Accepted Manuscript Changes in minimum inhibitory concentration of levofloxacin for Escherichia coli strains isolated from urine samples in mainland China, 2004 to 2014 Bo Zheng, Yun Li, Feng Xue, Sai-Nan Zhu, Yuan Lyu PII:
S1684-1182(16)30074-3
DOI:
10.1016/j.jmii.2016.06.009
Reference:
JMII 781
To appear in:
Journal of Microbiology, Immunology and Infection
Received Date: 24 May 2016 Revised Date:
30 May 2016
Accepted Date: 27 June 2016
Please cite this article as: Zheng B, Li Y, Xue F, Zhu S-N, Lyu Y, Changes in minimum inhibitory concentration of levofloxacin for Escherichia coli strains isolated from urine samples in mainland China, 2004 to 2014, Journal of Microbiology, Immunology and Infection (2016), doi: 10.1016/j.jmii.2016.06.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Changes in minimum inhibitory concentration of levofloxacin for Escherichia coli
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strains isolated from urine samples in mainland China, 2004 to 2014
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Yun Lia, Bo Zhenga,*, Feng Xuea, Sai-Nan Zhub, and Yuan Lyua
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China
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Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, PR
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Department of Biostatistics, Peking University First Hospital, Beijing 100034, PR China
*Corresponding author
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Institute of Clinical Pharmacology
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Peking University First Hospital
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No.8, Xishiku Street, Xicheng District, 100034,Beijing, China
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Tel: +86-10 8280 2548
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Fax: +86-10 6207 2817
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E-mail:
[email protected]
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Abstract
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E. coli urinary isolates were collected from 20 Chinese hospitals during five 1-year periods
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from 2004-2014. The susceptibility of E. coli to levofloxacin has remained stable during the
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past 11 years, 90% of strains had MICs of ≤32 mg/L. The urine-specific susceptibility
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breakpoints for levofloxacin should be reset based on more relevant clinical studies and the
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current pharmacokinetic/pharmacodynamic considerations in this field.
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Keywords: levofloxacin, Escherichia coli, uriniary tract infection, susceptibility
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Introduction
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Urinary tract infections (UTIs) are the most frequently occurring bacterial infections, both in
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the community and in hospitals. Escherichia coli is the most commonly encountered
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uropathogen. Several international guidelines recommend levofloxacin as the drug of choice
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for empirical treatment of UTIs, including catheter-associated UTIs1,2. However, the
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widespread use of levofloxacin for complicated or catheter-associated UTIs might result in
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reduced susceptibility of E. coli to levofloxacin 3.
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The aim of this study was to evaluate and compare the susceptibility pattern of E. coli
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urinary isolates to levofloxacin in mainland China during four 1-year periods from 2004 to
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2014.
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Materials and methods
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Isolates
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In total, 1127 nonreplicate clinical E. coli urinary isolates were collected from 20 widely
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dispersed tertiary hospitals during four 1-year periods (October 2004–September 2005,
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January 2007–December 2007, July 2009–June 2010, July 2011–June 2012, and July
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2013–June 2014). All isolates were sent to the Institute of Clinical Pharmacology, Peking
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University First Hospital, where they were stored at –80°C until further analysis.
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Antimicrobial susceptibility testing
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Susceptibility to antimicrobial agents was determined using the agar dilution method
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established by the Clinical and Laboratory Standards Institute. Extended-spectrum
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beta-lactamase (ESBL)-producing isolates were detected using previously described methods
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coli was ≥8 mg/L, and sensitivity was defined as a minimum inhibitory concentration (MIC)
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of ≤2 mg/L 4.
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. The control strain was ATCC 25922. The breakpoint for resistance to levofloxacin for E.
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Statistical analyses
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Statistical tests were performed using SPSS for Windows, version 14.0 (SPSS Inc., Chicago,
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IL, USA). Enumeration data were expressed as percentages. Differences in susceptibility
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between the groups were compared using the chi-squared test or Fisher’s exact test.
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Differences were considered statistically significant at a two-sided p-value of 20%8. In our clinical
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practice, the symptoms of many patients with lower UTIs resolved in 7 days after treatment
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with levofloxacin at 500 mg daily, but the urine culture revealed levofloxacin-resistant E. coli.
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The Clinical and Laboratory Standards Institute provided a urine-specific breakpoint for
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Enterobacteriaceae for some fluoroquinolones (lomefloxacin, ofloxacin, and norfloxacin),
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but not for levofloxacin. Although most clinical microbiology laboratories determine the
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ACCEPTED MANUSCRIPT susceptibilities of urinary isolates of Enterobacteriaceae to levofloxacin by applying
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non-urine-specific MIC breakpoints, this does not mean that levofloxacin is not a suitable
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treatment for UTIs caused by pathogens with “in vitro resistance” to the agent8. Previous
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studies have clearly demonstrated that the mean peak urinary concentration of levofloxacin
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(0.0–1.5 h) was 347 mg/L at a dose of 500 mg. Levofloxacin exhibited early (0.0- to 1.5-h
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time period) bactericidal activity in urine specimens in virtually all subjects against study
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isolates with MICs of ≤32 mg/L 9.
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The urine-specific susceptibility breakpoints for levofloxacin should be reset based on more
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relevant clinical studies, especially in regions with a high prevalence of UTIs caused by
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multidrug-resistant uropathogens. This is especially prudent give the current
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pharmacokinetic/pharmacodynamic considerations in this field. Fluoroquinolone resistance
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within society should also be meticulously investigated7.
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References
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Table Legends
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Table 1.
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Susceptibility of E. coli to levofloxacin, 2004–2014
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S = sensitive; I = intermediate; R = resistant
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*Compared with 10/2004–9/2005, p
