Update on Common Antimicrobials

CHAPTER 3 Update on Common Antimicrobials



K. Gary Magdesian



β-LACTAM ANTIMICROBIALS



Oral Administration


The aminobenzyl penicillins (ampicillin and amoxicillin) and first-generation cephalosporins are poorly absorbed in adult horses; however, they have reasonable to good bioavailability in foals. Cefadroxil (30 mg/kg, administered orally every 12 hours), a first-generation cephalosporin, has 99% bioavailability in 2-week-old foals, but this decreases to 14% by 5 months of age. Amoxicillin, administered orally at 13 to 20 mg/kg, every 8 to 12 hours, reaches serum concentrations effective for treatment of streptococcal and non-β-lactamase–producing staphylococcal infections in foals. Cephalexin can also be orally administered in foals at a dosage of 25 mg/kg every 6 hours.



Local Infusion of Penicillin


A relatively new use of penicillin in equine practice involves infusion of penicillin dissolved in gelatin into the guttural pouches for treatment of horses shedding the strangles organism (Streptococcus equi) and horses with chronic empyema. The gelatin penicillin formulation remains within the guttural pouches longer than aqueous solutions, and infusion of the gelatin maintains high local concentrations of penicillin. The gelatin can be administered into the guttural pouches through a Chamber catheter or uterine infusion pipette. The instructions for making 50 mL of the penicillin-gelatin mix are as follows:


1. Mix 2 g gelatin with 40 mL sterile water.

2. Heat (or microwave) mixture until gelatin powder dissolves.

3. Cool gelatin to 45 to 50° C (113 to 124° F).

4. Dilute 10 × 106 units of sodium or potassium penicillin in 10 mL of sterile water.

5. Mix penicillin with the cooled gelatin to bring the total volume to 50 mL.

6. Dispense mixture into 60-mL syringes and leave overnight at 4° C (39.2° F) to set before infusing into pouches.


Cephalosporins: New Drugs and Novel Administration


First-, second-, and third-generation cephalosporins have been used in horses for a number of years. Ceftiofur is a third-generation cephalosporin approved for use in horses by the intramuscular (IM) route only (the dose for streptococcal infections is 2.2 mg/kg, IM route, every 24 hours). Recently, the pharmacokinetics of ceftiofur was studied after intravenous (IV) and subcutaneous (SC) administration. The IV and SC routes yielded concentrations of ceftiofur and metabolites similar to those achieved after IM administration. The SC route is convenient for use in neonatal foals that do not have IV catheters in place. I and many other clinicians administer ceftiofur at doses up to 5 to 10 mg/kg, IV, every 6 to 12 hours in neonatal foals with the goal of achieving concentrations effective against bacteria that typically have higher minimum inhibitory concentration (MIC) values than Streptococcus spp. and are commonly associated with neonatal sepsis, especially gram-negative enteric microbes. These doses should not be used in adult horses because of the risk of inducing colitis.


Recently, fourth-generation cephalosporins were studied for use in foals. Cefepime is an example of a drug with expanded gram-positive and gram-negative coverage, and it is resistant to β-lactamase enzymes. It is similar to ceftazidime, a third-generation cephalosporin, in its activity against Pseudomonas spp. Cefepime has a wide volume of distribution and is effective in treating meningitis because of its ability to penetrate the blood-brain barrier. The deficits of cefepime include lack of activity against methicillin-resistant Staphylococcus aureus (MRSA) and enterococci. It is only variably effective against anaerobic bacteria. The recommended dose of cefepime in foals is 11 mg/kg, IV, every 8 hours. Cefepime should not be administered to adult horses because of the high risk of gastrointestinal disturbances observed under experimental conditions.


Cefquinome is a new fourth-generation cephalosporin licensed in the United Kingdom for use in foals with septicemia and horses with respiratory tract disease. The recommended dose is 1 mg/kg, IV or IM administration, every 12 hours (for foals with septicemia) or every 24 hours (in adults with respiratory tract disease).


Another new finding in cephalosporin pharmacology in horses is the use of cefpodoxime, an oral third-generation cephalosporin, in neonatal foals. Like cefotaxime and ceftiofur, cefpodoxime has potent antibacterial activity against numerous gram-positive and gram-negative bacteria. On the basis of the pharmacokinetics of cefpodoxime in foals, an oral dose of 10 mg/kg every 6 to 12 hours is recommended. Dosing every 6 to 8 hours is suggested for microbes with higher MIC values, including E. coli (75% of equine E. coli isolates) and Salmonella spp. Agents with lower MIC values, such as Streptococcus, Klebsiella, and Pasteurella spp., could be treated every 12 hours. Cefpodoxime is ineffective against Pseudomonas, Enterococcus, and Rhodococcus equi isolates in horses. The drug distributes well to synovial and peritoneal fluids and concentrates in urine, but it does not enter cerebrospinal fluid. Although cefpodoxime is absorbed in adult horses, two of six animals developed signs of colic in one experimental study.



Continuous-Rate Infusion of β-Lactam Drugs


Continuous-rate infusion (CRI) administration of antimicrobials is being used with increasing frequency in both human and veterinary medicine. This dosing regimen is intended to optimize the pharmacokinetics of antimicrobials on the basis of their specific pharmacodynamic properties. With β-lactam drugs such as the penicillins and cephalosporins, efficacy is dependent on the duration of time for which plasma concentrations remain above the organism’s MIC, as the bactericidal activity of these drugs is time dependent. Continuous maintenance of plasma concentrations above the MIC therefore offers an advantage over intermittent administration of the antimicrobial. Continuous administration of an antimicrobial is particularly advantageous in immunocompromised animals, such as neutropenic and hypoglobulinemic neonatal foals with sepsis.


I use CRI administration of β-lactam antimicrobials in horses with severe sepsis or septic shock and whenever fluid lines and automated pumps can be maintained, such as in foals and horses that are recumbent or stall-confined. Two methods of dose calculation are possible for determining CRI rates in clinical practice. The first is to administer the same total dose during continuous infusion as would be administered during intermittent infusion. For example, if a drug is conventionally administered at a dose of 20 mg/kg every 8 hours, the CRI dosing rate would be 2.5 mg/kg per hour to keep the same total daily dose.


Alternatively, doses can be arrived at on the basis of pharmacodynamic considerations of the drug. With β-lactam antimicrobials, the goal is to maintain plasma free-drug concentrations at four times the MIC of the offending microorganism. Being time-dependent rather than concentration-dependent, β-lactam drugs reach their maximum killing rate at concentrations no higher than four times the MIC. The desired concentration for β-lactam drugs is therefore four times the MIC of the agent. The dosing rate is calculated as the product of drug clearance and the desired average (steady state) plasma concentration of drug. For example, if the clearance of a drug is known to be 0.2 L/kg per hour and the desired steady-state concentration is 1 μg/mL (4 × MIC of the offending agent), the CRI dosing rate is as follows:



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The clearance of many drugs is known from pharmacokinetics studies; for drugs with unknown clearance (Cl) it can be determined from published values of half-life (t½

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May 28, 2016 | Posted by in EQUINE MEDICINE | Comments Off on Update on Common Antimicrobials

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