Survey of veterinarians in the Netherlands on antimicrobial use for surgical prophylaxis in dairy practice.

There is increased concern about the selection pressure of antimicrobial use (AMU) in humans as well in farm animals resulting in antimicrobial (AM) resistance. The introduction of monitoring of AMU in food-producing animals since 2011 has led to a considerable quantitative reduction of AMU in those animal species in the Netherlands. This survey was conducted to explore the possibilities to improve prudent use of AM in the cattle industry. We sent an online questionnaire to 373 veterinarians and asked which antimicrobial prophylaxis they used for their most recently performed cesarean section (CS) and left displaced abomasum (LDA) correction. With a response rate of 30%, we found that older graduates used more AM for CS than recently graduated veterinarians (odds ratio = 2.4 to 2.7 depending on category), whereas antimicrobial prophylaxis in LDA surgeries was significantly different for the available surgical correction methods. The results indicate that the respondents do not adjust the surgical antimicrobial prophylaxis for different conditions of the patient or the environment; 37 (38%) respondents consider that the risks of contamination are similar for CS and LDA. In CS and all LDA correction methods preoperative prophylaxis was significantly less often applied than postoperative antimicrobial treatments (odds ratio = 0.05 and 0.08, respectively). When preoperative prophylaxis was applied, the choice of (combinations of) the AM and the timing of administration were not adequate at the start of the surgical procedure (88% for CS and 90% for LDA). We conclude that considerable qualitative (timing, choice of antimicrobial, route of administration) and quantitative (limit AMU to indicated procedures) improvement on antimicrobial prophylaxis for CS and LDA is possible by appreciation of the risks of the type of surgery (CS, LDA) and its conditions as well as by selecting classes of AM and timing and routes of administration that result in effective drug concentrations at the start of the procedure.

Randomized prospective trials to study effects of reduced antibiotic usage in abdominal surgery in cows.

Societal concerns about antibiotic resistance prompted us to evaluate the use of prophylactic and postoperative antibiotic treatments following cesarean section (CS) and exploratory laparotomy (EL) in a surgery theater within the Farm Animal Health clinic. All procedures were performed by supervised veterinary students for training purposes. Cows undergoing CS (n = 100) received either a prophylaxis with a single 5-g injection of ampicillin-sodium i.v. only (CSL), or in combination with postoperative i.m. injections of ampicillin-trihydrate 20% for 3 d (10 mg/kg, twice a day; CSH). Cows undergoing EL (n = 110) received either no antibiotic prophylaxis (ELN) or were given a single 5-g injection of ampicillin-sodium i.v. (ELL). The primary outcome measure was healthy recovery after surgery, which we assessed according to the need to treat surgery-related complications within a 10-d follow-up period based on daily clinical observations. Cows in all groups had a normal temperature and feed intake, and a satisfying clinical appearance at the end of the follow-up period. The clinical need to treat cows with antibiotics to deal with postoperative complications was higher for the CS groups than the EL groups. Within both CS and EL groups, the number of complications for each protocol was the same. However, in terms of the secondary outcomes, we observed that CSL cows required, for example, more treatments for mastitis and other diseases unrelated to the surgery than CSH cows (odds ratio 2.8; confidence interval 1.2-7.2). The percentage of infected sutures was higher for ELN cows compared with ELL cows (odds ratio 2.6; confidence interval 1.5-4.9). We estimated that 29 CSH treatments were needed to prevent 1 CS cow with serious surgery-related complications in the CSL group. Likewise, 53 ELL treatments would prevent 1 EL cow with surgery-related complications in the ELN group. We therefore concluded that it is possible to reduce antibiotic prophylaxis in CS and EL cows. The low number cows of clinically detected complications were effectively treated with a postoperative antibiotic intervention at the moment of detection.

Saline is as effective as nitrogen scavengers for treatment of hyperammonemia.

Urea cycle enzyme deficiency (UCED) patients with hyperammonemia are treated with sodium benzoate (SB) and sodium phenylacetate (SPA) to induce alternative pathways of nitrogen excretion. The suggested guidelines supporting their use in the management of hyperammonemia are primarily based on non-analytic studies such as case reports and case series. Canine congenital portosystemic shunting (CPSS) is a naturally occurring model for hyperammonemia. Here, we performed cross-over, randomized, placebo-controlled studies in healthy dogs to assess safety and pharmacokinetics of SB and SPA (phase I). As follow-up safety and efficacy of SB was evaluated in CPSS-dogs with hyperammonemia (phase II). Pharmacokinetics of SB and SPA were comparable to those reported in humans. Treatment with SB and SPA was safe and both nitrogen scavengers were converted into their respective metabolites hippuric acid and phenylacetylglutamine or phenylacetylglycine, with a preference for phenylacetylglycine. In CPSS-dogs, treatment with SB resulted in the same effect on plasma ammonia as the control treatment (i.e. saline infusion) suggesting that the decrease is a result of volume expansion and/or forced diuresis rather than increased production of nitrogenous waste. Consequentially, treatment of hyperammonemia justifies additional/placebo-controlled trials in human medicine.

Influence of applying different units of measurement on reporting antimicrobial consumption data for pig farms.

BACKGROUND: Antimicrobial use in livestock is one of the factors contributing to selection and spread of resistant microorganisms in the environment. National veterinary antimicrobial consumption monitoring programs are therefore in place in a number of countries in the European Union. However, due to differences in methodology, results on veterinary antimicrobial consumption from these national monitoring programs cannot be compared internationally. International comparison is highly needed to establish regulations on veterinary antimicrobial use and reducing antimicrobial resistance. The aim of this study was to assess differences in the outcomes on veterinary antimicrobial consumption by applying three different sets of nationally established animal defined daily dosages to the same antimicrobial drug delivery dataset of Dutch pigs in 2012. METHODS: Delivery information for the complete Dutch pig sector for the year 2012 reported to the Netherlands Veterinary Medicines Authority (SDa) was analysed with three differently and nationally established animal defined daily dosages from the Netherlands and Denmark: the Defined Daily Dosage AnimalNL (DDDANL), the Animal Daily DosageDK (ADDDK) and Defined Animal Daily DosageDK (DADDDK). For each applied Dutch product equivalent, Danish products were identified based on authorization for pigs, active substance (including form), administration route, concentration and dosage regimen. RESULTS: Consumption in number of ADDDK/Y was lower than in number of DDDANL/Y for sows/piglets and finisher pigs, with proportions of 83.3 % and 98.3 %. Use in number of DADDDK/Y was even lower, 79.7 % for sows/piglets and 88.1 % for finisher pigs compared to number of DDDANL/Y. At therapeutic group level proportions of number of DADDDK/Y to number of DDDANL/Y were 63.6-150.4 % (sows/piglets) and 55.6-171.0 % (finisher pigs). Proportions were > 100 % for the polymyxines (sows/piglets 150.4 % and finisher pigs 149.9 %) and the macrolides/lincosamides (finisher pigs 171.0 %). CONCLUSIONS: Differences between nationally established animal defined daily dosages caused by different correction factors for long-acting products and national differences in authorized dosages, have a substantial influence on the results of antimicrobial consumption in pigs. To enable international comparison of veterinary antimicrobial consumption data, harmonized units of measurement, animal weights and animal (sub) categories are needed.

Site-specific intracoronary heparin delivery in humans after balloon angioplasty. A radioisotopic assessment of regional pharmacokinetics.

BACKGROUND: Demonstration and quantification of site-specific intracoronary administration of compounds has been confined thus far to the experimental animal laboratory. The aim of this study was to describe a scintigraphic method to demonstrate site-specific intracoronary drug delivery in humans. The methods allow on-line visualization and off-line quantification of site-specifically infused gamma-emitting compounds. METHODS AND RESULTS: In 12 patients after balloon angioplasty, 99mTc-labeled heparin was administered at the site of dilatation by use of a coil balloon. Both the infusion period and the washout period after the end of infusion were monitored with a gamma-camera. A curve of counts per pixel as a function of time was derived that showed an accumulation phase during infusion followed by washout phase after the end of infusion. Both phases were fitted by regression analysis and showed a linear accumulation pattern and a biexponential washout pattern. After correction for background counts, 99mTc decay, and body attenuation, peak heparin amount and regional bioavailability were calculated. Peak amount was defined as the initial point of the slow washout component of the biexponential curve (elimination component), and regional bioavailability was defined as the area under the curve of accumulation and washout phase. Half-life and retention time, define as seven half-lives, were obtained by use of the elimination component after correction for 99mTc decay. Mean peak delivered amount was 45 +/- 44 IU (236 +/- 228 micrograms), corresponding to an efficiency of delivery ranging from 1% to 8% of the totally infused dose. Total regionally bioavailable heparin reached 244 +/- 194 IU.h (1.28 +/- 1.01 mg.h). Retention time varied from 12 to 90 hours (mean, 50:33 +/- 22:50 hours:minutes). CONCLUSIONS: Site-specific intracoronary heparin delivery after angioplasty by means of the coil balloon was demonstrated in humans, and regional pharmacokinetics was quantified by use of a radioisotopic technique.

Site-specific intravascular administration of drugs: history of a method applicable in humans.

Demonstration and quantification of site-specific intracoronary administration of pharmacological compounds has been limited thus far to animal experimental models. Recently, a method applicable in humans has been developed. The aim of this study is to give an overview on the available methods to visualize and quantify intravascularly administered "labeled" drugs in animals and to describe the historical development of a method now applied in the clinical arena. The potential of this approach is briefly summarized.