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Antimicrobial Resistance Among Uropathogens That Cause Childhood Community-acquired Urinary Tract Infections in Central Israel

Yakubov, Renata MD; van den Akker, Machiel MD; Machamad, Kaba MD; Hochberg, Amit MD; Nadir, Erez MD; Klein, Adi MD

The Pediatric Infectious Disease Journal: January 2017 - Volume 36 - Issue 1 - p 113–115
doi: 10.1097/INF.0000000000001373
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In this retrospective study 829 positive urine cultures were analyzed. Escherichia coli bacterium was the leading uropathogen (86%). Almost 60% were resistant to ampicillin and first generation cephalosporins, and about 30% of them resistant to amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole. Almost none of them were resistant to second and third generation cephalosporins, aminoglycosides, ciprofloxacin or nitrofurantoin.

From the *Department of Pediatrics, Hillel Yaffe Medical Center, Hadera, Israel; Department of Pediatrics, Queen Paola Children’s Hospital, Antwerp, Belgium; and Department of Neonatology, Hillel Yaffe Medical Center, Hadera, Israel.

Accepted for publication June 16, 2016.

The authors have no funding or conflicts of interest to disclose.

Address for correspondence: Renata Yakubov, MD, Department of Pediatrics, Hillel Yaffe Medical Center, Ha-Shalom St, Hadera, 38100, Israel. E-mail: renataya@bezeqint.net.

Urinary tract infection (UTI) is a very common disorder in children. Although most patients have a good prognosis, UTI can cause significant morbidity, including renal scarring, hypertension and end-stage renal disease.1 Early and aggressive antibiotic therapy (within 72 hours of presentation) is necessary to prevent renal damage. Delayed therapy has been associated with increased severity of infection and greater likelihood of renal damage in experimental, retrospective, prospective and small randomized studies.2–6

UTI is usually treated empirically, before urine culture results are available, and the choice of antibiotics depends on the susceptibility patterns of the uropathogens. Knowledge of the prevalence of causative organisms and their sensitivity patterns are essential for effective treatment. Current data on the prevalence and patterns of resistance of uropathogens in children are limited. There is, however, a growing concern regarding antimicrobial resistance worldwide, because several countries have experienced rising resistance rates, particularly of Escherichia coli isolates to beta-lactam antibiotics. Approximately 50% of E. coli bacteria are resistant to amoxicillin or ampicillin.7–9 In addition, increasing rates of E coli resistance to first generation cephalosporin (eg, cephalexin), amoxicillin-clavulanic acid or ampicillin-sulbactam and trimethoprim-sulfamethoxazole have been reported in some communities.7,8,10 Increased resistance to extended-spectrum cephalosporin (cefotaxime, ceftazidime, cefepime) has been reported in children receiving prophylactic antibiotics.11–13

Third generation cephalosporin’s (eg, cefixime, cefotaxime, ceftriaxone) and aminoglycosides (eg, gentamicin, amikacin) are considered first-line agents for empiric treatment of UTI in children.14 Because of these emerging patterns of resistance, we investigated the prevalence and resistance patterns of uropathogens in a region of Israel, and analyzed the implications for rational therapy strategies in UTI.

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MATERIALS AND METHODS

A retrospective analysis was performed on all urine cultures examined at the microbiology laboratory of Hillel-Yaffe Medical Center, Hadera, Israel, between January 2007 and December 2014. Strains were isolated from inpatients and outpatients aged 1 week to 18 years old with symptoms of UTI, with or without fever.

The retrospective evaluation included all urine cultures, regardless of the following UTI parameters: complicated or uncomplicated, first or recurrent infection, nosocomial- or community-acquired, medical history of long-term antibacterial prophylaxis or the presence of anatomic anomalies of the urinary. The data were based solely on laboratory findings. Urine cultures were collected using midstream clean catch, catheterization and suprapubic aspiration. The study included only urine cultures that showed more than 100,000 colony forming units/mL of a single pathogen.

All samples were cultured on blood and McConkey agar plates according to standard procedures. The plates were incubated at 37°C for 24 hours and bacteria were identified by standard methods.

Antimicrobial susceptibility testing was performed by the disc diffusion method on cultures with significant bacteriuria, using a panel of antimicrobial agents, depending on the identified causative organism. Interpretation followed the national committee for clinical laboratory standards criteria.15

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RESULTS

Eight hundred twenty-nine positive urine cultures were analyzed. The patient population consisted of 707 female patients (85 %) and 122 male patients (15%), ages ranging from 1 week to 18 years old. Distribution of the organism in the urine cultures and the antimicrobial resistance are shown in Table 1.

TABLE 1

TABLE 1

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DISCUSSION

Febrile UTI is a very common disease in childhood. A course of antibiotic is usually the initial treatment of acute pyelonephritis or cystitis. Empiric therapy is initiated after urine culture has been obtained. It is important to start empirical treatment early in young children with febrile UTI, to minimize renal scarring that results from acute pyelonephritis.14 Urine culture results are usually ready in 1 to 2 days. Expected resistance patterns must be considered when selecting empirical antimicrobial treatment strategies for UTI. Consequently, antibiotic policy should be formulated according to local surveillance data. The present study provides information about the antimicrobial susceptibility of community-acquired UTIs, in relation to uropathogen agents (E. coli/non E. coli coliforms). We retrospectively analyzed the spectrum and the resistance pattern of uropathogens to common antimicrobial agents in the region of Hadera (Central Israel). The most common pathogen was E. coli (86.4%), followed by other Gram-negative bacteria of the enterobacteriaceae family (98.6% together). Such a distribution of coliform community-acquired UTI pathogens was observed in a few reports from the southern part of Europe,16–19 Latin America,20 Britain,21 Taiwan12 and Canada.22 About 60% of E. coli was resistant to ampicillin, and 80%–100% of all non E. coli coliform bacteria were resistant to ampicillin. Based on this data, the use of ampicillin as an agent for empirical treatment of a suspected UTI, or prevention of recurrent UTI, would not cover the majority of pathogens. High resistance rates were seen to trimethoprim-sulfamethoxazole (almost 40%), amoxicillin-clavulanic acid (30%) and first generation cephalosporin (almost 60%). These antibiotics are frequently used in Israel for empirical treatment of community-acquired infection in children. Resistance rates to second and third generation cephalosporin, ciprofloxacin and aminoglycosides were remarkably low. The same results were shown in numerous studies.10,23 The risk factors for the development of resistance to narrow-spectrum antibiotics include boys with an uncircumcised penis, exposure to antibiotic (poor empiric prescribing practices, nonselective use of prophylaxis), lack of urine testing and bowel and bladder dysfunction.24–27 The likelihood of a resistant uropathogen or a non E coli pathogen is increased with recurrent UTI.28 To curb the growing resistance rates, it is important to culture the urine and use local antibiograms, to only treat when indicated and tailor broad-spectrum therapy as able.29 Also of importance is the selective application of antibiotic prophylaxis to patients with high-grade vesicoureteral reflux and high-grade hydronephrosis, and checking the compliance.29 Maybe by shortening the duration of the antibiotic treatment and thus limiting the days of antibiotic exposure, it is possible to reduce the emergence of bacterial resistance.

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Keywords:

antimicrobial resistance; urinary tract infections; children

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