Antibacterial drug failure

Rifampin. Source, antibacterial activity, and routes of administration are described on p. 274. Albeit mostly well tolerated, this drug may cause several adverse effects including hepatic damage, hypersensitivity with flu-like symptoms, disconcerting but harmless red/orange discoloration of body fluids, and enzyme induction (failure of oral Liillmann, Color Atlas of Pharmacology... 

Nitrofurantoin is well absorbed after ingestion. It is metabolized and excreted so rapidly that no systemic antibacterial action is achieved. The drug is excreted into the urine by both glomerular filtration and tubular secretion. With average daily doses, concentrations of 200 mcg/mL are reached in urine. In renal failure, urine levels are insufficient for antibacterial action, but high blood levels may cause toxicity. Nitrofurantoin is contraindicated in patients with significant renal insufficiency. 

An interesting exception to the absolute validity of the tifth postulate is the considerable activity of chloramphenicol derivatives in cell-free model systems of protein synthesis when these derivatives are substituted with amino acyl residues instead of with dichloroacetyl as is the antibiotic itself (rev. in 2°)). This has been traced to the necessity of the dichloroacetyl grouping in aiding in the permeation of the antibiotic through the bacterial envelope 21 The amino acyl derivatives have very low antibacterial activity 20. Permeation failures of actinomycin D, macrolides and distamycin A with respect to certain families of bacteria occlude the action of these antibiotics on their intracellular drug receptors and target reactions but can be overcome experimentally by measures which render test organisms permeable. 

Four patients developed acute renal failure, which appeared to be reversible, during treatment with colistin. Three were given cefalotin concurrently and the fourth had previously been taking this antibacterial. An increase in renal toxicity associated with concurrent use has been described in another report. The reason for this reaction is not known. What is known suggests that renal function should be closely monitored if these drugs are given concurrently or sequentially. 

Evidence is very limited but it has been suggested that all patients given long-term minocycline treatment should be well screened for the development of pigmentation, particularly if they are taking other drugs such as the oral contraceptives that are known to induce hyperpigmentation. Remember also that very rarely contraceptive failure has been associated with the use of minocycline and other tetracyclines, see Hormonal contraceptives + Antibacterials Tetracyclines , p.983. 

The interactions between the oral contraceptives and tetracyclines summarised here are all that have been identified in the literature. Much of the evidence is anecdotal with insufficient controls (if any). These interactions are not adequately established and the whole issue remains controversial. Bearing in mind the extremely wide use of both drugs, any increase in the incidence of contraceptive failure above the accepted failure rate is clearly very low indeed. On the other hand, the personal and ethical consequences of an unwanted pregnancy can be very serious. For this reason, the Faculty of Family Planning and Reproductive Health Care (FFPRHC) Clinical Effectiveness Unit recommends that an additional form of contraception, such as condoms, should be used while taking a short course of antibacterials that do not induce liver eiKymes, and for 7 days after the antibacterial has been stopped. See Hormonal contraceptives + Antibacterials Penicillins , p.981, for more detailed information on how to manage this interaction. 

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