Empiric antibiotic therapy in urinary tract infection in patients with risk factors for antibiotic resistance in a German emergency department

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Abstract

Background

The aim of this study was to identify clinical risk factors for antimicrobial resistances and multidrug resistance (MDR) in urinary tract infections (UTI) in an emergency department in order to improve empirical therapy.

Methods

UTI cases from an emergency department (ED) during January 2013 and June 2015 were analyzed. Differences between patients with and without resistances towards Ciprofloxacin, Piperacillin with Tazobactam (Pip/taz), Gentamicin, Cefuroxime, Cefpodoxime and Ceftazidime were analyzed with Fisher’s exact tests. Results were used to identify risk factors with logistic regression modelling. Susceptibility rates were analyzed in relation to risk factors.

Results

One hundred thirty-seven of four hundred sixty-nine patients who met the criteria of UTI had a positive urine culture. An MDR pathogen was found in 36.5% of these. Overall susceptibility was less than 85% for standard antimicrobial agents. Logistic regression identified residence in nursing homes, male gender, hospitalization within the last 30 days, renal transplantation, antibiotic treatment within the last 30 days, indwelling urinary catheter and recurrent UTI as risk factors for MDR or any of these resistances. For patients with no risk factors Ciprofloxacin had 90%, Pip/taz 88%, Gentamicin 95%, Cefuroxime 98%, Cefpodoxime 98% and Ceftazidime 100% susceptibility. For patients with 1 risk factor Ciprofloxacin had 80%, Pip/taz 80%, Gentamicin 88%, Cefuroxime 78%, Cefpodoxime 78% and Ceftazidime 83% susceptibility. For 2 or more risk factors Ciprofloxacin drops its susceptibility to 52%, Cefuroxime to 54% and Cefpodoxime to 61%. Pip/taz, Gentamicin and Ceftazidime remain at 75% and 77%, respectively.

Conclusions

We identified several risk factors for resistances and MDR in UTI. Susceptibility towards antimicrobials depends on these risk factors. With no risk factor cephalosporins seem to be the best choice for empiric therapy, but in patients with risk factors the beta-lactam penicillin Piperacillin with Tazobactam is an equal or better choice compared to fluoroquinolones, cephalosporins or gentamicin. This study highlights the importance of monitoring local resistance rates and its risk factors in order to improve empiric therapy in a local environment.

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Most cited references 16

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A resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens.

Karen Bush (2015)

β-Lactamase inhibitors (BLIs) have played an important role in combatting β-lactam resistance in Gram-negative bacteria, but their effectiveness has diminished with the evolution of diverse and deleterious varieties of β-lactamases. In this review, a new generation of BLIs and inhibitor combinations is presented, describing epidemiological information, pharmacodynamic studies, resistance identification and current clinical status. Novel serine BLIs of major interest include the non-β-lactams of the diazabicyclo[3.2.1]octanone (DBO) series. The DBOs avibactam, relebactam and RG6080 inhibit most class A and class C β-lactamases, with selected inhibition of class D enzymes by avibactam. The novel boronic acid inhibitor RPX7009 has a similar inhibitory profile. All of these inhibitors are being developed in combinations that are targeting primarily carbapenemase-producing Gram-negative pathogens. Two BLI combinations (ceftolozane/tazobactam and ceftazidime/avibactam) were recently approved by the US Food and Drug Administration (FDA) under the designation of a Qualified Infectious Disease Product (QIDP). Other inhibitor combinations that have at least completed phase 1 clinical trials are ceftaroline fosamil/avibactam, aztreonam/avibactam, imipenem/relebactam, meropenem/RPX7009 and cefepime/AAI101. Although effective inhibitor combinations are in development for the treatment of infections caused by Gram-negative bacteria with serine carbapenemases, better options are still necessary for pathogens that produce metallo-β-lactamases (MBLs). The aztreonam/avibactam combination demonstrates inhibitory activity against MBL-producing enteric bacteria owing to the stability of the monobactam to these enzymes, but resistance is still an issue for MBL-producing non-fermentative bacteria. Because all of the inhibitor combinations are being developed as parenteral drugs, an orally bioavailable combination would also be of interest.

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β-lactamase-mediated resistance: a biochemical, epidemiological and genetic overview.

Gabriel Gutkind, José Di Conza, Pablo Power … (2013)

Early after the introduction of the first (narrow spectrum) penicillins into clinical use, penicillinase-producing staphylococci replaced (worldwide) the previously susceptible microorganisms. Similarly, the extensive use of broad-spectrum, orally administered β- lactams (like ampicillin, amoxicillin or cefalexin) provided a favorable scenario for the selection of gram-negative microorganisms producing broad spectrum β-lactamases almost 45 years ago. These microorganisms could be controlled by the introduction of the so called "extended spectrum cephalosporins". However, overuse of these drugs resulted, after a few years, in the emergence of extended-spectrum β-lactamases (ESBLs) through point mutations in the existing broad-spectrum β-lactamases, such as TEM and SHV enzymes. Overuse of extended-spectrum β-lactams also gave rise to chromosomal mutations in regulatory genes which resulted in the overproduction of chromosomal AmpC genes, and, in other regions of the world, in the explosive emergence of other ESBL families, like the CTX-Ms. Carbapenems remained active on microorganisms harboring these extended-spectrum β-lactamases, while both carbapenems and fourth generation cephalosporins remained active towards those with derepressed (or the more recent plasmidic) AmpCs. However, microorganisms countered this assault by the emergence of the so called carbapenemases (both serine- and metallo- enzymes) which, in some cases, are actually capable of hydrolyzing almost all β-lactams including the carbapenems. Although all these enzyme families (some of them represented by hundreds of members) are for sure pre-dating the antibiotic era in environmental and clinically significant microorganisms, it was the misuse of these antibiotics that drove their evolution. This paper describes in detail each major class of β-lactamase including epidemiology, genetic, and biochemical evaluations.

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Prevalence and risk factor analysis of trimethoprim-sulfamethoxazole- and fluoroquinolone-resistant Escherichia coli infection among emergency department patients with pyelonephritis.

Walter E. Stamm, Anusha Krishnadasan, David Talan … (2008)

High rates of resistance to trimethoprim-sulfamethoxazole (TMP-SMX) among uropathogenic Escherichia coli are recognized, and concerns exist about emerging fluoroquinolone resistance. Adults presenting to 11 US emergency departments with (1) flank pain and/or costovertebral tenderness, (2) temperature >38 degrees C, and (3) a presumptive diagnosis of pyelonephritis were enrolled; patients for whom 1 uropathogen grew on culture were analyzed. Epidemiologic and clinical data were collected at the time of care. The prevalence of E. coli in vitro antibiotic resistance and risk factors associated with TMP-SMX-resistant E. coli infection were determined. Among 403 women with uncomplicated pyelonephritis caused by E. coli, the mean site rate of E. coli resistance to TMP-SMX was 24% (range, 13%-45%). Mean site rates of E. coli resistance to ciprofloxacin and levofloxacin were 1% and 3%, respectively. Only TMP-SMX exposure within 2 days before presentation and Hispanic ethnicity were associated with E. coli resistance to TMP-SMX (compared with resistance rates of approximately 20% among women lacking these risk factors); antibiotic exposure within 3-60 days before presentation, health care setting exposure within 30 days before presentation, history of urinary tract infections, and age >55 years were not associated with E. coli resistance to TMP-SMX. Among 207 patients with complicated pyelonephritis, mean site rates of E. coli resistance to ciprofloxacin and levofloxacin were 5% and 6%, respectively. These results suggest that the prevalence of TMP-SMX-resistant infection among patients with uncomplicated pyelonephritis is > or =20% in many areas of the United States, and risk stratification cannot identify patients at low risk of infection. Rates of fluoroquinolone-resistant E. coli infection appear to be low among patients with uncomplicated pyelonephritis but higher among those with complicated infections. Fluoroquinolones should remain to be the preferred empirical treatment for women with uncomplicated pyelonephritis.

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Author and article information

Contributors

Sebastian Bischoff: s.bischoff@stud.uni-heidelberg.de

Thomas Walter: Thomas.Walter2@umm.de

Marlis Gerigk: Marlis.Gerigk@umm.de

Matthias Ebert: matthias.ebert@medma.uni-heidelberg.de

Roger Vogelmann:

ORCID: http://orcid.org/0000-0001-5730-1558

+49-(0)621-383-2901 , Roger.vogelmann@medma.uni-heidelberg.de

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 26 January 2018

Publication date PMC-release: 26 January 2018

Publication date Collection: 2018

Volume: 18

Electronic Location Identifier: 56

Affiliations

[1 ]ISNI 0000 0001 2162 1728, GRID grid.411778.c, Second Department of Internal Medicine, , University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, ; Theodor-Kutzer Ufer 1-3, D-68167 Mannheim, Germany

[2 ]ISNI 0000 0001 2162 1728, GRID grid.411778.c, Emergency Department, , University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, ; Theodor-Kutzer Ufer 1-3, D-68167 Mannheim, Germany

[3 ]ISNI 0000 0001 2162 1728, GRID grid.411778.c, Department of Microbiology, , University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, ; Theodor-Kutzer Ufer 1-3, D-68167 Mannheim, Germany

Author information

Roger Vogelmann http://orcid.org/0000-0001-5730-1558

Article

Publisher ID: 2960

DOI: 10.1186/s12879-018-2960-9

PMC ID: 5787273

PubMed ID: 29373965

SO-VID: e3a4a2ba-c325-4dfe-bcc2-c392434ca48e

License:

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

Date received : 2 May 2017

Date accepted : 12 January 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;

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ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: antimicrobial resistance,emergency medicine,infectious disease,multidrug resistance,risk factors,urinary tract infection,antibiotic therapy

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ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: antimicrobial resistance, emergency medicine, infectious disease, multidrug resistance, risk factors, urinary tract infection, antibiotic therapy

Empiric antibiotic therapy in urinary tract infection in patients with risk factors for antibiotic resistance in a German emergency department

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Point-of-Care Testing for Infectious Diseases Super Collection

Most cited references 16

A resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens.

β-lactamase-mediated resistance: a biochemical, epidemiological and genetic overview.

Prevalence and risk factor analysis of trimethoprim-sulfamethoxazole- and fluoroquinolone-resistant Escherichia coli infection among emergency department patients with pyelonephritis.

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