The impact of therapeutic-dose induced intestinal enrofloxacin concentrations in healthy pigs on fecal Escherichia coli populations.

BACKGROUND: Knowledge of therapy-induced intestinal tract concentrations of antimicrobials allows for interpretation and prediction of antimicrobial resistance selection within the intestinal microbiota. This study describes the impact of three different doses of enrofloxacin (ENR) and two different administration routes on the intestinal concentration of ENR and on the fecal Escherichia coli populations in pigs. Enrofloxacin was administered on three consecutive days to four different treatment groups. The groups either received an oral bolus administration of ENR (conventional or half dose) or an intramuscular administration (conventional or double dose). RESULTS: Quantitative analysis of fecal samples showed high ENR concentrations in all groups, ranging from 5.114 ± 1.272 µg/g up to 39.54 ± 10.43 µg/g at the end of the treatment period. In addition, analysis of the luminal intestinal content revealed an increase of ENR concentration from the proximal to the distal intestinal tract segments, with no significant effect of administration route. Fecal samples were also screened for resistance in E. coli isolates against ENR. Wild-type (MIC≤0.125 µg/mL) and non-wild-type (0.125 < MIC≤2 µg/mL) E. coli isolates were found at time 0 h. At the end of treatment (3 days) only non-wild-type isolates (MIC≥32 µg/mL) were found. CONCLUSIONS: In conclusion, the observed intestinal ENR concentrations in all groups showed to be both theoretically (based on pharmacokinetic and pharmacodynamic principles) and effectively (in vivo measurement) capable of significantly reducing the intestinal E. coli wild-type population.

Low Incubation Temperature During Late Incubation and Early Feeding Affect Broiler Resilience to Necrotic Enteritis in Later Life.

Resilient animals can cope with environmental disturbances in life with minimal loss of function. Resilience can be enhanced by optimizing early-life conditions. In poultry, eggshell temperature (EST) during incubation and early feeding are two early-life conditions that are found to alter neonatal chick quality as well as immune response in later life. However, whether these early-life conditions affect disease resilience of chickens at later ages has never been studied yet. Hence, we studied the effects of EST [(37.8°C (control) or 36.7°C (lower)] during late incubation (≥embryonic days 17-19.5) and feeding strategy after hatch [immediately (early feeding) or 51-54 h delayed (delayed feeding)] on later-life broiler resilience in a 2 × 2 factorial arrangement. At hatch, 960 broilers of both sexes from a 54-week-old Ross breeder flock were equally divided over 32 pens (eight replicate pens per treatment combination) and grown for 6 weeks. Necrotic enteritis was induced by a single inoculation of Eimeria spp. at d 21 and repeated Clostridium perfringens inoculation (3×/d) during d 21-25. Mortality and body weight (BW) gain were measured daily during d 21-35 as indicators of resilience. Additionally, disease morbidity was assessed (gut lesions, dysbacteriosis, shedding of oocysts, footpad dermatitis, and natural antibody levels in blood). Results showed a lack of interaction between EST and feeding strategy for the vast majority of the variables. A lower EST resulted in lower BW gain at d 5 and 8 post Eimeria inoculation (P = 0.02) and more Eimeria maxima oocysts in feces at d 8 post Eimeria inoculation compared to control EST (P < 0.01). Early feeding tended to lower mortality compared to delayed feeding (P = 0.06), but BW gain was not affected by feeding strategy. Morbidity characteristics were hardly affected by EST or feeding strategy. In conclusion, a few indications were found that a lower EST during late incubation as well as delayed feeding after hatch may each impair later-life resilience to necrotic enteritis. However, these findings were not manifested consistently in all parameters that were measured, and conclusions are drawn with some restraint.

Similar Gastro-Intestinal Exposure to Florfenicol After Oral or Intramuscular Administration in Pigs, Leading to Resistance Selection in Commensal Escherichia coli.

Florfenicol, which is licensed for veterinary use only, proves to be a potent antimicrobial for treatment of respiratory disease. However, the subsequent exposure of the gut microbiota to florfenicol is not well described. Hence, the effect of various administration protocols on both plasma and gastro-intestinal florfenicol concentrations in pigs was evaluated. In field situations were simulated by application of different administration routes and dosages [single oral bolus at 10 or 5 mg/kg body weight (BW), medicated feed at 10 or 5 mg/kg BW and intramuscular injections at 15 or 30 mg/kg BW]. After intramuscular administration of 30 mg florfenicol/kg BW, gastro-intestinal concentrations of florfenicol, quantified 10 h after the last administration, were significantly elevated in comparison with the other treatment groups and ranging between 31.5 and 285.8 µg/g over the different gut segments. For the other treatment groups, the influence of dose and administration route was not significantly different. Bacteriological analysis of the fecal samples from the animals at the start of the experiment, demonstrated the presence of both florfenicol susceptible (with minimal inhibitory concentration (MIC) values of 2-16 µg/mL) and florfenicol resistant (MIC ≥ 256 µg/mL) Escherichia coli isolates in all treatment groups. Following, at 10 h after the last administration the susceptible E. coli population was eradicated in all treatment groups due to the high intestinal florfenicol concentrations measured. Moreover, selection of the resistant E. coli strains during treatment occurred in all groups. This is likely related to the fact that the different treatment strategies led to high gastro-intestinal concentrations albeit not reaching the high magnitude of MIC values associated with florfenicol resistance (≥256 µg/mL). Conclusively, in our experimental setup the administration route and dose alterations studied, had no influence on monitored florfenicol resistance selection in E. coli from the microbiota.

Effect of administration route and dose alteration on sulfadiazine-trimethoprim plasma and intestinal concentrations in pigs.

Potentiated sulfonamides, such as sulfadiazine-trimethoprim (SDZ-TRIM), are frequently used antimicrobials in both human and veterinary medicine. To optimise their use in relation to the emerging problem of resistance selection, this paper studied the impact of dose and administration route of SDZ-TRIM on the exposure of the gut microbiota to these antimicrobials. An animal experiment was conducted with 36 pigs, divided into six different treatment groups (n = 6). Three different administration routes were outlined: oral (PO) gavage, intramuscular (IM) injection and medicated feed, with 5-day therapy duration. Conventional dosing (30 mg SDZ-TRIM/kg bodyweight [BW]) and half dosing (15 mg SDZ-TRIM/kg BW) was performed for the oral routes in two applications per day. For the IM route, a conventional dose of 15 mg SDZ-TRIM/kg BW or a double dose of 30 mg SDZ-TRIM/kg BW was administered once daily. After daily collection of blood and faeces, the intestinal content of all animals was sampled in different gastrointestinal tract (GIT) segments, and SDZ and TRIM were quantified. Remarkably, SDZ accumulated in distal GIT segments, independently of the administration route. High concentrations (mean ± standard deviation) up to 26.93 ± 8.36 µg/g, 11.15 ± 3.78 µg/g and 19.36 ± 1.86 µg/g after PO gavage, IM administration and medicated feed, respectively, were measured for SDZ. In contrast, TRIM concentrations decreased from proximal to distal segments and were mostly below the limit of quantification (0.025 µg/g). The high oral bioavailability of SDZ indicates gastrointestinal secretion is a substantial elimination route for SDZ.