Roswitha Merle

Cross-Sectional Study on Antibiotic Usage in Pigs in Germany

To be able to analyze the relationship between the level of resistance and the use of antimicrobials, it is necessary to collect detailed data on antimicrobial usage. For this reason, data on antimicrobial use on 495 pig farms from entire Germany were collected and analyzed. In Germany, each application and dispensing of medicines to food-producing animals is documented in detail obligatorily by the veterinarian. This information was collected retrospectively for the year 2011. The analyses undertook separate examinations on the age groups sow, piglet, weaner and fattening pig; both the route of administration and indication per active ingredient, and active ingredient class, were evaluated. In total, 20,374 kg of antimicrobial substances were used in the study population. Tetracyclines were used in highest amounts, followed by beta-lactams, trimethoprim-sulfonamides and macrolides. Concerning the frequency of using an active substance per animal, polypeptides were most commonly administered. In all age groups, respiratory infections were the main indication for using antimicrobials, followed by intestinal diseases in piglets, weaners and fattening pigs and diseases of reproductive organs in sows. Over a period of 100 days, the median number of treatment days with one antimicrobial substance for piglets was 15 days, for weaners about 6 days, for fattening pigs about 4 days and for sows about 1 day. A multifactorial ANOVA was conducted to investigate which factors are associated with the treatment frequency. The factors “veterinarian” and “age group” were related to the treatment frequency, just as the interaction between “veterinarian” and “farm size” as well as the interaction between “veterinarian” and “age group”.

Feasibility study of veterinary antibiotic consumption in Germany - comparison of ADDs and UDDs by animal production type, antimicrobial class and indication

BackgroundWithin a feasibility study the use of antibiotics in pigs and cattle was determined in 24 veterinary practices in Lower Saxony and on 66 farms in North Rhine-Westphalia in Germany. Focus was laid on the comparison of the Used Daily Doses (UDD) (dose per animal and day prescribed by the veterinarians) with the Defined Animal Daily Doses (ADD) (dose per animal and day calculated by means of recommended dosages and estimated live weights).ResultsFor piglets and calves most of the UDD (50% and 46% of nUDD, respectively) were above the ADD (i.e. UDD/ADD-ratio above 1.25). Regarding sows, fattening pigs, dairy and beef cattle, most of the UDDs (49% to 65% of nUDD) were lower than the respective ADD (i.e. UDD/ADD-ratio below 0.8). In pigs, the UDDs of beta-lactams, fluoroquinolones and cephalosporins, and in cattle, those of macrolides and beta-lactams were often below the ADDs. Tetracyclines were frequently used above the recommended dose.Enteric diseases were more often treated below the recommended dose than respiratory diseases, possibly due to overestimation of the live weight (diarrhea in young animals, respiratory diseases in elder animals) and consequently overestimation of the recommended dose.ConclusionComparisons between UDD and ADD can be used to observe differences between antimicrobials and trends in the usage of antibiotics. But individual treatment comparisons of UDD and ADD must be interpreted carefully, because they may be due to lower live weights than estimated. Correlating such data with data on the occurrence of resistant bacteria in future may help to improve resistance prevention and control.

Campylobacter spp. - prevalence on pig livers and antimicrobial susceptibility.

The objective of the study was to determine the prevalence of Campylobacter spp. on surfaces of slaughtered pig livers. Multilocus sequence typing (MLST) was performed to determine the sequence types (STs) of selected Campylobacter coli isolates. Additionally, C. coli and Campylobacter jejuni isolates were tested for antimicrobial susceptibility by the broth dilution method. The minimal inhibitory concentrations were determined for erythromycin, gentamicin, ampicillin, ampicillin/sulbactam, nalidixic acid, ciprofloxacin, tetracycline and trimethoprim/sulphamethoxazole. Samples were taken during the slaughtering process in a slaughterhouse in Lower Saxony, Germany. Altogether, 10% of 1500 surfaces of pig livers from 50 fattening herds was found to be Campylobacter positive, with C. coli as the predominant species (76%) followed by C. jejuni (21%). Resistance to erythromycin and tetracycline was higher in C. jejuni compared to C. coli, whereas C. coli were more resistant to quinolone compared to C. jejuni. Fluoroquinolone resistance is usually associated with cross-resistance to quinolone, but in the presented investigation C. coli as well as C. jejuni showed a higher resistance to ciprofloxacin (28.6% and 20.0%, respectively) than to nalidixic acid (9.5% and 0%, respectively). A high genetic diversity of the C. coli isolates was demonstrated by MLST. Differences in STs and antimicrobial resistance pattern indicate that the Campylobacter strains originated from the pig itself and not from the slaughterhouse. A comparison of the STs with those reported in the C. jejuni/coli PubMLST database showed an overlap of porcine and human isolates, indicating that C. coli isolates from pigs should be considered as potential sources of human infection.

Antibiotic Susceptibility of Salmonella, Campylobacter coli, and Campylobacter jejuni Isolated from Northern German Fattening Pigs

This study was conducted to assess the antimicrobial susceptibility rate of Salmonella and Campylobacter spp. isolated from Northern German fattening pigs. From 540 lymph node samples, 16 Salmonella Typhimurium, 1 Salmonella Brandenburg, 37 Campylobacter coli, and 11 Campylobacter jejuni strains were isolated. Antibiotic susceptibility testing was carried out by the broth dilution method. The 14 tested antibiotics for Salmonella were ampicillin, cefotaxime, ceftazidime, chloramphenicol, ciprofloxacin, colistin, florfenicol, gentamicin, kanamycin, nalidixic acid, streptomycin, sulfamethoxazole, tetracycline, and trimethoprim. The eight tested antibiotics for Campylobacter spp. were ampicillin, ampicillin-sulbactam (2:1), ciprofloxacin, erythromycin, gentamicin, nalidixic acid, sulfamethoxazole-trimethoprim (1:19), and tetracycline. In total, 93.7% (n = 16) of Salmonella Typhimurium, 75.7% (n = 37) of C. coli, and 54.5% (n = 11) of C. jejuni isolates were resistant to at least one of the tested antibiotics. Multiresistance to three antibiotics was observed in 75% of Salmonella Typhimurium, 16.2% of C. coli, and 0% of C. jejuni isolates. Pansusceptibility was detected in 6.3% of Salmonella Typhimurium, 24.3% of C. coli, and 45.5% of C. jejuni isolates. Multiresistance is defined as resistance to three or more antibiotics, and pansusceptibility is defined as not having resistance to any antibiotic. Regarding drugs of last resort--cefotaxime, ciprofloxacin, and nalidixic acid--resistance was not common among Salmonella (6.3%). The resistance rate of Campylobacter spp. to last-resort drugs--erythromycin, ciprofloxacin, and nalidixic acid--varied between species. The observed trend was not statistically significant. No C. coli isolates and few C. jejuni isolates (9.1%) were resistant to erythromycin. In contrast to C. jejuni, the C. coli isolates were more likely to be resistant to ciprofloxacin (9.1 and 18.9%, respectively) and nalidixic acid (0 and 13.5%, respectively). The same phenomenon was detected for tetracycline (27.3 and 62.2%, respectively), sulfamethoxazole (9.1 and 43.2%, respectively), and ampicillin (9.1 and 21.6%, respectively).

Prevalence of Pathogenic Yersinia enterocolitica Strains on Liver Surfaces of Pigs and Their Antimicrobial Susceptibility

A study to determine the occurrence of pathogenic Yersinia enterocolitica on surfaces of slaughtered pig livers and the antimicrobial resistant pattern of the isolates was carried out in a slaughterhouse in Lower Saxony, Germany. During the slaughtering process, 1,500 surfaces of pig livers from 50 fattening herds were swabbed in order to isolate and characterize Y. enterocolitica isolates by serotyping, detecting the virulence plasmid coding the yopT gene, and resistance testing. Of the livers tested, 4.7% were positive for Y. enterocolitica O:3, which was the only identified serotype. The virulence gene yopT was found in 90.0% of these isolates. Antimicrobial susceptibility was tested by the broth dilution method, and the MICs were determined for 13 antimicrobials. All isolates were resistant to ampicillin and sulfamethoxazole but were susceptible to ciprofloxacin, nalidixic acid, gentamicin, ceftiofur, tetracycline, kanamycin, cefotaxime, and chlorphenicol. Up to now, resistance to florfenicol has always been described in combination with resistance to chloramphenicol. In the present study, 15.3% of the isolates were resistant to florfenicol, while no chloramphenicol-resistant strains could be identified. Multiresistance to three or more antimicrobials was detected in 22 strains (27.3%). Nevertheless, third-generation cephalosporines or fluoroquinolones, which were recommended for extraintestinal Y. enterocolitica infection in humans, were not affected.

Erfassung des Antibiotikaeinsatzes bei Lebensmittel liefernden Tieren in der tierarztlichen Praxis

In einer Machbarkeitsstudie mit 20 freiwillig teilnehmenden tierarztlichen Praxen wurde gepruft, ob Verbrauchsmengen von Antibiotika in der Nutztierhaltung harmonisiert erfasst werden konnen. Dazu wurden die Informationen aller Arzneimittelanwendungs- und -abgabebelege der teilnehmenden Praxen in einer zentralen Datenbank erfasst und systematisch ausgewertet. Reine Nutztierpraxen setzten deutlich mehr Antibiotika je Nutztierarzt ein (Zahl der Einzelgaben je Tierarzt) als Praxen, die auch Kleintiere behandelten. Der Vergleich kleiner und groser Praxen zeigte, dass Nutztierarzte in kleinen Praxen Schweine eher weniger, Rinder aber eher mehr behandelten als die Kollegen in grosen Praxen (bezogen auf die Zahl der Einzelgaben je Nutztierarzt). Insgesamt wurden mit 50 % der eingesetzten Wirkstoffmenge am meisten Tetrazykline eingesetzt, gefolgt von den Beta-Laktamen (25 %) und Sulfonamiden einschl. Trimethoprim (11 %). Im Geflugelbereich fanden Polypeptide sowie Beta-Laktame den haufigsten Einsatz. Wahrend Cephalosporine nur beim Rind in nennenswerter Haufigkeit eingesetzt wurden, wurden Fluorchinolone bei Geflugel bei fast 12 % aller Einzelgaben (Einsatz eines Wirkstoffes an einem Tier und einem Tag) gegeben. Insgesamt konnte belegt werden, dass eine harmonisierte Erfassung des Arzneimitteleinsatzes in tierarztlichen Praxen einfach moglich ist, allerdings bereitet die Zuordnung zur behandelten Population Probleme, sodass dies in Zukunft angemessen berucksichtigt werden muss. Zur Bewertung des Arzneimitteleinsatzes ist die Zahl der Einzelgaben besser geeignet als die Menge in kg, da letztere von der Dosierung abhangig ist. Besonders hochdosierte Wirkstoffe wie z. B. Tetrazykline werden bei Betrachtung der Menge in ihrer Bedeutung uber-, besonders niedrig dosierte Wirkstoffe entsprechend unterschatzt

Verbrauchsmengenerfassung von Antibiotika beim Schwein in landwirtschaftlichen Betrieben

In 47 Betrieben mit Rinderhaltung mit ingesamt ca. 6500 Rindern eines Landkreises in Nordrhein-Westfalen wurde der Verbrauch von antibiotischen Wirkstoffen erfasst. Als Datenquellen wurden die tierarztlichen Arzneimittelanwendungs- und -abgabebelege (§13 TAHAV) und die Informationen aus Bestandsbuchern (ANTHV) der Betriebe herangezogen. Verbrauchsdaten vom Zeitraum eines Jahres (1. September 2006 bis 31. August 2007) wurden in einer zentralen Datenbank eingetragen. Der Verbrauch (Menge des freien Wirkstoffs in kg) war bei Beta-Laktamen mit insgesamt 48 % am hochsten, gefolgt vom Verbrauch aus der Gruppe „Sulfonamide & Trimethoprim“ (17 %) und den Tetrazyklinen (11 %). Insgesamt wurden im Studienkollektiv etwa 39 kg antibiotisch wirksame Stoffe (Menge freier Wirkstoffe) verabreicht. Bei der Betrachtung der Haufigkeit der Behandlungen zeigte sich ein ahnliches Bild, denn 35 % aller Behandlungen am Rind wurden mit Beta-Laktamen, und lediglich 9 % mit Tetrazyklinen durchgefuhrt. Am haufigsten wurden Rinder am Euter behandelt (45 % der eingesetzten freien Wirkstoffmenge, 56 % der Einzelgaben). Die Therapiehaufigkeit ist die durchschnittliche Anzahl der verabreichten Einzelgaben (Behandlungstage und Zahl der Wirkstoffe) je Alters- und Nutzungsgruppe innerhalb eines Zeitraumes und einer Population. Sie korrespondiert grundsatzlich mit den Angaben der DDD (Defined Daily Dose) aus den Niederlanden und der ADD (Defined Animal Daily Dose) aus Danemark, auch wenn durch unterschiedliche Rechenwege ein direkter Vergleich der Werte nicht statthaft ist. An 100 Tagen erhielt in den Studienbetrieben jedes Aufzuchtkalb durchschnittlich 0,7, jedes Milchrind 0,9 (inklusive Trockenstellen = 1 Tag) und jedes Mastrind 0,01 Einzelgaben

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Acinetobacter baumannii among horses entering a veterinary teaching hospital: The contemporary "Trojan Horse"

Pathogens frequently associated with multi-drug resistant (MDR) phenotypes, including extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and Acinetobacter baumannii isolated from horses admitted to horse clinics, pose a risk for animal patients and personnel in horse clinics. To estimate current rates of colonization, a total of 341 equine patients were screened for carriage of zoonotic indicator pathogens at hospital admission. Horses showing clinical signs associated with colic (n = 233) or open wounds (n = 108) were selected for microbiological examination of nostril swabs, faecal samples and wound swabs taken from the open wound group. The results showed alarming carriage rates of Gram-negative MDR pathogens in equine patients: 10.7% (34 of 318) of validated faecal specimens were positive for ESBL-E (94%: ESBL-producing Escherichia coli), with recorded rates of 10.5% for the colic and 11% for the open wound group. 92.7% of the ESBL-producing E. coli were phenotypically resistant to three or more classes of antimicrobials. A. baumannii was rarely detected (0.9%), and all faecal samples investigated were negative for Salmonella, both directly and after two enrichment steps. Screening results for the equine nostril swabs showed detection rates for ESBL-E of 3.4% among colic patients and 0.9% in the open wound group, with an average rate of 2.6% (9/340) for both indications. For all 41 ESBL-producing E. coli isolated, a broad heterogeneity was revealed using pulsed-field gel electrophoresis (PFGE) patterns and whole genome sequencing (WGS) -analysis. However, a predominance of sequence type complex (STC)10 and STC1250 was observed, including several novel STs. The most common genes associated with ESBL-production were identified as blaCTX-M-1 (31/41; 75.6%) and blaSHV-12 (24.4%). The results of this study reveal a disturbingly large fraction of multi-drug resistant and ESBL-producing E. coli among equine patients, posing a clear threat to established hygiene management systems and work-place safety of veterinary staff in horse clinics.

Drinking water test methods in crisis-afflicted areas: comparison of methods under field conditions.

To simplify the testing of drinking water in crisis-afflicted areas (as in Kosovo in 2007), rapid test methods were compared with the standard test. For Escherichia coli and coliform pathogens, rapid tests were made available: Colilert(®)-18, P/A test with 4-methylumbelliferyl-β-D-glucoronid, and m-Endo Broth. Biochemical differentiation was carried out by Enterotube™ II. Enterococci were determined following the standard ISO test and by means of Enterolert™. Four hundred ninety-nine water samples were tested for E. coli and coliforms using four methods. Following the standard method, 20.8% (n=104) of the samples contained E. coli, whereas the rapid tests detected between 19.6% (m-Endo Broth, 92.0% concordance) and 20.0% (concordance: 93.6% Colilert-18 and 94.8% P/A-test) positive samples. Regarding coliforms, the percentage of concordant results ranged from 98.4% (P/A-test) to 99.0% (Colilert-18). Colilert-18 and m-Endo Broth detected even more positive samples than the standard method did. Enterococci were detected in 93 of 573 samples by the standard method, but in 92 samples by Enterolert (concordance: 99.5%). Considering the high-quality equipment and time requirements of the standard method, the use of rapid tests in crisis-afflicted areas is sufficiently reliable.

Unterschiede in der Berechnung des betriebsbezogenen Antibiotika-Einsatzes in Monitoringsystemen in Deutschland – eine Übersicht

In Deutschland wird die Abgabe bzw. der Verbrauch von Antibiotika in der Nutztierhaltung kontinuierlich erfasst. Hierzu dienen unter anderem die nach Arzneimittelgesetz verpflichtende Dokumentation in der behordlichen HI-Tier Datenbank, die Dokumentation innerhalb des privatwirtschaftlichen Systems der Firma QS Qualitat und Sicherheit GmbH aber auch wissenschaftliche Untersuchungen wie das Projekt VetCAb („Veterinary Consumption of Antibiotics“) oder andere bestandsspezifische Untersuchungen. Diese Systeme berechnen die Haufigkeit des Antibiotikaeinsatzes uber die Therapiehaufigkeit oder aquivalente Maszahlen, die jedoch in jedem System unterschiedlich definiert werden. Da haufig keine detaillierte Beschreibung der genutzten Maszahl angefuhrt wird, kommt es bei der Interpretation immer wieder zu Missverstandnissen. Um eine Ubersicht uber die verwendeten Begriffe zu erhalten, werden vier der in Deutschland angewendeten Maszahlen und die dazugehorigen Grosen beschrieben: der Tierbehandlungsindex, der Therapieindex nach Definition der Fa. QS Qualitat und Sicherheit GmbH, die Therapiehaufigkeit nach Festlegung des Arzneimittelgesetzes sowie die Therapiehaufigkeit, die im Rahmen des Projektes VetCAb zur Anwendung kommt. Durch den Vergleich der Definitionen der Maszahlen sowie einzelner genutzter Variablen wird deutlich, dass in den errechneten Zielgrosen (nummerische) Unterschiede bestehen konnen und somit ein direkter Vergleich der vier Maszahlen nicht statthaft ist. Alle Maszahlen sind jedoch innerhalb des jeweiligen Systems geeignet, Trends zu analysieren und zu vergleichen.