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      Aminoglycoside therapy for childhood urinary tract infection due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae

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          Abstract

          Background

          The rate of urinary tract infections (UTIs) due to extended-spectrum β-lactamase (ESBL)-producing bacterial strains requiring carbapenem therapy has been increasing in children. This study was conducted to evaluate the effect of non-carbapenem antibiotic therapy on childhood UTIs caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.

          Methods

          Medical records of children diagnosed with febrile UTIs due to E. coli or K. pneumoniae between 2010 and 2014 were retrospectively reviewed. The enrolled children were divided into two groups: the ESBL group and the non-ESBL group. Clinical characteristics and therapeutic responses were compared between the two groups.

          Results

          A total of 211 episodes of UTI (204 caused by E. coli; seven caused by K. pneumoniae) were identified in 205 children. Twenty-two (10.4 %) episodes were categorized into the ESBL group. There was no significant difference in the type of antibiotic administered between the two groups. No carbapenems were administered; however, aminoglycosides were administered for 79.1 % of the total episodes. Although empirical antibiotics were appropriate for more episodes in the non-ESBL group compared with the ESBL group (100.0 % vs. 90.9 %, p = 0.011), there were no significant differences in the frequency of defervescence, bacterial eradication from the urine, acute pyelonephritis and vesicoureteral reflux or fever duration between the two groups.

          Conclusions

          Non-carbapenem antibiotics showed favourable therapeutic effects on childhood UTIs caused by ESBL-producing strains. Aminoglycosides can be an alternative to carbapenems in such cases.

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          Most cited references26

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          Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern.

          The medical community relies on clinical expertise and published guidelines to assist physicians with choices in empirical therapy for system-based infectious syndromes, such as community-acquired pneumonia and urinary-tract infections (UTIs). From the late 1990s, multidrug-resistant Enterobacteriaceae (mostly Escherichia coli) that produce extended-spectrum beta lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of UTIs. Recent reports have also described ESBL-producing E coli as a cause of bloodstream infections associated with these community-onset UTIs. The carbapenems are widely regarded as the drugs of choice for the treatment of severe infections caused by ESBL-producing Enterobacteriaceae, although comparative clinical trials are scarce. Thus, more rapid diagnostic testing of ESBL-producing bacteria and the possible modification of guidelines for community-onset bacteraemia associated with UTIs are required.
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            Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis.

            To study the comparative mortality associated with carbapenems and alternative antibiotics for the treatment of patients with extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae bacteraemia. We searched systematically PubMed and Scopus databases for studies providing data for mortality among patients treated with carbapenems, β-lactam/β-lactamase inhibitor combinations (BL/BLIs) or non-BL/BLIs (mainly cephalosporins and fluoroquinolones), preferably as monotherapy. Studies focusing on patients of all ages with community- and healthcare-associated bacteraemia were eligible. Data were pooled using the technique of meta-analysis. Twenty-one articles, studying 1584 patients, were included. Escherichia coli and Klebsiella pneumoniae were the most commonly studied bacteria. Delay in appropriate treatment up to 6 days was reported. Carbapenems were used mainly as definitive therapy. Carbapenems were associated with lower mortality than non- BL/BLIs for definitive [risk ratio (RR) 0.65, 95% CI 0.47-0.91] and empirical (RR 0.50, 95% CI 0.33-0.77) treatment. No statistically significant differences in mortality were found between carbapenems and BL/BLIs administered as definitive (RR 0.52, 95% 0.23-1.13) or empirical (RR 0.91, 95% CI 0.66-1.25) treatment. BL/BLIs were not associated with lower mortality than non-BL/BLIs administered either definitively (RR 1.59, 95% 0.83-3.06) or empirically (RR 0.82, 95% 0.48-1.41). Data regarding subgroups according to the setting, comorbidity and bacterial species could not be extracted. Based on data from non-randomized studies, carbapenems may be considered the treatment of choice for empirical treatment of patients with ESBL-producing Enterobacteriaceae bacteraemia. The role of BL/BLIs should be further evaluated for definitive treatment. Further research should focus on faster identification of ESBL-positive pathogens and potential differences in the treatment of each bacterial species.
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              Risk factors for community-onset urinary tract infections due to Escherichia coli harbouring extended-spectrum beta-lactamases.

              Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have been increasingly recognized in the community. The aim of this study was to determine the prevalence, types of ESBLs and risk factors for community-onset ESBL-producing E. coli in urinary tract infections (UTIs). Adults with community-onset UTIs due to ESBL-producing E. coli (cases) and non-ESBL-producing E. coli (controls) were identified through records of the clinical microbiology laboratory of the hospital. Two different periods were studied: from January 2000 to January 2001 and from October to December 2003. Controls were matched in a 3:1 ratio to case patients according to age, sex, date of isolation and residence in a long-term care facility. Potential risk factors were recorded. Isoelectric focusing as well as PCR and DNA sequencing were used to characterize the bla(TEM), bla(SHV) and bla(CTX-M) genes. A possible clonal relationship among the strains was determined by repetitive extragenic palindromic sequence PCR. The prevalence of infection due to ESBL-producing E. coli increased from 0.47% in 2000 to 1.7% in 2003 (P < 0.001). Community-onset ESBL-producing E. coli infection shifted from 50% in the first period to 79.5% in 2003 (P < 0.001). Nineteen cases and 55 matched controls of community-onset ESBL-producing E. coli UTI were included. ESBL-producing E. coli strains were clonally unrelated. On univariate analysis, genitourinary pathology (P < 0.03), previous bacterial infection (P = 0.01), intravenous antibiotic treatment (P = 0.01), hospitalization in the previous 12 months (P = 0.04) and previous exposure to oral second-generation cephalosporins (P < 0.05) were associated with community-onset infection due to ESBL-producing E. coli. In our regression model, only previous exposure to second-generation cephalosporins was strongly associated with E. coli harbouring ESBLs (OR, 21.42; CI 95%, 5.38-85.22; P < 0.05). In the first period, only TEM- and SHV-derived ESBLs were identified. The enzymes were characterized as members of the TEM group (60%), SHV group (16%) and CTX-M group (24%). We detected a marked increase in infections due to ESBL-producing E. coli, especially in the community, in the periods studied. Only previous exposure to the oxyimino cephalosporin cefuroxime, and not to ciprofloxacin, aminoglycosides or third-generation cephalosporins, was predictive of an ESBL-producing E. coli community-onset infection in our area. The emergence of the CTX-M type of beta-lactamase in E. coli follows closely the spread of ESBLs in community isolates.
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                Author and article information

                Contributors
                beomsid@catholic.ac.kr
                erdc87@naver.com
                82 32 280 5865 , sylee@catholic.ac.kr
                dcjeong@catholic.ac.kr
                kjhan@catholic.ac.kr
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                13 October 2015
                13 October 2015
                2015
                : 15
                : 414
                Affiliations
                [ ]Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
                [ ]The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
                [ ]Department of Pediatrics, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Dongsu-ro 56, Bupyeong-gu, Incheon, 403-720 Republic of Korea
                Article
                1153
                10.1186/s12879-015-1153-z
                4604622
                25567701
                d6bb723a-feb3-431a-a434-cff398705d2c
                © Han et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 7 May 2015
                : 28 September 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Infectious disease & Microbiology
                urinary tract infection,escherichia coli,klebsiella pneumoniae,beta-lactamase,child

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