The most commonly used antibiotics for calf pneumonia fall into a few key classes: macrolides (such as tulathromycin and tilmicosin), amphenicols (florfenicol), cephalosporins (ceftiofur), tetracyclines (oxytetracycline), and fluoroquinolones (enrofloxacin). The right choice depends on the pathogen involved, the calf’s age, and growing resistance patterns that have made some options less reliable than they were a decade ago.
Calf pneumonia, formally called bovine respiratory disease or BRD, is almost always triggered by a combination of viral stress and bacterial infection. The two bacteria most frequently cultured from sick calves are Pasteurella multocida and Mannheimia haemolytica. Treatment targets these organisms, and all the antibiotics discussed below are labeled for use against them.
Macrolides: Tulathromycin and Tilmicosin
Tulathromycin (sold as Draxxin) is one of the most widely used antibiotics for calf pneumonia. It is given as a single subcutaneous injection in the neck at 2.5 mg per kilogram of body weight, which works out to about 1.1 mL per 100 pounds. The single-dose convenience is a major practical advantage: you treat once and don’t need to handle the calf again. The meat withdrawal period is 18 days from the last treatment.
Tilmicosin (Micotil) is another macrolide option, also given as a single subcutaneous injection. It carries a well-known safety warning for humans: accidental self-injection can be fatal, so careful handling is essential.
The biggest concern with macrolides right now is resistance. A large Canadian surveillance study of feedlot cattle found that macrolide resistance was the most common resistance pattern in Mannheimia haemolytica isolates. Moderate to high resistance rates (above 10% and in some cases above 20%) were documented for tulathromycin, tilmicosin, tildipirosin, and gamithromycin. Resistance was also significantly higher at rehandling than at arrival, meaning calves that had already been in a feedlot environment carried more resistant bacteria. If your calves have been previously treated with a macrolide or come from a background where macrolide use is common, these drugs may be less effective.
Florfenicol
Florfenicol (Nuflor) is an amphenicol antibiotic that offers flexibility in how it’s administered. You can give it as two intramuscular injections 48 hours apart at 20 mg per kilogram (about 3 mL per 100 pounds), or as a single subcutaneous injection at the higher dose of 40 mg per kilogram (6 mL per 100 pounds). The single subcutaneous dose is also used for controlling respiratory disease in high-risk cattle before they get sick.
Florfenicol cannot be used in female dairy cattle 20 months of age or older, or in calves being raised for veal. A withdrawal period has not been established for pre-ruminating calves, so it is primarily suited for weaned calves and feedlot cattle.
Ceftiofur
Ceftiofur is a cephalosporin available in several formulations. The crystalline free acid version (Excede) is given subcutaneously in the base of the ear at 6.6 mg per kilogram, either as a single dose or as two doses spaced roughly 72 hours apart. The ear injection site is specific and important: it keeps residues away from edible tissues. The pre-slaughter withdrawal period is 13 days after the last injection.
Like florfenicol, ceftiofur has not had a withdrawal period established for pre-ruminating calves, and it is not approved for veal calves. One advantage of ceftiofur over some other options is that it can be used in lactating dairy cattle (depending on the formulation), making it useful when pneumonia hits dairy replacement heifers.
Oxytetracycline
Oxytetracycline is one of the oldest and least expensive options for treating calf pneumonia. It is typically given as an intramuscular or subcutaneous injection, and long-acting formulations can reduce the number of treatments needed. However, tetracycline resistance in BRD pathogens is well documented. The most common multi-drug resistance pattern identified in Mannheimia haemolytica isolates combined resistance to both macrolides and tetracycline. For mild cases or operations where susceptibility testing confirms effectiveness, oxytetracycline remains a reasonable first-line treatment. In herds with chronic or recurring BRD problems, it may not be reliable enough on its own.
Enrofloxacin
Enrofloxacin (Baytril 100) is a fluoroquinolone given as a single subcutaneous injection at 12.5 mg per kilogram. It is a potent option, but it comes with significant legal restrictions. It cannot be used in dairy cattle (except replacement heifers under 20 months), veal calves, or beef calves under two months of age. Most critically, extra-label use of fluoroquinolones in food-producing animals is prohibited by federal law. This means you can only use enrofloxacin exactly as described on the label, with no adjustments to dose, frequency, or species. Your veterinarian cannot legally prescribe it for off-label purposes the way they can with most other cattle antibiotics.
Penicillin and Sulfonamide Combinations
Penicillin and trimethoprim-sulfonamide combinations have been studied head-to-head with oxytetracycline for acute BRD in weaned beef calves. These are older, inexpensive drugs that still see use, particularly on smaller operations or when cost is a major factor. They generally require more frequent dosing than the newer long-acting injectables, which means more calf handling and more stress on already-sick animals. For operations managing large numbers of calves, the labor difference between a single-dose macrolide and a multi-day penicillin protocol can be substantial.
Anti-Inflammatory Drugs as Add-On Therapy
Antibiotics kill the bacteria, but the inflammation in the lungs is what makes calves feel miserable and stop eating. Adding a non-steroidal anti-inflammatory drug (NSAID) at the time of antibiotic treatment can speed recovery. Research has shown that calves treated with flunixin meglumine alongside an antibiotic had less abnormal lung tissue than calves receiving the antibiotic alone. Calves given ketoprofen with tulathromycin showed faster improvement in breathing effort and alertness compared to calves on the antibiotic by itself. Meloxicam has shown benefits for faster temperature normalization, and one study found that calves receiving oral meloxicam at feedlot arrival had a lower incidence of respiratory disease over the following 28 days.
A combination product (Draxxin KP) packages tulathromycin with ketoprofen in a single injection, simplifying the protocol. If you’re using a standalone antibiotic, asking your veterinarian about adding an NSAID is worth considering.
Recognizing When to Treat
Choosing the right antibiotic matters less if you’re treating too late or missing cases entirely. Calf respiratory scoring systems use a combination of visible signs to flag calves that need treatment: cough, ear droop or head tilt, and rectal temperature at or above 39.7°C (about 103.5°F). A calf showing at least two of these three signs has roughly a 31% chance of having active BRD. Calves with fewer than two signs had essentially no chance of active disease in validation studies, which helps avoid unnecessary antibiotic use.
For group housing situations, checking a sample of 10 calves about two weeks after arrival can tell you whether the group needs intervention. If three or more of those 10 calves score positive, there is a 94% chance that the batch has a BRD prevalence above 10%, the threshold where group-level action typically becomes warranted.
Resistance and Choosing Wisely
The rising resistance to macrolides and tetracyclines in Mannheimia haemolytica and Pasteurella multocida is reshaping treatment decisions. Resistance was significantly lower in cattle at arrival to feedlots compared to cattle sampled later after time in a group setting. This pattern suggests that antibiotic pressure within operations is driving resistance upward. Using culture and sensitivity testing when initial treatment fails, rotating drug classes rather than defaulting to the same macrolide every time, and reserving fluoroquinolones and cephalosporins for cases where first-line drugs have failed are all practical strategies for keeping your antibiotic options effective longer.