tulathromycin and florfenicol

In this field trial, a new combination product containing florfenicol and flunixin meglumine (FLOR-FM) was compared with commercially available products that contained only tulathromycin (TULA) or ceftiofur crystalline free acid (CCFA) for the treatment of undifferentiated fever (UF; rectal temperature >/=105.0 degrees F) in beef calves that received long-acting oxytetracycline at feedlot arrival. The overall mortality rate of the FLOR FM group (2.0%) was significantly (P less than .050) lower than the rates in the TULA and CCFA groups (10.0% and 20.0%, respectively; 50 animals/group), even though the first UF relapse rate of the FLOR FM group was significantly (P less than .050) higher than that of the TULA group. In the FLOR FM group, this resulted in per-animal economic advantages of Can$46.23 (versus TULA) and Can$108.77 (versus CCFA) based on equal costs for initial UF therapy. These results demonstrate that it is more cost-effective to administer FLOR FM than TULA or CCFA for initial UF therapy in feedlot calves at high risk for bovine respiratory disease that receive metaphylactic long-acting oxytetracycline at feedlot arrival.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cattle Diseases; Cephalosporins; Clonixin; Disaccharides; Drug Combinations; Fever; Heterocyclic Compounds; Housing, Animal; Thiamphenicol

A field trial was performed under commercial feedlot conditions in central Nebraska to assess the relative efficacy of tulathromycin (TULA) to florfenicol (FLOR) for the treatment of undifferentiated fever (UF) in feedlot calves that did not receive a metaphylactic antimicrobial or vaccines/bacterins containing Mannheimia haemolytica or Histophilus somni at feedlot arrival by comparing animal health, feedlot performance, and carcass characteristic variables. Two hundred recently weaned, auction market derived, crossbred beef calves that met the study-specific case definition of UF were randomly allocated in a 1:1 ratio to 1 of 2 experimental groups as follows: TULA, which received tulathromycin administered subcutaneously at the rate of 2.5 mg/kg body weight (BW) once at the time of allocation; or FLOR, which received florfenicol administered subcutaneously at the rate of 40 mg/kg BW once at the time of allocation. In terms of animal health, the first UF relapse (RR = 0.65), overall mortality (RR = 0.33), and BRD mortality (RR = 0.29) rates in the TULA group were significantly (P < 0.05) lower than in the FLOR group. There were no significant (P > or = 0.05) differences between the TULA and FLOR groups for the other animal health variables measured. There was no significant (P > or = 0.05) difference in average daily gain between the TULA and FLOR groups. There were no significant (P > or = 0.05) differences in the overall distributions of quality grade and yield grade between the experimental groups; however, a significantly (P < 0.05) higher proportion of carcasses in the TULA group graded yield grade USDA-4 as compared with the FLOR group. In the economic analysis, the benefits observed resulted in an economic advantage of $52.50 USD/animal in the TULA group due to lower first UF relapse and overall mortality rates, even though the occurrence of yield grade USDA-4 carcasses increased and the initial UF treatment cost was higher.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Nebraska; Pasteurellosis, Pneumonic; Recurrence; Thiamphenicol; Treatment Outcome; Weight Gain

The efficacy of tulathromycin in the treatment (phase 1) and prevention (phase 2) of bovine respiratory disease (BRD) was evaluated on commercial farms in France, Germany, Italy, and Spain. In phase 1, commingled cattle with clinical BRD were treated with tulathromycin (n = 128) or florfenicol (n = 125) on day 0. Similar percentages of animals showed sustained clinical improvement at day 14 (tulathromycin 83.3% versus florfenicol 81.0%) and had not relapsed by day 60 (tulathromycin 63.3% versus florfenicol 58.4%). In phase 2, healthy in-contact cattle were treated with tulathromycin (n = 492), tilmicosin (n = 494), or saline (n = 265) on day 0. Significantly more (P = .0001) tulathromycin-treated cattle remained healthy to day 14 (92.4%) than tilmicosin-treated (83.7%) or saline-treated (63.7%) cattle, and this was maintained through day 60 (tulathromycin 85.4% versus tilmicosin 75.1% and saline 56.2%). Tulathromycin was highly effective in the treatment and prevention of BRD.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Disease Outbreaks; Europe; Haemophilus somnus; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Mannheimia haemolytica; Mycoplasma bovis; Pasteurella multocida; Pasteurellosis, Pneumonic; Thiamphenicol; Tylosin

Three studies conducted at feedlots in Colorado, Idaho, and Texas examined the comparative efficacy of tulathromycin injectable solution for the treatment of cattle at high risk of developing undifferentiated bovine respiratory disease (BRD). Each study randomly allocated 250 calves to receive tulathromycin at 2.5 mg/kg and 250 calves to receive either tilmicosin at 10 mg/kg (Colorado site) or florfenicol at 40 mg/kg (Idaho and Texas sites) on arrival at the feedlot. Calves were housed by treatment group in pens with 50 calves/pen. Beginning 3 days after antimicrobial treatment, cattle were observed for signs of BRD daily until harvest. In all three studies, the treatment success rates at 28 days after treatment and at harvest were significantly higher (P < or = .013) for cattle treated with tulathromycin than for cattle treated with either tilmicosin or florfenicol. Fewer tulathromycin-treated cattle were removed from the group as "chronics" or "mortalities" at 28 days posttreatment (P < or = .014) in all three studies. Tulathromycin demonstrated superior efficacy compared with tilmicosin and florfenicol when treating groups of high-risk cattle before the onset of signs of BRD.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Male; Pasteurellosis, Pneumonic; Recurrence; Risk Factors; Severity of Illness Index; Thiamphenicol; Treatment Outcome; Tylosin; United States

The therapeutic efficacy and field safety of tulathromycin were evaluated in stocker calves with undifferentiated bovine respiratory disease (BRD) in three field studies conducted over two consecutive grazing seasons in Nebraska. Eight hundred calves exhibiting clinical signs of BRD and with rectal temperatures of 104 degrees F or higher were treated with tulathromycin (n = 340), florfenicol (n = 240), or tilmicosin (n = 220) and evaluated for approximately 60 days. Florfenicol and tilmicosin were administered as single SC injections according to labeled dosage. Tulathromycin was administered as a single SC injection of 2.5 mg/kg. In all three studies, the cure rate of calves 60 days after treatment with tulathromycin was significantly higher (P < or = .05) than that of calves treated with florfenicol or tilmicosin. Suspected adverse reactions were not reported for any of the study drugs. Tulathromycin proved to be significantly more effective than either florfenicol or tilmicosin in the treatment of BRD in stocker calves.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Male; Pasteurellosis, Pneumonic; Recurrence; Severity of Illness Index; Thiamphenicol; Treatment Outcome; Tylosin; United States; Weight Gain

Four studies conducted at feedlots in Greeley and Wellington, Colorado; Nebraska; and Texas compared the efficacy of tulathromycin to florfenicol or tilmicosin for the treatment of cattle with undifferentiated bovine respiratory disease (BRD) and subsequent feedlot performance and carcass characteristics. In each study, 100 calves with BRD were treated with tulathromycin given SC at 2.5 mg/kg body weight. At the Greeley, CO, and Nebraska study locations, 100 calves were treated with florfenicol given SC at 40 mg/kg body weight, and at the Wellington, CO, and Texas study locations, tilmicosin was given SC at 10 mg/kg body weight. Cure rate, a derived variable that included assessments of mortality, rectal temperature, and attitude and respiratory scores from day 3 to day 28 and day 3 through harvest, was the primary assessment of BRD efficacy. Cure rates of calves treated with tulathromycin were significantly (P < or = .009) higher than those calves treated with florfenicol. At Wellington, CO, the cure rate of calves treated with tulathromycin was significantly higher (P < or = .018) compared with tilmicosin-treated calves. The differences in cure rates between tulathromycin and tilmicosin treatment groups in the Texas study were not significantly different (P > .05). Tulathromycin was more efficacious in the treatment of undifferentiated BRD compared with florfenicol and, in one study, compared with tilmicosin.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Male; Pasteurellosis, Pneumonic; Recurrence; Severity of Illness Index; Thiamphenicol; Treatment Outcome; Tylosin; United States; Weight Gain

The clinical efficacy of tulathromycin in the treatment of natural outbreaks of swine respiratory disease (SRD) was evaluated at five European sites. Pigs (1 to 6 months of age) exhibiting clinical signs of SRD were treated intramuscularly with tulathromycin (n = 247) at 2.5 mg/kg on day 0 versus either tiamulin (n = 102) at 15 mg/kg on days 0, 1, and 2 (Germany, the Netherlands, and the United Kingdom) or florfenicol (n = 20) at 15 mg/kg on days 0 and 2 (France). Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae infections were the most frequently diagnosed pathogens. For both tulathromycin-treated animals and those treated with tiamulin or florfenicol, there were significant (P = .0001) reductions in mean rectal temperature and the severity of abnormal clinical signs on days 2 and 10 compared with day 0. There were no significant differences (P > .05) between treatments in average daily weight gain. Tulathromycin was found to be safe and highly effective in the treatment of natural outbreaks of SRD.

Topics: Animals; Anti-Bacterial Agents; Disaccharides; Disease Outbreaks; Diterpenes; Europe; Heterocyclic Compounds; Injections, Intramuscular; Pasteurellosis, Pneumonic; Severity of Illness Index; Swine; Swine Diseases; Thiamphenicol; Treatment Outcome

Developing baseline concentrations of serotonin in healthy white-tailed deer will allow for the development of a biomarker using non-invasive sample tissues in sick animals, for example, non-clinical cases of chronic wasting disease. It will also allow some further insight into whether the use of antibiotics as growth promoters (AGP), such as chlortetracycline, is affecting serotonin concentrations in white-tailed deer. Florfenicol and tulathromycin impacts on serotonin concentration changes were also investigated. An analytical method for the detection and confirmation of serotonin, 5-hydroxytryptamine (5-HT), in white-tailed deer tissues was developed and validated. Serum and urine samples were extracted with acetonitrile. Liquid chromatography separation was attained on a Phenomenex C

Topics: Animals; Anti-Bacterial Agents; Deer; Disaccharides; Female; Gastrointestinal Microbiome; Heterocyclic Compounds; Limit of Detection; Male; Reference Standards; Serotonin; Thiamphenicol

Actinobacillus pleuropneumoniae, Pasteurella multocida and Streptococcus suis are prevalent bacterial causes of swine infections. Morbidity, mortality and positively impacting the financial burden of infection occurs with appropriate antimicrobial therapy. Increasing antimicrobial resistance complicates drug therapy and resistance prevention is now a necessity to optimize therapy and prolong drug life. Mutant bacterial cells are said to arise spontaneously in bacterial densities of 107-109 or greater colony forming units/ml. Antibiotic drug concentration inhibiting growth of the least susceptible cell in these high density populations has been termed the mutant prevention concentration (MPC). In this study MPC and minimum inhibitory concentration (MIC) values of ceftiofur, enrofloxacin, florfenicol, tilmicosin and tulathromycin were determined against the swine pathogens A. pleuropneumoniae, P.multocida and S. suis. The following MIC90/MPC90 values (mg/L) for 67 A. pleuropneumoniae and 73 P. multocida strains respectively were as follows: A. pleuropneumoniae 0.031/0.5, ≤0.016/0.5, 0.5/2, 4/32, 2/32; P. multocida 0.004/0.25, 0.016/0.125, 0.5/0.5, 8/16, 0.5/1. For 33 S. suis strains, MIC90 values (mg/L) respectively were as follows: 1, 0.25, 4, ≥8 and ≥8. A total of 16 S. suis strains with MIC values of 0.063-0.5 mg/L to ceftiofur and 0.25-0.5 mg/L to enrofloxacin were tested by MPC; MPC values respectively were 0.5 and 1 mg/L respectively. MPC concentrations provide a dosing target which may serve to reduce amplification of bacterial subpopulations with reduced antimicrobial susceptibility. Drug potency based on MIC90 values was ceftiofur > enrofloxacin >florfenicol = tulathromycin > tilmicosin; based on MPC90 values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin.

Topics: Actinobacillus pleuropneumoniae; Animal Husbandry; Animals; Anti-Bacterial Agents; Cephalosporins; Disaccharides; Drug Resistance, Multiple, Bacterial; Enrofloxacin; Heterocyclic Compounds; Microbial Sensitivity Tests; Pasteurella multocida; Streptococcus suis; Swine; Swine Diseases; Thiamphenicol; Tylosin

Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points.

Topics: Animals; Anti-Bacterial Agents; Biological Availability; Cattle; Cephalosporins; Cross-Over Studies; Disaccharides; Enrofloxacin; Epithelial Cells; Extracellular Fluid; Fluoroquinolones; Heterocyclic Compounds; Lung; Male; Mannheimia haemolytica; Microbial Sensitivity Tests; Respiratory Mucosa; Thiamphenicol; Veterinary Drugs

Separate methods for the quantitation and confirmation of regulatory relevant residue concentrations of total florfenicol and tulathromycin residues in multiple tissue matrices were developed and validated. Total florfenicol residues, determined and expressed as florfenicol amine (FFA) equivalents, were quantified and confirmed over a concentration range of 100-4000ng/g, with an LOD of 33ng/g, while total tulathromyicn residues, determined as CP-60,300 and expressed as tulathromycin equivalents, were quantified and confirmed over a concentration range of 500-10,000ng/g, with an LOD of 300ng/g. A 2 or 1h acid digestion for the FFA and tulathromycin methods, respectively, followed by extraction, cleanup, and concentration using mixed-mode strong cation-exchange SPE cartridges was used. Quantitation and confirmation were accomplished using commercially available tri-deuterated FFA (FFA-D3) as internal standard and multiple reaction monitoring (MRM) of three transitions per target analyte. Mean recoveries and matrix effects were 60% and 25%; and 100% and 110%, respectively for the target analytes florfenicol amine and CP-60,300. Intra-lab method reproducibilities ranged from 7 to 11% RSD, which are within the AOAC recommended HORRATr guidelines for method reproducibilities estimated from single laboratory validation studies. Blind spikes showed that method bias was generally less than 15% for both methods within the calibration range. Both methods have been shown to meet requirements for use in national chemical residue monitoring programs.

Topics: Animals; Cattle; Chromatography, Liquid; Disaccharides; Heterocyclic Compounds; Horses; Hydrolysis; Kidney; Limit of Detection; Liver; Molecular Weight; Muscles; Reproducibility of Results; Sus scrofa; Tandem Mass Spectrometry; Thiamphenicol

Deep digital septic conditions represent some of the most refractory causes of severe lameness in cattle. The objective of this study was to determine the distribution of tulathromycin, gamithromycin and florfenicol into the synovial fluid of the metatarsophalangeal (MTP) joint of cattle after single subcutaneous administration of drug to evaluate the potential usefulness of these single-dose, long-acting antimicrobials for treating bacterial infections of the joints in cattle.. Twelve cross-bred beef cows were randomly assigned to one of the drugs. Following subcutaneous administration, arthrocentesis of the left metatarsophalangeal joint was performed at various time points up to 240 hours post-injection, and samples were analyzed for drug concentration. In synovial fluid, florfenicol pharmacokinetic parameters estimates were: mean Tmax 7 +/- 2 hours, mean t½ 64.9 +/- 20.1 hours and mean AUC0-inf 154.0 +/- 26.2 ug*h/mL. Gamithromycin synovial fluid pharmacokinetic parameters estimates were: mean Tmax 8 hours, mean t½ 77.9 +/- 30.0 hours, and AUC0-inf 6.5 +/- 2.9 ug*h/mL. Tulathromycin pharmacokinetic parameters estimates in synovial fluid were: Tmax 19 +/- 10 hours, t½ 109 +/- 53.9 hours, and AUC0-inf 57.6 +/- 28.2 ug h/mL.. In conclusion, synovial fluid concentrations of all three antimicrobials were higher for a longer duration than that of previously reported plasma values. Although clinical data are needed to confirm microbiological efficacy, florfenicol achieved a synovial fluid concentration greater than the MIC90 for F. necrophorum for at least 6 days.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Cattle; Disaccharides; Female; Half-Life; Heterocyclic Compounds; Injections, Subcutaneous; Macrolides; Synovial Fluid; Thiamphenicol

To determine bactericidal effects of enrofloxacin, florfenicol, tilmicosin, and tulathromycin on clinical isolates of Mannheimia haemolytica at various bacterial densities and drug concentrations.. 4 unique isolates of M haemolytica recovered from clinically infected cattle.. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined for each drug and isolate. Mannheimia haemolytica suspensions (10(6) to 10(9) CFUs/mL) were exposed to the determined MIC and MPC and preestablished maximum serum and tissue concentrations of each drug. Log10 reduction in viable cells (percentage of cells killed) was measured at various points.. Bacterial killing at the MIC was slow and incomplete. After 2 hours of isolate exposure to the MPC and maximum serum and tissue concentrations of the tested drugs, 91% to almost 100% cell killing was achieved with enrofloxacin, compared with 8% growth to 93% cell killing with florfenicol, 199% growth to 63% cell killing with tilmicosin, and 128% growth to 43% cell killing with tulathromycin over the range of inoculum tested. For all drugs, killing of viable organisms was evident at all bacterial densities tested; however, killing was more substantial at the MPC and maximum serum and tissue drug concentrations than at the MIC and increased with duration of drug exposure. Rank order of drugs by killing potency was enrofloxacin, florfenicol, tilmicosin, and tulathromycin.. Findings suggested that antimicrobial doses that equaled or exceeded the MPC provided rapid killing of M haemolytica by the tested drugs, decreasing opportunities for antimicrobial-resistant subpopulations of bacteria to develop during drug exposure.

Topics: Animals; Anti-Bacterial Agents; Cattle; Disaccharides; Enrofloxacin; Fluoroquinolones; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Pneumonia of Calves, Enzootic; Thiamphenicol; Tylosin; United States

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Cattle; Disaccharides; Feces; Female; Gastrointestinal Microbiome; Heterocyclic Compounds; Oxytetracycline; Retrospective Studies; Thiamphenicol; Treatment Outcome

Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Disaccharides; Drug Resistance, Multiple, Bacterial; Enrofloxacin; Fluoroquinolones; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Thiamphenicol; Tylosin; United States

The purpose of this study was to compare the relative cost-effectiveness of florfenicol with that of tulathromycin for treatment of undifferentiated fever (UF) in feedlot calves at ultra-high risk of developing UF that receive metaphylactic tulathromycin on arrival at the feedlot. Calves that received therapeutic florfenicol had lower overall mortality (P=.045) and bovine respiratory disease mortality (P=.050) compared with calves that received therapeutic tulathromycin, but no significant differences were detected in feedlot performance, carcass characteristics, or other animal health variables. There was a net advantage of Can$41.19/treated animal in the florfenicol group versus the tulathromycin group. This study demonstrates that it is more cost-effective to use florfenicol than tulathromycin for the initial treatment of UF in feedlot calves at ultra-high risk of developing UF that receive on-arrival metaphylactic tulathromycin.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cattle Diseases; Cost-Benefit Analysis; Disaccharides; Fever; Heterocyclic Compounds; Thiamphenicol; Treatment Outcome

The purpose of this study was to compare the efficacy and cost-effectiveness of florfenicol versus tulathromycin for initial treatment of undifferentiated fever in fall-placed steer calves that received metaphylactic tilmicosin on arrival at the feedlot. No significant differences (P > .10) were observed in undifferentiated fever relapses or the crude case fatality rate. Calves treated with florfenicol had a lower case fatality rate (P = .04) for bovine respiratory disease and Histophilus disease than did calves treated with tulathromycin. The net economic advantage of florfenicol over tulathromycin (Can$17.70/treated animal) was based on differences in costs for the trial drug and calf replacement owing to bovine respiratory disease and Histophilus disease case fatality.

Topics: Alberta; Animals; Animals, Newborn; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cost-Benefit Analysis; Disaccharides; Heterocyclic Compounds; Male; Random Allocation; Risk Factors; Thiamphenicol; Treatment Outcome