Antimicrobial agents/drugs combinations

Ceftiofur has been examined as a possible antimicrobial agent for use in PMMA delivery systems (Ethell et al 2000). Results demonstrate that it is also an appropriate antimicrobial agent for combination with PMMA. Its elution profile would suggest that it is released from the carrier rapidly and, therefore, should be placed in such a fashion that removal and replacement of expended beads is possible if prolonged drug levels are to be required. 

The IM and SC routes are by far the most frequently used extravascular parenteral routes of drug administration in farm animals. The less frequently used parenteral routes have limited application, in that they aim at directly placing high concentrations of antimicrobial agent close to the site of infection. These routes of administration include intra-articular or subconjuctival injection and intra-mammary or intra-uterine infusion. These local routes differ from the major parenteral routes in that absorption into the systemic circulation is not a prerequisite for delivery of drug to the site of action. The combined use of systemic and local delivery of drug to the site of infection represents the optimum approach to... 

Most infections should be treated with a single antimicrobial agent. Although indications for combination therapy exist, antimicrobial combinations are often overused in clinical practice. The unnecessary use of antimicrobial combinations increases toxicity and costs and may occasionally result in reduced efficacy due to antagonism of one drug by another. Antimicrobial combinations should be selected for one or more of the following reasons ... 

Certain combinations of antibiotics,such as (3-lactams and aminoglycosides, show synergism, that is, the combination is more effective than either of the drugs used separately. Because such synergism among antimicrobial agents is rare, they should only be used in special situations summarized in Figure 28.7)... 

Drug Discovery Today 7 25-27 Li AP (2004) In vitro approaches to evaluate ADMET drug properties. Curr Top Med Chem 4 701-706 Li W, Escarpe PA, Eisenberg EJ et al. (1998) Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071. Antimicrobial Agents and Chemotherapy 42 647-653 Los LE, Welsh DA, Herold EG et al. (1996) Gender differences in toxicokinetics, liver metabolism, and plasma esterase activity observations from a chronic (27-week) toxicity study of enalapril/diltiazem combinations in rats. Drug Metab Dispos 24 28-33... 

There are no drugs specifically approved by the FDA to treat Acanthamoeba, necessitating the compounding of all medications.Antimicrobial agents are generally used in combination to increase the likelihood of a successful response. Treatment is often prolonged as the mean time to healing is about 100 days. A small number of patients develop Acanthamoeba sclerokeratitis. It is not known whether this severe scleral inflammation is infective or immime mediated. 

Combination antimicrobial therapy is commonplace in equine practice. However, combination therapy has never been demonstrated to be superior to single drug therapy in controlled clinical trials. The use of multiple antimicrobial agents should be limited to certain situations. 

The sulfonamides are a group of organic compounds with chemotherapeutic activity they are antimicrobial agents and not antibiotics. They have a common chemical nucleus that is closely related to PABA, an essential component in the folic acid pathway of nucleic acid synthesis. The sulfonamides are synergistic with the diaminopyrim-idines, which inhibit an essential step further along the folate pathway. The combination of a sulfonamide and a diaminopyrimidine is advantageous because it is relatively non-toxic to mammalian cells (less sulfonamide is administered) and is less likely to select for resistant bacteria. Only these so-called potentiated sulfonamides are used in equine medicine. These drugs are formulated in a ratio of one part diaminopyrimidine to five parts sulfonamide, but the optimal antimicrobial ratio at the tissue level is 1 20, which is achieved because the diaminopyrimidines are excreted more rapidly than the sulfonamides. 

The recommendations for the treatment of EPM using pyrimethamine, trimethoprim and sulfadiazine were originally based on the use of these drugs for the treatment of malaria and toxoplasmosis in humans. Either pyrimethanune or trimethoprim in combination with sulfadiazine or sulfamethoxazole have been used with some success and have gained widespread acceptance as the treatment of choice for EPM. Pyrimethamine and trimethoprim are diaminopyrimidine antimicrobial agents that inhibit dihydrofolate reductase (DHFR see Ch. 2). These agents interfere with... 

It warrants mention that resistance to a particular antimicrobial agent in vitro may not preclude successful treatment with the drug as long as high concentrations are achieved in urine. Similarly, demonstrable susceptibility in vitro does not always guarantee a successful response to treatment. For example. Enterococcus spp. is often found to be susceptible to the potentiated sulfonamide combinations in vitro however, this pathogen is inherently resistant to these combinations in vivo (Jose-Cunilleras Hinchcliff 1999, Schott 1998). Antimicrobial therapy should be continued for at least 1 week for the treatment of lower UTIs and for 2-6 weeks for upper UTls in horses. Ideally, a voided, midstream urine sample should be submitted for bacterial culture 2-4 days after the initiation of therapy and again 1-2 weeks after treatment has been discontinued. 

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