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Therapeutics in Practice
Treating Foal Pneumonia*
Column Editor
Virginia Polytechnic Institute and State University Lower respiratory tract infections are common in foals and account for substantial morbidity and mortality. Foals are at risk for the development of pneumonia due to interactions between innate immunologic factors and management risk factors.
Immunologic factors include failure of passive transfer, delayed endogenous immunoglobulin production, and impaired cellular immunologic responses to challenge with organisms such as Rhodococcus equi.1 Management risks include the stresses ofweaning, sale preparation, transport, and/or confinement in crowded or dusty condi- tions, which can result in heavy exposure to potential respiratory pathogens.2 CLINICAL SYNDROMES
Neonates
Pneumonia in neonates is most often associated with septicemia but may also occur secondary to meconium or milk aspiration or hematogenous spread. Gram-negativebacteria are most commonly involved in neonatal pneumonia, although gram-positiveand mixed infections do occur. Treatment with a broad-spectrum drug or drug combi- nation is recommended. Neonatal foal pneumonia may also be complicated by rib frac- tures, inadequate surfactant production associated with prematurity, or severe systemicinflammation. Antiinflammatory therapy may aid in controlling pulmonary inflamma- COMPENDIUM tion, thereby improving pulmonary function and patient comfort. Supplemental oxygen C O N T I N U I N G E D U C A T I O N F O R V E T E R I N A R I A N S TM by nasal insufflation (5 to 10 L/min) is beneficial in severely affected neonates. Viral EQUINE EDITION pneumonia (resulting from equine herpesvirus [EHV] 1, equine arteritis virus, or ade- novirus) rarely occurs in neonates but is usually fatal.
Older Foals
Although still relatively rare, viral pneumonias (resulting from EHV1, EHV2, or EHV4; equine arteritis virus; or equine influenza virus) are more common in older foalsthan in neonates. Viral infections cause pulmonary inflammation and impair pulmonaryimmunity, predisposing foals to subsequent bacterial infections. Treatment consists ofantiinflammatory therapy and supportive care because premature use of antibiotics may result in resistant organisms. Bacterial pneumonia in older foals typically involves gram- positive bacteria, especially Streptococcus equi zooepidemicus and R. equi. Secondary infec- tion with gram-negative organisms is not uncommon, and affected foals may exhibit a poor response to treatment or deteriorate clinically despite treatment.
ANTIMICROBIAL THERAPIES
Selection of an antimicrobial regimen (Table 1) in foals with pneumonia is based on: editor@CompendiumEquine.com
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*A related article appears on p. 14.
48 Therapeutics in Practice
Table 1. Antimicrobials for Treating Foal Pneumonia
Trade Name,
Manufacturer
Frequency
Table 1. Antimicrobials for Treating Foal Pneumonia (continued)
Trade Name,
Manufacturer
Frequency
aPapich MG: Current concepts in antimicrobial therapy for horses. Proc AAEP 47:94–102, 2001.
bBased on the author’s clinical experience.
• Tissue distribution of the drug (therapeutic concen- neonates with poor aminoglycoside kinetics or docu- trations must be reached at the site of infection) mented multiresistant infections, and the drug shouldbe administered at 11 mg/kg IV or IM q8h. A new class Foals with pneumonia secondary to septicemia require of synthetic β-lactams, the carbapenems, exhibits a high broad-spectrum therapy because of either gram-nega- degree of stability in the presence of β-lactamases and tive or gram-positive involvement. Older foals with may be useful in critically ill foals with documented uncomplicated pneumonia may initially be treated with multiresistant infections. Imipenem–cilastatin has been a gram-positive regimen, but a poor response to treat- used in foals at an empiric dosage of 5 to 10 mg/kg IM ment represents a clear indication for institution of bid with apparent safety and efficacy.6 Intravenous broad-spectrum therapy. Evidence of pulmonar y administration substantially increases the expense7 and abscessation or a high index of suspicion for rhodococ- is associated with an increased incidence of adverse cal pneumonia in older foals requires treatment with a Aminoglycosides continue to be a primary class of β-Lactam antimicrobials are widely used in foal pneu- antimicrobials used in treating foal pneumonia, despite monia. Wide variations in bioavailability have limited the potential for nephrotoxicity, because of their excel- the use of semisynthetic penicillins and cephalosporins lent gram-negative spectrum and synergy with β-lactam by the oral route. A recent study suggested that cefpo- agents. Both the efficacy and safety of these compounds doxime proxetil may be useful in foals at a dosage of 10 can be enhanced by extended-interval dosing. Higher mg/kg PO q6–12h.3 Cephalexin at a dosage of 30 peak serum concentrations improve efficacy because of mg/kg PO q8h achieved appropriate serum levels in the concentration-dependent nature of aminoglycosides, adult horses.4 Because clinical efficacy has not been whereas safety is improved by allowing a longer period of established for these oral agents, β-lactams continue to time in which the drug is at trough level. Amikacin be primarily administered parenterally. Because of their should be administered to neonatal foals at 21 to 25 gram-positive spectrum, penicillins are often combined mg/kg IV q24h,8,9 whereas gentamicin should be admin- with an aminoglycoside to provide gram-negative cover- istered at 11 to 15 mg/kg IV q24h.8 As foals mature, the age. Use of a third-generation cephalosporin, such as dose administered should be gradually decreased to the ceftiofur, broadens the spectrum of coverage as a sole adult range (i.e., 6.6 mg/kg IV q24h for gentamicin, 7 to therapy but can be improved by adding an aminoglyco- 14.5 mg/kg IV q24h for amikacin).8,9 The volume of dis- side. New fourth-generation cephalosporins exhibit bet- tribution and half-life of aminoglycosides decrease as ter activity against gram-positive organisms, and the foals mature. These factors, combined with potentially pharmacokinetics of cefepime have been examined in substantial variations resulting from severe systemic dis- foals.5 Use of cefepime has been limited primarily to ease and renal insufficiency, can cause unpredictable 50 Therapeutics in Practice
aminoglycoside pharmacokinetics. The serum concentra- have not been established, an empiric dosage of 10 tions of these drugs should be monitored, especially if mg/kg PO q12h has been used based on adult horse they are to be used for more than 5 days.8 Serum samples pharmacokinetics established by Bryant et al.10 A more should be collected at 30 minutes and 8 hours following recent study,11 also of adult horses, suggests that a dosage drug administration, with the goal being a 30-minute of 20 mg/kg PO q12–24h may be more appropriate. In peak concentration of greater than 25 µg/ml for gentam- humans, it is recommended that doxycycline not be Evidence of pulmonary abscessation or a high index of suspicion for rhodococcal pneumonia in older foals requires treatment with a macrolide. icin and greater than 40 µg/ml for amikacin, with an 8- taken with milk because of the possibility of impaired hour trough concentration of 3 to 5 µg/ml for absorption, but doxycycline administered to calves in gentamicin or 15 to 20 µg/ml for amikacin.8,9 Failure to milk replacer has a reported bioavailability of 70%.12 achieve an adequate peak should be addressed by The treatment of rhodococcal pneumonia has tradi- increasing the dose administered, whereas a high 8-hour tionally included oral erythromycin in combination with trough concentration must be addressed by increasing rifampin. However, use of erythromycin can be associ- the treatment interval or decreasing the dose.8 ated with hyperthermia and colitis (in both the foal and Tetracycline antimicrobials have not been widely used dam). Newer macrolides that do not cause these adverse in treating foal pneumonia but are of interest because of effects are available. Azithromycin with rifampin their broad spectrum and good tissue penetration.
appears to be as effective as erythromycin with rifampin Although the pharmacokinetics of doxycycline in foals and should be administered at 10 mg/kg PO q24h for 5days, then q48h.13 With a broad spectrum of action,azithromycin is a reasonable choice in treating foalbronchopneumonia of an unknown cause. Administra-tion of clarithromycin and rifampin appears to be moreeffective than either of the previous combinations intreating rhodococcal pneumonia, and clarithromycinshould be dosed at 7.5 mg/kg PO q12h.14 Oral chloramphenicol has broad-spectrum activity and excellent tissue penetration, but use of this drug intreating foal pneumonia has been limited by concernsregarding potential human toxicity (fatal aplastic ane-mia). Reducing exposure of persons handling this drugis best accomplished by dissolving the tablets in wateror obtaining a compounded paste formulation and hav-ing the administrator wear gloves. There is evidencethat the actual incidence of aplastic anemia associatedwith chloramphenicol is dramatically lower than origi-nally believed, and this drug continues to be widelyused in human medicine.15 Chloramphenicol doesappear to be very useful clinically in treating foal pneu-monia when its use is typically limited to patients withdocumented multiresistant infections. Chlorampheni-col should be administered to foals at a dosage of 50mg/kg PO q6h.16 Topical administration of antimicrobials via the aerosol route has been investigated in adult horses, and this technique has been shown to achieve high levels of of cold and/or dry air and stimulation of irritant recep- antimicrobial within the airway lumen.17 This treatment tors within the respiratory mucosae.23 Ill foals should modality has efficacy in humans and has been used clin- not undergo stressful events such as weaning, transport, ically to treat foal pneumonia, typically in conjunction or sale. Temperature control is also important because with systemic antimicrobial therapy. Aminoglycosides foals with pneumonia exhibit impaired thermoregula- are particularly well suited for intermittent topical tion and are predisposed to hyperthermia. Environmen- administration, although cephalosporins may be admin- tal management is best achieved by turnout in a small istered by aerosolization, as well. Gentamicin should be grass paddock and/or by providing a stall with low-dust administered by nebulization at 2.2 mg/kg q24h, using a bedding such as pine shavings, rather than straw. Pro- 50-mg/ml solution, whereas ceftiofur should be admin- longed rest is often required because chronic inflamma- istered at 1 mg/kg q12h using a 25-mg/ml solution.17 tion may follow resolution of clinical disease.
Foals with pneumonia often benefit from treatment ANTIINFLAMMATORY THERAPIES
with bronchodilators because they decrease the work of NSAIDs are commonly used in treating foal pneumo- breathing and improve patient comfort and attitude nia to control fever and decrease patient discomfort (Table 2). Methylxanthines (i.e., aminophylline, theo- (Table 2). There is evidence in pneumonic calves that phylline) are not recommended because of their narrow NSAIDs not only control fever but also improve in- therapeutic index. β -Agonists (i.e., albuterol, clen- flammation and clinical signs associated with lower res- buterol) are readily used because they are easily adminis- piratory infections.18 However, administering NSAIDs tered by the oral or aerosol route and have additional to foals can be problematic because the most widely benefits, including enhancement of mucociliary clear- available products have a narrow therapeutic index.19,20 ance. Use of the aerosol route allows the use of smaller The use of steroidal antiinflammatory drugs (SAIDs) doses, thereby reducing the risk for systemic toxicity.
in treating lower respiratory infections is much more The anticholinergic bronchodilator ipratropium bro- controversial than the use of NSAIDs. The rationale be-hind the use of SAIDs in cases of pneumonia is thatproduction of the primary proinflammatory mediatorsinvolved is best suppressed by SAIDs because of theirability to interfere with nuclear transcription of the genesencoding these proinflammatory mediators.21 The pri-mary concern when considering the use of SAIDs intreating infectious disease is the potential for immuno-suppression, which is very real but primarily dose related.
The most interesting evidence concerning the use ofSAIDs in foal pneumonia was provided by a study byLakritz et al22 in which foals with severe bronchointersti-tial or interstitial pneumonia exhibited extremely poorsurvival rates unless treated with SAIDs. Low-dose oralsteroids (primarily prednisolone at 1 mg/kg PO sid) maybe clinically beneficial in some cases of foal pneumoniain terms of lessening the severity of pulmonary dysfunc-tion and shortening the course of illness, although con-trolled studies are required to definitively establish theirefficacy and safety.
ANCILLARY THERAPIES
The most important ancillary therapy is rest. Activity is likely to worsen respiratory distress by exacerbatingthe inflammatory response within the lower respiratorytract resulting from irritation associated with inhalation 52 Therapeutics in Practice
Table 2. Ancillary Drugs for Treating Foals with Pneumonia
Trade Name,
Manufacturer
Frequency
aBased on author’s clinical experience.
MDI = metered-dose inhaler.
mide (Atrovent, Boehringer Ingelheim) can be used either NSAIDs or SAIDs. Therefore, it is prudent to alone or in combination with a β -agonist (Combivent, treat foals with pneumonia with gastric acid suppressive Boehringer Ingelheim). Ipratropium is available only as drugs. Oral omeprazole (Gastrogard, Merial) is an aerosol preparation, either as a metered-dose inhaler extremely effective at suppressing gastric acid produc- or a solution for nebulization, and must therefore be tion24 and is my preferred prophylactic therapy. The administered by inhalation using a facemask.
effect of ranitidine in suppressing gastric acidity is less Clinically ill foals are at risk for gastrointestinal ulcer- profound and much shorter. Ranitidine must be admin- ation due to altered feeding patterns and physiologic istered every 8 hours as opposed to once-daily therapy stress, and the risk is worsened by administration of REFERENCES
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