Diagnosis and Management of Bacterial Pneumonia in Adult Horses

IN-DEPTH: RESPIRATORY

Harold C. McKenzie III, DVM, MS, Diplomate ACVIM

Author’s address: Marion duPont Scott Equine Medical Center, VA/MD Regional College of Veter- inary Medicine, Virginia Polytechnic and State University, 17690 Old Waterford Road, Leesburg, VA 20176; e-mail: [email protected]. © 2011 AAEP.

1. Introduction and mitigate this exposure, thereby preventing dis- Lower respiratory infections in adult horses often ease. The normal defense mechanisms consist of have an initial viral component because the effects the barrier represented by the filtration provided by of lower respiratory viral infections on local clear- the upper respiratory tract, the physical barrier rep- ance and immune function may predispose to sec- resented by the epithelial lining fluid and the respi- ondary bacterial involvement. Bacterial lower ratory mucosa, and the innate and specific immune respiratory infections have greater clinical impact responses that eliminate or inactivate infectious or- than viral infections because of the substantial risk ganisms that reach the lower respiratory tract. The of complications ranging from focal abscessation to development of infectious lower respiratory tract infec- pleuropneumonia. The development of compli- tions requires that these respiratory tract defenses be cated pneumonia cannot always be prevented, but, overcome, and this may occur as a result of impair- once present, requires early and aggressive inter- ment of the defenses or by overwhelming exposure. vention to achieve acceptable outcomes. Bacterial Viral respiratory infections can impair mucocili- pneumonia can present substantial therapeutic ary clearance and suppress local immunity within challenges to the clinician that requires careful con- the lower respiratory tract, thereby creating an en- sideration of both patient factors and pharmacologic vironment favoring the development of secondary principles when formulating one’s therapeutic plan. infections.1 Transport represents a well-described risk factor for lower respiratory infections, due to 2. Development of Disease the combined effects of prolonged periods of head The respiratory tract is the largest mucosal surface elevation, which physically impairs lower respira- in the body, with an enormous surface area con- tory clearance, with the immunosuppressive effects stantly exposed to the external environment. The of physiologic stress.2 Management situations that respiratory mucosa is exposed to large amounts of result in the intermingling of large numbers of potentially infectious material because each breath horses increase the risk of exposure to potential carries thousands of microscopic particles and mi- pathogens and induce stress that impairs pulmo- croorganisms into the respiratory tract. There are nary immunity. Individuals undergoing anesthe- numerous mechanisms that function to minimize sia are at risk of lower respiratory infections due to

NOTES

8 2011 ր Vol. 57 ր AAEP PROCEEDINGS IN-DEPTH: RESPIRATORY the temporary loss of the filtering function of the blood gas analysis may reveal hypoxia and hyper- upper respiratory tract and the immunosuppressive capnea in patients with diffuse lower respiratory effects of general anesthesia.3 Horses with dyspha- inflammation. Imaging studies may aid in the gia are also susceptible to lower respiratory tract staging and localization of lower respiratory infec- infections caused by aspiration of foreign material tions, with ultrasonography being particularly use- and large numbers of bacteria. ful in assessing the superficial pulmonary tissues Inhaled or aspirated bacteria from the upper re- and the pleural cavity. This can be performed in spiratory tract are the primary causes of bacterial the field, and even a linear reproductive probe can pneumonias in adult horses, unlike the situation in provide useful images when oriented lengthwise neonates, in which bacterial pneumonias are often of within the rib spaces. Thoracic radiographs are hematogenous origin. These infections develop ini- more challenging to obtain and are often not avail- tially on the surface of the respiratory mucosa but able in the field setting but provide a more global often progress to involve the pulmonary paren- assessment of pulmonary inflammation, allowing for chyma. Pulmonary abscessation can develop in sit- evaluation of the lung tissue below the pleural sur- uations in which physical and immunologic face. The sensitivity and specificity of radiographs clearance of the infectious organisms is incapable of can be low at times, however. Radiography is most completely resolving the infection. Pleuropneumo- useful in the detection of pathology deep within the nia develops when inflammation-associated injury lung and can be critically important in the diagnosis to the lung tissue secondary to bacterial broncho- of conditions such as pulmonary abscessation, neo- pneumonia breaks down the lung parenchyma and plasia, and equine multinodular pulmonary fibrosis. visceral pleura, allowing the infectious organisms Though not usually required in the initial evalu- access to the pleural space. When infection extends ation of patients with lower respiratory disease, air- into this space, it is difficult to resolve because it is way cytology is critical in the assessment of severe difficult for the immune system to mount an effec- or persistent lower respiratory infections. Airway tive immunologic response at this site, and the ac- cytology provides a clearer indication of the charac- cumulation of inflammatory cells and serous fluid ter of pulmonary inflammation, especially regarding within the pleural space provides an expanding res- the predominant type of inflammatory cells and the ervoir for infectious organisms. presence and type of bacteria, and is strongly indicated in patients that have undergone an unsuccess- 3. Diagnostic Evaluation ful course of antimicrobial therapy or those The clinical signs of pneumonia may include fever, presenting with evidence of severe lower respiratory cough, nasal discharge, tachypnea, dyspnea, depres- infection. Tracheal aspirates are easily obtained in sion, anorexia, and pain on palpation of the thoracic a sterile manner by either the percutaneous ap- wall (pleurodynia). The physical examination is key proach or the endoscopic approach, using a guarded in determining the extent and severity of lower respi- endoscopic aspiration catheter, allowing for culture ratory tract involvement, and this should include a of the sample. Bronchoalveolar lavage is less com- rebreathing examination in most cases. The re- monly used for the assessment of lower respiratory breathing test will greatly enhance the clinician’s abil- infections because of the potential for contamination ity to detect lower respiratory inflammation on occurring when the sampling device is advanced auscultation. This test should be avoided in patients through the upper respiratory tract that renders that are exhibiting severely increased respiratory ef- culture results suspect. Despite this limitation, the fort at rest. The presence of a cough on rebreathing is use of bronchoalveolar lavage can provide an impor- indicative of large airway inflammation/irritability. tant indication of small airway inflammation and Abnormal breath sounds indicate the presence of involvement, and the presence of suspected focal lower respiratory inflammation, with wheezes occur- pulmonary involvement is an indication for bron- ring as the result of small airway narrowing and choscopy and directed bronchial lavage.4 crackles being secondary to the presence of fluid ma- Thoracocentesis is indicated in cases in which terial in the small airways. The presence of very loud there is documented evidence of pleural fluid accu- airway sounds or the absence of airway sounds may mulation. This procedure can have both diagnostic indicate the presence of consolidated lung tissue or and therapeutic applications because it yields a ster- pleural effusion. The percussion test should not be ile sample for cytology and culture but also allows overlooked as a simple tool that can facilitate the iden- for the removal of fluid from the pleural cavity. tification of consolidated lung and/or pleural effusion. Draining of pleural effusion can be beneficial in de- Reluctance to move or the presence of pleural pain on creasing the degree of pulmonary dysfunction, in- palpation and/or percussion may indicate the presence creasing patient comfort, and removing large of pleural inflammation. amounts of inflammatory debris and large numbers Clinical pathology is important in evaluating the of bacterial organisms. Sterile lavage of the pleural animal with lower respiratory tract disease, with cavity through an indwelling thoracic drain can help to leukocytosis, neutrophilia, left shift, and hyperfi- remove additional inflammatory debris, and antimi- brinogenemia often accompanying the progression crobials can be added to the lavage fluid to achieve of lower respiratory bacterial infections. Arterial high local concentrations in the pleural cavity.

AAEP PROCEEDINGS ր Vol. 57 ր 2011 9 IN-DEPTH: RESPIRATORY Repeated airway cytology can also be useful in into respiratory secretions but only to levels less documenting the status of lower respiratory inflam- than observed in the systemic circulation.12 Be- mation but should not be required in most cases cause anaerobic involvement is likely in cases of showing clinical resolution. Changes in clinical pleuropneumonia, the treatment regimen should in- status often represent important indicators in the clude agents that will address this type of bacteria. progression of lower respiratory infections, however, Metronidazole is effective and well tolerated and and these include persistence and/or worsening of represents the gold standard for therapy of anaero- fever, changes in the character of coughing, and bic infections. signs of systemic inflammation. Such changes in Alternate routes of administration may be utilized clinical status represent an indication for thorough to achieve high concentrations of antimicrobials reassessment of the patient, potentially to include within the bronchial lumen, including intra- physical examination, clinicopathologic evaluation, bronchial and aerosol delivery.4,13 Concentration-de- imaging studies, and collection of respiratory secre- pendent antimicrobials are preferred for intrapulmo- tions for cytological assessment and culture. nary administration, with aminoglycosides being most commonly used in the horse.13,14 Time-dependent 4. Therapy antimicrobials such as the cephalosporins may be used Rest represents a critical component of the thera- by the intrapulmonary route but probably will require peutic plan for any lower respiratory infection, re- more frequent dosing, with ceftiofur typically being gardless of etiology, because the resolution of administered at 12-hour intervals.14 infection may take 1 to 2 weeks or more, and the Once an appropriate antimicrobial regimen has resolution of inflammation and healing of the respi- been selected, care should be taken to ensure that ratory epithelium may require an additional 2 to 4 the duration of therapy is adequate to ensure erad- weeks. Exercise before full resolution can expose ication of the infectious organisms within the lung, the lower respiratory tract to cold, dry air and high- which may take as long as 7 to 14 days for uncom- flow volumes, potentially resulting in further respi- plicated pneumonias but can require weeks to ratory epithelial injury and a resurgence of lower months in cases of pleuropneumonia. Repeated respiratory inflammation.5 This inflammation airway cytology may be useful in monitoring the could create an environment conducive to the recur- response to antimicrobial therapy because the deter- rence of infection or the development of secondary mination of resolution can be challenging, based on infection. Simple management tools may be of ben- clinical grounds alone. efit as well, and these would include feeding a diet Ancillary therapies such as bronchodilators and that minimizes the volume of inhaled antigenic ma- anti-inflammatories are not indicated in all cases of terial, such as a chopped forage or pelleted feed, as lower respiratory infection and may be counterpro- well as feeding from the floor level to encourage ductive by masking the clinical signs of lower respi- drainage of secretions from within the trachea. ratory involvement and encouraging owners or Bedding the stall in a low-dust material such as trainers to exercise these horses before healing is wood shavings, cardboard, or newspaper will de- complete. Horses exhibiting severe dyspnea or air- crease the volume of environmentally inspirable way hyperreactivity may benefit from bronchodila- particles, potentially decreasing the antigenic load tory therapy, however, because this may aid in on the lower respiratory tract.6 minimizing the severity of ventilation/perfusion The treatment of bacterial lower respiratory infec- mismatching as well as lessening the airway re- tions obviously depends on antimicrobial therapy, sponse to irritation. The beta-2 agonists (albuterol, but delivery of antimicrobials to the site of infection clenbuterol) are frequently used because they are can be challenging because of the barrier by the readily administered and have additional benefits, respiratory epithelium.7 The presence of infection including enhancement of mucociliary clearance. and/or inflammation can enhance the ability of an- The author prefers the aerosol route to the systemic timicrobials to cross the epithelium, but this effect route to achieve an immediate effect and to avoid may lessen as the inflammation resolves, impairing systemic toxicity. The beta-2 agonists should not antimicrobial delivery at the stage of final bacterial be administered continuously for more than 3 to 4 eradication. Therefore, the choice of antimicrobial weeks regardless of route because of the downregu- is dictated not only by a presumptive or established lation of the beta-2 receptors on the airway smooth sensitivity pattern but also by an understanding of muscle cells, which results in a loss of responsive- the drug’s intrapulmonary pharmacokinet- ness to these drugs. Anticholinergics, such as ipra- ics.8 Penicillins, cephalosporins, and aminoglyco- tropium bromide, are very useful and can be used sides9 penetrate only poorly into bronchial lining alone or in combination with a beta-2 ago- fluid, whereas macrolides10 and fluoroquinolones11 nist. Ipratropium bromide can only be adminis- can accumulate in the bronchial lining fluid and tered as an aerosol, most commonly using a airway macrophages to concentrations greater than metered-dose inhaler. The aerosol route minimizes the peak serum concentration. Other classes of an- the risk of ileus associated with other anticholin- timicrobials, specifically the tetracyclines and poten- ergics and provides very effective bronchodilation tiated sulfas, are expected to penetrate fairly well for up to 8 hours. Combination therapy with a be-

10 2011 ր Vol. 57 ր AAEP PROCEEDINGS IN-DEPTH: RESPIRATORY ta-2 agonist provides for a rapid but short-term ef- lower their heads to eat and drink. There may be fect (1.5 hours) from the beta-2 followed by a longer- some benefit to the use of immunomodulators before term effect from the anticholinergic (2 to 8 hours). transport to enhance lower respiratory immunity Nonsteroidal anti-inflammatory drugs (NSAIDs) during this period of stress. Horses with suspected are commonly used in the treatment of bacterial viral respiratory disease should be closely monitored lower respiratory infections, primarily to aid in sup- for changes in their condition, such as persistence of pressing fever and to decrease patient discomfort. fever beyond the first 2 to 3 days or a change in the There is some evidence from other species that character of the cough to moist and productive, be- NSAIDs not only control fever but also improve the cause these changes may signal the onset of second- clinical signs associated with lower respiratory inary bacterial infection. fections and modulate the inflammatory response, both within the lower respiratory tract and system- References and Footnotes 15,16 ically. Flunixin meglumine is the NSAID most 1. Delclaux C, Azoulay E. Inflammatory response to infectious commonly used by the author in adult horses and pulmonary injury. Eur Respir J Suppl 2003;42:10s–14s. appears to be effective while also exhibiting reason- 2. Raidal SL, Love DN, Bailey GD. Inflammation and increased numbers of bacteria in the lower respiratory tract of able safety. Firocoxib is a promising new drug that horses within 6 to 12 hours of confinement with the head appears to be clinically effective as an analgesic, but elevated. Aust Vet J 1995;72:45–50. less is known about the anti-inflammatory capabil- 3. Ciepichal J, Kubler A. Effect of general and regional anes- ity of this drug when treating bacterial infections. thesia on some neutrophil functions. Arch Immunol Ther Regardless of the drug used, care should be taken to Exp (Warsz) 1998;46:183–192. 4. McKenzie H. Bronchoscopic lavage for the treatment of focal discontinue NSAID therapy as soon as it is no longer pneumonia. 23rd ACVIM Veterinary Medical Forum, 2005. clearly indicated because of the risk of renal and 5. Davis MS, Lockard AJ, Marlin DJ, et al. Airway cooling and gastrointestinal toxicity. Care should be taken mucosal injury during cold weather exercise. Equine Vet J when monitoring the response to treatment in pa- Suppl 2002:413–416. 6. Woods PS, Robinson NE, Swanson MC, et al. Airborne dust tients on NSAID therapy because the suppression of and aeroallergen concentration in a horse stable under two fever by NSAIDs may be interpreted as a positive different management systems. Equine Vet J 1993;25:208– response to antimicrobial therapy. For this reason, 213. it is recommended to monitor the patient’s rectal 7. Chiu LM, Amsden GW. Intrapulmonary pharmacokinetics temperature immediately before administration of of antibacterial agents: implications for therapeu- tics. Am J Respir Med 2002;1:201–209. the next dose of NSAID because one may be able to 8. Cazzola M, Blasi F, Terzano C, et al. Delivering antibacte- appreciate an upward trend in the temperature at rials to the lungs: considerations for optimizing outcomes. this time that would otherwise be missed. Am J Respir Med 2002;1:261–272. Immunomodulatory therapy may be of some ben- 9. McKenzie HC 3rd, Murray MJ. Concentrations of gentamicin in serum and bronchial lavage fluid after intravenous and efit in shortening the time to recovery, and, although aerosol administration of gentamicin to horses. Am J Vet well-controlled studies are lacking, these com- Res 2000;61:1185–1190. pounds are used in many settings. Examples 10. Womble AY, Giguere S, Lee EA, et al. Pharmacokinetics of would include Propionibacterium acnes prepara- clarithromycin and concentrations in body fluids and bron- tionsa, mycobacterial cell wall extractsb, Parapoxvi- choalveolar cells of foals. Am J Vet Res 2006;67:1681–1686. 11. Hawkins EC, Boothe DM, Guinn A, et al. Concentration of rus ovis preparationsc, and products with undefined ® enrofloxacin and its active metabolite in alveolar macro- bacterial components (BI-KB , Bacterial Immuno- phages and pulmonary epithelial lining fluid of dogs. J Vet modulator–Killed Bacteria). Pharmacol Ther 1998;21:18–23. 12. Aoun M, Klastersky J. Drug treatment of pneumonia in the 5. Prevention hospital. What are the choices? Drugs 1991;42:962–973. 13. McKenzie HC 3rd, Murray MJ. Concentrations of gentami- Management is critical in reducing the incidence of cin in serum and bronchial lavage fluid after once-daily aero- viral respiratory infections, specifically Equine In- sol administration to horses for seven days. Am J Vet Res fluenza virus and Equine Herpes viruses 1 and 4 to 2004;65:173–178. decrease the risk of secondary bacterial infections. 14. McKenzie HC. Characterization of antimicrobial aerosols for administration to horses. Vet Ther 2003;4:110–119. Quarantine of new arrivals on the farm for a mini- 15. Bednarek D, Szuster-Ciesielska A, Zdzisinska B, et al. mum of 2 weeks decreases the likelihood of exposure The effect of steroidal and non-steroidal anti-inflammatory for the resident horses on the farm and is critical in drugs on the cellular immunity of calves with experimentally- situations with frequent travel and high turnover. induced local lung inflammation. Vet Immunol Immuno- pathol 1999;71:1–15. Vaccination, though not consistently effective in pre- 16. Bednarek D, Zdzisinska B, Kondracki M, et al. Effect of venting disease, may be helpful in enhancing the steroidal and non-steroidal anti-inflammatory drugs in com- individual’s immunity to these viruses and lessening bination with long-acting oxytetracycline on non-specific im- the severity of clinical disease and may aid in slow- munity of calves suffering from enzootic bronchopneumonia. ing the spread of disease throughout the farm pop- Vet Microbiol 2003;96:53–67. ulation after exposure. High stocking densities should be avoided because these promote the spread aEqstim®, Neogen Corporation, 944 Nandino Blvd., Lexington, KY 40511-1205. of infectious respiratory diseases. Transport bEquimune IV®, Bioniche Animal Health Inc., 1551 Jennings should include periods of rest at intervals of every 6 Mille Rd., Bogart, GA 30622. to 8 hours, during which time horses are allowed to cZylexis®, Pfizer Animal Health, Exton, PA 19341.

AAEP PROCEEDINGS ր Vol. 57 ր 2011 11