Tierärztliche Hochschule Hannover Untersuchung zur angemessenen Behandlungsdauer bei Fohlen mit abszedierender Bronchopneumonie und Kinetik des ...
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Tierärztliche Hochschule Hannover 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
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
Meiner Familie
Inhaltsverzeichnis 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
1. Einleitung 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). 1
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, 2
um zu evaluieren, ob SAA ein nützlicher Parameter ist, um die individuelle Dauer der Behandlung von abszedierenden Pneumonien zu beurteilen. 3
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 4
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 duration; Ultrasonographic examination 5
Abscessing bronchopneumonia in foals – The adequate treatment period and its determination A. Lankenfeld et al. Pferdeheilkunde – Equine Medicine 37 (2021) 4 (July/August) 1–9 DOI 10.21836/PEMLankenfeld Abscessing bronchopneumonia in foals – The adequate treatment period and its determination 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 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 bronchopneu- monia 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 Introduction Parameters used to guide the decision on the duration of treatment include the resolution of clinical findings (Prescott Abscessing bronchopneumonia is a frequent and significant et al. 1985), resolution of abnormalities detected by thoracic disease of foals on breeding farms. Rhodococcus equi (R. findings at sonography of the thorax and plasma fibrinogen equi) and Streptococcus equi subsp. zooepidemicus are of- (Giguère 2010). The suggestions in literature for successful ten the bacteria responsible for pulmonary disorders in foals therapy vary between 2–12 weeks (Giguère 2010), to 4–9 between 3 weeks and 5 months of age and induce similar weeks (Giguère 2001) and 6–8 weeks (Prescott et al. 1985) clinical findings (Hoffmann et al. 1993, Lavoie et al. 1994). depending on the severity of the initial lesions and the re- sponse to therapy. Monitoring of the sick foals including ultra- The use of a macrolide antibiotic in combination with rifampin sonographic, haematological and clinical examinations can for the treatment of R. equi pneumonia is well validated. In help to reduce the number of affected foals treated without recent years, newer-generation macrolides, such as azithro- increasing the foals losses (Cohen et al. 2002, Muscatello et mycin and clarithromycin (Giguère et al. 2004), as well as al. 2007, Arnold-Lehna et al. 2019). However, there are some tulathromycin (Venner et al. 2007, Rutenberg et al. 2017), concerns that a too early discontinuation of the therapy may have replaced erythromycin in combination with rifampin. Re- lead to relapses (Giguère et al. 1997). cent evidence suggests that the resistance to macrolides and rifampin in R. equi isolates is increasing (Giguère et al. 2017), The objective of the present study was to analyse whether which raises the question how antibiotics can be used in a a treatment duration of 2 weeks is sufficient for a complete more targeted way, including the tailored choice of the drugs recovery without relapses on a farm with endemic broncho- and the appropriate duration of treatment. pneumonia in foals. Pferdeheilkunde – Equine Medicine 37 (2021) 1 6
Abscessing bronchopneumonia in foals – The adequate treatment period and its determination A. Lankenfeld et al. Materials and methods 13 and 19 days, the four-week period varied between 27 and 33 days and the six-week period between 41 and 47 days. Study population The examining vets were not aware of the foal’s allocation to the groups. The study was a prospective, randomised and blinded clinical trial during the 2018 breeding season on a Warmblood stud. In participating foals, clinical examination was done once The stud has a history of foal pneumonia due to R. equi. weekly. Twice weekly, the WBC were counted and the diam- Multiple former studies performed at the stud showed that R. eter of lung lesions measured at ultrasonographical exam- equi was isolated from tracheobronchial aspirates of 39 % ination of the lung. Antibiotic therapy was ended, if no more (n = 17/44) to 54 % (n = 118/217) of the foals with ultraso- consolidations were seen at the sonography of the lung. Oth- nographic evidence of pneumonia (Venner et al. 2007, Ven- erwise, the treatment was extended for 14 days. After ending ner et al. 2007). In the context of another study during 2018, the treatment, the examinations were continued once a week R. equi was also isolated in the tracheal aspirate of foals with up to the age of five and a half months. pneumonia on the same farm (Hennig 2020 in print). As part of the randomised pathogen examination of tracheobronchi- al aspirates of foals suffering from pneumonia, 26 foals of Table 1 Data from the 165 foals in the study from group 1 (mo- derate pneumonia) and group 2 (severe pneumonia). | Daten der the current study were sampled. In nine foals, R. equi was 165 Fohlen in der Studie aus Gruppe 1 (mittelgradige Pneumonie) und detected and in 18 foals Streptococcus equi subsp. zooepi- Gruppe 2 (hochgradige Pneumonie). demicus; in the sample of one foal, both pathogens were detected. group 1 group 2 total participating foals n = 92 n = 73 General monitoring of the foals on the stud foals with successful treatment n = 90 n = 60 foals removed from the study n=2 n = 13 Every foal was submitted to a weekly examination from birth to the age of 5.5 months, including measurement of the body range of abscess score at day of 15–19.5 cm 20–34.5 cm diagnosis temperature, evaluation of nasal discharge and mandibular lymph nodes, auscultation of trachea and lung, the white median abscess score at day of diagnosis 16 cm 22.5 cm blood cell (WBC) count and a thoracic ultrasonography. The median clinical score at day of diagnosis 3 4 pulmonary ultrasound examination was performed by using portable equipment with a 7.5 MHz linear transducer (Esaote median age of the foals at day of 100 days 111 days Tringa Linear, Milano, Italy). This involves ultrasonography of diagnosis 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- Table 2 Clinical score | Klinischer Score fined as a hypoechoic area of consolidation. The diameter of Characteristic Findings Score all consolidations with a diameter above 0.5 cm were added to a total abscess score in cm. normal 0 nasal discharge serous 1 Study design and inclusion criteria mucous, purulent 2 Normal (≤ 38.9°C) 0 The foals that were included in the study were randomly al- located to six groups. Foals, older than 4 weeks and without body temperature Mildly elevated (39.0–39.4°C) 1 signs of dyspnoea, were included as soon as a moderate to Highly elevated (≥ 39.5°C) 2 severe pneumonia (n = 165) was diagnosed by sonography (Table 1). The number of foals admitted per group corre- normal 0 mandibular lymph node sponds to the expected number of affected foals with the re- enlarged 1 spective severity of pneumonia per year at the stud. normal 0 Every foal with an abscess score above 15 cm and below moderately exacerbated (raw 1 20 cm was allocated to group 1 (n = 92) and was treated with lung auscultation sounds) rifampin (10 mg/kg PO, q 24 h) and tulathromycin (2.5 mg/kg extremely exacerbated (rattle, IM, q 7 days) and was considered to have a moderate pneu- 2 rhonchus) monia. In the case of an abscess score ≥ 20 cm, the foals normal 0 were allocated to group 2 (n = 73) and received a treatment with rifampin and azithromycin (both: 10 mg/kg PO, q 24 h) moderately exacerbated (raw 1 and were considered to have a severe pneumonia. The du- trachea auscultation sounds) ration of therapy in each group depended on the random extremely exacerbated (rattle, assignment to the subgroups 1a and 2a (2 weeks), 1b and 2b 2 rhonchus) (4 weeks) or 1c and 2c (6 weeks). Due to the organisation of maximum clinical score achievable 9 the stud, the treatment duration of 2 weeks ranged between 2 Pferdeheilkunde – Equine Medicine 37 (2021)
Abscessing bronchopneumonia in foals – The adequate treatment period and its determination A. Lankenfeld et al. Exclusion criteria Data analysis Foals that developed dyspnoea in the course of treatment or The statistical analyses of the data were accomplished using if clinical and sonographic findings worsened or stagnated the Statistical Analysis System for Windows SAS®, version 9.4, and they required a change in treatment because of these by using the SAS® Enterprise Guide® version 7.1 Client. An findings or another disease, they were taken out of the study error probability of P < 0.05 was assumed for the statistical (n = 15/165). If a foal was excluded of the study due to these tests performed in order to detect significant differences. The findings, this was considered a treatment failure and the data abscess score, the clinical score, the age of the foals at diag- from these foals were processed and analysed separately until nosis and the WBC count of the foals were tested for normal their removal from the study. distribution by the Shapiro-Wilk test. In consequence, the me- dian and the percentiles (25th; 75th) in brackets were used. Data collection Comparisons of the number of foals recovering in the planned duration of treatment with the number of foals who need- The following clinical parameters were collected for each ed a prolongation of therapy in the different subgroups were foal included in the study and were assigned a clinical performed using the Fisher’s exact test (reliable results even score (Table 2): rectal temperature, nasal discharge, lymph with a fewer number of observations) and binomial test (Chi- node size and auscultation of trachea and lungs. This clin- square test for specified proportions) to compare the sub- ical score, the WBC count and the abscess score deter- groups. Furthermore, a logistic regression was used to anal- mined by thoracic sonography, the age of the foals at day yse and compare the development of the categorial variables of diagnosis, the treatment duration and recurrence rates of the clinical parameters. The effect of the time after initiation were recorded. The results of all examinations were sum- of treatment on the values abscess score, clinical score and marised in time blocks by assigning several days to weekly WBC count was analysed with the Friedman test (permuta- segments (Figure 1). Since the foals at the stud cannot all tion test) with a post hoc Sidak test for multiple pairwise com- be examined on the same day, this classification made it parisons. The Kruskal-Wallis test and Wilcoxon two-sample possible to assign every bi-weekly examinations to one of test were used to compare abscess score, clinical score and these half-weekly intervals. WBC count between independent groups and subgroups. To Fig. 1 Examination days of foals with pneu- monia 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. Fig 2 Number of foals (in percent) within group 1 (moderate pneumonia, n = 90) and group 2 (severe pneumonia, n = 60) showing clin- ical 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). Pferdeheilkunde – Equine Medicine 37 (2021) 3
Abscessing bronchopneumonia in foals – The adequate treatment period and its determination A. Lankenfeld et al. determine whether there was a causality between age of the Table 3 Treatment duration (A: end of treatment after planned foals at diagnosis of pneumonia and response to treatment duration, without the need for prolongation, B: prolongation of 2 the Kruskal-Wallis variance analysis was performed. weeks, C: two times prolongation of 2 weeks, a total of 4 weeks pro- longation) 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 Results the frequency; the below the percentage distribution within each sub- group. | Behandlungsdauer (A: Behandlungsende nach geplanter Clinical findings and WBC count during treatment 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 The clinical score in both groups was significantly higher = 90) und Gruppe 2 (hochgradige Pneumonie, n = 60) (a: 2 Wochen (P ≤ 0.0001) on the day of diagnosis compared to the fol- Behandlung, b: 4 Wochen Behandlung, c: 6 Wochen Behandlung). lowing examination at half-weekly intervals after the initiation Die obere Zahl stellt die Häufigkeit dar, die untere die prozentuale Ver- of therapy (Figure 3B). Initially, the clinical score of foals with teilung innerhalb jeder Untergruppe. severe pulmonary changes was higher than the one of foals Subgroup A B C Total with moderate pneumonia (P = 0.004). The individual clin- ical findings (e.g. body temperature, nasal discharge, aus- 1a 23 7 0 30 cultation of trachea and lung) in both groups also decreased 76.7% 23.3% 0.0% significantly during the first 2 weeks of therapy (P < 0.0001). 1b 29 1 0 30 Almost all foals returned to normal clinical findings after the first 2 weeks of treatment (Figure 2). The WBC count on the 96.7% 3.3% 0.0% day of diagnosis of pneumonia and the following 2 weeks of 1c 30 0 0 30 treatment did not differ significantly between both groups and 100.0% 0.0% 0.0% subgroups. Regardless of severity of pneumonia, the highest counts were found 0.5 week or 1 week after the initiation of Total group 1 82 8 0 90 treatment (Figure 3C). 91.1% 8.9% 0.0% 2a 15 5 0 20 Abscess score during therapy 75.0% 25.0% 0.0% 2b 19 0 1 20 The abscess score at diagnosis in foals with moderate pneu- monia (group 1) ranged between 15 and 19.5 cm (median 95.0% 0.0% 5.0% 16 cm) and in foals with severe pneumonia (group 2), foals 2c 20 0 0 20 with an abscess score from 20 to 34.5 cm (median 22.5 cm). The score in both groups decreased significantly between 100.0% 0.0% 0.0% the day of diagnosis and 1.5 weeks of treatment (Figure 3A). Total group 2 54 5 1 60 There were no differences in the change in the abscess score 90.0% 8.3% 1.7% between the subgroups within the groups. Despite different 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 pneu- monia, 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. 4 Pferdeheilkunde – Equine Medicine 37 (2021)
Abscessing bronchopneumonia in foals – The adequate treatment period and its determination A. Lankenfeld et al. treatment protocols according to the severity of the pneumo- ference between the number of foals, which recovered after nia, no difference in the development of the abscess score the planned duration of treatment in each subgroup (Table 3) during the treatment period was found. (Figure 4). 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 sub- Response to treatment and recurrence rates groups 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) In foals in group 1 (moderate pulmonary changes; n = 90), of the foals of group 1b, respectively, 80 % (n = 24/30) of the consolidations detected at sonography of the lung resolved the foals of group 1c as their sonographic findings had fully after 2 weeks of treatment in 76.7 % (n = 23/30) of foals from resolved by then. One foal treated for a duration of 2 weeks group 1a (duration of treatment: 2 weeks). In this subgroup, developed a new pneumonia 77 days after the end of the first 23.3 % (n = 7/30) of the foals needed a prolonged treatment treatment period. of 2 weeks to recover. In group 1b (duration of treatment: 4 weeks), 96.7 % (n = 29/30) of the foals recovered during the The foals in group 2 (severe pulmonary changes; n = 60) planned 4 weeks of treatment and in group 1c (duration of were treated with rifampin and azithromycin. In subgroup treatment: 6 weeks) 100 % (n = 30/30) of the foals recovered 2a (duration of treatment: 2 weeks), 75 % (n = 15/20) of the during the 6 weeks of treatment. There was no significant dif- foals recovered within 2 weeks of therapy, 25 % (n = 5/20) Fig. 4 Abscess score in cm (absolute av- erage) 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. Pferdeheilkunde – Equine Medicine 37 (2021) 5
Abscessing bronchopneumonia in foals – The adequate treatment period and its determination A. Lankenfeld et al. needed a prolongation of 2 weeks (Table 3). In group 2b Association between age at diagnosis and response to (duration of treatment: 4 weeks) 95 % (n = 19/20) of the treatment foals recovered during the planned 4 weeks of treatment and in group 2c (duration of treatment: 6 weeks) 100 % The age of the foals at diagnosis was evaluated in relation (n = 20/20) of the foals recovered during the 6 weeks of to their response to treatment. The foals of subgroup 1a and treatment. There was no significant difference between the 2a, which needed no prolongation of therapy and all foals, rates of foals recovering in their planned treatment duration who had recovered within 2 weeks of treatment were joined (P = 0.49/0.87/0.39). The number of foals needing a pro- in group A without considering their allocation to subgroup b longation of treatment was significantly lower in subgroup or c. All foals needing treatment longer than 2 weeks were al- 2b (duration of treatment: 4 weeks) and 2c (duration of located to group B. Foals, who were removed from the study, treatment: 6 weeks), as almost all foals recovered during were allocated to group C. 165 foals were allocated into one the predetermined treatment duration (P = 0.025). One of these groups: A (n = 112) , B (n = 38) and C (n = 15). The foal from group 2b needed a double prolongation. It would foals that recovered after 2 weeks of treatment were 114 days have been possible to end the therapy for 65 % (n = 13/20) old (25th/75th: 88.5/127.5) at diagnosis, whereas the foals of the foals from group 2b and 80 % (n = 16/20) of the for which a two-week therapy was not sufficient were 102.5 foals from group 2c after a duration of 2 weeks as after this days old (25th/75th: 61/121) and, therefore, significantly time, the lungs were without ultrasonographic findings. Two younger at the time of diagnosis (P = 0.004). Compared to foals with severe pneumonia showed a relapse: one foal 24 the foals from group A and B, the foals in group C were also days after a treatment of 4 weeks and the other one 79 days significantly younger again (P < 0.0001/P = 0.003) with an after a treatment of 2 weeks. 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). Foals removed from the study Fifteen foals (two foals with moderate pneumonia and 13 Discussion foals with severe pneumonia) were removed from the study. Three foals were removed after 4 to 7 days of treatment, be- The shorter and tailored therapy, which can be extended indi- cause their abscess score increased or stagnated (Figure 5, vidually beyond a two-week interval, allows antibiotics to be Chart 1). Five foals were removed as they developed dys- used more purposefully. The best method to minimise the fur- pnoea within the first three days of treatment (Figure 5, Chart ther development of resistance problems arising, which have 2). All these foals had fever (> 39.5 °C) up to the day of de- intensified in recent years (Giguère et al. 2017), especially on veloping dyspnoea and their abscess score did not improve farms where antimicrobial mass treatment was applied after during the therapy. Seven foals developed an interstitial pneu- establishing screening programmes (Burton et al. 2013), is to monia between day 1 and day 14 after initiation of therapy limit the use of antimicrobial agents to individuals that really (Figure 5, Chart 3). 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 (age in days at date of diagnosis) (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 antimi- crobial drugs. The resistogram is not applicable to R. equi as an intracellular pathogen due to the lack of transferability of in vitro Fig. 6 Age (in days) of the foals at diagnosis of pneumonia in sensitivity to in vivo situation. correlation with response to treatment. Group A: foals which showed no more pulmonary findings at ultrasonography after 2 weeks of The duration of treatment required to heal pneumonia due treatment, group B: all foals that needed a treatment longer that 2 to R. equi in foals is described between 2 and 12 weeks weeks, group C: foals that were removed from the study. | Alter (Giguère 2010), but also 4 and 9 weeks (Giguère 2001) or (in Tagen) der Fohlen bei Diagnose der Pneumonie in Korrelation mit dem Ansprechen auf die Behandlung. Gruppe A: Fohlen, die 6 and 8 weeks (Prescott et al. 1985), where longer duration nach 2 Wochen Behandlung keinen Befund mehr im Ultraschall is generally chosen in order to prevent relapses. In the current zeigten, Gruppe B: alle Fohlen, die eine Behandlung länger als 2 study, 75 % of the foals with abscessing bronchopneumonia Wochen benötigten, Gruppe C: Fohlen, die aus der Studie aus- recovered completely after a treatment duration of 2 weeks, geschieden sind. with no difference between foals with moderate (rifampin/ 6 Pferdeheilkunde – Equine Medicine 37 (2021)
Abscessing bronchopneumonia in foals – The adequate treatment period and its determination A. Lankenfeld et al. tulathromycin) or severe (rifampin/azithromycin) pulmonary with treatment failure were significantly younger at the time lesions. Therapy could be stopped after the planned duration of diagnosis than the foals who responded well to therapy. in almost all cases. However, the ultrasound examination in This suggests that older foals are more likely to clear infec- many foals with long therapy duration of 4 or 6 weeks showed tion more effectively during treatment, as has been observed a complete recovery of pleural lesions already after 2 weeks before in an experimentally induced R. equi pneumonia in of treatment. The change in the abscess score during the first which spontaneous resolution was more likely in older foals 2 weeks after treatment initiation shows that both antimicro- than in neonates (Martens et al. 1989, Venner et al. 2012). bial combinations have led to a fast therapeutic success in Therefore, the course of therapy in very young foals should be the severity of pneumonia in which they were used. The ques- monitored very precisely in order to detect a possible treat- tion whether the two antibiotic protocols are similarly efficient ment failure. needs to be examined in further studies. However, the possibility of treatment failure must be consid- Conclusions ered in each case. In the current study, fewer foals needed a change of antimicrobial drugs in the moderately ill group The results of the current study show that a duration of treat- (2.2 %) compared to the severely affected foals (17.8 %). ment of 2 weeks of foals with bronchopneumonia with mod- This might be associated to the fact that early treatment of erate pulmonary changes (treated with tulathromycin/rifamp- foals with pneumonia enhances and facilitates the chances in) and severe pulmonary changes (treated with azithromycin/ of a successful response to the therapy (Chaffin 2006). In rifampin) leads to a complete recovery in 75 % of the cases. a previous study, the response to treatment in foals with In addition, there is no increased risk of recurrence in the higher abscess scores was also worse than in foals with current approach. As the foals affected in this study are pa- comparatively lower abscess scores (Venner et al. 2012), tients in which diagnosis was made early due to a monitoring which further confirms the importance of severity of pulmo- programme of the stud, care should be taken in extending nary lesions for assessing the response to treatment. Foals those statements on the length of time required in cases of with therapy failure did not show a decrease in abscess severe and later diagnosed pneumonia. Nonetheless, the score and frequently showed fever. Hence, the monitoring response to treatment should be monitored by ultrasono- via clinical and sonographic examination during treatment, graphy of the lung, especially in the first week after initiation especially in the initial phase, is essential for early detection of therapy to detect cases of treatment failure. The younger of treatment failure. a foal becomes ill, the more likely it will require more than 2 weeks of therapy or even the treatment will fail. Decision to Three of 150 foals showed a relapse of pneumonia in the stop the treatment should include clinical and sonographic current study. The time up to recurrence of pneumonia was findings of the lung. This approach describes an individually 24, 77 and 79 days, respectively; therefore, it is question- tailored treatment that supports the efforts of using antimicro- able whether it was a relapse or a new infection. The risk of bials only as long as necessary for a successful treatment of reoccurrence of pneumonia that may occur if treatment is dis- pneumonia in foals. continued too early (Giguère et al. 1997, Slovis et al. 2005) seems, on the base of the data of the current study, very small. References In addition to the ultrasonographic findings, clinical signs and blood parameters are used to guide the duration of treatment Arnold-Lehna D., Venner M., Berghaus L., Berghaus R., Giguère S. (2019) „Changing policy to treat foals with Rhodococcus equi (Prescott et al. 1985, Muscatello et al. 2007). Moreover, foals pneumonia in the later course of disease decreases antimicrobi- often appear clinically healthy before the lung consolidations al usage without increasing mortality rate.” Equine Vet. J. 2020; are resolved, as has been shown previously (Falcon et al. 52(4), 531–537 DOI 10.1111/evj.13219 1985, Slovis et al. 2005). Looking at the development of the Burton A. J., Giguere S., Sturgill T. L., Berghaus L. J., Slovis N. M., clinical signs, the abnormal findings quickly regressed within Whitman J. L., Levering C., Kuskie K. R., Cohen N. D. (2013) „Ma- the first 2 weeks of therapy, but the severity of pneumonia is crolide- and rifampin-resistant Rhodococcus equi on a horse bree- not necessarily correlated with clinical signs as was shown ding farm, Kentucky, USA.” Emerg. Infect. Dis. 19, 282–285; DOI before (Falcon et al. 1985, Slovis et al. 2005). Consequently, 10.3201/eid1902.121210 the clinical findings alone cannot reliably help to answer the Chaffin M. K. (2006) „Treamtment and Chemoprophylaxis of Rhodo- question of the appropriate duration of treatment. The WBC coccus equi pneumonia in foals.” Ann. ACVIM 24 count was recommended in a previous study on diagnostics Cohen N. D., Chaffin M. K., Martens R. J. (2002) How to prevent and and early detection (Giguère et al. 2003). On the other hand, controll caused by Rhodococcus equi at affected farms. Proc. Am. the current results suggest that the WBC count, as it does not Assoc. Equine Pract. 48, 295–299 Falcon J., Smith, B. P., O’Brien T. R., Carlson G. P., Biberstein E. correlate to the abscess score, is not a reliable parameter for (1985) Clinical and radiographic findings in Corynebacterium the assessment of response to treatment in cases of pneumo- equi pneumonia of foals. J. Am. Vet. Med. Assoc. 186, 593–597 nia in foals. Giguère S. (2001) Rhodococcus equi pneumonia. Proc. Am. Assoc. Equine Pract. 47, 456–467 Furthermore, the age of the foals at the time of diagnosis Giguère S. (2010) Therapie of Rhodococcus equi infections in foals. might influence the duration of treatment and the risk of treat- Proc. Am. Assoc. Equine Practnrs. 56, 125–128 ment failure. The current data show that the foals who recov- Giguère S., Berghaus L. J., Willingham-Lane J. M. (2017) Antimicro- ered after 2 weeks of treatment were significantly older than bial resistance in Rhodococcus equi. Microbiol. Spectr. 5(5): ARBA- those, which required more than 2 weeks of therapy. All foals 0004-2016. 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J. 192, 293–298; DOI 10.1016/j. 2746/042516407 × 209217 tvjl.2011.07.004 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 8 Pferdeheilkunde – Equine Medicine 37 (2021)
Abscessing bronchopneumonia in foals – The adequate treatment period and its determination A. Lankenfeld et al. 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 Pferdeheilkunde – Equine Medicine 37 (2021) 9
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