Current controversies in equine antimicrobial therapy

Controversies exist regarding the use, misuse and potential overuse of antimicrobial treatments in foals and adults. When antimicrobials are required for treatment of infectious diseases, veterinarians should follow a logical approach and not simply reach for the newest drug. Targeted, single drug therapy is probably best, and culture and sensitivity testing should be undertaken. The most likely infectious agent, potential drug toxicities, and age‐appropriate dose and route should be considered. The development of an increasing number of different multiple drug resistant pathogens requires that veterinarians use antimicrobial drugs responsibly to protect veterinary patients and the public at large.     

Management of anesthesia in the foal

Several unique pharmacologic and physiologic factors must be considered when attempting to anesthetize premature or neonatal foals. Juvenile foals are similar to adults in their physiology and metabolism. Anesthetic drug and protocol selection should reflect the differences between these two age groups. Neonates are best anesthetized using an inhalation technique, whereas older foals can be safely anesthetized with either parenteral or inhalation anesthetic agents. Careful monitoring is absolutely essential when anesthetizing foals. The clinician should plan to routinely administer fluids and measure electrolyte levels. A basic plan and knowledge of the methods and agents used to treat hypovolemia, severe cardiopulmonary collapse, and life-threatening arrhythmias can result in survival of many critically ill foals.     

Geriatric pharmacology.

When faced with the geriatric dog or cat, the practitioner should consider the following: 1. Avoid using any drugs at all unless there are definite therapeutic indications. If the patient has some degree of renal insufficiency, try to select drugs that are hepatically metabolized and excreted in bile rather than eliminated by the kidneys (eg, doxycycline, tolfenamic acid). If hepatic insufficiency is present, select drugs that do not undergo metabolism before renal excretion (eg, penicillins, cephalosporins). 2. If therapeutic drug monitoring is available, tailor the drug dosage regimen to that specific patient (eg, phenobarbital, digoxin, amino-glycosides). 3. If therapeutic drug monitoring is unavailable, determine if there are clinically proven adjusted dosage regimens for specific drugs. The package insert on human pharmaceutics often gives guidelines for adjusting dosages in geriatric patients. 4. If the drug has not been sufficiently studied to have dosage adjustment recommendations, determine if there is sufficient information about its kinetics to estimate the proper drug dose in a geriatric patient. Some general guidelines for commonly used drugs in geriatric veterinary patients are provided in Table 1. In general, if the Vd changes in your patient, change the dose. If the elimination half-life changes, change the dosing interval. 5. Carefully monitor treated patients for signs of efficacy and toxicity.     

Systemic antimicrobial therapy in foals

Antimicrobial agents are commonly used in neonatal foals for the treatment or prevention of sepsis. However, due to concerns about the development of antimicrobial resistance and increasing pressure on veterinarians to rationalise antimicrobial use, we should be trying to reduce the unnecessary use of antimicrobials. This article reviews many of the important considerations when selecting an antimicrobial for use in neonatal foals. Firstly, we consider general differences in neonatal pharmacology and physiology. Secondly, we review common antimicrobial drugs and their indications. Finally, we review antimicrobial stewardship.     

Metabolic encephalopathies in foals – pay attention to the serum biochemistry panel!

Careful assessment of the biochemistry panel and familiarity with normal biochemistry values for neonatal foals is imperative in the workup of any critically ill neonate, particularly those with neurological signs. The importance of rapidity of change compared to the absolute value of the biochemical abnormality must be emphasised. Serial biochemical panels ideally assist in assessing rapidity of change. Many foals can have severe biochemical derangements in the absence of seizures. Identifying values that are significantly out of range should spur immediate therapy to correct them and potentially additional diagnostic testing to determine the cause of the abnormalities. A temporal relationship between correction of biochemical abnormalities and resolution of seizures and encephalopathic signs supports causation.     

Effects of prior feeding on pharmacokinetics and estimated bioavailability after oral administration of a single dose of microencapsulated erythromycin base in healthy foals

OBJECTIVE: To determine effects of prior feeding on pharmacokinetics and estimated bioavailability of orally administered microencapsulated erythromycin base (MEB) in healthy foals. ANIMALS: 6 healthy foals, 3 to 5 months old. PROCEDURE: Foals were given 2 doses of MEB (25 mg/kg of body weight, PO). One dose was administered after food was withheld overnight, and the other was administered after foals had consumed hay. The study used a crossover design with a 2-week period between doses. Blood was collected via a jugular vein prior to and at specific times after drug administration. Concentrations of erythromycin A and anhydroerythromycin A in plasma were determined, using high-performance liquid chromatography. Results pharmacokinetic analysis of plasma concentration-time data for food-withheld and fed conditions were compared. RESULTS: Plasma concentrations of erythromycin A for foals were lower after feeding than concentrations when food was withheld. Area under the plasma concentration-time curve, maximum plasma concentration, and estimated bioavailability were greater in foals when food was withheld than when foals were fed. Anhydroerythromycin A was detected in plasma after administration of MEB in all foals. CONCLUSIONS AND CLINICAL RELEVANCE: Foals should be given MEB before they are fed hay. Administration of MEB to foals from which food was withheld overnight apparently provides plasma concentrations of erythromycin A that exceed the minimum inhibitory concentration of Rhodococcus equi for approximately 5 hours. The dosage of 25 mg/kg every 8 hours, PO, appears appropriate.     

Haematological and blood biochemical characteristics of Dutch warmblood foals managed under three different rearing conditions from birth to 5 months of age

Reference values for haematological and blood biochemical variables may vary per breed and are influenced by age and, to a certain extent, by rearing conditions. To investigate the influence of age and rearing conditions, these variables were measured in Dutch Warmblood foals from birth to 5 months of age. The foals were divided into three groups with different exercise regimens: 14 foals got boxrest with no exercise; 14 foals were kept in comparable boxes, but received daily exercise; and 15 foals were maintained on pasture with free exercise. Blood samples were collected each month and 36 haematological and biochemical variables were measured. The influence of age and rearing conditions was statistically evaluated. Significant age effects were found for all variables with the exception of band-shaped leucocytes, eosinophilic leucocytes, basophilic leucocytes, monocytes, platelets, pCO2, and sodium, potassium, calcium, magnesium, creatinine and creatine phosphokinase levels. Rearing conditions appeared to influence the haemoglobin, packed cell volume, pH, base excess, bicarbonate, chloride, urea, and alkaline phosphatase values. Most age-related differences can be explained by growth and differentiation-related processes that are specific for young animals. Differences due to the different rearing conditions can partly be explained by the higher metabolism and greater maturation of tissues in foals maintained on pasture with free exercise. Some other differences were minor and were probably of no clinical relevance. The conclusion is that haematological and blood biochemical variables in the Dutch Warmblood foal mainly depend on age, thus warranting the use of specific age-related reference values for foals of this breed.     

Resuscitation and emergency management for neonatal foals.

Early intervention can dramatically alter outcome in foals. Cardio-pulmonary cerebral resuscitation can be successful and clinically worthwhile when applied to foals that arrest as part of the birthing process. Readily available equipment and an ordered plan starting with addressing the respiratory system (airway and breathing) followed by the circulatory system (circulation and drugs) are the keys to success. Hypoglycemia is common in foals that are not nursing and in septic foals. Support of serum glucose can be an important emergency treatment. Respiratory support with oxygen therapy should be considered in all foals following resuscitation and dystocia. Other foals that are likely to benefit from oxygen are those that are dyspneic, cyanotic, meconium-stained after birth,or recumbent. Emergency therapies, applied correctly, are expected to result in decreased mortality and morbidity.     

Anesthesia of the sighthound

The sighthounds are an ancient group of dog breeds that have been selectively bred for high-speed pursuit of prey by sight. Probably as a consequence of this selection process, these dogs have a number of idiosyncrasies that can potentially adversely affect their anesthetic management. These include (1) nervous demeanor which can lead to stress-induced clinical complications, such as hyperthermia; (2) lean body conformation with high surface-area-to-volume ratio, which predisposes these dogs to hypothermia during anesthesia; (3) hematological differences such as a higher packed cell volume and lower serum protein compared with other dog breeds which may complicate interpretation of preanesthetic blood work; (4) Impaired biotransformation of drugs by the liver resulting in prolonged recovery from certain intravenous anesthetics, especially thiopental; and increased risks of drug interactions. Safe anesthetic management of sighthounds should include sedative premedication and appropriate use of analgesic drugs to minimize perioperative stress. Thiopental, or any other thiobarbiturate, should not be used in these dogs. Propofol, ketamine/diazepam combination, and methohexital are recommended alternative intravenous anesthetics. Avoid coadministration of agents that inhibit drug biotransformation, such as chloramphenicol. Inhalation anesthesia using isoflurane is the preferred anesthetic maintenance technique. Core body temperature should be monitored closely and techniques to minimize hypothermia should be employed both during anesthesia and into the recovery period.     

Acute lung injury/acute respiratory distress syndrome in 15 foals

REASONS FOR PERFORMING STUDY: Few reports exist in the veterinary medical literature describing clinical and pathological findings resembling conditions described as (ALI) and acute respiratory distress syndrome (ARDS) in man. OBJECTIVES: To document history, clinical, laboratory and diagnostic findings, treatment and outcome of foals age 1-12 months diagnosed with ALI/ARDS at a referral hospital. METHODS: Medical records, including radiographic, cytological, microbiological, serological and post mortem findings, were reviewed in a retrospective manner to identify foals with acute onset of respiratory distress, a partial pressure of arterial oxygen (PaO2) to fraction of oxygen in inspired gases (FiO2) ratio of < or = 300 mmHg, pulmonary infiltrates on thoracic radiographs or post mortem findings consistent with ALI/ARDS. RESULTS: Fifteen foals age 1.5-8 months were included in the study. Seven foals had previously been treated for respiratory disease, and all foals developed acute respiratory distress <48 h prior to presentation. Findings on presentation included tachycardia and tachypnoea in all foals, with fever recorded in 8 cases. Eight cases met the criteria for ALI and 7 for ARDS. Radiographic findings demonstrated diffuse bronchointerstitial pattern with focal to coalescing alveolar radiopacities. An aetiological agent was identified in foals ante mortem (n = 6) and post mortem (n = 4). All foals were treated with intranasal oxygen and antimicrobial drugs; 13 received corticosteroids. Nine patients survived, 4 died due to respiratory failure and 2 were subjected to euthanasia in a moribund state. Follow-up was available for 7 foals; all performed as well as age mates or siblings, and one was racing successfully. CONCLUSIONS: A condition closely meeting the human criteria for ALI/ARDS exists in foals age 1-12 months and may be identical to previously described acute bronchointerstitial pneumonia in young horses. POTENTIAL RELEVANCE: ALI/ARDS should be suspected in foals with acute severe respiratory distress and hypoxaemia that is minimally responsive to intranasal oxygen therapy. Treatment with systemic corticosteroids, intranasal oxygen and antimicrobials may be beneficial in foals with clinical signs compatible with ALI/ARDS.     

Successful treatment and polymerase chain reaction (PCR) confirmation of Tyzzer's disease in a foal and clinical and pathologic characteristics of 6 additional foals (1986-2005)

BACKGROUND: Tyzzer's disease is a rapidly progressive and highly fatal hepatitis of foals caused by Clostridium piliforme. Survival of a confirmed case has not been reported previously. HYPOTHESIS: Successful therapy of C. piliforme infection in foals is possible. Polymerase chain reaction (PCR) can be used to diagnose Tyzzer's disease antemortem or postmortem. ANIMALS: Seven foals were included in the study. METHODS: Retrospective study was made to evaluate the clinical and pathologic characteristics of foals with Tyzzer's disease. Medical records of the Veterinary Medical Teaching Hospital at University of California Davis were reviewed. Foals <3 months old were included in the study if typical clinical signs were present and histologic examination identified multifocal coagulative necrosis and hepatitis with intracytoplasmic filamentous bacilli, consistent with C. piliforme. A real-time TaqMan assay was developed to detect C. piliforme gene sequences in liver tissue from affected foals. RESULTS: Median survival time from onset of disease in nonsurviving foals was 30 hours (mean 34.5 +/- 20.1; range, 16-62 hours). Common clinical findings included lethargy, recumbency, seizures, and fever. Laboratory findings included metabolic acidosis, hypoglycemia and increased activity of hepatobiliary enzymes. Treatment consisted of IV fluids, antimicrobial and antiinflammatory drugs, and parenteral nutrition. One filly survived, whereas 6 died. Postmortem examination of the 6 foals that died disclosed hepatomegaly with multifocal necrosis. Liver tissue from 4 foals was positive for C. piliforme gene sequences using PCR. CONCLUSIONS AND CLINICAL IMPORTANCE: Although the mortality rate of Tyzzer's disease is high, successful outcome is possible if intensive care is initiated promptly. PCR can be used for early and specific diagnosis.     

Septic arthritis in foals

In the neonatal foal septic arthritis is an important cause of morbidity that may limit future athletic performance. This is often despite a good prognosis for resolution of joint infection. This article presents a review of the diagnosis and treatment of septic arthritis in foals less than 2 months of age, including an overview of our current understanding of inflammatory joint disease in the neonate. Management options are described, with emphasis on tailoring therapy to the individual foal based on accurate staging and monitoring of the disease process. Special considerations relevant to the immature animal are addressed.     

Insulin, glucagon, and leptin in critically ill foals

Background: Endocrine dysregulation of hormones of energy metabolism is well documented in critically ill humans, but limited information exists in septic foals. The purpose of this study was to provide information on the hormonal response to energy metabolism in critically ill foals, focusing on insulin, glucagon, and leptin. Hypothesis: Concentrations of insulin, glucagon, leptin, and triglycerides will be higher, whereas glucose concentration will be lower in septic foals than in healthy and sick nonseptic foals. The magnitude of these differences will be associated with severity of disease and nonsurvival. Animals: Forty‐four septic, 62 sick nonseptic, and 19 healthy foals <7 days of age. Methods: In this prospective multicenter cross‐sectional study, blood samples were collected at admission. Foals with positive blood culture or sepsis score ≥12 were considered septic. Results: Septic foals had lower glucose and insulin and higher triglyceride and glucagon concentrations than did healthy foals. Glucagon concentrations were not different between septic foals that died (n = 14) or survived (n = 30). Higher insulin and lower leptin concentrations were associated with mortality. Quantitative insulin‐sensitivity check index was higher in septic foals. Conclusions and Clinical Importance: Energy metabolism and the endocrine response of related hormones in septic foals are characterized by hypoglycemia, hypertriglyceridemia, low insulin concentration, and high glucagon concentration. Leptin and insulin may have prognostic value for nonsurvival in septic foals. The hormonal response related to energy metabolism in critical illness differs between foals and humans.     

Gastrointestinal diseases of foals

Few foals escape gastrointestinal disease during the first weeks of life. Diarrhea is an extremely common problem; fortunately, however, it is usually mild and self-limiting. When it is not, the underlying cause is often an infectious agent, such as rotavirus or Salmonella spp. Our understanding of many of the infectious agents causing neonatal diarrhea is far from complete. Gastric and duodenal ulcers are a less common disease of neonatal foals. There has been an apparent increase in the incidence of ulcer disease in foals during the past few years. The most effective way of decreasing serious gastrointestinal disease in foals is through the use of good management practices. Environmental and dietary stress must be minimized, and good hygienic practices should be followed. Unfortunately, the needs of the neonate are often ignored, while attention is focused on the mare during the breeding season.     

Treatment of Corynebacterium equi pneumonia of foals: a review

Combined antimicrobial drug treatment was recommended for foals with Corynebacterium equi pneumonia. The preferred combination is orally administered erythromycin estolate (25 mg/kg of body weight, QID) plus rifampin (10 mg/kg, BID). Erythromycin estolate also can be combined for synergistic effect with sodium benzyl penicillin given IV (100,000 IU/kg, QID) or with ampicillin given IV (11 to 15 mg/kg, QID). A third choice is sodium benzyl penicillin IV with gentamicin IM (2.2 mg/kg, TID) or with kanamycin IM (10 mg/kg, QID). Gentamicin should be combined with penicillin G or ampicillin and not used for longer than one week without monitoring for nephrotoxicosis. Rifampin should be used only in combination with erythromycin or penicillin. Erythromycin or rifampin and gentamicin give antagonistic interactions in vitro. Chloramphenicol or trimethoprim-sulfamethoxazole may be effective if given in high doses but are not preferred drugs. Treatment response should be monitored clinically and radiographically and treatment should be continued for 2 weeks after the foal is clinically and radiographically normal.     

Clinical experiences of treating septic arthritis in the equine by repeated joint lavage: a series of 39 cases

The condition of septic arthritis was treated in 12 foals with 21 affected joints (Group I) and in 27 adult horses. The adult horses were divided into three groups, based on aetiology of the condition: haematogenous (Group II, n = 6), iatrogenic (Group III, n = 6), and perforating trauma (Group IV, n = 15). The treatment consisted of an initial systemic antibiotic that anticipated the microbial agents that were considered most likely per group, repeated through-and-through joint lavages every other day and non-steroidal anti-inflammatory drugs. The antibiotics were adjusted to the results of bacteriological culture and susceptibility tests. Joint lavages were continued until the white blood cell count dropped below 15 G/l and bacteriological culture was negative, after which a single dose of a short-acting corticosteroid was administered intra-articularly. Joint recovery rate in group I was 71%. Patient recovery rate of the foals, however, was lower (42%). Three foals were killed for reasons other than arthritis; one foal because of an arthritis-related problem and three foals because of persistent arthritis. Overall joint recovery rate, equalling patient recovery rate, in the adult horses was 81%. The expected predominance of Streptococcus spp. in haematogenous arthritis in adult horses was not confirmed, indicating that in these cases also, an initial antibiotic treatment with a broad-spectrum combination is preferable. It is concluded that with intensive treatment, the prognosis of septic arthritis in the adult horse can be classified as fair to even good. Results in the foals are not as good, but this seems to be more due to the specific problems surrounding the equine neonate than to unresponsiveness to the treatment.     

Helicobacter equorum is highly prevalent in foals

Faecal samples of sixty-six 3-day- to 6-month-old foals were screened for Helicobacter equorum DNA by means of a PCR amplifying a 1074 bp fragment of the 23S rRNA gene with primers specific for this enterohepatic Helicobacter species. H. equorum DNA was demonstrated in faeces from 28.6% of the less than 1-month-old foals, while 67.8% of foals from 1 to 6 months of age tested positive. In a previous study, H. equorum was demonstrated in faeces of 0.8-7.9% of adult horses. These results indicate that the prevalence of H. equorum in horses differs with the age of the investigated horse population. The organism seems highly prevalent in foals between 1 and 6 months of age but the possible association with intestinal disease in this age group needs further investigation.     

Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration

The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two-compartment open model. Mean plasma elimination-rate constant (beta) and clearance (ClB) for ticarcillin were significantly less (P less than 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P less than 0.05), in the foals at 3 days compared with 28 days of age. This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3-day-old foals. The mean elimination rate constant for clavulanate was significantly less (P less than 0.01) at 3 days than at 28 days of age. Values of the major kinetic terms describing the disposition of ticarcillin after i.m. administration to five 3-day-old foals were not significantly different from values of these parameters in the same foals at 28 days of age. After i.m. administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P less than 0.01), and the elimination-rate constant (kd) for clavulanate was significantly less (P less than 0.01), in 3-day-old foals than in 28-day-old foals. The bioavailabilities of ticarcillin and clavulanate after i.m. administration in 3-day-old foals were 100% and 88.3%, respectively, and in 28-day-old foals were 100% and 27.4%, respectively. Mean plasma ticarcillin concentrations exceeded 16 micrograms/ml for a longer period after i.m. administration of the drug combination than after i.v. administration to foals of both age groups. By virtue of the frequency of administration required and the painful response elicited by i.m. injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC less than or equal to 16 micrograms/ml), it should be administered i.v. four times daily.     

Respiratory problems in foals

Despite major advances in our knowledge and ability to treat respiratory diseases in neonatal foals, neonatal respiratory medicine is still in its infancy. It is hoped that this article may serve as a guideline for diagnosis and treatment. Specific antibiotic regimens and emergency procedures are covered in other articles in this symposium. Because management factors play a critical role in the pathogenesis of respiratory disease, education of clients as to their importance would help both prophylactically and therapeutically. The necessity of very careful monitoring of neonates, which is critical to early detection of disease, should be stressed. As respiratory diseases can be fulminant and rapidly fatal, it is imperative not to delay diagnosis and therapy. Thorough examination and implementation of appropriate diagnostic techniques, as well as prompt early referral to a more sophisticated facility when indicated, would prevent many deaths. Although sophisticated support systems are vital for survival of some of these foals, good basic intensive nursing care combined with selection of appropriate drug therapy very early in the course of the disease is all that many foals require and can significantly improve survival rates.     

Hypercapnic respiratory acidosis: A protective or harmful strategy for critically ill newborn foals?

This paper reviews both the beneficial and adverse effects of permissive hypercapnic respiratory acidosis in critically ill newborn foals. It has been shown that partial carbon dioxide pressure (PCO₂) above the traditional safe range (hypercapnia), has beneficial effects on the physiology of the respiratory, cardiovascular, and nervous system in neonates. In human neonatal critical care medicine permissive hypercapnic acidosis is generally well-tolerated by patients and is more beneficial to their wellbeing than normal carbon dioxide (CO₂) pressure or normocapnia. Even though adverse effects of hypercapnia have been reported, especially in patients with central nervous system pathology and/or chronic infection, critical care clinicians often artificially increase PCO₂ to take advantage of its positive effects on compromised neonate tissues. This is referred to as therapeutic hypercapnia. Hypercapnic respiratory acidosis is common in critically ill newborn foals and has traditionally been considered as not beneficial. A search of online scientific databases was conducted to survey the literature on the effects of hypercapnia in neonates, with emphasis on newborn foals. The dynamic status of safety levels of PCO₂ and data on the effectiveness of different carbon dioxide levels are not available for newborn foals and should be scientifically determined. Presently, permissive hypercapnia should be implemented or tolerated cautiously in compromised newborn foals and its use should be based on relevant data from adult horses and other species.