Fluoroquinolone resistance of  Staphylococcus epidermidis  isolated from healthy conjunctiva and analysis of their mutations in quinolone-resistance determining region

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Abstract

Background

Staphylococcus epidermidis is the most common pathogen in postoperative endophthalmitis and causes various infectious eye diseases. However, there is very little information on fluoroquinolone antibiotic resistance to S. epidermidis identified in conjunctival microbe and analysis of related genes. Here, the authors investigated the rate of resistance to fluoroquinolones of Staphylococcus epidermidis isolated from normal conjunctival microbes and mutations in the quinolone-resistance determining region (QRDR).

Methods

377 eye samples from 187 patients who underwent intravitreal injection and cataract surgery were included. Specimens were taken from the bilateral lower conjunctival sacs using a cotton swab and cultured. The cultures were identified using MALDI-TOP MS and gyrA, gyrB, parC, and parE gene mutations of QRDR were confirmed by DNA extraction from resistant strains of S. epidermidis with a micro-dilution method using ciprofloxacin, levofloxacin, and moxifloxacin .

Results

The culture positive rate was 61.8% (231) for 374 eye samples. Of the 303 total strains cultured, S. epidermidis was the most common with 33.7% (102). Ten types of gene mutations were observed in the resistant S. epidermidis of 21 strains. One-point mutation was observed mainly in gyrA and parC, and a small number of mutations were observed in parE in the form of a double point mutations. When there were multiple point mutations in both gyrA and parC, the highest minimum inhibitory concentration was observed.

Conclusions

The quinolone resistance rate of S. epidermidis increased in comparison with previous studies, and resistant S. epidermidis showed mostly QRDR mutations, which were mainly found in gyrA and parC, and showed strong resistance when mutated in both genes.

Related collections

Most cited references 29

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Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study.

Jessica Kelsey, A Vine, B H Doft … (1996)

To determine the microbiologic spectrum and antibiotic susceptibilities of infecting organisms in postoperative endophthalmitis and to evaluate the effects of operative factors on the microbiologic spectrum. Patients with bacterial endophthalmitis presenting within six weeks of cataract extraction or secondary intraocular lens implantation (IOL) were evaluated. Cultures and Gram stains were performed on intraocular specimens and susceptibility tests on the isolates. Confirmed microbiologic growth was demonstrated from intraocular specimens from 291 of 420 patients (69.3%). Gram-positive bacteria were isolated from 274 patients (94.2%) with confirmed growth and gram-negative bacteria from 19 (6.5%). Two hundred twenty-six of the 323 isolates obtained (70.0%) were gram-positive, coagulase-negative micrococci, 32 (9.9%) Staphylococcus aureus, 29 (9.0%) Streptococcus species, seven (2.2%) Enterococcus species, ten (3.1%) miscellaneous gram-positive species, and 19 (5.9%) gram-negative species. All gram-positive isolates tested were susceptible to vancomycin. Seventeen gram-negative isolates (89%) were susceptible to both amikacin and ceftazidime and two (11%) were resistant to both. Anterior chamber or secondary IOL implantations were associated with higher rates of infection with gram-positives other than coagulase-negative micrococci than were posterior chamber IOL implantations (P = .022) or primary cataract extractions (P = .024). Gram-positive, coagulase-negative micrococci predominated in this series. Vancomycin was active against all gram-positive isolates tested. Amikacin and ceftazidime showed equivalent activity against gram-negative isolates. Secondary or anterior chamber lens implantations were associated with a possible spectrum shift toward gram-positive organisms other than the coagulase-negative micrococci.

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George Jacoby (2005)

The increased use of fluoroquinolones has led to increasing resistance to these antimicrobials, with rates of resistance that vary by both organism and geographic region. Resistance to fluoroquinolones typically arises as a result of alterations in the target enzymes (DNA gyrase and topoisomerase IV) and of changes in drug entry and efflux. Mutations are selected first in the more susceptible target: DNA gyrase, in gram-negative bacteria, or topoisomerase IV, in gram-positive bacteria. Additional mutations in the next most susceptible target, as well as in genes controlling drug accumulation, augment resistance further, so that the most-resistant isolates have mutations in several genes. Resistance to quinolones can also be mediated by plasmids that produce the Qnr protein, which protects the quinolone targets from inhibition. Qnr plasmids have been found in the United States, Europe, and East Asia. Although Qnr by itself produces only low-level resistance, its presence facilitates the selection of higher-level resistance mutations, thus contributing to the alarming increase in resistance to quinolones.

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Surveillance and correlation of antibiotic prescription and resistance of Gram-negative bacteria in Singaporean hospitals.

Vincent Tam, Andrea L H Kwa, Thean-Yen Tan … (2010)

A surveillance study was performed in four Singapore public hospitals from 2006 to 2008 to determine the correlation between antibiotic prescription and Gram-negative bacterial antimicrobial resistance. Targeted organisms included ceftriaxone- and ciprofloxacin-resistant Escherichia coli and Klebsiella pneumoniae, as well as imipenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days every quarter. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated via cross-correlation analysis. Results over 3 years indicated significantly rising incidence densities of ceftriaxone- and ciprofloxacin-resistant E. coli and imipenem-resistant Acinetobacter spp. (blood isolates only). Antimicrobial-resistant Klebsiella pneumoniae rates declined. The prescription rates of piperacillin-tazobactam, ertapenem, meropenem, ciprofloxacin, and levofloxacin increased significantly, while imipenem and moxifloxacin prescription decreased. Cross-correlation analysis demonstrated possible associations between prescription of fluoroquinolones and ciprofloxacin-resistant E. coli (R(2) = 0.46), fluoroquinolones and ceftriaxone-resistant E. coli (R(2) = 0.47), and carbapenems and imipenem-resistant Acinetobacter spp. (R(2) = 0.48), all at zero time lag. Changes in meropenem prescription were associated with a similar trend in imipenem-resistant Acinetobacter blood isolates after a 3-month time lag. No correlation was found between cephalosporin use and resistance. In conclusion, our data demonstrated correlation between prescription of and Gram-negative bacterial resistance to several, but not all, key antimicrobial agents in Singapore hospitals. In areas where Gram-negative bacterial resistance is endemic and prescription of broad-spectrum antimicrobial agents is high, factors other than antimicrobial usage may be equally important in maintaining high resistance rates.

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Author and article information

Contributors

Sang Joon Lee:

ORCID: http://orcid.org/0000-0001-6673-569X

hhiatus@gmail.com

Journal

Journal ID (nlm-ta): Antimicrob Resist Infect Control

Journal ID (iso-abbrev): Antimicrob Resist Infect Control

Title: Antimicrobial Resistance and Infection Control

Publisher: BioMed Central (London )

ISSN (Electronic): 2047-2994

Publication date (Electronic): 4 November 2020

Publication date PMC-release: 4 November 2020

Publication date Collection: 2020

Volume: 9

Electronic Location Identifier: 177

Affiliations

[1 ]GRID grid.411144.5, ISNI 0000 0004 0532 9454, Department of Ophthalmology, , Kosin University College of Medicine, ; 262 Gamchun-ro, Seo-gu, Busan, South Korea

[2 ]GRID grid.411144.5, ISNI 0000 0004 0532 9454, Department of Laboratory Medicine, , Kosin University College of Medicine, ; Busan, South Korea

[3 ]GRID grid.411144.5, ISNI 0000 0004 0532 9454, Department of Microbiology, , Kosin University College of Medicine, ; Busan, South Korea

Author information

Sang Joon Lee http://orcid.org/0000-0001-6673-569X

Article

Publisher ID: 841

DOI: 10.1186/s13756-020-00841-3

PMC ID: 7640383

PubMed ID: 33148329

SO-VID: 8905a8ed-d937-48aa-958d-b19348f361bf

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

History

Date received : 3 August 2020

Date accepted : 27 October 2020

Custom metadata

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: staphylococcus epidermidis,quinolone resistance,qrdr,mutation,conjunctiva,microbes

Data availability:

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: staphylococcus epidermidis, quinolone resistance, qrdr, mutation, conjunctiva, microbes

Fluoroquinolone resistance of Staphylococcus epidermidis isolated from healthy conjunctiva and analysis of their mutations in quinolone-resistance determining region

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