The efficacy of sulbactam-ampicillin in the therapy of respiratory disease associated with ampicillin resistant Pasteurella species in housed calves

Sulbactam-ampicillin is a combination of sulbactam, a beta-lactamase inhibitor, and ampicillin, a broad spectrum beta-lactam antibiotic. The efficacy of sulbactam-ampicillin was evaluated in the treatment of calf respiratory disease associated with ampicillin-sensitive and ampicillin-resistant strains of Pasteurella haemolytica and Pasteurella multocida. Treatment with sulbactam-ampicillin was compared with treatment with ampicillin alone in 123 Friesian calves, between three and five weeks old, exhibiting clinical signs of respiratory disease. Seven of the 59 calves treated with ampicillin died whereas only one death occurred in the 64 calves treated with sulbactam-ampicillin. In the calves which survived, treatment with sulbactam-ampicillin resulted in a significantly better clinical response, as measured by the reduction in severity of clinical signs. The results of bacteriological examinations indicated that there was a marked increase in the proportion of ampicillin-resistant isolates of P haemolytica subsequent to treatment with ampicillin, whereas the proportion of ampicillin-resistant isolates of P. haemolytica recovered from calves treated with sulbactam-ampicillin had declined. The superior efficacy of sulbactam-ampicillin observed in this study is explained by the inhibitory effect of sulbactam on beta-lactamases produced by resistant bacteria, thus rendering them susceptible to the ampicillin.     

Efficacy of Sulbactam, a B-lactamase Inhibitor, Combined with Ampicillin in the Therapy of Ampicillin-resistant Pneumonic Pasteurellosis in Veal Calves

Two field efficacy studies, involving a total of 92 naturally infected, pneumonic veal calves, were conducted to compare the efficacy of the β-lactamase inhibitor sulbactam plus ampicillin to ampicillin alone in the treatment of bacterial pneumonia. Cultures from nasal swabs and lung tissue during the 10 or 11 day studies were predominantly ampicillin-resistant Pasteurella multocida. Ampicillin (6.6 mg/kg) or sulbactam-ampicillin (3.3 mg/kg sulbactam + 6.6 mg/kg ampicillin) was injected intramuscularly once daily for either three days or six days. Sulbactam-ampicillin administered once daily for three or six days resulted in lower (P≤0.05) average body temperature with a concomitant clinical improvement (P≤0.05), and produced numerical advantages and/or statistical improvements over ampicillin in mortality, weight gain, and overall response of calves to treatment. The combined mortality for the two studies in the ampicillin and sulbactam-ampicillin treated groups was 43% and 14%, respectively. We concluded that sulbactam-ampicillin was superior to ampicillin in the treatment of ampicillin-resistant bacterial pneumonia in veal calves.     

The plasma kinetics of sulbactam-ampicillin administered to calves by the intramuscular and subcutaneous routes

Sulbactam-ampicillin combines ampicillin, a broad spectrum beta-lactam antibiotic, with sulbactam, an irreversible beta-lactamase inhibitor. The sulbactam component prevents the degradation of ampicillin by several major classes of bacterial beta-lactamases and restores the activity of ampicillin against most strains of bacteria in which resistance is mediated by beta-lactamase production.A crossover study was conducted in Friesian calves of 98–119 kg bodyweight in which the plasma kinetics of sulbactam-ampicillin adminstered by the intramuscular and subcutaneous routes were defined, and the plasma kinetics of ampicillin derived from sulbactam-ampicillin and a commercially available formulation of ampicillin trihydrate were compared. Subsequent to both intramuscular and subcutaneous administration of sulbactam-ampicillin, peak plasma concentrations of sulbactam and ampicillin were recorded two hours post-injection. Higher peak plasma concentrations of both sulbactam and ampicillin were achieved by the subcutaneous route of administration and, for ampicillin, the difference between the two routes was statistically significant (p < 0·01). However, there was no significant difference in bioavailability (as measured by area under the curve) between the two routes of administration for either component. In addition, there were no significant differences between the peak plasma concentrations or areas under the curves for ampicillin derived from intramuscular administration of sulbactam-ampicillin, and ampicillin alone, indicating that combination with sulbactam does not alter the plasma kinetics of ampicillin.     

Efficacy of Sulbactam, a B-lactamase Inhibitor, Combined with Ampicillin in the Therapy of Ampicillin-resistant Pneumonic Pasteurellosis in Feedlot Calves

Two field efficacy studies, involving a total of 80 naturally infected feedlot calves, were conducted to compare the efficacy of sulbactam-ampicillin with that of penicillin-dihydrostreptomycin in the treatment of pneumonic pasteurellosis. Cultures from pretreatment nasal swabs were predominantly ampicillin/ penicillin resistant Pasteurella haemolytica. Clinical observations revealed that cattle treated with penicillin-dihydrostreptomycin responded poorly, whereas those treated with sulbactam-ampicillin responded promptly. Twenty-four hours after initiation of treatment, mean body temperatures of the calves in the sulbactam-ampicillin groups had decreased by 2.1°C, whereas, in the penicillin-dihydrostreptomycin calves there was little change. The difference between the two treatments was statistically significant (P≤0.01). The combined mortality for the two studies in the penicillin-dihydrostreptomycin treated groups was 18%. No mortality occurred in the sulbactam-ampicillin treated groups. Our data show that sulbactam-ampicillin was more effective than penicillin-dihydrostreptomycin in the treatment of pneumonia caused by ampicillin/penicillin resistant strains of Pasteurella in feedlot calves.     

Efficacy of sulbactam-ampicillin in an induced Pasteurella haemolytica pneumonia model in calves

Therapeutic efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ampicillin was evaluated in an ampicillin-resistant Pasteurella haemolytica pneumonia model in cattle, using an IV agar emboli method of infection. Groups of cattle given vehicle (group 1, n = 19) or ampicillin (group 2, n = 8) had 74% and 50% mortality, respectively, whereas group 3 (n = 11) given sulbactam-ampicillin had no mortality. Morbidities were 100% in groups 1 and 2 and 27% in group 3. Retrospectively, mortalities and morbidities were significantly (P less than 0.001) lower for group 3 given sulbactam-ampicillin when compared with those in groups 1 and 2 given vehicle or ampicillin, respectively. Evidence of embolic pneumonic pasteurellosis was observed histologically.     

Clinical and pathological evaluation of sulbactam/ampicillin for treatment of experimental bovine pneumonic pasteurellosis

An experiment was conducted to evaluate the efficacy of sulbactam/ampicillin for treatment of bovine pneumonic pasteurellosis. Twenty-one Hereford calves were experimentally infected with bovine herpesvirus-1 and an ampicillin-resistant strain of Pasteurella haemolytica, then treated for three days with either sulbactam/ampicillin, chloramphenicol, or a placebo. The treatments were evaluated by comparing clinical illness scores, total sick days, weight changes, mortality rates, and postmortem lung scores between treatment groups. Both antibiotics were highly effective in reducing respiratory disease in the experimentally infected calves. The clinical response to sulbactam/ampicillin treatment was comparable with that of chloramphenicol and was significantly improved compared with the response to the placebo treatment. These findings suggest that the efficacy of sulbactam/ampicillin may be comparable to that of chloramphenicol for treatment of pneumonic pasteurellosis involving ampicillin-resistant strains of P. haemolytica.     

Efficacy of halofuginone lactate in the prevention of cryptosporidiosis in suckling calves

The efficacy of halofuginone lactate in the prevention of cryptosporidiosis in suckling calves was evaluated in a multicentre, control versus placebo, randomised, double-blind clinical trial. Seventy-eight six- to 48-hour-old calves were treated daily with 120 microg/kg bodyweight of halofuginone lactate administered orally for seven consecutive days, while 80 calves received a placebo. Faecal samples were collected on the first day of dosing and four, seven, 14 and 21 days later, and Cryptosporidium parvum oocysts were counted and faecal indices for diarrhoea were determined after a clinical examination. An analysis of variance for repeated measurements showed a highly significant difference in favour of halofuginone lactate for both the oocyst counts (P=0.0002) and the faecal diarrhoea indices (P=0.0001) throughout the trial. The difference was greatest after seven days, when the mean oocyst count of the placebo group was 2.5 times and its mean faecal index was twice the mean of the halofuginone lactate group. One day after the end of the treatment the calves which received halofuginone lactate excreted 44 per cent fewer C parvum oocysts and 44 per cent fewer of them had diarrhoea. The reduction was even greater (65 per cent) when liquid diarrhoea was assessed, with 32.5 per cent of the calves in the placebo group having liquid diarrhoea compared with 11.5 per cent in the halofuginone lactate group. The treatment was well tolerated and easily administered.     

Activity of beta-lactamase inhibitor sulbactam plus ampicillin against animal isolates of Pasteurella, Haemophilus, and Staphylococcus

Antibiotic susceptibilities of Pasteurella sp, Haemophilus pleuropneumoniae, and Staphylococcus aureus isolates were determined. The combination of sodium sulbactam, a beta-lactamase inhibitor, and ampicillin had a synergistic effect against all ampicillin-resistant pathogens, rendering them susceptible to ampicillin. Studies of cell-free beta-lactamase from Pasteurella and Haemophilus isolates confirmed the presence of a constitutive penicillinase. Inhibitory concentrations of sulbactam-ampicillin were bactericidal, as demonstrated by killing curves. Ampicillin-resistant Pasteurella and Haemophilus isolates did not develop resistance to sulbactam-ampicillin when passed as many as 8 times in the presence of sublethal concentrations of sulbactam-ampicillin. The in vitro synergistic activity of sulbactam-penicillin also was seen in an in vivo synergistic response in mice challenge exposed to an ampicillin-resistant P haemolytica.     

A comparison of two oral rehydration solutions in experimental models of dehydration and diarrhoea in calves

Two oral rehydration solutions (ORS 1 and ORS 2) were evaluated in isolated intestinal loops of anaesthetised calves, in an experimental model of dehydration in the calf, in calves with experimentally induced diarrhoea and in 164 calves with clinical diarrhoea. The studies in isolated intestinal loops indicated that water absorption was significantly greater from ORS 2 than from ORS 1. After the intraperitoneal administration of hypertonic mannitol combined with intravenous diuretics, the plasma volume of calves was reduced by about 30 per cent, and was more rapidly expanded after treatment with ORS 2 than ORS 1. The plasma volume remained significantly reduced (P less than 0.01) three hours after dosing with ORS 1 whereas after treatment with ORS 2 it was not significantly different from the initial value. Acidosis was corrected to a significantly (P less than 0.01) greater extent after treatment with ORS 2, and peripheral perfusion also returned to normal more rapidly in calves given ORS 2. In newly purchased calves in which diarrhoea was induced experimentally with an E coli challenge, base deficit and diarrhoea were corrected more rapidly in the calves receiving ORS 2. When the solutions were tested in the treatment of 164 clinical cases of diarrhoea and dehydration there was no statistically significant difference in mortality between the formulations, although the overall mortality was 4.8 per cent in the calves treated with ORS 2, compared with 8.6 per cent in the calves treated with ORS 1. It was concluded that ORS 2 performed better than ORS 1 especially in the expansion of plasma volume and the correction of acidosis.     

Comparative pharmacokinetics of ampicillin-sulbactam combination in calves and sheep

The pharmacokinetics of ampicillin and sulbactam administered in combination were studied in calves and sheep. The animals were administered an aqueous solution of ampicillin/sulbactam (2: 1, w/w) intravenously and intramuscularly at doses of 13.2 and 6.6 mg.kg^-1, respectively. A microbiological method was used to detect ampicillin, and HPLC was used to detect sulbactam in serum. Following intravenous (i, v.) administration, the distribution phases were rapid and similar (about 15 min) for both drugs in both species, whereas sulbactam in calves and ampicillin in sheep showed a faster elimination rate. After intramuscular (i.m.) administration both drugs showed peak concentrations higher in calves than in sheep: the peak time of sulbactam was shorter in calves than in sheep. No other significant differences in the pharmacokinetics of the combination were observed between the species after i.m. injection. The mean residence and absorption times, calculated by non-compartmental analysis, for both calves and sheep suggested that the differences in ampicillin and sulbactam phgrmacokinetics could be attributable to the different molecular structures.     

Some husbandry factors affecting mortality and morbidity on a calf-rearing unit

The influence of some husbandry factors on morbidity and mortality was studied in 1996 artificially reared, dairy bred calves over the period from purchase until about six weeks of age. The effects of housing (indoors versus outdoors), penning (individual versus group), breed, time since purchase and season of purchase were examined. The overall mortality rate was approximately 4 per cent and calves were more likely to die if reared in groups outdoors than if reared either singly or in groups indoors. The mortality rate was significantly lower in calves purchased between April and June than at other times of year. Pneumonia was the most common disease symptom (48.3 per cent of calves) with diarrhoea the second most common (14.1 per cent). Neither the type of penning nor housing affected the incidence of pneumonia but diarrhoea was most common in individually penned calves. Case mortality rates for diarrhoeic calves in group pens were higher than for those in single pens and case mortality rates for pneumonia were highest for calves reared in groups outdoors. More than half the cases of pneumonia occurred between one and three weeks after purchase whereas two-thirds of the cases of diarrhoea occurred within the first week after purchase. However, case mortality rates for both conditions appeared to increase with time since purchase.     

The effect of organic acids on the control of porcine post-weaning diarrhoea

Post-weaning diarrhoea syndrome (PWDS) of piglets is caused mainly by Enterotoxigenic Escherichia coli (ETEC) strains. Six organic acids were tested for their efficacy in the control of PWDS, using a total of 384 weaned piglets, in eight groups, during a 28-day period. One group (negative control) was offered a diet free of antimicrobials, one group (positive control) was offered the same diet medicated with 44 p.p.m. of lincomycin and 44 p.p.m. spectinomycin (Lincospectin 22 premix, Upjohn), and six groups were offered feed supplemented with either 1.0 per cent propionic acid, 1.6 per cent lactic acid, 1.2 per cent formic acid, 1.2 per cent malic acid, 1.5 per cent citric acid or 1.5 per cent fumaric acid. Groups were compared with regard to the appearance of clinical signs, mortality, weight gain and feed conversion. All groups supplemented with organic acids had reduced incidence and severity of diarrhoea, and performed significantly better than the negative control group (P<0.05). At the end of the trial, ETEC strains were detected in the control group not receiving antibiotics but not in the treated group. Organic acids and especially lactic acid are a useful tool in controlling PWDS.     

Efficacy of halofuginone lactate in the prevention of cryptosporidiosis in dairy calves

To evaluate the efficacy of halofuginone lactate (Halocur; Intervet) when used prophylactically against cryptosporidiosis in dairy calves, 513 Holstein heifer calves were randomly distributed between two experimental groups. Those in the treatment group (n=259) received 0.1 mg halofuginone base per kg bodyweight daily in a 10 ml solution, for the first seven days following birth, while those in the control group (n=254) received an equal volume of a placebo solution. Faecal samples were collected weekly from all calves until three weeks of age to test for Cryptosporidium oocysts and to assess the diarrhoeal status. Growth parameters of the calves were also recorded at approximately four months of age. Calves that received halofuginone were significantly less likely to shed Cryptosporidium oocysts during the course of the study than placebo-treated calves (odds ratio 0.6, 95 per cent confidence interval 0.4 to 0.9, P=0.009). Mean growth measurements of calves in the treated group were consistently higher than those of the control calves (hipometer-derived P=0.052, wither height P=0.097) and mortality was lower in the treated group (P=0.07). However, these differences were not statistically significant (P>0.05). No association was found between the prophylactic use of halofuginone and the incidence of calf diarrhoea.     

Diarrhoea in dairy calves reduced by feeding colostrum from cows vaccinated with rotavirus

Forty-two dairy calves remained with their dams for two days after birth, and then were removed to a calf rearing shed. Calves were allocated to three groups for the next 14 days, and received twice daily either whole milk, whole milk with a 10 per cent supplement of pooled normal bovine colostrum or whole milk with 10 per cent supplement of colostrum from cows vaccinated with rotavirus. A natural outbreak of diarrhoea occurred, affecting 28 of the 42 calves. Feeding immune colostrum delayed the onset of diarrhoea, and reduced its incidence, duration and severity. Live weight gains were consequently improved. The group fed normal colostrum had diarrhoea intermediate in severity between that of control calves and those fed immune colostrum. The aetiology of the diarrhoea was complex, with calves excreting rotavirus, enteropathogenic Escherichia coli and cryptosporidia.     

Microbiology of calf diarrhoea in southern Britain

Faeces samples from calves with diarrhoea in 45 outbreaks were examined for six enteropathogens. Rotavirus and coronavirus were detected by ELISA in 208 (42 per cent) and 69 (14 per cent) of 490 calves respectively; calici-like viruses were detected by electron microscopy in 14 of 132 calves (11 per cent). Cryptosporidium were detected in 106 of 465 (23 per cent), Salmonella species in 58 of 490 (12 per cent) and enterotoxigenic Escherichia coli bearing the K99 adhesin (K99+ E coli) in nine of 310 calves (3 per cent). In the faeces of 20 per cent of calves with diarrhoea more than one enteropathogen was detected; in 31 per cent no enteropathogen was found. Faces samples from 385 healthy calves in the same outbreaks were also examined. There was a significant statistical association of disease with the presence of rotavirus, coronavirus, Cryptosporidium and Salmonella species (P less than 0.001). Healthy calves were not examined for calici-like viruses and the association of K99+ E coli with disease was not analysed because there were too few positive samples. Rotavirus infections were more common in dairy herds and single suckler beef herds whereas Salmonella infections were more often found in calf rearing units. Cryptosporidium were more common in single and multiple suckler beef herds. K99+ E coli were found in one dairy herd and one multiple suckler beef herd both with unhygienic calving accommodation. Variations in coronavirus detection among different farm types were not statistically significant. In this survey rotavirus was the most commonly detected agent in calf diarrhoea and Cryptosporidium were found in approximately one quarter of affected calves. Infection with Salmonella species was widespread, but K99+ E coli infections were less common in the United Kingdom than in other countries.     

Aetiology of diarrhoea in young calves

Faeces samples were collected from 302 untreated calves on the day of onset of diarrhoea and from 49 healthy calves at 32 farms experiencing outbreaks of diarrhoea. At least four diarrhoeic calves were sampled on each farm, and samples were examined for rotavirus, coronavirus, cryptosporidium, enterotoxigenic Escherichia coli and Salmonella species. Although all these enteropathogens were excreted more frequently by the diarrhoeic than by the healthy calves, the difference was significant overall only for rotavirus. Rotavirus was excreted by 18 per cent of healthy calves, coronavirus by 4 per cent, cryptosporidium by 14 per cent, and no enterotoxigenic E coli or Salmonella species were detected. The most common enteropathogen in diarrhoeic calves was rotavirus, which was excreted by more than half the diarrhoeic calves on 18 farms. Coronavirus was excreted at a similar high prevalence on one farm, cryptosporidium on five farms and enterotoxigenic E coli on three farms. Concurrent infection with two or more microorganisms occurred in 15 per cent of diarrhoeic calves. There was no difference in the isolation rate of campylobacters between diarrhoeic and healthy calves.     

Antimicrobial susceptibility of Salmonella isolates recovered from calves with diarrhoea in Australia

OBJECTIVE To identify the common serotypes and antimicrobial resistance patterns of Salmonella spp. associated with diarrhoea in Australian dairy calves under the age of 6 weeks. DESIGN Cross-sectional study. METHODS Faecal samples were collected from outbreaks of diarrhoea in dairy and dairy beef calves less than 6 weeks old. Samples were screened for Salmonella using standard enrichment culture techniques. The antimicrobial susceptibility to 12 commonly used veterinary and human antimicrobials was assessed using the Kirby-Bauer disk diffusion method and the susceptibility profiles of dairy and dairy beef properties were compared using Fisher's exact test. RESULTS Salmonella ser. Dublin, S. ser. Typhimurium and S. ser. Bovismorbificans were the three most common salmonella serotypes isolated. The majority of properties had one serotype. Most of the Salmonella isolates were not resistant to any of the antimicrobials tested. No resistance was seen to amikacin and nalidixic acid, and only one isolate was resistant to ceftiofur or amoxicillin-clavulanic acid. The most common antimicrobial resistance was to streptomycin, ampicillin or combination sulfonamides. Multi-drug resistance was detected in S. ser. Anatum, S. ser. Bovismorbificans, S. ser. Muenster, S. ser. Newport and S. ser. Typhimurium. Isolates from dairy beef properties were more likely to be resistant to ampicillin, kanamycin, neomycin, sulfamethoxazole/trimethoprim and tetracycline (P < 0.05) and were more likely to exhibit multi-drug resistance. CONCLUSION The prevalence of antimicrobial resistance in Salmonella isolates from dairy calves in Australia is low compared with that reported overseas. From a human health perspective, resistance to antimicrobials used in the treatment of human salmonellosis was infrequent.     

Persistent excretion of rotavirus by pregnant cows

In a study of the epizootiology and prevalence of enteropathogens which may be involved in neonatal calf diarrhoea, 10 in-calf cows from a herd with a history of rotavirus-induced calf diarrhoea were monitored over a period of six to seven months. All the cows excreted rotavirus intermittently without showing any clinical signs, and 21.8 per cent of faecal samples contained rotavirus. Reoviruses were isolated from 87 per cent of the samples from the cows, and from all the 10 calves born to them. However, rotavirus was detected in only one calf, and diarrhoea developed only in this calf even though the calves were housed in communal pens. Campylobacter jejuni was isolated from six of the 10 dams and from five of the 10 calves, not including the calf with diarrhoea. Other potential enteropathogens such as cryptosporidium, salmonella, Clostridium difficile, coronavirus and other viruses were not found, but two cows and two calves shed enterotoxigenic Escherichia coli.     

Prevalence of four enteropathogens in the faeces of young diarrhoeic dairy calves in Switzerland

The prevalences of Cryptosporidium parvum, rotavirus, bovine coronavirus (bcv), and enterotoxigenic Escherichia coli (E coli k99) were determined in diarrhoeic dairy calves aged one to 21 days on 71 dairy farms in western Switzerland during the winter of 2005 to 2006. Faecal samples from 147 untreated calves suffering from acute diarrhoea were analysed by standardised diagnostic methods, and the immunoglobulin status of each calf was evaluated. The prevalences of C parvum, rotavirus, bcv and E coli k99 were 55.0 per cent, 58.7 per cent, 7.8 per cent and 5.5 per cent, respectively. The proportions of herds positive for the respective pathogens among the herds with diarrhoeic calves were 41.7 per cent, 52.1 per cent, 2.1 per cent and 2.1 per cent. The immunoglobulin concentration in the serum of 90.5 per cent of the diarrhoeic calves was below 8 g/l.     

Effect of dried oregano leaves versus neomycin in treating newborn calves with colibacillosis

Treatment with neomycin (as a positive control) and dried oregano leaves on mortality, number of days scouring and severity of scours due to Escherichia coli were examined in 30 Holstein calves. Calves were assigned to one of the treatments following clinical signs of diarrhoea (i.e. faecal score >2), and treated either with an oral solution of neomycin sulphate, to provide 10 mg neomycin sulphate per kg calf body weight per 24 h, or dried oregano leaves, to provide 10 mg oregano essential oil per kg calf body weight per 24 h. The number of scouring days, severity of scouring and mortality rates were similar between the treatments. This study indicates that dried oregano leaves administered as an oral solution to calves with diarrhoea may be as effective in the treatment of colibacillosis as neomycin.