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.
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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

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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