Antimicrobial resistance

Antimicrobial resistance - Microorganisms have evolved in the presence of antibiotics, which are antimicrobial agents produced naturally by bacteria and fungi. They have therefore developed multiple resistance mechanisms (categorised in Fig. 6.14) to all classes of antimicrobial agent (antibiotics and their derivatives). Resistance may be an innate property of a microorganism (intrinsic resistance) or may be acquired, by either spontaneous mutation or horizontal transfer of genetic material from another organism. For some agents, e.g. penicillins, a degree of resistance occurs in vivo when the bacterial load is high and the molecular target for the antimicrobial is down-regulated (an ‘inoculum effect’).

Antimicrobial Resistance

Antimicrobial Resistance

The mecA gene encodes a low-affinity penicillin-binding protein, which confers resistance to meticillin and other penicillinase-resistant penicillins in Staph. aureus. It is common for plasmids to encode resistance to multiple antimicrobials, which may be transferred horizontally. Extended spectrum â-lactamases (ESBL) are encoded on plasmids, which are transferred relatively easily between bacteria including Enterobacteriaceae. Plasmid-mediated carbapenemases have been detected in strains of Klebsiella pneumoniae. Glycopeptide resistance in enterococci is also transferred on mobile genetic elements. Strains of MRSA have been described that exhibit intermediate resistance to glycopeptides, through the development of a relatively impermeable cell wall (GISA).

Factors implicated in the emergence of antimicrobialresistance include the inappropriate use of antibiotics when not indicated (e.g. in viral infections) inadequate dosage or treatment duration, excessive use of broad- spectrum agents, and use of antimicrobials as growth-promoters in agriculture. However any antimicrobial use exerts a selection pressure that favours the development of resistance. Combination antimicrobial therapy may reduce the emergence of resistance. This is recommended in treatment of patients infected with HIV, which is highly prone to spontaneous mutation (p. 406). 

Despite use of combination therapy for M. tuberculosis, multidrug-resistant TB (MDR-TB, resistant to isoniazid and rifampicin) and extremely drug-resistant TB (XDR-TB,  resistant to isoniazid and rifampicin, any fluoroquinolone, and at least one injectable antimicrobial antituberculous agent) have been reported worldwide and are increasing in incidence (p. 693).