Plasma and pulmonary disposition of ceftiofur and its metabolites after intramuscular administration of ceftiofur crystalline free acid in weanling foals

The objectives of this study were to determine the plasma and pulmonary disposition of ceftiofur crystalline free acid (CCFA) in weanling foals and to compare the plasma pharmacokinetic profile of weanling foals to that of adult horses. A single dose of CCFA was administered intramuscularly to six weanling foals and six adult horses at a dose of 6.6 mg/kg of body weight. Concentrations of desfuroylceftiofur acetamide (DCA) were determined in the plasma of all animals, and in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells of foals. After intramuscular (IM) administration to foals, median time to maximum plasma and PELF concentrations was 24 h (12-48 h). Mean (± SD) peak DCA concentration in plasma (1.44 ± 0.46 μg/mL) was significantly higher than that in PELF (0.46 ± 0.03 μg/mL) and BAL cells (0.024 ± 0.011 μg/mL). Time above the therapeutic target of 0.2 μg/mL was significantly longer in plasma (185 ± 20 h) than in PELF (107 ± 31 h). The concentration of DCA in BAL cells did not reach the therapeutic level. Adult horses had significantly lower peak plasma concentrations and area under the curve compared to foals. Based on the results of this study, CCFA administered IM at 6.6 mg/kg in weanling foals provided plasma and PELF concentrations above the therapeutic target of 0.2 μg/mL for at least 4 days and would be expected to be an effective treatment for pneumonia caused by Streptococcus equi subsp. zooepidemicus at doses similar to the adult label.     

Effects of the bronchoalveolar lavage procedure on lung function in horses with clinical exacerbation of recurrent airway obstruction

OBJECTIVE: To evaluate whether bronchoalveolar lavage (BAL) alters respiratory mechanics of horses with recurrent airway obstruction (ie, heaves) over a 48-hour period. ANIMALS: 6 horses affected with heaves. PROCEDURES: Horses were subjected to a complete BAL procedure, which included sedation with xylazine and butorphanol, intratracheal administration of lidocaine, and instillation and aspiration of two 250-mL boluses of saline (0.9% NaCl) solution through an endoscope (study 1). To evaluate the effects of saline solution, horses were subjected to the same procedure without saline solution instillation and aspiration (study 2). Lastly, the endoscope was similarly introduced into the lower airways, without sedation or saline instillation and aspiration (study 3). Respiratory mechanics were performed at baseline (time 0) and at 3, 6, 12, 24, and 48 hours after each procedure. RESULTS: In study 1, BAL induced a significant decrease in pulmonary resistance lasting up to 6 hours. This may have resulted from clearance of mucus in large airways. We also observed a significant increase in lung elastance and transpulmonary pressure at 12 hours after BAL in all 3 studies, which may be attributed to a circadian effect. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that the temporal effects of BAL procedures on lung mechanics should be taken into account when designing research protocols involving horses with heaves. Future studies should address the immediate effects of BAL on lung function.     

Pharmacokinetics of macrolides in foals

Macrolides are used for treatment of pneumonia and extrapulmonary conditions caused by Rhodococcus equi. In foals, macrolides have an extraordinary capacity to accumulate in different lung tissue compartments. These drugs show unique pharmacokinetic features such as rapid and extensive distribution and long persistence in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells from foals. This article reviews the pharmacokinetic characteristics of erythromycin, azithromycin, clarithromycin, tulathromycin, telithromycin, gamithromycin, and tilmicosin in foals, with emphasis on PELF and BAL cell concentrations.     

Study of the duration and distribution of equine influenza virus subtype 2 (H3N8) antigens in experimentally infected ponies in vivo.

The purpose of this experiment was to study the duration and distribution of equine influenza virus in actively infected ponies over a 3 wk period. Pony foals (6-8 mo old) were infected experimentally by nebulizing equine influenza subtype-2 virus ultrasonically through a face mask. Successful infection was clinically apparent as each of the foals (n = 6) had a febrile response, a deep hacking cough and mucopurulent nasal discharge for 7 to 10 d. The virus was isolated from nasopharyngeal swabs of all the ponies 3 and 5 d after infection and all the ponies seroconverted to the virus. Samples were taken from the nasopharynx, mid-trachea and the mainstem bronchus with cytology brushes through an endoscope as well as from bronchoalveolar lavage fluid. On days 3 to 7 post-infection, ciliacytophtorea (the presence of cilia and ciliated plates separated from columnar epithelial cells) was recognized on routine cytological stain. Indirect immunoperoxidase staining utilizing polyclonal antibodies demonstrated viral antigen in intact and fragmented ciliated epithelial cells and in fragments of ciliated plates. The infected cells and cell fragments were particularly evident on days 3 and 5 post-infection in the nasopharynx, mid-trachea and mainstem bronchus and on days 3 to 7 post-infection in the bronchoalveolar lavage samples. On days 7 and 21 post-infection, viral antigen was identified in vacuoles of alveolar macrophage-like cells collected by bronchoalveolar lavage. It can be concluded from this study that equine influenza virus can infect not only the upper airways but also the bronchial epithelium and that viral antigen can persist up to 21 d post-infection.     

Bronchoalveolar lavage cytology in cynomolgus monkeys and identification of cytologic alterations following sequential saline lavage

Total and differential cell counts were determined on cytolytic specimens obtained by fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) of five normal cynomolgus monkeys. Total nucleated cell counts ranged from 100 to 430 cells/microliters. Macrophages were approximately 91% of total nucleated cells, while lymphocytes were 3%, neutrophils 4%, and eosinophils 2% of the initial BAL from each monkey. Less than 1% of the cells were mast cells and ciliated or nonciliated epithelial cells. The effects of repeated saline BAL on pulmonary cell populations were evaluated. Saline lavage of individual lung lobes resulted in a marked rise in circulating blood neutrophils at 4 hr after BAL; there was a similar rise in neutrophils in lavage fluids 24 hr after the initial lavage. Differential and total cell counts of both blood and lavage fluid returned to normal if subsequent lavages were spaced at 48-hr intervals. Lymphocytes were not present in saline-lavaged lung lobes, and protein levels of lavage fluids did not rise significantly. BAL produced a transient, reversible, intra-alveolar influx of neutrophils which was preceded by mobilization of bone marrow-stored neutrophils. Neutrophilia in the lavage fluid and blood was not detectable if lavage and blood sampling procedures were done at 48-hr intervals (which did not alter Ia antigen expression among BAL cells). These observations indicate that BAL is a valid method for sampling and assessing pulmonary cellular and fluid constituents if the procedures are done at intervals of at least 48 hr.     

Comparison of endoscopic tracheal washing, bronchoalveolar lavage and visual detection of blood following instillation of blood into the airways of horses

In an experimental study of endoscopic tracheal washings and bronchoalvveolar lavage specimens collected prior to and following instillation of 0,250, 500 or 1000 ml of autologous citrated blood into the airways of nonexercising, adult horses, there was no apparent correlation between the amount of blood or exudate seen endoscopically, the volume of washing fluid recovered, or the cytologic evaluation of numbers of erythrophages or siderophages. Tracheal washing and bronchoalveolar lavage specimens appear to be complementary for detection of erythrophages or siderophages in cytologic specimens since these cell types may be present in one, or the other, or both types of specimens. There may be an advantage to collecting two BAL specimens since more erythrophages or siderophages were seen in the second BAL in some horses. Further studies of experimentally-instilled blood and spontaneouslyoccurring exercise-induced pulmonary hemorrhage are needed to further characterize the mechanisms by which pulmonary hemorrhage is resolved and/or characterize the cytologic methods best suited for detection and/or quantitation of pulmonary hemorrhage.     

Pulmonary disposition of erythromycin, azithromycin, and clarithromycin in foals

The objectives of the present study were to determine and compare the pulmonary disposition of azithromycin, clarithromycin, and erythromycin in foals. A single dose (10 mg/kg) of azithromycin, clarithromycin, or erythromycin was administered intragastrically to six healthy 1- to 3-month-old foals using an orthogonal design. Activity of the drugs was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells by use of a microbiologic assay. Peak drug activity in PELF was significantly higher in foals treated with clarithromycin (48.96+/-13.26 microg/mL) than in foals treated with azithromycin (10.00+/-7.46 microg/mL). Quantifiable erythromycin activity in PELF was only found in two of six foals. Peak drug activity in BAL cells was not significantly different between azithromycin (49.92+/-26.94 microg/mL) and clarithromycin (74.20+/-45.80 microg/mL) but activity for both drugs was significantly higher than that of erythromycin (1.02+/-1.11 microg/mL). Terminal half-life of azithromycin in serum (25.7+/-15.4 h), PELF (34.8+/-30.9 h), and BAL cells (54.4+/-17.5 h) was significantly longer than that of both clarithromycin and erythromycin. Peak azithromycin and clarithromycin activity was significantly higher in BAL cells, followed by PELF, and serum. In contrast, peak erythromycin activity in BAL cells was not significantly different from that of serum.     

Flexible bronchoscopy and bronchoalveolar lavage in 68 cats (2001-2006)

BACKGROUND: Bronchoscopy is an important tool for identifying an underlying etiology for respiratory disease in cats. However, the procedure is challenging, because feline airways are small and prone to bronchoconstriction. HYPOTHESIS: Bronchoscopy and bronchoalveolar lavage (BAL) are appropriate and safe diagnostic procedures in the cat. ANIMALS: Sixty-eight cats. METHODS: Flexible bronchoscopy was performed in all cats with the cats under propofol infusion with jet ventilation. The procedures were reviewed for BAL volumes instilled and recovered and for the number and type of complications with the use of 3 flexible endoscopes < 5.0-mm outer diameter. The BAL procedure was compared among scopes by using a one-way analysis of variance. Complication rates were compared by using chi-square analysis. Significance was set at P < .05. RESULTS: Clinical diagnoses included inflammatory airway disease in 46 of 68 cats, pneumonia in 10 of 68, neoplastic disease in 8 of 68, and other conditions in 4 of 68 cats. Mean lavage volumes instilled for the 3 scopes were 2.62-5.05 mL/kg (range, 0.77-9.38 mL/kg). Mean percent fluid recovered for the 3 scopes was 51-73%, (range, 0-140%). BAL cell counts were adequate for cytologic assessment (> 300 cells/microL) in 61 of 64 cats (97%), and in 107 of 120 samples (89%) collected. Complications occurred in 38% of procedures; however, these were mild in 24% of cats; 6% of cats died or were euthanized after the procedure. Complications were not associated with fluid volume instilled or recovered, and could not be related to the underlying disease process. CONCLUSIONS AND CLINICAL IMPORTANCE: Flexible bronchoscopy with BAL was well tolerated in most cats examined.     

Comparison of transtracheal aspirate and bronchoalveolar lavage cytology in 50 horses with chronic lung disease

Comparisons were made between transtracheal aspirate (TTA) and bronchoalveolar lavage (BAL) cytology obtained from 50 horses with chronic lung disease and from 10 control horses. There was no significant correlation between the TTA cytology and the BAL cytology, suggesting that the cell population in the trachea is not representative of the cell population in the lower airways. In control horses the range of differential cell counts obtained from TTA fluid was remarkably large, whereas the variability in cell populations observed in BAL fluid was smaller. In the principal horses the total and differential cell counts of the TTA and BAL fluids were within the 95 per cent confidence interval in 38 and 24 per cent of cases, respectively; and an increase in percentage neutrophils was most common. It was concluded that BAL may be a useful diagnostic aid when evaluating horses with chronic lung disease, but that the clinical usefulness of cytological evaluations of TTA fluid may be limited in these cases.     

Use of a modified stomach tube for bronchoalveolar lavage in dogs

A technique that did not require use of a bronchoscope for bronchoalveolar lavage (BAL) in dogs was developed. An inexpensive, readily available 16-F Levin-type stomach tube was modified for the procedure. The technique was effective for collecting BAL fluid in 9 dogs that ranged from 9.3 to 26.2 kg (20.5 to 57.6 lb). Recovered fluid was consistent with fluid collected bronchoscopically. Mean recovery volume was 84/125 ml (67%), mean WBC counts were high (> 300 cells/microl), and > 70% of cells were macrophages. Complications from use of the technique were not detected on the basis of pulse oximetry, thoracic radiography, and clinical observation. This effective, simple, and safe technique for BAL can be readily performed in clinical settings that do not have bronchoscopic capabilities. It also provides a less costly alternative than bronchoscopic BAL.     

Use of a protected catheter brush for culture of the lower respiratory tract in horses with small airway disease.

A protected catheter brush introduced by fiberoptic bronchoscopy was used to sample the tracheai and bronchial mucosa in 28 horses with small airway disease. Tracheal and bronchial brushings were examined for the presence of fungi, aerobic and anaerobic bacteria, and a cytoiogical evaluation was also done on fluid collected by the bronchoalveolar lavage (BAL) technique. Microorganisms (bacteria and fungi) were isolated more often in tracheal brushings (53.6%) than in bronchial brushings (10.7%). Anaerobic bacteria were not isolated. Results of this study indicate that fiberoptic bronchoscopy using a protected catheter brush is an easy and practical technique to obtain minimally contaminated samples for isolation of microorganisms from the lower respiratory tract of horses. However, no association was observed between isolation of high numbers of microorganisms from the bronchi and severity of small airway disease.     

Clinical alterations and mRNA levels of IL-4 and IL-5 in bronchoalveolar cells of horses with transient pulmonary eosinophilia

The aim of this study was to assess clinical signs and altered pulmonary cell expression of cytokines related to eosinophil kinetics in horses with pulmonary eosinophilia. Pulmonary eosinophilia was detected by bronchoalveolar lavage (BAL) in a group of standardbreds in training. Horses had detailed clinical examination, bronchoscopy, endobronchial biopsy and BAL on three occasions at approximately 6 month intervals. During the second sampling period BAL eosinophils were significantly elevated (p>0.010), with five horses having from 5% to 37% eosinophils in BAL. Neither detailed clinical examination parameters nor gene expression of IL-4 and IL-5 mRNA (real-time-PCR) were associated with BAL eosinophilia. Pulmonary eosinophilia abated without treatment apart from deworming. It appears that pronounced lung eosinophilia in horses can be transient, abate without specific treatment, and in this instance, lack correlation to upregulation of expression of either IL-4 or IL-5.     

Bronchoscopy in small animal medicine: indications, instrumentation, and techniques

Bronchoscopy is a useful tool in the evaluation and management of canine and feline respiratory diseases. Diagnostic indications include the evaluation of structural diseases (tracheobronchial collapse, stricture, intraluminal mass); inflammatory conditions (chronic bronchitis, pneumonia); and traumatic injuries. Several airway-sampling techniques are available with bronchoscopy; bronchoalveolar lavage has proved to be the most satisfactory specimen-collection technique. Therapeutic indications of bronchoscopy at this time in veterinary medicine are mainly limited to foreign body removal. As advances are made in veterinary bronchopulmonary medicine, other therapeutic applications of the bronchoscope may be realized.     

Comparison of tracheal aspirates and bronchoalveolar lavage in racehorses. 1. Evaluation of cytological stains and the percentage of mast cells and eosinophils

OBJECTIVE: To compare a fast Romanowsky cytological stain (Diff-Quik) and Leishman's stain for the detection of mast cells in samples from the lower airways of racehorses, and to compare the proportion of mast cells and eosinophils in the total inflammatory cells in tracheal aspirate (TA) with those in paired bronchoalveolar lavage (BAL) samples. DESIGN: Retrospective case series of 48 young Thoroughbred and Standardbred racehorses. PROCEDURE: Fifty-one paired TA and BAL samples were collected after treadmill exercise from 48 horses with poor racing performance. Two slides were prepared from each sample; one was stained with Diff-Quik stain and the other with Leishman's stain. Differential cell counts of eosinophils and mast cells were recorded from each slide. Comparison of the suitability of the stains for the detection of mast cells, and comparisons of eosinophil and mast cell percentages in TA and BAL samples were analysed using the non-parametric Wilcoxon matched pairs test. RESULTS: Percentages of mast cells were significantly higher in Leishman than in Diff-Quik stained slides in both TA (P = 0.03) and BAL samples (P < 0.0001). Mast cell percentages were significantly higher in BAL than in TA samples using Leishman's stain (P < 0.0001). There was no significant difference in eosinophil percentages between TA and BAL samples (P = 0.07). CONCLUSIONS: Fast Romanowsky type stains (for example Diff-Quik) are not appropriate for the detection of mast cells in samples from the equine lower respiratory tract. Therefore, a metachromatic stain that reliably identifies mast cells (for example Leishman's) should be used if evaluation of mast cells in lower respiratory tract is undertaken. Mast cells are predominantly found in the distal small airways and alveoli sampled with a BAL. In contrast, eosinophils appear to be evenly distributed in the lower respiratory tract. However, high percentages of eosinophils are occasionally found only in TA samples. We recommend that both a TA and BAL be used for the evaluation of eosinophils and mast cells within the equine lower respiratory tract.     

Bronchodilators in bronchoscopy-induced airflow limitation in allergen-sensitized cats

This study investigated the effect of bronchoscopy and bronchoalveolar lavage (BAL) on respiratory function, determined by barometric whole-body plethysmography (BWBP), of healthy and allergen-sensitized cats. Furthermore, the efficacy of inhaled bronchodilators in preventing changes in respiratory function was determined. For test 1, 18 healthy experimental cats were investigated on day 1 by BWBP. On day 2, the cats underwent BWBP after sedation (medetomidine), after anesthesia induction (propofol), and after bronchoscopy and BAL. Enhanced pause (Penh) was significantly increased after bronchoscopy and BAL (1.64 +/- 0.17 versus 1.23 +/- 0.07, P < .05). For test 2, 6 cats were sensitized to ovalbumin (OVA), 6 cats were sensitized to Ascaris suum (AS), and 6 cats served as controls. On day 0, OVA- and AS-sensitized cats underwent an inhaled allergen challenge, whereas controls were exposed to saline. On days 1 and 2, the same protocol as described for test 1 was repeated. Post-BAL Penh of the AS-sensitized cats was significantly higher than at test 1 (2.28 +/- 0.22 versus 1.69 +/- 0.33, P < .05) and was correlated with BAL fluid neutrophil count (r = 0.55, P < .05). During tests 3, 4, and 5, the same protocol as used for test 2 was applied to each cat group, with the animals being randomly treated before sedation with inhaled salbutamol (200 microg), ipratropium bromide (40 microg), or a combination of both (200 + 40 microg). Post-BAL Penh of the AS-sensitized group was significantly decreased after the salbutamol + ipratropium bromide treatment (1.56 +/- 0.18 versus 2.28 +/- 0.22, P < .05). This study suggests that bronchoscopy and BAL induce airflow limitation in cats, which is more severe in the presence of lower airway inflammation. Inhaled salbutamol + ipratropium bromide reduce BAL-induced bronchoconstriction in AS-challenged cats and might be recommended as preventive treatment of asthmatic cats undergoing bronchoscopy.     

Changes in the bacterial flora of the upper and lower respiratory tracts and bronchoalveolar lavage differential cell counts in feedlot calves treated for respiratory diseases.

Serial nasopharyngeal swab and bronchoalveolar lavage cultures were used to estimate changes in the bacterial flora of the respiratory tracts of calves during the first month after arrival in the feedlot. Bronchoalveolar lavage (BAL) differential cell counts served to evaluate pulmonary inflammatory changes during this period. Two groups of calves were studied, one consisting of clinically normal controls (n = 60), the other, of cases (n = 59) which received treatment for respiratory disease (penicillin +/- trimethoprimsulfadoxine). A variety of organisms, including Pasteurella multocida, Pasteurella haemolytica, Haemophilus somnus, Mycoplasma bovis and Mycoplasma bovirhinis, were present in the upper and lower airways of both groups during the postarrival period. With the exception of M. bovis, an overall decline in the prevalence of these organisms was observed during the course of the study. In cases, there was a marked decrease in the number of Pasteurella spp. and H. somnus isolates immediately following treatment. For the Pasteurella spp., however, this effect was shortlived as they often appeared to recolonize the respiratory tract within eight days of terminating antimicrobial therapy. Treatment did not appear to affect the frequency of isolating M. bovis. Its prevalence, in both groups of calves, increased to levels approaching 100% during the course of the study. All Pasteurella spp. isolates were tested for susceptibility to several commonly used antimicrobials. Resistance was only evident among P. haemolytica isolated from cases and in every instance this was to a combination of penicillin, ampicillin and tetracycline. Significantly more isolates were resistant after treatment than before. There were BAL differential cell count abnormalities indicative of inflammation in both cases and controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary disposition of tilmicosin in foals and in vitro activity against Rhodococcus equi and other common equine bacterial pathogens

The objectives of this study were to determine the serum and pulmonary disposition of tilmicosin in foals and to investigate the in vitro activity of the drug against Rhodococcus equi and other common bacterial pathogens of horses. A single dose of a new fatty acid salt formulation of tilmicosin (10 mg/kg of body weight) was administered to seven healthy 5- to 8-week-old foals by the intramuscular route. Concentrations of tilmicosin were measured in serum, lung tissue, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils. Mean peak tilmicosin concentrations were significantly different between sampling sites with highest concentrations measured in blood neutrophils (66.01+/-15.97 microg/mL) followed by BAL cells (20.1+/-5.1 microg/mL), PELF (2.91+/-1.15 microg/mL), lung tissue (1.90+/-0.65 microg/mL), and serum (0.19+/-0.09 microg/mL). Harmonic mean terminal half-life in lung tissue (193.3 h) was significantly longer than that of PELF (73.3 h), bronchoalveolar cells (62.2 h), neutrophils (47.9 h), and serum (18.4 h). The MIC90 of 56 R. equi isolates was 32 microg/mL. Tilmicosin was active in vitro against most streptococci, Staphylococcus spp., Actinobacillus spp., and Pasteurella spp. The drug was not active against Enterococcus spp., Pseudomonas spp., and Enterobacteriaceae.     

Clinical, radiographic, endoscopic, bronchoalveolar lavage and lung biopsy findings in horses with exercise-induced pulmonary hemorrhage

A clinical study was performed to determine whether clinical, endoscopic, radiographic, bronchoalveolar lavage (BAL) cytological, and pulmonary biopsy findings could be correlated in horses with exercise-induced pulmonary hemorrhage (EIPH) compared with controls. Racing standardbred horses were selected as either EIPH (n = 10) or control (n = 10), based on repeated postexertional endoscopy of the lower airways. Complete physical and respiratory examinations were performed and blood samples were submitted for arterial blood gas analysis, hematologic study, and fibrinogen determination. Bilateral chest radiographs were taken with the horse standing, and a BAL sample was obtained for cytological examination. Lung was biopsied transcutaneously. Weighted scores were calculated for clinical, radiographic, and pulmonary biopsy findings. The conclusion was that only routine physical examination may help the clinician when EIPH is suspected in horses, especially when there are abnormal findings on percussion of the caudodorsal areas of the chest.     

Quantitative bacterial cultures and cytological examination of bronchoalveolar lavage specimens in dogs

Cytology and quantitative bacterial cultures of lower respiratory tract secretions are widely used in human medicine to differentiate airway infection from simple bacterial colonization. A retrospective study was conducted to determine the usefulness of quantitative aerobic cultures and Gram stain intracellular bacteria counts from bronchoalveolar lavage (BAL) specimens in dogs in diagnosing lower respiratory tract infection (LRTI) and to determine whether chronic bronchitis is associated with marked bacterial growth in dogs. The threshold determined to define clinically relevant bacterial growth was 1.7 x 10(3) colony-forming units per milliliter of BAL fluid. We used this threshold and found that diagnostic sensitivity and specificity were 86% and 100%, respectively. With a threshold for infection of >2 intracellular bacteria observed in any of 50 fields, microscopic examination of Gram stain BAL preparations had a sensitivity of 71% and a specificity of 97% in establishing LRTI. There was a high correlation between bacterial morphology on BAL Gram stain and bacterial cultures. Combining the results of intracellular bacteria counts from the BAL Gram stain with those from the quantitative cultures, the sensitivity in diagnosing LRTI was 87% and the specificity was 97%. BAL quantitative cultures as well as quantitating intracellular bacteria on Gram stain BAL cytology were revealed to be useful in identifying LRTI in dogs. Chronic bronchitis does not appear to be associated with marked bacterial growth in dogs.     

Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals.

OBJECTIVE: To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals. ANIMALS: 6 healthy 6- to 10-week-old foals. PROCEDURE: Azithromycin (10 mg/kg of body weight) was administered to each foal via i.v. and intragastric (i.g.) routes in a crossover design. After the first i.g. dose, 4 additional i.g. doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. RESULTS: Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min x kg, and apparent volume of distribution at steady state was 18.6 L/kg. After i.g. administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated i.g. administration, peak serum concentration was 0.63 +/- 0.10 microg/ml. Peritoneal and synovial fluid concentrations were similar to serum concentrations. Bronchoalveolar cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than concurrent serum concentrations, respectively. No adverse reactions were detected after repeated i.g. administration. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of pharmacokinetic values, minimum inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate.