scholarly journals Establishing defined daily doses (DDDs) for antimicrobial agents used in pigs, cattle and poultry in Japan and comparing them with European DDD values

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0245105
Author(s):  
Kyoko Fujimoto ◽  
Mai Kawasaki ◽  
Reiko Abe ◽  
Takashi Yokoyama ◽  
Takeshi Haga ◽  
...  

Monitoring of antimicrobial use is essential in the management of the development and selection of antimicrobial resistance. A variety of indicators has become available to monitor antimicrobial use in human and animal medicine. One of them is an indicator based on defined daily dose (DDD). By using the number of DDDs administered and normalising it by the population at risk of being treated over a defined period, one can estimate the number of treatment days with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values of DDD (DDDvet) for food-producing animals. In this study, we defined Japanese defined daily doses for antimicrobial agents (DDDjp) using DDD values that we previously assigned for antimicrobial products approved for use in pigs, cattle and poultry in Japan and compared them with DDDvet values. For the comparison, the quotient of Japanese and European values (QDDD) was calculated and the effect of the administration route and the number of active substances contained in the preparation was investigated. A total of 59 DDDjp values were defined for 43 antimicrobial agents using the data of 276 products approved for use in pigs. Likewise, a total of 55 DDDjp values were defined for 32 antimicrobial agents using the data of 196 products for use in cattle, and a total of 27 DDDjps values were defined for 25 antimicrobial agents using the data of 131 products approved for use in poultry. A comparison was made for 42, 28 and 17 pairs of DDDjp and DDDvet values for antimicrobial agents used for pigs, cattle and poultry respectively. The comparison showed median QDDD value of 0.61 and 0.66 for antimicrobial agents used for pigs and cattle respectively (p<0.01), indicating that the Japanese daily doses are significantly lower than the corresponding EMA values in these species. For the antimicrobial agents used for poultry, no significant difference was observed between DDDjp and DDDvet values with a median QDDD value of 1.15. The difference between DDDvet and DDDjp values and absence of DDDvet values for some antimicrobial agents marketed in Japan indicate that DDDjp rather than DDDvet should be used as the basis for the calculation of antimicrobial use monitoring in farm animals in Japan.

2020 ◽  
Author(s):  
Kyoko Fujimoto ◽  
Mai Kawasaki ◽  
Reiko Abe ◽  
Takashi Yokoyama ◽  
Takeshi Haga ◽  
...  

AbstractMonitoring of antimicrobial use is essential to manage the development and selection of antimicrobial resistance. A variety of indicators has become available to monitor antimicrobial use in human and animal medicine. One of them is an indicator based on defined daily dose (DDD). By using the number of DDDs used and normalizing it by the population at risk of being treated in a defined period, one can estimate the number of treatment days with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values of DDD (DDDvet) for food-producing animals. In this study, we defined Japanese defined daily doses for antimicrobial agents (DDDjp) using DDD values that we previously assigned for antimicrobial products approved for use in pigs, cattle and poultry in Japan and compared them with DDDvet values. For the comparison, the quotient of Japanese and European values (QDDD) was calculated and the effect of the administration route and the number of active substances contained in the preparation was investigated. A total of 59, 51 and 27 DDDjp values were defined for 43, 32 and 25 antimicrobial agents using the data of 269, 195 and 131 products approved for use in pigs, cattle and poultry respectively. A comparison was possible for 44, 27 and 17 pairs of DDDjp and DDDvet values for antimicrobial agents used for pigs, cattle and poultry respectively. The comparison showed median QDDD value of 0.66 and 0.63 for antimicrobial agents used for pigs and cattle respectively (P<0.01), indicating that the Japanese daily doses are significantly lower than the corresponding EMA values in these species. For the antimicrobial agents used for poultry, no siginificant difference was observed between DDDjp and DDDvet values with median QDDD value of 1.17. The difference between DDDvet and DDDjp values and absence of DDDvet values for some antimicrobial agents marketed in Japan indicate that DDDjp rather than DDDvet should be used as the basis for the calculation of antimicrobial use monitoring in farm animals in Japan.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255632
Author(s):  
Kyoko Fujimoto ◽  
Mai Kawasaki ◽  
Yuko Endo ◽  
Takashi Yokoyama ◽  
Itsuro Yamane ◽  
...  

Defined daily doses (DDD) have been established in human medicine to standardize the measurement of treatment in a population. In veterinary medicine, the European Medicine Agency published defined daily dose (DDDvet) values for antimicrobial agents used in food-producing animals in 2016. National defined doses (DDDjp) for antimicrobials used for pigs in Japan have recently been determined. The aim of this study was to compare the results of calculated antimicrobial use in the field using the DDDjp and DDDvet values. Data from 74 pig farms in Japan relative to antimicrobial use in 2019 was collected. The numbers of DDDs (the weight of biomass treated in kg-days) using DDDjp and DDDvet values for each farm and for different antimicrobial classes were compared. Associations between calculated numbers of DDDjp and DDDvet on farm level were investigated. In addition, differences in antimicrobial use were investigated between different production types of farms (farrowing, finishing and farrow-to-finish farms). Using DDDjp and DDDvet values, the aggregated number of DDDs for 74 farms were 4,099,188 and 2,217,085 respectively, with the former being larger by 1.85 times than the latter. The most frequently used antimicrobial class was penicillin regardless of whether DDDjp or DDDvet was used. The absence of DDDvet values for certain antimicrobial agents used in Japan and the differences in the number of DDDjps/PCU and DDDvets/PCU indicated the need for Japanese DDDs. The number of DDDs per kg population correction unit (PCU) per farm tended to be higher in farrowing farms than in farrow-to-finish farms and finishing farms, with no significant difference (P = 0.19).


2014 ◽  
Vol 25 (2) ◽  
pp. 113-117 ◽  
Author(s):  
Shiona K Glass-Kaastra ◽  
Rita Finley ◽  
Jim Hutchinson ◽  
David M Patrick ◽  
Karl Weiss ◽  
...  

INTRODUCTION: Monitoring the volume and patterns of use of antimicrobial agents is important in light of antimicrobial resistance.OBJECTIVE: To assess the use of three antimicrobial groups – tetracycline, sulfonamide-trimethoprim and ‘other’ antimicrobials – within Canadian provinces over time.METHODS: Prescription counts from 1995 to 2010 were acquired for the tetracycline and sulfonamide-trimethoprim groups of antimicrobials, and from 2001 to 2010 for the ‘other’ antimicrobial group. Linear mixed models were produced to assess differences among provinces and over time while accounting for repeated measurements. Prescription rate, defined daily dose per 1000 inhabitant-days and defined daily doses per prescription measures for the year 2009 were also compared with those reported by participating European Union countries to determine where Canadian provinces rank in terms of antimicrobial use among these countries.RESULTS: Prescribing of all three groups varied according to province and over time. Tetracycline and sulfonamide-trimethoprim group prescribing were significantly reduced over the study period, by 36% and 61%, respectively. Prescribing of the ‘other’ antimicrobial group increased in all provinces from 2001 to 2010 with the exception of Prince Edward Island, although by varying amounts (10% to 61% increases).DISCUSSION: The overall use of antimicrobials in Canada has dropped from 1995 to 2010, and the tetracycline and sulfonamide-trimethoprim groups have contributed to this decline. The use of the ‘other’ antimicrobials has increased, however. These results may suggest that switches are being made among these groups, particularly among the antimicrobials used to treat urinary tract infections.


Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 707 ◽  
Author(s):  
Clair Firth ◽  
Annemarie Käsbohrer ◽  
Christa Egger-Danner ◽  
Klemens Fuchs ◽  
Beate Pinior ◽  
...  

Antimicrobial use in livestock production is a controversial subject. While antimicrobials should be used as little as possible, it is still necessary, from both an animal health and welfare point of view, to treat infected animals. The study presented here aimed to analyse antimicrobial use on Austrian dairy farms by calculating the number of Defined Course Doses (DCDvet) administered per cow and year for dry cow therapy. Antimicrobial use was analysed by production system and whether farmers stated that they used blanket dry cow therapy (i.e., all cows in the herd were treated) or selective dry cow therapy (i.e., only cows with a positive bacteriological culture or current/recent history of udder disease were treated). A statistically significant difference (p < 0.001) was determined between antimicrobial use for blanket (median DCDvet/cow/year: 0.88) and selective dry cow therapy (median DCDvet/cow/year: 0.41). The difference between antimicrobial use on conventional and organic farms for dry cow therapy as a whole, however, was not statistically significant (p = 0.22) (median DCDvet/cow/year: 0.68 for conventional; 0.53 for organic farms). This analysis demonstrates that selective dry cow therapy leads to a lower overall use of antimicrobials and can assist in a more prudent use of antimicrobials on dairy farms.


2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Lothar Kreienbrock

<p>The use of antibiotics in veterinary medicine and a resulting development of antimicrobial resistance is a topic of major concern. Especially for primary care, evidence is needed to guarantee the efficacy of anti­biotic drugs in future. For this, the correct dosage is an essential measure to prevent antibiotic resistance. Because veterinarians used practice differs from the manufacturer’s recommendations, data is needed to describe evidence-based defined daily doses for animals (DDDA).</p><p>In 2011 data was collected on the usage of antibiotics in farm animals in conjunction with the Vet­CAb-study (Veterinary consumption of antibiotics) in Germany (see vetcab-s.de, van Rennings et al., 2015). Since then, data is continuously collected on the kind of antibiotics, the number of doses, number of animals treated and treatment frequencies. For this presentation the antibiotic usage in 2011 of 500 German pig farms totalling 18,150 treatment courses were recorded and analysed with regard to their dosage. The used daily dosage (UDD) was calculated from the amount of the drug used and a defined standard weight for the four different age groups in pig production: sows (200kg), piglets (4kg), weaners (15kg) and fattening pigs (50 kg).</p><p>Apart from the UDD the expertise of pharmacologists was also taken into account to determine a DDDA for each antibiotic. This definition of DDDA is pinpointed by the recommendation of the EMA and has to be determined for each drug in combination with animal species and the form of application.</p><p>The study showed that in pig production, the antibiotic groups tetracycline and ß-lactams are mainly used. More than 90% of all treatments are given orally. For tetracycline the manufacturers recommend a dose of approximately 80 mg / kg orally in pigs. The DDDAs determined from expert opinions are around 50mg/ kg. In the present study with 500 analysed pig farms the average UDD was 39.6 mg / kg. Previous stud­ies in Germany identified an identical image of evaluations in pig farms (Merle et al, 2014). This example shows the difference between the manufacturer’s recommendations, expert opinions and in practice actually administered doses.</p><p>These data therefore form a basis for the determination of DDDA. The next necessary step would be to develop Europe-wide DDDAs for each antibiotic, animal species and form of application.</p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" />


2021 ◽  
Vol 74 (1) ◽  
Author(s):  
Lydia R Rahem ◽  
Bénédicte Franck ◽  
Hélène Roy ◽  
Denis Lebel ◽  
Philippe Ovetchkine ◽  
...  

Background: Antimicrobial stewardship is a standard practice in health facilities to reduce both the misuse of antimicrobials and the risk of resistance. Objective: To determine the profile of antimicrobial use in the pediatric population of a university hospital centre from 2015/16 to 2018/19. Methods: In this retrospective, descriptive, cross-sectional study, the pharmacy information system was used to determine the number of days of therapy (DOTs) and the defined daily dose (DDD) per 1000 patient-days (PDs) for each antimicrobial and for specified care units in each year of the study period. For each measure, the ratio of 2018/19 to 2015/16 values was also calculated (and expressed as a proportion); where the value of this proportion was ≤ 0.8 or ≥ 1.2 (indicating a substantial change over the study period), an explanatory rating was assigned by consensus. Results: Over the study period, 94 antimicrobial agents were available at the study hospital: 70 antibiotics (including antiparasitics and antituberculosis drugs), 14 antivirals, and 10 antifungals. The total number of DOTs per 1000 PDs declined from 904 in 2015/16 to 867 in 2018/19. The 5 most commonly used antimicrobials over the years, expressed as minimum/maximum DOTs per 1000 PDs, were piperacillin-tazobactam (78/105), trimethoprim-sulfamethoxazole (74/84), ampicillin (51/69), vancomycin (53/68), and cefotaxime (55/58). In the same period, the care units with the most antimicrobial use (expressed as minimum/ maximum DOTs per 1000 PDs) were hematology-oncology (2529/2723), pediatrics (1006/1408), and pediatric intensive care (1328/1717). Conclusions: This study showed generally stable consumption of antimicrobials from 2015/16 to 2018/19 in a Canadian mother-and-child university hospital centre. Although consumption was also stable within drug groups (antibiotics, antivirals, and antifungals), there were important changes over time for some individual drugs. Several factors may explain these variations, including disruptions in supply, changes in practice, and changes in the prevalence of infections. Surveillance of antimicrobial use is an essential component of an antimicrobial stewardship program. RÉSUMÉ Contexte : La gestion des antimicrobiens est une pratique courante dans les centres hospitaliers afin de réduire l’utilisation inappropriée des antimicrobiens et le risque de résistance. Objectif : Décrire l’évolution de l’utilisation des antimicrobiens dans un centre hospitalier universitaire de 2015-16 à 2018-19. Méthodes : Dans cette étude rétrospective, descriptive et transversale, les dossiers pharmacologiques ont servi à déterminer le nombre de jours de traitement (NJT) et la dose définie journalière (DDD) par 1000 jours-présence (JP) pour chaque antimicrobien et pour chaque unité de soins par année de l’étude. Pour chaque mesure, on a également comparé le ratio de 2018-19 à celui de 2015-16, qui est exprimé en proportion; lorsque la valeur de cette proportion était ≤ 0,8 ou ≥ 1,2, ce qui indiquait un changement important durant la période de l’étude, une note explicative a été attribuée par consensus. Résultats : Durant la période à l’étude, 94 antimicrobiens ont été disponibles dans notre centre : 70 antibiotiques (dont les antiparasitaires et les antituberculeux), 14 antiviraux et 10 antifongiques. Le nombre total de NJT par 1000 JP a diminué de 904 en 2015-16 à 867 en 2018-19. Les cinq antimicrobiens utilisés le plus fréquemment et présentés en minimum / maximum de NJT par 1000 JP étaient les suivants : piperacilline-tazobactam (78/105), trimethoprim-sulfamethoxazole (74/84), ampicilline (51/69), vancomycine (53/68) et cefotaxime (55/58). Pendant la même période, les unités de soins qui faisaient la plus grande utilisation d’antimirobiens (exprimée en minimum / maximum de NJT par 1000 JP) étaient hématologie-oncologie (2529/2723), pédiatrie (1006/1408) et soins intensifs pédiatriques (1328/1717). Conclusions : Cette étude démontre une consommation stable d’antimicrobiens entre 2015-16 et 2018-19 dans un centre hospitalier universitaire mère-enfant canadien. Malgré le fait que la consommation entre les groupes d’antimicrobiens (antibiotiques, antiviraux, antifongiques) était stable, on a constaté d’importantes variations concernant certains médicaments individuels. Plusieurs facteurs peuvent expliquer cette variation, notamment des ruptures d’approvisionnement, des changements de pratique et des changements dans la prévalence d’infections. La surveillance de la consommation des antimicrobiens est une partie essentielle de tout programme d’antibiogouvernance.


2020 ◽  
Vol 31 ◽  
pp. 36-43
Author(s):  
S. V. Derevianko ◽  
A. V. Vasylchenko ◽  
N. I. Maharramzade

Objective. Study the biological activity of nickel nanoparticles (Ni NPs) against pathogenic viruses and fungi, pathogens of farm animals and plants, investigate their bactericidal and growthregulating properties. Methods. Virological, microbiological and statistical. Virucidal activity of NiNPs was evaluated by the difference of virus titres in the control and under the action of NPs, bactericidal — by the difference of bacterial titres, fungicidal and fungistatic — by the difference of diameters of fungal colonies, growth-regulating — by the difference in leaf blade length and roots ofgerms of winter wheat. The antiviral activity of NPs was determined in the culture of versenalisedembryonic porcine kidney cells. Bactericidal activity was investigated in a liquid digest medium.Fungistatic activity was determined on wort agar. Wheat germs were germinated in Petri dishesaccording to generally accepted methods. The viral titre was calculated by Reed-Muench method.The bacterial titre was determined by seeding the suspensions on agar medium. Statistical processing was performed in Microsoft Office Excel and statsoft STATISTICA 12, using Student's t-test,post-hoc tests: Fisher’s least significant difference test and Duncan’s new multiple range test.Results. It was found that Ni NPs show high virucidal activity against Teschovirus A strainDniprovskyi-34, reducing the virus titre by 2.46 lg TCD50/cm3, and have a chemotherapeutic indexof 4. Ni NPs have low fungistatic activity against Acremonium cucurbitacearum 502, reducing theaverage diameter of colonies by 6.58 to 20.22 %. Regarding Acremonium strictum 048 and Fusarium sp. 072, Ni NPs have a slight stimulating activity, increasing the average diameter of the colonies by 10.18 to 12.44 % and 14.84 to 22.18 %, respectively. Under the action of Ni NPs, the titre ofBacillus subtilis ІМВ В-7023 and Pseudomonas chlororaphis subsp. aureofaciens UKM B-306(2687) upon the cultivation of bacteria in meat-peptone broth significantly (by 80.96 to 82.77 %and 15.67 to 36.39 %, respectively) increases. Ni NPs exhibits growth-promoting properties onwheat germs, increasing the average length of leaf blades and roots by 41.79 and 36.76 %, respectively. Conclusion. According to the study findings, Ni NPs cannot be recommended for the creation of antifungal preparations. Further research is needed to develop Ni NP-based antiviral preparations, virucidal and disinfecting agents, growth- regulating products for cultivated plants, and toincrease the titre of beneficial soil bacteria.


Author(s):  
Ai-Yu Yang ◽  
Hung-Chun Chen

AbstractBackground Previously, dapagliflozin was limited to patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, while empagliflozin can be used for those with an eGFR ≥ 45 mL/min/1.73 m2. Therefore dapagliflozin was switched to empagliflozin in many patients when eGFR decreased. However, the clinical efficacy and safety of these switcfhes are not clear. Objective In this study, we compared the efficacy and renal safety between patients switching from dapagliflozin to empagliflozin in patients. Setting This is a retrospective study of adult patients (aged ≥ 20 years) who had attended the Kaohsiung Medical University Hospital. Method This retrospective observational study included patients who were switched from dapagliflozin to empagliflozin. To assess the effect of other hypoglycemic drugs on efficacy, the types and dose alterations of other hypoglycemic drugs were classified on the defined daily dose (DDD). Main outcome measure The primary outcome measure was the change in hemoglobin A1c (HbA1c) level after 6 months. Patients with HbA1c levels at or lower than the baseline value after 6 months were defined as effective and patients with levels higher than the baseline were defined as invalid. Safety was evaluated by comparing the difference of eGFR between the baseline value and 6 months after treatment. Results Overall, 111 patients were enrolled in the study. Six months after switching from dapagliflozin to empagliflozin, HbA1c significantly reduced, with no statistically significant difference observed in eGFR. In our study, 78 patients were assigned to the effective group (70.3%) and 33 patients were invalid (29.7%). When the other hypoglycemic drugs were grouped by total dosage, fasting plasma glucose and HbA1c only decreased significantly in the "DDD decrease" and "DDD increase" groups. Conclusion Our study showed that switching from dapagliflozin to empagliflozin in patients with type 2 diabetes was effective for blood glucose maintenance and caused no significant changes in renal function. In addition, compared to similar sodium-glucose co-transporter-2 inhibitors, other hypoglycemic drugs may be factors that influence the efficacy of sugar-lowering treatments.


Author(s):  
Matthew Rico ◽  
Rand Sulaiman ◽  
Rachel MacLeod

Abstract Purpose The purpose of this study was to evaluate the effect of an antimicrobial stewardship bundle on the management of asymptomatic bacteriuria (ASB). Methods In this quasi-experimental study, patients were selected by retrospective, consecutive sampling of patients with a positive urine culture report in 3 separate groups: preintervention, postdiagnostic intervention, and posteducation. Patients met the prespecified criteria for non–catheter-associated ASB. The diagnostic intervention involved a new urinalysis/urine culture ordering process in place of urinalysis with reflex to urine culture. Additionally, an educational intervention involved pharmacist-led sessions to educate providers with patient cases and guideline-based recommendations. The primary outcome of this study was the difference in the rate of inappropriate management of ASB, defined as the use of antimicrobial agents intended to treat ASB. Secondary outcomes included length of antimicrobial therapy, length of stay, and change in urine culture orders per 1,000 patient-days. Results A total of 120 patients were included. There was a significant reduction in the inappropriate management of ASB between the preintervention and postdiagnostic intervention groups (P = 0.0349). This was not seen when comparing the postdiagnostic intervention and posteducation groups (P = 0.93). Additionally, there was a significant difference in urinalysis/urine culture ordering between the preintervention and postdiagnostic intervention groups (370 vs 224 urinalysis orders per 1,000 days present, P &lt; 0.0001; 131 vs 54 urine culture orders per 1,000 days present, P &lt; 0.0001). Conclusion An antimicrobial stewardship bundle involving a diagnostic stewardship intervention and pharmacist-led education reduced treatment of ASB in patients without urinary catheters.


2019 ◽  
Vol 40 (3) ◽  
pp. 375-379
Author(s):  
Shutaro Murakami ◽  
Junko Hiroi ◽  
Yasuharu Tokuda ◽  
Ed Casabar ◽  
Hitoshi Honda

AbstractUnderestimating antimicrobial use based on days of therapy (DOT) is recognized for certain antimicrobial agents. We investigated the difference between DOT and therapeutic drug monitoring (TDM)–based exposure days in estimating vancomycin use and demonstrated that DOT may underestimate vancomycin exposure by ∼10%.


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