Anaphylactic reaction in a cow due to parenteral administration of penicillin-streptomycin.

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Case Report Rapport de cas
Anaphylactic reaction in a cow due to parenteral administration
of penicillin-streptomycin
Arash Omidi
Abstract — Anaphylactic reaction rarely occurs after the 1st injection of penicillin-streptomycin in cattle.
Immediately following intramuscular injection of a Holstein-Friesian cow with penicillin-streptomycin, the cow
showed abnormal clinical signs that included respiratory distress, urticaria, and lacrimation. Recovery took approxi-
mately 2 h after intramuscular injection of dexamethasone. This report presents clinical findings recorded 20 and
40 h later.
Résumé — Réaction anaphylactique chez une vache due à une administration parentérale de pénicilline-
streptomycine. Une réaction anaphylactique se produit rarement après la première injection de pénicilline-
streptomycine chez le bétail. Immédiatement après une injection intramusculaire chez une vache Holstein-Friesian
avec de la pénicilline-streptomycine, la vache a manifesté des signes cliniques anormaux qui incluaient la détresse
respiratoire, l’urticaire et la sécrétion de larmes. Le rétablissement a duré environ 2 heures après l’injection
intramusculaire de dexaméthasone. Ce rapport présente les résultats cliniques enregistrés 20 et 40 heures plus tard.
(Traduit par Isabelle Vallières)
Can Vet J 2009;50:741–744
I n human medicine, severe immediate type I hypersensitiv-ity (anaphylaxis) is a major cause of adverse drug reactions.
Antibiotics (particularly penicillin and cephalosporins), nar-
cotic and nonsteroidal anti-inflammatory drugs are the major
culprits (1). Anaphylaxis is defined as a “severe allergic reaction
that may cause death,” and in human medicine a consensus
definition has recently been proposed (2). In veterinary practice,
anaphylactic reactions are usually seen after injections of sera
or bacterins. These reactions are usually observed during the
2nd or 3rd injection following an initial “sensitizing” dose (3).
Immediate-type hypersensitivity reactions to penicillin are rarely
reported in veterinary medicine (4), especially after the 1st injec-
tion of penicillin in cattle (5), although the incidence of allergic
reactions in this setting is unknown (4).
Case description
A 5-year-old Holstein Friesian cow was given an intramuscular
injection of combined penicillin and streptomycin (Penicillin G
procaine 3 MIU & Dihydrostreptomycin sulfate eq. to 3 g base;
Nasr, Fariman, Iran) to treat a wound in the leg. This cow had not been treated with either agent previously. Before the injec-
tion, clinical findings were normal and were as follows: body
temperature of 38.5°C, heart rate of 80 beats per min (bpm),
respiratory rate of 20 breaths per min, and ruminal motility rate
at 4 contractions per 5 min. Less than a minute following the
injection, the cow showed respiratory distress (severe dyspnea),
incoordination, anxiety, salivation, urticaria, facial and perineal
edema, lacrimation, rhinitis, and shock. Elevation of the body
temperature (40°C), heart rate (132 bpm), and respiratory rate
(32 breaths per min) was observed and the ruminal motility rate
decreased to 1 contraction per 5 min. Edema was observed in
Department of Animal Sciences, Faculty of Agriculture,
University of Birjand, Birjand, Iran.
Address all correspondence to Dr. Arash Omidi; e-mail:
arashomidi2@gmail.com
Use of this article is limited to a single copy for personal study.
Anyone interested in obtaining reprints should contact the
CVMA office (hbroughton@cvma-acmv.org) for additional
copies or permission to use this material elsewhere.
Figure 1. Severe facial edema especially around the eyes
(facial-conjunctival angioedema) and lacrimation observed within
minutes of the intramsucular injection of penicillin-streptomycin.

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the eyelids (Figure 1), lips, face, udder (Figure 2) and external
surface of the vulva and anal area (Figure 3). On auscultation
of the chest, respirations were wheezy and labored, and rhinitis
was observed (Figure 4). This was related to edema and an
increase in permeability of pulmonary vessels (5). Epinephrine
was not available, so dexamethasone was given intramuscularly
(Dexamethasone 0.4%; Nasr), 5 mg/kg body weight (BW).
There was marked improvement within 2 h, but redness and
urticaria of the mammary gland persisted for 40 h.
Discussion
Penicillin has a wide safety margin, and is usually well-tolerated.
Penicillin and its metabolites have an affinity for proteins and
may form hapten conjugates, which trigger immediate-type
hypersensitivity reactions that is mediated by IgE and is directed
against various allergenic determinants in the penicillin mol-
ecule. In humans, the response usually appears to be directed
against a single “major determinant” (benzylpenicilloyl radical),
or against certain “minor determinants” (benzylpenicilloic acid
and penicillenic acid) (6). Streptomycin is a relatively large
molecule which contains several nitrogen atoms; this may pos-
sibly be of significance in the induction of antibody formation
(7). Reports of anaphylactic reactions to combined penicillin
and streptomycin in humans are fewer than to penicillin and
streptomycin separately (8).
Anaphylaxis is a severe multiple organ system immediate-
type reaction, affecting the skin, respiratory, cardiovascular, and
gastrointestinal systems within minutes to an hour of exposure
to a precipitating agent (2). Lethal anaphylaxis is characterized
by severe (upper or lower) airway obstruction, and/or shock with
profound hypotension. In the absence of cardiovascular monitor-
ing, the observable features of anaphylaxis need to be recognized
if appropriate emergency treatment is to be provided. However,
it should be noted that in humans, patients may simply suffer
a sudden cardiac arrest without any signs of anaphylaxis (9).
In cattle, the observed features of anaphylaxis include sudden
development of local or diffuse transient subcutaneous edema
(angioneurotic edema), affecting the head in most cases, but also
the perineum and udder. There is usually diffuse edema of the
muzzle, eyelids, conjunctiva, and occasionally the cheeks. This
Figure 2. Urticaria on the caudal surface of the mammary gland; a — immediately after the intramsucular injection of penicillin-
streptomycin, b — 20 h after treatment, c — 40 h after teatment. Note the decrease in redness from a to c.

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is characterized by doughy swelling that pits on pressure; when
pressed firmly with the fingertips it retains the indentation for a
considerable period of time (10). A rise in temperature (40°C) is
likely due to muscle tremor (5). Isolated urticaria (mild hyper-
sensitivity), without involvement of other organ systems, may
also result from parenteral administration of penicillin (10) or
streptomycin (7). Urticarial reactions may appear within min-
utes, or up to 5 wk after the administration of penicillin (11).
In the latter case (delayed onset), the reactions are probably not
IgE-mediated.
Treatment should be administered immediately. A few min-
utes delay may result in the death of the animal. Most treatment
recommendations are based on studies of small animals and
humans. Epinephrine administered intramuscularly is often
immediately effective (12). However, most anaphylactic reac-
tions are usually of moderate severity and will spontaneously
Figure 3. Edema in the anal and external genital area; a — within minutes of the intramsucular injection of penicillin-
streptomycin, b — recovery 20 h after treatment.
Figure 4. Severe dyspnea and rhinitis; a — immediately after the intramuscular injection with penicillin-streptomycin,
b — recovery 20 h after treatment.

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resolve over minutes or a few hours in otherwise healthy animals
and humans (13). Corticosteroids are said to potentiate the
effect of epinephrine and may be given immediately follow-
ing the epinephrine in order to maintain vascular integrity
and to decrease permeability of pulmonary vessels, although
the evidence for this presumption is minimal (5). In the case
presented here, it is more likely that the gradual improvement
over several hours reflected the natural recovery rather than the
response to therapy.
Studies in cattle have found that antihistamines and
5-hydroxytryptamine antagonists fail to protect cattle in experi-
mental hypersensitivity. Sodium meclofenamate has been more
successful in antagonizing experimental anaphylaxis in cattle
and horses. Acetylsalicylic acid was more effective than anti-
histamines or antiserotonin agents in providing symptomatic
relief in experimental acute interstitial pneumonia of calves
(5). Oxygen can also be given as soon as possible and preferably
under positive pressure to combat pulmonary edema (12). It is
important to prevent obstruction of the airways.
Anaphylaxis is rare after the first injection of a conventional
drug such as penicillin, because the known mechanisms of
penicillin hypersensitivity (via IgE) require prior sensitization.
With the increasing use of antibiotics as growth promoters, it is
possible that some animals may be sensitized by unrecognized
exposure to common determinants (for example common
determinants between amoxicillin, ampicillin, penicillin, and a
variety of cephalosporins (14).
Acknowledgments
This case report was carried out with support from the
University of Birjand. I am grateful to Dr. Simon Brown for
technical support and Dr. Wassim Tawbi for critical reading of
the manuscript. CVJ
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