Untersuchung zur angemessenen Behandlungsdauer bei Fohlen mit abszedierender Bronchopneumonie und Kinetik des Serum-Amyloid-A-Wertes im Behandlungsverlauf

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Untersuchung zur angemessenen Behandlungsdauer bei Fohlen mit abszedierender Bronchopneumonie und Kinetik des Serum-Amyloid-A-Wertes im Behandlungsverlauf

INAUGURAL – DISSERTATION zur Erlangung des Grades einer Doktorin der Veterinärmedizin

– Doctor medicinae veterinariae – (Dr. med. vet.)

vorgelegt von Anna Lankenfeld

Osnabrück

Hannover 2021

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Wissenschaftliche Betreuung: PD, Dr. Monica Venner, PhD, Dipl. ECEIM Klinik für Pferde

Tierärztliche Hochschule Hannover

1. Gutachterin: PD, Dr. Monica Venner, PhD, Dipl. ECEIM Klinik für Pferde

2. Gutachter: Univ.-Prof. Dr. Martin Ganter, Dipl. ECSRHM Klinik für kleine Klauentiere

Tag der mündlichen Prüfung: 21.05.2021

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Meiner Familie

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1. Einleitung ... 1

2. Publikation 1: ... 4

Abscessing bronchopneumonia in foals – The adequate treatment period and its determination ... 4

3. Publikation 2: ... 15

Kinetics of serum amyloid A during the treatment period of foals with pneumonia ... 15

4. Übergreifende Diskussion ... 26

4.1. Abszedierende Bronchopneumonie beim Fohlen ... 26

4.2. Behandlungsdauer ... 29

4.3. Kinetik des SAA-Wertes und klinischer Nutzen ... 31

4.4. Schlussfolgerungen ... 34

5. Zusammenfassung ... 36

6. Summary ... 39

7. Literaturverzeichnis ... 42

8. Danksagung ... 50

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Die abszedierende Bronchopneumonie ist eine häufige und bedeutende Erkrankung von Fohlen und hat daher erheblichen wirtschaftlichen Einfluss in Zuchtbetrieben (MUSCATELLO 2012a). Rhodococcus equi (R. equi) und Streptococcus equi subspec.

zooepidemicus sind pathogene Bakterien, die häufig für Lungenerkrankungen bei Fohlen im Alter von 3 Wochen bis zu 5 Monaten verantwortlich sind und ähnliche klinische Befunde hervorrufen (HOFFMANN et al. 1993, LAVOIE et al. 1994, GIGUÈRE und PRESCOTT 1997).

Da die abszedierende Pneumonie häufig zunächst subklinisch verläuft, werden Screening-Programme empfohlen, um betroffene Fohlen frühestmöglich zu erkennen.

Eine frühe Diagnose ist mit einer geringeren Sterblichkeit und einer kürzeren Behandlungsdauer verbunden (COHEN et al. 2005, GIGUÈRE et al. 2011a). Zum Nachweis einer Pneumonie bei Fohlen ist die sonographische Untersuchung der Lunge ein zuverlässiges diagnostisches Verfahren (SLOVIS et al. 2005). Hingegen haben sich die klinische Untersuchung und die Hämatologie, insbesondere die Leukozytenzahl und das Fibrinogen, im Vergleich zur Sonographie als weniger sensitiv erwiesen (GIGUÈRE et al. 2003).

Ein weiterer Blutparameter, das Akute-Phase-Protein Serum Amyloid A (SAA), könnte aufgrund seiner schnellen Reaktion als Entzündungsmarker bei der Beurteilung einer Pneumonie bei Fohlen hilfreich sein. Das SAA zeigt Entzündungsreaktionen und Gewebeschäden im Körper mit einem deutlichen Anstieg um das bis zu Hundertfache innerhalb von sechs bis zwölf Stunden an, wobei Spitzenwerte bei Pferden nach ca.

48 Stunden beobachtet werden (JACOBSEN und ANDERSEN 2007). Einerseits wird SAA zusammen mit dem klinischen Status des Fohlens als nützlicher Parameter genannt, um eine Pneumonie im Rahmen von Überwachungsprogrammen frühzeitig zu erkennen (HULTÉN und DEMMERS 2002, BELGRAVE et al. 2013), andererseits zeigten sich Sensitivität und Spezifität in zwei aktuellen Studien zu gering, um den SAA als alleiniges, zuverlässiges Diagnostikum einsetzen zu können (GIGUÈRE et al.

2016, THOMÉ et al. 2018b).

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Zur Behandlung der R. equi-Pneumonie hat sich der Einsatz eines Makrolid- Antibiotikums in Kombination mit Rifampicin bewährt. Die Kombination von Rifampicin mit Makroliden der neueren Generation, wie Azithromycin und Clarithromycin (GIGUÈRE et al. 2004) sowie Tulathromycin (RUTENBERG et al. 2017), hat in den letzten Jahren die Behandlung mit Erythromycin ersetzt. Jüngste Hinweise deuten darauf hin, dass die Resistenz gegen Makrolide und Rifampicin bei R. equi-Isolaten in USA zunimmt (GIGUÈRE et al. 2017). Dies wirft die Frage auf, wie Antibiotika gezielter eingesetzt werden können, einschließlich der passenden Auswahl der Medikamente und einer geeigneten Behandlungsdauer.

Als Parameter für die Entscheidung über die Behandlungsdauer werden unter anderem die Rückbildung der klinischen Befunde (PRESCOTT und SWEENY 1985), die Rückbildung der bei der Thoraxsonographie festgestellten Läsionen und das Plasmafibrinogen (GIGUÈRE 2010) herangezogen. Die Vorschläge für die Dauer einer erfolgreichen Therapie variieren in der Literatur zwischen zwei bis zwölf Wochen (GIGUÈRE 2010), vier bis neun Wochen (GIGUÈRE 2001) und sechs bis acht Wochen (PRESCOTT und SWEENY 1985), abhängig vom Schweregrad der anfänglichen Läsionen und des Ansprechens auf die Behandlung. Die Überwachung der erkrankten Fohlen einschließlich ultrasonographischer, hämatologischer und klinischer Untersuchungen kann dazu beitragen, die Anzahl der behandelten erkrankten Fohlen zu reduzieren, ohne die Verluste der Fohlen zu erhöhen (COHEN et al. 2002, MUSCATELLO et al. 2007, ARNOLD-LEHNA et al. 2019). Allerdings gibt es Bedenken, dass ein zu frühes Absetzen der Behandlung zu Rezidiven führen kann (GIGUÈRE und PRESCOTT 1997).

Ziel der vorliegenden Studie war es erstens, zu analysieren, ob eine Behandlungsdauer von zwei Wochen für eine vollständige Genesung ohne ein erhöhtes Rezidivrisiko auf einem Betrieb mit endemischer Bronchopneumonie bei Fohlen ausreichend ist.

Zweitens wurde die Kinetik von SAA während der Behandlung einer Pneumonie bei Fohlen untersucht und mit dem Verlauf der ultrasonographischen Befunde verglichen,

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Behandlung von abszedierenden Pneumonien zu beurteilen.

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4 2. Publikation 1:

Abscessing bronchopneumonia in foals – The adequate treatment period and its determination

Pferdeheilkunde – Equine Medicine 37 (2021) 4 (July/August) 1-9

Anna Lankenfeld¹ , Juliane Fels¹ , Karl Rohn² and Monica Venner³

1 Equine Clinic, University of Veterinary Medicine Hanover, Hanover, Germany

2 Department of Biometry and Epidemiology, University of Veterinary Medicine

1 Hanover, Hanover, Germany

3 Equine Clinic Destedt, Germany

Correspondence and requests should be addressed to:

PD Dr. Monica Venner, PhD., Dipl. ECEIM, FEI-Tierärztin, Pferdeklinik Destedt GmbH, Trift 4 38162 Destedt

Germany E-Mail: mvenner@gmx.de

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The objective of the present study was to analyse whether a treatment duration of 2 weeks in cases of abscessing bronchopneumonia in foals is sufficient for a complete recovery without relapses. Antimicrobial treatment with durations of 4 weeks and more for foals is empirical practice on many farms with endemic foal pneumonia. In the prospective, randomised blind study foals with an abscess score of 15 to 19.5 cm (moderate pneumonia) at sonography of the thorax were included in group 1 (n = 92, treatment: rifampin/tulathromycin). If the abscess score was ≥ 20 cm (severe pneumonia), foals were allocated to group 2 (n = 73, treatment: rifampin/azithromycin).

The treatment duration (2, 4 or 6 weeks) in groups 1 and 2 depended on the random assignment to these subgroups. Tracheobronchial aspirates from foals with pneumonia were randomly tested for bacterial pathogens by microbiological culture. In enrolled foals clinical examination was done once weekly and WBC counting and ultrasound examination of the lung twice weekly. Foals that required a treatment change because findings worsened or stagnated or the occurrence of another disease, they were taken out of the study (n = 15/165). Such an exclusion of the study was classified as treatment failure and the data from these foals were processed separately until their removal from the study.

In foals with moderate or severe pneumonia, about 75% recovered after two weeks of treatment and 25% needed longer therapy. Clinical signs almost completely regressed during the first two weeks of treatment. The WBC count was not helpful in assessing the course of pneumonia. Three of 150 foals had a recurrence of pneumonia three or more weeks after the end of treatment. The duration of treatment of 2 weeks of moderate and severe abscessing bronchopneumonia seems sufficient in most foals.

The younger a foal is at the day of diagnosis of pneumonia, the more likely it will require more than 2 weeks of therapy or even the treatment will fail. Altogether, the duration of therapy should be tailored to the patient and unnecessary prolonged use of antibiotics can be avoided.

Keywords: Foal; Pneumonia; Treatment duration; Ultrasonographic examination

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Pferdeheilkunde – Equine Medicine 37 (2021) 1

Pferdeheilkunde – Equine Medicine 37 (2021) 4 (July/August) 1–9

Abscessing bronchopneumonia in foals – The adequate treatment period and its determination

Anna Lankenfeld¹, Juliane Fels¹, Karl Rohn² and Monica Venner³

2 Department of Biometry and Epidemiology, University of Veterinary Medicine Hanover, Hannover, Germany

3 Veterinary Clinic Destedt, Germany

Summary: The objective of the present study was to analyse whether a treatment duration of 2 weeks in cases of abscessing bronchopneumonia in foals is sufficient for a complete recovery without relapses. Antimicrobial treatment with durations of 4 weeks and more for foals is empirical practice on many farms with endemic foal pneumonia. In the prospective, randomised blind study foals with an abscess score of 15 to 19.5 cm (moderate pneumonia) at sonography of the thorax were included in group 1 (n = 92, treatment: rifampin/tulathromycin). If the abscess score was ≥ 20 cm (severe pneumonia), foals were allocated to group 2 (n = 73, treatment: rifampin/azithromycin). The treatment duration (2, 4 or 6 weeks) in groups 1 and 2 depended on the random assignment to these subgroups. Tracheobronchial aspirates from foals with pneumonia were randomly tested for bacterial pathogens by microbiological culture. In enrolled foals clinical examination was done once weekly and WBC counting and ultrasound examination of the lung twice weekly. Foals that required a treatment change because findings worsened or stagnated or the occurrence of another disease, they were taken out of the study (n = 15/165). Such an exclusion of the study was classified as treatment failure and the data from these foals were processed separately until their removal from the study. In foals with moderate or severe pneumonia, about 75 % recovered after two weeks of treatment and 25 % needed longer therapy. Clinical signs almost completely regressed during the first two weeks of treatment. The WBC count was not helpful in assessing the course of pneumonia. Three of 150 foals had a recurrence of pneumonia three or more weeks after the end of treatment. The duration of treatment of 2 weeks of moderate and severe abscessing bronchopneumonia seems sufficient in most foals. The younger a foal is at the day of diagnosis of pneumonia, the more likely it will require more than 2 weeks of therapy or even the treatment will fail. Altogether, the duration of therapy should be tailored to the patient and unnecessary prolonged use of antibiotics can be avoided.

Keywords: foal, pneumonia, treatment period, ultrasonographic examination

Citation: Lankenfeld A., Fels J., Rohn K., Venner M. (2021) Abscessing bronchopneumonia in foals – The adequate treatment period and its determination Pferdeheilkunde 37, 1–9; DOI 10.21836/PEMLankenfeld

Correspondence: PD Dr. Monica Venner PhD, Veterinary Clinic Destedt, Trift 4, 38162 Destedt, Germany; mvenner@gmx.de Submitted: January 4, 2021 | Accepted: March 9, 2021

DOI 10.21836/PEMLankenfeld

Introduction

Abscessing bronchopneumonia is a frequent and significant disease of foals on breeding farms. Rhodococcus equi (R.

equi) and Streptococcus equi subsp. zooepidemicus are of- ten the bacteria responsible for pulmonary disorders in foals between 3 weeks and 5 months of age and induce similar clinical findings (Hoffmann et al. 1993, Lavoie et al. 1994).

The use of a macrolide antibiotic in combination with rifampin for the treatment of R. equi pneumonia is well validated. In recent years, newer-generation macrolides, such as azithromycin and clarithromycin (Giguère et al. 2004), as well as tulathromycin (Venner et al. 2007, Rutenberg et al. 2017), have replaced erythromycin in combination with rifampin. Re- cent evidence suggests that the resistance to macrolides and rifampin in R. equi isolates is increasing (Giguère et al. 2017), which raises the question how antibiotics can be used in a more targeted way, including the tailored choice of the drugs and the appropriate duration of treatment.

Parameters used to guide the decision on the duration of treatment include the resolution of clinical findings (Prescott et al. 1985), resolution of abnormalities detected by thoracic findings at sonography of the thorax and plasma fibrinogen (Giguère 2010). The suggestions in literature for successful therapy vary between 2–12 weeks (Giguère 2010), to 4–9 weeks (Giguère 2001) and 6–8 weeks (Prescott et al. 1985) depending on the severity of the initial lesions and the response to therapy. Monitoring of the sick foals including ultrasonographic, haematological and clinical examinations can help to reduce the number of affected foals treated without increasing the foals losses (Cohen et al. 2002, Muscatello et al. 2007, Arnold-Lehna et al. 2019). However, there are some concerns that a too early discontinuation of the therapy may lead to relapses (Giguère et al. 1997).

The objective of the present study was to analyse whether a treatment duration of 2 weeks is sufficient for a complete recovery without relapses on a farm with endemic bronchopneumonia in foals.

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Pferdeheilkunde – Equine Medicine 37 (2021)

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13 and 19 days, the four-week period varied between 27 and 33 days and the six-week period between 41 and 47 days.

The examining vets were not aware of the foal’s allocation to the groups.

In participating foals, clinical examination was done once weekly. Twice weekly, the WBC were counted and the diameter of lung lesions measured at ultrasonographical examination of the lung. Antibiotic therapy was ended, if no more consolidations were seen at the sonography of the lung. Oth- erwise, the treatment was extended for 14 days. After ending the treatment, the examinations were continued once a week up to the age of five and a half months.

Materials and methods Study population

The study was a prospective, randomised and blinded clinical trial during the 2018 breeding season on a Warmblood stud.

The stud has a history of foal pneumonia due to R. equi.

Multiple former studies performed at the stud showed that R.

equi was isolated from tracheobronchial aspirates of 39 % (n = 17/44) to 54 % (n = 118/217) of the foals with ultrasonographic evidence of pneumonia (Venner et al. 2007, Ven- ner et al. 2007). In the context of another study during 2018, R. equi was also isolated in the tracheal aspirate of foals with pneumonia on the same farm (Hennig 2020 in print). As part of the randomised pathogen examination of tracheobronchial aspirates of foals suffering from pneumonia, 26 foals of the current study were sampled. In nine foals, R. equi was detected and in 18 foals Streptococcus equi subsp. zooepi- demicus; in the sample of one foal, both pathogens were detected.

General monitoring of the foals on the stud

Every foal was submitted to a weekly examination from birth to the age of 5.5 months, including measurement of the body temperature, evaluation of nasal discharge and mandibular lymph nodes, auscultation of trachea and lung, the white blood cell (WBC) count and a thoracic ultrasonography. The pulmonary ultrasound examination was performed by using portable equipment with a 7.5 MHz linear transducer (Esaote Tringa Linear, Milano, Italy). This involves ultrasonography of both sides of the thorax in each intercostal space and docu- mentation of pleural oriented lesions in dorsal, middle, and ventral sections of the lungs. A pulmonary abscess was de- fined as a hypoechoic area of consolidation. The diameter of all consolidations with a diameter above 0.5 cm were added to a total abscess score in cm.

Study design and inclusion criteria

The foals that were included in the study were randomly allocated to six groups. Foals, older than 4 weeks and without signs of dyspnoea, were included as soon as a moderate to severe pneumonia (n = 165) was diagnosed by sonography (Table 1). The number of foals admitted per group corre- sponds to the expected number of affected foals with the re- spective severity of pneumonia per year at the stud.

Every foal with an abscess score above 15 cm and below 20 cm was allocated to group 1 (n = 92) and was treated with rifampin (10 mg/kg PO, q 24 h) and tulathromycin (2.5 mg/kg IM, q 7 days) and was considered to have a moderate pneumonia. In the case of an abscess score ≥ 20 cm, the foals were allocated to group 2 (n = 73) and received a treatment with rifampin and azithromycin (both: 10 mg/kg PO, q 24 h) and were considered to have a severe pneumonia. The duration of therapy in each group depended on the random assignment to the subgroups 1a and 2a (2 weeks), 1b and 2b (4 weeks) or 1c and 2c (6 weeks). Due to the organisation of the stud, the treatment duration of 2 weeks ranged between

Table 1 Data from the 165 foals in the study from group 1 (moderate pneumonia) and group 2 (severe pneumonia). | Daten der 165 Fohlen in der Studie aus Gruppe 1 (mittelgradige Pneumonie) und Gruppe 2 (hochgradige Pneumonie).

group 1 group 2

total participating foals n = 92 n = 73

foals with successful treatment n = 90 n = 60

foals removed from the study n = 2 n = 13

range of abscess score at day of

diagnosis 15–19.5 cm 20–34.5 cm

median abscess score at day of diagnosis 16 cm 22.5 cm median clinical score at day of diagnosis 3 4 median age of the foals at day of

diagnosis 100 days 111 days

Table 2 Clinical score | Klinischer Score

Characteristic Findings Score

nasal discharge

normal 0

serous 1

mucous, purulent 2

body temperature

Normal (≤ 38.9°C) 0

Mildly elevated (39.0–39.4°C) 1 Highly elevated (≥ 39.5°C) 2

mandibular lymph node normal 0

enlarged 1

lung auscultation

normal 0

moderately exacerbated (raw

sounds) 1

extremely exacerbated (rattle,

rhonchus) 2

trachea auscultation

normal 0

moderately exacerbated (raw

sounds) 1

extremely exacerbated (rattle,

rhonchus) 2

maximum clinical score achievable 9

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Exclusion criteria

Foals that developed dyspnoea in the course of treatment or if clinical and sonographic findings worsened or stagnated and they required a change in treatment because of these findings or another disease, they were taken out of the study (n = 15/165). If a foal was excluded of the study due to these findings, this was considered a treatment failure and the data from these foals were processed and analysed separately until their removal from the study.

Data collection

The following clinical parameters were collected for each foal included in the study and were assigned a clinical score (Table 2): rectal temperature, nasal discharge, lymph node size and auscultation of trachea and lungs. This clinical score, the WBC count and the abscess score deter- mined by thoracic sonography, the age of the foals at day of diagnosis, the treatment duration and recurrence rates were recorded. The results of all examinations were summarised in time blocks by assigning several days to weekly segments (Figure 1). Since the foals at the stud cannot all be examined on the same day, this classification made it possible to assign every bi-weekly examinations to one of these half-weekly intervals.

Data analysis

The statistical analyses of the data were accomplished using the Statistical Analysis System for Windows SAS^®, version 9.4, by using the SAS^® Enterprise Guide^® version 7.1 Client. An error probability of P < 0.05 was assumed for the statistical tests performed in order to detect significant differences. The abscess score, the clinical score, the age of the foals at diagnosis and the WBC count of the foals were tested for normal distribution by the Shapiro-Wilk test. In consequence, the median and the percentiles (25th; 75th) in brackets were used.

Comparisons of the number of foals recovering in the planned duration of treatment with the number of foals who needed a prolongation of therapy in the different subgroups were performed using the Fisher’s exact test (reliable results even with a fewer number of observations) and binomial test (Chi- square test for specified proportions) to compare the subgroups. Furthermore, a logistic regression was used to analyse and compare the development of the categorial variables of the clinical parameters. The effect of the time after initiation of treatment on the values abscess score, clinical score and WBC count was analysed with the Friedman test (permuta- tion test) with a post hoc Sidak test for multiple pairwise comparisons. The Kruskal-Wallis test and Wilcoxon two-sample test were used to compare abscess score, clinical score and WBC count between independent groups and subgroups. To

Fig 2 Number of foals (in percent) within group 1 (moderate pneumonia, n = 90) and group 2 (severe pneumonia, n = 60) showing clinical findings during treatment (I: body temperature, II: auscultatory lung findings, III: auscultatory trachea findings, IV: mucosal-purulent nasal discharge). | Anzahl der Fohlen (in Prozent) innerhalb der Gruppe 1 (mittelgradige Pneumonie, n = 90) und der Gruppe 2 (hochgradige Pneumonie, n = 60) welche klinische Befunden während der Behandlung gezeigt haben (I: erhöhte Körpertemperatur, II: auskultatorischer Lun- genbefunde, III: auskultatorische Trachealbefunde, IV: schleimig-eitriger Nasenausfluss).

Fig. 1 Examination days of foals with pneumonia during the treatment period summarised in blocks based on weekly time. | Untersuchungs- tage von Fohlen mit Pneumonie während des Be- handlungszeitraums zusammengefasst in Blöcken basierend auf der Wochenzeit.

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determine whether there was a causality between age of the foals at diagnosis of pneumonia and response to treatment the Kruskal-Wallis variance analysis was performed.

Results

Clinical findings and WBC count during treatment

The clinical score in both groups was significantly higher (P ≤ 0.0001) on the day of diagnosis compared to the following examination at half-weekly intervals after the initiation of therapy (Figure 3B). Initially, the clinical score of foals with severe pulmonary changes was higher than the one of foals with moderate pneumonia (P = 0.004). The individual clinical findings (e.g. body temperature, nasal discharge, auscultation of trachea and lung) in both groups also decreased significantly during the first 2 weeks of therapy (P < 0.0001).

Almost all foals returned to normal clinical findings after the first 2 weeks of treatment (Figure 2). The WBC count on the day of diagnosis of pneumonia and the following 2 weeks of treatment did not differ significantly between both groups and subgroups. Regardless of severity of pneumonia, the highest counts were found 0.5 week or 1 week after the initiation of treatment (Figure 3C).

Abscess score during therapy

The abscess score at diagnosis in foals with moderate pneumonia (group 1) ranged between 15 and 19.5 cm (median 16 cm) and in foals with severe pneumonia (group 2), foals with an abscess score from 20 to 34.5 cm (median 22.5 cm).

The score in both groups decreased significantly between the day of diagnosis and 1.5 weeks of treatment (Figure 3A).

There were no differences in the change in the abscess score between the subgroups within the groups. Despite different

Table 3 Treatment duration (A: end of treatment after planned duration, without the need for prolongation, B: prolongation of 2 weeks, C: two times prolongation of 2 weeks, a total of 4 weeks prolongation) of group 1 (moderate pneumonia, n = 90) and group 2 (severe pneumonia, n = 60) (subgroups a: 2 weeks treatment, b: 4 weeks treatment, c: 6 weeks treatment). The upper number represents the frequency; the below the percentage distribution within each subgroup. | Behandlungsdauer (A: Behandlungsende nach geplanter Dauer, ohne Verlängerungsbedarf, B: Verlängerung um 2 Wochen, C:

zweimalige Verlängerung um 2 Wochen, insgesamt 4 Wochen Ver- längerung) der Untergruppen Gruppe 1 (mittelgradige Pneumonie, n

= 90) und Gruppe 2 (hochgradige Pneumonie, n = 60) (a: 2 Wochen Behandlung, b: 4 Wochen Behandlung, c: 6 Wochen Behandlung).

Die obere Zahl stellt die Häufigkeit dar, die untere die prozentuale Ver- teilung innerhalb jeder Untergruppe.

Subgroup A B C Total

1a 23 7 0 30

76.7% 23.3% 0.0%

1b 29 1 0 30

96.7% 3.3% 0.0%

1c 30 0 0 30

100.0% 0.0% 0.0%

Total group 1 82 8 0 90

91.1% 8.9% 0.0%

2a 15 5 0 20

75.0% 25.0% 0.0%

2b 19 0 1 20

95.0% 0.0% 5.0%

2c 20 0 0 20

100.0% 0.0% 0.0%

Total group 2 54 5 1 60

90.0% 8.3% 1.7%

Fig. 3 Abscess score in cm (A), clinical score (B) and white blood cell count in G/L (C) during treatment in foals (group 1, moderate pneumonia, rifampin/tulathromycin, n = 90/ group 2, severe pneumonia, rifampin/azithromycin, n = 60). Significant differences in progress of each group are marked with *. | Abszess-Score in cm (A), klinischer Score (B) und Anzahl der weißen Blutkörperchen in G/L (C) während der Behandlung bei Fohlen (Gruppe 1, mittelgradige Pneumonie, Rifampin/Tulathromycin, n = 90/ Gruppe 2, hochgradige Pneumonie, Rifampin/

Azithromycin, n = 60). Signifikante Unterschiede im Verlauf der einzelnen Gruppen sind mit * gekennzeichnet.

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treatment protocols according to the severity of the pneumonia, no difference in the development of the abscess score during the treatment period was found. (Figure 4).

Response to treatment and recurrence rates

In foals in group 1 (moderate pulmonary changes; n = 90), the consolidations detected at sonography of the lung resolved after 2 weeks of treatment in 76.7 % (n = 23/30) of foals from group 1a (duration of treatment: 2 weeks). In this subgroup, 23.3 % (n = 7/30) of the foals needed a prolonged treatment of 2 weeks to recover. In group 1b (duration of treatment: 4 weeks), 96.7 % (n = 29/30) of the foals recovered during the planned 4 weeks of treatment and in group 1c (duration of treatment: 6 weeks) 100 % (n = 30/30) of the foals recovered during the 6 weeks of treatment. There was no significant dif-

ference between the number of foals, which recovered after the planned duration of treatment in each subgroup (Table 3) in foals with moderate pneumonia (group 1), in which foals were treated with rifampin and tulathromycin. More foals of subgroup 1a needed a prolongation of treatment than in subgroups 1b and 1c (P = 0.03/P = 0.008). The treatment could have been stopped after 2 weeks of time for 73 % (n = 22/30) of the foals of group 1b, respectively, 80 % (n = 24/30) of the foals of group 1c as their sonographic findings had fully resolved by then. One foal treated for a duration of 2 weeks developed a new pneumonia 77 days after the end of the first treatment period.

The foals in group 2 (severe pulmonary changes; n = 60) were treated with rifampin and azithromycin. In subgroup 2a (duration of treatment: 2 weeks), 75 % (n = 15/20) of the foals recovered within 2 weeks of therapy, 25 % (n = 5/20)

Fig. 4 Abscess score in cm (absolute average) and abscess score in percent (relative average) of group 1 (moderate pneumonia, n

= 90) and group 2 (severe pneumonia, n = 60) in the first 2.5 weeks of treatment. | Abszess-Score in cm (absoluter Durchschnitt) und Abszess-Score in Prozent (relativer Durch- schnitt) von Gruppe 1 (mittelgradige Pneu- monie, n = 90) und Gruppe 2 (hochgradige Pneumonie, n = 60) in den ersten 2,5 Wochen der Behandlung.

Fig. 5 Abscess score during treatment in the removed foals needing a change of antimicrobial treatment (1), foals developing dyspnoea (2) and foals with an additional interstitial pneumonia (3). The average course of the foals of group 1 and 2 is included for orientation. The dotted line represents foals with hyperthermia. | Abszess-Score während der Behandlung bei den ausgeschiedenen Fohlen, die einen Wechsel der antimikrobiellen Behandlung benötigten (1), Fohlen, die Dyspnoe entwickelten (2) und Fohlen mit einer zusätzlichen interstitiellen Pneumonie (3).

Zur Orientierung ist der durchschnittliche Verlauf der Fohlen der Gruppe 1 und 2 eingezeichnet. Die gestrichelte Linie stellt Fohlen mit Hyperther- mie dar.

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needed a prolongation of 2 weeks (Table 3). In group 2b (duration of treatment: 4 weeks) 95 % (n = 19/20) of the foals recovered during the planned 4 weeks of treatment and in group 2c (duration of treatment: 6 weeks) 100 % (n = 20/20) of the foals recovered during the 6 weeks of treatment. There was no significant difference between the rates of foals recovering in their planned treatment duration (P = 0.49/0.87/0.39). The number of foals needing a prolongation of treatment was significantly lower in subgroup 2b (duration of treatment: 4 weeks) and 2c (duration of treatment: 6 weeks), as almost all foals recovered during the predetermined treatment duration (P = 0.025). One foal from group 2b needed a double prolongation. It would have been possible to end the therapy for 65 % (n = 13/20) of the foals from group 2b and 80 % (n = 16/20) of the foals from group 2c after a duration of 2 weeks as after this time, the lungs were without ultrasonographic findings. Two foals with severe pneumonia showed a relapse: one foal 24 days after a treatment of 4 weeks and the other one 79 days after a treatment of 2 weeks.

Foals removed from the study

Fifteen foals (two foals with moderate pneumonia and 13 foals with severe pneumonia) were removed from the study.

Three foals were removed after 4 to 7 days of treatment, because their abscess score increased or stagnated (Figure 5, Chart 1). Five foals were removed as they developed dyspnoea within the first three days of treatment (Figure 5, Chart 2). All these foals had fever (> 39.5 °C) up to the day of developing dyspnoea and their abscess score did not improve during the therapy. Seven foals developed an interstitial pneumonia between day 1 and day 14 after initiation of therapy (Figure 5, Chart 3).

Association between age at diagnosis and response to treatment

The age of the foals at diagnosis was evaluated in relation to their response to treatment. The foals of subgroup 1a and 2a, which needed no prolongation of therapy and all foals, who had recovered within 2 weeks of treatment were joined in group A without considering their allocation to subgroup b or c. All foals needing treatment longer than 2 weeks were allocated to group B. Foals, who were removed from the study, were allocated to group C. 165 foals were allocated into one of these groups: A (n = 112) , B (n = 38) and C (n = 15). The foals that recovered after 2 weeks of treatment were 114 days old (25th/75th: 88.5/127.5) at diagnosis, whereas the foals for which a two-week therapy was not sufficient were 102.5 days old (25th/75th: 61/121) and, therefore, significantly younger at the time of diagnosis (P = 0.004). Compared to the foals from group A and B, the foals in group C were also significantly younger again (P < 0.0001/P = 0.003) with an age of 63 days at diagnosis (25th/75th: 50/70). In summary, the older the foal was at diagnosis of pneumonia the better was the response to treatment (Figure 6; P < 0.0001).

Discussion

The shorter and tailored therapy, which can be extended individually beyond a two-week interval, allows antibiotics to be used more purposefully. The best method to minimise the further development of resistance problems arising, which have intensified in recent years (Giguère et al. 2017), especially on farms where antimicrobial mass treatment was applied after establishing screening programmes (Burton et al. 2013), is to limit the use of antimicrobial agents to individuals that really benefit from their use, to choose the adequate drugs and the proper duration of treatment (Venner et al. 2013).

The success of treatment of an abscessing bronchopneumonia due to R. equi depends on different factors: age of the foal (Ven- ner et al. 2013), severity of the initial lesions, the subclinical detection and the response to the selected antimicrobial agent (Giguère 2001). The current study included foals from a stud with well-organised monitoring and, thus, the foals with pneumonia are detected early, which might be a factor that helps reducing the treatment duration (Muscatello 2012). Furthermore, it must be emphasised that in any foal with pneumonia, treatment must be chosen with consideration of the isolation of pathogens from respiratory samples. In a breeding farm with endemic rhodococ- cosis, it is obligatory to regularly sample sick foals in order to identify the pathogens and make the adequate choice of antimicrobial drugs. The resistogram is not applicable to R. equi as an intracellular pathogen due to the lack of transferability of in vitro sensitivity to in vivo situation.

The duration of treatment required to heal pneumonia due to R. equi in foals is described between 2 and 12 weeks (Giguère 2010), but also 4 and 9 weeks (Giguère 2001) or 6 and 8 weeks (Prescott et al. 1985), where longer duration is generally chosen in order to prevent relapses. In the current study, 75 % of the foals with abscessing bronchopneumonia recovered completely after a treatment duration of 2 weeks, with no difference between foals with moderate (rifampin/

(age in days at date of diagnosis)

Fig. 6 Age (in days) of the foals at diagnosis of pneumonia in correlation with response to treatment. Group A: foals which showed no more pulmonary findings at ultrasonography after 2 weeks of treatment, group B: all foals that needed a treatment longer that 2 weeks, group C: foals that were removed from the study. | Alter (in Tagen) der Fohlen bei Diagnose der Pneumonie in Korrelation mit dem Ansprechen auf die Behandlung. Gruppe A: Fohlen, die nach 2 Wochen Behandlung keinen Befund mehr im Ultraschall zeigten, Gruppe B: alle Fohlen, die eine Behandlung länger als 2 Wochen benötigten, Gruppe C: Fohlen, die aus der Studie aus- geschieden sind.

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tulathromycin) or severe (rifampin/azithromycin) pulmonary lesions. Therapy could be stopped after the planned duration in almost all cases. However, the ultrasound examination in many foals with long therapy duration of 4 or 6 weeks showed a complete recovery of pleural lesions already after 2 weeks of treatment. The change in the abscess score during the first 2 weeks after treatment initiation shows that both antimicrobial combinations have led to a fast therapeutic success in the severity of pneumonia in which they were used. The question whether the two antibiotic protocols are similarly efficient needs to be examined in further studies.

However, the possibility of treatment failure must be considered in each case. In the current study, fewer foals needed a change of antimicrobial drugs in the moderately ill group (2.2 %) compared to the severely affected foals (17.8 %).

This might be associated to the fact that early treatment of foals with pneumonia enhances and facilitates the chances of a successful response to the therapy (Chaffin 2006). In a previous study, the response to treatment in foals with higher abscess scores was also worse than in foals with comparatively lower abscess scores (Venner et al. 2012), which further confirms the importance of severity of pulmonary lesions for assessing the response to treatment. Foals with therapy failure did not show a decrease in abscess score and frequently showed fever. Hence, the monitoring via clinical and sonographic examination during treatment, especially in the initial phase, is essential for early detection of treatment failure.

Three of 150 foals showed a relapse of pneumonia in the current study. The time up to recurrence of pneumonia was 24, 77 and 79 days, respectively; therefore, it is question- able whether it was a relapse or a new infection. The risk of reoccurrence of pneumonia that may occur if treatment is dis- continued too early (Giguère et al. 1997, Slovis et al. 2005) seems, on the base of the data of the current study, very small.

In addition to the ultrasonographic findings, clinical signs and blood parameters are used to guide the duration of treatment (Prescott et al. 1985, Muscatello et al. 2007). Moreover, foals often appear clinically healthy before the lung consolidations are resolved, as has been shown previously (Falcon et al.

1985, Slovis et al. 2005). Looking at the development of the clinical signs, the abnormal findings quickly regressed within the first 2 weeks of therapy, but the severity of pneumonia is not necessarily correlated with clinical signs as was shown before (Falcon et al. 1985, Slovis et al. 2005). Consequently, the clinical findings alone cannot reliably help to answer the question of the appropriate duration of treatment. The WBC count was recommended in a previous study on diagnostics and early detection (Giguère et al. 2003). On the other hand, the current results suggest that the WBC count, as it does not correlate to the abscess score, is not a reliable parameter for the assessment of response to treatment in cases of pneumonia in foals.

Furthermore, the age of the foals at the time of diagnosis might influence the duration of treatment and the risk of treatment failure. The current data show that the foals who recovered after 2 weeks of treatment were significantly older than those, which required more than 2 weeks of therapy. All foals

with treatment failure were significantly younger at the time of diagnosis than the foals who responded well to therapy.

This suggests that older foals are more likely to clear infection more effectively during treatment, as has been observed before in an experimentally induced R. equi pneumonia in which spontaneous resolution was more likely in older foals than in neonates (Martens et al. 1989, Venner et al. 2012).

Therefore, the course of therapy in very young foals should be monitored very precisely in order to detect a possible treatment failure.

Conclusions

The results of the current study show that a duration of treatment of 2 weeks of foals with bronchopneumonia with moderate pulmonary changes (treated with tulathromycin/rifampin) and severe pulmonary changes (treated with azithromycin/

rifampin) leads to a complete recovery in 75 % of the cases.

In addition, there is no increased risk of recurrence in the current approach. As the foals affected in this study are pa- tients in which diagnosis was made early due to a monitoring programme of the stud, care should be taken in extending those statements on the length of time required in cases of severe and later diagnosed pneumonia. Nonetheless, the response to treatment should be monitored by ultrasonography of the lung, especially in the first week after initiation of therapy to detect cases of treatment failure. The younger a foal becomes ill, the more likely it will require more than 2 weeks of therapy or even the treatment will fail. Decision to stop the treatment should include clinical and sonographic findings of the lung. This approach describes an individually tailored treatment that supports the efforts of using antimicro- bials only as long as necessary for a successful treatment of pneumonia in foals.

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Erweiterte Zusammenfassung

Abszedierende Bronchopneumonie beim Fohlen – Die angemessene Behandlungsdauer und deren Ermittlung

Die abszedierende Bronchopneumonie ist eine häufige und bedeutende Erkrankung von Fohlen in Zuchtbetrieben. Rhodococcus equi und Streptococcus equi ssp. zooepidemicus sind häufige bakterielle Erreger für Pneumonien bei Fohlen im Alter von 3 Wochen bis 5 Monaten.

Eine Behandlungsdauer von 4 Wochen und mehr ist bei der antimikrobiellen Therapie dieser Fohlen auf vielen Betrieben empirische Praxis. Als Parameter für die Entscheidung über die Behandlungsdauer werden u. a. die Entwicklung der klinischen Befunde und der sonographisch dar- stellbaren Läsionen der Lunge und das Plasmafibrinogen herangezogen. Die Vorschläge in der Literatur für eine erfolgreiche Therapie variieren von 2–12 Wochen, bis 4–9 Wochen oder 6–8 Wochen, abhängig vom Schweregrad der anfänglichen Läsionen und dem Ansprechen auf die Behandlung. Ein zu frühes Beenden der Behandlung birgt dabei das Risiko von Rezidiven.

Ziel der vorliegenden Studie war es, zu analysieren, ob eine Behandlungsdauer von 2 Wochen bei abszedierender Bronchopneumonie bei Fohlen auf einem Gestüt mit endemischer Problematik ausreicht, um einen stabilen Behandlungserfolg ohne erhöhte Rezidivrate zu erzielen.

Fohlen, die älter als 4 Wochen waren und keine Anzeichen von Dyspnoe aufwiesen, wurden in die prospektive, randomisierte Blindstudie aufgenommen, sobald eine mittelgradige bis hochgradige Pneumonie (n = 165) sonographisch diagnostiziert wurde (Tabelle 1). Am Tag der Diagnose wurden klinische Befunde (Körpertemperatur, Auskultation von Trachea und Lunge, Nasenausfluss, Mandibular-Lymphknoten) (Ta- belle 2) und die Befunde einer Ultraschalluntersuchung des Thorax dokumentiert (Konsolidierungen des pleuranahen Lungengewebes wurden in einem Abszess-Score in cm eingeteilt) und es wurde eine Blutprobe entnommen, um die Leukozytenzahl zu bestimmten. Wenn die Fohlen im Verlauf der Behandlung eine Dyspnoe entwickelten oder sich die klinischen und sonographischen Befunde verschlechterten oder stagnierten und sie aufgrund dessen oder einer anderen Erkrankung einen Behandlungswechsel benötigten, wurden sie aus der Studie ausgeschlossen.

Wurde ein Fohlen aufgrund dieser Befunde aus der Studie ausgeschlossen, wurde dies als Therapieversagen gewertet und die Daten dieser Fohlen wurden bis zu ihrem Ausscheiden aus der Studie verarbeitet und gesondert analysiert. Fohlen mit einem Abszess-Score von 15 bis 19,5 cm (mittelgradige Pneumonie) bei der Sonographie des Thorax wurden in Gruppe 1 (n = 92, Behandlung: Rifampin 10 mg/kg p.o.

1 × täglich/Tulathromycin 2,5 mg/kg i.m., 1× wöchentlich) zusammengefasst. Bei einem Abszess-Score ≥ 20 cm (hochgradige Pneumonie) wurden die Fohlen der Gruppe 2 (n = 73, Behandlung: Rifampin/Azithromycin jeweils 10 mg/kg p.o.,1× täglich) zugeordnet. Die Therapie- dauer in jeder Gruppe war abhängig von der randomisierten Zuordnung in die Untergruppen 1a und 2a (2 Wochen), 1b und 2b (4 Wochen) oder 1c und 2c (6 Wochen). Bei den Fohlen wurde einmal wöchentlich eine klinische Untersuchung und zweimal wöchentlich eine Leukozyten- Zählung und eine Ultraschalluntersuchung der Lunge durchgeführt. Die klinischen Symptome (zusammengefasst im klinischen Score) haben sich in den ersten zwei Wochen der Behandlung fast vollständig zurückgebildet (Abbildung 3B). Bei Diagnosestellung war der klinische Score der Fohlen mit hochgradiger Pneumonie höher als der der Fohlen mit mittelgradiger Pneumonie (P = 0,004). Auch die einzelnen klinischen Befunde (Körpertemperatur, Nasenausfluss, Auskultation von Trachea und Lunge) nahmen in beiden Gruppen in den ersten 2 Wochen der Behandlung signifikant ab (P < 0,0001) (Abbildung 2). Die Leukozyten-Zahl dagegen war nicht hilfreich bei der Beurteilung des Verlaufs der Lungenentzündung (Abbildung 3C). Der Abszess-Score bei der Diagnose lag bei Fohlen mit mittelgradiger Pneumonie (Gruppe 1) zwischen

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15 und 19,5 cm und bei Fohlen mit hochgradiger Pneumonie (Gruppe 2) im Bereich zwischen 20 und 34,5 cm. In beiden Gruppen stellte sich dieser Score nach der Diagnose der Pneumonie im Verlauf und den ersten 1,5 Wochen der Behandlung signifikant rückläufig dar (Abbildung 3A). Trotz unterschiedlicher Behandlungsprotokolle (je nach Schweregrad der Pneumonie) wurde kein Unterschied in der Entwicklung des Abszess-Scores während des Behandlungszeitraums festgestellt. (Abbildung 4).

Bei Fohlen der Gruppe 1 (mittelgradiger Pneumonie, n = 90) bildeten sich die bei der Ultraschalluntersuchung der Lunge festgestellten Kon- solidierungen bei 76,7 % (n = 23/30) der Fohlen aus Gruppe 1a zurück (Behandlungsdauer: 2 Wochen). In dieser Untergruppe benötigten 23,3 % (n = 7/30) der Fohlen eine um weitere 2 Wochen verlängerte Behandlung, um sich zu erholen. In Gruppe 1b (Behandlungsdauer:

4 Wochen) erholten sich 96,7 % (n = 29/30) der Fohlen und in Gruppe 1c (Behandlungsdauer: 6 Wochen) erholten sich 100 % (n = 30/30) der Fohlen. Es gab keinen signifikanten Unterschied in den Untergruppen zwischen der Anzahl der in geplanter Behandlungsdauer gene- senen Fohlen (Tabelle 3). Eine Therapieverlängerung benötigten in der Untergruppe 1a mehr Fohlen als in den Untergruppen 1b und 1c (P = 0,03/P = 0,008). Bei 73 % (n = 22/30) der Fohlen der Gruppe 1b bzw. 80 % (n = 24/30) der Fohlen der Gruppe 1c hätte die Behand- lung nach 2 Wochen beendet werden können, da sich ihre sonographischen Befunde bis dahin bereits vollständig zurückgebildet hatten. Ein einziges Fohlen aus der Gruppe 1a entwickelte 77 Tage nach Ende des ersten Behandlungserfolgs eine erneute Pneumonie. In der Gruppe 2 (hochgradige Pneumonie, n = 60) erholten sich 75 % (n = 15/20) der Fohlen aus der Untergruppe 2a (Behandlungsdauer: 2 Wochen);

25 % (n = 5/20) benötigten eine Verlängerung von 2 Wochen (Tabelle 3). In Gruppe 2b (Behandlungsdauer: 4 Wochen) erholten sich 95 % (n = 19/20) der Fohlen und in Gruppe 2c (Behandlungsdauer: 6 Wochen) erholten sich 100 % (n = 20/20) der Fohlen innerhalb der geplanten Behandlungszeit. Es gab keinen signifikanten Unterschied zwischen der Anzahl der Fohlen, die sich innerhalb der geplanten Behandlungsdauer erholten (P = 0,49/0,87/0,39). Die Anzahl der Fohlen, die eine Verlängerung der Behandlung benötigten, war in den Untergruppen 2b (Be- handlungsdauer: 4 Wochen) und 2c (Behandlungsdauer: 6 Wochen) signifikant geringer, da sich fast alle Fohlen innerhalb der vorgegebenen Behandlungsdauer erholten (P = 0,025). Bei 65 % (n = 13/20) der Fohlen aus Gruppe 2b und 80 % (n = 16/20) der Fohlen aus Gruppe 2c hätte die Therapie nach einer Dauer von 2 Wochen beendet werden können, da die ultrasonographische Untersuchung der Lungen zu diesem Zeitpunkt ohne besonderen Befund war. Zwei Fohlen der Gruppe 2 zeigten eine erneute Pneumonie: ein Fohlen 24 Tage nach Beendigung einer 4-wöchigen Behandlung und das andere 79 Tage nach Beendigung einer 2-wöchigen Behandlung. Fünfzehn Fohlen (zwei Fohlen mit mittelgradiger Pneumonie und 13 Fohlen mit hochgradiger Pneumonie) schieden aus der Studie aus. Drei dieser Fohlen schieden aus, da der Abszess-Score nach 4 bis 7 Tagen der Behandlung weiter anstieg oder stagnierte (Abbildung 5, Grafik 1). Fünf Fohlen schieden aus, da sie innerhalb der ersten drei Tage der Behandlung Dyspnoe entwickelten (Abbildung 5, Grafik 2). Sieben Fohlen entwickelten eine zusätzliche interstitielle Pneumonie zwischen Tag 1 und Tag 14 nach Beginn der Therapie (Abbildung 5, Grafik 3) und schieden aus diesem Grund aus der Studie aus. Desweiteren wurde der Einfluss des Alters der Fohlen bei der Diagnose in Hinblick auf ihr Ansprechen auf die Behandlung ausgewertet. Die Fohlen der Untergruppe 1a und 2a, die keine Verlängerung der Therapie benötigten, und alle Fohlen, die sich innerhalb von 2 Wochen nach der Behandlung erholt hatten, wurden in der Gruppe A zusammengefasst, ohne Berücksichtigung ihrer Zuordnung zu Untergruppe b oder c. Alle Fohlen, die eine Behandlung länger als 2 Wochen benötigten, wurden der Gruppe B zugeordnet. Fohlen, die aus der Studie entfernt wurden, wurden der Gruppe C zugeteilt. Alle 165 Fohlen wurden demnach in eine dieser Gruppen eingeteilt: A (n = 112), B (n = 38) und C (n = 15). Die Fohlen, die sich nach zweiwöchiger Behandlung erholten, waren bei der Diagnose 114 Tage alt (1. und 3.

Quartil: 88,5/127,5), während die Fohlen, für die eine zweiwöchige Therapie nicht ausreichte, 102,5 Tage alt (1. und 3. Quartil: 61/121) und damit zum Zeitpunkt der Diagnose signifikant jünger waren (P = 0,004). Im Vergleich zu den Fohlen aus den Gruppen A und B waren die Fohlen der Gruppe C mit einem Alter von 63 Tagen bei der Diagnose (1. und 3. Quartil: 50/70) ebenfalls wieder signifikant jünger (P < 0,0001/P = 0,003). Zusammenfassend lässt sich also sagen, je älter das Fohlen bei der Diagnose der Pneumonie war, desto besser war das Ansprechen auf die Behandlung (Abbildung 6; P < 0,0001).

Die Ergebnisse der aktuellen Studie zeigen, dass eine Behandlungsdauer von 2 Wochen bei Fohlen mit Bronchopneumonie mit mittelgradiger Pneumonie (behandelt mit Rifampin/Tulathromycin) und hochgradiger Pneumonie (behandelt mit Rifampin/Azithromycin) in 75 % der Fälle zu einer vollständigen Abheilung der Läsionen führt. Dabei besteht kein erhöhtes Rezidivrisiko. Da es sich bei den betroffenen Fohlen in dieser Studie um Patienten handelt, bei denen die Diagnose aufgrund eines Screening-Programms des Gestüts frühzeitig gestellt wurde, sind die Aus- sagen über die Dauer der Behandlung bei schwereren und später diagnostizierten Pneumonien mit Vorsicht zu treffen. Nichtsdestotrotz sollte das Ansprechen auf die Behandlung durch eine Ultraschalluntersuchung der Lunge überwacht werden, insbesondere in der ersten Woche nach Beginn der Behandlung, um mögliche Fälle von Therapieversagen frühzeitig zu erkennen. Je jünger ein Fohlen erkrankt, desto wahrscheinli- cher ist es, dass es mehr als 2 Wochen Therapie benötigt oder es zu einem Therapieversagen kommen kann. Die Entscheidung zur Beendigung der Behandlung sollte sich auf die klinischen und sonographischen Befunde der Lunge stützen. Insgesamt sollte die Behandlung individuell auf den Patienten abgestimmt sein, sodass antimikrobielle Mittel nur so lange eingesetzt werden, wie es für eine erfolgreiche Behandlung der Pneumonie bei Fohlen notwendig ist und ein unnötig langer Einsatz von Antibiotika vermieden wird.

Schlüsselwörter: Fohlen, Pneumonie, Behandlungsdauer, ultrasonographische Untersuchung

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15

Kinetics of serum amyloid A during the treatment period of foals with pneumonia

Pferdeheilkunde – Equine Medicine 37 (2021) 2 (March/April) 128-135

Anna Lankenfeld¹ , Corinna Weber² , Karl Rohn³ and Monica Venner⁴

2 LABOKLIN GmbH&Co.KG, Bad Kissingen, Germany

3 Department of Biometry and Epidemiology, University of Veterinary Medicine

1 Hanover, Hanover, Germany

4 Equine Clinic Destedt, Germany

Correspondence and requests should be addressed to:

PD Dr. Monica Venner, PhD., Dipl. ECEIM, FEI-Tierärztin, Pferdeklinik Destedt GmbH, Trift 4 38162 Destedt

Germany E-Mail: mvenner@gmx.de