the final analysis, and yielded 840 positive cultures and antimicrobial susceptibility data for 657 E. coli and K. pneumoniae isolates. Fosfomycin was the single oral treatment option with resistance prevalence <20% in both E. coli and K. pneumoniae in community settings. Tigecycline and fosfomycin were the only options for treatment of catheter-associated UTIs with resistance prevalence <20%, whilst the prevalence of resistance to meropenem was 21.3% in K. pneumoniae .. Patient-based surveillance of AMR in E. coli and K. pneumoniae causing UTIs indicates that resistance to the commonly available empirical treatment options is high in Indonesia. Smart AMR surveillance strategies are needed to inform policy makers and to guide interventions.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Catheter-Related Infections; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Indonesia; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Population Surveillance; Tertiary Care Centers; Thienamycins; Tigecycline; Urinary Tract Infections; Young Adult

The purpose of this study was to characterize the New Delhi metallo-beta lactamase (NDM)-7-producing Enterobacteriaceae isolated in the Arabian Peninsula.. Enterobacteriaceae identified to carry bla. Four NDM-7-producing Escherichia coli isolated in Kuwait, Oman, and the UAE, respectively, were identified. They were clonally unrelated, carried a few virulence determinants only, and belonged to clonal complexes CC10 and CC23, or ST448. They were all multi-drug resistant but remained susceptible to fosfomycin, tigecycline, and colistin. In all isolates, bla. Our findings show that IncX3 type plasmids play an important role in the spread of the currently rare NDM-7 variant in the Arabian Peninsula. This association of bla

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Gene Expression; Humans; Kuwait; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Oman; Phylogeny; Plasmids; Saudi Arabia; Tigecycline; United Arab Emirates

Urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR) are often caused by uropathogens with a high rate of drug resistance and are associated with a high rate of recurrence with a single pathogen. In this study, we evaluated the incidence of recurrent UTI and the drug resistance pattern of Escherichia coli in children with VUR. We also evaluated whether combination therapy comprising fosomycin plus one other antimicrobial agent is effective for treatment of recurrent UTIs.. We retrospectively reviewed the medical records of all children with VUR who developed at least one episode of UTI during the period January 1, 2003 to December 31, 2013 at a single medical center. The effectiveness of fosfomycin plus amikicin for Enterobacteriaceae or ceftazidime for Pseudomonas aeruginosa infections was prospectively studied in six children with recurrent relapsing UTIs.. The study population comprised 129 children (age range, from 1month to 15 years; mean ± standard deviation, 2.37 ± 2.91 years) with VUR who developed at least one UTI during the 10-year study period; 68 (52.7%) had recurrent UTIs. The presence of an underlying urinary tract anomaly was predictive of recurrence (p = 0.028). The rates of susceptibility of E. coli to cefazolin (p < 0.001) and cefotaxime (p < 0.001) were significantly lower in patients with recurrent UTIs. Combination therapy with fosfomycin plus amikacin or ceftazidime was shown to be an effective therapeutic option for recurrent UTIs due to a single uropathogen.. The rates of susceptibility of E. coli to commonly used antimicrobials were significantly lower in children who developed more than one episode of UTI. The empiric choice of cefazolin or cefotaxime was usually ineffective. Administration of fosfomycin plus amikacin or ceftazidime was an effective therapeutic and preventive strategy in children with VUR and recurrent relapsing UTI.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Ceftazidime; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Infant; Male; Pilot Projects; Recurrence; Retrospective Studies; Taiwan; Urinary Tract Infections; Vesico-Ureteral Reflux

The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Norway has been steadily increasing during the last 10-15 years as part of a global pandemic. ESBL producers frequently express co-resistance to other important antimicrobial drug classes, limiting therapeutic options. This has led to regained interest in older antimicrobial agents. The aim of this study was to evaluate the antimicrobial activity of mecillinam, nitrofurantoin, temocillin and fosfomycin, as well as to perform a comparative analysis of resistance patterns in a nationwide collection of ESBL-producing E. coli.. A nationwide collection of all 105 clinical isolates of ESBL-producing E. coli from the Norwegian Organisation for Surveillance of Antimicrobial Resistance (NORM) during 2010-2011 was analyzed. Detection and identification of ESBL-encoding genes were performed by PCR and sequencing for confirmation of ESBL variants of blaTEM and blaSHV (2010) or microarray (2011). Minimum inhibitory concentrations (MICs) or MIC correlates were determined using MIC gradient tests or VITEK 2, respectively. Comparative analysis of resistance patterns was performed.. All isolates were susceptible to fosfomycin, temocillin (urinary tract breakpoint) and meropenem. For mecillinam and nitrofurantoin, 6% and 9% of the isolates, respectively, were non-susceptible. A high level of susceptibility was also observed for amikacin (95%). In contrast, the non-susceptibility proportions to ampicillin (100%), cefotaxime (97%), ceftazidime (77%), aztreonam (87%), gentamicin (42%), tobramycin (52%), ciprofloxacin (76%) and trimethoprim-sulfamethoxazole (71%) were higher.. Overall, the in vitro susceptibility to nitrofurantoin, fosfomycin, mecillinam and temocillin was high, indicating that these drugs are good options for treating uncomplicated urinary tract infections caused by ESBL-producing E. coli.

Topics: Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Nitrofurantoin; Norway; Polymerase Chain Reaction; Sequence Analysis, DNA

Bolivia is among the lowest-resourced South American countries, with very few data available on antibiotic resistance in bacterial pathogens. The phenotypic and molecular characterization of bacterial isolates responsible for urinary tract infections (UTIs) in the Bolivian Chaco are reported here.. All clinical isolates from UTIs collected in the Hospital Basico Villa Montes between June 2010 and January 2014 were analyzed (N=213). Characterization included susceptibility testing, extended-spectrum beta-lactamase (ESBL) detection, identification of relevant resistance determinants (e.g., CTX-M-type ESBLs, 16S rRNA methyltransferases, glutathione S-transferases), and genotyping of CTX-M producers.. Very high resistance rates were observed. Overall, the lowest susceptibility was observed for trimethoprim-sulphamethoxazole, tetracycline, nalidixic acid, amoxicillin-clavulanic acid, ciprofloxacin, and gentamicin. Of E. coli and K. pneumoniae, 11.6% were ESBL producers. Resistance to nitrofurantoin, amikacin, and fosfomycin remained low, and susceptibility to carbapenems was fully preserved. CTX-M-15 was the dominant CTX-M variant. Four E. coli ST131 (two being H30-Rx) were identified. Of note, isolates harbouring rmtB and fosA3 were detected.. Bolivia is not an exception to the very high resistance burden affecting many South American countries. Optimization of alternative approaches to monitor local antibiotic resistance trends in resource-limited settings is strongly encouraged to support the implementation of effective empiric treatment guidelines.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamases; Bolivia; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Methyltransferases; RNA, Ribosomal, 16S; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The objectives of this study were to elucidate the genetic context of a novel plasmid-mediated fosA variant, fosA6, conferring fosfomycin resistance and to characterize the kinetic properties of FosA6.. The genome of fosfomycin-resistant Escherichia coli strain YD786 was sequenced. Homologues of FosA6 were identified through BLAST searches. FosA6 and FosA(ST258) were purified and characterized using a steady-state kinetic approach. Inhibition of FosA activity was examined with sodium phosphonoformate.. Plasmid-encoded glutathione-S-transferase (GST) FosA6 conferring high-level fosfomycin resistance was identified in a CTX-M-2-producing E. coli clinical strain at a US hospital. fosA6 was carried on a self-conjugative, 69 kb IncFII plasmid. The ΔlysR-fosA6-ΔyjiR_1 fragment, located between IS10R and ΔIS26, was nearly identical to those on the chromosomes of some Klebsiella pneumoniae strains (MGH78578, PMK1 and KPPR1). FosA6 shared >99% identity with chromosomally encoded FosA(PMK1) in K. pneumoniae of various STs and 98% identity with FosA(ST258), which is commonly found in K. pneumoniae clonal complex (CC) 258 including ST258. FosA6 and FosA(ST258) demonstrated robust GST activities that were comparable to each other. Sodium phosphonoformate, a GST inhibitor, reduced the fosfomycin MICs by 6- to 24-fold for K. pneumoniae and E. coli strains carrying fosA genes on the chromosomes and plasmids, respectively.. fosA6, probably captured from the chromosome of K. pneumoniae, conferred high-level fosfomycin resistance in E. coli. FosA6 functioned as a GST and inactivated fosfomycin efficiently. K. pneumoniae may serve as a reservoir of fosfomycin resistance for E. coli.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; DNA, Bacterial; Drug Resistance, Bacterial; Enzyme Inhibitors; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Foscarnet; Fosfomycin; Genome, Bacterial; Glutathione Transferase; Humans; Kinetics; Microbial Sensitivity Tests; Plasmids; Sequence Analysis, DNA; Urine

Understanding the relationship between antibiotic exposure and amplification of bacterial subpopulations with reduced drug susceptibility over time is important for evaluating the adequacy of dosing regimens. We utilized a hollow-fiber infection model to identify the fosfomycin intravenous dosing regimens that prevented the amplification of Escherichia coli bacterial subpopulations with reduced fosfomycin susceptibility. The challenge isolate was E. coli ATCC 25922 (agar MIC with glucose-6-phosphate, 1 mg/liter; agar MIC without glucose-6-phosphate, 32 mg/liter). The fosfomycin dosing regimens studied were 1 to 12 g every 8 h for 10 days to approximate that planned for clinical use. The studies included a no-treatment control regimen. Two bacterial subpopulations were identified, one with reduced susceptibility with agar MIC values ranging from 32 to 128 mg/liter and the other resistant with agar MIC values of 256 to >1,024 mg/liter on plates containing 5× and 256× the baseline MIC value, respectively. An inverted-U-shaped function best described the relationship between the amplification of the two bacterial subpopulations and drug exposure. The lowest fosfomycin dosing regimen that did not amplify a bacterial subpopulation with reduced susceptibility was 4 g administered every 8 h. Nearly immediate amplification of bacterial subpopulations with reduced susceptibility was observed with fosfomycin dosing regimens consisting of 1 to 2 g every 8 h. These data will be useful to support the selection of fosfomycin dosing regimens that minimize the potential for on-therapy amplification of bacterial subpopulations with reduced susceptibility.

Topics: Anti-Bacterial Agents; Diffusion Chambers, Culture; Drug Administration Schedule; Drug Dosage Calculations; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Models, Biological

Urinary tract infections (UTIs) are among the most common bacterial infections in adult population. They are prevalent in all age groups both in women and men. Also, UTIs are the most frequent indication for empirical antibiotic treatment in emergency department. The aim of this study was to determine the antibiotic resistance rates in the treatment of uncomplicated UTIs. Adult patients admitted to emergency department with uncomplicated UTIs were included in this cross-sectional study. Mid-stream urine samples were obtained under sterile conditions and cultured quantitatively. After 24 hours, the samples showing 10(5) colony forming unit per milliliter (CFU/mL) were tested for antibiotic susceptibility. Resistance to fosfomycin-trometamol (FT), amoxicillin-clavulanic acid (AC), ciprofloxacin (CIP), trimethoprim-sulfamethoxazole (TMP-SMX) and cefpodoxime (CEF) was tested by Kirby-Bauer disc diffusion system. Escherichia (E.) coli accounted for the vast majority (93.4%) of the organisms isolated in the study. Among the E. coli positive patients, resistance to TMP-SMX was the most common antibiotic resistance. The E. coli species detected in our study group were least resistant to FT (2.4%). The resistance rates, especially to CEF, AC and CIP, were significantly higher in patients over 50 years of age. In conclusion, in the treatment of uncomplicated UTIs, TMP-SMX should be excluded from empirical treatment, while fosfomycin could be a viable option in all age groups.

Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefpodoxime; Ceftizoxime; Ciprofloxacin; Cross-Sectional Studies; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

Increasing resistance in Escherichia coli and Klebsiella pneumoniae to firstline antibiotics makes therapeutic options for urinary tract infections (UTIs) challenging. This study investigated the in vitro efficacies of 6 antibiotics against multidrug resistant (MDR) uropathogens.. Minimum inhibitory concentrations to ceftibuten, cefpodoxime, fosfomycin, mecillinam, temocillin, and trimethoprim were determined against 155 MDR-isolates of E. coli and K. pneumoniae. The presence of extended-spectrum beta-lactamases (ESBL) and plasmid-borne AmpC enzymes was determined by phenotypic testing with genotyping performed by multiplex polymerase chain reaction.. Temocillin demonstrated highest susceptibility rates for both E. coli (95%) and K. pneumoniae (95%) when breakpoints for uncomplicated UTIs were applied; however, temocillin susceptibility was substantially lower when "systemic infection" breakpoints were used. Fosfomycin demonstrated the best in vitro efficacy of the orally available agents, with 78% and 69% of E. coli and K. pneumoniae isolates susceptible, respectively. The next most effective antibiotics were ceftibuten (45%) and mecillinam (32%). ESBL and ampC genes were present in 47 (30%) and 59 (38%) isolates.. This study demonstrated few oral therapeutic options for MDR-uropathogens, with fosfomycin demonstrating the best in vitro activity.

Topics: Amdinocillin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefpodoxime; Ceftibuten; Ceftizoxime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genotype; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multiplex Polymerase Chain Reaction; Penicillins; Singapore; Trimethoprim; Urinary Tract Infections

Fosfomycin is increasingly called upon for the treatment of multi drug-resistant (MDR) organisms causing urinary tract infection (UTI). We reviewed oral fosfomycin use for UTI treatment in a large UK hospital. The primary goal was to audit our clinical practice against current national guidelines. Secondary aims were to identify factors associated with treatment failure, and to investigate the potential for using fosfomycin in patients with co-morbidities.. We retrospectively studied 75 adult patients with UTI who received 151 episodes of treatment with fosfomycin from March 2013 to June 2015. We collected clinical data from our electronic patient record, and microbiology data pre- and post- fosfomycin treatment. We recorded additional data for patients receiving prolonged courses in order to make a preliminary assessment of safety and efficacy. We also reviewed >18,000 urinary tract isolates of Escherichia coli and Klebsiella spp. processed by our laboratory over the final year of our study period to determine the prevalence of fosfomycin resistance.. There was a significant increase in fosfomycin treatment episodes over the course of the study period. Co-morbidities were present in 71 % of patients. The majority had E. coli infection (69 %), of which 59 % were extended spectrum beta-lactamase (ESBL)-producers. Klebsiella infections were more likely than E. coli to fail treatment, and more likely to be reported as fosfomycin resistant in cases of relapse following treatment. There were no adverse events in five patients treated with prolonged fosfomycin. Among all urinary isolates collected over a year, fosfomycin resistance was documented in 1 % of E. coli vs. 19 % of Klebsiella spp. (p < 0.0001).. We report an important role for oral fosfomycin for MDR UTI treatment in a UK hospital population, and based on the findings from this study, we present our own local guidelines for its use. We present preliminary data suggesting that fosfomycin is safe and effective for use in patients with complex comorbidities and over prolonged time periods, but may be less effective against Klebsiella than E. coli.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Klebsiella; Klebsiella Infections; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome; Urinary Tract Infections; Young Adult

A clinical strain of extended-spectrum β-lactamase-producing Escherichia coli E265, with a fosfomycin MIC of 512 μg ml(-1), was isolated from an inpatient with hospital-acquired pneumonia. This strain was negative for known fos genes, had no mutation in the target enzyme by polymerase chain reaction amplification and had functional transport systems for fosfomycin uptake. Fosfomycin resistance could be transferred from strain E265 to E. coli J53 azide(R) by conjugation. The DNA fragment containing fosfomycin resistance determinants was cloned into E. coli TOP10. The minimal inhibitory concentrations of fosfomycin for the transconjugant and transformant were 512 and 1024 μg ml(-1). By sequencing, a plasmid-mediated fosA subtype, designated fosA5, was found and characterized. The fosA5 gene was 420 bp in length and encoded a 139-amino-acid protein that shared 69 to 80% identity with FosA, FosA2, FosA3 and FosA4, and 31, 14 and 25% identity with FosB, FosC and FosX, respectively. The analysis of genetic environment of fosA5 suggested that a strain such as Klebsiella pneumoniae CG4 might be the origin of plasmid-mediated fosA5, with IS10 playing an important role in its mobilization.. This study aimed to clone and characterize a plasmid-mediated fosA subtype gene, fosA5, in a clinical strain of ESBL-producing Escherichia coli, which confers fosfomycin resistance. Detection of the fosA5 gene clarified the mechanism of fosfomycin resistance in a strain that was negative for known fosfomycin resistance genes. Monitoring and surveillance will be important to follow the changes in fosfomycin resistance and prevent further dissemination of fos genes.

Topics: Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Polymerase Chain Reaction; Sequence Analysis, DNA

For chronic bacterial prostatitis, there are few oral antibiotics available that are active against common uropathogens and are able to penetrate the non-inflamed prostate at therapeutic concentrations. Oral options to treat chronic prostatitis due to Gram-negative bacillary multidrug-resistant organisms are even more limited. We report a case of persistent extended-spectrum β-lactamase (ESBL)-positive Escherichia coli chronic prostatitis refractory to antibiotic therapy. Prolonged courses of fosfomycin failed to eradicate the infection. Re-treatment with high-dose fosfomycin again failed to clear the infection. After repeated courses of fosfomycin, the ESBL-positive E. coli remained susceptible to fosfomycin. Transrectal ultrasound revealed prostatic calcifications that were thought to be the reason for antibiotic failure. Following transurethral resection of the prostate (TURP) to remove the prostatic calcifications, the prostatic calcifications remained and the infection persisted. Although the patient's ESBL-positive E. coli was resistant to doxycycline, he was treated with a combination of fosfomycin plus doxycycline. Treatment with fosfomycin and doxycycline rapidly cured his chronic prostatitis.

Topics: Anti-Bacterial Agents; beta-Lactamases; Doxycycline; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Male; Middle Aged; Prostatitis; Treatment Outcome

This study aims to characterize antimicrobial resistance and antimicrobial resistance genetic determinants of an Escherichia coli clinical isolate HD0149 from China in 2012. This strain displayed high-level resistance to cephalosporins, carbapenems, fluoroquinolones, aminoglycosides and fosfomycin. A range of antimicrobial resistance genes was detected responsible for its multiple antimicrobial resistances, involving the blaCMY-2, blaCTX-M-65, blaNDM-1, blaSFO-1, blaTEM-1, fosA3, rmtB, sul1 and sul2 genes. Four amino acid substitutions were detected in the quinolone resistance-determining regions (QRDRs) of GyrA (S83L and D87N), ParC (S80I) and ParE (S458A). Conjugation experiments revealed two multiresistance plasmids present in E. coli HD0149. The blaSFO-1 gene associated with blaNDM-1 gene was located in a 190 kb IncA/C plasmid and the blaCTX-M-65, fosA3 and rmtB genes were located in a 110 kb IncF plasmid. This is the first identification of the blaSFO-1 gene in an E. coli isolate and on a conjugative IncA/C plasmid. This may dramatically enhance the international prevalence and dissemination of blaSFO-1 among Enterobacteriaceae.

Topics: Anti-Bacterial Agents; beta-Lactamases; China; Conjugation, Genetic; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Gene Transfer, Horizontal; Genes, Bacterial; Humans; Middle Aged; Plasmids

The appearance of extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria in urinary tract infection (UTI) constitutes an important therapeutic challenge. The aim of this study was to describe drug susceptibility profiles of ESBL-producing bacteria isolated from urine samples. We also determined the antimicrobial co-resistance to several agents, including fosfomycin.. The computerized database was used to identify ESBL-positive urine samples. We analyzed E. coli and Klebsiella isolates obtained from urine cultures, and duplicate isolates and isolates not tested against fosfomycin were excluded. The cases were further categorized according to UTI definition [community-acquired (CoA) UTI, community-onset health care-associated (HCA) UTI, and hospital-acquired (HA) UTI]. ESBL isolates were stratified according to their origin into two groups: urology and non-urology isolates.. Antimicrobial susceptibilities of the strains to fosfomycin were tested in 277 ESBL-positive strains, 217 ESBL-EC strains, and 60 ESBL-KP strains. The most effective agents were carbapenems, such as imipenem and meropenem. The least active substances were ciprofloxacin (20.7 %), levofloxacin (22.7 %), trimethoprim-sulfamethoxazole (34.3 %), and ampicillin-clavulanate (42.9 %). Overall, 243 out of the 277 (87.7 %) isolates tested were susceptible to fosfomycin. Higher fosfomycin sensitivity was observed in E. coli (94.9 %) compared to Klebsiella (61.7 %) (p = 0.001). ESBL-positive isolates from urological (68 isolates) and non-urological patients (209 isolates) showed similar susceptibility profiles. Other than carbapenems, isolates from CoA-UTI showed higher sensitivity to fosfomycin (100 %) and nitrofurantoin (93.1 %), isolates from HCA-UTI showed higher sensitivity to amikacin (94.1 %), and isolates from HA-UTI showed overall poor sensitivity to antibiotics.. Fosfomycin could be an alternative treatment option for UTIs related to ESBL-producing E. coli spp. and CoA-UTI, but not for UTIs related to ESBL-producing Klebsiella spp. Antimicrobial susceptibilities of ESBL-producing strains were different according to the UTI classification. Fosfomycin showed decreased activity against isolates from HCA-UTI and HA-UTI. However, further clinical verification is required to assess the clinical efficacy of fosfomycin for the treatment of UTIs caused by ESBL-producing E. coli isolates.

Topics: Adolescent; Adult; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Outcome Assessment, Health Care; Republic of Korea; Retrospective Studies; Urinary Tract Infections

To investigate the efficacy of fosfomycin against extended-spectrum β-lactamases (ESBL) producing Escherichia coli in Taiwan and the resistance mechanisms and characterization of human and pig isolates, we analyzed 145 ESBL-producing isolates collected from two hospitals (n = 123) and five farms (n = 22) in Taiwan from February to May, 2013. Antimicrobial susceptibilities were determined. Clonal relatedness was determined by PFGE and multi-locus sequence typing. ESBLs, ampC, and fosfomycin resistant genes were detected by PCR, and their flanking regions were determined by PCR mapping and sequencing. The fosfomycin resistant mechanisms, including modification of the antibiotic target (MurA), functionless transporters (GlpT and UhpT) and their regulating genes such as uhpA, cyaA, and ptsI, and antibiotic inactivation by enzymes (FosA and FosC), were examined. The size and replicon type of plasmids carrying fosfomycin resistant genes were analyzed. Our results revealed the susceptibility rates of fosfomycin were 94% for human ESBL-producing E. coli isolates and 77% for pig isolates. The PFGE analysis revealed 79 pulsotypes. No pulsotype was found existing in both human and pig isolates. Three pulsotypes were distributed among isolates from two hospitals. ISEcp1 carrying blaCTX-M-group 9 was the predominant transposable elements of the ESBL genes. Among the thirteen fosfomycin resistant isolates, functionless transporters were identified in 9 isolates. Three isolates contained novel amino acid substitutions (Asn67Ile, Phe151Ser and Trp164Ser, Val146Ala and His159Tyr, respectively) in MurA (the target of fosfomycin). Four isolates had fosfomycin modified enzyme (fosA3) in their plasmids. The fosA3 gene was harboured in an IncN-type plasmid (101 kbp) in the three pig isolates and an IncB/O-type plasmid (113 kbp) in the human isolate. In conclusion, we identified that 6% and 23% of the ESBL-producing E. coli from human and pigs were resistant to fosfomycin, respectively, in Taiwan. No clonal spread was found between human and pig isolates. Functionless transporters were the major cause of fosfomycin resistance, and the fosA3-transferring plasmid between isolates warrants further monitoring.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; DNA Transposable Elements; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Plasmids; Swine; Taiwan

Fosfomycin is recommended as one of the first-line agents for treatment of urinary tract infections (UTIs) in the latest guidelines endorsed by the Infectious Diseases Society of America (IDSA) and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). We evaluated the use of fosfomycin among inpatients at a tertiary care hospital between 2009 and 2013. UTI cases were defined using physician diagnosis and the National Healthcare Safety Network (NHSN) surveillance definitions. The number of patients treated with fosfomycin increased from none in 2009 to 391 in 2013. Among 537 patients who received fosfomycin for any indication during this period, UTI was the most common indication (74%), followed by asymptomatic bacteriuria (10%). All except 19 patients received a single dose of fosfomycin. Escherichia coli was the most common organism involved (52%). For 119 patients with UTIs, after exclusion of those with negative urine culture results, negative urinalysis results, receipt of additional agents, or indeterminate clinical outcomes, the clinical success rate at 48 h was 74.8%. Of 89 patients who met the criteria for NHSN-defined UTIs, 89.9% had successful outcomes. Recurrent infections occurred in 4.3% of cases, and mild adverse events were observed in 2.0%. All 100 randomly selected extended-spectrum β-lactamase (ESBL)-producing E. coli clinical isolates from this period were susceptible to fosfomycin. In conclusion, the use of fosfomycin has increased substantially since implementation of the updated guidelines at this hospital. Fosfomycin was used mainly for the treatment of physician-diagnosed UTIs, and the clinical outcomes were generally favorable. Fosfomycin maintained activity against E. coli despite the increased use of the agent.

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Inpatients; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Urinary Tract Infections

Escherchia coli isolated, from urine samples were studied for their antibiotic susceptibility patterns, with special reference to the new antimicrobial compound fosfomycin and their correlation with various virulence factors.. The mid stream urine samples received in the department were processed and identification was done by using the standard culture and identification techniques. The antibiotic susceptibility testing was done by modified Kirby-Bauer disk diffusion and the disk diffusion method was used to confirm the ESBL, AmpC, MBL production by the UPEC. Various virulence factors like hemolysin, haemagglutinaton, gelatinase, siderophore production, biofilm formation, serum resistance and hydrophobicity were detected.. Fosfomycin was found to be most effective agent (100%) against uropathogenic E.coli followed by netilmicin (89.5%). The least effective agents were ampiciilin and cotrimoxazole. Twenty nine percent (29%) isolates were found to be multi drug resistant (MDR).. The testing of the newer therapeutic agents like fosfomycin will add on to therapeutics for UTI's.

Topics: Ampicillin; Anti-Bacterial Agents; Biofilms; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Netilmicin; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Urine; Uropathogenic Escherichia coli; Virulence Factors

The role of antimicrobial therapy for Shiga toxin-producing Escherichia coli (STEC) infection has not been clearly defined. A prospective study identified antibiotic use as a significant risk factor for subsequent development of haemolytic-uraemic syndrome (HUS). However, early treatment with fosfomycin, a bacteriostatic antibiotic, resulted in a significantly decreased risk of HUS. The aim of this study was to evaluate a role of fosfomycin therapy in the development of HUS in children who contracted STEC infection. The study included 118 children who contracted a STEC infection between 1997 and 2013. A pre-defined questionnaire was utilised to collect patient information regarding age, sex, presenting symptoms (fever, abdominal pain, diarrhoea and bloody stool), results of stool culture examination, initial results of white blood cell counts and C-reactive protein (CRP), use of antibiotics, the timing of introduction of antibiotics, and complications including HUS. Of the 118 patients, 64 were diagnosed with HUS and the remaining 54 did not develop HUS. Multivariate analysis showed that three independent factors (age, initial values of CRP and use of fosfomycin) were significantly associated with the occurrence of HUS; of particular note, the adjusted odds ratio for use of fosfomycin was 0.15 (95% confidence interval 0.05-0.45). Use of fosfomycin within the first 5 days of illness may decrease the development of STEC-related HUS in children.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Escherichia coli Infections; Female; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Infant; Infant, Newborn; Male; Shiga-Toxigenic Escherichia coli; Surveys and Questionnaires

Fosfomycin resistance in Escherichia coli is rare in the United States. An extended-spectrum β-lactamase-producing E. coli clinical strain identified in Pennsylvania, USA, showed high-level fosfomycin resistance caused by the fosA3 gene. The IncFII plasmid carrying this gene had a structure similar to those found in China, where fosfomycin resistance is commonly described.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Pennsylvania; Sequence Analysis, DNA

Since the end of the last century resistance to oxyimino β-lactams has steadily increased in Enterobacteriaceae. In the present work we studied extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae strains isolated in the teaching hospital of Clermont-Ferrand, France, between 2006 and 2009. A total of 1368 ESBL-producing isolates were collected. Most of these isolates (69%) were CTX-M-producing Escherichia coli. During the study, the clinical incidence increased by more than 400%, even in the emergency department, and especially in community-acquired infections, as is the case elsewhere in the world. Most of the ESBL-producing isolates remained susceptible to furans and fosfomycin, but only 50% to fluoroquinolons. In conclusion, ESBL-producing bacteria constantly increased during the study period. Unlike many studies, this increase was associated with the wide dissemination of three different CTX-M enzymes: CTX-M-14, CTX-M-15 and CTX-M-1.

Topics: Anti-Bacterial Agents; beta-Lactamases; Community-Acquired Infections; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; France; Furans; Hospitals, Teaching; Humans; Microbial Sensitivity Tests; Retrospective Studies

We tested 868 urinary isolates of Escherichia coli collected from 2010 to 2013 as part of the Canadian national surveillance study CANWARD against fosfomycin by using the Clinical and Laboratory Standards Institute (CLSI) agar dilution method with MIC interpretation in accordance with the CLSI M100-S23 (2013) criteria. The concentrations of fosfomycin inhibiting 50 and 90% of the isolates were ≤1 and 4 μg/ml; 99.4% of the isolates were susceptible to fosfomycin.

Topics: Anti-Bacterial Agents; Canada; Drug Resistance, Bacterial; Epidemiological Monitoring; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

The efficacy of fosfomycin alone or combined with cefoxitin was investigated in vitro and in a murine model of urinary tract infection due to susceptible Escherichia coli CFT073-RR and its transconjugant CFT073-RR Tc (pblaCTX-M-15) harbouring a plasmid carrying the blaCTX-M-15 gene. In vitro, the combination of cefoxitin and fosfomycin was synergistic and bactericidal and prevented the emergence of fosfomycin-resistant mutants of CFT073-RR and CFT073-RR Tc (pblaCTX-M-15) that were selected with fosfomycin alone. In vivo, the combination conferred an advantage in terms of kidney sterilisation of mice infected with either strain compared with fosfomycin monotherapy.

Topics: Animals; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cefoxitin; Drug Synergism; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Mice; Mice, Inbred CBA; Microbial Sensitivity Tests; Urinary Tract Infections

Topics: Animals; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Chickens; China; Conjugation, Genetic; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Genotype; Humans; Methyltransferases; Molecular Sequence Data; Plasmids; Poultry Diseases; Public Health; Sequence Analysis, DNA

As a result of extensive use of fluroquinlones and cephalosporins, urinary tract pathogens producing extended-spectrum beta-lactamase (ESBL) pose a considerable clinical challenge in the treatment of UTIs. In the present study we retrospectively assessed the susceptibility of E. coli strains to fosfomycin trometamol and other antibiotics commonly used for the treatment of such infections.. A total of 908 nonreplicate clinical E. coli urinary isolates were collected from 20 Chinese hospitals over four consecutive 1-year periods between October 2004 and June 2012. Susceptibility to antimicrobial agents fosfomycin trometamol, piperacillin-tazobactam, cefuroxime, cefotaxime, cefepime, imipenem, amikacin, levofloxacin, and nitrofurantoin was determined using the agar dilution method. A reference strain E. coli (ATCC 25922) was used as a positive control. Results were analyzed using Chi-square test or Fisher's exact tests.. Fosfomycin trometamol, piperacillin-tazobactam, amikacin, and imipenem were consistently the most active agents against most of the isolates. There was a decline in susceptibility to cefuroxime, cefotaxime, and cefepime between 2004 and 2010. We showed that 528 of the 908 E. coli isolates (58.1%) produced ESBLs. The ESBL-positive rates increased from 41.7% in 2004-2005 to 60.9% in 2011-2012. ESBL-producing E. coli isolates showed significantly higher resistance rates to levofloxacin than the ESBL-negative isolates. Fosfomycin trometamol, piperacillin-tazobactam, amikacin, and imipenem had good activity against both levofloxacin-susceptible and levofloxacin- nonsusceptible isolates (sensitivity rate > 90%). However susceptibility of levofloxacin-resistant isolates to cefuroxime, cefotaxime, cefepime, amikacin, and nitrofurantoin was significantly lower than that of levofloxacin-susceptible isolates.. Owing to the increase in the bacterial resistance across the world, the European Urology Association has recommended fosfomycin trometamol as the drug of choice in its Guidelines on Urological Infections released in 2013. Our results confirm this recommendation for use in China and continued monitoring of the susceptibility of E. coli to fosfomycin trometamol is need with the widely use of the drug in China.

Topics: Anti-Bacterial Agents; China; Epidemiological Monitoring; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Tromethamine; Urine

The number of reports concerning Escherichia coli clinical isolates that produce glutathione S-transferases responsible for fosfomycin resistance (FR-GSTs) has been increasing. We have developed a disk-based potentiation test in which FR-GST producers expand the growth inhibition zone around a Kirby-Bauer disk containing fosfomycin in combination with sodium phosphonoformate (PPF). PPF, an analog of fosfomycin, is a transition-state inhibitor of FosA(PA), a type of FR-GST from Pseudomonas aeruginosa. Considering its mechanism of action, PPF was expected to inhibit a variety of FR-GSTs. In the presence of PPF, zone enlargement around the disk containing fosfomycin was observed for FosA3-, FosA4-, and FosC2-producing E. coli clinical isolates. Moreover, the growth inhibition zone was remarkably enlarged when the Mueller-Hinton (MH) agar plate contained 25 μg/ml glucose-6-phosphate (G6P). When we retrospectively tested 12 fosfomycin-resistant (MIC, ≥256 μg/ml) E. coli clinical isolates from our hospital with the potentiation test, 6 FR-GST producers were positive phenotypically by potentiation disk and were positive for FR-GST genes: 5 harbored fosA3 and 1 harbored fosA4. To identify the production of FR-GSTs, we set the provisional cutoff value, 5-mm enlargement, by adding PPF to a fosfomycin disk on the MH agar plates containing G6P. Our disk-based potentiation test reliably identifies FR-GST producers and can be performed easily; therefore, it will be advantageous in epidemiological surveys and infection control of fosfomycin-resistant bacteria in clinical settings.

Topics: Agar; Anti-Bacterial Agents; Culture Media; DNA, Bacterial; Drug Tolerance; Escherichia coli; Escherichia coli Infections; Foscarnet; Fosfomycin; Glutathione Transferase; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Pseudomonas aeruginosa; Sequence Analysis, DNA

Topics: Animals; Cats; Cattle; Chickens; Dogs; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genes, Bacterial; Livestock; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Swine

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Topics: Anti-Bacterial Agents; Cefepime; Cell Survival; Cephalosporins; Ciprofloxacin; Community-Acquired Infections; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Nitrofurantoin; Penicillins; Republic of Korea; Sulfadoxine; Treatment Outcome; Trimethoprim; Urinary Tract Infections

Topics: Aged; Amoxicillin; Anti-Infective Agents, Urinary; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Germany; Humans; Male; Microbial Sensitivity Tests; Nitroquinolines; Outpatients; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

A 69-year-old man with diabetes mellitus was diagnosed with a prostate abscess. Although the pathogen was fluoroquinolone-resistant Escherichia coli and the oral administration of trimethoprim-sulfamethoxazole was initiated, the infection recurred after three months. The antibiotic therapy was subsequently changed to intravenous fosfomycin, and the patient's condition promptly improved. Four weeks of fosfomycin therapy was successfully continued without any adverse events. In the era of antibiotic resistance, revival of forgotten drugs is an important issue for clinicians. Fosfomycin can be applied as an alternative option for prostate infections, considering the remaining susceptibility of multidrug-resistant pathogens to fosfomycin and the good pharmacokinetics of this drug in prostatic tissue.

Topics: Aged; Anti-Bacterial Agents; Diabetes Mellitus; Drug Resistance, Bacterial; Escherichia coli Infections; Fosfomycin; Humans; Male; Prostatic Diseases

The increasing rate of antibiotic resistance in Escherichia coli, the most common pathogen of urinary tract infections (UTIs), leads to difficulties in choosing appropriate antibiotic treatment and achieving treatment success. The aim of this study was to investigate in vitro activity of fosfomycin, presented as a favorable choice for the treatment of UTIs caused especially by extended-spectrum beta-lactamase (ESBL)-producing strains. A total of 244 E.coli strains, of them 118 were ESBL positive and 126 were negative, isolated from urine samples of inpatients and outpatients between May 2011-May 2012, were included in the study. Antibiotic susceptibilities of the isolates were determined by disk diffusion method (DDM) and ESBL production was confirmed by double-disc diffusion method according to the CLSI (Clinical and Laboratory Standards Institute) recommendations. Minimum inhibitor concentration (MIC) values for fosfomycin were detected by E-test method. Fosfomycin zone diameters and MIC values of isolates were interpreted according to the breakpoints of both CLSI and EUCAST (European Committee on Antimicrobial Susceptibility Testing). Susceptibilities of ESBL positive and negative isolates to fosfomycin and other antibiotics, and the results of fosfomycin susceptibility tests obtained by different methods were compared. The correlation between fosfomycin zone diameters and MIC values was calculated. In the study, the resistance rates of ESBL-producing isolates to ciprofloxacin, trimethoprim-sulfamethoxazole, gentamicin and amikacin were detected as 67%, 51%, 51% and 19%, respectively, while those rates were as 9%, 21%, 4% and 11%, respectively in non-ESBL producers. The difference between the two groups were found statistically significant (p< 0.001). Fosfomycin resistance of ESBL-producing and non-producing isolates were 3% and 1%, respectively, indicating no significant difference between the two groups (p= 0.356). According to fosfomycin MIC breakpoints defined by CLSI, 98.3% of ESBL-producing isolates and 100% of non-producing isolates were found susceptible to fosfomycin. According to EUCAST recommendations 98.3% of ESBL-producing isolates and 99.2% of non-producing isolates were found susceptible to fosfomycin. There was no significant difference between ESBL-positive and -negative strains according to CLSI and EUCAST recommendations (p= 0.233 and p= 0.611, respectively). When the methods were compared with each other, there were significant diff

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Disk Diffusion Antimicrobial Tests; Escherichia coli Infections; Female; Fosfomycin; Humans; Inpatients; Male; Microbial Sensitivity Tests; Middle Aged; Outpatients; Urinary Tract Infections; Uropathogenic Escherichia coli

To determine the in vitro activity of Fosfomycin tromethamine against extended spectrum beta-lactamase producing uropathogens.. Experimental study.. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from October 2011 to October 2012.. A total of 381 culture positive ESBL producing isolates from 2400 urine samples submitted over a period of one year were included in this study. Identification of isolates was done by standard biochemical profile of the organisms. The antimicrobial susceptibility of culture positive isolates was performed by disk diffusion method as recommended by Clinical Laboratory Standard Institute guidelines (CLSI).. The antimicrobial activity of Fosfomycin to various isolates revealed that 93% of E. coli, 64% Klebsiella spp. 50% Proteus spp. 75% Enterobacter cloacae, 100% Citrobacter freundii, 100% Burkholderia spp. 100% Serratia spp. and 50% Stenotrophomonas maltophilia were susceptible to this chemical compound.. Fosfomycin showed excellent effectiveness to most of the common ESBL producing bacteria such as E. coli, Klebsiella and Proteus spp.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Child; Child, Preschool; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Urinary Tract; Urinary Tract Infections; Uropathogenic Escherichia coli; Young Adult

To ascertain the adequacy of empirical antimicrobial treatment in pregnant women with acute pyelonephritis.. We have conducted a retrospective observational study of women admitted to the hospital with acute pyelonephritis between May 2004 and April 2011. Patients were included if the results of urine cultures and susceptibility testing to antibiotics were available. Epidemiological, clinical, therapeutical and outcome variables were collected from chart review. We considered inappropriate empirical antimicrobial treatment (IEAT) as the occurrence of microorganism that were not effectively treated at the time when the causative microorganism and its antibiotic susceptibility were known.. Fifty women with appropriate microbiological data from a total of 93 cases of acute pyelonephritis were included in the study. The women's mean age was 26.4 years, and 58% were nulliparous. Pyelonephritis was developed in the 2nd and 3rd trimester in 88% of cases. Previous urinary tract infections were recorded in 34%. Escherichia coli was the most frequent microorganism (70%). The proportion of patients who received IEAT was 10%. Amoxicillin-clavulanate and cephalosporines were the most predominant antibiotics used, with a proportion of IEAT of 10.3% and 5.9%, respectively.. Pregnant women with pyelonephritis received IEAT in a small but significant number of cases. Amoxicillin-clavulante and cephalosporines were adequate in most cases. More studies are needed to define the clinical impact of IEAT on prognosis.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactams; Comorbidity; Escherichia coli Infections; Female; Fosfomycin; Hospitals, University; Humans; Inappropriate Prescribing; Microbial Sensitivity Tests; Obstetrics and Gynecology Department, Hospital; Pregnancy; Pregnancy Complications, Infectious; Pyelonephritis; Recurrence; Retrospective Studies; Spain; Treatment Outcome; Young Adult

Escherichia coli is the most important uropathogen. The appearance of extended- spectrum beta-lactamase (ESBL)-producing E.coli in urinary tract infections (UTI) constitutes an important therapeutic challenge that requires the study of its evolution throughout time in order to establish a suitable empirical treatment. Our aim was to determine the prevalence of ESBL-producing E. coli urinary isolates in 2005, 2009 and 2011. We also determined the antimicrobial coresistance to several agents, including fosfomycin.. We analyzed 5053, 6324 and 6644 E. coli isolates obtained from urine cultures in 2005, 2009 and 2011 respectively. Duplicate isolates were excluded. Antimicrobial susceptibility was determined by the Wider microdilution system (Soria Melguizo S.A.) and the phenotypic pattern of resistance that indicated a BLEE-producing E.coli was selected (CLSI 2009).. 3.9% of strains (198) were ESBL producers in 2005, 7.3% (463) in 2009 and 8.7% (584) in 2011. Resistance to carbapenems was detected in 2009, they inhibited more than the 95% of strains in 2011. Among the non-beta-lactams, colistin was the most active antibiotic followed by nitrofurantoin. Ciprofloxacin and sulfamethoxazole-trimethoprim were not effective with 80% and 60% resistant isolates, respectively. An increasing resistance trend, from 0% to 9.3% in 2009 and 14.4% in 2011 was observed for fosfomycin.. From 2005 our institution had an increasing prevalence of ESBL-producing E. coli rising to 8.7% in 2011. Carbapenems are still the most active agents. The increase of resistance was significant for fosfomycin.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Prevalence; Urinary Tract Infections; Urine

We examined the prevalence and mechanism of fosfomycin resistance in CTX-M-producing Escherichia coli isolates from healthy Japanese individuals. One hundred thirty-eight CTX-M-producing E. coli isolates were subjected to fosfomycin susceptibility testing. The presence of acquired fosfomycin resistance genes such as fosA, fosA3, and fosC2 was explored, and the transmissibility of fosfomycin resistance, replicon type of plasmid, and genetic environment of fosA3 were investigated. Eight isolates (5.8%) showed resistance to fosfomycin, five of which harbored fosA3, which was in genetic linkage with blaCTX-M. The replicon types of the five transferred fosA3-carrying plasmids were as follows: IncI1 (n=2), IncN (n=1), and IncFII (n=2). Each fosA3 gene was located close to the blaCTX-M gene and was flanked by IS26 elements. These genetic environments of fosA3 in E. coli from healthy individuals were quite similar to those observed in the clinical and veterinary settings. Our results indicate that fosA3 genes possibly inserted by small mobile genetic elements flanked by two IS26 elements have already spread throughout the plasmids along with the blaCTX-M genes of commensal E. coli colonizing in healthy Japanese people.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carrier State; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genetic Linkage; Humans; Japan; Microbial Sensitivity Tests; Plasmids; Replicon; Retroelements

A total of 1878 non-duplicate clinical Escherichia coli isolates (comprising 1711 urinary isolates and 167 blood-culture isolates), which were collected from multiple centres in Hong Kong during 1996-2008, were used to investigate the prevalence and molecular epidemiology of plasmid-mediated fosfomycin (fos) resistance genes. Eighteen of the 1878 clinical E. coli isolates were fosfomycin resistant, of which six were fosA3 positive and two were positive for another fosA variant (designated fosKP96). No isolates had the fosC2 gene. The clones of the eight isolates were diverse: sequence type (ST) 95 (n = 2), ST118 (n = 1), ST131 (n = 1), ST617 (n = 1), ST648 (n = 1), ST1488 (n = 1) and ST2847 (n = 1). In the isolates, fosA3 and blaCTX-M genes were co-harboured on conjugative plasmids with F2:A-:B- (n = 2), N (n = 1), F-:A-:B1 and N (n = 1) and untypable (n = 2) replicons. Both fosKP96-carrying plasmids belonged to replicon N. RFLP analysis showed that the two F2:A-:B- plasmids carrying fosA3 and blaCTX-M-3 genes shared the same pattern. Complete sequencing of one of the two F2:A-:B- plasmids, pFOS-HK151325 (69 768 bp) demonstrated it to be >99 % identical to the previously sequenced plasmid pHK23a originating from a pig E. coli isolate in the same region. This study demonstrated the dissemination of fosA3 genes in diverse E. coli clones on multiple blaCTX-M-carrying plasmid types, of which F2:A-:B- plasmids closely related to pHK23a were shared by isolates from human and animal sources.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genes, Bacterial; Hong Kong; Humans; Molecular Epidemiology; Multilocus Sequence Typing; Plasmids; Prevalence; Sequence Homology; Swine; Urinary Tract Infections

To characterize a representative self-transmissible multidrug resistance plasmid pHN7A8 isolated from an Escherichia coli from a dog in China, classified as F33:A-:B- by replicon sequence typing and carrying the bla(TEM-1b), bla(CTX-M-65), fosA3 and rmtB genes conferring resistance to penicillins, cephalosporins, fosfomycin and aminoglycosides, respectively.. pHN7A8 was sequenced using a whole-genome shotgun approach and the sequence analysed by comparison with reference plasmids.. pHN7A8 is a circular molecule of 76 878 bp. bla(CTX-M-65), fosA3 and rmtB are found in known contexts, interspersed with different mobile elements including ISEcp1, IS1, Tn2, IS1294, IS903 and four copies of IS26. This multiresistance region has only a single nucleotide difference from that of pXZ, an F2:A-:B- plasmid isolated from poultry in China. The pHN7A8 backbone carries genes encoding addiction and partitioning systems that promote plasmid maintenance and has a similar organization to pXZ, as well as IncFII plasmids such as R100, pC15-1a/pEK516 and pHK23, isolated in Japan, Canada/the UK and China, respectively, but with varying levels of identity, suggesting recombination.. pHN7A8 is a chimera that may have resulted from the acquisition, by recombination in the plasmid backbone, of the multiresistance region found in pXZ. This region appears to have evolved from the resistance determinant R100 through the stepwise integration of multiple antimicrobial resistance determinants from different sources by the actions of mobile elements and recombination. The successful dissemination of this multidrug resistance plasmid presents further challenges for the prevention and treatment of Enterobacteriaceae infections.

Topics: Animals; Base Sequence; beta-Lactamases; China; Dogs; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; F Factor; Fosfomycin; Methyltransferases; Molecular Sequence Data

Previous studies have reported plasmid-mediated fosA3 among Escherichia coli originating from human and companion animals. In this study, the plasmid, designated pHK23a originating from a multidrug-resistant E. coli isolate recovered from a slaughter pig in December 2008 in Hong Kong, China was sequenced. In conjugation, the plasmid readily transferred to E. coli J53 at high frequencies. It belongs to the narrow host range IncFII incompatibility group and is 73,607 bp in length. Sequence alignment showed that pHK23a has a 59.1 kb backbone which shares high homology with the prototype R100 plasmid and a 14.5 kb variable region. The variable region includes three genes mediating antimicrobial resistance (fosA3, Δbla(TEM-1), bla(CTX-M-3)), ten mobile genetic elements (four copies of IS26, insA, ΔinsB, ΔTn2, IS1, ΔISEcp1, Δintl1), the tir transfer inhibition protein, the pemI/pemK addiction system and eight ORFs of unknown functions (orf1, orf2, Δorf3, orf20, orf23, orf24, ycdA and ycdB). The three resistance genes were organized in a novel IS26-composite transposon-like structure. In conclusion, this is the first report of fosA3 containing plasmid in an isolate of pig origin. Since IncFII plasmids spread efficiently in Enterobacteriaceae, the detection of fosA3 with bla(CTX-M) is worrisome and might become a public health concern.

Topics: Animals; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Hong Kong; Plasmids; Sequence Analysis, DNA; Sus scrofa; Swine

To investigate the occurrence of plasmid-mediated fosfomycin resistance genes among Escherichia coli from food animals in China.. A total of 892 E. coli isolates collected from individual pigs (n=368), chickens (n=196), ducks (n=261), geese (n=35), pigeons (n=20) and partridges (n=12) in Guangdong Province during 2002-08 were screened for the presence of fosA3, fosA and fosC2 by PCR amplification and sequencing. The clonal relationship of fosA3-positive isolates, plasmid content and other associated resistance genes were also characterized.. Twelve (1.3%) E. coli isolates showed resistance to fosfomycin and 10 (1.1%) isolates (4 from pigs, 2 from chickens, 2 from ducks, 1 from a goose and 1 from a pigeon) were positive for fosA3. None of the E. coli isolates was positive for fosA or fosC2. All of the isolates carrying fosA3 were CTX-M producers, and three of them carried rmtB. Most of the fosA3-harbouring isolates were found to be clonally unrelated. The fosA3 genes were flanked by IS26. Two fosA3 genes co-localized with rmtB and blaCTX-M-65 on indistinguishable F33:A-:B- plasmids that carried three addiction systems (pemI/pemK, hok/mok/sok and srnB). Four, one and one fosA3 genes were found to be associated with IncN (ST8 type), IncI1 and F2:A-:B- plasmids, respectively.. We discovered that fosA3 is always associated with blaCTX-M, which facilitates its quick dispersal. The emergence of fosA3 in food animals could impact on human medicine by the potential transfer of resistance through the food chain.

Topics: Animals; Animals, Domestic; China; Cluster Analysis; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genotype; Humans; Molecular Sequence Data; Phylogeny; Plasmids; Polymerase Chain Reaction; Sequence Analysis, DNA

To investigate plasmid-mediated fosfomycin resistance related to fosA3 in Escherichia coli isolates collected from different animals in Hong Kong, China, 2008-2010.. In total, 2106 faecal specimens from 210 cattle, 214 pigs, 460 chickens, 398 stray cats, 368 stray dogs and 456 wild rodents were cultured. The faecal colonization rates of fosfomycin-resistant E. coli were as follows: 11.2% in pigs, 8.6% in cattle, 7.3% in chickens, 2.4% in dogs, 0.8% in cats and 1.5% in rodents. The cultures yielded 1693 isolates of which 831 were extended-spectrum β-lactamases (ESBL) producers. Fosfomycin-resistant isolates were more likely than fosfomycin-susceptible isolates to be producers of ESBL and to have resistance to chloramphenicol, ciprofloxacin, cotrimoxazole, gentamicin and tetracycline. Of the 101 fosfomycin-resistant isolates, 97 (96.0%) isolates were fosA3 positive and 94 (93.1%) were bla(CTX) (-M) positive. PCR mapping showed that the fosA3-containing regions were flanked by IS26, both upstream and downstream in 81 (83.5%) isolates, and by an upstream bla(CTX-M-14) -containing transposon-like structure (ΔISEcp1-bla(CTX-M-14) -ΔIS903 or ISEcp1-IS10 -bla(CTX-M-14) -ΔIS903) and a downstream IS26 in 14 (14.4%) isolates. For the remaining two isolates, fosA3 was flanked by a downstream IS26 but the upstream part cannot be defined. In a random subset of 18 isolates, fosA3 was carried on transferable plasmids with sizes of 50-200 kb and the following replicons: F2:A-B- (n = 3), F16:A1:B- (n = 2), F24:A-B- (n = 1), N (n = 1), B/O (n = 1) and untypeable (n = 3).. This study demonstrates the emergence of fosA3-mediated fosfomycin resistance among multidrug-resistant E. coli isolates from various animals. IS26 transposon-like structures might be the main vehicles for dissemination of fosA3.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cats; Cattle; Chickens; DNA Transposable Elements; DNA, Bacterial; Dogs; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Feces; Fosfomycin; Hong Kong; Livestock; Microbial Sensitivity Tests; Plasmids; Polymerase Chain Reaction; Rodentia; Swine

Limited antimicrobial agents are available for the treatment of implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli. We compared the activities of fosfomycin, tigecycline, colistin, and gentamicin (alone and in combination) against a CTX-M15-producing strain of Escherichia coli (Bj HDE-1) in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration in logarithmic phase (MBC(log)) and stationary phase (MBC(stat)) were 0.12, 0.12, and 8 μg/ml for fosfomycin, 0.25, 32, and 32 μg/ml for tigecycline, 0.25, 0.5, and 2 μg/ml for colistin, and 2, 8, and 16 μg/ml for gentamicin, respectively. In time-kill studies, colistin showed concentration-dependent activity, but regrowth occurred after 24 h. Fosfomycin demonstrated rapid bactericidal activity at the MIC, and no regrowth occurred. Synergistic activity between fosfomycin and colistin in vitro was observed, with no detectable bacterial counts after 6 h. In animal studies, fosfomycin reduced planktonic counts by 4 log(10) CFU/ml, whereas in combination with colistin, tigecycline, or gentamicin, it reduced counts by >6 log(10) CFU/ml. Fosfomycin was the only single agent which was able to eradicate E. coli biofilms (cure rate, 17% of implanted, infected cages). In combination, colistin plus tigecycline (50%) and fosfomycin plus gentamicin (42%) cured significantly more infected cages than colistin plus gentamicin (33%) or fosfomycin plus tigecycline (25%) (P < 0.05). The combination of fosfomycin plus colistin showed the highest cure rate (67%), which was significantly better than that of fosfomycin alone (P < 0.05). In conclusion, the combination of fosfomycin plus colistin is a promising treatment option for implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Biofilms; Colistin; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Foreign Bodies; Fosfomycin; Gentamicins; Guinea Pigs; Male; Microbial Sensitivity Tests; Minocycline; Polytetrafluoroethylene; Prostheses and Implants; Tigecycline

To describe the incidence and drug susceptibility profiles of uropathogenic extended-spectrum-β-lactamase-producing Escherichia coli (ESBL-EC) during a 10-year period and to identify differences in resistance patterns between urological and non-urological ESBL-EC isolates.. Retrospective analysis of 191,564 urine samples obtained during 2001 to 2010 at the University Hospital Basel, Switzerland. The computerized database of the Clinical Microbiology Laboratory and the Division of Infectious Diseases and Hospital Epidemiology was used to identify ESBL-EC positive urine samples. ESBL-EC isolates were stratified according their origin into two groups: Urology and non-Urology isolates.. The rate of ESBL-EC positive urine samples increased significantly during the study period (3 in 2001 compared to 55 in 2010, p < 0.05). The most active agents were imipenem, meropenem, and fosfomycin (100%), followed by amikacin (99.1%) and nitrofurantoin (84%). The least active substances were ampicillin-clavulanate (20%), sulfamethoxazole (28%), and ciprofloxacin (29.6%). ESBL-EC isolates from urological and non-urological patients showed similar susceptibility profiles. However, ESBL-EC isolates from urological patients were significantly less susceptible to ciprofloxacin compared to non-urological isolates (14.7 vs. 32.7%, p < 0.05).. The rate of urinary ESBL-EC isolates is increasing. Their susceptibility to nitrofurantoin, fosfomycin, and carbapenems is excellent, whereas ampicillin-clavulanate, sulfamethoxazole, and ciprofloxacin demonstrate only low susceptibility. In particular, the use of ciprofloxacin should be strictly avoided in urologic patients with suspicion for an ESBL-EC urinary tract infection as well as routine antibiotic prophylaxis prior to urological interventions if not explicit indicated by current international guidelines or local resistance patterns.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Ciprofloxacin; Contraindications; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Middle Aged; Nitrofurantoin; Prevalence; Retrospective Studies; Treatment Failure; Treatment Outcome; Urinary Tract; Urinary Tract Infections; Young Adult

To determine whether the overexpression of chromosomal genes can confer fosfomycin resistance, genomewide screening of a complete set of 5,272 plasmid-expressed open reading frames of Escherichia coli (ASKA collection) was performed. Major results are that (i) no clinical level of resistance is achieved by overexpressing chromosomal genes, except murA; (ii) this level is reached at a low fitness cost; and (iii) this cost is much lower than that imposed by other mutations conferring fosfomycin resistance.

Topics: Alkyl and Aryl Transferases; Anti-Bacterial Agents; Bacterial Proteins; Biological Transport; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Gene Expression; Gene Expression Profiling; Genetic Fitness; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Mutation; Sequence Analysis, DNA

The serotype, Shiga toxin (Stx) type, and antimicrobial resistance patterns of 138 Stx-producing Escherichia coli (STEC) strains isolated from humans between 2003 and 2007 in Shizuoka Prefecture, Japan were characterized. The predominant O serogroups of the STEC isolates were O157, O26, and O111. Antimicrobial susceptibility testing of the STEC isolates showed that 31 of the 138 isolates (22.5%) were resistant to antibiotics. Compared to the results reported in the previous studies, a higher rate of STEC O157 isolates were susceptible to all the antimicrobial agents used in this study. However, antimicrobial susceptibility data from this study showed that antimicrobial resistance patterns have increased by 6 compared to the survey performed by Masuda et al. between 1987 and 2002 (Jpn. J. Food Microbiol., 21, 44-51, 2004). This indicates that STEC isolates have evolved to show a variety of antimicrobial resistance patterns. It is important to consider the population of isolates showing decreased susceptibility to clinically relevant drugs such as ciprofloxacin (CPFX) and fosfomycin (FOM). All the 3 STEC isolates resistant to nalidixic acid showed low susceptibility to CPFX (MIC, 0.25-0.5 μg/ml). In addition, a decreased susceptibility to FOM was clearly observed in the E. coli O26 isolates. Our findings also showed that 1 STEC O26 strain could possibly be a chromosomal AmpC β-lactamase hyperproducer. These results suggest that antimicrobial therapy may be less effective in patients with non-O157 STEC infections than in those with STEC O157 infections.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Disease Outbreaks; Drug Resistance, Bacterial; Escherichia coli Infections; Escherichia coli Proteins; Female; Fosfomycin; Humans; Japan; Male; Microbial Sensitivity Tests; Serotyping; Shiga Toxins; Shiga-Toxigenic Escherichia coli; Virulence

There is currently an emerging need for developing improved approaches for preventing urinary tract infections (UTIs) occurring during diagnostic or interventional procedures of the lower urinary tract. We aimed to establish a rat model to assess the use of transurethral antibiotic administration and to provide evidence that this could be used as a preventive therapy.. Animals received fosfomycin trometamol (FOF) either urethrally or orally prior to the procedure. A third group was generated as treatment controls and did not receive any medication. Urethral dilation was conducted to recapitulate an interventional procedure prior to intravesical Escherichia coli administration in all three groups. Finally, sham-operated animals were introduced as a fourth group which did not receive antibiotics or E. coli. Colony counts of urine and tissue cultures for the identification of E. coli and histopathological examinations of the bladder and prostate were conducted.. Evaluation of infection intensities in cultures as well as histopathological examination of the bladder and prostate demonstrated a preventative role of transurethral FOF administration. In terms of efficiency, local administration of FOF was similar to oral administration.. These results suggest that transurethral antibiotic administration is a promising alternative for preventing UTIs occurring during diagnostic or interventional procedures of the lower urinary tract.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Colony Count, Microbial; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Fosfomycin; Male; Rats; Rats, Wistar; Urethra; Urinary Tract Infections

To investigate the prevalence of plasmid-mediated fosfomycin resistance determinants among extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and their genetic environments.. A total of 347 non-duplicate ESBL-producing E. coli (165) and K. pneumoniae (182) were collected. The fosfomycin MICs were determined by the agar dilution method according to CLSI guidelines. PCR was used to detect the plasmid-encoded fosfomycin resistance genes (fosA, fosA3, fosB and fosC2). For isolates harbouring plasmid-encoded fosfomycin resistance genes, sequence types (STs) were determined. The transformation experiment was performed using E. coli TOPO10 (Invitrogen, USA) as a recipient strain. With the plasmids from the transformants, plasmid replicon typing was performed and the nucleotide sequences adjacent to fosA3 were determined.. The susceptibility to fosfomycin was 92.9% in E. coli and 95.2% in K. pneumoniae. Of the 21 isolates non-susceptible to fosfomycin (8 E. coli and 13 K. pneumoniae), 7 (5 E. coli and 2 K. pneumoniae) isolates harboured fosA3 and all of them co-harboured bla(CTX-M-1group) or bla(CTX-M-9group). The STs of the isolates harbouring fosA3 were diverse (E. coli: ST1, ST1, ST533, ST2 and ST86; K. pneumoniae: ST11 and ST101). The plasmid replicon types of transformants co-harbouring bla(CTX-M-1group) and bla(CTX-M-9group) were IncF and IncN, respectively. By sequence analysis, we found the common feature that the fosA3 gene, connected to bla(CTX-M) via insertion sequences, was located between two IS26 elements oriented in the opposite direction, composing an IS26-composite transposon.. An IS26-composite transposon appears to be the main vehicle for dissemination of fosA3 in E. coli and K. pneumoniae of diverse clones.

Topics: Anti-Bacterial Agents; beta-Lactamases; DNA Transposable Elements; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Korea; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Polymerase Chain Reaction; Prevalence; Sequence Analysis, DNA; Transformation, Bacterial

Guideline recommendations on therapy in urinary tract infections are based on antibiotic resistance rates. Due to a lack of surveillance data, little is known about resistance rates in uncomplicated urinary tract infection (UTI) in general practice in Germany. In a prospective observational study, urine cultures of all women presenting with urinary tract infections in general practice were analysed. Resistance rates against antibiotics recommended in German guidelines on UTI are presented.. In a prospective, multi-center observational study general practitioner included all female patients ≥ 18 years with clinically suspected urinary tract infection. Only patients receiving an antibiotic therapy within the last two weeks were excluded.. 40 practices recruited 191 female patients (mean age 52 years; range 18-96) with urinary tract infections. Main causative agent was Escherichia coli (79%) followed by Enterococcus faecalis (14%) and Klebsiella pneumoniae (7.3%).Susceptibility of E.coli as the main causative agent was highest against fosfomycin and nitrofurantoin, with low resistance rates of 4,5%; 2,2%. In 17,5%, E.coli was resistant to trimethoprim and in 8,5% to ciprofloxacin.. Resistance rates of uropathogens from unselected patients in general practice differ from routinely collected laboratory data. These results can have an impact on antibiotic prescribing and treatment recommendations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Fosfomycin; General Practice; Germany; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Microbial Sensitivity Tests; Middle Aged; Nitrofurantoin; Prospective Studies; Trimethoprim; Urinary Tract Infections; Young Adult

Therapeutic options for multi-drug resistant (MDR) Escherichia coli in dogs or cats are limited. The objective of this study was to establish in vitro susceptibility of canine and feline E. coli to fosfomycin. Two sources of isolates were categorized based on susceptibility as to no resistance (NDR), single drug resistance (SDR), multidrug resistance (MDR) or extreme drug resistance (XDR). Clinical isolates were collected from throughout the US from dogs (n=157) or cats (n=43) with naturally occurring infection between March 2008 and January 2010. Experimental isolates were collected from fecal samples of dogs treated with no drug (NDR), amoxicillin (expressing SDR) or enrofloxacin (expressing MDR or XDR). Fosfomycin minimum inhibitory concentrations (MIC) were determined using E-Test(®). For clinical isolates, most (165/200) originated from the urinary tract, with the number of isolates per resistant category being: NDR (N=44, 22%), SDR (N=65, 32.5%), MDR (N=74, 37%), and XDR (N=17, 8.5%). Of these isolates, 99% (197/200) were susceptible to fosfomycin with the MIC(90) and MIC(50) being 2 and 1 μg/ml, respectively (range: 0.25-196 μg/ml). The number of experimental isolates in each category was NDR (3), SDR (23), MDR (38), and XDR (11) (29.3, 44, and 14.7%, respectively). Of these, 100% were susceptible to fosfomycin with MIC(90) and MIC(50) being 1.5 and 1 μg/ml (range: 0.38-4 μg/ml), respectively. The susceptibility of canine and feline MDR and XDR E. coli to fosfomycin at concentrations well below the susceptible breakpoint supports further investigation for its use when treating E. coli resistant to alternative antimicrobials.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Cats; Dogs; Drug Resistance, Bacterial; Enrofloxacin; Escherichia coli; Escherichia coli Infections; Feces; Fluoroquinolones; Fosfomycin; Microbial Sensitivity Tests; Phenotype; Urine

Escherichia coli and the antimicrobial pressure exerted on this microorganism can be modulated by factors dependent on the host. In this paper, we describe the distribution of antimicrobial resistance to amikacin, tobramycin, ampicillin, amoxicillin clavulanate, cefuroxime, cefoxitin, cefotaxime, imipenem, ciprofloxacin, fosfomycin, nitrofurantoin, and trimetoprim-sulfametoxazole in more than 100,000 E. coli isolates according to culture site and patient age, gender, and location. Bayesian inference was planned in all statistical analysis, and Markov chain Monte Carlo simulation was employed to estimate the model parameters. Our findings show the existence of a marked difference in the susceptibility to several antimicrobial agents depending on from where E. coli was isolated, with higher levels of resistance in isolates from medical devices, the respiratory system, and the skin and soft tissues; a higher resistance percentage in men than in women; and the existence of a clear difference in antimicrobial resistance with an age influence that cannot be explained merely by means of an increase of resistance after exposure to antimicrobials. Both men and women show increases in resistance with age, but while women show constant levels of resistance or slight increases during childbearing age and greater increases in the premenopausal age, men show a marked increase in resistance in the pubertal age. In conclusion, an overwhelming amount of data reveals the great adaptation capacity of E. coli and its close interaction with the host. Sex, age, and the origin of infection are determining factors with the ability to modulate antimicrobial resistances.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Ampicillin; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Imipenem; Infant; Male; Middle Aged; Nitrofurantoin; Retrospective Studies; Tobramycin; Young Adult

An Escherichia coli isolate with New Delhi metallo-beta-lactamase was isolated from a patient with pyelonephritis and prostatitis who returned to Canada after recent hospitalization in India. The patient was successfully treated with ertapenem and fosfomycin. This patient highlights the role of international travel in the spread of antimicrobial drug resistance and blaNDM-1.

Topics: Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Canada; Carbapenems; Drug Resistance, Multiple, Bacterial; Ertapenem; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; India; Male; Microbial Sensitivity Tests; Prostatitis; Pyelonephritis; Travel; Urine

Urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae have become clinical problems because of limited therapeutic options. The role of fosfomycin in the era of growing bacteria resistance has been widely discussed recently. In this study, we aimed to know the local antimicrobial susceptibilities, fosfomycin susceptibility in particular, of urinary ESBL-producing E coli and K pneumoniae isolates in Taiwan.. We collected 200 urine isolates, including 134 ESBL-producing E coli (ESBL-EC) and 66 ESBL-producing K pneumoniae (ESBL-KP) isolates from July 2008 to December 2009 in a university-affiliated teaching hospital in Taiwan. We used disk diffusion method to determine susceptibility to fosfomycin. Fosfomycin may have lower susceptibility when using disk diffusion method compared with agar dilution method. Broth microdilution test was also used to determine minimal inhibitory concentrations (MICs) and susceptibilities to other antimicrobial agents.. Imipenem was active against ESBL-EC and ESBL-KP. Fosfomycin had good susceptibility to ESBL-EC (95.5%), including in hospital-acquired isolates, but lower antimicrobial activity against ESBL-KP (57.6%). Trimethoprim-sulfamethoxazole had the highest resistance rate to ESBL-EC and ESBL-KP. Comparing with non-hospital-acquired isolates, hospital-acquired ESBL-KP was associated with significantly lower susceptibility of gentamicin (13.3% vs. 66.7%), trimethoprim-sulfamethoxazole (8.9% vs. 38.1%), ciprofloxacin (26.7% vs. 61.9%), and amikacin (46.1% vs. 81.0%) (p<0.05). The resistance of some strains to ciprofloxacin was significantly associated with lower susceptibilities of gentamicin (32.6% in ESBL-EC), nitrofurantoin (2.4% in ESBL-KP) and trimethoprim-sulfamethoxazole (9.8% in ESBL-KP) (p<0.05) but not accompanied with decreasing susceptibility of fosfomycin.. Fosfomycin had the excellent activity against ESBL-EC but not ESBL-KP in this study. Based on the study findings, we suggest that fosfomycin can be a therapeutic option for UTIs with ESBL-EC. Nitrofuranoin was actively against ESBL-EC. Nitrofurantoin may be an alternative option for uncomplicated UTIs with ESBL-EC in Taiwan.

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Fosfomycin; Hospitals, Teaching; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Nitrofurantoin; Taiwan; Urinary Tract Infections

The aim of this study was to obtain data on susceptibility patterns of pathogens responsible for both community and hospital urinary tract infections (UTIs); and analyzed risk factors for infection caused by ciprofloxacin-resistant Escherichia coli and extended-spectrum β-lactamase (ESBL)-producing strains in Rwanda. Of 1,012 urine cultures prospectively studied, a total of 196 (19.3%) yielded significant growth of a single organism. The most common isolate (60.7%) was Escherichia coli. The antibiotics commonly used in UTIs are less effective except Fosfomycin-trometamol and imipinem. The use of ciprofloxacin in the previous 6 months (odds ratio [OR] = 7.59 [1.75-32.74]), use of other antibiotics in the previous 6 months (OR = 1.02 [1.02-2.34]), and production of ESBL (OR = 19.32 [2.62-142.16]) were found to be associated with ciprofloxacin resistance among the E. coli isolates. Risk factors for ESBL positivity were the use of ciprofloxacin and third-generation cephalosporin in the preceding 6 months (OR = 3.05 [1.42-6.58] and OR = 9.78 [2.71-35.25], respectively); and being an inpatient (OR = 2.27 [1.79-2.89]). Fosfomycin-trometamol could be included as a reasonable alternative for the therapy of uncomplicated UTI in Rwanda.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Ciprofloxacin; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Inpatients; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Outpatients; Practice Guidelines as Topic; Prospective Studies; Risk Factors; Rwanda; Urinary Tract Infections; Young Adult

Numerous antibiotics have proven to be effective at ameliorating the clinical symptoms of urinary tract infections (UTIs), but recurrent and chronic infections continue to plague many individuals. Most UTIs are caused by strains of uropathogenic Escherichia coli (UPEC), which can form both extra- and intracellular biofilm-like communities within the bladder. UPEC also persist inside host urothelial cells in a more quiescent state, sequestered within late endosomal compartments. Here, we tested a panel of 17 different antibiotics, representing seven distinct functional classes, for their effects on the survival of the reference UPEC isolate UTI89 within both biofilms and host bladder urothelial cells. All but one of the tested antibiotics prevented UTI89 growth in broth culture, and most were at least modestly effective against bacteria present within in vitro-grown biofilms. In contrast, only a few of the antibiotics, including nitrofurantoin and the fluoroquinolones ciprofloxacin and sparfloxacin, were able to eliminate intracellular bacteria in bladder cell culture-based assays. However, in a mouse UTI model system in which these antibiotics reached concentrations in the urine specimens that far exceeded minimal inhibitory doses, UPEC reservoirs in bladder tissues were not effectively eradicated. We conclude that the persistence of UPEC within the bladder, regardless of antibiotic treatments, is likely facilitated by a combination of biofilm formation, entry of UPEC into a quiescent or semiquiescent state within host cells, and the stalwart permeability barrier function associated with the bladder urothelium.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Cell Membrane Permeability; Cells, Cultured; Drug Resistance, Bacterial; Endosomes; Escherichia coli; Escherichia coli Infections; Female; Humans; Mice; Mice, Inbred CBA; Microbial Sensitivity Tests; Recurrence; Urinary Bladder; Urinary Tract Infections; Urothelium

Foreign travel has been suggested to be a risk factor for the acquisition of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. To our knowledge, this has not previously been demonstrated in a prospective study. Healthy volunteers traveling outside Northern Europe were enrolled. Rectal swabs and data on potential travel-associated risk factors were collected before and after traveling. A total of 105 volunteers were enrolled. Four of them did not complete the study, and one participant carried ESBL-producing Escherichia coli before travel. Twenty-four of 100 participants with negative pretravel samples were colonized with ESBL-producing Escherichia coli after the trip. All strains produced CTX-M enzymes, mostly CTX-M-15, and some coproduced TEM or SHV enzymes. Coresistance to several antibiotic subclasses was common. Travel to India was associated with the highest risk for the acquisition of ESBLs (88%; n = 7). Gastroenteritis during the trip was an additional risk factor (P = 0.003). Five of 21 volunteers who completed the follow-up after 6 months had persistent colonization with ESBLs. This is the first prospective study demonstrating that international travel is a major risk factor for colonization with ESBL-producing Enterobacteriaceae. Considering the high acquisition rate of 24%, it is obvious that global efforts are needed to meet the emergence and spread of CTX-M enzymes and other antimicrobial resistances.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Lactamases; Child; Child, Preschool; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sweden; Travel; White People; Young Adult

An increase in extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli has been observed in outpatient settings. Consequently, 100 ESBL-positive E. coli isolates from ambulatory patients with clinically confirmed urinary tract infections were collected by a single laboratory between October 2004 and January 2008. Antimicrobial susceptibility testing was carried out using the oral antibiotics fosfomycin, pivmecillinam, and nitrofurantoin and the parenteral antibiotic ertapenem. Susceptibility rates indicate that fosfomycin (97%), nitrofurantoin (94%), and pivmecillinam (85%) could be considered important oral treatment options.

Topics: Amdinocillin Pivoxil; Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Nitrofurantoin; Urinary Tract Infections

To clarify the molecular mechanisms of fosfomycin resistance in clinical isolates of Escherichia coli, the murA, glpT, uhpT, uhpA, ptsI and cyaA genes were sequenced from six fosfomycin-resistant isolates. Two strains were found to harbour a mutation in the murA gene that leads to an amino acid substitution (Asp369Asn or Leu370Ile) in the target protein. The remaining four strains carried specific mutations in the glpT gene; one strain possessed a mutation and the other three strains possessed truncated versions of the GlpT transporter owing either to the presence of insertion sequences or a deletion in the coding region of the gene. Two of the strains with truncated GlpT had also lost the entire uhpT gene, which encodes another fosfomycin transporter. Uptake of specific substrates for the transporters was either totally blocked or reduced in strains possessing truncated forms of GlpT or those lacking the uhpT gene. Escherichia coli strains expressing an amino-acid-substituted MurA were at least eight-fold more resistant to fosfomycin than the strain overproducing wild-type MurA. In conclusion, novel amino acid substitutions in MurA or the loss of function of transporters were identified as mechanisms of fosfomycin resistance in clinical isolates of E. coli.

Topics: Anti-Bacterial Agents; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; INDEL Mutation; Microbial Sensitivity Tests; Mutation, Missense; Sequence Analysis, DNA

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Microbial Sensitivity Tests; United Kingdom; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Drug Synergism; Escherichia coli; Escherichia coli Infections; Fosfomycin; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

To document fosfomycin susceptibility of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC), analyse trends in fosfomycin use and investigate fosfomycin resistance in ESBL-EC isolated from urinary tract infections (UTIs).. Twenty-seven Spanish hospitals participating in the European Antimicrobial Resistance Surveillance Network were requested to collect up to 10 sequential ESBL-EC for centralized susceptibility testing and typing. EUCAST guidelines were followed for antibiotic susceptibility testing, and bla(ESBL) type, phylogroups and O25b serotype were determined by PCR and sequencing. In addition, the trend in fosfomycin resistance among ESBL-EC causing UTIs was determined in 9 of the 27 hospitals. Total fosfomycin use for ambulatory care was established by WHO-recommended methods.. A total of 231 ESBL-EC (42.4% CTX-M-15, 34.2% SHV-12 and 23.4% CTX-M-14) were collected. The overall rate of fosfomycin resistance was 9.1%, but varied according to ESBL type (5.6% of CTX-M-14 isolates, 5.1% of SHV-12 and 15.3% of CTX-M-15). Of 67 O25b/B2 isolates, 11 (16.4%) were fosfomycin resistant. Predictors of infection with fosfomycin-resistant ESBL-EC were O25b/phylogroup B2 isolates, female gender and nursing home residence. Among 114 197 UTIs caused by E. coli 4740 (4.2%) were due to ESBL-EC. Fosfomycin resistance increased in these isolates from 4.4% (2005) to 11.4% (2009). The use of fosfomycin grew from 0.05 defined daily doses per 1000 inhabitants per day (1997) to 0.22 (2008), a 340% increase.. Key factors related to increased fosfomycin resistance in ESBL-EC causing UTIs could be the rapid growth in community use of fosfomycin, the widespread distribution of the 025b/B2 E. coli clone and the existence of a susceptible population comprising women residing in nursing home facilities.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactamases; DNA Fingerprinting; Drug Resistance, Bacterial; Drug Utilization; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Genotype; Humans; Male; Microbial Sensitivity Tests; Phylogeny; Polymerase Chain Reaction; Sequence Analysis, DNA; Serotyping; Spain; Urinary Tract Infections

The aim of this observational prospective study was to compare the effect of fosfomycin tromethanol (FT) and carbapenems (meropenem or imipenem cilastatin) in the treatment of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli-related complicated lower urinary tract infection (CLUTI). Inclusion criteria were: patients who were aged >18 yr with dysuria or problems with frequency or urgency in passing urine; those with >20 leukocytes/mm³ in urine microscopy and culture-proven ESBL-producing carbapenem or FT-sensitive E. coli in the urine (>10⁵ cfu/mm³); no leukocytosis or fever; and who were treated with ft (oral 3 g sachet x 1 every other night, three times) or carbapenems between march 2005 and January 2006 in our outpatient clinic and hospital. A total of 47 CLUTI attacks in 47 patients (27 FT group, 20 carbapenem group) were observed prospectively. Clinical and microbiological success in the carbapenem and ft groups was similar (19/20 vs 21/27 and 16/20 vs 16/27 p>0.05). Drug acquisition costs were significantly lower in the FT group (p<0.001). Although it is not a randomized controlled study, these data show that ft may be a suitable, effective and cheap alternative in the treatment of ESBL-producing E. coli-related CLUTI.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Urinary Tract Infections; Young Adult

To describe trends in fosfomycin resistance in urinary isolates of Escherichia coli producing extended-spectrum beta-lactamases (ESBLs) in relation to fosfomycin consumption and to characterize representative fosfomycin-resistant isolates.. In 2007-08, an unexpected increase in fosfomycin resistance in ESBL-producing urinary E. coli was observed. Laboratory records were reviewed and a prospective surveillance study was initiated on all urinary tract infections caused by ESBL-producing, fosfomycin-resistant E. coli. bla(ESBL) types, phylogroups, genetic environment and afa/dra operon were determined by PCR and sequencing. Molecular epidemiology was analysed by PFGE and multilocus sequence typing. To elucidate possible mechanisms of fosfomycin resistance, uhpT, glpT, uhpA, ptsI, cyaA and murA genes were analysed. Fosfomycin consumption was determined as recommended by WHO.. From 2004 to 2008, fosfomycin consumption increased by 50%, while fosfomycin resistance in ESBL producers increased from 2.2% to 21.7%. Of 26 isolates studied, 24 produced CTX-M-15 and belonged to the O25b-ST131-phylogroup B2 clonal strain. PFGE revealed two clusters. Cluster I included 18 isolates, 16 of them indistinguishable from strains producing CTX-M-15 previously described in Madrid. The five isolates of Cluster II had the IS26 linked to bla(CTX-M-15) and the afa/dra operon. In Cluster I isolates, no mutations in glpT, uhpT, uhpA, ptsI, cyaA and murA were detected. Cluster II isolates showed a 15 bp deletion (A(169)-C(183)) in uhpA.. Fosfomycin resistance in urinary E. coli has increased due to the acquisition of this resistance by a previously circulating CTX-M-15-producing E. coli O25b-ST131-phylogroup B2 strain. This happened during a period when the use of fosfomycin increased by 50%.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactamases; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Genotype; Humans; Polymerase Chain Reaction; Prevalence; Sequence Analysis, DNA; Urinary Tract Infections

Although in certain countries in Europe fosfomycin trometamol (FT) has been used for many years, in Turkey FT has become available in recent years. FT has a broad-spectrum activity against most of gram-positive and gram-negative bacteria. In this study, we aimed to evaluate the effect of FT, a new alternative antimicrobial agent in the treatment of patients with Escherichia coli related uncomplicated lower urinary tract infection (UTI). For this purpose, between May 2007-July 2008, FT susceptibility of 771 nonduplicate E. coli strains, isolated from urine samples of patients with uncomplicated lower UTI (bacteria > or = 10(5) cfu/mL), was determined by disk diffusion method according to Clinical and Laboratory Standarts Institute (CLSI) criteria. Simultaneously, extended-spectrum beta-lactamase (ESBL) detection was performed by double disk synergy test in all isolates. Among all E. coli isolates, FT resistance rate was 0.4% (3/771) and ESBL positivity was 19.5% (150/771). The rates of ESBL producing strains isolated from inpatients and outpatients were 34.1% (70/205) and 14.1% (80/566), respectively, and the difference was found statistically significant (p = 0.0001). Although resistance to FT was not detected in non-ESBL producing E. coli isolates (n = 621), FT resistance rate was 2% (3/150) in ESBL producers. As far as the current literature was concerned this was the largest scale study investigating the activity of FT in Turkey. Resistance to antimicrobials that had been used frequently as therapeutic options for the treatment of E. coli related UTIs, has been increasing. In the present study high susceptibility rates to FT was determined for urinary E. coli isolates. In conclusion, these data suggest that FT may be a good alternative for the treatment of uncomplicated UTIs as a first line antimicrobial agent.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteriuria; beta-Lactamases; Child; Child, Preschool; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Urinary Tract Infections; Young Adult

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella Infections; Nitrofurantoin

Uncomplicated urinary tract infections (UTIs) are common among female patients. According to the national guidelines of the Dutch College of General Practitioners (GPs), the drugs of first and second choice as therapy for UTIs are nitrofurantoin and trimethoprim with resistance percentages of 2% and 23%, respectively. The third choice is fosfomycin tromethamine for which no current resistance data from The Netherlands are available. The aim of this study was to determine these resistance percentages.. During 2003-04, urine samples were collected from a representative sample of 21 general practices spread over The Netherlands, the Sentinel Stations of The Netherlands Institute for Health Services Research (NIVEL). Escherichia coli isolated from female patients visiting their GP with symptoms of an acute, uncomplicated UTI were used. Fosfomycin tromethamine susceptibility was determined by Etests. An MIC of fosfomycin tromethamine of 64 mg/L or lower was considered to indicate susceptibility, and MIC values of 96 mg/L or higher were considered to indicate resistance. E. coli ATCC 25922 was used as a reference strain.. In total, 1705 E. coli strains were tested, of which 11 (0.65%) were resistant to fosfomycin tromethamine. The MIC(50) and MIC(90) values for this population were 1 and 4 mg/L, respectively. Within the inhibition zone of 162 susceptible E. coli, resistant mutant colonies were observed, of which after repetition of the susceptibility testing 68 were resistant. In total, 79 (5%) strains were resistant to fosfomycin tromethamine. There was no cross-resistance observed between fosfomycin tromethamine and other antimicrobial agents tested previously.. The high in vitro susceptibility to fosfomycin tromethamine in this population and the lack of cross-resistance between fosfomycin tromethamine and other agents together with the extensive global clinical experience support the choice of the national guidelines of the Dutch College of GPs to include fosfomycin tromethamine as a therapeutic option in general practice for uncomplicated UTIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Community-Acquired Infections; Escherichia coli Infections; Family Practice; Female; Fosfomycin; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Middle Aged; Netherlands; Urinary Tract Infections; Urine

In this study, we evaluated the in vitro activity of fosfomycin and 7 other comparator agents against 307 Escherichia coli isolates including ciprofloxacin-resistant or extended-spectrum beta-lactamase (ESBL)-producing isolates. Bacterial isolates were collected from urine and blood from patients at a Korean tertiary-care hospital. Among 307 E. coli isolates, 30.3% were resistant to ciprofloxacin (MIC(90), >32 mg/L) and 7.8% produced ESBLs. The highest resistance rate was observed in ampicillin (69.7%), followed by trimethoprim-sulfamethoxazole (43.0%), and then amoxicillin-clavulanate (32.2%). All isolates were susceptible to imipenem (MIC(90), 0.125 mg/L). All but 1 isolate was susceptible to fosfomycin (MIC(90), 16 mg/L), regardless of the collected sources, ciprofloxacin resistance, and ESBL production. The data showed excellent activity of fosfomycin against E. coli isolates including fluoroquinolone-resistant strains. The clinical usefulness of fosfomycin, as a 1st-line therapy for urinary tract infection, should be evaluated further, especially in regions where ciprofloxacin resistance rates are high.

Topics: Anti-Bacterial Agents; beta-Lactamases; Blood; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections; Urine

The aim of this study was to investigate the susceptibilities of Escherichia coli strains isolated from urine samples, against fosfomycin tromethamine and different antibiotics in the period of October-December 2004 in a local hospital in Ankara, Turkey. A total of 120 E. coli strains isolated from urine cultures of subjects who were admitted to outpatient clinics were included to the study. The identification and antimicrobial susceptibility tests (against amikacin, amoxicillin/clavulanate, ampicillin, cefepime, cefoxitin, cefotaxime, cefuroxime, cefalotin, ciprofloxacin, gentamicin, levofloxacin, meropenem, nitrofurantoin, piperacillin, piperacillin/tazobactam and trimethoprim/sulphametoxazole) were performed by a commercial automatized system (Phoenix, Becton Dickinson, USA). Fosfomycin tromethamine susceptibility was studied by Kirby Bauer disk diffusion method according to the CLSI criteria. Only one strain (0.8%) was found resistant to fosfomycin tromethamine, while no resistance was determined against amikacin and meropenem. Most of the isolates were found susceptible to nitrofurantoin (90%), cefoxitin (82.5%), gentamicin (81%), piperacillin/tazobactam (81%), cefepime (79%) and cefotaxime (%79%). All of the E. coli isolates which were resistant to ciprofloxacin and levofloxacin (44% and 43%, respectively) were found susceptible to fosfomycin tromethamine. In conclusion, since E. coli is by far the most prevalent community acquired urinary tract pathogen, fosfomycin tromethamine seems to be a reasonable alternative for the ampirical therapy of uncomplicated urinary tract infections.

Topics: Anti-Bacterial Agents; Bacteriuria; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Tromethamine; Turkey; Urinary Tract

An in vitro pharmacokinetic/pharmacodynamic perfusion model that simulates a two-compartment open model of serum drug concentration-time profiles following intravenous bolus injection and infusion was developed and mathematically described. In the present apparatus model, flow was kept in a one-way mode to avoid liquid traffic, and the washout effect seen in dilution models was overcome by embedding the tested bacteria in low melting point agarose gel. The validity of the equations and the reproducibility of the apparatus model were ascertained by simulating the concentration-time profiles of cefazolin and fosfomycin by substitution of their pharmacokinetic parameters obtained from humans for the equations. An empirical regimen 1X(q24h) of 1 g with cefazolin administered by intravenous infusion effectively killed a Staphylococcus aureus strain. The same regimen with fosfomycin produced a marked kill-curve with a fosfomycin-susceptible enterohaemorrhagic Escherichia coli O157:H7, whereas considerable regrowth was observed with a resistant strain. These results indicated that the present model was able to provide a convenient and reliable method for evaluating the efficacy of antimicrobial agents administered by intravenous infusion.

Topics: Anti-Bacterial Agents; Body Fluid Compartments; Cefazolin; Escherichia coli Infections; Escherichia coli O157; Fosfomycin; Humans; Infusions, Intravenous; Microbial Sensitivity Tests; Models, Biological; Pharmaceutical Preparations; Staphylococcal Infections; Staphylococcus aureus

Resistance to fosfomycin develops rapidly in experimental conditions, although despite its frequent use in UTI, resistance in E. coli, the main uropathogen, is very low (1-3%), and has remained so for many years. The objective of this study was to ascertain whether E. coli fosfomycin-resistant strains have less fitness than those that are fosfomycin-sensitive in competing, and would therefore tend to disappear in their competition with fosfomycin-sensitive strains in the absence of antibiotics. Fosfomycin-resistant strains (n=11) with different phenotypes of resistance to other antibiotics were used. All but one were lactose (+). Fosfomycin-susceptible strains (n=15) that had the same phenotypes of resistance to other antibiotics as the resistant strains and which had the opposite pattern of lactose fermentation were also used. Thirty-three (33) competition experiments by pairs of strains were conducted in nutrient broth. Equal amounts of the strains were challenged (approx. 50% and approx. 50%) for 4 days, with a daily change to a new medium. Five differential counts were performed on days 0, 1, 2, 3 and 4. In 20 experiments (60.6%) there was a relative increase in the fosfomycin-sensitive strain. In 6 experiments (18.2%) there was a relative increase in the fosfomycin-resistant strain. In 7 experiments (21.2%), on the fourth day none of the strains reached 60%. When the data of the 26 (20+6) experiments in which there were changes were analyzed by the chi2 test there was a statistically significant difference (p=0.044). Resistance to fosfomycin could entail a biological cost (less fitness) for the majority of the E. coli strains assayed.

Topics: Colony Count, Microbial; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fermentation; Fosfomycin; Humans; Lactose; Phenotype; Selection, Genetic; Urinary Tract Infections

The agar dilution, broth microdilution, and disk diffusion methods were compared to determine the in vitro susceptibility of 428 extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin. Fosfomycin showed very high activity against all ESBL-producing strains. Excellent agreement between the three susceptibility methods was found for E. coli, whereas marked discrepancies were observed for K. pneumoniae.

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Mutation; Rifampin

Fosfomycin is a possible oral treatment for lower urinary tract infections caused by Escherichia coli with CTX-M extended-spectrum beta-lactamases but is vulnerable to mutational resistance. Hypermutability among natural E. coli populations might facilitate the emergence of resistance to fosfomycin. We therefore examined the prevalence of mutators amongst urinary isolates of E. coli producing CTX-M beta-lactamases.. Urinary E. coli isolates with CTX-M beta-lactamases (n = 220) were screened for resistance to both rifampicin and fosfomycin, as well as a mutator phenotype, by rifampicin and fosfomycin disc assays. Mutation frequencies for 10 isolates, identified as mutators by the initial disc screen, were determined in triplicate on agar with rifampicin or fosfomycin at 4x MIC and with fosfomycin or nitrofurantoin at 256 mg/L.. The disc screen identified 10 likely mutators and quantitative tests indicated that 9 of these had mutation frequencies of 8.0 x 10(-6)-1.5 x 10(-4) for fosfomycin and 0.1-2.3 x 10(-6) for rifampicin. These mutators were diverse in terms of PFGE type and 4 of the 10 were confirmed as strong mutators with rifampicin and fosfomycin. Only the strongest mutator isolate and hypermutable MutS(-) control strain consistently gave single-step mutants resistant to 256 mg/L fosfomycin. No nitrofurantoin-resistant mutants were selected from any isolate, although they could be selected from the hypermutable MutS(-) control strain.. Mutator phenotypes were found among E. coli expressing CTX-M beta-lactamases and were independent of strain type. These had an increased propensity to fosfomycin resistance.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Mutation; Urinary Tract Infections

Infection due to extended-spectrum beta-lactamase (ESBL)-producing microorganisms is an emerging problem in the community; a high proportion of these microorganisms have been isolated from urine samples of women with uncomplicated urinary tract infections (UTI). The options for oral treatment of uncomplicated UTI are limited because of the multiple drug resistance typical of ESBL-producing strains.. The in vitro activity of fosfomycin (FOS) was determined against 428 ESBL-producing strains, including 290 (68%) E. coli and 138 (32%) K. pneumoniae. Activity of fosfomycin was compared with that of amoxicillin-clavulanate (AMC), ciprofloxacin (CIP) and cotrimoxazole (SxT). MICs of AMC, CIP, and SxT, and detection of ESBL production were tested by the broth microdilution method, whereas FOS MICs were determined by the agar dilution method. ESBLs were characterized by isoelectric focusing, polymerase chain reaction (PCR) and direct sequencing of encoding genes. The genetic relationship among the isolates was determined by REP-PCR.. Among the 428 ESBL-producing isolates studied, 417 (97.4%) were susceptible to FOS (MIC < or = 64 microg/mL). The resistance rate of E. coli to FOS was 0.3%, and was lower than resistance to AMC (11.7%), whereas the resistance rate of K. pneumoniae was 7.2% and was equal to resistance to AMC. SxT and CIP were the least active antibiotic agents against ESBL-producing isolates (sensitivity < 50%). There were no differences in fosfomycin activity against strains expressing different types of ESBLs.. Fosfomycin showed maintained activity against ESBL-producing strains and did not present co-resistance with other antimicrobial groups.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Ciprofloxacin; Cross Infection; Escherichia coli; Escherichia coli Infections; Fosfomycin; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multicenter Studies as Topic; Substrate Specificity; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Neonatal Escherichia coli meningitis is a serious disease with high mortality and poor outcome. Ventriculitis, brain abscess and subdural empyema are frequent, with no homogeneous recommendations available for these complications. The case of a newborn infant who developed sepsis and meningitis caused by E. coli is presented. During intravenous treatment with ampicillin, cefotaxime and gentamycin in recommended doses, the patient developed severe subdural abscesses detected on MRI. After consequent antibiotic therapy over 2 months with fosfomycin, amikacin and meropenem the patient improved clinically and the abscesses regressed and disappeared without neurosurgical intervention. At the age of 6.5 months the infant is healthy and well developed. The conservative treatment of subdural abscesses complicating neonatal Escherichia coli meningitis without neurosurgical intervention is possible. The treatment of the individual case should be discussed between pediatrician and neurosurgeon.

Topics: Amikacin; Brain; Drug Therapy, Combination; Echoencephalography; Empyema, Subdural; Escherichia coli Infections; Female; Fosfomycin; Humans; Infant, Newborn; Intensive Care, Neonatal; Magnetic Resonance Imaging; Meningitis, Escherichia coli; Meropenem; Microbial Sensitivity Tests; Patient Care Team; Thienamycins; Treatment Outcome

Edema disease (ED) of pigs is an enterotoxaemic disease caused by enterotoxaemic Escherichia coli (ETEEC) infection. Antimicrobial therapy for pigs with ED is controversial because it may induce death of sickish piglets. In this study, we investigated the effects in vitro of 7 antimicrobial agents, ampicillin, gentamicin, colistin, bicozamycin, fosfomycin, sulfamethoxazole-trimethoprim and enrofloxacin, on the release and production of shiga toxin (Stx) 2e by ETEEC strains. We found that more Stx 2e accumulated in the bacterial cells than was released into supernatant. Associated with inhibition of cell wall synthesis, the exposure to ampicillin or fosfomycin increased the release of Stx 2e. The production levels of Stx 2e in all antimicrobial-treated cultures were equal to the level in the control or less than in the control. These results suggest that cell wall synthesis inhibitors, such as ampicillin and fosfomycin, may change for the worse in the signs in ETEEC infectious pigs. On the other hand, gentamicin, colistin, bicozamycin and enrofloxacin may be useful for the treatment of pigs with ED.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Cell Wall; Colistin; Edema Disease of Swine; Enrofloxacin; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; Gentamicins; Quinolones; Shiga Toxin 2; Sus scrofa; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Fifty-seven Shiga toxin-producing Escherichia coli (STEC) strains isolated from pigs with edema disease (ED) from 1997 to 2001 in Japan were examined for antimicrobial susceptibilities. The susceptibilities were compared with those of E. coli ATCC 23546 isolated from pig with ED in the 1950's. Consequently, the isolated STECs showed high susceptibility to peptides and bicozamycin in a way similar to the reference strain. On the other hand, the STECs showed low susceptibility to beta-lactams, tetracyclines, novobiocin, fosfomycin, trimethoprim, and old quinolones. It became clear that the susceptibilities of the isolated STECs had diminished in regard to antimicrobials.

Topics: 4-Quinolones; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bridged Bicyclo Compounds, Heterocyclic; Edema Disease of Swine; Escherichia coli; Escherichia coli Infections; Fosfomycin; Japan; Lactams; Microbial Sensitivity Tests; Novobiocin; Peptides; Swine; Tetracyclines; Trimethoprim

Antibiotic fosmidomycin will know as inhibitor of the nonmevalonate pathway of isoprenoid biosynthesis and as possible antimalarial drug, was shown to possess a certain protective effect on mice experimentally infected with tularemia, tiphus or coli-septicemia. Positive effect on mice with chronic form of tuberculosis was not observed when the animals were given 1 mg of fosmidomycin per capita twice a day. Under oxidative conditions an ESR signal of long living nitroxil free radicals were registered in the water solution of fosmidomycin. The radicals are supposed to be involved in the therapeutic effect of the antibiotic.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Escherichia coli Infections; Fosfomycin; Mice; Salmonella Infections; Tuberculosis, Pulmonary; Tularemia; Typhus, Epidemic Louse-Borne

The aim is to evaluate the effectiveness of AM3 (Inmunoferon) in the treatment of the recurrent cystitis in women in order to know the rate of good results, previously to design a clinical trial.. Twenty-four women who had been diagnosed of two cystitis episodes in the previous 6 months without cure by antibiotic treatment were admitted to the study. Standard antibiotic treatment and 3 daily grammes of AM3 was given for 9 months. Infection and irritative symptoms during micturition rate were evaluated at the inclusion date and afterwards, at the first, third, sixth and nineth month.. Nineteen patients finished the study. The infection rate decreased from 100% at the inclusion date to 26% in the first month and then it became stable about 50%. Irritative symptoms during micturition decreased from 46% at the inclusion date to a rate lower than 10% in the 4 controls running.. AM3 reduced evident urinary infection in a 50% and irritative symptoms during micturition in a 90%. Control clinical trials are needed to confirm the AM3 effects on this pathology.

Topics: Adjuvants, Immunologic; Amoxicillin; Calcium Phosphates; Ciprofloxacin; Clavulanic Acid; Cystitis; Drug Evaluation; Drug Therapy, Combination; Escherichia coli Infections; Female; Follow-Up Studies; Fosfomycin; Glycopeptides; Humans; Pilot Projects; Recurrence; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vaginosis, Bacterial

Escherichia coli (E. coli) is the most commonly isolated microorganism in uncomplicated lower urinary tract infections (UTI). Due to the increased isolation of E. coli strains resistant to quinolones, it is important to have available alternative drugs to this class of antibiotics as therapy for UTIs caused by this pathogen. Among the large number of currently available antimicrobial agents, fosfomycin trometamol is a useful alternative due to its peculiar microbiological and pharmacokinetic properties. Therefore, we tested the in vitro susceptibility of 79 quinolone-resistant clinical urinary isolates of E. coli to fosfomycin trometamol in comparison with amoxicillin, chloramphenicol, cotrimoxazole, netilmicin, nitrofurantoin and tetracycline. Fosfomycin trometamol showed high activity with a MIC90 of 4 mg/l. While no strains were resistant to fosfomycin trometamol, 83.5%, 63.3%, 58.2%, and 48.1% of the isolates were resistant to tetracycline, amoxicillin, chloramphenicol and cotrimoxazole, respectively. Nitrofurantoin and netilmicin resistance was present only in 12.7% and 6.3% of the strains, respectively. In conclusion, fosfomycin trometamol has retained its activity against quinolone-resistant strains of E. coli and cross-resistance with other classes of antimicrobial agents is not presently a problem. The strains tested did present high levels of resistance to other classes of antibiotics.

Topics: 4-Quinolones; Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

To evaluate the sensitivity patterns of Escherichia coli isolates obtained from urine specimens from patients with community-acquired urinary tract infections, with a special emphasis on fosfomycin trometamol for the treatment of UTI.. Retrospective analysis of the sensitivity pattern of 16,227 E. coli isolates recovered from urine cultures performed at the Microbiology Laboratory of Madrid Area 11 from 1997 to 2000. The antimicrobial agents tested included ampicillin, amoxycillin-clavulanate, cephalotin, cefuroxime, trimethoprim-sulphamethoxazol, fosfomycin trometamol, nitrofurantoin, and ciprofloxacin. Antibiotic sensitivity testing was performed with the Vitek automatic microdilution system (bioMèrieux, France).. E. coli represented 80.1% of all uropathogens recovered. The percentages of sensitive strains to ampicillin, amoxycillin-clavulanate, cephalotin, cefuroxime, trimethoprim-sulphamethoxazol, nitrofurantoin, and ciprofloxacin were 42.25%, 81.5%, 58.75%, 87.5%, 70%, 94.75%, and 84.75%, respectively. Fosfomycin trometamol was the antibiotic with the highest activity against E. coli, with 95.5% of sensitive isolates.. Fosfomycin trometamol (single dose) is a good alternative that should be considered for the treatment of non-complicated lower urinary tract infections.

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Retrospective Studies; Urinary Tract Infections

Shiga toxin-producing Escherichia coli (STEC) cause significant disease; treatment is supportive and antibiotic use is controversial. Ciprofloxacin but not fosfomycin causes Shiga toxin-encoding bacteriophage induction and enhanced Shiga toxin (Stx) production from E. coli O157:H7 in vitro. The potential clinical relevance of this was examined in mice colonized with E. coli O157:H7 and given either ciprofloxacin or fosfomycin. Both antibiotics caused a reduction in fecal STEC. However, animals treated with ciprofloxacin had a marked increase in free fecal Stx, associated with death in two-thirds of the mice, whereas fosfomycin did not. Experiments that used a kanamycin-marked Stx2 prophage demonstrated that ciprofloxacin, but not fosfomycin, caused enhanced intraintestinal transfer of Stx2 prophage from one E. coli to another. These observations suggest that treatment of human STEC infection with bacteriophage-inducing antibiotics, such as fluoroquinolones, may have significant adverse clinical consequences and that fluoroquinolone antibiotics may enhance the movement of virulence factors in vivo.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Toxins; Ciprofloxacin; Coliphages; Disease Models, Animal; Escherichia coli Infections; Escherichia coli O157; Fosfomycin; Humans; Intestines; Male; Mice; Shiga Toxins

We report three cases of enterocolitis associated with pathogenic Escherichia coli infection in renal transplant recipients.. Patients presented with abdominal pain and diarrhea at 1, 3 and 7 years after living-related renal transplantation. Pathogens of enterocolitis were identified by stool culture as verotoxin-2-producing O157:H7 E. coli, non-verotoxin-producing E. coli 06 and 0125. All patients were basically treated with fluid replacement with additional fosfomycin administration in the patient with O157:H7 E. coli infection. Immunosuppressive drugs were kept at maintenance doses throughout the treatment.. All patients recovered uneventfully within 10 days after the onset of enterocolitis without severe complications.

Topics: Adult; Anti-Bacterial Agents; Enterocolitis; Escherichia coli Infections; Female; Fluid Therapy; Fosfomycin; Humans; Kidney Transplantation; Male; Postoperative Complications

There have been some reservations about the treatment of enterohemorrhagic Escherichia coli (EHEC) infection with antibiotics to prevent the occurrence of hemolytic uremic syndrome (HUS). However, the administration of antimicrobial agents for EHEC infection is under discussion. Therefore, we used an experimental mouse model to assess the advantage/disadvantage of two major antibiotics, levofloxacin (LVFX) and fosfomycin (FOM). Germ-free IQI mice were inoculated with EHEC O157 strain EDL931 or #7. Bacteria colonized feces at 10(9)-10(10) CFU/g, and Shiga toxins (STXs) were detected in the feces. From 1 day after infection, mice were assigned to LVFX (20 mg/kg) once daily or FOM (400 mg/kg) once daily. A significant decrease in overall mortality was observed after treatment of LVFX, with EHEC disappearing immediately from the feces of mice. FOM also reduced mortality for one strain, the STX level decreased gradually. LVFX exhibited higher therapeutic efficacy than FOM. Strain differences were observed in the model during the treatment.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Toxins; Diarrhea; Disease Models, Animal; Escherichia coli Infections; Escherichia coli O157; Feces; Fosfomycin; Germ-Free Life; Humans; Levofloxacin; Mice; Ofloxacin; Shiga Toxins; Treatment Outcome

Antibiotic therapy for infection with Shiga-toxin-producing Escherichia coli O157:H7 is controversial because of the possibility of its inducing hemolytic uremic syndrome and acute encephalopathy. In a previous study, mice with protein-calorie malnutrition were found to be highly susceptible to this pathogen. The efficacy of oral antibiotic therapy in malnourished mice infected with O157 organisms was assessed. Mice fed a low-protein calorie diet were infected intragastrically with 2 x 10(6) colony-forming units of a Shiga-toxin-producing strain of Escherichia coli O157:H7. Infected mice were orally given a therapeutic dose of an antibiotic, including norfloxacin, fosfomycin, kanamycin, ampicillin, clarithromycin or trimethoprim-sulfamethoxazole for 3 days: mice on protocol A received the antibiotic on days 1-3, starting on the day after infection, and mice on protocol B received the antibiotic on days 3-5. The duration of fecal pathogen excretion was shorter and the toxin level in the stool and blood lower in the mice that received protocol A than in untreated mice; all of the mice treated on protocol A survived the lethal infection. All antibiotics except trimethoprim-sulfamethoxazole, administered on protocol B, exhibited the same effect as that exhibited by the respective antibiotic administered on protocol A. Only the mice treated with protocol B of trimethoprim-sulfamethoxazole had a higher toxin level in the blood than untreated controls, resulting in 95% mortality. These results suggest that the antibiotics used in this study, except for trimethoprim-sulfamethoxazole, could reduce the risk of hemolytic uremic syndrome and acute encephalopathy following Escherichia coli O157:H7 infection in humans, and that fosfomycin, in particular, may be relevant for testing in humans.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Bacterial Toxins; Brain Chemistry; Disease Models, Animal; Disease Progression; Escherichia coli Infections; Escherichia coli O157; Feces; Fosfomycin; Kanamycin; Mice; Mice, Inbred C57BL; Norfloxacin; Protein-Energy Malnutrition; Reference Values; Sensitivity and Specificity; Shiga Toxins; Statistics, Nonparametric; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study is to evaluate the therapeutic effect of the antimicrobial agents, fosfomycin (FOM), minocycline (MINO), kanamycin (KM) and norfloxacin (NFLX) in the enterohemorrhagic Escherichia coli (EHEC) infected mouse model which we established previously (Infect. Immun. 62 (1994) 3447-3453). Each of the antimicrobial agents, 1/16 LD(50), was given to the mice per os (p.o. ) or intraperitoneally (i.p.) for 3 days after bacterial inoculation and then we observed their mortality rate for 2 weeks. The mortality rates of mice administered with MINO (p.o./i.p.), KM (p.o.), NFLX (p. o./i.p.) were significantly lower than those of the control group. Both the bacterial number and VT2c level in the feces of the FOM group were lower than those of the NFLX group on day 1, but reversed on day 3. In an in vitro experiment, each of the four drugs in combination with mitomycin C (MMC) caused a more significant decrease in the bacterial number than sole MMC, and they consequently indicated the suppressive effect on the release of VT2c.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Toxins; Colony Count, Microbial; Drug Synergism; Enterotoxins; Escherichia coli Infections; Escherichia coli O157; Feces; Fosfomycin; Injections, Intraperitoneal; Kanamycin; Male; Mice; Mice, Inbred ICR; Minocycline; Mitomycin; Norfloxacin; Shiga Toxin 2

Though O157 can cause a life-threatening diseases, the therapeutic protocol using antibiotics for the infection is still controversial. Main reasons for hesitating the uses of antibiotics for the infection is their possibility to enhance the release of verotoxins (VT). We have recently established the mouse model of O157 infection using germfree mice. Using this animal model of O157 infection, we examined therapeutic efficacy of antibiotics. Fosfomycin (FOM) and norfloxacin (NFLX) were selected for in vivo examination, because of their lower MIC under anaerobic condition (MIC:FOM = 0.78; NFLX = 0.10 microgram/ml) than those of the other antibiotics including kanamycin, doxycycline, minocycline, choramphenicol, cefaclor and ampicilin. When germfree BALB/c mice were orally infected with 1 x 10(5)CFU of O157 (clinically-isolated strain, TI001) at day 0, all mice died at 8 to 9 d after the infection. Oral treatment of the mice with FOM (500 mg/kg/d, twice a day) or NFLX (50 mg/kg/d, twice a day) everyday for 5 days starting at 3 hr after the infection significantly improved the survival rate from 0% to 83.3%, and 100%, respectively. VT could not be detected in the feces of the mice in either groups, suggesting that neither of these antibiotics enhanced the release of VT. Interestingly, when FOM treatment was started at 3, 6, 12 or 24 hr after the infection, the survival rate was 100%, 100%, 0% and 0%, respectively. Thus, in conclusion, FOM and NFLX are both useful as the therapeutic agents for O157 infection. However, the treatment should be started in the early phase after the infection.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Toxins; Disease Models, Animal; Escherichia coli Infections; Escherichia coli O157; Fosfomycin; Germ-Free Life; Male; Mice; Mice, Inbred BALB C; Norfloxacin; Shiga Toxin 1; Time Factors

Between the end of November 1996 and the beginning of March 1997, there was an outbreak of Escherichia coli O26:H11 infection in Asahikawa. The strain produced only verotoxin type 1. The minimal inhibitory concentrations (microgram/ml) of the strain under aerobic condition and those of anaerobic were as follows: chloramphenicol (1.56, 0.78), minocycline (12.5, 3.13), kanamycin (3.13, 25), ampicillin (> 100, > 100), fosfomycin (12.5, 1.56), norfloxacin (0.1, 0.1), and cefaclor (6.25, 3.13). Forty-one episodes of antibiotic therapy to 32 children, who were treated in Asahikawa Kosei Hospital, Asahikawa Municipal Hospital, and Asahikawa Red Cross Hospital, were evaluated bacteriologically. In 26 episodes treated with fosfomycin, the pathogen from stools of 19 were eradicated, 4 were not eradicated, and 3 were isolated again within 2 weeks after the cessation of therapy. Eight episodes treated with norfloxacin and 5 episodes in kanamycin were all eradicated.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Child; Disease Outbreaks; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Japan; Kanamycin; Norfloxacin; Retrospective Studies

The drug-resistance patterns and plasmid profiles of 147 isolates (patient origin 142 and food origin 5 isolates) from the outbreak of enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection in Obihiro-city Hokkaido in late October, 1996, were examined. Thirty-six isolates were resistant to tetracycline (TC) (24.5%), 15 of which were resistant to both streptomycin and TC. The minimal growth inhibitory concentration (MIC) of fosfomycine (FOM) was examined, confirming that MIC changed by the cultivation conditions, that is 12.5 micrograms/ml at the aerobic condition, 1.6 micrograms/ml at the anaerobic condition and 3.2 micrograms/ml on blood agar plates. Furthermore, though E. coli O157 could not be detected once by the FOM medication, FOM sensitivity of the patient origin O157 isolates who became O157-positive again was examined. Any changes in FOM sensitivity were not observed. Plasmid profiles of all isolates were divided by 4 patterns from A to D. The most dominant pattern was type A, and plasmid profiles of food origin O157 belonged to pattern A. In 9 examples of the person-to-person infection in the family, plasmid patterns of O157 isolates were the same to each other, even though drug-resistant patterns were different. In 13 patients developing the duration of excretion of EHEC, the changes of the drug-resistance patterns were correlated with the changes of plasmid profiles. By comparing plasmid profiles and TC resistance, it was suggested that TC resistance was controlled on a plasmid. Since food origin O157 isolates were sensitive to all drugs and presenting the same plasmid profiles, demonstrating that TC resistance and plasmid are newly added to the bacterial cells while food origin O157 isolates passe inside the human body.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child, Preschool; Disease Outbreaks; Drug Resistance, Microbial; Escherichia coli Infections; Escherichia coli O157; Female; Fosfomycin; Humans; Japan; Male; Plasmids; Streptomycin; Tetracycline

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Child; Escherichia coli Infections; Escherichia coli O157; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Japan; Organosilicon Compounds; Risk Factors; Surveys and Questionnaires; Trisaccharides

In 1996, Japan had several large outbreaks of enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection. We surveyed physicians who examined and treated these patients, and found that most of the patients (95.9%) received antimicrobial agents as treatments, in particular, fosfomycin comprised 84.0% of the prescribed treatment. Since the administration of antimicrobial agents for EHEC infection is under discussion, we also analyzed the effects of 7 antimicrobial agents including fosfomycin on the production and release of Vero toxins (VTs) by EHEC. The addition of fosfomycin into EHEC culture in CAYE broth at 5 h after the start of incubation caused a marked increase of VT1 release and production, as revealed by an immunological toxin assay (RPLA). However, a cytotoxicity assay of Vero cells showed a small increase of biological activity in the specimens treated with fosfomycin because the Vero cell assay reflects total cytotoxicity of VT1 and VT2. These results indicate that further study is necessary before concluding whether antimicrobial agents actually worsen an EHEC infection.

Topics: Animals; Anti-Bacterial Agents; Bacterial Toxins; Biological Assay; Cells, Cultured; Child; Child, Preschool; Chlorocebus aethiops; Culture Media, Conditioned; Cytotoxicity Tests, Immunologic; Disease Outbreaks; Escherichia coli Infections; Escherichia coli O157; Female; Fosfomycin; Humans; Infant; Infant, Newborn; Japan; Male; Microbial Sensitivity Tests; Shiga Toxin 1; Vero Cells

An outbreak of O-157:H7 diarrheal illnesses occurred in junior schools of Sakai-city, Osaka prefecture, in last July, 1996. At the beginning of the outbreak, many patients rushed to outpatient clinics. From the practical experiences, we examined the necessity of fluid therapy in patients regarding their initial clinical features. The risk factors for development of HUS were noted as presence of fever, WBC counts of more than 10,000/microliter and more than 1.0 mg/dl of CRP. During the prodoromal illness, administration with available antimicrobial agents would be advisable for high risk patients, while it would yet be remain to be further investigated. The majority of the patients with clinical manifestations showed neither signs for dehydration nor electrolyte abnormalities based on the blood examination data and biochemical analysis of the serum. Therefore, the fluid therapy did not appear necessary for majority of patients except a few high risk patients, when outpatient clinics were crowded with emergency patients.

Topics: Administration, Oral; Anti-Bacterial Agents; Anti-Infective Agents; Child; Disease Outbreaks; Emergencies; Escherichia coli Infections; Escherichia coli O157; Female; Foodborne Diseases; Fosfomycin; Humans; Male; Norfloxacin

Predictive factors for the development of hemolytic uremic syndrome (HUS) were evaluated in 88 inpatients who suffered from enterohemorrhagic E. coli infections in the outbreak in Sakai, 1996. All in- and outpatients received oral or intravenous fosfomycin within acute phase of hemorrhagic colitis, and HUS complicated 1.4% of them. Persistence of bloody stools and diarrhea were longer in HUS patients than in non-HUS patients, but persistence of abdominal pain was not different in either group. Leukocytosis with leukocyte counts over 15,000/microliters and/or elevated CRP level over 2.0 mg/dl at admission, and fever and/or vomiting in the course of hemorrhagic colitis were more frequent in HUS patients than in non-HUS patients. Early intensive treatments including gammaglobulin, urinastatin, aspirin, and dipyridamole were employed in 34 high risk patients for prevention of HUS. These patients were estimated to be at risk of developing HUS because of incomplete HUS, nephropathy, elevated LDH level, thrombocytopenia, or age younger than two years old. These treatments were clinically effective.

Topics: Abdominal Pain; Adolescent; Age Factors; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Child; Diarrhea; Dipyridamole; Escherichia coli Infections; Female; Fever; Fosfomycin; gamma-Globulins; Glycoproteins; Hemolytic-Uremic Syndrome; Humans; Kidney Diseases; Leukocyte Count; Liver Diseases; Male; Melena; Platelet Aggregation Inhibitors; Risk Factors; Sex Factors; Time Factors

In July, 1996, a massive outbreak of hemorrhagic enterocolitis involving more than 5,000 people was caused by enterohemorragic Escherichia coli (EHEC) O157:H7 occurred mainly among elementary school children of Sakai City, Japan. The antibacterial activities in vitro against EHEC from stool specimens were determined. Norfloxacin showed the highest antibacterial activity, and fosfomycin, kanamycin, ampicillin, cefaclor were considered as effective drugs. But doxycycline showed lower antibacterial activities compared to other examined drugs, and it appears necessary to take antibiotic resistance of Escherichia coli into consideration when a treatment regimen is determined. As a result of the oral administration of fosfomycin to 95 patients of hemorrhagic enterocolitis and carrier, no patients developed complications with hemolytic uremic syndrome (HUS). However, a study of 17 patients with HUS demonstrated the fact that most of them were subjected to intravenous administration of fosfomycin. It may be needed to consider oral administration route of effective antibiotics in the treatment of enterocolitis in order to maintain high concentrations of a drug in the intestine.

Topics: Administration, Oral; Ampicillin; Anti-Bacterial Agents; Cefaclor; Cephalosporins; Child; Disease Outbreaks; Drug Resistance, Microbial; Enterocolitis; Escherichia coli Infections; Escherichia coli O157; Fosfomycin; Humans; Japan; Kanamycin; Penicillins

Two new nucleotide antibiotics, fosfadecin and fosfocytocin, have been isolated from the culture filtrates of Pseudomonas viridiflava PK-5 and Pseudomonas fluorescens PK-52, respectively. These antibiotics were purified by column chromatographies using adsorption, gel filtration and ion exchange resins. On the basis of the spectroscopic and degradation studies, the chemical structures of fosfadecin and fosfocytocin were determined. These antibiotics were either enzymatically or chemically hydrolyzed to generate fosfomycin and a new antibiotic, fosfoxacin, which are also produced in the culture filtrates. They showed antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial activity of these nucleotide antibiotics was weaker than that of fosfomycin and fosfoxacin.

Topics: Adenosine Diphosphate; Animals; Anti-Bacterial Agents; Bacteria; Chromatography; Cytidine Diphosphate; Cytidine Monophosphate; Escherichia coli Infections; Fermentation; Fosfomycin; Hydrolysis; Magnetic Resonance Spectroscopy; Mice; Molecular Structure; Pseudomonas; Staphylococcal Infections

The effect of fosfomycin (FM) has been examined on the "footpad swelling reaction" (FPSR) as a model for cellular immunity and on the course of experimental infection with FM resistant E. coli using normal and immunocompromised mice. FM given the day of immunization improved FPSR response progressively up to a dose of 30 mg/kg, higher doses had no effect. If FM was injected 1 or 3 days after immunization doses of 30 mg/kg induced a considerable stimulation, whereas higher doses were inhibitory. In contrast to the high dose of 50 mg of FM per kg, 30 mg/kg increased the stimulatory effect induced by small doses of CY and reduced the inhibitory effect of high CY doses. The depressing effect of hydrocortisone (HC) was also reduced by 30 mg/kg of FM, but not by the higher one. In experimental infection with E. coli, FM in doses of 30 mg/kg was more effective than the higher ones in reducing mortality rate. Comparable results were obtained with CY pretreated animals.

Topics: Animals; Cyclophosphamide; Escherichia coli Infections; Fosfomycin; Hydrocortisone; Immunity, Cellular; Male; Mice; Mice, Inbred BALB C

Topics: Animals; Cystitis; Drug Combinations; Drug Evaluation, Preclinical; Escherichia coli Infections; Fosfomycin; Klebsiella Infections; Norfloxacin; Pipemidic Acid; Proteus Infections; Rats; Rats, Inbred Strains; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Oral single-dose therapy with fosfomycin-trometamol (F-T) was used in 18 patients with lower urinary tract infections. The isolated bacterial strains presented a minimum inhibitory concentration of greater than 128 micrograms/ml in vitro. In spite of this 'resistance' in vitro, a clinical and bacteriological cure was obtained in 12 cases (66%). There were relapses in 2 cases, and clinical and bacteriological failure in only 2 cases. These results are due to the high urinary levels and prolonged bactericidal activity of urine after single-dose therapy with 3-5 g F-T. The clinical and biological tolerance was very good.

Topics: Administration, Oral; Adult; Aged; Drug Administration Schedule; Drug Resistance, Microbial; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Middle Aged; Urinary Tract Infections

Topics: Amniotic Fluid; Ampicillin; Animals; Anti-Bacterial Agents; Bile; Cefaclor; Cephalexin; Escherichia coli Infections; Fosfomycin; Gentamicins; Humans; In Vitro Techniques; Kanamycin; Klebsiella Infections; Microbial Sensitivity Tests; Urine

Topics: Anti-Bacterial Agents; Binding, Competitive; Cephalexin; Drug Combinations; Drug Synergism; Drug Therapy; Enzyme Inhibitors; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella Infections; Proteus Infections; Salmonella Infections; Staphylococcal Infections; Streptococcal Infections

Two models of pneumonia--the experimental E. coli-pleuropneumonia and "intrapulmonary" E. coli-pneumonia--were employed in these studies. Only fosfomycin was effective in both models even at the low dosage of 100 mg/kg/d. The comparative drugs cefotaxime and cefoxitin, however, were not able to reduce the bacteria in both lungs even at very high dosages of 900 mg/kg and 300 mg/kg per day respectively over 6 days.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Cefoxitin; Cephalosporins; Dose-Response Relationship, Drug; Escherichia coli Infections; Female; Fosfomycin; Kinetics; Pleuropneumonia; Rats

Fosfomycin inhibits the development of severe pyogenic infection by Staphylococcus aureus in kidneys if administered during establishment of infection. It inhibits the development of lethal infection by Escherichia coli. It has a positive therapeutic effect on listeria infection in mice even with a fosfomycin resistant mutant.

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Microbial; Escherichia coli Infections; Fosfomycin; Kidney; Listeriosis; Mice; Nephritis; Staphylococcal Infections

The effect of calcium salt of fosfomycin in the treatment of 43 neonates suffering from acute gastroenterocolitis produced by enteropathogenic E. coli is evaluated. The minimal inhibitory concentration of these E. coli was, generally, lower than 128 mug/ml. Dosages of 150-200 mg/kg body weight/day were administered orally every 8 h. This treatment lasted for 4 days only. Clinical evolution was favorable in 38 (88%) babies and bacteriological evolution in 30 (70%). In eight cases a different flora to the initial was selected during the treatment with fosfomycin. None of the cases treated showed any toxic alteration attributed to the antibiotic.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Drug Evaluation; Escherichia coli Infections; Female; Fosfomycin; Gastroenteritis; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male

A left parietal parasagittal meningioma was removed in a 67-year-old female patient. In the postoperative period she had a neurosurgical cerebral suppurating infection: subdural, epidural and epicranial, connected to the exterior by several fistulas. In the operative revision and after a culture, the germ causing the infection, E. coli, was isolated. Treatment was begun with 16 g of intravenous fosfomycin and 120 mg daily of 6-methylprednisolone intramuscularly, and this treatment cured the patient.

Topics: Aged; Anti-Bacterial Agents; Brain Neoplasms; Drug Therapy, Combination; Escherichia coli Infections; Female; Fosfomycin; Humans; Meningioma; Methylprednisolone; Surgical Wound Infection

We have examined the antibacterial activity of the new antibiotic, fosfomycin (FOM) in vitro and in vivo. The following results were obtained. 1. FOM showed a broad antibacterial spectrum. 2. The antibacterial activity of FOM was enhanced in the medium at pH 6 and pH 7, and was also influenced by the addition of rabbit serum, calf serum, glucose-6-phosphate or defibrilated sheep blood to the growth medium, and by the size of inoculum. 3 FOM showed especially strong bactericidal action upon the bacteria at the logarithmic phase. 4. FOM showed remarkable therapeutic effect against most strains of gram-positive and gram-negative bacteria tested in experimental infections of mice. 5. The therapeutic effect of FOM was especially remarkable for infection with Salmonella. 6. The therapeutic effect of FOM was more potent than the other drugs tested against infection of Pseudomonas aeruginosa. 7. It seems that FOM is more active in vivo than in vitro with respect to antibacterial activity.

Topics: Animals; Anti-Bacterial Agents; Drug Evaluation, Preclinical; Escherichia coli; Escherichia coli Infections; Fosfomycin; Haemophilus influenzae; Klebsiella Infections; Male; Mice; Microbial Sensitivity Tests; Proteus; Proteus Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Salmonella; Salmonella Infections, Animal; Serratia marcescens; Staphylococcal Infections; Staphylococcus