Bacteria, resistance

Development of Resistance. One of the principal disadvantages of sulfonamide therapy is the emergence of dmg-resistant strains of bacteria. Resistance develops by several mechanisms overproduction of PABA (38) altered permeabiUty of the organisms to sulfonamides (39) and reduced affinity of dihydropteroate synthetase for sulfonamides while the affinity for PABA is retained (40). Sulfonamides also show cross-resistance to other sulfonamides but not to other antibacterials. In plasmodia, resistance may occur by means of a bypass mechanism in which the organisms can use preformed foHc acid (41). 

Acylation of 7-ACA with 2-thienylacetylchloride gives the amide cephalothin (43). Displacement of the allylic acetyl group by pyridine affords the corresponding pyridinium salt cephalori-dine (44). Both these compounds constitute useful injectable antibiotics with some activity against bacteria resistant to penicillin by reason of penicillinase production. 

De Leo C, Eftimiadi C, Schito GC Rapid disappearance from the intestinal tract of bacteria resistant to rifaximin. Drugs Exp Clin Res 1986 12 979-981. 

Two mechanisms of resistance have been discovered with respect to fluoroquinolones a change in subunits A of DNA-gyrase, and reduced permeability of the outer membrane of the bacteria. Resistance is mediated by chromosomes, and not plasmids in the bacteria. The development of resistance while using the drugs is very rarely observed. 

Chopra, I. et al. (1997). The search for anti-microbial agents effective against bacteria resistant to multiple antibiotics. 

Mycoplasma, Legionella and Chlamydia. Hospital-acquired lower RTI are frequently caused by gramnegative bacteria. Resistant pathogens must be considered in an intensive care setting. 

As antibiotics came into widespread use, an unanticipated problem arose in the rapid development of resistance by bacteria. The problem was made acute by the fact that resistance genes are easily transferred from one bacterium to another by the infectious R-factor plasmids.a-d Since resistance genes for many different antibiotics may be carried on the same plasmid, "super bacteria," resistant to a large variety of antibiotics, have developed, often in hospitals. 

Streptomycin (Boxes 20-B, 20-H) was introduced into clinical use against tuberculosis in about 1943. However, resistant mutants always survived until newer drugs were developed. Isonicotinylhydrazide (isoniazid) is especially effective in combinations with suitable antibiotics and other drugs.8 The four-drug combination isoniazid, rifampicin (Box 28-A), pyrazinamide, and ethambutol is often used. Nevertheless, bacteria resistant to all of these have developed. 

Peschel, A. How do bacteria resist human antimicrobial peptides , Trends Microbiol 10 (2002) 179-186. 

Utility Treatment of Bacteria Resistant to Multiple Antibiotics... 

Linezolid is licensed in the UK for skin, soft tissue and respiratory tract infections, and it is usually restricted on grounds of cost to those caused by multiply resistant pathogens. The oral formulation may prove useful for follow-on therapy of severe and chronic infections caused by bacteria resistant to other agents, e.g. MRSA osteomyelitis. 

Amikacin 0.14-0.22 (adult), 0.4-0.6 (foal) 1-3 (adult), 5 (foal) Base RE Infections with bacteria resistant to gentamicin 6mg/kg i.v, i.m., s,c. once daily 20 mg/kg i,v once daily in neonatal foals... 

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