Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children.

BACKGROUND: Despite its broad spectrum and excellent safety profile, fosfomycin is still rarely used in pediatrics, with very limited experience from clinicians. METHODS: We retrospectively reviewed the medical records of all children admitted to Bambino Gesù Children's Hospital, IRCCS, Rome, Italy, and treated with fosfomycin for any serious infection. Children with immunodeficiency and oncologic diseases were excluded. Of each, we reported and analyzed demographic and clinical data. RESULTS: The clinical charts of 20 patients were reviewed and analyzed. The mean age was 10.2 years. Most children were males (85%). Most patients treated had an osteo-articular infection (65%). In our sample, 7 patients (35%) had an underlying comorbidity. The causative agent was isolated in 14 cases (70%). All patients were treated with a combination of 2-3 antibiotics, including fosfomycin. The average duration of antibiotic treatment was 18 days. After treatment, 8 patients (40%) experienced a mild adverse reaction, possibly correlated with the administration of fosfomycin. All patients were discharged in good clinical condition. CONCLUSIONS: The present study reports on a sample of pediatric patients with complicated infections where administration of fosfomycin led to eradication of the disease with little or no side effects. Role of the underlying condition and concomitant medication in causing the reaction could not be ruled out. These data suggest that fosfomycin is an effective and safe antibiotic in the pediatric population, particularly for deep-seated infections sustained by multi-drug resistant pathogens.

Parenteral Fosfomycin in Gastrointestinal Surgery: A Systematic Review.

BACKGROUND: To investigate if perioperative parenteral administration of fosfomycin given before or during gastrointestinal surgery could protect against postoperative infectious complications and characterise the administration of fosfomycin and its harms. METHODS: This systematic review included original studies on gastrointestinal surgery where parental administration of fosfomycin was given before or during surgery to≥5 patients. We searched three databases on March 24 2023 and registered the protocol before data extraction (CRD42020201268). Risk of bias was assessed with Cochrane Handbook risk of bias assessment tool or the Newcastle-Ottawa Scale. A narrative description was undertaken. For infectious complications, results from emergency and elective surgery were presented separately. RESULTS: We included 15 unique studies, reporting on 1,029 patients that received fosfomycin before or during gastrointestinal surgery. Almost half of the studies were conducted in the 1980s to early 1990s, and typically a dose of 4 g fosfomycin was given before surgery co-administered with metronidazole and often repeated postoperatively. The risk of bias across studies was moderate to high. The rates of infectious complications were low after fosfomycin; the surgical site infection rate was 0-1% in emergency surgery and 0-10% in elective surgery. If reported, harms were few and mild and typically related to the gastrointestinal system. CONCLUSION: There were few postoperative infectious complications after perioperative parenteral administration of one or more doses of 4 g fosfomycin supplemented with metronidazole in various gastrointestinal procedures. Fosfomycin was associated with few and mild harms.

Fosfomycin-induced agranulocytosis: a case report and review of the literature.

BACKGROUND: The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal. CASE PRESENTATION: A 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count. CONCLUSION: This is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.

Effectiveness of fosfomycin-based antimicrobial prophylaxis for transrectal ultrasound-guided prostate biopsy: A Korean multicenter study.

PURPOSE: Recent studies have highlighted increasing infectious complications due to fluoroquinolone (FQ)-resistant organisms in men undergoing transrectal ultrasound-guided prostate biopsy (TRUSPB). This study investigated whether fosfomycin (FM)-based antibiotic prophylaxis reduces infections after TRUSPB and identified risk factors for infective complications. MATERIALS AND METHODS: A multicenter study was conducted in the Republic of Korea from January 2018 to December 2021. Patients undergoing prostate biopsy with FQ or FM-based prophylaxis were included. The primary outcome was the post-biopsy infectious complication rate after FQ (group 1) or FM-based antibiotic prophylaxis with FM alone (group 2) or FQ and FM (group 3). Risk factors for infectious complications after TRUSPB were secondary outcomes. RESULTS: Patients (n=2,595) undergoing prostate biopsy were divided into three groups according to the type of prophylactic antibiotics. Group 1 (n=417) received FQ before TRUSPB. Group 2 (n=795) received FM only and group 3 (n=1,383) received FM and FQ before TRUSPB. The overall post-biopsy infectious complication rate was 1.27%. The infectious complication rates were 2.4%, 1.9%, and 0.5% in groups 1, 2, and 3, respectively (p=0.002). In multivariable analysis, predictors of post-biopsy infectious complications included an association with health care utilization (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.74-12.4; p=0.002) and combination antibiotic prophylaxis (FQ and FM) (adjusted OR, 0.26; 95% CI, 0.09-0.69; p=0.007). CONCLUSIONS: In comparison with monotherapy with FM or FQ, combination antibiotic prophylaxis (FQ and FM) showed a lower rate of infectious complications after TRUSPB. Utilization of health care was an independent risk factor for infectious complications after TRUSPB.

[Rationale for choosing an antibiotic for the treatment of cystitis: recommendations of clinical pharmacologists: A review].

In recent years, the harmonization of domestic and foreign clinical recommendations for the treatment of cystitis has been achieved. Nitrofurans and fosfomycin trometamol are recommended as first line therapy antibiotics, and oral 3rd generation of cephalosporins are recommended as alternative antibiotics; fluoroquinolones are excluded from the recommended medications due to an unfavorable safety profile. The main rationale for inclusion of antibiotics in the recommendations as a first line therapy of cystitis is the level of resistance of uropathogens to antibiotics, primarily Escherichia coli. Stable low level of resistance of E. coli in Russia was noted to nitrofurans and fosfomycin (5%), higher to cephalosporins. Among nitrofurans, furazidine is characterized by higher activity against E. coli compared to nitrofurantoin. The potassium salt of furazidine in dosage form with magnesium carbonate is preferred, since it is characterized by higher bioavailability and provides a therapeutic level of concentrations in urine above the MIC during the entire dosing period. Due to the global increase in the resistance of uropathogens observed in recent years, experts have begun to pay more and more attention to the ecological safety of antimicrobial therapy in order to minimize the risk of concomitant (collateral) damage, contributing to the selection of multi-drug resistant strains of microorganisms. In the latest WHO document of 2021, experts divided antibiotics into three groups (ACCESS, WATCH, RESERVE) according to the priority of choice. The ACCESS group of drugs for the treatment of cystitis includes nitrofurantoin and furazidine as agents with minimal collateral effect, while fosfomycin trometamol and cephalosporins are listed in the WATCH group. Thus, from the standpoint of ecological safety, WHO experts recommend prescribing nitrofurans in the treatment of cystitis in the first line of therapy.

[The efficiency of combined regimens for the treatment of urinary tract infections in women using the herbal drug Canephron N].

INTRODUCTION: Currently, empiric antibiotic therapy is considered the standard for acute cystitis. However, additional treatment may be required to alleviate the patient's condition and shorten the time to subjective recovery. AIM: To evaluate the efficiency of the combined administration of fosfomycin trometamol and herbal drug Canephron N in comparison with a single oral dose of fosfomycin trometamol in women with uncomplicated bacterial cystitis. MATERIALS AND METHODS: A randomized, comparative, open-label study was carried put between January 2018 and June 2019. The study included 112 women with symptoms of acute uncomplicated cystitis, who were randomized between two groups in a 1:1 ratio. In the main group, patients received a single oral dose of fosfomycin in combination with Canephron N (2 tablets t.i.d. for 2 weeks), while in the control group patients received only a single dose of fosfomycin (3 g). Symptoms were assessed using the Russian version of the Acute Cystitis Symptom Score (ACSS), completed daily for a week. Also, all patients underwent urine analysis on the 1st, 3rd, 5th and 7th days of therapy. The mean time to complete recovery based on the ACSS questionnaire and the time to resolution of pyuria were compared using the Mann-Whitney U test. Comparison of the proportion of patients with complete cure, according to the questionnaire, or with the elimination of pyuria was carried out using the chi-square test. RESULTS: The final analysis included 46 patients who received fosfomycin in combination with Canephron and 47 patients who received fosfomycin as monotherapy. In the group of combination therapy, patient-reported complete recovery (assessed by the ACSS questionnaire) was seen on average after 1 day, while in patients treated with monotherapy, the median time to subjective recovery was 3 days (p=0.00012). A significant difference between the groups in the proportion of patients with complete resolution of symptoms of acute cystitis was observed on days 1, 2, and 3 (p<0.05). The therapy was well tolerated in both groups. The most frequent adverse events were dyspepsia (8.7% in the combination group compared to 6.4% in the control group) and headache (in 4.3% and 6.4% of patients, respectively). CONCLUSION: the combined use of fosfomycin trometamol and the herbal drug Canephron N allows to reduce the duration of symptoms in patients with acute cystitis, thereby accelerating return to their usual lifestyle patterns.

[Rationale for the choice of an antibiotic for urinary tract infections with an emphasis on the environmental safety of therapy].

Difficulties in prescribing antibiotics for lower urinary tract infections (UTI) are associated with a fact that such patients can be treated not only by urologists, but also by general practitioners, internists, pediatricians, and gynecologists. Therefore, it is important to adapt the practical recommendations for the treatment of cystitis for different medical disciplines. When creating clinical guidelines, experts take into account the different factors in choosing antibiotic therapy. First of all, pharmacokinetics is of importance and drugs with renal excretion should be preferred. Secondly, the natural activity of the antibiotic against the pathogens, which cause cystitis, has to be considered. In uncomplicated infections, E. coli predominates, while in complicated and recurrent infections E. coli and other enterobacteria are commonly isolated, as well as Enterococci. In addition, local resistance pattern is reviewed. In the Russian Federation E. coli has minimal resistance to nitrofurans and fosfomycin. Lastly, antibiotics can negatively affect the gastrointestinal and urinary tract microbiota and contribute to the increase of antibiotic resistance and the selection of antibiotic-resistant strains, therefore the environmental safety of therapy should be considered. The effect of antibiotics on the resident flora of the gastrointestinal tract, urinary tract and vagina is called collateral effect, or concomitant (parallel) damage, and it may exceed the therapeutic effect of some antibiotics. Cephalosporins and fluoroquinolones can cause ecologically unfavorable effects with the risk of selection of resistant strains; therefore, these drugs are currently considered as second-line agents for UTI. When choosing an antibiotic, preference should be given to drugs with the narrow spectrum and minimal collateral damage, i.e., the principle of "minimum sufficiency" is of importance. Nitrofurans and fosfomycin trometamol are the optimal drugs in terms of efficiency and environmental safety in UTI. WHO experts consider nitrofurans as the most environmentally safe antibiotics with a minimally sufficient spectrum of activity. The environmental safety of antimicrobial therapy is an important component of preventing antibiotic resistance at the global and local levels.

Elimination of fosfomycin during dialysis with the Genius system in septic patients.

To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4-6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.

[Recurrent lower urinary tract infection in women: treatment and prevention].

INTRODUCTION: Antibiotics represent the main drugs for the treatment and prevention of recurrent lower urinary tract infections (UTIs). At the same time, there is no consensus regarding the duration of therapy and the interval between courses. MATERIAL AND METHODS: A total of 50 women aged 18 to 65 years (mean age 44.6+/-13.2 years) with recurrent lower UTIs in the acute stage were treated. All patients were prescribed fosfomycin trometamol (Fosfomycin Esparma, Esparma GmbH, Germany) at a dose of 3 g once every 10 days for 3 months. The changes of clinical and laboratory parameters were evaluated on the 3rd day after the first administration of fosfomycin, and then after 1, 3 and 6 months from the start of treatment. RESULTS: A decrease in the severity of clinical manifestations of cystitis was seen on the next day after first administration of fosfomycin. By the 3rd day, the ACSS score decreased from the initial 9.2+/-2.1 to 1.4+/-1.0 (p<0.001), while the average urinary frequency changed from 12.3+/-2.3 to 7.5+/-1.4 (p<0.05). After 3 months of therapy, the clinical results virtually did not differ from results on the 3rd day. The therapy was well tolerated; adverse events were noted in 10 patients, but they didnt result in discontinuation of the drug. During follow-up for 3 months after the completion of therapy, 47 (94%) women didnt have recurrence of lower UTI. CONCLUSION: the results of the study suggest a high efficiency and good tolerability of fosfomycin when it is prescribed according to specific scheme for the treatment and prevention of recurrent lower UTIs in women.

A comparison of different antibiotic regimens for the treatment of infective endocarditis.

BACKGROUND: Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016. OBJECTIVES: To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively. MAIN RESULTS: Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled. The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size. The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31). The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55). The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life. AUTHORS' CONCLUSIONS: This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.

Efficacy and Safety of Two Fosfomycin Regimens as Antimicrobial Prophylaxis for Transrectal Prostate Biopsy: A Randomised Study.

PURPOSE: Prostate biopsy is the gold standard for prostate cancer diagnosis; unfortunately, this procedure is not free from complications. Recent studies have shown an increase in antibiotic resistance. The aim of our prospective randomized study was to evaluate the efficacy and safety of a prostate biopsy prophylaxis protocol using 2 vs. 3 fosfomycin doses. METHODS: Two hundred and ninety-seven patients undergoing transrectal systematic ultrasound (US)-guided (n = 277) or transrectal fusion prostate biopsy (n = 20) were prospectively evaluated and randomized by date of birth, to receive 2 (even years, group A) versus 3 doses of fosfomycin (odd years, group B), and prospectively evaluated. RESULTS: Two hundred and ninety-seven patients were randomized to group A (n = 162) or group B (n = 135). The 2 groups were comparable with respect to age, comorbidity, PSA value, prostate volume, operative time and urine culture results. Out of 297 patients, 44 (14.8%) developed complications after the procedure; 2.7% (8/297) of patients developed fever >38° requiring hospitalization (6 [3.7%] in group A and 2 [1.5%] in group B, p = 0.29). Patients who underwent fusion biopsy were more frequently readmitted in comparison with patients undergoing US-guided prostate biopsy (p = 0.000). CONCLUSION: The low fever and prostatitis rate suggest that fosfomycin prophylaxis is safe and efficient. There is no significant difference in clinical outcome between the 2 dosage regimens.

Intraperitoneal administration of fosfomycin, metronidazole, and granulocyte-macrophage colony-stimulating factor in patients undergoing appendectomy is safe: a phase II clinical trial.

We aimed to investigate the safety of intraperitoneal administration of the combination of fosfomycin, metronidazole, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients undergoing appendectomy. We conducted a prospective phase II clinical trial in 14 otherwise healthy men suffering from uncomplicated appendicitis. After appendectomy, the trial treatment was administered intraperitoneally and left in the abdominal cavity. Trial treatment consisted of 4 g fosfomycin, 1 g metronidazole, and 50 µg rhGM-CSF in a total volume of 500 ml. Safety was evaluated through white blood cell count where a toxic effect was predefined. We evaluated harms and adverse events, repeated biochemical markers, vital signs, and length of stay. White blood cell count did not drop below the toxic range. The recorded harms were dizziness, discomfort when breathing deeply, no flatus, and bloating. Adverse events included three patients with diarrhoea after discharge and one patient with a hypotensive episode. No serious adverse events or infectious complications occurred. Intraperitoneal administration of fosfomycin, metronidazole, and rhGM-CSF was safe in otherwise healthy men undergoing laparoscopic appendectomy. There were some possible harms and adverse events but we were unable to assess if they were related to anaesthesia, surgery, or the trial treatment.

Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial.

Importance: The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI). Objective: To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis. Design, Setting, and Participants: Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel. Interventions: Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection. Main Outcomes and Measures: The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events. Results: Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively). Conclusions and Relevance: Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion. Trial Registration: ClinicalTrials.gov Identifier: NCT01966653.

Intravenous fosfomycin for pulmonary exacerbation of cystic fibrosis: Real life experience of a large adult CF centre.

BACKGROUND: The increased prevalence of multi-drug resistant strains of P.aeruginosa and allergic reactions among adult patients with cystic fibrosis (CF) limits the number of antibiotics available to treat pulmonary exacerbations. Fosfomycin, a unique broad spectrum bactericidal antibiotic, might offer an alternative therapeutic option in such cases. AIM: To describe the clinical efficacy, safety and tolerability of intravenous fosfomycin in combination with a second anti-pseudomonal antibiotic to treat pulmonary exacerbations in adult patients with CF. METHOD: A retrospective analysis of data captured prospectively, over a 2-years period, on the Unit electronic medical records for patients who received IV fosfomycin was performed. Baseline characteristics in the 12 months prior treatment, lung function, CRP, renal and liver function and electrolytes at start and end of treatment were retrieved. RESULTS: 54 patients received 128 courses of IV fosfomycin in combination with a second antibiotic, resulting in improved FEV1 (0.94 L vs 1.24 L, p < 0.01) and reduced CRP (65 mg/L vs 19.3 mg/L, p < 0.01). Renal function pre- and post-treatment remained stable. 4% (n = 5) of courses were complicated with AKI at mid treatment, which resolved at the end of the course. Electrolyte supplementation was required in 18% of cases for potassium and magnesium and 7% for phosphate. Nausea was the most common side effect (48%), but was well controlled with anti-emetics. CONCLUSION: Antibiotic regimens including fosfomycin appear to be clinically effective and safe. Fosfomycin should, therefore, be considered as an add-on therapy in patients who failed to respond to initial treatment and with multiple drug allergies.

Evaluation of perioperative prophylaxis with fosfomycin tromethamine in ureteroscopic stone removal: an investigator-driven prospective, multicenter, randomized, controlled study.

PURPOSE: To compare efficacy, safety, and cost-effectiveness of fosfomycin tromethamine with other standard-of-care antibiotics in patients undergoing ureteroscopic lithotripsy. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Efficacy and safety of fosfomycin-trometamol in the prophylaxis for transrectal prostate biopsy. Prospective randomized comparison with ciprofloxacin.

OBJECTIVE: Prostate biopsy is the standardized diagnostic method for prostate cancer. However, although there is not a standardized protocol, there are recommendations in order to reduce the incidence of complications. The objective of the present work is to assess the efficacy and safety of antibiotic prophylaxis in the prostate biopsy by comparing two antibiotic regimes: two doses of fosfomycin-trometamol 3g (FMT) every 48 hours with 10 doses of oral ciprofloxacin 500 mg every 12 hours during 5 days. MATERIAL AND METHODS: Randomized prospective study was performed with 671 patients who had undergone to walking transrectal ultrasound guided prostate biopsy. Patients of group A (n=312) were treated with ciprofloxacin, and patients of group B (n=359) with FMT. Efficacy and tolerability of two prophylactic regimes were compared. Urine culture was carried out at 2 weeks after biopsy. Initially, patients with asymptomatic bacteriuria were not treated with antibiotics; urine culture was repeated after 1 month, persistent bacteriuria was treated according to antibiogram. RESULTS: No differences between groups were found in age (P=.78), cancer presence (P=.9) or number of biopsy cylinders (P=.93). The mean number of cores obtained was 11.3 ± 3.25 (range 6-20). Digestive intolerance was observed for 9 patients (2.9%) of group A and 10 patients (2.8%) in group B. One patient (.3%) of group A showed severe allergic reaction. In total, 167 patients (24.6%) had complications: 16 (2.4%) fever, 47 (6.9%) hemospermia, 81 (11.9%) hematuria, 7 (1%) rectal bleeding and 16 (2.4%) urinary retention. No statistically differences between groups were observed (27.6% vs. 22.6%; P=.17). However, hemospermia was more frequent in group A (9.9% vs. 4.5%; P=.006). Bacteriuria after biopsy was detected in 44 patients (6.6%), being more frequent in group B patients (4.2% vs. 8.6%; P=.02) although a higher number of second treatment cycles were not needed (53.9% vs. 29%; P=.17). The likelihood of resistance to ciprofloxacin in patients with bacteriuria in A was greater than that of FMT in B (69.2% vs. 41.9%; P=.0004). CONCLUSIONS: Antibiotic prophylaxis with FMT (2 doses of 3g) in prostate biopsy is an alternative as effective and safe as ciprofloxacin (10 doses of 500 mg), which carries lower rate of resistance. According to our experience, this drug is a safe, well-tolerated, and easily manageable prophylactic option, facilitating patient compliance. More prospective multicenter studies are necessary to confirm these findings.

Recurrent uncomplicated cystitis in women: allowing patients to self-initiate antibiotic therapy.

Acute uncomplicated cystitis is a lower urinary tract infection occurring in the absence of anatomic or functional abnormalities of the urinary tract or any other complicating factors.The organism responsible is often an enterobacterium, especially Escherichia coli. What is the role of antibiotic therapy for non-pregnant women with recurrent acute uncomplicated cystitis? We reviewed the available evidence using the standard Prescrire methodology. A single oral dose of fosfomycin trometamol is the antibiotic of choice for treating an episode of acute uncomplicated cystitis. Alternative antibiotics are certain fluoroquinolones or co-trimoxazole (a fixed-dose combination of sulfamethoxazole and trimethoprim). For recurrent acute uncomplicated cystitis, cranberry juice has modest efficacy in reducing the frequency of episodes. A number of non-drug measures are typically proposed, although their effects are unproven: drinking sufficient fluids and urinating regularly; urinating after sexual intercourse; and avoiding spermicides. The strategy that results in the lowest antibiotic exposure is a short course of antibiotics for each episode of urinary tract infection, initiated as soon as clinical symptoms appear. Long-term antibiotic therapy is sometimes offered. According to one systematic review, women taking long-term prophylactic antibiotic therapy had about 6 times fewer clinical recurrences than with placebo. According to one randomised trial, 3 g of fosfomycin trometamol taken as a single dose every ten days reduced the frequency of recurrence, resulting in 0.14 episodes of infection per year on average versus about 3 episodes with placebo (p < 0.001). The amount of antibiotic used when fosfomycin trometamol is taken every 10 days for 6 months is equivalent to treatment of 18 acute episodes of cystitis. When cystitis appears to be associated with sexual intercourse, two small randomised trials suggest that routine postcoital antibiotic treatment is more effective than placebo and as effective as long-term antibiotic therapy. Adverse effects, some of which can be serious, depend on the antibiotic used. The development of resistance among enterobacteria is one argument for limiting the use of antibiotics, in order to preserve their efficacy in serious infections. In practice, the strategy that uses the fewest antibiotics is to treat each episode as soon as the first clinical symptoms appear. Cases in which the frequency of recurrence warrants regular antibiotic prophylaxis are rare. The optimal antibiotic regimen in these cases has not been determined, either in clinical trials or by consensus.