title: The rise of ampicillin-resistant Enterococcus faecium high-risk clones as a frequent intestinal colonizer in oncohaematological neutropenic patients on levofloxacin prophylaxis: a risk for bacteraemia?
abstract: Levofloxacin extended prophylaxis (LEP), recommended in oncohaematological neutropenic patients to reduce infections, might select resistant bacteria in the intestine acting as a source of endogenous infection. In a prospective observational study we evaluated intestinal emergence and persistence of ampicillin-resistant Enterococcus faecium (AREfm), a marker of hospital adapted high-risk clones. AREfm was recovered from the faeces of 52 patients with prolonged neutropenia after chemotherapy, at admission (Basal), during LEP, and twice weekly until discharge (Pos-LEP). Antibiotic susceptibility, virulence traits and population structure (pulsed-field gel electrophoresis and multilocus sequence typing) were determined and compared with bacteraemic isolates. Gut enterococcal population was monitored using a quantitative PCR quantification approach. AREfm colonized 61.4% of patients (194/482 faecal samples). Sequential AREfm acquisition (25% Basal, 36.5% LEP, 50% Pos-LEP) and high persistent colonization rates (76.9-89.5%) associated with a decrease in clonal diversity were demonstrated. Isolates were clustered into 24 PFGE-patterns within 13 sequence types, 95.8% of them belonging to hospital-associated Bayesian analysis of population structure subgroups 2.1a and 3.3a. Levofloxacin resistance and high-level streptomycin resistance were a common trait of these high-risk clones. AREfm-ST117, the most persistent clone, was dominant (60.0% isolates, 32.6% patients). It presented esp gene and caused 18.2% of all bacteraemia episodes in 21% of patients previously colonized by this clone. In AREfm-colonized patients, intestinal enrichment in the E. faecium population with a decline in total bacterial load was observed. AREfm intestinal colonization increases during hospital stay and coincides with enterococci population enrichment in the gut. Dominance and intestinal persistence of the ST117 clone might increase the risk of bacteraemia.
authors: Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.
authors: A M
authors: AM
authors: Sánchez-Díaz
authors: Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors: C
authors: C
authors: Cuartero
authors: Servicio de Hematología, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
authors: J D
authors: JD
authors: Rodríguez
authors: Servicio de Hematología, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
authors: S
authors: S
authors: Lozano
authors: Servicio de Hematología, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
authors: J M
authors: JM
authors: Alonso
authors: Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.
authors: M
authors: M
authors: Rodríguez-Domínguez
authors: Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors: A P
authors: AP
authors: Tedim
authors: Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.
authors: R
authors: R
authors: Del Campo
authors: Servicio de Hematología, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
authors: J
authors: J
authors: López
authors: Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain. Electronic address: rafael.canton@salud.madrid.org.
authors: R
authors: R
authors: Cantón
authors: Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.
authors: P
authors: P
authors: Ruiz-Garbajosa
mesh_terms: D000328:Adult; D000368:Aged; D000667:Ampicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis / Q000009:adverse effects / Q000379:methods; D016470:Bacteremia / Q000453:epidemiology* / Q000382:microbiology; D001769:Blood / Q000382:microbiology; D016521:Electrophoresis, Gel, Pulsed-Field; D016984:Enterococcus faecium / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000453:epidemiology*; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D064704:Levofloxacin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D009503:Neutropenia / Q000150:complications*; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D000667:Ampicillin
keywords: Bacteraemia; Enterococcus faecium; colonization; fecal carriage; levofloxacin prophylaxis; neutropenic patients