Activities of Fosfomycin and Rifampin on Planktonic and Adherent Enterococcus faecalis Strains in an Experimental Foreign-Body Infection Model
Male
0301 basic medicine
Guinea Pigs
Microbial Sensitivity Tests
Calorimetry
Bacterial Adhesion
03 medical and health sciences
Daptomycin
Fosfomycin
Acetamides
Enterococcus faecalis
Animals
Gram-Positive Bacterial Infections
Oxazolidinones
Linezolid
Foreign Bodies
acetamides; ampicillin; animals; anti-bacterial agents; bacterial adhesion; biofilms; calorimetry; daptomycin; disease models; animal; drug therapy; combination; enterococcus faecalis; foreign bodies; fosfomycin; gentamicins; gram-positive bacterial infections; guinea pigs; linezolid; male; microbial sensitivity tests; oxazolidinones; rifampin; vancomycin
Anti-Bacterial Agents
3. Good health
Disease Models, Animal
Biofilms
Ampicillin
Drug Therapy, Combination
Gentamicins
DOI:
10.1128/aac.02583-12
Publication Date:
2013-10-22T02:41:14Z
AUTHORS (6)
ABSTRACT
ABSTRACT
Enterococcal implant-associated infections are difficult to treat because antibiotics generally lack activity against enterococcal biofilms. We investigated fosfomycin, rifampin, and their combinations against planktonic and adherent
Enterococcus faecalis
(ATCC 19433)
in vitro
and in a foreign-body infection model. The MIC/MBC
log
values were 32/>512 μg/ml for fosfomycin, 4/>64 μg/ml for rifampin, 1/2 μg/ml for ampicillin, 2/>256 μg/ml for linezolid, 16/32 μg/ml for gentamicin, 1/>64 μg/ml for vancomycin, and 1/5 μg/ml for daptomycin. In time-kill studies, fosfomycin was bactericidal at 8× and 16× MIC, but regrowth of resistant strains occurred after 24 h. With the exception of gentamicin, no complete inhibition of growth-related heat production was observed with other antimicrobials on early (3 h) or mature (24 h) biofilms. In the animal model, fosfomycin alone or in combination with daptomycin reduced planktonic counts by ≈4 log
10
CFU/ml below the levels before treatment. Fosfomycin cleared planktonic bacteria from 74% of cage fluids (i.e., no growth in aspirated fluid) and eradicated biofilm bacteria from 43% of cages (i.e., no growth from removed cages). In combination with gentamicin, fosfomycin cleared 77% and cured 58% of cages; in combination with vancomycin, fosfomycin cleared 33% and cured 18% of cages; in combination with daptomycin, fosfomycin cleared 75% and cured 17% of cages. Rifampin showed no activity on planktonic or adherent
E. faecalis
, whereas in combination with daptomycin it cured 17% and with fosfomycin it cured 25% of cages. Emergence of fosfomycin resistance was not observed
in vivo
. In conclusion, fosfomycin showed activity against planktonic and adherent
E. faecalis
. Its role against enterococcal biofilms should be further investigated, especially in combination with rifampin and/or daptomycin treatment.
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