fosfomycin and Pyelonephritis

The rising incidence of MDR uropathogens has driven increased use of oral fosfomycin for treatment of complicated urinary tract infections (cUTIs). However, there are limited data to support its use for cUTI, especially pyelonephritis.. We performed a retrospective review of all oral fosfomycin prescriptions between 1 January and 31 December 2017 in the Los Angeles County Department of Health Service system, the second largest US municipal health system. We examined demographics, clinical characteristics, adverse events and 30 day treatment success for patients with cUTI. Follow-up urine cultures till 31 December 2018 were examined for emergence of fosfomycin resistance.. Of 154 patients prescribed fosfomycin, 99 (64%) had cUTI. Of these, 39 (39%) had lower tract, 37 (37%) pyelonephritis and 23 (23%) non-pyelonephritis upper tract cUTI. Escherichia coli ESBL producers were the predominant pathogens (73%). Of the 63 patients with 30 day follow-up, 49 (78%) had clinical success, including 16/20 (80%) treated for pyelonephritis. Treatment failure was associated with male sex (P < 0.01), urological abnormalities (P = 0.05), non-E. coli cUTI (P = 0.03) and receipt of <25% IV therapy prior to fosfomycin switch (P = 0.03). Of patients prescribed fosfomycin (n = 154), fosfomycin-resistant E. coli were found in 9/64 (14%) of the patients with follow-up urine cultures >30 days after initial treatment.. Despite the lack of data supporting its use, we found that most patients receiving oral fosfomycin off-label for cUTI, including pyelonephritis, had clinical success. However, emergence of subsequent resistance warrants caution. Prospective comparative studies should be done to better evaluate oral fosfomycin use for cUTI.

Topics: Anti-Bacterial Agents; Delivery of Health Care; Escherichia coli; Fosfomycin; Habits; Humans; Male; Prospective Studies; Pyelonephritis; Retrospective Studies; Urinary Tract Infections

Fosfomycin is a bactericidal antibiotic available since the 1970s whose intravenous formulation has been available in many countries outside the USA. Given the rise in drug-resistant bacteria, its introduction into the US market has become a necessity for addressing these organisms. This review provides an overview of the microbiology, clinical pharmacology and initial clinical experiences of the intravenous fosfomycin product (ZTI-01) that is undergoing clinical development in the USA for the treatment of complicated urinary tract infections and acute pyelonephritis.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Combinations; Drug Resistance, Bacterial; Fosfomycin; Hospitalization; Humans; Injections; Microbial Sensitivity Tests; Pyelonephritis; Treatment Outcome; United States; Urinary Tract Infections

Topics: Anti-Infective Agents, Urinary; Bacteriuria; Cephalosporins; Chronic Disease; Cystitis; Drug Resistance, Bacterial; Fluoroquinolones; Fosfomycin; Humans; Microbial Sensitivity Tests; Nitrofurantoin; Pyelonephritis; Recurrence; Risk Factors; Sepsis; Tromethamine; Urinary Tract Infections

ZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States.. Hospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g intravenous (IV) piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days.. Of 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic modified intent-to-treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% confidence interval [CI]: -0.4, 20.8). Clinical cure rates at test of cure (TOC, day 19-21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in m-MITT were 69.0% (127/184) for ZTI-01 versus 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mild and transient.. ZTI-01 was effective for treatment of cUTI including AP and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gram-negative infections.. NCT02753946.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Load; Drug Resistance, Bacterial; Female; Fosfomycin; Humans; Injections; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Treatment Outcome; Urinary Tract Infections; Young Adult

In a controlled open study of 38 patients with acute pyelonephritis, treatment with fosfomycin 8 g b.i.d. was compared to treatment with ampicillin 2 g t.i.d., both for one week. The most common pathogen in both groups was Escherichia coli, susceptible to fosfomycin. However, 17% were resistant to ampicillin. The success rate was 44% in the fosfomycin treated group and 28% in the ampicillin group. The difference was not significant (p greater than 0.20). Peak concentrations of fosfomycin in serum were 395 mg/l and in tissue fluid 85 mg/l. Urine concentrations ranged from 6990 to 24,320 mg/l.

Topics: Acute Disease; Ampicillin; Fosfomycin; Humans; Pyelonephritis; Random Allocation

Topics: Fosfomycin; Humans; Piperacillin; Pyelonephritis; Tazobactam; Urinary Tract Infections

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Cystitis; Diagnosis, Differential; Diagnostic Tests, Routine; Female; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Pyelonephritis; Reagent Strips; Risk Assessment; Risk Factors; Treatment Outcome; Urinary Tract Infections; Urine

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

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

The nephrotoxicity, pharmacokinetic and therapeutic activity of fosfomycin were investigated in female wistar-rats. Measures of nephrotoxicity were urinary excretion of tubular cells and of the enzymes MDH, LDH, and GOT. Histological investigations and estimation of serum urea concentration and proteinuria were also evaluated. The doses of 500, 1000, 2000, 3000, and 5000 mg/kg/d were administered in 9 single doses with 12 hours interval. The lowest dose which induced a significantly increased tubular cell excretion was 1000 mg/kg/d and therefore in the same range as the tubulotoxic threshold doses of cephalosporins. Chemotherapy of the chronic estrogen induced pyelonephritis revealed equally favourable results for fosfomycin and cefuroxim at dosages of 2 X 150 mg/kg/d. The pharmacokinetics of fosfomycin at a single dose of 150 mg/kg/d were equivalent to those of cefuroxim. These animal experiments showed fosfomycin to be of value as a therapeutic alternative to cephalosporin antibiotics.

Topics: Animals; Anti-Bacterial Agents; Female; Fosfomycin; Kidney Diseases; Kinetics; Pyelonephritis; Rats

Authors have carried out a retrospective study in vitro on the bacteria isolated from renal parenchyma and stones in patients with CPN associated to kidney stones. Results show a different inhibitory action of the some antibiotics to Proteus, E. coli and P. aeruginosa. Fosfomycin inhibits the growth of bacteria in a wide range of concentration (50-1000 microgram/ml). A prospective study in vivo shows an excellent therapeutic action of fosfomycin in recurrent urinary infections, and a very good one in CPN and in some forms associated to kidney stones.

Topics: Adult; Aged; Anti-Bacterial Agents; Chronic Disease; Dose-Response Relationship, Drug; Escherichia coli; Female; Fosfomycin; Humans; Kidney Calculi; Male; Middle Aged; Proteus; Pseudomonas aeruginosa; Pyelonephritis

Topics: Anti-Bacterial Agents; Bacterial Infections; Fosfomycin; Humans; Kidney Diseases; Polycystic Kidney Diseases; Pyelitis; Pyelonephritis