ceftiofur and Respiratory-Tract-Infections

Cephalosporins are an important class of antibacterial agents in use today for both humans and animals. Four generations of cephalosporins have evolved, all of which contain the beta-lactam sub-structure first found in penicillin. The range of cephalosporins available for use in food-producing animals, which is the subject of this review, is limited compared to humans. A few first- and second-generation cephalosporins are approved worldwide strictly for treatment of mastitis infections in dairy cattle. A third-generation cephalosporin, ceftiofur, and a fourth-generation cephalosporin, cefquinome, have been developed strictly for veterinary use. Cefquinome has been approved in several countries for the treatment of respiratory disease in cattle and swine, foot rot in cattle and for mastitis in dairy cattle. Ceftiofur has worldwide approvals for respiratory disease in swine, ruminants (cattle, sheep and goats) and horses and has also been approved for foot rot and metritis infections in cattle. Ceftiofur has also been approved in various countries for early mortality infections in day-old chicks and turkey poults. This review summarizes cephalosporin use in general terms, and provides an overview of ceftiofur, in terms of its spectrum of activity, indications, metabolism, and degradation in the environment. The safety of ceftiofur is also reviewed, with respect to food-animal residues, rapid metabolism and degradation, and non-persistence of ceftiofur in the environment. The environmental fragility of cephalosporins have not been explored generally, but may be an important characteristic of this antibiotic class with respect to safety of use in animals.

Topics: Animals; Cephalosporins; Humans; Respiratory Tract Infections; Ruminants; Soil Pollutants; Structure-Activity Relationship

Three non-steroidal anti-inflammatory drugs (NSAIDs), flunixin, ketoprofen and carprofen, were used in conjunction with ceftiofur, in the treatment of naturally occurring bovine respiratory disease. Sixty-six mixed-breed beef cattle weighing on average 197 kg met the inclusion criteria of pyrexia of at least 40 degrees C, an illness score indicating at least moderate illness and at least moderate dyspnoea. They were allocated randomly to four treatment groups. All the groups received ceftiofur for three days at a dose rate of 1.1 mg/kg by intramuscular injection, and three groups received, in addition, a single dose of either flunixin (2.2 mg/kg by intravenous injection) or ketoprofen (3 mg/kg by intravenous injection) or carprofen (1.4 mg/kg by subcutaneous injection). During the first 24 hours of the study, the pyrexia of the three groups treated with a NSAID was reduced significantly more than the pyrexia of the group treated with ceftiofur alone, and two and four hours after treatment the reduction in pyrexia was significantly greater in the groups treated with flunixin and ketoprofen than in the group treated with carprofen. There were no statistically significant differences between the four groups with respect to depression, illness scores, dyspnoea or coughing. There was less lung consolidation in the three groups treated with a NSAID than in the animals treated with ceftiofur alone, but the difference was significant only in the group treated with flunixin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Carbazoles; Cephalosporins; Clonixin; Drug Therapy, Combination; Ketoprofen; Respiratory Tract Infections

Three experiments were conducted to determine preliminary efficacy of sustained release needle-less implants in effecting cure in calves with bovine respiratory disease. One hundred and twenty beef calves with a rectal temperature > or = 40 degrees C and shallow or labored respiration and coughing were used in these experiments. Four groups (1-ceftiofur sodium injections [days 1, 2, and 3], 2-ceftiofur sodium needle-less implants [days 1, 2, and 3], 3-ceftiofur sodium needle-less implants [days 1 and 3], and 4-ceftiofur sodium needle-less implants [day 1] were included. All treatments contained 250 mg of ceftiofur sodium and were administered intramuscularly in the neck after diagnosis of bovine respiratory disease. Experiment 1 included 20 calves (group 1-10 calves and group 3-10 calves; 213 to 255 kg) and calves were monitored for clinical efficacy. Experiment 2 included five calves per group (all four groups; 164 to 192 kg) and calves were bled frequently after treatment for desfuroylceftiofur (the primary ceftiofur metabolite) concentrations. Experiment 3 included 20 calves per group (all four groups; 160 to 205 kg) and calves were monitored for clinical efficacy. Blood desfuroylceftiofur concentrations remained above the minimum inhibitory concentration for Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus for 24 hours after injection and 72 hours after implantation (P < 0.05). Mortalities and the number of calves with a positive response and relapse response were similar (P < 0.25) among the four groups. In summary, the administration of one-250 mg ceftiofur sodium needle-less sustained release implant was as efficacious in treating bovine respiratory disease as three daily 250 mg injections of ceftiofur sodium.

Topics: Animals; Cattle; Cattle Diseases; Cephalosporins; Drug Implants; Male; Respiratory Tract Infections

The purpose of the present clinical studies was to determine the clinical efficacy of a combined parenteral and oral treatment with Bisolvon in combination with antibiotics in bovines suffering from acute respiratory disease. To this end four trials were conducted in respiratory diseased bovines; a total of 619 animals were evaluated. The animals were randomly assigned to one of two treatment groups within each study and were treated either with enrofloxacin, cefquinome, ceftiofur or florfenicol. The Bisolvon group was additionally treated with Bisolvon over 5 consecutive days. Daily clinical examinations were carried out over a period of 6 days. The clinical respiratory score, the primary parameter, representing a summation of the scoring points for the parameters respiratory rate, nasal discharge, spontaneous coughing, lung sounds and grade of dyspnoea and the clinical index score, which additionally included the general parameters fever, demeanour and feed intake, were significantly lower in the Bisolvon groups compared to the controls at all examinations after initiation of therapy in all trials with the exception of day 2 in one study. Lower values correspond to a less severe clinical condition. This consistent result as well as the evaluation of the single parameters are indicative of an acceleration of the recovery of the animals additionally treated with Bisolvon.

Topics: Acute Disease; Administration, Oral; Animals; Anti-Infective Agents; Bromhexine; Cattle; Cattle Diseases; Cephalosporins; Drug Therapy, Combination; Enrofloxacin; Fluoroquinolones; Injections; Quinolones; Respiratory Tract Infections; Thiamphenicol

Ceftiofur sodium was evaluated as a therapy for respiratory infections in horses. This cephalosporin antimicrobial was administered intramuscularly every 24 h and at a dose of 2.2 mg/kg (1.0 mg/lb) of body weight. The efficacy of ceftiofur sodium was compared with that of a positive control drug, ampicillin sodium (recommended dose of 6.6 mg/kg [3 mg/lb], given every 12 h). Both treatments were continued for 48 h after clinical symptoms were no longer evident (maximum of 10 days). Fifty-five (55) horses with naturally acquired respiratory infections were included in the study; 28 were treated with ceftiofur and 27 with ampicillin. Clinical improvement was recorded for 92.9% of the patients treated with ceftiofur and 92.6% of the animals receiving ampicillin. Both therapies reduced body temperatures to an afebrile level after 2 days of treatment. Complete recovery/cure was noted for 78.6% of the ceftiofur patients and 59.3% of the horses treated with ampicillin. Supporting variables (depression/malaise, respiration/dyspnoea, nasal discharge) were assessed and these also substantiated the effectiveness of the treatments. Both antibiotics were well tolerated. Neither pain nor swelling were noted at the ceftiofur injection site(s). None of the animals developed diarrhoea. Data from this study indicated that ceftiofur sodium is an effective and safe treatment for respiratory infections in horses.

Topics: Ampicillin; Animals; Body Temperature; Cephalosporins; Depression; Female; Horse Diseases; Horses; Injections, Intramuscular; Male; Nasal Mucosa; Respiration; Respiratory Tract Infections

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Delayed-Action Preparations; Female; Horse Diseases; Horses; Injections, Intramuscular; Respiratory Tract Infections

In vitro activity of ceftiofur and six other antimicrobial agents was assessed for 516 Streptococcus equi subsp zooepidemicus isolates collected from horses with lower respiratory tract infections in North America in 2007 and 2008 and 239 equine S. equi subsp zooepidemicus isolates received from US and Canadian veterinary diagnostic laboratories between 1989 and 2007. The lowest concentration of ceftiofur inhibiting the growth of 90% of the isolates (MIC90) was 0.12 microg/ml for both groups of isolates. The Clinical and Laboratory Standards Institute susceptible breakpoint set for ceftiofur against this organism is a minimal inhibitory concentration value of ≤ 0.25 microg/ml. The MIC90 values remained consistent for isolates collected over 19 years.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Bacterial; Horse Diseases; Horses; Microbial Sensitivity Tests; North America; Respiratory Tract Infections; Streptococcal Infections; Streptococcus equi; Time Factors

In vitro activity of ceftiofur and six other antimicrobial agents was evaluated against 79 Streptococcus equi subsp zooepidemicus isolates collected from horses with respiratory disease in Europe during 2007 and 2008. In addition, the in vitro activity of ceftiofur and other antimicrobial drugs was assessed against 59 S. equi subsp zooepidemicus and 49 S. equi subsp equi isolates collected by veterinary diagnostic laboratories in Europe from 2002 to 2006. The lowest concentration of ceftiofur that inhibited the growth of 90% of the isolates (MIC90) was 0.12 microg/ml, with the Clinical Laboratory Standards Institute-approved susceptible breakpoint set at ≤ 0.25 microg/ml for ceftiofur against S. equi subsp zooepidemicus. The MIC90 values remained consistent when comparing the isolates collected from diagnostic laboratories or from the field study.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Bacterial; Europe; Horse Diseases; Horses; Microbial Sensitivity Tests; Respiratory Tract Infections; Streptococcal Infections; Streptococcus equi; Time Factors

Extended-spectrum beta-lactamases (ESBLs), mainly of the CTX-M family, have been associated with Escherichia coli strains of animal origin in Europe. An in vivo experiment was performed to study the effects of veterinary beta-lactam drugs on the selection and persistence of ESBL-producing E. coli in the intestinal flora of pigs. Twenty pigs were randomly allocated into three treatment groups and one control group. All pigs were inoculated intragastrically with 10(10) CFU of a nalidixic acid (NAL)-resistant mutant derived from a CTX-M-1-producing E. coli strain of pig origin. Treatment with amoxicillin, ceftiofur, or cefquinome according to the instructions on the product label was initiated immediately after bacterial inoculation. Feces were collected from the rectum before inoculation and on days 4, 8, 15, 22, and 25 after the start of treatment. The total and resistant coliforms were counted on MacConkey agar with and without cefotaxime (CTX). Furthermore, MacConkey agar with CTX and NAL was used to count the number of CFU of the inoculated strain. Significantly higher counts of CTX-resistant coliforms were observed in the three treatment groups than in the control group for up to 22 days after the discontinuation of treatment. Ceftiofur and cefquinome exerted larger selective effects than amoxicillin, and the effects persisted beyond the withdrawal times recommended for these cephalosporins. The inoculated strain was detected in only nine animals on day 25. The increase in the number of CTX-resistant coliforms was mainly due to the proliferation of indigenous CTX-M-producing strains and the possible emergence of strains that acquired CTX-M genes by horizontal transfer. The study provides evidence that the cephalosporins used in pig production select for CTX-M-producing E. coli strains. Their use in animals should be carefully considered in view of the critical importance of cephalosporins and the zoonotic potential of ESBL-producing bacteria.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cephalosporins; Colony Count, Microbial; Escherichia coli; Female; Genes, Bacterial; Intestines; Mutation; Nalidixic Acid; Respiratory Tract Infections; Sus scrofa; Swine Diseases

Topics: Actinobacillus pleuropneumoniae; Animals; Cattle; Cattle Diseases; Cephalosporins; Mannheimia haemolytica; Microbial Sensitivity Tests; Pasteurella multocida; Pasteurellaceae; Pasteurellaceae Infections; Respiratory Tract Infections; Swine; Swine Diseases

Ceftiofur, an extended-spectrum cephalosporin, is active against a variety of animal pathogens, including organisms associated with swine respiratory disease. However, minimum inhibitory concentration (MIC) breakpoint and disk diffusion interpretive criteria have not been established for swine pathogens. Susceptibility tests were performed by broth microdilution MIC and disk diffusion methods on 246 bacterial species that cause swine respiratory disease. Ceftiofur was active against Salmonella sp., Pasteurella multocida, Actinobacillus pleuropneumoniae, Streptococcus suis, and Escherichia coli but was not active against Bordetella bronchiseptica measured by MIC. Based on pharmacokinetic studies of ceftiofur in swine after a single intramuscular injection of 3 or 5 mg/kg body weight of ceftiofur and on the MIC and disk diffusion data, we recommend MIC breakpoints and disk diffusion distances, respectively, of < or = 2 micrograms/ml and > or = 21 mm for susceptible, 4 micrograms/ml and 18-20 mm for intermediate, and > or = 8 micrograms/ml and > or = 17 mm for resistant classification for swine pathogens. When these breakpoints were applied to data from a previous study using bovine pathogens, only 1 minor interpretive error occurred.

Topics: Actinobacillus pleuropneumoniae; Animals; Bordetella bronchiseptica; Cattle; Cattle Diseases; Cephalosporins; Escherichia coli; Injections, Intramuscular; Microbial Sensitivity Tests; Pasteurella multocida; Respiratory Tract Infections; Salmonella; Streptococcus suis; Swine; Swine Diseases

Topics: Actinobacillus pleuropneumoniae; Animals; Bacterial Infections; Cephalosporins; Microbial Sensitivity Tests; Pasteurella multocida; Respiratory Tract Infections; Swine; Swine Diseases

Topics: Ampicillin; Animals; Cephalosporins; Horse Diseases; Horses; Respiratory Tract Infections

The antimicrobial susceptibilities of 421 Pasteurella haemolytica and 158 P. multocida isolates recovered from cattle with respiratory disease were determined with a microdilution minimal inhibitory concentration test system. Isolates were analyzed for patterns of resistance to ampicillin, ceftiofur, erythromycin, gentamicin, penicillin, spectinomycin, sulfachlorpyridazine, sulfadimethoxine, tetracycline, and tylosin. All isolates tested were found susceptible to ceftiofur and sulfachlorpyridazine. Pasteurella haemolytica isolates were resistant to ampicillin, penicillin, sulfadimethoxine, tetracycline, and tylosin. Pasteurella multocida isolates were resistant to sulfadimethoxine, tetracycline, and tylosin.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Drug Resistance, Microbial; Gentamicins; Microbial Sensitivity Tests; Pasteurella; Pasteurella Infections; Respiratory Tract Infections; Sulfachlorpyridazine