Ecological impact of ciprofloxacin on commensal enterococci in healthy volunteers.
The ecological impact of ciprofloxacin on commensal enterococci is unknown.



Forty-eight healthy volunteers received ciprofloxacin from day (D) 0 to D14; stools were collected on D7, D14 and D42. Fluoroquinolone-susceptible and -resistant enterococci (FQ-SE and FQ-RE) were detected and quantified by culture, and identified by MALDI-TOF MS. The relative abundance of FQ-RE over FQ-SE was determined. The genetic basis of fluoroquinolone resistance was deciphered by partial sequencing of gyrA and parC genes. Clonal relatedness was determined by random amplification of polymorphic DNA PCR. Clinical trial no.: NCT00190151.



Enterococci were carried by 47/48 (98%) subjects. Total counts were reduced during ciprofloxacin therapy (4.0 and 3.9 log cfu/g on D7 and D14 versus 5.9 log cfu/g before and 6.9 log cfu/g after treatment; P  < 0.05). Twenty-one out of 48 (44%) carried FQ-RE; among them, 21/21 carried Enterococcus faecium , 19 carried Enterococcus faecalis and 11 carried other species. Five out of 48 (10%) harboured FQ-RE (ciprofloxacin MIC >4 mg/L) before treatment (all E. faecium ), 6 on D7 (3 E. faecium and 3 E. faecalis ), 8 on D14 (4 E. faecium and 4 E. faecalis ) and 10 (21%) on D42 (9 E. faecium and 1 E. faecalis ). The relative abundance of FQ-RE increased from 44% on D0 to 73% and 75% on D7 and D14, respectively. No acquisition of fluoroquinolone resistance among endogenous D0 strains was evidenced. All (14/14) distinct Fluoroquinolone-resistant E. faecalis clones were gyrA / parC double mutants with high-level resistance (ciprofloxacin MIC >64 mg/L). In contrast, 34/35 E. faecium exhibited low-level resistance (ciprofloxacin MIC 4-32 mg/L) with no gyrA / parC mutation, but overexpressed the chromosomal Efm qnr gene. As compared with Fluoroquinolone-susceptible strains, Fluoroquinolone-resistant E. faecium were more frequently ampicillin resistant and Fluoroquinolone-resistant E. faecalis were more highly resistant to gentamicin.



Although intrinsically poorly susceptible to fluoroquinolones, gut populations of enterococci are highly impacted both quantitatively and qualitatively by ciprofloxacin.
IAME, UMR-1137, Inserm and Université Paris Diderot, Paris, France.|Service de Médecine Interne, Hôpital Beaujon, APHP, Paris, France.
Victoire
V
de Lastours
Université de Caen Normandie, EA4655 (équipe 'Antibio-Résistance'), Caen, France.
Elena
E
Maugy
Université de Caen Normandie, EA4655 (équipe 'Antibio-Résistance'), Caen, France.
Vincent
V
Mathy
IAME, UMR-1137, Inserm and Université Paris Diderot, Paris, France.
Françoise
F
Chau
IAME, UMR-1137, Inserm and Université Paris Diderot, Paris, France.|Service de Médecine Interne, Hôpital Beaujon, APHP, Paris, France.
Benjamin
B
Rossi
Université de Caen Normandie, EA4655 (équipe 'Antibio-Résistance'), Caen, France.|CNR de la Résistance aux Antibiotiques (Laboratoire Associé 'Entérocoques'), Caen, France.
François
F
Guérin
Université de Caen Normandie, EA4655 (équipe 'Antibio-Résistance'), Caen, France.|CNR de la Résistance aux Antibiotiques (Laboratoire Associé 'Entérocoques'), Caen, France.
Vincent
V
Cattoir
IAME, UMR-1137, Inserm and Université Paris Diderot, Paris, France.|Service de Médecine Interne, Hôpital Beaujon, APHP, Paris, France.
Bruno
B
Fantin
D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D016983:Enterococcus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D013293:Enterococcus faecalis / Q000235:genetics / Q000302:isolation & purification; D016984:Enterococcus faecium / Q000235:genetics / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology; D064368:Healthy Volunteers; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000187:drug effects; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013559:Symbiosis
D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase