ceftiofur and Escherichia-coli-Infections

A new, extended long-acting tilmicosin (TLAe) preparation was tested against intramammary ceftiofur (CEF) using a non-inferiority trial model during dry-cow therapy (DCT) in a farm with high bovine population density and deficient hygiene application.. To evaluate the possibility that TLAe administered parenterally can achieve non-inferiority status compared to CEF administered intramammary for DCT.. TLAe and CEF had overall cure rates of 57% and 53% (. This study is the first successful report of parenteral DCT showing comparable efficacy as CEF, the gold-standard. The extended long-term pharmacokinetic activity of TLAe explains these results.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Delayed-Action Preparations; Escherichia coli; Escherichia coli Infections; Female; Injections, Subcutaneous; Mastitis, Bovine; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Tylosin

The objective of this study was to describe weekly quarter-level somatic cell count (QSCC) after occurrence of nonsevere clinical mastitis (CM) that was diagnosed as culture negative, or caused by Escherichia coli or Klebsiella pneumoniae. All cases occurred in cows enrolled in negatively, controlled randomized clinical trials. We hypothesized that after occurrence of CM, QSCC patterns would vary among etiologies and this effect would not be mitigated by treatment using intramammary (IMM) ceftiofur. Data from two previously published randomized clinical trials performed on 3 Wisconsin dairy farms were used. Only cases confirmed as culture negative (NG) or E. coli or Kleb. pneumoniae (GRAMNEG) were used for analysis. In NG, cows were assigned to no antimicrobial treatment (negative control, n = 44) or 5 d of once daily IMM (n = 41) infusions with an approved product containing ceftiofur hydrochloride. In GRAMNEG, cows were assigned to IMM treatment with the same ceftiofur product for 2 different durations (2 d, n = 36; or 8 d, n = 38) or no antimicrobial treatment (negative control, n = 36). For quarters enrolled in NG, no significant differences were identified for weekly QSCC between quarters in the treated or negative control groups (5.4 log

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Klebsiella Infections; Klebsiella pneumoniae; Longitudinal Studies; Mammary Glands, Animal; Mastitis, Bovine; Milk

Antibiotic use in beef cattle is a risk factor for the expansion of antimicrobial-resistant Salmonella populations. However, actual changes in the quantity of Salmonella in cattle feces following antibiotic use have not been investigated. Previously, we observed an overall reduction in Salmonella prevalence in cattle feces associated with both ceftiofur crystalline-free acid (CCFA) and chlortetracycline (CTC) use; however, during the same time frame the prevalence of multidrug-resistant Salmonella increased. The purpose of this analysis was to quantify the dynamics of Salmonella using colony counting (via a spiral-plating method) and hydrolysis probe-based qPCR (TaqMan® qPCR). Additionally, we quantified antibiotic-resistant Salmonella by plating to agar containing antibiotics at Clinical & Laboratory Standards Institute breakpoint concentrations. Cattle were randomly assigned to 4 treatment groups across 16 pens in 2 replicates consisting of 88 cattle each. Fecal samples from Days 0, 4, 8, 14, 20, and 26 were subjected to quantification assays. Duplicate qPCR assays targeting the Salmonella invA gene were performed on total community DNA for 1,040 samples. Diluted fecal samples were spiral plated on plain Brilliant Green Agar (BGA) and BGA with ceftriaxone (4 μg/ml) or tetracycline (16 μg/ml). For comparison purposes, indicator non-type-specific (NTS) E. coli were also quantified by direct spiral plating. Quantity of NTS E. coli and Salmonella significantly decreased immediately following CCFA treatment. CTC treatment further decreased the quantity of Salmonella but not NTS E. coli. Effects of antibiotics on the imputed log10 quantity of Salmonella were analyzed via a multi-level mixed linear regression model. The invA gene copies decreased with CCFA treatment by approximately 2 log10 gene copies/g feces and remained low following additional CTC treatment. The quantities of tetracycline or ceftriaxone-resistant Salmonella were approximately 4 log10 CFU/g feces; however, most of the samples were under the quantification limit. The results of this study demonstrate that antibiotic use decreases the overall quantity of Salmonella in cattle feces in the short term; however, the overall quantities of antimicrobial-resistant NTS E. coli and Salmonella tend to remain at a constant level throughout.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Cattle; Cephalosporins; Chlortetracycline; Colony Count, Microbial; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Foodborne Diseases; Longitudinal Studies; Male; Microbial Sensitivity Tests; Prevalence; Red Meat; Salmonella; Salmonella Infections, Animal

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Dairying; Escherichia coli; Escherichia coli Infections; Farms; Female; Klebsiella Infections; Klebsiella pneumoniae; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Random Allocation

Ceftiofur (CEF) is a third-generation cephalosporin that is the most widely used antimicrobial in the dairy industry. Currently, violative meat residues in cull dairy cattle are commonly associated with CEF. One potential cause for violative residues is altered pharmacokinetics of the drug due to disease, which could increase the time needed for the residue to deplete. The objectives of this study were (a) to determine the absolute bioavailability of CEF crystalline-free acid (CFA) in healthy versus diseased cows; (b) to compare the plasma and interstitial fluid pharmacokinetics and plasma protein binding of CEF between healthy dairy cows and those with disease; and (c) to determine the CEF residue profile in tissues of diseased cows. For this trial, disease was induced through intramammary Escherichia coli infusion. Following disease induction and CEF CFA administration, for plasma concentrations, there was not a significant effect of treatment (p = 0.068), but the treatment-by-time interaction (p = 0.005) was significant. There was a significantly greater concentration of CEF in the plasma of the DIS cows at T2 hr (p = 0.002), T8 hr (p < 0.001), T12 hr (p = 0.001), and T16 hr (p = 0.002). For PK parameters in plasma, the slope of the terminal phase of the concentration versus time curve was significantly lower (p = 0.007), terminal half-life was significantly longer (p = 0.014), and apparent volume of distribution during the elimination phase was significantly higher (p = 0.028) diseased group. There was no difference in plasma protein binding of CEF and interstitial fluid pharmacokinetics. None of the cows had kidney CEF residues above the US tolerance level following observation of the drug's withdrawal period, but one cow with a larger apparent volume of distribution and longer terminal half-life had tissue residues slightly below the tolerance. Whereas these findings do not support the hypothesis that severely ill cows need longer withdrawal times, alterations in the terminal half-life suggest that it is theoretically possible.

Topics: Animals; Biological Availability; Cattle; Cephalosporins; Escherichia coli Infections; Female; Mastitis, Bovine; Tissue Distribution

The use of antimicrobials in food animals and the emergence of antimicrobial resistance are global concerns. Ceftiofur is the only third-generation cephalosporin labeled for veterinary use in the USA, and it is the drug of choice in the majority of dairy farms for the treatment of mastitis. Here, we use next-generation sequencing to describe longitudinal changes that occur in the milk microbiome before, during, and after infection and treatment with ceftiofur. Twelve animals were intramammary challenged with Escherichia coli in one quarter and randomly allocated to receive intramammary treatment with ceftiofur (5d) or untreated controls. Serial samples were collected from -72 to 216 h relative to challenge from the challenged quarter, an ipsilateral quarter assigned to the same treatment group, and from a third quarter that did not undergo intervention.. Infection with E. coli dramatically impacted microbial diversity. Ceftiofur significantly decreased LogCFUs but had no significant effect on the milk microbiome, rate of pathogen clearance, or somatic cell count. At the end of the study, the microbial profile of infected quarters was indistinguishable from pre-challenge samples in both treated and untreated animals. Intramammary infusion with ceftiofur did not alter the healthy milk (i.e., milk devoid of clots or serous appearance and collected from a mammary gland that shows no clinical signs of mastitis) microbiome.. Our results indicate that the mammary gland harbors a resilient microbiome, capable of reestablishing itself after experimental infection with E. coli independent of antimicrobial treatment.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Mammary Glands, Animal; Mastitis, Bovine; Microbiota; Milk

This study assessed the dynamics of cephalosporin resistant (CR) E. coli populations during the life cycle of pigs treated early in life with ceftiofur or tulathromycin. The study was conducted at eight conventional pig farms; four for each treatment with ceftiofur or tulathromycin. At each farm, 70 7-day-old piglets were divided into two groups: a control group (n = 30) and a treatment group (n = 40). Faecal samples were collected on day 0 and on days 2, 7 and 180 post-treatment. Sows were also sampled on day 0. CR E. coli were selected on MacConkey agar with ceftriaxone. On five farms, 7-day-old piglets excreted CR E. coli before treatment associated with the presence of CR E. coli in sows. The occurrence of CR E. coli positive animals decreased with increasing piglet age. The remaining three farms tested negative for CR E. coli during the study period. Results demonstrated great variability in the frequency of CR E. coli positive animals between farms, independent of treatment. Treatment with ceftiofur resulted in a transitory increase in the counts of CR E. coli after 48 h. However, other risk factors including the presence of CR E. coli in sows and animal age were more important than antimicrobial treatment. Accordingly, intervention strategies targeting sows would likely have a beneficial effect in reducing the occurrence of antimicrobial resistance in primary pig production.

Topics: Animal Husbandry; Animals; Anti-Bacterial Agents; Bacterial Shedding; Cephalosporin Resistance; Cephalosporins; Disaccharides; Escherichia coli; Escherichia coli Infections; Feces; Heterocyclic Compounds; Risk Factors; Spain; Swine; Swine Diseases

The study objective was to compare the efficacy of 3 commercial dry cow mastitis formulations regarding quarter-level prevalence of intramammary infections (IMI) postcalving, cure of preexisting infections over the dry period, prevention of new infections during the dry period, and risk for a clinical mastitis case between calving and 100d in milk (DIM). A total of 1,091 cows (4,364 quarters) from 6 commercial dairy herds in 4 different states (California, Iowa, Minnesota, and Wisconsin) were enrolled and randomized to 1 of the 3 treatments at dry-off: Quartermaster (QT; 1,000,000 IU of procaine penicillin G and 1 g of dihydrostreptomycin; Pfizer Animal Health, New York, NY), Spectramast DC (SP; 500 mg of ceftiofur hydrochloride; Pfizer Animal Health), or ToMorrow Dry Cow (TM; 300mg of cephapirin benzathine; Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Quarter milk samples were collected for routine bacteriological culture before dry cow therapy treatment at dry-off, 0 to 6 DIM, and 7 to 13 DIM and an on-farm record-keeping system was used to retrieve data on clinical mastitis cases. Noninferiority analysis was used to evaluate the effect of treatment on the primary outcome, risk for a bacteriological cure during the dry period. Multivariable logistic regression techniques were used to describe the effect of treatment on risk for presence of IMI postcalving and risk of a new IMI during the dry period. Cox proportional hazards regression was used to describe the effect of treatment on the risk and time for quarters to experience an episode of clinical mastitis between calving and 100 DIM. The overall crude quarter-level prevalence of infection at dry-off was 19.2%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative Staphylococcus, followed by Aerococcus spp. and other Streptococcus spp. Noninferiority analysis showed no effect of treatment on risk for a cure between dry-off and calving [least squares means (LSM): QT=93.3%, SP=92.6%, and TM=94.0%] and secondary analysis showed no effect of treatment on risk for presence of an IMI at 0 to 6 DIM (LSM: QT=16.5%, SP=14.1%, and TM=16.0%), risk for development of a new IMI between dry-off and 0 to 6 DIM (LSM: QT=14.8%, SP=12.3%, and TM=14.2%), or risk of experiencing a clinical mastitis event between calving and 100 DIM (LSM: QT=5.3%, SP=3.8%, and TM=4.1%). In conclusion, no difference was observed in efficacy among the 3 products evaluated when assessing the aforementi

Topics: Animals; Anti-Bacterial Agents; California; Cattle; Cephalosporins; Cephapirin; Dihydrostreptomycin Sulfate; Escherichia coli Infections; Female; Lactation; Mastitis, Bovine; Milk; Minnesota; New York; Penicillin G; Staphylococcal Infections; Streptococcal Infections; Wisconsin

The objective of this study was to evaluate the efficacy of intramammary treatment with ceftiofur hydrochloride of nonsevere, clinical coliform mastitis. One hundred four cases on 5 farms met the enrollment criteria for the study. Escherichia coli was the most common coliform species identified in milk samples from cows with mild to moderate clinical mastitis, followed by Klebsiella spp. and Enterobacter spp. At enrollment, a milk sample from the affected quarter was taken and used for on-farm culture or submitted to the laboratory. For cows in the treatment group, treatment was initiated with ceftiofur hydrochloride via intramammary infusion at 24-h intervals for 5 d according to label standards. Cows in the control group did not receive treatment. Culture results were available on the day after enrollment and only cows with coliform mastitis continued in the treatment and untreated control groups. Bacteriological cure was defined based on 2 posttreatment milk samples. Molecular typing was used for final definition of bacteriological cure. Treatment of nonsevere clinical gram-negative mastitis with ceftiofur hydrochloride resulted in a significant increase in bacteriological cure compared with nontreated controls in animals infected with E. coli or Klebsiella spp. Treated animals clinically improved significantly more compared with control cows. No significant differences were observed between treated and control animals in milk production or linear score before or after clinical mastitis. Treated animals left the study less frequently compared with control animals.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Klebsiella Infections; Mammary Glands, Animal; Mastitis, Bovine

The objectives of this study were to determine the efficacy of intramuscular administration of ceftiofur to reduce the incidence of case-related death and culling following severe clinical mastitis in lactating dairy cattle. A total of 104 cows with severe clinical mastitis (systemic signs) were enrolled in the study and randomly assigned to one of two treatment groups. Immediately after detection of the case, one group was administered 2.2 mg/kg of ceftiofur intramuscularly, and the dose repeated at 24-h intervals for a total of five doses. The second group of cows did not receive systemic antibacterial therapy. Additionally, all cows in both treatment groups received intramammary pirlimycin (Pirsue) in the affected quarter every 24 h for a total of up to three doses. Also at the onset of the case, all cows on the trial were administered a supportive therapeutic regimen of fluids and anti-inflammatory agents that varied from farm to farm, but was standard within each herd at the discretion of the herd manager and veterinarian. Of all cases 14/104 (13.5%) resulted in a lost cow (died or culled). The proportion of cases that resulted in a lost cow and were treated with ceftiofur (4/51; 7.8%) did not statistically differ from cows that were not treated with ceftiofur (10/53; 18.9%). However, the proportion of cases that resulted in lost cows was higher for those cases that yielded a coliform organism on culture (14/56; 25.0%) than cases that did not yield coliforms (0/48; 0.0%; P < 0.001). Thus, among coliform cases, cows that were not treated with ceftiofur were more likely to be culled or die (10/27, 37.0%; P < 0.05) than cows treated with ceftiofur (4/29, 13.8%). We conclude that intramuscular administration of ceftiofur did not affect the outcome of severe clinical mastitis when all etiologic agents are included in the analysis. However, for severe clinical mastitis cases caused by coliform organisms, ceftiofur therapy reduced the proportion of cases that resulted in cow death or culling. This benefit may be realized because of the amelioration of bacteremic-related pathogenesis.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Clindamycin; Escherichia coli; Escherichia coli Infections; Female; Injections, Intramuscular; Klebsiella; Klebsiella Infections; Mastitis, Bovine; Milk

Dogs are a potential source of drug-resistant Escherichia coli, but very few large-scale antimicrobial resistance surveillance studies have been conducted in the canine population. Here, we assess the antimicrobial susceptibility patterns, identify temporal resistance and minimum inhibitory concentration (MIC) trends, and describe associations between resistance phenotypes among canine clinical E. coli isolates in the northeastern United States. Through a retrospective study design, we collected MICs from 7709 E. coli isolates from canine infections at the Cornell University Animal Health Diagnostic Center between 2007 and 2020. The available clinical data were limited to body site. Isolates were classified as resistant or susceptible to six (urinary) and 22 (non-urinary) antimicrobials based on Clinical and Laboratory Standards Institute breakpoints. We used the Mann-Kendall test (MKT) and Sen's slope to identify the presence of a significant trend in the percent of resistant isolates over the study period. Multivariable logistic regression (MLR) models were built with ceftiofur, enrofloxacin, or trimethoprim-sulfamethoxazole resistance as the outcome and either body site and isolation date, or resistance to other antimicrobials as predictors. MIC trends were characterized with survival analysis models, controlling for body site and year of isolation. Overall, 16.4% of isolates were resistant to enrofloxacin, 14.3% to ceftiofur, and 14% to trimethoprim-sulfamethoxazole. The MKT and Sen's slope revealed a significant decreasing temporal trend for gentamicin and trimethoprim-sulfamethoxazole resistance among non-urinary isolates. No significant temporal resistance trends were detected by MKT for other antimicrobials. However, controlling for body-site in MLR models identified a decrease in resistance rates to enrofloxacin and trimethoprim-sulfamethoxazole after 2010. Similarly, survival analysis data confirmed these findings and showed a decrease in MIC values after 2010 for gentamicin and trimethoprim-sulfamethoxazole, but an increase in cephalosporin MICs. MLR showed that non-urinary isolates were significantly more likely than urinary isolates to demonstrate in vitro resistance to ceftiofur, enrofloxacin, and trimethoprim-sulfamethoxazole after controlling for year of isolation. We identified a higher level of ceftiofur resistance among enrofloxacin resistant isolates from urinary and non-urinary origins. Our findings confirmed that dogs are still a non

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Cephalosporins; Dog Diseases; Dogs; Drug Resistance, Bacterial; Enrofloxacin; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Gentamicins; Microbial Sensitivity Tests; New York; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Success in the global fight against antimicrobial resistance (AMR) is likely to improve if surveillance can be performed on an epidemiological scale. An approach based on agars with incorporated antimicrobials has enormous potential to achieve this. However, there is a need to identify the combinations of selective agars and key antimicrobials yielding the most accurate counts of susceptible and resistant organisms. A series of experiments involving 1,202 plates identified the best candidate combinations from six commercially available agars and five antimicrobials, using 18 Escherichia coli strains as either pure cultures or inocula-spiked feces. The effects of various design factors on colony counts were analyzed in generalized linear models. Without antimicrobials, Brilliance E. coli and CHROMagar ECC agars yielded 28.9% and 23.5% more colonies, respectively, than MacConkey agar. The order of superiority of agars remained unchanged when fecal samples with or without spiking of resistant E. coli strains were inoculated onto agars with or without specific antimicrobials. When antimicrobials were incorporated at various concentrations, it was revealed that ampicillin, tetracycline, and ciprofloxacin were suitable for incorporation into Brilliance and CHROMagar agars at all defined concentrations. Gentamicin was suitable for incorporation only at 8 and 16 μg/ml, while ceftiofur was suitable only at 1 μg/ml. CHROMagar extended-spectrum β-lactamase (ESBL) agar supported growth of a wider diversity of extended-spectrum-cephalosporin-resistant E. coli strains. The findings demonstrate the potential for agars with incorporated antimicrobials to be combined with laboratory-based robotics to deliver AMR surveillance on a vast scale with greater sensitivity of detection and strategic relevance.

Topics: Agar; Animals; Anti-Bacterial Agents; Cephalosporins; Diagnostic Tests, Routine; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Humans; Livestock; Microbial Sensitivity Tests

The transfer of antimicrobial resistance genes commonly occurs via vertical and horizontal gene transfer, as such genes are often found on the same mobile genetic element. This occurrence can lead to the co-selection of resistance to antimicrobials without their application. Dairy cattle located in the south-western United States were enrolled in a matched-pair longitudinal study to evaluate the effects of a two-dose ceftiofur treatment for metritis on levels of third-generation cephalosporin resistance among faecal Escherichia coli temporally. Escherichia coli chosen for further investigation were isolated on selective media, harboured extended-spectrum beta-lactam, fluoroquinolone and macrolide resistance genes. This combination has previously been unreported; importantly, it included genes encoding for resistance to antibiotics that can only be used in dairy cattle less than 20 months of age. Fluoroquinolones, macrolides and third and higher generation cephalosporins are considered critically important and highest priority for human medicine by the World Health Organization.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporin Resistance; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Gene Transfer, Horizontal; Longitudinal Studies; Macrolides; Plasmids; Selection, Genetic; United States

Mastitis affects cows in all regions of the world and Escherichia coli (E. coli) is by far the most common reason of mastitis. Now antibiotic therapy is still the preferred approach of treating mastitis. However, antibiotic usage is easy to lead to antibiotic resistance. There is an urgent need for developing efficacious alternative antimicrobials. Pheromonicin-NM (PMC-NM) is a new engineered bactericidal peptide consisting of colicin Ia and an anti-porin A antibody mimetic. It can lead to the dissipation of cellular energy and therefore kill the bacteria rapidly. The aim of the present study was to investigate the comparative effects of PMC-NM and antibiotic ceftiofur on antibacterial and innate immune responses of bovine mammary epithelial cells (BMEC) to E. coli infection. We found that E. coli growth was inhibited by PMC-NM from 0.5 h after treatment and was completely inhibited at 3 h, indicating a rapid antibacterial activity for PMC-NM. The mRNA expression of TLR2, IL-1β, IL-8, lactoferrin, LAP, TAP and DEFB1 was increased by PMC-NM treatment at 2 h after E. coli infection, suggesting the enhanced inflammatory responses induced by PMC-NM contribute to pathogens clearance at early phase. By contrast, in E. coli-infected BMECs, ceftiofur treatment upregulated TLR2 and NOD2 levels at 12 h, and extremely elevated transcription levels of TNF-α, IL-1β, IL-8, lactoferrin, LAP, TAP, BNBD5, DEFB1 at 6 h. The excessive expression of these genes at later phase can induce uncontrolled inflammatory responses and finally cause damage. Taken together, PMC-NM might be used as an ideal antibacterial agent against E. coli mastitis.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cells, Cultured; Cephalosporins; Cytokines; Epithelial Cells; Escherichia coli; Escherichia coli Infections; Female; Immunologic Factors; Mammary Glands, Animal; Mastitis, Bovine; Mucin-1

1. The aim of this study was to analyse the association between Escherichia coli isolates recovered from turkeys and the expression of beta-lactamase genes, such as extended spectrum beta-lactamase (ESBL) and ampicillin class C (AmpC). The phenotype of the resistance profile was examined using the association between amoxicillin and ceftiofur resistance. 2. Results showed that 84% from the turkey isolates harboured 4 or 5 genes associated with the CoIV plasmid. In an antibiogram test, 82% of the isolates were multidrug-resistant, the highest levels of resistance being against erythromycin (99%) and amoxicillin (76.1%). ESBL-positive groups were 31% positive for the ctx-m-2 gene, 6.8% were positive for ctx-m-8 and 70% harboured the tem wild gene. 3. All positive isolates from the AmpC beta-lactamase-positive group harboured the cmy-2 gene. The presence of the cmy-2 gene was associated with both the CTX-group genes and resistance to ceftiofur. 4. There was a high prevalence of avian pathogenic E. coli in suspected cases of colibacillosis in turkeys and a high antimicrobial resistance index. The results highlighted the risk of ceftiofur resistance and the presence of both ESBL and AmpC beta-lactamase E. coli in the turkey production chain.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Phenotype; Poultry Diseases; Prevalence; Turkeys

Escherichia coli strains producing extended-spectrum β-lactamases (ESBLs), especially CTX-M-type, have been largely described in companion animals; however, genomic data are lacking to clarify the clinical impact of ESBL-producing isolates in these hosts. The aim of this study was to present the genomic features of a highly virulent, ceftiofur-resistant, CTX-M-8-producing E. coli isolate from a case of pneumonia in a domestic cat with fatal outcome.. Genomic DNA was sequenced using an Illumina NextSeq 500 platform and was assembled using CLC Genomic Workbench. Genomic data were analysed using online bioinformatics tools.. The genome size was evaluated at 5.1Mb, with 5334 protein-coding sequences. The strain was assigned to sequence type 224 (ST224) and presented genes conferring resistance to β-lactams (bla. This draft genome sequence might provide important data for a better understanding of genomic aspects regarding the dissemination of CTX-M-8-producing E. coli in the human-animal-environment interface.

Topics: Animals; Animals, Domestic; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Cat Diseases; Cats; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fatal Outcome; Genome, Bacterial; Virulence

Topics: Animals; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cephalosporins; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Microbial Sensitivity Tests

Antimicrobials are frequently used for the prevention of avian colibacillosis, with gentamicin used for this purpose in Québec until 2003. Ceftiofur was also used similarly, but voluntarily withdrawn in 2005 due to increasing resistance. Spectinomycin-lincomycin was employed as a replacement, but ceftiofur use was partially reinstated in 2007 until its definitive ban by the poultry industry in 2014. Gentamicin resistance frequency increased during the past decade in clinical Escherichia coli isolates from broiler chickens in Québec, despite this antimicrobial no longer being used. Since this increase coincided with the use of spectinomycin-lincomycin, co-selection of gentamicin resistance through spectinomycin was suspected. Therefore, relationships between spectinomycin, gentamicin, and ceftiofur resistance determinants were investigated here. The distribution of 13 avian pathogenic E. coli virulence-associated genes and their association with spectinomycin resistance were also assessed. A sample of 586 E. coli isolates from chickens with colibacillosis in Québec between 2009 and 2013 was used. The major genes identified for resistance to ceftiofur, gentamicin, and spectinomycin were bla

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Chickens; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Gentamicins; Integrons; Plasmids; Poultry Diseases; Quebec; Spectinomycin; Virulence

The extra-label use of ceftiofur in Canadian hatcheries was cause for concern due to an increased prevalence of ceftiofur resistant Salmonella Heidelberg in chickens and humans in Québec. Due to on-going concerns related to human health the use of ceftiofur was eventually phased out of the poultry production industry in 2014-2015. Simultaneous resistance to amoxicillin-clavulanic acid, ceftiofur and cefoxitin, a pattern known as A2C, caused by the presence of bla

Topics: Amoxicillin; Animal Husbandry; Animals; Anti-Bacterial Agents; Canada; Cefoxitin; Cephalosporins; Chickens; Clavulanic Acid; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Poultry Diseases; Risk Factors

We determined if antibiotics residues that are excreted from treated animals can contribute to persistence of resistant bacteria in agricultural environments. Administration of ceftiofur, a third-generation cephalosporin, resulted in a ∼ 3 log increase in ceftiofur-resistant Escherichia coli found in the faeces and pen soils by day 10 (P = 0.005). This resistant population quickly subsided in faeces, but was sustained in the pen soil (∼ 4.5 log bacteria g(-1)) throughout the trial (1 month). Florfenicol treatment resulted in a similar pattern although the loss of florfenicol-resistant E. coli was slower for faeces and remained stable at ∼ 6 log bacteria g(-1) in the soil. Calves were treated in pens where eGFP-labelled E. coli were present in the bedding (∼ 2 log g(-1)) resulting in amplification of the eGFP E. coli population ∼ 2.1 log more than eGFP E. coli populations in pens with untreated calves (day 4; P < 0.005). Excreted residues accounted for > 10-fold greater contribution to the bedding reservoir compared with shedding of resistant bacteria in faeces. Treatment with therapeutic doses of ceftiofur or florfenicol resulted in 2-3 log g(-1) more bacteria than the estimated ID50 (2.83 CFU g(-1)), consistent with a soil-borne reservoir emerging after antibiotic treatment that can contribute to the long-term persistence of antibiotic resistance in animal agriculture.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Drug Residues; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Oxytetracycline; Soil; Soil Microbiology; Thiamphenicol

We report for the first time the isolation of CTX-M-15-producingEscherichia colistrains belonging to sequence type (ST) 410, ST224, and ST1284 in commercial swine in Brazil. TheblaCTX-M-15gene was located on F-::A9::B1 and C1::A9::B1 IncF-type plasmids, surrounded by a new genetic context comprising the IS26insertion sequence truncated with the ISEcp1element upstream ofblaCTX-M-15 These results reveal that commercial swine have become a new reservoir of CTX-M-15-producing bacteria in South America.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Brazil; Cephalosporin Resistance; Cephalosporins; DNA Transposable Elements; Escherichia coli; Escherichia coli Infections; Gene Expression; Genotype; Meat; Microbial Sensitivity Tests; Plasmids; Swine; Swine Diseases

The aim of the experiment was to evaluate under controlled conditions the impact on the excretion of 3GC-resistant Escherichia coli of the injection of one-day-old chicks with ceftiofur, a third-generation cephalosporin (3GC). Three isolators containing specific-pathogen-free chicks were used. In the first one, 20 birds were injected with ceftiofur then ten of them were orally inoculated with a weak inoculum of a 3GC-resistant E. coli field isolate containing an IncI1/ST3 plasmid encoding a blaCTX-M-1 beta-lactamase. The other chicks were kept as contact birds. None of the 20 birds in the second isolator were injected with ceftiofur, but ten of them were similarly inoculated with the 3GC-resistant strain and the others kept as contact birds. A third isolator contained ten non-injected, non-inoculated chicks. Fecal samples were collected regularly over one month and the E. coli isolated on non-supplemented media were characterized by antimicrobial agar dilution, detection of selected resistance genes and determination of phylogenetic group by PCR. The titers of 3GC-resistant E. coli in individual fecal samples were evaluated by culturing on 3GC-supplemented media. Results showed that the inoculated strain rapidly and abundantly colonized the inoculated and contact birds. The ceftiofur injection resulted in significantly higher percentages of 3GC-resistant E. coli isolates among the analyzed E. coli. No transfer of the 3GC-encoding plasmid to other isolates could be evidenced. In conclusion, these results highlight the dramatic capacity of 3GC-resistant E. coli to colonize and persist in chicks, and the selecting pressure imposed by the off-label use of ceftiofur.

Topics: Animals; Anti-Bacterial Agents; Cephalosporin Resistance; Cephalosporins; Chickens; Escherichia coli; Escherichia coli Infections; Feces; Gastrointestinal Microbiome; Poultry Diseases

We compared the occurrences of 3rd-generation cephalosporin-resistant (3GC

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporin Resistance; Cephalosporins; Coinfection; Cross-Sectional Studies; Enterococcus; Escherichia coli; Escherichia coli Infections; Feces; Female; Gene Expression; Genes, Bacterial; Gram-Positive Bacterial Infections; Nebraska; Salmonella enterica; Salmonella Infections, Animal

To investigate the mechanisms leading to an increase in the prevalence of blaCMY -2 conferring resistance to ceftiofur in pigs receiving a feed medicated with chlortetracycline and penicillin, and to examine the effect of supplementation with a clay mineral on this phenomenon.. In 138 blaCMY -2 -positive Escherichia coli isolates from faeces of pigs receiving feed supplemented or not with 2% clinoptilolite, from day 2 to day 28 after weaning, isolates from the two groups differed significantly with respect to their phylogenetic group: phylotype A predominated in the supplemented group, whereas phylotypes B1 and D predominated in the control group, as determined by PCR. In 36 representative isolates, pulsed-field gel electrophoresis and antimicrobial susceptibility testing revealed that the blaCMY -2 -positive E. coli isolates were polyclonal with diverse antimicrobial resistance patterns and blaCMY -2 -carrying plasmids of incompatibility (Inc) groups, A/C, I1 and ColE were observed in transformants as detected by PCR. Enterobacter cloacae possessing blaCMY -2 -carrying IncA/C plasmids were found in the pens before introduction of this batch of pigs. The blaCMY -2 -positive E. coli isolates were more clonally diverse in the control group than the supplemented group.. The blaCMY -2 gene appears to have spread both horizontally and clonally in this batch of pigs and may have spread from previous batches of pigs via plasmids carried by Ent. cloacae and expanded in animals of the present batch in the presence of the selection pressure due to administration of chlortetracycline and penicillin in the feed. Feed supplementation may have an effect on clonal diversity of blaCMY -2 -positive isolates.. Implementation of improved hygiene measures, decreased administration of certain antimicrobials on farm and feed supplementation with certain ingredients may limit antimicrobial resistance spread between and within batches of animals.

Topics: Aluminum Silicates; Animal Feed; Animals; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Chlortetracycline; Clay; Dietary Supplements; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Farms; Feces; Phylogeny; Plasmids; Swine; Swine Diseases; Weaning

The aim of this study was to investigate the evolution with time of ceftiofur-resistant Escherichia coli clinical isolates from pigs in Québec, Canada, between 1997 and 2012 with respect to pathotypes, clones and antimicrobial resistance. Eighty-five ceftiofur-resistant E. coli isolates were obtained from the OIE (World Organisation for Animal Health) Reference Laboratory for Escherichia coli. The most prevalent pathovirotypes were enterotoxigenic E. coli (ETEC):F4 (40%), extraintestinal pathogenic E. coli (ExPEC) (16.5%) and Shiga toxin-producing E. coli (STEC):F18 (8.2%). Susceptibility testing to 15 antimicrobial agents revealed a high prevalence of resistance to 13 antimicrobials, with all isolates being multidrug-resistant. blaCMY-2 (96.5%) was the most frequently detected β-lactamase gene, followed by blaTEM (49.4%) and blaCTX-M (3.5%). Pulsed-field gel electrophoresis (PFGE) applied to 45 representative E. coli isolates revealed that resistance to ceftiofur is spread both horizontally and clonally. In addition, the emergence of extended-spectrum β-lactamase-producing E. coli isolates carrying blaCTX-M was observed in 2011 and 2012 in distinct clones. The most predominant plasmid incompatibility (Inc) groups were IncFIB, IncI1, IncA/C and IncFIC. Resistance to gentamicin, kanamycin and chloramphenicol as well as the frequency of blaTEM and IncA/C significantly decreased over the study period, whereas the frequency of IncI1 and multidrug resistance to seven antimicrobial categories significantly increased. These findings reveal that extended-spectrum cephalosporin-resistant porcine E. coli isolates in Québec belong to several different clones with diverse antimicrobial resistance patterns and plasmids. Furthermore, blaCMY-2 was the major β-lactamase gene in these isolates. From 2011, we report the emergence of blaCTX-M in distinct clones.

Topics: Animals; Anti-Bacterial Agents; Cephalosporin Resistance; Cephalosporins; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Genetic Variation; Genotype; Molecular Typing; Prevalence; Quebec; Swine; Swine Diseases

The aim of this study was to evaluate if the treatments with ceftiofur and amoxicillin are risk factors for the emergence of cephalosporin resistant (CR) E. coli in a pig farm during the rearing period. One hundred 7-day-old piglets were divided into two groups, a control (n = 50) group and a group parenterally treated with ceftiofur (n = 50). During the fattening period, both groups were subdivided in two. A second treatment with amoxicillin was administered in feed to two of the four groups, as follows: group 1 (untreated, n = 20), group 2 (treated with amoxicillin, n = 26), group 3 (treated with ceftiofur, n = 20), and group 4 (treated with ceftiofur and amoxicillin, n = 26). During treatment with ceftiofur, fecal samples were collected before treatment (day 0) and at days 2, 7, 14, 21, and 42 posttreatment, whereas with amoxicillin, the sampling was extended 73 days posttreatment. CR E. coli bacteria were selected on MacConkey agar with ceftriaxone (1 mg/liter). Pulsed-field gel electrophoresis (PFGE), MICs of 14 antimicrobials, the presence of cephalosporin resistance genes, and replicon typing of plasmids were analyzed. Both treatments generated an increase in the prevalence of CR E. coli, which was statistically significant in the treated groups. Resistance diminished after treatment. A total of 47 CR E. coli isolates were recovered during the study period; of these, 15 contained blaCTX-M-1, 10 contained blaCTX-M-14, 4 contained blaCTX-M-9, 2 contained blaCTX-M-15, and 5 contained blaSHV-12. The treatment with ceftiofur and amoxicillin was associated with the emergence of CR E. coli during the course of the treatment. However, by the time of finishing, CR E. coli bacteria were not recovered from the animals.

Topics: Amoxicillin; Animal Husbandry; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; Cephalosporins; Drug Utilization; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Feces; Genotype; Microbial Sensitivity Tests; Molecular Typing; Plasmids; Swine

This study aimed to identify changing antimicrobial resistance patterns in isolates commonly obtained from equine clinical submissions. Laboratory records from 1999 to 2012 were searched for equine samples from which Escherichia coli or Streptococcus species was isolated. Susceptibility to enrofloxacin, ceftiofur, gentamicin, penicillin G, trimethoprim sulfamethoxazole (TMPS) and tetracyclines was noted. Isolates were divided into those identified between 1999 and 2004 (Early) and between 2007 and 2012 (Late). The proportion of isolates resistant to each antimicrobial and multiple drug-resistant (MDR) isolates (≥3 antimicrobial classes) was compared between time periods. There were 464 isolates identified (242 Early; 222 Late). A significant increase in the percentage of E coli isolates resistant to ceftiofur (7.3-22.7 per cent, P=0.002), gentamicin (28.5-53.9 per cent, P<0.001), tetracyclines (48.4-74.2 per cent, P=0.002) and MDR (26.6-49.4 per cent, P=0.007) was identified. There was a significant increase over time in the percentage of all streptococcal species resistant to enrofloxacin, ranging from 0 per cent (Early) up to 63 per cent (Late) depending on species. For Streptococcus zooepidemicus, resistance over time to tetracyclines and MDR increased. There was also a decrease in the proportion of S zooepidemicus resistant to TMPS over time. An increase in resistance over time of common equine pathogens to a number of commonly used antimicrobials supports the responsible use of antimicrobials.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Drug Combinations; Drug Resistance, Bacterial; Enrofloxacin; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Gentamicins; Horse Diseases; Horses; Microbial Sensitivity Tests; Penicillin G; Streptococcus; Streptococcus equi; Sulfamethizole; Tetracyclines; Trimethoprim; United Kingdom

Resistance to extended-spectrum cephalosporins (ESCs) is an important health concern. Here, we studied the impact of the administration of a long-acting form of ceftiofur on the pig gut microbiota and ESC resistance in Escherichia coli. Pigs were orally inoculated with an ESC-resistant E. coli M63 strain harboring a conjugative plasmid carrying a gene conferring resistance, bla CTX-M-1. On the same day, they were given or not a unique injection of ceftiofur. Fecal microbiota were studied using quantitative PCR analysis of the main bacterial groups and quantification of short-chain fatty acids. E. coli and ESC-resistant E. coli were determined by culture methods, and the ESC-resistant E. coli isolates were characterized. The copies of the bla CTX-M-1 gene were quantified. After ceftiofur injection, the main change in gut microbiota was the significant but transitory decrease in the E. coli population. Acetate and butyrate levels were significantly lower in the treated group. In all inoculated groups, E. coli M63 persisted in most pigs, and the bla CTX-M-1 gene was transferred to other E. coli. Culture and PCR results showed that the ceftiofur-treated group shed significantly more resistant strains 1 and 3 days after ESC injection. Thereafter, on most dates, there were no differences between the groups, but notably, one pig in the nontreated group regularly excreted very high numbers of ESC-resistant E. coli, probably leading to a higher contamination level in its pen. In conclusion, the use of ESCs, and also the presence of high-shedding animals, are important features in the spread of ESC resistance.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Escherichia coli; Escherichia coli Infections; Gastrointestinal Microbiome; Swine

Healthy farm animals have been found to act as a reservoir of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli). Therefore, the objective of the study was to determine the input of antimicrobial active ceftiofur metabolites in the stable via faeces and urine after intramuscular administration of the drug to pigs and the elucidation of the Escherichia coli ESBL resistance pattern of treated and untreated pigs housed in the same barn during therapy.. For determination of the minimal inhibitory concentration (MIC) the method of microdilutionaccording to the recommended procedure of the Clinical and Laboratory Standards Institute was used. Inaddition to that, a qualitative determination was performed by agar dilution. Unsusceptible E. coli speciesselected via agar dilution with cefotaxime were confirmed by MALDI-TOF and ESBL encoding genes wereidentified by PCR. The amounts of ceftiofur measured as desfuroylceftiofur (DFC) in the different probes (plasma, urine, faeces and dust) were analysed by UPLC-MS/MS.. In a first experiment two groups of pigs (6 animals per group) were housed in the same barn in two separated boxes. One group (group B) were treated with ceftiofur according to the licence (3 mg/kg administered intramuscularly (i.m.) on three consecutive days, day 1-3). During a second treatment period (day 29-31) an increased rate of ESBL resistant E. coli was detectable in these treated pigs and in the air of the stable. Moreover, the second group of animals (group A) formerly untreated but housed for the whole period in the same stable as the treated animals revealed increased resistance rates during their first treatment (day 45-47) with ceftiofur. In order to investigate the environmental input of ceftiofur during therapy and to simulate oral uptake of ceftiofur residues from the air of the stable a second set of experiments were performed. Pigs (6 animals) were treated with an interval of 2 weeks for 3 days with different doses of ceftiofur (3 mg/kg, 1 mg/kg and 0.3 mg/kg i.m.) as well as with 3 mg/kg per os) and the renal and biliary excretion of ceftiofur as its active metabolite were measured in comparison to the plasma levels. In addition to that, probes of the sedimentation dust and the air of the stable were analysed for drug residues.. The present study shows that treatment of several animals in a stable with ceftiofur influences the resistance pattern of intestinal Escherichia coli of the treated as well as untreated animals housed in the same stable. During therapy with the drug which was administered by injection according to the licence we detected nameable amounts of ceftiofur and its active metabolites in the dust and air of the stable.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Disease Susceptibility; Drug Resistance, Bacterial; Escherichia coli Infections; Feces; Female; Housing, Animal; Injections, Intramuscular; Microbial Sensitivity Tests; Swine; Swine Diseases

This study investigated antimicrobial resistance, screened for the presence of virulence genes involved in intestinal infections, and determined phylogenetic groups of Escherichia coli isolates from untreated poultry and poultry treated with ceftiofur, an expanded-spectrum cephalosporin. Results show that none of the 76 isolates appeared to be Shiga toxin-producing E. coli or enteropathogenic E. coli. All isolates were negative for the major virulence factors/toxins tested (ehxA, cdt, heat-stable enterotoxin [ST], and heat-labile enterotoxin [LT]). The few virulence genes harbored in isolates generally did not correlate with isolate antimicrobial resistance or treatment status. However, some of the virulence genes were significantly associated with certain phylogenetic groups.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Chickens; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Poultry Diseases; Virulence Factors

The use of extended-spectrum cephalosporins in food animals has been suggested to increase the risk of spread of Enterobacteriaceae carrying extended-spectrum β-lactamases to humans. However, evidence that selection of extended-spectrum cephalosporin-resistant bacteria owing to the actual veterinary use of these drugs according to criteria established in cattle has not been demonstrated. In this study, we investigated the natural occurrence of cephalosporin-resistant Escherichia coli in dairy cattle following clinical application of ceftiofur. E. coli isolates were obtained from rectal samples of treated and untreated cattle (n = 20/group) cultured on deoxycholate-hydrogen sulfide-lactose agar in the presence or absence of ceftiofur. Eleven cefazoline-resistant isolates were obtained from two of the ceftiofur-treated cattle; no cefazoline-resistant isolates were found in untreated cattle. The cefazoline-resistant isolates had mutations in the chromosomal ampC promoter region and remained susceptible to ceftiofur. Eighteen extended-spectrum cephalosporin-resistant isolates from two ceftiofur-treated cows were obtained on ceftiofur-supplemented agar; no extended-spectrum cephalosporin-resistant isolates were obtained from untreated cattle. These extended-spectrum cephalosporin-resistant isolates possessed plasmid-mediated β-lactamase genes, including bla(CTX-M-2) (9 isolates), bla(CTX-M-14) (8 isolates), or bla(CMY-2) (1 isolate); isolates possessing bla(CTX-M-2) and bla(CTX-M-14) were clonally related. These genes were located on self-transmissible plasmids. Our results suggest that appropriate veterinary use of ceftiofur did not trigger growth extended-spectrum cephalosporin-resistant E. coli in the bovine rectal flora; however, ceftiofur selection in vitro suggested that additional ceftiofur exposure enhanced selection for specific extended-spectrum cephalosporin-resistant β-lactamase-expressing E. coli clones.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cattle; Cattle Diseases; Cefpodoxime; Ceftizoxime; Cephalosporin Resistance; Cephalosporins; Disk Diffusion Antimicrobial Tests; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Japan; Risk

A randomized controlled field trial was conducted to evaluate the effects of two sets of treatment strategies on ceftiofur and tetracycline resistance in feedlot cattle. The strategies consisted of ceftiofur crystalline-free acid (CCFA) administered to either one or all of the steers within a pen, followed by feeding or not feeding a therapeutic dose of chlortetracycline (CTC). Eighty-eight steers were randomly allocated to eight pens of 11 steers each. Both treatment regimens were randomly assigned to the pens in a two-way full factorial design. Non-type-specific (NTS) E. coli (n = 1,050) were isolated from fecal samples gathered on Days 0, 4, 12, and 26. Antimicrobial susceptibility profiles were determined using a microbroth dilution technique. PCR was used to detect tet(A), tet(B), and bla CMY-2 genes within each isolate. Chlortetracycline administration greatly exacerbated the already increased levels of both phenotypic and genotypic ceftiofur resistance conferred by prior CCFA treatment (P<0.05). The four treatment regimens also influenced the phenotypic multidrug resistance count of NTS E. coli populations. Chlortetracycline treatment alone was associated with an increased probability of selecting isolates that harbored tet(B) versus tet(A) (P<0.05); meanwhile, there was an inverse association between finding tet(A) versus tet(B) genes for any given regimen (P<0.05). The presence of a tet(A) gene was associated with an isolate exhibiting reduced phenotypic susceptibility to a higher median number of antimicrobials (n = 289, median = 6; 95% CI = 4-8) compared with the tet(B) gene (n = 208, median = 3; 95% CI = 3-4). Results indicate that CTC can exacerbate ceftiofur resistance following CCFA therapy and therefore should be avoided, especially when considering their use in sequence. Further studies are required to establish the animal-level effects of co-housing antimicrobial-treated and non-treated animals together.

Topics: Animals; Anti-Bacterial Agents; Antiporters; Bacterial Proteins; beta-Lactamases; Cattle; Cattle Diseases; Cephalosporins; Chlortetracycline; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Microbial Sensitivity Tests

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cattle; Cattle Diseases; Cephalosporins; Chlortetracycline; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Plasmids; United States

In the United States, the blaCMY-2 gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum-cephalosporin-resistant (ESC(r)) Escherichia coli strains from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in cattle may increase the prevalence of ESC(r) E. coli. We report that herd ESC(r) E. coli fecal and hide prevalences throughout the residency of cattle at a feedlot, including during the period of greatest ceftiofur use at the feedlot, were either not significantly different (P ≥ 0.05) or significantly less (P < 0.05) than the respective prevalences at arrival. Longitudinal sampling of cattle treated with ceftiofur demonstrated that once the transient increase of ESC(r) E. coli shedding that follows ceftiofur injection abated, ceftiofur-injected cattle were no more likely than untreated members of the same herd to shed ESC(r) E. coli. Pulsed-field gel electrophoresis (PFGE) genotyping, antibiotic resistance phenotyping, screening for presence of the blaCMY-2 gene, and plasmid replicon typing were performed on 312 ESC(r) E. coli isolates obtained during six sampling periods spanning the 10-month residence of cattle at the feedlot. The identification of only 26 unique PFGE genotypes, 12 of which were isolated during multiple sampling periods, suggests that clonal expansion of feedlot-adapted blaCMY-2 E. coli strains contributed more to the persistence of blaCMY-2 than horizontal transfer of IncA/C plasmids between E. coli strains at this feedlot. We conclude that therapeutic use of ceftiofur at this cattle feedlot did not significantly increase the herd prevalence of ESC(r) E. coli.

Topics: Animals; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carrier State; Cattle; Cephalosporins; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Feces; Molecular Epidemiology; Molecular Typing; Prevalence; Skin

The U.S. Food and Drug Administration recently issued new rules for using ceftiofur in food animals in part because of an increasing prevalence of enteric bacteria that are resistant to 3(rd)-generation cephalosporins. Parenteral ceftiofur treatment, however, has limited effects on enteric bacteria so we tested the hypothesis that excreted ceftiofur metabolites exert significant selection pressure for ceftiofur-resistant Escherichia coli in soil. Test matrices were prepared by mixing soil with bovine feces and adding urine containing ceftiofur metabolites (CFM) (0 ppm, ∼50 ppm and ∼100 ppm). Matrices were incubated at 23°C or 4°C for variable periods of time after which residual CFM was quantified using a bioassay. Bla(CMY-2) plasmid-bearing ceftiofur resistant (cef(R)) E. coli and one-month old calves were used to study the selection effects of CFM and transmission of cef(R) bacteria from the environment back to animals. Our studies showed that urinary CFM (∼13 ppm final concentration) is biologically degraded in soil within 2.7 days at 23°C, but persists up to 23.3 days at 4°C. Even short-term persistence in soil provides a >1 log(10) advantage to resistant E. coli populations, resulting in significantly prolonged persistence of these bacteria in the soil (∼two months). We further show that resistant strains readily colonize calves by contact with contaminated bedding and without antibiotic selection pressure. Ceftiofur metabolites in urine amplify resistant E. coli populations and, if applicable to field conditions, this effect is far more compelling than reported selection in vivo after parenteral administration of ceftiofur. Because ceftiofur degradation is temperature dependent, these compounds may accumulate during colder months and this could further enhance selection as seasonal temperatures increase. If cost-effective engineered solutions can be developed to limit ex vivo selection, this may limit proliferation for ceftiofur resistant enteric bacteria while preserving the ability to use this important antibiotic in food animal production.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Population Dynamics; Selection, Genetic; Soil Microbiology; Temperature; Urine

A cross-sectional study on 32 different Belgian broiler farms was performed in 2007 and 2008 to identify risk factors for ceftiofur resistance in Escherichia coli. On each farm, one E. coli colony was isolated from 30 random birds. Following susceptibility testing of 14 antimicrobials, an on-farm questionnaire was used to obtain information on risk factors. Using a multilevel logistic regression model two factors were identified at the animal level: resistance to amoxicillin and to trimethoprim-sulfonamide. On the farm level, besides antimicrobial use, seven management factors were found to be associated with the occurrence of ceftiofur resistance in E. coli from broilers: poor hygienic condition of the medicinal treatment reservoir, no acidification of drinking water, more than three feed changes during the production cycle, hatchery of origin, breed, litter material used, and treatment with amoxicillin. This study confirms that not only on-farm antimicrobial therapy, but also management- and hatchery-related factors influence the occurrence of antimicrobial resistance.

Topics: Animals; Anti-Bacterial Agents; Belgium; Cephalosporins; Chickens; Cross-Sectional Studies; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Risk Factors; Surveys and Questionnaires

The objective of this study was to investigate the association between ceftiofur use policy in finishing swine barns and recovery of fecal Escherichia coli or Salmonella spp. resistant to ceftriaxone. The study population included 54 finishing swine barns from three companies located in North Carolina. The barns were each classified according to their reported therapeutic ceftiofur use rates of "Rare," "Moderate," and "Common." Fecal samples from the barns were cultured for the presence of E. coli and Salmonella spp. resistant to ceftriaxone using selective media designed to recover rare organisms expressing the AmpC β-lactamase phenotype. A total of 1899 swine fecal samples yielded 1193 E. coli (63%) resistant to ceftriaxone. Recovery rates by ceftiofur use classification were 45% for Rare, 73% for Moderate, and 68% Common ceftiofur use groups. Barns reporting Rare ceftiofur use had a lower odds of recovery of E. coli (OR=0.32; p<0.001) resistant to ceftriaxone compared to Common use barns. The overall Salmonella spp. prevalence was 63.8% (n=714). Of these, 65 Salmonella were resistant to ceftriaxone with the highest rate (6%) found in the Common ceftiofur use group, followed by Rare (4.1%) and Moderate (0.15%). The odds of recovery of Salmonella resistant to ceftriaxone were similar for barns with ceftiofur use classified as Rare and Common. Samples from barns with ceftiofur use classified as Moderate had a lower odds (OR=0.02; p<0.01) of recovery of Salmonella resistant to ceftriaxone than barns classified as Common. Our result is consistent with the hypothesis that the use of ceftiofur in finishing swine barns, beyond its rare application, may influence the recovery of enteric E. coli with resistance to cephalosporin drugs, although other unmeasured factors appear to be important in the recovery of cephalosporin-resistant Salmonella. The dissemination of enteric bacteria with resistance to cephalosporins has the potential to impact both veterinary and human therapeutic treatment options.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Cross-Sectional Studies; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Humans; Logistic Models; Microbial Sensitivity Tests; North Carolina; Salmonella; Salmonella Infections, Animal; Swine; Swine Diseases

We characterized 67 Escherichia coli isolates with reduced susceptibility to cefotaxime or ceftiofur obtained from healthy broilers housed in five Italian farms. The bla(CTX-M-1), bla(CTX-M-32) and bla(SHV-12) beta-lactamase genes were identified on IncI1, IncN, or IncFIB plasmids. Considerable genetic diversity was detected among the extended-spectrum beta-lactamase (ESBL)-producing isolates, and we identified indistinguishable strains in unrelated farms and indistinguishable plasmids in genetically unrelated strains. The detection of highly mobile plasmids suggests a potential animal reservoir for beta-lactamase genes.

Topics: Amplified Fragment Length Polymorphism Analysis; Animals; beta-Lactamases; Cephalosporin Resistance; Chickens; Disease Reservoirs; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Genes, Bacterial; Genetic Variation; Humans; Italy; Microbial Sensitivity Tests; Plasmids

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Denmark; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Swine; Swine Diseases

Three groups of five pigs were inoculated intratracheally with Escherichia coli lipopolysaccharides, and 24 hours later with 10 x 10(9) colony-forming units of a non-toxigenic strain of Pasteurella multocida type A; a fourth group was left uninoculated as controls. The three inoculated groups received either no treatment (positive controls), or were treated with 3 mg/kg ceftiofur intramuscularly once a day for five consecutive days, either alone or combined with 2 mg/kg flunixin intramuscularly once a day for three consecutive days. The sustained coughing and hyperthermia recorded in the positive controls disappeared after two days and three days of treatments, respectively, in the treated animals, and the reductions in daily weight gain and changes in breathing pattern observed in the controls were not observed in the treated animals. There were no significant differences between the pigs treated with ceftiofur alone or ceftiofur combined with flunixin. In the positive controls, the number of inflammatory cells in samples of bronchoalveolar lavage fluid continued to increase up to 15 days after inoculation, whereas in the treated animals there were similar increases at six days but the numbers had decreased to baseline levels after 15 days. Similarly, in the treated animals the volume of the lung lesions was significantly less than in the control animals, but the inclusion of flunixin in the treatment regimen had no significant additional effect.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Bronchopneumonia; Cephalosporins; Clonixin; Cough; Escherichia coli; Escherichia coli Infections; Female; Lipopolysaccharides; Male; Pasteurella Infections; Pasteurella multocida; Swine; Swine Diseases; Treatment Outcome

Healthy calves (n = 96, 1 to 9 weeks old) from a dairy herd in central Pennsylvania were examined each month over a five-month period for fecal shedding of ceftiofur-resistant gram-negative bacteria. Ceftiofur-resistant Escherichia coli isolates (n = 122) were characterized by antimicrobial resistance (disk diffusion and MIC), serotype, pulsed-field gel electrophoresis subtypes, beta-lactamase genes, and virulence genes. Antibiotic disk diffusion assays showed that the isolates were resistant to ampicillin (100%), ceftiofur (100%), chloramphenicol (94%), florfenicol (93%), gentamicin (89%), spectinomycin (72%), tetracycline (98%), ticarcillin (99%), and ticarcillin-clavulanic acid (99%). All isolates were multidrug resistant and displayed elevated MICs. The E. coli isolates belonged to 42 serotypes, of which O8:H25 was the predominant serotype (49.2%). Pulsed-field gel electrophoresis classified the E. coli isolates into 27 profiles. Cluster analysis showed that 77 isolates (63.1%) belonged to one unique group. The prevalence of pathogenic E. coli was low (8%). A total of 117 ceftiofur-resistant E. coli isolates (96%) possessed the bla(CMY2) gene. Based on phenotypic and genotypic characterization, the ceftiofur-resistant E. coli isolates belonged to 59 clonal types. There was no significant relationship between calf age and clonal type. The findings of this study revealed that healthy dairy calves were rapidly colonized by antibiotic-resistant strains of E. coli shortly after birth. The high prevalence of multidrug-resistant nonpathogenic E. coli in calves could be a significant source of resistance genes to other bacteria that share the same environment.

Topics: Animals; Cattle; Cattle Diseases; Cephalosporins; Dairying; DNA Primers; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Microbial Sensitivity Tests; Molecular Epidemiology; Pennsylvania; Polymerase Chain Reaction

In vitro resistance to 8 antimicrobials among enterotoxigenic Escherichia coli from piglets and calves over a 13-year period was evaluated. Least resistance occurred against ceftiofur for all, followed by apramycin and gentamicin for porcine and florfenicol for bovine isolates. No significant differences were found between the first 8 and last 5 years.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Diarrhea; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Swine; Swine Diseases

Topics: Amoxicillin; Animals; Animals, Newborn; Anti-Bacterial Agents; Cephalosporins; Colistin; Diarrhea; Drug Resistance, Microbial; Enrofloxacin; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Microbial Sensitivity Tests; Nebramycin; Neomycin; Quinolones; Spain; Swine; Swine Diseases

Antibiotic resistance among Escherichia coli isolates from diarrhoeal disease in cattle was studied. Many of the isolates were multiply resistant to beta-lactams, including expanded-spectrum cephalosporins, aminoglycosides, sulphonamides, tetracycline and fluoroquinolones. In many of the isolates, IEF revealed a strong beta-lactamase band compatible with overexpression of the AmpC beta-lactamase, either alone or in addition to TEM-type enzymes. Several of the isolates also possessed genes encoding virulence factors associated with animal and human diarrhoeal diseases. These results suggest that the use of antibiotics in animals could lead to a reservoir of antibiotic-resistant bacteria that could potentially infect humans.

Topics: Animals; beta-Lactamases; beta-Lactams; Cattle; Cattle Diseases; Cephalosporin Resistance; Cephalosporins; Diarrhea; Escherichia coli; Escherichia coli Infections; Humans; Isoelectric Focusing; Microbial Sensitivity Tests; Polymerase Chain Reaction; Virulence

Eight Holstein cows, 4 inoculated intracisternally in 1 quarter of the mammary gland with Escherichia coli and 4 noninfected controls, were administered ceftiofur sodium (3 mg/kg of body weight, IV, q 12 hours) for 24 hours, beginning at 14 hours after inoculation of infected cows. All challenge-exposed cows became infected, with mean +/- SEM peak log10 bacterial concentration in milk of 5.03 +/- 0.69 colony-forming units/ml. The infection resulted in systemic signs (mean peak rectal temperature, 41.5 +/- 0.3 C; anorexia; signs of depression) and local inflammation (mean peak albumin concentration in milk, 7.89 +/- 1.71 mg/ml). Ceftiofur was detectable in milk from all challenge-exposed cows, compared with only 1 of 4 noninfected cows, and the mean period after inoculation that ceftiofur was detectable in milk was longer (P < 0.05) in infected (147.7 +/- 27.5 hours) than noninfected cows (1.3 +/- 1.3 hours). However, maximal ceftiofur concentration attained in milk for all cows was 0.28 microgram/ml, and was 0.20 microgram/ml or less for all but 2 milk samples collected for 10 days after challenge exposure. Mean serum concentration of ceftiofur peaked at 1.0 +/- 0.3 microgram/ml and 0.7 +/- 0.1 microgram/ml for infected and noninfected cows, respectively. After each ceftiofur dose, mean peak and trough concentrations of ceftiofur in serum did not differ between groups; however, concentration of ceftiofur in serum was higher at 7 hours after each dose in noninfected cows, suggesting more rapid clearance of the drug in infected cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Temperature; Cattle; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Mammary Glands, Animal; Mastitis, Bovine; Metabolic Clearance Rate; Milk; Reference Values

Ceftiofur hydrochloride was tested for effectiveness against induced colibacillosis in neonatal swine. In this model, pigs less than 12 hours old were inoculated via stomach tube with a virulent, K99+, nalidixic acid-resistant strain of Escherichia coli. Six hours after challenge exposure, 1 dose of ceftiofur was administered either IM or orally in experiment 1 and orally only in experiment 2. Mortality, shedding of bacteria, fecal consistency scores, and body weight changes were monitored for 10 days. In experiment 1 (n = 383 pigs), all treatments at dosage that ranged between 0.5 and 64.0 mg of ceftiofur/kg of body weight significantly (P less than 0.001) reduced mortality, bacterial shedding, and diarrhea and increased weight gain, compared with findings in untreated controls. There were no detectable differences between oral and IM routes, except that there was greater reduction in bacteria shedding associated with the oral route of administration. In experiment 2 (n = 505 pigs), ceftiofur was administered orally either once at 6 hours after challenge exposure or twice at 6 and at 48 hours after the first dose. Dosage of ceftiofur was 0, 5, 10, 20, 30, or 60 mg/kg administered once, or half the same dose was administered at each of 2 times. At the optimal dosage (10 mg/kg), a single dose was as effective as 2 doses. The single administration at all dosages reduced mortality, bacterial shedding, and diarrhea scores and increased body weight gain, compared with findings in untreated pigs (P less than 0.01). In this induced infection model, the optimal treatment dosage was determined to be 10 mg/kg administered once.

Topics: Administration, Oral; Animals; Animals, Newborn; Cephalosporins; Dose-Response Relationship, Drug; Drug Evaluation; Escherichia coli Infections; Feces; Female; Injections, Intramuscular; Male; Swine; Swine Diseases; Time Factors