title: Bactericidal activity of penicillin, ceftriaxone, gentamicin and daptomycin alone and in combination against Aerococcus urinae.
abstract: Aerococcus urinae can cause severe infections (bacteraemia and endocarditis) that are associated with high mortality. However, data on the bactericidal and synergistic activity for clinically implemented antibiotics are scarce. Time-kill analyses were performed on two clinical isolates (AU1 and AU2) and the reference strain ATCC 700306 for penicillin (PG), ceftriaxone (CRO), gentamicin (GEN), daptomycin (DAP) and their combinations. AU1 and AU2 were CRO-resistant (MICs, 2 µg/mL) and ATCC 700306 was high-level GEN-resistant (MIC, 512 µg/mL), whereas all strains were PG- and DAP-susceptible (MICs, ≤0.125 and ≤1 µg/mL, respectively). CFU counts were determined at various time points from 0 to 48 h. All experiments were performed at 0.5×, 1×, 2× and 4× MIC. PG and CRO were not bactericidal for all strains, whereas DAP exhibited bactericidal activity at all concentrations for AU2 and ATCC 700306. The combination of PG or CRO with GEN was bactericidal for AU1 and AU2 at antibiotic concentrations ≥1× MIC. Bactericidal synergism was detected for PG or CRO combined with GEN in the two clinical isolates. PG plus CRO showed non-bactericidal synergism for ATCC 700306. DAP with GEN was synergistic at 1× MIC for AU1, whereas the killing activity of DAP was too pronounced to detect potential synergism in AU2. The combination of PG or CRO with GEN is synergistic and bactericidal. Moreover, these in vitro data suggest that DAP may represent a potential bactericidal treatment alternative against A. urinae. This finding could be important for the treatment of patients with a β-lactam allergy or renal insufficiency.
authors.affiliation: Department of Infectious Diseases, Bern University Hospital (Inselspital), University of Bern, Poliklinik Trakt 2, CH-3010 Bern, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Hirzel
authors.affiliation: Department of Infectious Diseases, Bern University Hospital (Inselspital), University of Bern, Poliklinik Trakt 2, CH-3010 Bern, Switzerland; Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, CH-3010 Bern, Switzerland.
authors.forename: Lea
authors.initials: L
authors.lastname: Hirzberger
authors.affiliation: Department of Infectious Diseases, Bern University Hospital (Inselspital), University of Bern, Poliklinik Trakt 2, CH-3010 Bern, Switzerland.
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.affiliation: Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, CH-3010 Bern, Switzerland. Electronic address: andrea.endimiani@ifik.unibe.ch.
authors.forename: Andrea
authors.initials: A
authors.lastname: Endimiani
mesh_terms: D056570:Aerococcus / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D017576:Daptomycin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005839:Gentamicins / Q000494:pharmacology*; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D013997:Time Factors; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D047090:beta-Lactams; D017576:Daptomycin
keywords: Aerococcus urinae; Bactericidal; Synergism; Time–kill