Antimicrobial alternatives for calf diarrhea: enteric responses to Escherichia coli, deferoxamine, or gallium in neonatal calves

Intestinal malabsorption or transferable resistance in enteric bacteria are potentially serious complications of routine oral administrations of antibiotics. On the basis of reports on antimicrobial effects of host iron sequestration and on synthetic iron chelators or competitors in vitro, 2 iron antagonists were studied for their potential as alternative antimicrobials for Escherichia coli diarrhea. Deferoxamine, a fungal iron chelator used to treat acute iron intoxication, and elemental gallium, a competitive inhibitor of iron activity in metabolic enzyme systems, were examined for their effects on enteric morphology and function in neonatal calves. Twelve male calves were allotted to 4 groups: (1) given nonpathogenic E coli (control); (2) given enterotoxigenic B44 E coli; (3) given deferoxamine (50 mg/kg, twice a day); and (4) given gallium (4 mg/kg, twice a day). Calves were studied for 8 days, including the conduct of oral glucose and lactose tolerance tests on days 1, 3, and 7. By day 7, according to oral glucose and lactose tolerance tests, peak plasma glucose concentrations in all calves of groups 2, 3, and 4 were lower than those values in controls. The frequency of diarrhea was significant in all treated calves, and disease was most severe in the deferoxamine-treated calves. Quantitative cultural examination on day 8 showed significant numerical increases of jejunal and ileal E coli and ileal lactobacilli in deferoxamine-treated calves (group 3) and of ileal streptococci in gallium-treated calves (group 4) and showed jejunal and ileal overgrowths of Saccharomyces yeast in deferoxamine-treated calves.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antimicrobial use in the treatment of calf diarrhea

Calves with diarrhea often have small intestinal overgrowth with Escherichia coli bacteria, regardless of the inciting cause for the diarrhea, and 30% of systemically ill calves with diarrhea have bacteremia, predominantly because of E coli. Antimicrobial treatment of diarrheic calves should therefore be focused against E coli in the small intestine and blood, the 2 sites of infection. Fecal bacterial culture and antimicrobial susceptibility testing is not recommended in calves with diarrhea because fecal bacterial populations do not accurately reflect small intestinal or blood bacterial populations and because the break points for susceptibility test results have not been validated. Antimicrobial efficacy is therefore best evaluated by the clinical response of a number of calves to treatment, with calves randomly assigned to treatment groups. Amoxicillin, chlortetracycline, neomycin, oxytetracycline, streptomycin, sulfachloropyridazine, sulfamethazine, and tetracycline administered PO are currently labeled in the United States for the treatment of calf diarrhea. On the basis of published evidence for the oral administration of these antimicrobial agents, only amoxicillin can be recommended for the treatment of diarrhea. Dosage recommendations are amoxicillin trihydrate (10 mg/kg PO q12h) or amoxicillin trihydrate-clavulanate potassium (12.5 mg combined drug/kg PO q12h) for at least 3 days; the latter constitutes extra-label drug use. Parenteral administration of broad-spectrum beta-lactam antimicrobials--ceftiofur (2.2 mg/kg IM or SC q12h) and amoxicillin or ampicillin (10 mg/kg IM q12h)--or potentiated sulfonamides (25 mg/kg IV or IM q24h) is recommended for treating calves with diarrhea and systemic illness; both constitute extra-label drug use. In calves with diarrhea and no systemic illness (normal appetite for milk, no fever), it is recommended that the health of the calf be monitored and that oral or parenteral antimicrobials not be administered.     

Effect of flunixin meglumine on Escherichia coli heat-stable enterotoxin-induced diarrhea in calves

In a study to evaluate the effect of flunixin meglumine on secretory diarrhea, 11 calves were assigned to 3 groups: group 1 (n = 3) served as controls, group-2 calves (n = 4) were given 2.2 mg of flunixin meglumine/kg, IM at 7 AM and 3 PM, and group-3 calves (n = 4) were given 2.2 mg of flunixin meglumine/kg, IM at 7 AM, 11 AM, and 3 PM. All calves were given approximately 200 micrograms of heat-stable Escherichia coli enterotoxin (STa) orally at 8 AM. Mean cumulative fecal output for groups 1, 2, and 3 was 1,331.0 +/- 317.2 g, 1,544.3 +/- 154.4 g, and 785.5 +/- 276.5 g, respectively. There was a significant (P less than 0.05) reduction in mean fecal output in group-3 calves, compared with that in groups 1 and 2. Calves in group 2 tended to have a delay, but not a reduction, in their fecal output. At 12 hours, hemoconcentration was significantly (P less than 0.05) greater in group-1 calves than in group-2 or group-3 calves.     

Effects of maternal protein-energy malnutrition and cold stress on neutrophil function of bovine neonates

The effects of maternal protein or calorie deprivation (or both) on the bactericidal activity of neutrophils and sera from newborn calves subjected to cold stress were studied. Nutritional deficiencies in the dam had little effect on in vitro bactericidal activity of neutrophils and base-line sera taken at birth. Neutrophils obtained at birth destroyed Staphylococcus aureus but not Escherichia coli when incubated with either unheated or heated autologous base-line sera. Heat treatment of base-line sera to inactivate complement did not alter bacterial growth. When incubated in the presence of autologous base-line sera, neutrophils from 3-day-old calves were no more active in the destruction of either bacterium than were neutrophils from newborn calves. However, addition of day 3 (immunoglobulin-containing) sera enabled day 3 neutrophils to destroy E coli (P < 0.0001). The increased destruction of E coli by day 3 neutrophils and day 3 sera was not affected by heat treatment of the sera. Maternal protein deficiency significantly increased (P < 0.05) destruction of E coli by day 3 neutrophils and sera. This effect was independent of energy levels. There were no differences observed in the bactericidal activity of neutrophils and sera taken from calves exposed to 1 C or 21 C environmental chambers for 3 days. Also, cold stress-nutritional stress interactions were not detected.     

Hemodynamics, plasma eicosanoid concentrations, and plasma biochemical changes in calves given multiple injections of Escherichia coli endotoxin

Twelve male neonatal calves (39 to 50 kg) were allotted to 3 groups of 4 calves each. All calves were anesthetized with halothane, and then Escherichia coli endotoxin was given intravenously (3 times) and intraperitoneally (3 times) during a 6-hour period. Group-1 calves were untreated, group-2 calves were pretreated with a low dose of flunixin meglumine (1.1 mg/kg of body weight), and group-3 calves were pretreated with a high dose of flunixin meglumine (4.4 mg/kg). In calves of group 1, the mean systemic arterial blood pressure (MABP) and cardiac output (CO) decreased, but pulmonary arterial pressure increased after the initial intravenous and intraperitoneal injections of endotoxin. In calves of this group, these changes were accompanied by increased plasma thromboxane B2 (TxB2) concentration. During this period, increased plasma TxB2 concentration or hemodynamic changes were not detected in calves of groups 2 and 3. Only calves of group 1 had altered hemodynamics early in the experiment; however, after 6 hours, calves of all 3 groups had similarly decreased CO and MABP. In calves of the untreated group, plasma 6-keto-prostaglandin (PG)F1 alpha concentration increased steadily from the beginning of the experiment until 3 hours later. The CO and MABP were low at the time when serum 6-keto-PGF1 alpha concentration was high; however, these 2 measurements also were low in treated calves who did not have correspondingly high plasma 6-keto-PGF1 alpha concentration. Regional blood flow analysis did not reveal correlations between prostanoid concentrations and altered blood flow to selected tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

An evaluation of iron-dextran supplementation in piglets administered by injection on the first, third or fourth day after birth

The aims of the study were to evaluate the effect of iron-dextran injection given on the first, third or fourth day after birth on haematology in piglets. An advanced automated blood analyser; Technicon H*1, which performs a complete blood cell count and leukocyte differential counts was used to analyse the blood. Six litters of Norwegian Landrace x Yorkshire piglets were included in the study. The day after birth (day 1), half of the piglets in each litter (split litters) were injected subcutaneously with 180 mg iron as iron-dextran (1.5 ml Idofer). The untreated piglets from two of the litters were injected with the same amount of iron-dextran on day 3, and those from the remaining four litters on day 4. The piglets were weighed and blood samples collected on days 1, 3 or 4, 7, 14 and 21. Erythropoiesis, but not leukocyte count, responded to injection on day 1 compared with injection on the third or fourth day. The difference between groups in haematological parameters was greatest on day 7. The two groups of piglets treated on day 1 had a haemoglobin concentration (Hb) +/-SD of 92 g litre-1(+/-9) and 94 g litre-1(+/-9), and the piglets treated on day 3 had a Hb of 81 g litre-1(+/-7) and the one treated on day 4 had a Hb of 78 g litre-1(+/-7) on day 7. On days 14 and 21 there were no differences between groups. This study indicates that some piglets were anaemic and responded to subcutaneous iron injection on day 1.     

Hemodynamic effects of acute pneumonia experimentally induced in newborn calves inoculated with Pasteurella haemolytica

Hemodynamic responses to acute pneumonia and to hypoxia were investigated in 10 newborn calves. Experiments were performed on heparinized, anesthesized and ventilated calves. Control calves were inoculated intratracheally with bovine fetal serum. Pneumonia was induced in treated calves by intratracheal inoculation with P haemolytica suspended in bovine fetal serum. Before inoculation (base line), at the time of inoculation (T = 0), and at 30-minute intervals for 3 hours, pulmonary arterial pressure (Ppa), systemic arterial pressure, cardiac output (CO), arterial blood gases, pulmonary vascular resistance (PVR), and systemic vascular resistance were determined. At T = 0, calves in both groups became hypoxemic, alveolar-arterial O2 difference, PVR, and Ppa increased, and CO and systemic vascular resistance remained unchanged. At subsequent measurement intervals, all values returned to base-line in control calves, whereas treated calves had progressive hypoxemia associated with a decrease in Ppa and PVR, with no change in CO. Three hours after inoculation and after inhalation of 10% O2 in N2, PVR increased significantly in the control calves. In the treated group, hypoxia did not increase the resistance, compared with base-line and 3-hour values. The data indicate decreased Ppa during pneumonic pasteurellosis is because of a decrease in PVR and that pneumonia may attenuate the normal pulmonary hypoxic vasoconstrictor response.     

Effects of parenteral supply of iron and copper on hematology, weight gain, and health in neonatal dairy calves

The objective of the present study was to examine the effects of parenteral administration of iron and copper on hematological parameters, weight gain, and health of neonatal dairy calves in the period when iron and copper deficiency could be existed. Twenty-four Holstein calves were used for the experiment and randomly assigned to four different treatments. Treatments consisted of (1) control (no injections of Fe and Cu), (2) test 1 (1000 mg Fe as fe-dextran was injected to each calf at day 2 of age), (3) test 2 (160 mg Cu as methionine-copper complex was injected to each calf at day 14 of age), and (4) test 3 (Fe and Cu were injected to each calf as mentioned previously). Blood samples were collected from all of the calves within 24-48 hours after birth and at 7, 14, 21 and 28 days of age for measuring hematological parameters and within 24-48 hours after birth and at 14, 21 and 28 days of age for the determination of iron, copper, TIBC concentrations, and AST activity. Anti-coagulated blood was analyzed shortly after collection for: number of red blood cell (RBC), hemoglobin (Hb), heamatocrit (HCT), total leukocyte count (WBC), Platelet (Plt), MCH, MCV, MCHC, and differential leukocyte counts. The amounts of iron, copper, TIBC, and AST were measured in serum. Group had significant effects on the amounts of HCT, RBC, hemoglobin, MCV, neutrophil, weekly weight gain, and daily gain during each week (p < 0.05). Sampling time had significant effects on the amounts of RBC, MCV, MCH, MCHC, WBC, neutrophil, lymphocyte, monocyte, platelet, fibrinogen, copper, TIBC, AST, weight, weekly gain and, daily gain during each week (p < 0.05). significant interactions between sampling time and group were seen for HCT, RBC, hemoglobin, MCV, platelet, total protein, fibrinogen, iron, and TIBC (p < 0.05). Improved RBC parameters and MCV were seen in calves of group 4 (test 3) in comparing with control group. Total and daily gains were also significantly improved in test groups in comparing with control group (p < 0.05). No significant difference was seen for the days of treatment between groups.     

Pharmacokinetics of gentamicin at steady-state in ponies: serum, urine, and endometrial concentrations

Gentamicin (GT) was administered IM to 6 healthy mature mare ponies at a dosage of 5 mg/kg of body weight every 8 hours for 7 consecutive days (total, 21 doses). Two venous blood samples were collected before (trough) and at 1 hour (peak) after the 5th, 10th, 14th, and 19th doses. An endometrial biopsy was done of each mare on days 4 and 7. On the 7th day, just before the 21st administration of GT, base-line blood samples were collected, and 22 blood samples were collected over a period of 48 hours after GT was given. The mares were catheterized on the 7th day, and urine was collected for 24 hours. Serum, urine, and endometrial GT concentrations were determined by a radioimmunoassay technique (sensitivity of 0.3 micrograms/ml of serum). Serum GT concentration data obtained from the terminal phase were best fitted by a 1-compartment open model with a biological half-life of 2.13 +/- 0.43 hours. Total body clearance and renal clearance were 1.69 +/- 0.41 and 1.40 +/- 0.26 ml/min/kg, respectively. Mean endometrial concentrations on day 4 and day 7 were 5.02 +/- 3.3 and 12.75 +/- 1.6 micrograms/g. To achieve mean serum GT concentrations (micrograms/ml) at steady state of 6.47 +/- 1.51, a maximum steady-state concentration of 12.74 +/- 1.60, and a minimum steady-state concentration of 1.43 +/- 0.57, a dosage of 5 mg/kg every 8 hours is recommended. Serum urea nitrogen, serum creatinine, and the fractional clearance of sodium sulfanilate were determined before and after GT treatment. Renal function remained within the base-line range during 7 days of GT administration.     

The effect of "Ferrodex", vitamin A and "Rovimix beta-carotene" on the iron and copper levels in blood plasma of calves

The effect of Ferrodex, vitamin A and synthetic beta-carotene on the content of iron and copper in the blood serum has been investigated in three groups of calves: I control group without vitamin supplements, II group received only once with the first colostrum dose 1.5 million IU of vitamin A, III group received Rovimix beta carotene containing 10 per cent of the synthetic beta carotene with Mlekomix from the 21st day to the 13th week of life. Moreover half of the calves from each group received Ferrodex intramusculary. Content of iron, total iron binding capacity by serum proteins, level of indirect and direct copper as well as the content of ceruloplasmin were determined in the blood serum of calves. Moreover hematocrit and hemoglobin content in the blood were determined. The results obtained show that a triple intramuscular injection of Ferrodex caused an increase of the level of iron, copper and ceruloplasmin in the blood serum of calves. However, a single administration of vitamin A to the calves or a continuous administration of Rovimix beta-carotene decreased significantly the level of iron and ceruloplasmin copper in blood serum as well as caused a more dynamic ceruloplasmin synthesis with a simultaneous increase in its utilization.     

Evaluation of lasalocid as a coccidiostat in calves: titration, efficacy, and comparison with monensin and decoquinate

Two experiments were conducted to evaluate lasalocid as a coccidiostat in Holstein calves and to compare lasalocid with monensin and decoquinate. In experiment 1, calves in 3 groups (6 calves/group) were each inoculated with 500,000 sporulated oocysts, 88% of which were Eimeria bovis and 12% were E zuernii. Calves in each group were given lasalocid-medicated feed at 0.50 (group 3), 0.75 (group 4), or 1 mg/kg (group 5) of body weight/day for 45 days. Two control groups (6 calves/group) were also evaluated; calves in control group 2 were inoculated and nontreated, and calves in control group 1 were noninoculated and nontreated. At 0.50, 0.75, or 1 mg/kg/day, lasalocid was equally effective in preventing induced coccidiosis (E bovis and E zuernii) in calves. Compared with inoculated nontreated controls, treated calves had significantly (P less than 0.05) fewer oocysts in feces and had fewer clinical signs of coccidiosis from days 16 to 30 after inoculation. Experiment 2 was conducted to compare the effectiveness of monensin, lasalocid, and decoquinate for the prevention of experimentally induced coccidiosis. Calves (n = 48) were allotted into 4 groups (12 calves/group); each was inoculated orally with 275,000 sporulated oocysts, predominantly E bovis and E zuernii, and each was given nonmedicated feed (group 6) or feed medicated with 33 mg of lasalocid (group 7), decoquinate (group 8), or monensin (group 9)/kg of feed for 46 days. Calves given medicated rations had significantly (P less than 0.05) fewer oocysts in their feces and fewer clinical signs of coccidiosis than did calves given nonmedicated rations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Passive transfer of antibodies to Shiga toxin-producing Escherichia coli O26, O111 and O157 antigens in neonatal calves by feeding colostrum

To study whether or not passive immunity of neonatal calves against Shiga toxin-producing Escherichia coli (STEC) O26, O111, and O157 was obtained by colostrum administration, serum antibodies in calves after the feeding were determined by enzyme-linked immunosorbent assay (ELISA) in comparison with antibodies in colostrum and sera from donor dams. The highest antibody titers to STEC in colostrum from dams were detected soon after parturition. The antibody titers were found to be elevated in sera of neonatal calves (4-9 hr after birth) orally administered with colostrum with high antibody titers, suggesting that passive immunity of neonatal calves to STEC infection may be obtained by feeding colostrum. These results suggest that colostrum administration to neonatal calves may play an important role in elevating serum antibodies against STEC in neonatal calves.     

Effects of peroral insulin and glucose on circulating insulin-like growth factor-I, its binding proteins and thyroid hormones in neonatal calves

There is disagreement in the literature about the ability of neonatal calves to absorb perorally administered insulin. This study evaluated the absorption of a bolus of insulin administered alone or with an energy souce and its effects on the circulating insulin-like growth factor system and thyroid hormones in newborn Holstein-Friesian calves. Within 1 h of dosing, mean serum insulin and triiodothyronine (T3) concentrations had increased considerably, whether the insulin was applied alone (n = 4) or together with glucose (n = 4), accompanied by marked hypoglycemia. No significant changes were observed in control calves (n = 4) given the vehicle solution. Increased serum glucose and T3 concentrations with no change in insulinemia occurred in a 4th group of calves given glucose alone. At 32 h of age and after 3 meals of colostrum there were no differences in glycemia, insulinemia, or proteinemia among the 4 groups of calves examined. Mean serum insulin-like growth factor-I (IGF-I) tended to decrease over this period in the control group. The decrease was more pronounced in the insulin-treated group but absent in both groups that received glucose. These differences were associated with equivalent differences in abundance of the 40-45K IGF-binding protein-3 (IGFBP-3); however, lower molecular mass IGFBPs were not affected. The results show that a pharmacological peroral dose of insulin can lead to rapid systemic alterations in the IGF/IGFBP system in neonatal calves that can be modified by simultaneous administration of a small energy supply in the form of glucose.     

Comparative therapeutic effect of toltrazuril, sulphadimidine and amprolium on Eimeria bovis and Eimeria zuernii given at different times following infection in buffalo calves (Bubalus bubalis)

We compared the therapeutic effect of three anticoccidial drugs (toltrazuril, sulphadimidine and amprolium) in buffalo (Bubalus bubalis) calves experimentally infected with Eimeria bovis (E. bovis) and E. zuernii oocysts (3 x 104oocyst/calf). Buffalo calves (1.5-4 month old, 70-kg body weight) were randomly allocated into 3 groups (9 calves each). Group T was experimentally infected with oocysts and treated with toltrazuril (20 mg/kg BW twice orally at a 1-week interval). Group S was experimentally infected with oocysts and treated with sulphadimidine (125 mg/kg injected IM followed by half dose for 4 successive days). Group A was experimentally infected with oocysts and treated with amprolium (50 mg/kg orally for 7 successive days). Each group had three subgroups (three calves/subgroup) to represent timing of the drug administration: 1st day of coccidia infection (FD), onset of clinical signs of coccidiosis (CC), and onset of oocyst shedding into the faeces (OS). Clinical signs, body-weight gain (BWG) and number of oocysts per gram feces (OPG) were monitored daily for 35 days post-infection (DPI). The OPG were reduced (but the BWG was not different) in the T calves compared to S and A calves. Within the same group, treatment from the 1st day of infection reduced the OPG and increased the BWG compared to the later treatment timings.     

Relationship between occurrence of white diarrhea and changes of properties and components of blood and milk in their dams after parturition in Japanese Black calves.

We investigated the diet content and properties of blood and milk in 11 pairs of Japanese Black cows and their calves for the one month following delivery. Four pairs (group A) had been no cases of white diarrhea during the year prior to this study, and 7 pairs (group B) had been a high occurrence of white diarrhea in calves during the same period. Properties of dams' diet in groups A and B before the onset of white diarrhea in calves were as follows: TDN fullness rate 98 +/- 2% vs. 110 +/- 5%, DCP fullness rate 151 +/- 2% vs. 200 +/- 33%, and starch content 5 +/- 2% vs. 14 +/- 3%. Blood and milk samples were collected from cows weekly and at the onset of white diarrhea in calves. No calves in group A had white diarrhea, while 5 out of 7 calves in group B had the diarrhea in this study. All cows were fed mixed hay, but 3 out of 5 cows whose calves had white diarrhea had been additionally given 3.0-3.5 kg of corn-silage a day from 4-5 days before onset. In all cows in the white diarrhea development group, the fat content of milk increased by 2.94 +/- 1.82% at the day of onset in comparison before. Serum TG and BUN, respectively, increased by 3.8 +/- 1.3 mg/dl and 3.7 +/- 2.0 mg/dl. Feeding cows a low-starch diet and additional corn-silage may induce a transient increase in blood TG, BUN and milk fat, which may contribute to the occurrence of white diarrhea in calves.     

Erythrocyte changes, serum iron concentration and performance following iron injection in neonatal beef calves

The injection of iron-dextran into beef calves at an early age immediately increased values for erythrocyte (RBC) numbers, hemoglobin (Hb) concentration, packed cell volume (PCV), mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV), even though the calves were not anemic. There were no significant differences in average daily gain (ADG) from birth through 15 wk between those that were injected and those that were not injected. Hereford calves had lower values for PCV, Hb, MCH and MCV than Angus and crossbred calves, and both Hereford and Angus calves had lesser body weight and slower ADG than crossbred calves. Serum iron (Fe) concentrations were higher in calves born in the spring and pastured in the summer than in calves born in late summer and fall and pastured in the fall. The serum Fe concentration of calves at first sampling (during first week of life) was positively correlated with their weight at that and subsequent times to 15 wk. Mean corpuscular volume and MCH in cows before calving were positively correlated with the MCV and MCH in their calves at first sampling. Serum Fe concentration in cows before calving was negatively correlated with the ADG of their calves through 15 wk.     

Effect of infection with bovine viral diarrhea virus alone,bovine rotavirus alone,or concurrent infection with both on enteric disease in gnotobiotic neonatal calves

OBJECTIVE: To compare experimentally induced concurrent infection with bovine viral diarrhea virus (BVDV) and bovine rotavirus (BRV) with infection of either virus alone in calves. ANIMALS: Seventeen 1-day-old gnotobiotic calves. PROCEDURE: Calves were allotted to 8 treatments as follows: group 1, mock-infected control calves (n = 2); group 2, inoculated with BVDV on day 1 (2); groups 3, 5, and 7, inoculated with BRV on days 1 (2), 4 (1), or 7 (2), respectively; and groups 4, 6, and 8, inoculated with BVDV on day 1 and with BRV on days 1 (2), 4 (2), or 7 (4), respectively. Concentrations of BVDV in serum and ileal tissues were measured, and BRV shedding in feces was determined. Histologic examination and immunohistochemical analysis were conducted to detect lesions and viral antigens. RESULTS: Neonatal calves inoculated with BVDV alone or with BVDV on day 1 and BRV on day 7 developed villus atrophy and submucosal inflammation of the intestines. Concurrent BVDV and BRV infections acted synergistically in the intestinal tract, causing more severe enteric disease than infection with either virus alone. Severe lymphoid depletion was associated with BVDV infection in calves regardlesss of concurrent BRV infection. CONCLUSIONS AND CLINICAL RELEVANCE: Infection with BVDV played direct and indirect roles in enteritis in neonatal calves, causing villus atrophy in the duodenum and submucosal inflammation of the intestines. Also, BVDV potentiated effects of BRV. Concurrent infection with BVDV and BRV resulted in more severe enteric disease in neonatal calves than infection with BRV or BVDV alone.     

Clinical pharmacokinetics of five oral cephalosporins in calves

The minimal inhibitory concentrations (MIC) of cephalexin, cephradine, cefaclor, cefatrizine and cefadroxil for Salmonella species, Escherichia coli and Pasteurella multocida isolated previously from young calves were determined. The MIC90 values for cephalexin, cephradine and cefadroxil ranged between 3.12 micrograms ml-1 and 12.5 micrograms ml-1, whereas those of cefatrizine and cefaclor were 3.12 micrograms ml-1 and 0.78 microgram ml-1, respectively. Each drug was administered intravenously and orally to groups of pre-ruminating calves and orally to early ruminating calves. Although the pharmacokinetic characteristics of the drugs after intravenous injection were similar to other beta-lactam antibiotics, significant differences between the cephalosporins examined were found in respect of certain kinetic parameters. The drugs showed rapid absorption into the systemic circulation after oral administration to pre-ruminating calves but the elimination half-life values (t1/2 beta) varied between three hours (cefaclor and cefadroxil) and nine hours (cefatrizine). The bioavailability of the drugs was about 35 per cent of the administered dose. Co-administration of probenecid with each antibiotic caused a twofold or greater increase in peak serum drug concentrations (Cmax) but the effect on t1/2 beta was variable. Cephalexin, cephradine and cefaclor given to the ruminating calves resulted in very low serum or plasma concentrations and their use should be restricted to younger calves. Cefadroxil was found to give the highest serum concentrations in this age group but had significantly lower bioavailability when compared with the unweaned calves. Provisional oral dosage regimens were computed for each cephalosporin on the basis of the MIC data and the kinetic parameters derived from intravenous and oral drug administration.     

Interaction between Pasteurella haemolytica, sulfadiazine/trimethoprim, and bovine viral diarrhea virus

A study was designed to develop and define a sc tissue chamber as a suitable device for establishing a soft-tissue infection model in cattle and to use this model to study the interaction between Pasteurella haemolytica, sulfadiazine/trimethoprim, and bovine viral diarrhea virus (BVDV). Thermoplastic tissue chambers were implanted in the paralumbar fossae of 20 calves. At 35 days after implantation, calves were allotted to 4 groups of equal size and the calves in 2 groups were inoculated intratracheally with a New York-1 strain of BVDV. At 45 days after implantation, all chambers were inoculated with a 6-hour culture of P haemolytica serotype 1. Starting 36 hours after bacterial inoculation, sulfadiazine/trimethoprim was administered IV once a day to half of the virus-inoculated calves and to half of those calves that had not been exposed to virus. Inoculation of P haemolytica into tissue chambers resulted in the establishment of a localized soft-tissue infection, characteristic of pneumonic pasteurellosis. Despite the maintenance of chamber antimicrobial concentrations that exceeded minimal bactericidal concentrations established in vitro, the infections were not sterilized. This lack of efficacy was associated with decreased pH and increased protein concentrations in chamber fluids after inoculation. Infection with BVDV, which is thought to depress host defenses, had no effect on the response of P haemolytica to sulfadiazine/trimethoprim administration. Observation of responsive antibody titers, bacterial phagocytosis, and high leukocyte viability within P haemolytica-infected chambers documented functional host defenses within tissue chambers.     

Plasma pentachlorophenol concentrations in calves exposed to treated wood in the environment

Six calves were fed grain and hay from a pentachlorophenol (PCP)-treated feeder twice daily. Samples of blood were collected twice a week. Plasma PCP concentrations increased rapidly to a maximum of 1,086 microgram/L within 10 days. After the 3rd week, calves were denied access to the treated feeder; PCP values returned rapidly to near base line (before calves were fed from the treated feeder). After base-line plasma PCP values were reached, 4 of the 6 calves were housed in a total confinement building and exposed (by inhalation) to lumber that was commercially treated with PCP. The building itself was free of structural PCP-treated lumber. The ratio of building volume to treated wood surface was approximately 49 to 1. During the 3 weeks the calves were confined, PCP values did not increase and were markedly lower than those associated with oral exposure to treated wood. Oral dosing of calves with PCP in capsules--0.05 and 0.5 mg/kg--resulted in maximal plasma PCP values of 1,449 and 9,555 micrograms/L, respectively. Oral exposures (feeding from contaminated feeder; capsule) appeared to be more important than inhalation in causing increased plasma PCP concentrations in cattle. Exposure from these sources may be estimated by comparison with experimental values from dose-response studies. Feeding from treated feeders resulted in lower plasma PCP values than did dosing with 0.05 mg/kg daily.