Equis ISSN 2398-2977

Therapeutics: respiratory system

Contributor(s): Tim Brazil, Timothy Mair, Graham Munroe, Miss Katie Snalune, Vetstream Ltd

Antimicrobials

  • Most common organisms involved are opportunistic bacteria originating from resident microflora of upper respiratory tract.
  • These bacteria are not capable of primary invasion and require decreased pulmonary defense mechanisms to cause disease, eg long distance transport, post-viral infection or recurrent airway obstruction; or overwhelming lung contamination, such as aspiration, post-exercise or impaired upper airway function:
  • Ideally an etiologic agent should be identified from either tracheobronchial aspirates or pleural fluid samples allowing antimicrobial sensitivity to be determined.
  • In vitro culture and sensitivity results can sometimes be misleading.
  • Dose, dosing interval and route of administration must achieve effective levels of antimicrobial in the specific infected area of the respiratory tract.
  • Initial antimicrobial choice should be based on:
    • Severity of clinical signs.
    • Knowledge of common pathogens.
    • Gram staining of tracheal secretions.
  • In the absence of bacterial culture results, broad spectrum antibiotics should be used as the majority of horses have mixed infections of gram-positive and gram-negative organisms.

Broad spectrum therapy

  • Lower respiratory tract infections are most likely to be sensitive in vitro to ceftiofur   Ceftiofur  , cefquinome, penicillin   Therapeutics: beta-lactam antibacterials  , fluoroquinolones   Therapeutics: nitrofurans / nitroimidazoles / quinolones  and tetracyclines   Therapeutics: tetracyclines  , the latter two being effective against mycoplasma   Lung: pneumonia - bacterial  also.
  • Streptococcal infections are most common:
    • Procaine penicillin G   Penicillin G  22,000 IU/kg IM BID or sodium penicillin G 22,000 IU/kg IV QID.
  • If polymicrobial infection, gentamicin   Gentamicin  6.6 mg/kg IV SID, or enrofloxacin 7.5 mg/kg IV or PO SID, should be added.
  • Gentamicin and enrofloxacin are rarely indicated as sole therapies.
  • Ceftiofur   Ceftiofur   5 mg/kg IM BID, appropriate choice for common pathogens - often successful as sole therapy for uncomplicated pneumonia.
  • Cefquinome is a time-dependent bactericidal antibiotic with:
  • Licensed for treatment of equine respiratory diseases caused by Streptococcus equisubsp zooepidemicusat 1 mg/kg IV or IM SID.
  • Tetracyclines   Therapeutics: tetracyclines  :
    • Are active against many gram-positive organisms, some gram-negative organisms, including Actinbacillus equuli  Actinobacillus equuli  , and have good tissue penetration in lung, but resistance is common.
    • Oxytetracycline   Oxytetracycline   5-10 mg/kg IV BID.
    • Doxycycline 10 mg/kg PO BID, is useful for treatment of chronic lower respiratory tract infections and as secondary treatment to initial parenteral therapy. However, low bioavailability when administered as a top dressing has been reported.
  • Rifampicin   Rifampicin   5-10 mg/kg PO BID:
    • Widely distributed with good intracellular penetration and excellent activity against Rhodococcus equi  Rhodococcus equi   in foals.
    • Resistance develops rapidly, so frequently administered in combination with a macrolide, eg clarithromycin at 7.5 mg/kg PO BID.
  • Long-term therapy is often required hence initial IV or IM therapy should be followed by oral antimicrobials.
  • Trimethoprim and sulfamethoxazole   Sulfadoxine with Trimethoprim   30 mg/kg PO BID:
    • Ease of administration and cost effective.
    • Good tissue penetration and achieves good intracellular concentrations but inactivated by purulent and necrotic material; better if airway secretion non-purulent, which excludes efficacy against common Streptococcal lower airway infections.
    • Resistance to Enterobacteriaceae   Enterobacter / Aerobacter spp   common.
    • Not appropriate as first line therapy or in acute severe infection, unless highly susceptible organism isolated.

Anerobic pleuropneumonia

Metronidazole is a prohibited substance for food producing animals - check passport.

Metronidazole has no activity against aerobic bacteria and should only be used in combination therapy.

  • Initial therapy often used: procaine penicillin G   Penicillin G  22,000 IU/kg IM BID or sodium penicillin G 22,000 IU/kg IV QID + gentamicin   Gentamicin   6.6 mg/kg IV SID + metronidazole   Metronidazole  15 mg/kg IV or PO SID.

Do not initiate oral therapy until the horse's condition is stable and improving, as blood levels obatined by this route are not as high as those reached following parenteral routes.

Alternative routes of administration

Nebulization

  • Good administration technique, including  the use of good equipment, maintaining a good seal between the mask and the patient, and synchronization of actuation with inspiration, are vital to the success of this route of drug delivery.
  • Requires a spacer device that is robust and comfortable for the horse, easy to use, effective and clean. Three have been specifically designed for the horse; the Equine Haler    Respiratory: Equine Haler - in use  , the Flexineb    Respiratory: Flexineb - in use   and the AeroHippus Equine Aerosol Chamber.

No inhaled medicines are licensed for equine use and should only be administered to animals not intended for human consumption, after due consideration of the drug cascade.

Human paediatric spacers should be used with caution because of their lack of inspiratory valves.

  • A device to produce a drug aerosol of 1-5 mm average particle/droplet size is also required. Several types are available:
    • Ultrasonic nebulizer.
    • Compressed air (jet) nebulizer.
    • Pressurized metered dose inhalers (MDI).
    • Dry powder inhalers (inspiration-driven) requires a specialized airtight mask.
  • The inhaled route is still controversial for antimicrobial delivery in the horse. 
  • Potential benefits are: 
    • Focal delivery within the bronchial tree.
    • High dose levels achievable.
    • Rapid delivery of high concentrations to the fluid lining the pulmonary epithelium.
    • An alternative route for administration of systemically adverse drugs, eg some antifungals, high doses of aminoglycosides.
  • Potential disadvantages:
    • Local inflammatory effect of some antibiotics.
    • ? Ability to penetrate lung parenchyma - should not be used in patients with significant lung consolidation or interstitial involvement.
    • Drug administration time can be prolonged: 15-20 min.
    • Some formulations can cause bronchoconstriction by direct irritation.
    • There may be interactions between the drug, propellant and equipment used resulting in wide discrepancies between the dose administered and that delivered to the smaller airways (usually particle-size related), and subsequent systemic levels achieved. 
  • Pre-treatment with salbutamol   Salbutamol sulfate  may facilitate passage to small airways.
  • Aminoglycosides   Therapeutics: aminoglycosides  are ideal for aerosol delivery because their efficacy is directly related to peak drug concentrations and they can be administered less frequently because of their post-antibiotic effect.
  • Concentrations <100 mg/ml in 0.23-0.45% saline should be used:
    • Gentamicin   Gentamicin  1000 mg: 50 mg/ml nebulized in sterile saline BID via nebulizer.
    • Ceftiofur   Ceftiofur  300 mg: 50 mg/ml nebulized in sterile saline BID via nebulizer.
    • Marbofloxacin 300 mg: 25 mg/ml.
    • Cefquinome 225 mg (4.5%): in sterile salnie via jet nebulizer.
  • Further clinical research needs to be done to determine indications, dosages and drug concentrations. New nebulizing apparatus is already being developed and it is probable that this route of treatment will increase in importance in the future.

Anti-inflammatories

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Bronchodilators

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Expectorants, mucolytics and mucokinetics

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Immunomodulators

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Use of inhalation therapy in LRT disease

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Further Reading

Publications

Refereed papers
  • Recent references fromPubMed andVetMedResource.
  • Bertin F R, Ivester K M & Couëtil L L (2011)Comparative efficacy of inhaled albuterol between two hand-held delivery devices in horses with recurrent airway obstruction. Equine Vet J 43(4), 393-398PubMed.
  • Matera M G, Calzetta L, Rogliani P, Bardaro F, Page C P & Cazzola M (2011)Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi. Pulm Pharmacol Ther 24(2), 221-226PubMed.
  • Winther L, Honoré Hansen S, Baptiste K E & Friis C (2011)Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part II. Doxycycline.  J Vet Pharmacol Ther 34(3), 285-289PubMed.
  • Winther L, Guardabassi L, Baptiste K E & Friis C (2011)Antimicrobial disposition in pulmonary epithelial lining fluid of horses. Part I. Sulfadiazine and trimethoprim.  J Vet Pharmacol Ther 34(3), 277-284PubMed.
  • Leclere M, Lefebvre-Lavoie J, Beauchamp G & Lavoie J P (2010)Efficacy of oral prednisolone and dexamethasone in horses with recurrent airway obstruction in the presence of continuous antigen exposure.  Equine Vet J 42(4), 316-321PubMed.
  • Kearns C F & McKeever K H (2009)Clenbuterol and the horse revisited.  Vet J182(3), 384-391PubMed.
  • Roberts C A (2009)The impact of long-term clenbuterol on athletic performance in horses.  Vet J 182(3), 377PubMed.
  • Robinson N E, Berney C, Behan A & Derksen F J (2009)Fluticasone propionate aerosol is more effective for prevention than treatment of recurrent airway obstruction.  J Vet Intern Med23(6), 1247-1253PubMed.
  • Haggett E F & Wilson W D (2008)Overview of the use of antimicrobials for the treatment of bacterial infections in horses. Equine Vet Educ20, 433-448.
  • Art T, de Moffarts B, Bedoret D, van Erck E & Lekeux P (2007)Pulmonary function and antimicrobial concentration after marbofloxacin inhalation in horses.  Vet Rec 161(10), 348-350PubMed.
  • Laan T T, Bull S, van Nieuwstadt R A & Fink-Gremmels J (2006)The effect of aerosolized and intravenously administered clenbuterol and aerosolized fluticasone propionate on horses challenged with Aspergillus fumigatus antigen.  Vet Res Commun 30(6), 623-635.PubMed.
  • Laan T T, Bull S, Pirie R S & Fink-Gremmels J (2006)The anti-inflammatory effects of IV administered clenbuterol in horses with recurrent airway obstruction.  Vet J 171(3), 429-437PubMed.
  • McKenzie H C 3rd & Murray M J (2004)Concentrations of gentamicin in serum and bronchial lavage fluid after once-daily aerosol administration to horses for seven days.  Am J Vet Res 65(2), 173-178PubMed.
  • McKenzie H C 3rd & Murray M J (2000)Concentrations of gentamicin in serum and bronchial lavage fluid after intravenous and aerosol administration of gentamicin to horses.  Am J Vet Res 61(10), 1185-1190PubMed.
  • Foreman J H (1999)Equine respiratory pharmacology. Vet Clin North Am Equine Pract15(3), 665-686, ix-xPubMed.
  • Bertone J J (1997)Antimicrobial therapy for respiratory disease. Vet Clin North Am Equine Pract13(3), 501-517PubMed.
  • Van Duijkeren E, Vulto A G & Van Miert A S (1994)Trimethoprim/sulfonamide combinations in the horse - a review. J Vet Pharmacol Ther17(1), 64-73PubMed.
  • Baggot J D & Prescott J F (1987)Antimicrobial selection and dosage in the treatment of equine bacterial infections. Equine Vet J19(2), 92-96PubMed.
  • Mair T S (1987)Equine pleuropneumonia - the importance of anaerobic bacteria and the potential value of metronidazole in treatmentVet Rec121(5), 109-110PubMed.

Other sources of information

  • Durham A (2011) Inhalation Therapy for LRT Disease.In: Handbook of Presentations, BEVA Congress 2011. MSD Animal Health. pp 226.
  • Kohn C W (2011) Systemic Antibacterial Therapy for Lower Respiratory Tract Disease.In: Handbook of Presentations, BEVA Congress 2011. MSD Animal Health. pp 222-223.
  • McGorum B (2011) Systemic Anti-Inflammatory Therapy for LRT Disease.In: Handbook of Presentations, BEVA Congress 2011. MSD Animal Health. pp 224-225.
  • Durham A E (2006)The Value of Inhalation Therapy for Lower Airway Disease. In: Handbook of Presentations & Free Communications, BEVA Congress 2006. Schering-Plough Animal Health, Middlesex, UK. pp 225-226.
  • Rush B R & Davis E G (2006)Pharmacology and Therapeutics of Pulmonary Medications.In: Equine Respiratory Medicine and Surgery. Eds: McGorum B C, Dixon P M, Robinson N E & Schumacher J. Elsevier, Edinburgh.
  • Rush B R (2004)Inhalation Therapy for the Respiratory System. In: Equine Clinical Pharmacology. Eds: Bertone J J & Horspool L J I. Saunders, Philadelphia. pp 311-325. ISBN: 0 7020 2484 8.


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