The Prevalence of Fluoroquinolone Resistance Mechanisms in ColonizingEscherichia coliIsolates Recovered from Hospitalized Patients

e18681 Background: Patients undergoing chemotherapy treatment are at risk for bacterial infection during their period of neutropenia. However, not all neutropenic patients are at high risk for developing infection. The purpose of this study was to evaluate the efficacy and safety of prophylactic oral levofloxacin in high, intermediate, and low infection risk patients with cancer in the ambulatory care setting. Methods: This was a retrospective chart review of 100 cancer patients with high, intermediate, and low overall infection risk who were prescribed outpatient oral levofloxacin prophylaxis between October 2019 and July 2020. This quality improvement project included adults with a history of malignancy and presence of neutropenia who have received chemotherapy treatment and oral levofloxacin therapy for overall infection prophylaxis. The primary efficacy outcome was the rate of hospital admission due to febrile neutropenia. The primary safety outcome was the occurrence of side effects of levofloxacin therapy. Secondary outcomes evaluated the duration of levofloxacin therapy, the rate of fluoroquinolone resistance in positive bacterial cultures, progression to sepsis in hospitalized patients and the rate of death due to mult-idrug resistance including fluoroquinolones. Results: Hospital admission due to febrile neutropenia after a chemotherapy cycle occurred in 18% of patients prescribed levofloxacin. Among hospitalized patients due to febrile neutropenia, 2% had low to intermediate overall infection risk and 16% had high overall infection risk. The primary safety outcome occurred in 25% of patients. The incidence of QTc prolongation occurred in 8% of patients; dermatologic side effects occurred in 9% of patients; the rate of Clostridioides difficile infection was 6%, and the rate of tendon rupture was 2%. Median duration of levofloxacin prophylaxis in the low overall infection risk group was 7 days, compared to the intermediate overall infection risk group (8.5 days) and the high overall infection risk group (14 days) with Kruskal-Wallis test p-value of 0.0009. The rate of fluoroquinolone resistance in positive bacterial cultures was 10%. Progression to sepsis in hospitalized patients occurred in 17% of patients. The rate of death due to multi-drug resistance including fluoroquinolone was 2%. Conclusions: Our findings signify preserved efficacy of levofloxacin prophylaxis in the ambulatory setting. Our findings should be considered to develop rational strategies to reduce fluoroquinolone overprescribing or limit duration of levofloxacin prophylaxis. If patients present with solid tumors and experience neutropenia, the use of antibacterial prophylaxis is not recommended because in general, patients recover from neutropenia quickly.

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Imipenem-resistant Pseudomonas aeruginosa gastrointestinal carriage among hospitalized patients: risk factors and resistance mechanisms

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2009.08.014 ◽

2010 ◽

Vol 66 (1) ◽

pp. 1-6 ◽

Cited By ~ 16

Author(s):

Didier Lepelletier ◽

Anne Cady ◽

Nathalie Caroff ◽

Julie Marraillac ◽

Alain Reynaud ◽

...

Keyword(s):

Risk Factors ◽

Pseudomonas Aeruginosa ◽

Resistance Mechanisms ◽

Hospitalized Patients

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First characterization of fluoroquinolone resistance mechanisms in CTX-M-producing Escherichia coli from Mongolia

Infection Genetics and Evolution ◽

10.1016/j.meegid.2015.12.010 ◽

2016 ◽

Vol 38 ◽

pp. 79-81 ◽

Cited By ~ 2

Author(s):

Cheng-Yen Kao ◽

Uuganbayar Udval ◽

Hsiu-Mei Wu ◽

Enkhbaatar Bolormaa ◽

Jing-Jou Yan ◽

...

Keyword(s):

Escherichia Coli ◽

Resistance Mechanisms ◽

Fluoroquinolone Resistance

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Fluoroquinolone Resistance: Mechanisms, Restrictive Dosing, and Anti-Mutant Screening Strategies for New Compounds

Antibiotic Discovery and Development ◽

10.1007/978-1-4614-1400-1_14 ◽

2011 ◽

pp. 485-514 ◽

Cited By ~ 5

Author(s):

Karl Drlica ◽

Xilin Zhao ◽

Muhammad Malik ◽

Tal Salz ◽

Robert Kerns

Keyword(s):

Resistance Mechanisms ◽

Fluoroquinolone Resistance ◽

Mutant Screening ◽

Screening Strategies ◽

New Compounds

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Acquisition of extensive drug-resistant Pseudomonas aeruginosa among hospitalized patients: risk factors and resistance mechanisms to carbapenems

Journal of Hospital Infection ◽

10.1016/j.jhin.2011.05.014 ◽

2011 ◽

Vol 79 (1) ◽

pp. 54-58 ◽

Cited By ~ 28

Author(s):

Y.S. Park ◽

H. Lee ◽

B.S. Chin ◽

S.H. Han ◽

S.G. Hong ◽

...

Keyword(s):

Risk Factors ◽

Pseudomonas Aeruginosa ◽

Resistance Mechanisms ◽

Hospitalized Patients ◽

Drug Resistant

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Overexpression of Efflux Pumps, Mutations in the Pumps’ Regulators, Chromosomal Mutations, and AAC(6′)-Ib-cr Are Associated With Fluoroquinolone Resistance in Diverse Sequence Types of Neonatal Septicaemic Acinetobacter baumannii: A 7-Year Single Center Study

Frontiers in Microbiology ◽

10.3389/fmicb.2021.602724 ◽

2021 ◽

Vol 12 ◽

Author(s):

Subhasree Roy ◽

Somdatta Chatterjee ◽

Amrita Bhattacharjee ◽

Pinaki Chattopadhyay ◽

Bijan Saha ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Efflux Pump ◽

Critical Role ◽

Holistic Approach ◽

Efflux Pumps ◽

Resistance Mechanisms ◽

Fluoroquinolone Resistance ◽

Active Efflux ◽

Chromosomal Mutations ◽

Sequence Types

This study investigates susceptibility toward three fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), multiple fluoroquinolone-resistance mechanisms, and epidemiological relationship of neonatal septicaemic Acinetobacter baumannii. Previous studies on fluoroquinolone resistance in A. baumannii focused primarily on ciprofloxacin susceptibility and assessed a particular mechanism of resistance; a more holistic approach was taken here. Epidemiological relationship was evaluated by Multi Locus Sequence Typing. Minimum Inhibitory Concentrations of fluoroquinolones was determined with and without efflux pump inhibitors. Overexpression of efflux pumps, resistance-nodulation-cell-division (RND)-type, and multidrug and toxic compound extrusion (MATE)-type efflux pumps were evaluated by reverse transcriptase-qPCR. Mutations within regulatory proteins (AdeRS, AdeN, and AdeL) of RND-pumps were examined. Chromosomal mutations, presence of qnr and aac(6′)-Ib-cr were investigated. A. baumannii were highly diverse as 24 sequence-types with seven novel STs (ST-1440/ST-1441/ST-1481/ST-1482/ST-1483/ST-1484/ST-1486) were identified among 47 A. baumannii. High resistance to ciprofloxacin (96%), levofloxacin (92%), and particularly moxifloxacin (90%) was observed, with multiple mechanisms being active. Resistance to 4th generation fluoroquinolone (moxifloxacin) in neonatal isolates is worrisome. Mutations within GyrA (S83L) and ParC (S80L) were detected in more than 90% of fluoroquinolone-resistant A. baumannii (FQRAB) spread across 10 different clonal complexes (CC1/CC2/CC10/CC25/CC32/CC126/CC149/CC216/CC218/CC513). Efflux-based FQ resistance was found in 65% of FQRAB with ≥2 different active pumps in 38% of strains. Overexpression of adeB was highest (2.2−34-folds) followed by adeJ, adeG, and abeM. Amino acid changes in the regulators (AdeRS/AdeN/AdeL) either as single or multiple substitutions substantiated the overexpression of the pumps. Diverse mutations within AdeRS were detected among different CCs whereas mutations within AdeN linked to CC10 and CC32. Chromosomal mutations and active efflux pumps were detected simultaneously among 64% of FQRAB. Presence of aac(6′)-Ib-cr was also high (74% of FQRAB) but qnrS were absent. As most FQRABs had chromosomal mutations, this was considered predominant, however, isolates where pumps were also active had higher MIC values, establishing the critical role of the efflux pumps. The high variability of FQ susceptibility among FQRAB, possessing the same set of mutations in gyrA, parC, and efflux pump regulators, was also noted. This reveals the complexity of interpreting the interplay of multiple resistance mechanisms in A. baumannii.

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Contribution of Different Mechanisms to Ciprofloxacin Resistance in Salmonella spp.

Frontiers in Microbiology ◽

10.3389/fmicb.2021.663731 ◽

2021 ◽

Vol 12 ◽

Author(s):

Man-Xia Chang ◽

Jin-Fei Zhang ◽

Yin-Huan Sun ◽

Rong-Sheng Li ◽

Xiao-Ling Lin ◽

...

Keyword(s):

Resistance Mechanisms ◽

Quinolone Resistance ◽

Gene Location ◽

Fluoroquinolone Resistance ◽

Salmonella Spp ◽

Resistance Development ◽

Bacterial Fitness ◽

Ciprofloxacin Resistance ◽

Gyra Mutation ◽

Chromosomal Mutations

Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes (gyrAB and parCE) encoding the target bacterial topoisomerase enzymes, increased expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176 Salmonella isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in Salmonella from the food chain.

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Genomic Sequences of Uropathogenic Escherichia coli Strains with Various Fluoroquinolone Resistance Profiles

Microbiology Resource Announcements ◽

10.1128/mra.00199-20 ◽

2020 ◽

Vol 9 (38) ◽

Author(s):

Kayo Okumura ◽

Masako Kaido ◽

Eiki Yamasaki ◽

Yasumasa Akai ◽

Hisao Kurazono ◽

...

Keyword(s):

Escherichia Coli ◽

Resistance Mechanisms ◽

Uropathogenic Escherichia Coli ◽

Fluoroquinolone Resistance ◽

Whole Genome ◽

Drug Resistant ◽

Valuable Resource ◽

Sequencing Data ◽

Content Type ◽

Tract Infections

ABSTRACT The emergence of drug-resistant uropathogenic Escherichia coli (UPEC) has hampered antibiotic therapy for urinary tract infections. To elucidate the resistance mechanisms of UPEC, we performed whole-genome sequencing of eight UPEC strains with different fluoroquinolone resistance levels. Here, we report our sequencing data, providing a valuable resource for understanding such mechanisms.

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