fosfomycin and Fever

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

This study sought to evaluate the antibacterial effect of fosfomycin tromethamine (FT) on the bacteria inside urinary infection stones.. The internal structures of urinary stones were observed via scanning electron microscopy to verify the presence of internal bacteria. We randomly assigned equal numbers of patients with kidney stones who met the inclusion criteria into two groups in a prospective study and treated them with different perioperative antibiotics. One group (experimental group) was treated with FT, and the other (control group) was treated with cefuroxime sodium. All stone specimens were collected via percutaneous nephrolithotomy (PCNL). The primary infection stones were screened via a stone component analysis, 30 cases in the experimental group and 31 cases in the control group. High-performance liquid chromatography (HPLC)-mass spectrometry was used to measure the drug concentration inside the stones, the bacterial count was calculated via stone culture, and the clinical infection index were monitored for between-group comparisons.. Compared with the control group, the experimental group had a higher internal drug concentration, a higher drug sensitivity against various pathogenic bacteria, a lower bacterial colony count in the stone culture, and a lower incidence of postoperative clinical infection.. FT is more effective than cefuroxime, which is commonly used during the perioperative period of urinary stones, and exerts a high antibacterial effect on these internal bacteria, and effectively reduces the probability of infection and sepsis after urinary stone surgery. FT can be used as an antibiotic during the perioperative period of urinary stones.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteria; Cefuroxime; Colony Count, Microbial; Female; Fever; Fosfomycin; Humans; Kidney Calculi; Male; Middle Aged; Nephrolithotomy, Percutaneous; Postoperative Complications; Prospective Studies; Sepsis

To compare efficacy, safety, and cost-effectiveness of fosfomycin tromethamine with other standard-of-care antibiotics in patients undergoing ureteroscopic lithotripsy.. This study was a prospective, multicenter, randomized, controlled trial. Eligible patients scheduled for ureteroscopic lithotripsy were randomly assigned to receive either fosfomycin (fosfomycin group, N = 101 patients) or standard-of-care antibiotic therapy as prophylaxis (control group, N = 115 patients). The incidence of infectious complications and adverse events was analyzed between the two groups, as well as the cost-benefit analysis.. The incidence of infections following lithotripsy was 3.0% in the fosfomycin group and 6.1% in the control group (p > 0.05). Only asymptomatic bacteriuria was reported in fosfomycin group. In the control group was reported asymptomatic bacteriuria (3.5%), fever (0.9%), bacteremia (0.9%), and genitourinary infection (0.9%). The rate of adverse events was very low, with no adverse event reported in the fosfomycin group and only one in the control group (forearm phlebitis). The average cost per patient of antibiotic therapy with fosfomycin was 151.45 ± 8.62 yuan (22.7 ± 1.3 USD), significantly lower compared to the average cost per patient of antibiotics used in the control group 305.10 ± 245.95 yuan (45.7 ± 36.9 USD; p < 0.001).. Two oral doses of 3 g fosfomycin tromethamine showed good efficacy and safety and low cost in perioperative prophylaxis of infections following ureteroscopic stone removal.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bacteriuria; Cost-Benefit Analysis; Female; Fever; Fosfomycin; Humans; Lithotripsy; Male; Middle Aged; Perioperative Care; Prospective Studies; Standard of Care; Ureteral Calculi; Ureteroscopy

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

It has been demonstrated that fosmidomycin has good tolerability and rapid onset of action, but late recrudescences preclude its use alone; in vitro, clindamycin has been shown to act synergistically with fosmidomycin against Plasmodium falciparum. We conducted a study in pediatric outpatients with P. falciparum malaria in Gabon to evaluate the efficacy and safety of an oral combination of fosmidomycin-clindamycin of 30 mg/kg and 10 mg/kg of body weight, respectively, every 12 h. Patients 7-14 years old were recruited in cohorts of 10. The first 10 patients were treated for 5 days. The duration of treatment was then incrementally shortened in intervals of 1 day if >85% of the patients in a cohort were cured by day 14. All dosing regimens were well tolerated, and no serious adverse events occurred. Asexual parasites and fever rapidly cleared in all patients. Cure ratios of 100% on day 14 were achieved with treatment durations of 5 (10/10 patients), 4 (10/10 patients), 3 (10/10 patients), and 2 days (10/10 patients); 1 day of treatment led to a cure ratio of 50% (5/10 patients). Fosmidomycin-clindamycin is safe and well tolerated, and short-course regimens achieved high efficacy in children with P. falciparum malaria. Fosmidomycin-clindamycin is a promising novel treatment option for malaria.

Topics: Administration, Oral; Adolescent; Animals; Antimalarials; Blood; Child; Clindamycin; Drug Therapy, Combination; Female; Fever; Fosfomycin; Gabon; Humans; Malaria, Falciparum; Male; Parasitemia; Plasmodium falciparum

Until now, studies confirming the safety of glycopeptide restriction in the empirical treatment of prolonged fever and neutropenia included only nine children. In an open-label observational study, the use of teicoplanin in paediatric oncology patients was investigated. A period of unrestricted use (2001-2003) was compared with a second period (2004) following implementation of a restrictive treatment guideline. Empirical first-line treatment consisted of piperacillin/tazobactam; in 2004, fosfomycin was added after 72 h as the second-line combination instead of teicoplanin. In total, 213 episodes (n=163 in 2001-2003; n=50 in 2004) managed with teicoplanin or fosfomycin (only 2004) were eligible. Empirical treatment of fever of unknown origin with teicoplanin was reduced by 97%. In 2004, the mean length of stay was 0.4 days shorter, no infection-related death occurred and no vancomycin-resistant enterococci were detected. Restriction of empirical glycopeptides is safe in paediatric cancer patients after first-line treatment with piperacillin/tazobactam. Fosfomycin appears to offer a feasible and cost-saving alternative in second-line combination therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Fever of Unknown Origin; Fosfomycin; Glycopeptides; Humans; Infant; Length of Stay; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Teicoplanin; Treatment Outcome

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

Topics: Adult; Aged; Ampicillin; Anti-Bacterial Agents; Cephaloridine; Female; Fever; Fosfomycin; Humans; Injections, Intramuscular; Male; Middle Aged; Surgical Wound Infection; Time Factors