Drug-induced Crystalluria in Sulfamethoxazole, High Dose Ciprofloxacin and High Dose Amoxicillin

Universitair Ziekenhuis Brussel290 enrolled

Overview

This study examines in hospitalized patients, treated with sulfamethoxazole, high dose ciprofloxacin or high dose iv amoxicillin, the incidence of drug-induced urinary crystal formation and its association with acute kidney injury development.

This is a prospective study which evaluates in hospitalized patients treated with sulfamethoxazole (po or iv), high dose ciprofloxacin (po or iv) or high dose iv amoxicillin, regardless the indication of the antibiotic treatment, the incidence of development of drug-induced urinary crystal formation. In addition, the association between development of AKI and the development of drug-induced crystalluria will be assessed for each of these antibiotics. Moreover, demographic, clinical and biochemical factors associated with the development of drug-induced crystalluria will be evaluated, as well as the timing of crystalluria development and potential AKI development. In eligible patients who have provided informed consent first voided morning urine samples will be evaluated for the presence of drug-induced crystals by crystalluria examination at predefined moments, depending on the specific antibiotic treatment (day 2, 4, 6, 8 and 11 after start of antibiotic treatment for amoxicillin treatment, day 3 and 7 after start of antibiotic treatment for ciprofloxacin treatment, day 3, 7 and 11 after start of antibiotic treatment for sulfamethoxazole treatment). Renal function determination by serum creatinine in case of amoxicillin and ciprofloxacin treatment and by serum creatinine and serum urea in case of sulfamethoxazole treatment will be performed at baseline and other predefined moments after the start of antibiotic treatment, depending on the specific antibiotic treatment ( day 1-3, 4-7, 8-11 and 12-14 after the start of antibiotic treatment for amoxicillin treatment, day 3-7 and 8-12 after the start of antibiotic treatment for ciprofloxacin treatment, day 1-4, 5-9, 10-14 after the start of antibiotic treatment for sulfamethoxazole treatment). Occurrence of acute kidney injury will be evaluated. Demographic, clinical and biochemical data will be collected from the electronic medical records, including data on demographics, medical history, medical treatment, data on the antibiotic treatment including dosing and biochemical parameters, including baseline renal function renal function (serum creatinine and eGFR (CKD-EPI), serum urea), CRP. Patients will remain included up to 14 days of antibiotic treatment or until discharge, whatever comes first.

Study Type

INTERVENTIONAL

Allocation

Conditions

Drug-induced Crystalline Nephropathy Drug-induced Crystalluria Infections Treated With Sulfamethoxazole, High Dose Ciprofloxacin or High Dose iv Amoxicillin

Interventions

Crystalluria examinationDIAGNOSTIC_TEST

Crystalluria examination

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years * Able to give informed consent without the intervention of a legal representative * Treatment with * sulfamethoxazole/trimethoprim, with minimum dose of * ≥ 800/160 mg q12h oral administration (PO) or intravenous administration (IV) for eGFR ≥ 30 ml/min * ≥ 400/80 mg q12h OR or IV for eGFR \< 30 ml/min OR * high dose ciprofloxacin, defined as * ≥ 750 mg q12h PO or ≥ 400 mg q8h IV for eGFR ≥ 60 ml/min * ≥ 750 mg q24h PO or ≥ 400 mg q12h IV for eGFR 15-59 m/min * ≥ 750 mg q24h PO OR ≥ 400 mg q24h IV for eGFR \< 15 ml/min OR * high dose amoxicillin, defined as * ≥ 2g q6h IV for eGFR ≥ 30 ml/min * ≥ 2g q8h IV for eGFR 15-29 ml/min * ≥ 2g q12h IV for eGFR \< 15 ml/min * Treatment for min 24 hours and sufficiently long to perform one crystalluria investigation as defined in the protocol * Baseline renal function up to 72 hours prior to the start of antibiotic treatment available (evaluated by serum creatinine and eGFR (CKD-EPI)) for all study groups and additional serum urea for the sulfamethoxazole group). Exclusion Criteria: * Unable to give informed consent without the intervention of a legal representative * No baseline renal function up to 72 hours prior to the start of antibiotic treatment available, evaluated by serum creatinine and eGFR (CKD-EPI)) for all study groups and additional serum urea for the sulfamethoxazole group. * Treatment duration \< 24 hours or insufficiently long to perform one crystalluria inves-tigation as defined in the protocol * Patients treated with hemodialysis or peritoneal dialysis, anuric patients before start of antibiotic treatment * Patients with urinary diversions

Locations (1)

Universitair Ziekenhuis Brussel

Brussels, Belgium

RECRUITING

Outcomes

Primary Outcomes

Incidence of drug-induced crystalluria in patients treated with sulfamethoxazole

The presence of sulfamethoxazole-induced crystalluria will be evaluated by microscopic crystalluria examination in first voided morning urine samples on day 3, 7 and 11 after start of treatment and will be reported as a dichotomous parameter (present/absent).

Time frame: Up to 11 days after start of treatment

Incidence of drug-induced crystalluria in patients treated with high dose ciprofloxacin

The presence of ciprofloxacin-induced crystalluria will be evaluated by microscopic cyrstalluria examination in first voided morning urine samples on day 3 and 7 after start of treatment and will be reported as a dichotomous parameter (present/absent).

Time frame: Up to day 7 after start of treatment

Incidence of drug-induced crystalluria in patients treated with high dose iv amoxicillin

The presence of amoxicillin-induced crystalluria will be evaluated by microscopic cyrstalluria examination in first voided morning urine samples on day 2, 4, 6, 8 and 11 after start of treatment and will be reported as a dichotomous parameter (present/absent).

Time frame: Up to 11 days after start of treatment

Incidence of AKI in patients treated with high dose iv amoxicillin

Acute kidney injury is defined as an increase in serum creatinine by ≥ 0.3 mg/dl within 48 hours or ≥ 1.5 times baseline within the prior 7 days. The occurrence of acute kidney injury will be performed by calculating the difference between serum creatinine at baseline and during antibiotic treatment at 4 different moments after start of antibiotic treatment, namely day 1-3, day 4-7, day 8-11 and day 12-14.

Time frame: Up to 14 days after start of treatment

Secondary Outcomes

Incidence of AKI in patients treated with sulfamethoxazole

Central Contacts

Els Van de Perre, MD

CONTACT

0032 2 477 60 55 els.vandeperre@uzbrussel.be

Data from ClinicalTrials.gov

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