Impact of Fluoroquinolones on Human Microbiota. Focus on the Emergence of Antibiotic Resistance

Lastours, Victoire de; Fantin, Bruno

doi:10.2217/fmb.15.40

Cited by 48 publications

(36 citation statements)

References 84 publications

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“…Similarly, during bacterial translocation from the gut leading to bacteremia, the translocating bacteria, including E. coli, have been found to be mostly the dominant gut colonizer (15). Antibiotic exposure changes the respective proportions of gut E. coli populations and reduces the barrier effect, promoting the growth of resistant strains, as found here (16). As each day approximately 10 10 E. coli per human are excreted into the environment, a high load of ESBL E. coli is likely to lead to dissemination, especially in a closed environment such as hospitals.…”

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confidence: 60%

Prospective Cohort Study of the Relative Abundance of Extended-Spectrum-Beta-Lactamase-Producing Escherichia coli in the Gut of Patients Admitted to Hospitals

Lastours

Jacquier

d’Humières

et al. 2016

Antimicrob Agents Chemother

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A total of 458 patients were prospectively included at hospital admission and screened for extended-spectrum-beta-lactamaseproducing (ESBL) Escherichia coli carriage in 2007 and in 2010 to 2012. A 4-fold increase in ESBL carriage (3% to 12%), a 5-fold increase in numbers of community patients among ESBL carriers, and a higher number of multiple ESBL strains was found in the 2010 to 2012 period. ESBL E. coli represented the dominant E. coli strain (relative abundance, >50%) in 10/32 (31%) of ESBL carriers. This represents a major threat in terms of infectious risk and dissemination.T he epidemiology of Escherichia coli infections has recently been profoundly modified with the global emergence of strains resistant to third-generation cephalosporins (3GC), specifically, strains producing extended-spectrum ␤-lactamases (ESBL), in both hospitals and the community (1). CTX-M-type ESBLs, which have spread in a polyclonal manner on all continents, constitute a major public health concern worldwide (1).Gut colonization is the first step toward infections by E. coli (2). Recently, it has been shown that a high relative abundance (RA) of ESBL E. coli in the feces increases the risk of urinary tract infection (UTI) by ESBL E. coli (3). Additionally, a high ESBL E. coli RA has been associated with longer fecal carriage time, increasing the numbers of excreted E. coli in the environment and the potential risk of dissemination of these resistant strains (4). However, most studies focusing on ESBL fecal carriage have described the presence or absence of ESBL E. coli in the gut but have lacked quantitative data. Moreover, whether the ESBL populations are dominant was not specified. Here, we characterized and determined the prevalence, bacterial load, and diversity of ESBL E. coli in the gut of patients at hospital admission at two different time periods and determined factors associated with high relative abundance of ESBL carriage.We used samples collected in two previous prospective clinical trials (5, 6) (https://clinicaltrials.gov/ct2/show/NCT00520715 and https://clinicaltrials.gov/ct2/show/NCT01209247). In both works, clinical data (age, sex, Charlson comorbidity index, hospitalization ward, history of immunosuppression, previous hospitalization in the last 12 months, previous antibiotic exposure in the last 3 months, and antibiotic class) as well as a rectal swab had been collected from patients at admission in the same two tertiarycare hospitals from the Paris region in France (5, 6). The first collection period (P1) was between May and November 2007, and the second period (P2) was between October 2010 and July 2012. Both studies were approved by the local institutional review board (IRB 00008522), and patients gave informed consent (5, 6). Rectal swabs were discharged in 1 ml of brain heart infusion (BHI) broth with glycerol and stored at Ϫ80°C in duplicates (5, 6). After thawing, 50 l was plated on Drigalski agar plates (Pasteur Diagnostics, Paris, France), one containing no antibiotics and one containing 1 g/ml cefotax...

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confidence: 60%

Prospective Cohort Study of the Relative Abundance of Extended-Spectrum-Beta-Lactamase-Producing Escherichia coli in the Gut of Patients Admitted to Hospitals

Lastours

Jacquier

d’Humières

et al. 2016

Antimicrob Agents Chemother

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“…Nem ismert, hogy a nem megfelelő indikáció, a magasabb dózisok, a hosszabb kezelés vagy a terápiaszűkítés hiánya áll-e a magas fluorokinolonfelhasználás hátterében. A fluorokinolonok rezisztenciaindukáló hatása különösen nagy [16][17][18], és hazánkban az invazív izolátumok fluorokinolonrezisztenciája minden vizsgált baktériumtörzs esetén magasabb, mint az euró-pai átlag [19]. Ezenkívül az ECDC legutóbbi pontprevalencia-vizsgálata alapján a Clostridium difficile-fertő-zések hazai aránya rendkívül magas [16], ami mögött részben a magas fluorokinolonhasználat valószínűsíthe-tő.…”

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Hazai kórházi antibiotikum-alkalmazás az elmúlt két évtizedben (1996–2015)

et al. 2016

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Bevezetés: A bakteriális rezisztencia közegészségügyet fenyegető probléma, amely mérsékelhető, lassítható megfelelő antibiotikum-alkalmazással. Célkitűzés: A hazai fekvőbeteg-ellátás szisztémás antibiotikum-felhasználásának bemutatása. Módszer: A kórházi antibiotikum-felhasználási adatokat az Egészségügyi Világszervezet anatómiai-terápiás-ké-miai rendszere szerint osztályozták és a Defined Daily Dose metodika szerint kvantifikálták. A standardizálás kórházi betegforgalmi mutatókra, valamint -a nemzetközi összehasonlítás végett -populációra történt. Eredmények: A fekvőbetegszektor antibiotikum-felhasználása az elmúlt 20 évben mennyiségileg kiegyenlített volt (22,4 ± 1,5 DDD/100 ápolási nap), mintázata folyamatos változáson ment keresztül. Megfigyelhettük a parenteralis készítmények alkalmazásának emelkedését (1996-ban 26,4%, 2015-ben 41,6%). Kiemelendő a felhasználás összetételének homogenizáló-dása az amoxicillin-klavulánsav térnyerése miatt, a fluorokinolon (2,3 vs. 4,2 DDD/100 ápolási nap) és a harmadik generációs cefalosporinfelhasználás (1,0 vs. 2,9 DDD/100 ápolási nap) jelentős emelkedése, valamint a szűk spektrumú penicillinek kiszorulása. Következtetés: A hazai kórházi antibiotikum-felhasználás mennyiségileg alacsony. Ez, illetve a felhasználás mintázatában tapasztalt, nemzetközi mércével is alátámasztott alul-vagy felülreprezentált felhasználás okának és indokoltságának megítélése további vizsgálatot igényel. Orv. Hetil., 2016, 157(46), 1839-l846. Kulcsszavak: antibiotikum-felhasználás, kórházi ellátás, trend, mintázat, antibiotikum-surveillance Antibiotic use in the Hungarian hospitals in the last two decades (1996-2015)Introduction: Growing bacterial resistance threatens public health, which can be tempered by prudent antibiotic use. Aim: To quantify systemic antibacterial use in Hungarian hospitals. Method: Consumption data were analysed using the Anatomical-Therapeutic-Chemical -Defined Daily Dose (ATC/DDD) methodology. Data were standardized for patient turnover and also for population to enable international benchmarking. Results: Hospital antibiotic use was quite constant (22.4 ± 1.5 DDD/100 patient-days), but its composition changed substantially. The use of parenteral products rose gradually (in 1996 26.4% and in 2015 41.6%). The pattern of use was homogenised due to the headway of co-amoxiclav use. A substantial increase of fluoroquinolone (2.3 vs. 4.2 DDD/100 patient-days) and third generation cephalosporin (1.0 vs. 2.9 DDD/100 patient-days) use was detected. In parallel the use of narrow spectra penicillins diminished. Conclusion: Hungarian hospital antibiotic use is low. The causes and the justification of this low use together with the internationally outstanding use of certain antibacterials should be addressed in future studies.

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“…They are used to treat a great variety of infections, including urinary tract, bone, joint, respiratory tract, and enteric infections (18). Even if fluoroquinolones are poorly or moderately active against enterococci and generally not used for the treatment of enterococcal infections, they can have profound collateral effects on bacterial populations of the microbiota, including enterococci (19). This is particularly true for the gut microbiota of hospitalized patients for which exposure to antibiotics results in major modifications, with facilitation of colonization by drug-resistant E. faecium (20,21).…”

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confidence: 99%

Subinhibitory Concentrations of Ciprofloxacin Enhance Antimicrobial Resistance and Pathogenicity of Enterococcus faecium

Sinel

Cacaci

Meignen

et al. 2017

Antimicrob Agents Chemother

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Enterococcus faecium has emerged as a major opportunistic pathogen for 2 decades with the spread of hospital-adapted multidrug-resistant clones. As members of the intestinal microbiota, they are subjected to numerous bacterial stresses, including antibiotics at subinhibitory concentrations (SICs). Since fluoroquinolones are extensively prescribed, SICs are very likely to occur in vivo, with potential effects on bacterial metabolism with subsequent modulation of opportunistic traits. The aim of this study was to evaluate globally the impact of SICs of ciprofloxacin on antimicrobial resistance and pathogenicity of E. faecium. Transcriptomic analysis was performed by RNA sequencing (RNA-seq) (HiSeq 2500; Illumina) using the vanB-positive reference strain E. faecium Aus0004 in the absence or presence of ciprofloxacin SIC (0.38 mg/liter, i.e., 1/8 of the MIC). Several genetic and phenotypic tests were used for validation. In the presence of ciprofloxacin SIC, 196 genes were significantly induced, whereas 286 genes were significantly repressed, meaning that 16.8% of the E. faecium genome was altered. Among upregulated genes, EFAU004_02294 (fold change, 14.3) encoded a protein (Qnr of E. faecium [EfmQnr]) homologue of Qnr proteins involved in quinolone resistance in Gram-negative bacilli. Its implication in intrinsic and adaptive fluoroquinolone (FQ) resistance in E. faecium was experimentally ascertained. Moreover, EFAU004_02292, coding for the collagen adhesin Acm, was also induced by the SIC of ciprofloxacin (fold change, 8.2), and higher adhesion capabilities were demonstrated phenotypically. Both EfmQnr and Acm determinants may play an important role in the transition from a commensal to a pathogenic state of E. faecium that resides in the gut of patients receiving fluoroquinolone therapy.KEYWORDS transcriptome, RNA-seq, fluoroquinolones, E. faecium, VRE, Qnr, Acm A lthough considered to be slightly virulent since they are natural inhabitants of the gastrointestinal tract of humans, enterococci have emerged as major opportunistic pathogens, now being responsible for 5 to 10% of hospital-acquired infections and numerous outbreaks (1). In addition, there is a spread of vancomycin-resistant enterococcus (VRE) clinical isolates, especially within the species Enterococcus faecium, which is increasingly reported (2). Notably, E. faecium is part of the ESKAPE (E. faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) multidrug-resistant (MDR) opportunistic pathogens (3). The epidemiological success of E. faecium mainly results from the

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Impact of Fluoroquinolones on Human Microbiota. Focus on the Emergence of Antibiotic Resistance

Cited by 48 publications

References 84 publications

Prospective Cohort Study of the Relative Abundance of Extended-Spectrum-Beta-Lactamase-Producing Escherichia coli in the Gut of Patients Admitted to Hospitals

Prospective Cohort Study of the Relative Abundance of Extended-Spectrum-Beta-Lactamase-Producing Escherichia coli in the Gut of Patients Admitted to Hospitals

Hazai kórházi antibiotikum-alkalmazás az elmúlt két évtizedben (1996–2015)

Subinhibitory Concentrations of Ciprofloxacin Enhance Antimicrobial Resistance and Pathogenicity of Enterococcus faecium

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