Bactericidal 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. 

It is bactericidal drug and exerts its action by combining with bacterial ribosome and induces misreading of mRNA codons. Also in sensitive bacteria, disruption of cytoplasmic membrane occurs resulting in leakage of amino acids, ions, leading to bacterial death. 

Trimethoprim plus sulfamethoxazole When the two drugs are used in combination, antimicrobial synergy results from the sequential blockade of folate synthesis (Figure 46-1). The drug combination is bactericidal against susceptible organisms. 

The answer is d. (Hardman, pp 909-910.) It is now recognized that infection with fi pylon is a major etiologic factor in peptic ulcer disease. Bismuth salts are bactericidal for many organisms but especially for spirochetes. Colloidal bismuth salts such as bismuth subsalicylate also have a coating or cytoprotective action. Antimicrobials and GI antisecretory drugs are also used in combination with bismuth compounds. 

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. 

It is bactericidal and highly effective in leprosy. A single monthly dose of 600 mg may be used in combination with other antileprosy drugs to avoid any probable risk of rifampicin resistant M. leprae. 

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. 

The current approach is to treat tuberculosis in two phases an initial phase where a combination of three drugs is used to reduce the bacterial level as rapidly as possible, and a continuation phase in which a combination of two drugs is employed. Front-line drugs are isoniazid, rifampicin, streptomycin and ethambutol. Pyrazinamide, which has good meningeal penetration, and is thus particularly useful in tubercular meningitis, may be used in the initial phase to produce a highly bactericidal response. 

Fig. 6.4 Types of combined action of two antimicrobial drugs on a homogeneous microbial population. Schematic representation of bactericidal action in vitro showing the possible types of results seen when one drug, or two drugs, act on a homogeneous population of bacteria under conditions permitting growth.

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