Aebi, C.

Ammann, R.A.

Bianchetti, M.G.

Droz, S.

Fritzsche, M.

RERO DOC Digital Library

Eur J Clin Microbiol Infect Dis (2005) 24: 233–235DOI 10.1007/s10096-005-1301-2BRIEF REPORTM. Fritzsche · R. A. Ammann · S. Droz ·M. G. Bianchetti · C. AebiChanges in antimicrobial resistance of Escherichia coli causingurinary tract infections in hospitalized childrenPublished online: 17 March 2005C© Springer-Verlag 2005Urinary tract infections (UTI) are among the most commonbacterial infections of childhood. Rapid recognition andappropriate antimicrobial therapy relieve symptoms andprevent renal damage [1]. Since therapy for suspected UTIis usually initiated before the responsible organism and itssusceptibility to antimicrobial agents are known, the ra-tional choice of an antibiotic relies on local epidemiologicdata. In infants and young children without a known urinarytract malformation, Escherichia coli is responsible for thevast majority of episodes [2, 3]. Recent studies suggest thatin these patients intravenous antibiotic therapy for acutepyelonephritis may no longer be warranted, and that mostpatients can be treated safely with oral third-generationcephalosporins [3, 4]. However, since outpatient oraltherapy for acute pyelonephritis requires certainty thatthe drug used is active against the expected pathogens,this trend is somewhat at odds with the increasing antimi-crobial resistance detected among isolates of Escherichiacoli in recent years [5–7]. The aim of the retrospectivestudy reported here was to investigate changes in theantimicrobial resistance of Escherichia coli causing acutepyelonephritis in children hospitalized with a UTI during2 decades.Two study periods were chosen for investigation. Thefirst period from 1980 to 1991 was based on referencedata provided by a previous study conducted by one of thepresent authors (M.G.B.) at the same study site [8]. A powerM. Fritzsche · R. A. Ammann · C. Aebi ()Department of Pediatrics and Institute for Infectious Diseases,University of Bern,3010 Bern, Switzerlande-mail: christoph.aebi@insel.chTel.: +41-31-6329487Fax: +41-31-6329468S. DrozInstitute for Infectious Diseases, University of Bern,3010 Bern, SwitzerlandM. G. BianchettiOspedale San Giovanni,6500 Bellinzona, Switzerlandanalysis based on this study’s data gave us a comparatorgroup size of 150 patients to detect a 10% difference inresistance to amoxicillin-clavulanate (power, 80%; α level,5%) between the Escherichia coli isolates examined in thefirst period [8] compared with those obtained during a sec-ond, more recent, study period. Thus, the duration of thesecond study period was set to allow for the inclusion of150 patients <16 years of age who were diagnosed andhospitalized most recently with their first UTI. The dura-tion of this period consequently extended from 1 January2000 to 31 December 2003.Inclusion criteria were identical in both periods and con-sisted of (i) significant Escherichia coli bacteriuria, definedas ≥105 colony forming units/ml of bag-collected or mid-stream urine or ≥104 colony forming units/ml of urineobtained by transurethral catheterization, and (ii) severeor moderate UTI defined by clinical criteria. Severe UTIwas recorded if at least one of the following four criteriawere present: (i) Escherichia coli bacteremia, (ii) urinaryleukocyte casts, (iii) sonography findings characteristic forpyelonephritis, (iv) serum creatinine >50 µmol/l above theage-related upper limit of the normal range. Moderate UTIrequired at least three of the following criteria for diag-nosis: (i) age <1 year, (ii) costovertebral angle tender-ness, (iii) C-reactive protein >30 mg/l or erythrocyte sedi-mentation rate >30 mm/h, (iv) peripheral leukocyte count>15.0×109/l, (v) left-shift with >12% band forms. Ex-clusion criteria included a history of previous UTI, knownurinary tract malformation, neurogenic bladder dysfunc-tion, renoparenchymal disorders, immunodeficiency or re-cent transurethral catheterization prior to that used in thepresent episode.Urine specimens were transported to the laboratory usingBD Vacutainer tubes (BD Vacutainer, C&S Kit, FranklinLakes, NJ, USA). Standard techniques were used for cul-ture and identification of Escherichia coli. Susceptibilitytesting was performed using the disk diffusion techniqueaccording to the guidelines of the National Committee ofClinical Laboratory Standards. Organisms with intermedi-ate susceptibility were considered sensitive. Comparisonsbetween the study periods were made using the two-tailed234Table 1 Comparison of antimicrobial resistance in Escherichia coliisolates obtained from Swiss children hospitalized with acute urinarytract infection during two study periodsAntimicrobial agent No. (%) of resistant isolates p value1980–1991 [8](n=203)2000–2003(n=151)Ampicillin 67 (33) 78 (51) <0.001Amoxicillin-clavulanate 30 (17) 17 (11) 0.16Cotrimoxazole 32 (16) 38 (25) 0.031Cephalothin nt 25 (17) –Cefuroxime nt 2 (1.3) –Cefuroxime-axetil nt 2 (1.3) –Ceftriaxone nt 0 (0) –nt, not testedFisher exact test. Statistical significance was defined as a pvalue of <0.05.In the first (1980–1991) [8] and second (2000–2003)study periods, 203 and 151 patients, respectively, werecompared. There were no statistically significant differ-ences in age (median age, 6 months [range, 1 week–15years] vs. 11 months [1 week–12 years]), gender (female,53% vs. 66%), and proportion of severe vs. moderate UTI(36% vs. 28%) between the first and second study periods,respectively. More detailed data on urinary findings wereavailable for cases in the second study period as follows.Ninety (60%) patients had specimens collected by bag,36 (24%) by catheterization, and 25 (17%) by mid-streamvoiding collection. In 25 (17%) specimens, a second bac-terial pathogen was isolated. Thirteen (9%) patients hadbeen treated with an oral antibiotic at the time of hospitaladmission.Table 1 lists the rates of Escherichia coli resistance foundduring both study periods. Resistance to ampicillin andcotrimoxazole increased significantly. The decrease in re-sistance to amoxicillin-clavulanate was not significant. Ofthe 38 strains that demonstrated resistance to cotrimoxa-zole in the second study period, 36 (95%), 12 (32%), and11 (29%) were also resistant to ampicillin, amoxicillin-clavulanate, and cephalothin, respectively. Forty-seven(31%) isolates were resistant to at least two of theantibiotics tested, and 19 (13%) were resistant to atleast three agents.In comparison with previous reports [5–6], this studycovers an extended observation period and care wastaken to ensure that Escherichia coli isolates originatedfrom patients with comparable clinical disease, i.e.,community-acquired UTI with a high likelihood ofrenal involvement in previously healthy children. Sincestandard management of febrile UTI in Switzerland entailshospitalization, our findings are representative of allfebrile UTI episodes occurring in this study area during thetwo study periods.Previous studies have mostly reported susceptibility datawithout considering clinical data in detail. Our major find-ings are consistent with those of recent pediatric studiesfrom the UK [5], Israel [6], and Germany [7], and theydemonstrate a statistically significant increase in resistanceto ampicillin and cotrimoxazole over 2 decades but mainte-nance of full susceptibility to second- and third-generationcephalosporins. While few data from Switzerland are avail-able for comparison, one hospital-based study from Zurichshowed lower rates of ampicillin resistance (44%) buthigher rates of amoxicillin-clavulanate (33%) and cotri-moxazole (42%) resistance in children [9]. Among UTI iso-lates from Swiss women in 2000 substantially lower ratesof resistance were detected (ampicillin, 27%; amoxicillin-clavulanate, 2.5%; cotrimoxazole, 19%) [10]. The trulyunexpected finding in our study was the decrease in re-sistance to amoxicillin-clavulanate, since resistance ratesare known to be influenced by local preferences in theuse of antibiotics [11] and sales of pediatric formulationsof amoxicillin-clavulanate in Switzerland have continu-ously risen over the past decade. Thus, one would ex-pect an increase in selective pressure as a growing pro-portion of UTI patients have been previously exposedto this antibiotic.Our findings have a direct impact on the choice of an an-timicrobial agent for the empiric treatment of pediatric UTIin Switzerland. Amoxicillin should no longer be used. Ina child with cystitis (i.e., who is afebrile and has a normalC-reactive protein level), amoxicillin-clavulanate and cot-rimoxazole can still be used for first-line therapy. However,physicians electing to treat febrile UTI orally should use asecond- or third-generation cephalosporin in order to avoidtreatment failure caused by antimicrobial resistance. Usingceftriaxone as a marker, third-generation cephalosporinswere found to be fully susceptible (Table 1), and compar-ative clinical studies have documented their efficacy in theoral therapy of infants and children with acute pyelonephri-tis [2, 3].It is possible that our data overestimate the overall rates ofresistance in the community for a number of reasons. First,our analysis of hospitalized children may be biased towardshigher rates of resistance compared with those found forpatients treated in an outpatient setting, even though only9% of our patients had received oral antibiotic therapy atthe time of hospital admission. Second, urinary pathogenscausing mild UTI, which were excluded from our study,may show lower rates of resistance. Antimicrobial resis-tance in the group of patients with moderate UTI, however,was not significantly different from that in the group withsevere UTI (data not shown). Third, the impact of in vitroresistance on clinical outcome is not clear. Since drugs suchas β-lactam agents and cotrimoxazole reach high urinaryconcentrations for prolonged periods of time, it is possiblethat in vitro findings do not accurately predict treatmentfailure. However, existing data for UTI in adults suggestthat infection with resistant organisms may adversely af-fect clinical outcome [12].References1. Larcombe J (1999) Urinary tract infection. Br Med J 319:1173–11752352. Benador D, Neuhaus TJ, Papzyan JP, Willi UV, Engel-Bicik I,Nadal D, Slosman B, Mermillod B, Girardin E (2001) Random-ized controlled trial of three day versus 10 day intranvenousantibiotics in acute pyelonephritis; effect on renal scarring. ArchDis Child 84:241–2463. Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, MajdM, Kearney DH, Reynolds EA, Ruley J, Janosky JE (1999) Oralversus initial intravenous therapy of urinary tract infections inyoung febrile children. Pediatrics 104:79–864. Bloomfield P, Hodson EM, Craig JC (2003) Antibiotics foracute pyelonephritis in children. Cochrane Database Syst Rev3:CD0037725. Ladhani S, Grandsen W (2003) Increasing antibiotic re-sistance among urinary tract isolates. Arch Dis Child 88:444–4456. Prais D, Straussberg R, Avitzur Y, Nussinovitch M, Harel L,Amir J (2003) Bacterial susceptibility to oral antibiotics in com-munity acquired urinary tract infection. Arch Dis Child 88:215–2187. Haller M, Brandis M, Berner R (2004) Antibiotic resistance ofurinary tract pathogens and rationale for empirical intravenoustherapy. Pediatr Nephrol 19:982–9868. Bianchetti MG, Markus-Vecerova D, Schaad UB (1995)Antibiotics in the treatment of urinary infections in hospitalizedchildren. Schweiz Med Wochenschr 125:201–2069. Schweizerische Arbeitsgruppe fu¨r Pa¨diatrische Nephrologie:Behandlung der Harnwegsinfektionen beim Kind. Available atwww.swiss-pediatrics.org/paediatrica/vol12/n1/pyelo_ge.htm10. Kahlmeter G (2003) An international survey of the antimicrobialsusceptibility of pathogens from uncomplicated urinary tract in-fections: the ECOSENS project. J Antimicrob Chemother 41:69–7611. Howard AJ, Magee JT, Fitzgerald KA, Dunstan FDJ (2001) Fac-tors associated with antibiotic resistance in coliform organismsfrom community urinary tract infections in males. J AntimicrobChemother 47:305–31312. Mazzulini WT (2002) Resistance trends in urinary tractpathogens and impact on management. J Urol 168:1720–1722

Changes in antimicrobial resistance of Escherichia coli causing urinary tract infections in hospitalized children

http://doc.rero.ch/record/317741/files/10096_2005_Article_1301.pdf

Changes in antimicrobial resistance of Escherichia coli causing urinary tract infections in hospitalized children

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library