Bacteriostatic drugs combinations

In many therapeutic situations the drug combinations are completely misused (12). Adding another drug to a combination does not reduce the need for sound clinical judgement in therapy. Although there are many disease situations in which the use of more than one antibacterial agent may be justified, generalizations about various combinations of bactericidal or bacteriostatic antibiotics or admixtures have not proven valid. Basically, antibiotic combinations should be avoided as a common practice unless they have shown a clear increase in effectiveness as reported in the literature. 

Antibacterial drugs can be either bactericidal or bacteriostatic The effectiveness of bacteriostatic drugs depends on an intact host immune system. Antimicrobial agents may be administered singly or in combination. Some combinations induce synergy and/or delay emergence of resistance. 

For some indications combination chemotherapy is indicated however then bacteriostatic or bactericidal agents should not be mixed. Synergism between the actions of different drugs is one of the aims of combination therapy. Other indications are delay of development of resistance or the treatment of mixed infections. 

Trimethoprim, a trimethoxybenzylpyrimidine, selectively inhibits bacterial dihydrofolic acid reductase, which converts dihydrofolic acid to tetrahydrofolic acid, a step leading to the synthesis of purines and ultimately to DNA (Figure 46-2). Trimethoprim is about 50,000 times less efficient in inhibition of mammalian dihydrofolic acid reductase. Pyrimethamine, another benzylpyrimidine, selectively inhibits dihydrofolic acid reductase of protozoa compared with that of mammalian cells. As noted above, trimethoprim or pyrimethamine in combination with a sulfonamide blocks sequential steps in folate synthesis, resulting in marked enhancement (synergism) of the activity of both drugs. The combination often is bactericidal, compared with the bacteriostatic activity of a sulfonamide alone. 

Ethambutol Inhibits mycobacterial arabinosyl transferases, which are involved in the polymerization reaction of arabinoglycan an essential component of the mycobacterial cell wall Bacteriostatic activity against susceptible mycobacteria Given as four-drug initial combination therapy for tuberculosis until drug sensitivities are known also used for atypical mycobacterial infections Oral t mixed clearance (half-life 4 h) dose must be reduced in renal failure Toxicity Retrobulbar neuritis... 

The sulfonamide antibiotics were the first synthetic antibiotics to have general utility in human therapy (B-79MI10806). Of the numerous compounds thus developed, comparatively few are presently used in veterinary practice. They include sulfapyridine (40), sulfamethazine (41) and sulfadimethoxine (42). They are much less potent than the /3-lactams (dose 100-200 mg kg-1), and have a bacteriostatic effect. They are commonly used in combination with trimethoprim (43), when a synergistic effect is observed, i.e. the combination is more potent than either drug alone, and species of bacteria which are unaffected by the drugs individually are susceptible to the combination. 

The sulfas, including co-trimoxazole (sulfamethoxazole plus trimethoprim, see p. 293), are bacteriostatic. These drugs are active against selected enterobacteria, chlamydia, Pneumocystis, and nocardia. Typical clinical applications are shown in Figure 29.3. In addition, sulfadiazine [sul fa DYE a zeen] in combination with the dihydrofolate reductase inhibitor pyrimethamine [py ri METH a meen] is the only effective form of chemotherapy for toxoplasmosis (p. 353). 

Ethambutol [e THAM byoo tole] is bacteriostatic and specific for most strains of M- tuberculosis and M- kansasii. Resistance is not a serious problem if the drug is employed with other antituberculous agents. Ethambutol can be used in combination with pyrazinamide, isoniazid, and rifampin to treat tuberculosis. Absorbed on oral administration, ethambutol is well distributed throughout the body. Penetration into the central nervous system (CNS) is therapeutically adequate in tuberculous meningitis. Both parent drug and metabolites are excreted by glomerular filtration and tubular secretion. The most important adverse effect is optic neuritis, which results in... 

Aminosalicylate competitively antagonizes metabolism of para-aminobenzoic acid, resulting in bacteriostatic activity against Mycobacterium tuberculosis. Aminosalicylate is indicated in the treatment of tuberculosis (in combination with other antituberculous drugs) caused by susceptible strains of tubercle bacilli. 

Erythromycin and clindamycin are the most common used topical antibiotics for the treatment of acne [14]. Topical antibiotics have a bacteriostatic and bactericidal effect, reducing P. acnes colonization of the sebaceous follicle. However, topical antibiotics have not to be used in monotherapy due to the high risk of increasing P. acnes resistance. The development of resistance is less frequent in patients who are treated with combination therapy (benzoyl peroxide/erythromycin benzoyl peroxide/clindamycin). These associations enhance the bactericidal effect, reducing the risk of drug-resistance. 

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