Piperacillin/Tazobactam Versus Carbapenems in Non-bacteremic UTI Due to -ESBL-producing Enterobacteriaceae
Piperacillin/Tazobactam Versus Carbapenems in Non-bacteremic UTI Due to -ESBL-producing Enterobacteriaceae
This study evaluates the efficacy in achieving clinical cure in non-bacteremic urinary tract
 infections (UTI) caused by Escherichia coli or Klebsiella pneumoniae producers of
 extended-spectrum β-lactamases (ESBL) in adult patients. Half of participants will receive
 Piperacillin/Tazobactam as treatment, while the other half will receive Carbapenems.

 The investigators will verify that Piperacillin/Tazobactam is not inferior in achieving
 clinical cure, and that is not associated with a higher risk of adverse events in the
 directed treatment of non-bacteremic UTI compared to Carbapenems.

 The researchers hope to improve the use of antibiotics in the non-bacteremic UTI, reducing
 the "collateral damage" related to a deterioration in the prognosis of patients and the
 generation of resistant germs caused by the use of broad-spectrum antibiotics as carbapenems.
Urinary tract infection (UTI) is a common cause of hospitalization worldwide, the prevalence
 throughout the life of UTI has been reported in about 50,000 cases per 100,000 women and
 13,000 per 100,000 men in the United States. Hospitalization for community-acquired UTI is
 about 33%. Furthermore, the UTI related to bladder catheterization during hospitalization is
 the most common type of infection acquired, representing 40% of all nosocomial infections.
 UTI hospitalization is associated with a high cost to the healthcare system.

 The diagnosis of UTI is based on demonstrating the presence of bacteria urine in patients
 with suggestive clinical manifestations and verifying the host's inflammatory response to
 infection. The most common etiological agents include Escherichia coli, Klebsiella spp, and
 Proteus spp, with different prevalence and antibiotic susceptibility profiles among different
 populations.

 Currently the appropriate treatment of UTI is a growing concern in the medical community
 because Gram-negative, specifically Enterobacteriaceae, bacteria have acquired genes encoding
 antibiotic resistance mechanisms. The β-lactamase spread spectrum (ESBL) are documented with
 increasing frequency among microorganisms causing UTI. Current treatment options for ESBL
 bacteria include nitrofurantoin, fosfomycin, piperacillin-tazobactam, carbapenems, and
 aminoglycosides.

 Carbapenems and piperacillin-tazobactam are antibiotics used in medical practice for many
 years, both therapies are licensed for the treatment of non-bacteremic UTI; however, so far
 there is not enough evidence to discriminate the best choice for the treatment of
 non-bacteremic UTI (although carbapenems are considered drugs of choice for infections caused
 by these microorganisms), but carbapenems use has been associated with an increased risk of
 "collateral damage" related to the generation of resistant germs.

 The investigators will compare between piperacillin/tazobactam and carbapenems the
 effectiveness in achieving clinical cure for non-bacteremic UTI caused by ESBL
 microorganisms. Researchers principal hypothesis is that Piperacillin/tazobactam is not
 inferior to carbapenems in achieving clinical cure in the targeted treatment of UTI caused by
 non-bacteremic due to E. coli or K. pneumoniae ESBL in adults requiring hospitalization.
 Researchers will verify too if Piperacillin/Tazobactam is not associated with increased risk
 of adverse events during the targeted treatment of non-bacteremic ITU caused by E. coli or K.
 pneumoniae ESBL in adults requiring hospital admission, compared with Carbapenems therapy.

 To perform the protocol researchers follows the recommendations for the design of trials
 investigating treatment options for resistant bacteria multidrug (Uncomplicated Urinary Tract
 Infections: Developing Drugs for Treatment) of the United States Agency for Food and Drug
 Administration (FDA).

 Participants will be included in the study with informed consent. The study variables will be
 obtained by patient interview and review of medical history. Variables will be recorded in a
 computerized database developed specifically for this study, with exclusive access for the
 researchers.

 The estimated project duration is 2 years expected to begin in april of 2019.
Inclusion Criteria:

 -  Adults (≥18 years) with hospital admission for non-bacteremic UTI caused by E. coli or
 K. pneumoniae ESBL susceptible to piperacillin/tazobactam and carbapenems.

 -  Presence of any risk factor associated with UTI due to ESBL germs: older age 64 years,
 diabetes mellitus, bladder catheter, previous antibiotics in the last 6 months,
 hospitalization in the last 6 months, urological surgery in the last 30 days,
 infections recurrent urinary.

 -  Diagnosis of UTI confirmed by: 1) fever, 2) urine culture> 100000 CFU with isolation
 E. coli or K. pneumoniae ESBL susceptible to piperacillin / tazobactam and
 carbapenems, and 3) lumbar and / or abdominal pain with or without low urinary
 symptoms (dysuria, tenesmus, urgency), and 4) no other cause that explains the
 patient's symptoms

 -  Signed informed consent.

 -  Negative pregnancy test in fertile women.

 Exclusion Criteria:

 -  Non-acceptance of participation in the study.

 -  Pregnancy.

 -  Hypersensitivity and/or previous intolerance to penicillins, piperacillin/tazobactam
 or carbapenems.

 -  Bacteremia, hematogenous infection or other concomitant infection.

 -  Immunosuppression.

 -  In case of obstructive uropathy, lack of early surgical resolution.

 -  Evidence of acute or chronic prostatitis.

 -  Renal abscess

 -  Polycystic disease in the kidneys.

 -  Palliative care or life expectancy <90 days.

 -  Heart failure (NYHA) functional class III or IV.

 -  Liver cirrhosis.

 -  Renal insufficiency in dialysis treatment.

 -  Empirical active treatment against bacteria isolated by urine cultures other than E.
 coli or K. pneumoniae BLEE.

 -  Participation in another clinical trial for infections.

 -  Hypersensitivity to amide-type local anesthetics.