Fosfomycin Versus Meropenem or Ceftriaxone in Bacteriemic Infections Caused by Multidrug Resistance in E.Coli

• Status: Completed
• Trial end date: 2019-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Enterobacterieaceae (and specially Escherichia coli) showing resistance due to multidrug-resistant Escherichia coli, plasmid mediated AmpC or quinolone resistance caused by chromosomal mechanisms have spread worldwide during the last decades. This is important because many of these isolates are also resistant to other first-line agents such as fluoroquinolones or aminoglycosides, leaving few available options for therapy, and this condition is associated with increased morbidity- mortality and length of hospital stay. While carbapenems are considered the drugs of choice for multidrug-resistant Escherichia coli and AmpC producers, recent data suggests that certain alternatives may be suitable for some types of infections.

At the present time, finding therapeutic alternatives to carbapenems and cephalosporins for the treatment of invasive infections due to multidrug-resistant Escherichia coli is critical. Fosfomycin was discovered more than 40 years ago but was not investigated according to present standards, and thus is not used in clinical practice except in desperate situations. It is one of the so-considered neglected antibiotics with high potential interest for the future.

With the aim of demonstrate the clinical non-inferiority of intravenous fosfomycin compared to meropenem or ceftriaxone in the treatment of bacteraemic urinary tract infections caused by multidrug-resistant Escherichia coli . The investigators propose a "real practise" randomised, controlled, multicentre phase III clinical trial to compare the clinical and microbiological efficacy and safety of intravenous fosfomycin (4 grammes every 6 hours) with meropenem (1 gramme every 8 hours) or ceftriaxone (1 gramme every 24 hours) as targeted therapy of the previously specified infection; change to oral therapy according to predefined options is allowed in both arms after 5 days. Follow-up for the study is planned up to 60 days.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Collaborator: Spanish Network for Research in Infectious Diseases
• Treatments: Ceftriaxone; Fosfomycin; Meropenem; Pharmaceutical Solutions; Thienamycins

Criteria

Inclusion Criteria:

• ≥18 years old hospitalized patients

• Negative pregnancy test in fertile women

• Episode of clinically-significant monomicrobial urinary BSI due to multidrug-resistant E.coli susceptible to fosfomycin and meropenem or ceftriaxone

• Urinary sepsis with multidrug resistant E. coli isolation from the blood cultures, requires at least one clinical criteria and one of the following urinalysis criteria:

Clinical criteria

• UTI symptoms (dysuriac, urgency, suprapubic pain or pollakiuria)

• Lumbar back pain

• Cost-vertebral angle tenderness

• Altered mental status in people up to 70 years old

• Intermittent or permanent indwelling foley catheter (or withdrawal during 24 hours previous) even without urinary symptoms urinalysis criteria

• Urine dipstick test positive for either nitrites or leukocyte esterase

• Positive urine culture - Signed informed consent form (ICF) executed prior to protocol screening assessments

Exclusion Criteria:

• Polymicrobial bacteremia

• No drainage of renal abscess or obstructive uropathy unresolved

• Pregnant or careening women

• Haematogenous infection

• Other concomitant infection

• Renal transplantation recipients

• Polycystic kidney

• Hypersensitivity and/or intolerance to meropenem or fosfomycin or ceftriaxone

• Palliative care or life expectance < 90 days

• Septic shock at time of randomization

• New York Heart Association (NYHA) functional Class IV, hepatic cirrhosis or renal impairment receiving dialysis

• Active empiric treatment >72 hours

• Late randomization >24 hours after multidrug resistant.coli blood culture´s identification

• Participation in other clinical trial with active treatment