Chloramphenicol, lincomycin and oxytetracycline disposition in calves with experimental pneumonic pasteurellosis

The effects of pneumonia on the pharmacokinetics of chloramphenicol, lincomycin, and oxytetracycline were evaluated in two-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures directly through the thoracic wall into each lung. Six days prior to induction of pneumonia, the antibiotics were administered in a single i.v. dose. The antibiotics were administered again 48 (i.v.), 60 and 72 h (i.m.) following injection of P. haemolytica. The pharmacokinetics of chloramphenicol (25 mg/kg) and lincomycin (10 mg/kg) were not significantly different in calves with pneumonia. The hybrid rate constant beta for oxytetracycline was increased in calves with pneumonia from 0.0034 +/- 0.0003/min to 0.0048 +/- 0.0007/min between 2 h and 8 h. Thus the elimination half-life in serum was shortened from 212.4 +/- 20.3 min to 149.3 +/- 19.5 min. In addition, there was an apparent but not statistically significant decrease in K12 with pneumonia. These findings accentuate the need for observance of 12-h dose intervals with oxytetracycline.     

Evidence that blood-borne infection is involved in the pathogenesis of bovine pneumonic pasteurellosis

Five calves were inoculated intravenously with 10(8) colony forming units (cfu) of Pasteurella haemolytica A1; the mean score for pneumonic consolidation 3 days post-inoculation was 28%, and the mean clinical score was 7.8. Five calves inoculated intratracheally with 10(9) cfu of the same strain of P. haemolytica had comparable scores (34% and 8.8). Histological lesions of fibrinous pneumonia were similar in all calves. P. haemolytica was recovered from all but one of the affected lungs. From one calf killed in extremis 3 hours after intravenous inoculation, numbers of bacteria recovered from lung were 1,000-fold greater than from liver and spleen. A similar difference in bacterial numbers was also obtained from a gnotobiotic calf killed in extremis, 12 hours after intravenous inoculation of 10(8) cfu P. haemolytica. Evidence from these experiments supports the hypothesis that the blood-borne route is important in the pathogenesis of bovine pneumonic pasteurellosis.     

Characterization of a Pasteurella multocida (serotype B) bovine pneumonic pasteurellosis model and the effect of antimicrobials during peracute infection

A method to produce bovine pneumonic pasteurellosis for experimental purposes was studied and the clinical response of experimentally infected calves to selected antimicrobials was characterized. Male Holstein calves stressed with multiple hot and cold water applications followed by intratracheal inoculation of broth cultures of Pasteurella multocida serotype B developed acute clinical illness consistent with pneumonia. Infected, untreated calves consistently developed classic pneumonic pasteurellosis, infected calves treated with either oxytetracycline or sulfadimethoxine recovered from acute clinical disease, and the uninfected controls remained healthy. This disease model offers potential for use in pharmacokinetic and target tissue drug concentration studies and for dosage titration of drugs intended for treatment of bacterial pneumonias.     

Evaluation of structural and functional alterations of circulating neutrophils in calves with experimentally induced pneumonic pasteurellosis

OBJECTIVES: To determine the structural and functional alterations in circulating neutrophils that may lead to sequestration in lung microvasculature and endothelial injury in calves with experimentally induced pneumonic pasteurellosis. ANIMALS: 10 healthy, 2- to 4-week-old male Holstein calves. PROCEDURES: Holstein calves were anesthetized and inoculated intrabronchially with Dulbecco phosphate buffered saline (0.9% NaCl) solution (DPBSS; 5 control calves) or 1 x 10(9) Pasteurella haemolytica organisms (5 infected calves). Blood samples were collected before and 1, 2, 4, and 6 hours after inoculation. Total and differential WBC count, dilute whole blood leukocyte deformability, neutrophil size distribution, and neutrophil surface CD11b expression were measured in blood samples. RESULTS: A progressive decrease in leukocyte deformability and increase in neutrophil size was detected 1, 2, 4, and 6 hours after inoculation of P haemolytica. Neutrophil surface CD11b expression was greater than baseline values at 6 hours after inoculation of P haemolytica. Two populations of neutrophils with an increase in size were detected in P haemolytica-infected calves. Both subpopulations had increased CD11b expression, compared with neutrophils that were typical in size. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophils circulate in an activated and nondeformable state in calves with experimentally induced pneumonic pasteurellosis. A decrease in neutrophil deformability and neutrophil aggregation may contribute to neutrophil trapping in the lung microvasculature during pneumonic pasteurellosis in calves.     

Single-dose treatment of neonatal calf pneumonia with the new macrolide antibiotic tilmicosin

Tilmicosin, a new macrolide antibiotic, 20-deoxo-20-(3,5-dimethylpiperidin-l-yl)desmycosin, formerly identified as EL-870, has been evaluated in three experiments as a single subcutaneous injection at dosages of 10, 20 or 30 mg/kg for the treatment of naturally occurring pneumonia in neonatal calves. Male Holstein calves, under five days of age, were shipped from Wisconsin and housed in pens. They were assigned sequentially to a treatment group when their temperature was greater than or equal to 39.7 degrees C for two consecutive days or greater than or equal to 39.7 degrees C and signs of respiratory disease were present. Clinical signs were evaluated daily for 14 days after the tilmicosin treatment. Calves that died and those that survived for the 14 day experimental period were examined post mortem. Treatment with tilmicosin was effective at all dosage levels, as determined by significant (P less than or equal to 0.05) reductions in body temperature within 24 hours, in the number of animals that died, in the incidence and severity of clinical signs, in the number of Pasteurella species found in lung tissue and in the severity of the pneumonic lesions. In two of the three experiments severe outbreaks of cryptosporidiosis resulted in significant mortalities within a few days after the arrival of the calves. Treatment with tilmicosin was effective against respiratory disease even in the presence of this severe concurrent disease.     

Influence of recombinant bovine interferon gamma and dexamethasone on pneumonia attributable to Haemophilus somnus in calves

The influence of recombinant bovine interferon gamma (rBoIFN-gamma) treatment on resistance of clinically normal and dexamethasone-treated calves to Haemophilus somnus infection was evaluated. Four groups of 6 calves each were treated with saline solution (controls), dexamethasone (0.04 mg/kg of body weight/for 3 days), rBoIFN-gamma (2 micrograms/kg for 2 days), or dexamethasone and rBoIFN-gamma (aforementioned dosages). All treatments were started 24 hours before intrabronchial challenge exposure with 5 x 10(9) colony-forming units of H somnus. Rectal temperature and WBC count were monitored daily. Two of the dexamethasone-treated calves died of pneumonia 4 days after challenge exposure and were necropsied. All other calves were euthanatized and necropsied 7 days after challenge exposure. All calves had pneumonia of variable intensity. Dexamethasone-treated calves had increased volume of pneumonic lung (P less than 0.05) and increased severity of pneumonia, compared with control calves. Recombinant bovine interferon gamma treatment resulted in reduction in pneumonic lung volume and severity of pneumonia in dexamethasone-treated calves (P less than 0.05), although it did not influence severity of pneumonia in nondexamethasone-treated calves.     

Proliferation of Pasteurella haemolytica in the calf respiratory tract after an abrupt change in climate

Two groups of four calves were exposed to a poly-disperse aerosol of 1.3 X 10(4) to 16 X 10(4) colony forming units (CFU) of nalidixic acid resistant Pasteurella haemolytica type A1 litre-1 of air with a mass median aerodynamic diameter of 2.6 +/- 0.8 microns. One group of calves was kept at 5 degrees C, 72 per cent relative humidity (RH) and the second was subjected to an abrupt change in climate directly after aerosol exposure from 5 degrees C, 75 per cent RH to 13 degrees C, 84 per cent RH. Clearance of the organism from the respiratory tract of the calves was monitored over the subsequent 23 hours by a method of tracheal and nasopharyngeal swabbing. Clearance measured at the trachea in all calves in both groups was not a continuous, uninterrupted process but exhibited a temporary decline between eight and 14 hours. Calves subjected to an abrupt change in climate after aerosol challenge had raised respiratory rates eight to 14 hours later and P haemolytica proliferated in the nasopharynx over the entire 23 hours. There was no apparent effect of climate on P haemolytica in the trachea. It is suggested that rapid growth of P haemolytica accompanying a change in climate may be an important aetiological factor in pneumonic pasteurellosis of calves.     

Volume-controlled bronchopulmonary lavage of normal and pneumonic calves

Saline bronchopulmonary lavage of the right lung of 16 anesthetized calves was performed using a single-lumen cuffed endotracheal tube. The initial volume of saline introduced was based on the functional residual capacity (FRC) of the right lung lobes as determined from the proportional weights of the right (58% of total FRC) and left (42% of total FRC) lung lobes. Calves were divided into "pneumonic" and "normal" groups based on clinical signs. Five sequential washes were done on each calf. There was no difference in the percentage of total lavage fluid volume recoverable between normal (83.8 +/- 4.2%) and pneumonic (81.1 +/- 8.2%) calves. Cell yield in the initial wash was consistently greater than in subsequent washes for both normal (12.7 +/- 6.6 X 10(6) cells/kg body weight) and pneumonic (58.1 +/- 37.6 X 10(6) cells/kg body weight) calves, and constituted 62.0% (normal) and 75.4% (pneumonic) of the total recoverable cell yield. Total cell yields were higher (P less than 0.05) in pneumonic calves, primarily due to neutrophil leukocytes (PMN). Neutrophils constituted 53.7 +/- 25% of the total cell yield in the pneumonic calves, but only 12.3 +/- 9.5% in the normal calves. The pulmonary alveolar macrophage (PAM) was the major recoverable cell in normal calves (85.7 +/- 8.7% of total lavage cells). Macrophages constituted a smaller (42.9 +/- 23.5) percentage of the total lavage cells in the pneumonic group due to increased PMN numbers. Viability of recovered cells from the pneumonic calves (91.5 +/- 4.8%) was lower than for the normal calves (94.1 +/- 2.5%), but the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of platelet-activating factor in alveolar septal injury associated with experimentally induced pneumonic pasteurellosis in calves

OBJECTIVE: To determine whether platelet-activating factor (PAF) is involved in acute lung microvascular injury associated with pneumonic pasteurellosis in calves. ANIMALS: 15 healthy 2- to 4-week-old male Holstein calves. PROCEDURE: Calves were anesthetized and inoculated intrabronchially with saline (0.9% NaCl) solution (n = 5) or 1x10(9) Pasteurella haemolytica organisms (n = 10). Of the 10 calves inoculated with P haemolytica, 5 also were treated with WEB 2086, a potent inhibitor of PAF, and 5 were treated with vehicle. Blood and bronchoalveolar lavage samples were collected before and 1, 2, 4, and 6 hours after inoculation of P. haemolytica. Blood samples were analyzed to evaluate total number and differential counts of leukocytes, dilute whole-blood leukocyte deformability, size of neutrophils, and neutrophil CD11b expression. Bronchoalveolar lavage samples were analyzed for total number and differential counts of nucleated cells, total protein concentration, and hemoglobin concentration. Size and gross and histologic appearance of lung lesions also was determined. RESULTS: Treatment of calves with WEB 2086 reduced size of lung lesions, attenuated the increase in microvascular permeability, and reduced neutrophil infiltration in the first 4 hours after inoculation. Treatment with WEB 2086 also attenuated a decrease in leukocyte deformability, increase in size of neutrophils, and CD11b expression by circulating neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: It appears that PAF is a major mediator for altered lung microvascular permeability and activation of circulating neutrophils in the first 4 hours after onset of pneumonic pasteurellosis in calves.     

Immunogenicity of a soluble antigen against Pasteurella haemolytica-associated pneumonia in calves

Three experiments were performed to evaluate the immunogenic potency of a soluble fraction of Pasteurella haemolytica against pneumonic pasteurellosis in calves. A soluble antigen was extracted by a 2.5% saline solution from P. haemolytica. Weaned Holstein bull calves, seronegative for infectious bovine rhinotracheitis virus ( IBRV ) and the pasteurella antigen, were vaccinated either by repeated subcutaneous (SC) vaccination, or by exposure 3 times to the aerosol of P. haemolytica antigen. Challenge exposure to aerosol of P. haemolytica was preceded by infection with IBRV , or in experiments 2 and 3, the virus exposures were combined with a stress treatment. The lung lesions were examined at necropsy 3 to 8 days post infection. In the first experiment, all the vaccinated calves produced specific antibody response to the pasteurella antigen, and none of the calves including controls showed significant lesions in the lung. In the second experiment 2 aerogenically vaccinated calves had no lesions. One of the two SC-vaccinated calves had mild consolidated lesions. Two control calves, one of which died 3 days following the challenge, developed severe fibrinous pneumonia with consolidation of 50% or more of the lung surfaces. P. haemolytica was isolated only from the 2 control animals. In the third experiment, 2 of the 3 control calves developed moderate to severe consolidation, but P. haemolytica was isolated only from one of them. Two of the three aerosol-vaccinated calves also developed significant lesions and one of them yielded the bacteria from the lung. Three SC-vaccinated calves had slight lesions and the organism was not isolated from their lungs. The results did not consistently indicate an immunogenic potential of the soluble antigen against P. haemolytica-related pneumonia. The effect of stress on the pathogenesis of bovine viral pneumonia and correlation between pneumonic lesions and antibacterial resistance in situ are discussed.     

Antibiotic disposition in experimental pneumonic pasteurellosis: gentamicin and tylosin.

The effects of severe respiratory disease on the disposition of antibiotics were evaluated using two drugs chosen because of their widely differing solubility characteristics. The experiments were carried out in series, using five calves for each drug. The drugs were given to seven week old calves before and after induction of pneumonia by bilateral intrapulmonary administration of 3 mL of 5 X 10(7) colony forming units of Pasteurella haemolytica. Following inoculation, the calves developed clinical signs of pneumonia and were given gentamicin (5 mg/kg) or tylosin (10 mg/kg) 48, 60 and 72 hours after Pasteurella administration. There was a statistically significant decrease in distribution rate but not elimination rate of gentamicin. For tylosin, there was a significant increase in elimination rate. These results indicate the kinetics of tylosin but not gentamicin are sufficiently altered as to support a need for increased frequency of administration with severe respiratory disease in calves.     

Serum and tissue concentrations of erythromycin in calves with induced pneumonic pasteurellosis

The effects of pneumonia on the pharmacokinetics of erythromycin administered IM and the tissue concentration changes with time were evaluated in 2-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures through the thoracic wall into each lung. Six days prior to induction of pneumonia, erythromycin (15 mg/kg) was administered in a single IM dose. Erythromycin was administered again 48, 72, and 96 hours after injection of P haemolytica. On the third day of erythromycin administration (96 hours), the calves were serially euthanatized in groups of 4 calves each at 2, 5, 8, 12, 18, and 24 hours after the final dose was given. Tissue concentrations of erythromycin in kidney, liver, lung, muscle, CSF, and serum were determined. Neither the serum concentrations nor the overall pharmacokinetic values were significantly (P less than or equal to 0.05) changed by pneumonia. The concentrations of erythromycin were maximal at 5 hours for liver, muscle, and serum and at 8 hours for CSF, kidney, and lung. Serum and muscle concentrations were similar, whereas concentrations in CSF were lower than in serum and higher in kidney, liver, and lung. The lung/serum ratios were approximately 2.5 to 3 at 8 through 24 hours after IM administration. The peak concentration in lung was approximately 6 micrograms/g at 8 hours.     

Pneumonic pasteurellosis induced experimentally in gnotobiotic and conventional calves inoculated with Pasteurella haemolytica

Experimental pneumonia caused by Pasteurella haemolytica was induced in 2-week-old gnotobiotic (n = 4) and conventional (n = 6) calves by endobronchial inoculation into the right caudal lung lobe of 7.9 x 10(10) +/- 0.6 x 10(10) (mean +/- SD) colony-forming units of P haemolytica in the 6-hour log phase of growth. The calves were studied for 24 hours or less. Regression lines for the relationship between clinical index and time for the gnotobiotic group and conventional group of calves were compared, and the clinical index was found to be significantly (P less than or equal to 0.005) more rapid in the gnotobiotic group. There was also a significant difference in the preinoculation, absolute segmented neutrophil count (P less than or equal to 0.05), and in the total serum protein, albumin, and globulin values (P less than or equal to 0.05). Comparison of the preinoculation and post inoculation blood cell and blood chemical values revealed a significant increase (P less than or equal to 0.05) in the numbers of band neutrophils and fibrinogen in conventional calves, and a significant decrease (P less than or equal to 0.05) in the total WBC count in gnotobiotic calves. Necropsy of both groups of calves revealed a circular to oblong lesion that was congested, edematous, and firm, and which occupied 20% to 100% of the right caudal lung lobe and involved the remaining lung lobes to a more minor degree. When mean lesion scores of the 2 groups of calves were compared, no significant difference (P less than or equal to 0.05) was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pulmonary clearance of Pasteurella hemolytica in calves infected with bovine parainfluenza-3 virus.

The purpose of this study was to determine if parainfluenza-3 virus in calves interfered with normal pulmonary bacterial clearance. Three groups (A, B and C) of four calves each were exposed to an aerosol of parainfluenza-3 virus. Three days later the four hour pulmonary clearance of Pasteurella hemolytica was determined on the first group (A), seven days later on the second (B) and 11 days later on the third (C). Group A had a mean pulmonary bacterial retention of 3.6 +/- 3.5%. Group B was 83.1 +/- 35.9% and Group C was 41.2 +/- 30.9%. The results demonstrate that parainfluenza-3 virus interfered with the pulmonary bacterial clearance of Pasteurella hemolytica particularly on day 7 and also on day 11 but not on day 3. This inhibition of pulmonary clearance caused by the virus may be a key factor in the pathogenesis of pneumonic pasteurellosis. Histological examination of the lungs did not demonstrate a correlation between pulmonary retention of bacteria and the development of pathological changes.     

Detection of annexins I and IV in bronchoalveolar lavage fluids from calves inoculated with bovine herpes virus-1

Annexins are phospholipid-binding proteins and are abundant in the lung. Annexins I and IV, but not II and VI, have been detected in bronchoalveolar lavage (BAL) fluids from calves inoculated with Pasteurella haemolytica, the pathogen for calf pneumonia. In this study, BAL fluids from calves with experimental pneumonia induced by inoculation to right lung lobes of bovine herpes virus-1 (BHV-1), the major viral pathogen for pneumonia, were examined for detection of annexins I and IV. Of 6 calves inoculated with BHV-1, annexins I and IV were coincidentally detected in BAL fluids from right lung lobes of 4 calves, but not in BAL fluids from left lung lobes of 6 inoculated calves or those from left and right lung lobes of 3 control calves. Annexin II and VI were not found in any BAL fluids examined. These results, together with previous findings on calves inoculated with Pasteurella haemolytica, suggest that the release of annexins I and IV onto the alveolar surface is an essential event occurring in response to pulmonary infections of BHIV-1 and Pasteurella haemolytica.     

Consequences of short term fluctuations of the environmental temperatures in calves--Part 2: Effects on the health status of animals within three weeks after exposure

The aim of the present study was to examine consequences of sudden changes in ambient temperature over a 4-hour period (see part 1 [ELMER & REINHOLD, 2002]) on respiratory health in clinically healthy calves. Therefore, the relationship between short-term changes in ambient temperature and the occurrence of clinical respiratory disease was checked over a period of 3 weeks after exposure in 10 calves exposed to 5 degrees C, in 9 calves exposed to 35 degrees C and in 8 control calves (kept at 18-20 degrees C). Within the period beginning 3 days before exposure and lasting until up to 21 days after exposure, each calf was examined clinically. Rectal temperature and respiratory rate were measured daily. All calves were euthanised on day 21 after exposure. Macroscopically visible pneumonic lesions were evaluated using a semiquantitative system. Tissue samples from tonsils, bronchi, trachea, lung and mediastinal lymph nodes were examined bacteriologically. In contrast to non-exposed control calves, severe respiratory illness was observed in individual calves of both exposed groups (5 degrees C, 35 degrees C). Significant increases in body temperature, respiratory rate and animal losses (2 calves died in the group exposed to 5 degrees C, one calf died in the group exposed to 35 degrees C) were the main clinical findings. At necropsy (3 weeks after exposure), no pneumonic lesions were observed in control calves--despite the fact that this group had the highest microbiological colonisation rates in tonsils and in large airways, i.e. trachea and bronchi, within all groups. However, variable pneumonic lung lesions were seen in remaining calves exposed to cold or warm air (5 degrees C, 35 degrees C). The microbiological examination confirmed that mainly Mycoplasma spp. were identified in the lung tissue of calves exposed to 5 degrees C while Pasteurella multocida and/or Mannheimia haemolytica were the only germs found in the lung tissue of calves exposed to 35 degrees C. The results of parts 1 and 2 of the present study related to health issues of calves should be taken into account for future legislation on animal welfare.     

Induction of immunity against pneumonic pasteurellosis following experimental infection in calves.

Immunity against pneumonic pasteurellosis was studied in calves after recovery from experimental respiratory disease with Pasteurella haemolytica. Nine calves were exposed to aerosols of parainfluenza-3 virus and Pasteurella haemolytica A1 six days apart to produce respiratory disease. After recovery from the disease, these nine principal and four control calves were challenged with aerosols of bovine herpesvirus 1 and P. haemolytica A1 four days apart. With this viral-bacterial challenge, the nine principal animals failed to develop clinical responses to this bacterial challenge and their lungs did not show the growth of P. haemolytica on cultures, whereas two of four control calves had elevated temperatures and developed necropurulent pneumonia with the isolation of P. haemolytica from the lungs. The principal calves had developed high levels of cytotoxin neutralizing antibodies in their sera following parainfluenza-3 virus-P. haemolytica infection. This demonstrated that immunity against pneumonic pasteurellosis can be achieved, with a suggestion that further search for an effective vaccine for P. haemolytica is warranted.     

A model for the induction of Pasteurella multocida type-A pneumonia in pigs.

A model for the induction of pneumonia caused by Pasteurella multocida type-A was developed. Anesthetized pigs were dosed intratracheally with 10(10) colony forming units of P. multocida type-A suspended in a total dose of saline based on the pig's body weight (8 mL/kg). A severe bronchopneumonia was present when the treated pigs were euthanized seven days postinfection. The mean percentage of pneumonic lesions in the treated pigs, as determined by morphometric measurement, was 14.03 +/- 7.01 (X +/- SD). In contrast, in the control pigs, the mean percentage of pneumonic lesions was 0.59 +/- 0.52. For the treated pigs during the period following induction of pneumonia, weight gain and feed intake were reduced significantly (p less than 0.05) compared to the controls. It was shown that severe pneumonia could be induced without the use of other infectious agents, which could potentially confound the experimental model.     

Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin.

Twenty four (24) healthy male Holstein calves (< 70 kg) were each experimentally infected by intrabronchial inoculation of 4.0 x 10(9) viable cells of Pasteurella haemolytica-AI (B122) at Time = 0 h. At 1 h following inoculation animals received either: 1) Sham treatment with sterile 0.85% saline SC (n = 12); or 2) a single injection of 10 mg tilmicosin per kg body weight (n = 12). Calves that were non-infected and tilmicosin-treated were also included for determining tilmicosin concentrations in serum and lung tissue at 1, 2, 4, 6, 8, 24, 48, and 72 h (n = 3-per time). In the infected calves, response to therapy was monitored clinically. Serum samples were collected for determination of tilmicosin concentrations using HPLC. Any animal becoming seriously ill was humanely killed. Complete necropsy examinations were performed on all animals and included gross pathologic changes, bacteriologic analysis, histopathology, and determination of pulmonary concentrations of tilmicosin. Tilmicosin treated animals responded significantly better to therapy than saline-treated control calves. Clinical assessment of calves during the study indicated that tilmicosin-treated calves had significantly improved by T = 8 h compared to satine-treated animals (P < 0.05). At necropsy tilmicosin-treated calves had significantly less severe gross and histological lesions (P < 0.05) of the pulmonary tissue. Of the 12 saline-treated calves, 92% (11/12) had Pasteurella haemolytica-A1 in lung tissue, while of the tilmicosin-treated calves 0% (0/12) cultured positive for P. haemolytica. Mean (+/- standard error) serum tilmicosin concentrations in infected calves peaked at 1 h post-injection (1.10 +/- 0.06 micrograms/mL) and rapidly decreased to 0.20 +/- 0.03 microgram/mL, well below the MIC of 0.50 microgram/mL for P. haemolytica-A1 (B122), by 12 h. These serum concentrations were very similar to serum concentrations of tilmicosin in non-infected tilmicosin-treated calves. Lung tissue concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experimentally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight.     

Bovine pneumonic pasteurellosis: model for Pasteurella haemolytica- and Pasteurella multocida-induced pneumonia in cattle

Pneumonic lesions in calves were induced with Pasteurella haemolytica or P multocida. The inoculum, consisting of a suspension of either organism, was administered by transthoracic intrapulmonic injection to 23 calves. Three died of septicemia; the 20 remaining, killed 96 hours after inoculation, had an expanding unifocal pneumonia qualitatively comparable with that of acute pneumonic pasteurellosis (shipping fever). The concentration of bacteria that consistently produced a lesion was a 5-ml volume containing 10(9) colony-forming units of bacteria; a concentration of 10(6) colony-forming units inconsistently produced lesions. Bacteria, except in calves that developed septicemia and died, remained localized at the injection site. The inflammatory process spread within the lungs, not only through airways, but through the interlobular and interalveolar septa as well.