Bacterial Infections
Antimicrobial Resistance Lindsay E Nicolle
Professor, Department of Internal Medicine and Medical Microbiology, University of Manitoba, Health Sciences Centre, Winnipeg
Abstract
Antimicrobial resistance is an important and continually evolving issue that affects the clinical management of infections. Currently, treatment of many infections in the community and healthcare settings is compromised by antimicrobial resistance of bacteria that were previously susceptible. Addressing this problem requires a multifaceted approach. Continuous monitoring of antimicrobial resistance locally and globally is necessary to identify new resistance as it emerges, characterise the spread of resistance and measure the prevalence. Development of new, effective antimicrobials is important, together with optimising the use of currently available antibiotics in community and healthcare facilities. Public health, healthcare infection control and addressing the intensive use of antimicrobials in agriculture are also important interventions for limiting resistance.
Keywords Antimicrobials, resistance, antimicrobial stewardship, infection control, methicillin-resistant Staphylococcus aureus (MRSA)
Disclosure: Lindsay E Nicolle is on a Leo Pharmaceutical Advisory Board and a Cerexa Advisory Board. Received: 12 February 2011 Accepted: 3 April 2011 Citation: European Infectious Disease, 2011;5(2):92–7 Correspondence: Lindsay E Nicolle, Professor, Department of Internal Medicine and Medical Microbiology, University of Manitoba, Health Sciences Centre, Room GG443 - 820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada. E:
lnicolle@hsc.mb.ca
The development and effective use of antimicrobials for the treatment of infections is one of the triumphs of 20th century medicine. However, the flipside of this success has been the consistent emergence of micro-organisms resistant to previously effective antimicrobials. Antimicrobial resistance is not exceptional, nor a new phenomenon. Some bacteria have intrinsic resistance to selected antimicrobials. For example, streptococci and enterococci are resistant to aminoglycosides and Pseudomonas aeruginosa is resistant to penicillin G. For others, the development of antimicrobial resistance is a predictable response of bacteria following exposure to a toxin. The consistent emergence of bacterial resistance when confronted by antimicrobial pressure is evidence of the remarkable plasticity of the bacterial genome, allowing micro-organisms to persist and thrive in a hostile environment.
Resistance occurs in all classes of micro-organisms – bacteria, fungi, parasites and viruses. This article addresses only antimicrobial resistance in bacteria, an important current concern for the management of both community- and healthcare-acquired infections.
Mechanisms
While there is a universe of distinct bacterial species and a substantial library of antimicrobial classes and individual agents, bacterial resistance is achieved through only a limited number of mechanisms (see Table 1).1
These include drug inactivation; inhibition of entry into the cell with changes in outer membrane permeability or decreased cytoplasmic membrane transport; increased efflux of antimicrobials out of the cell; and modification or, less commonly, bypassing the antimicrobial target.
However, a large number of distinct resistance elements may mediate any given mechanism of resistance. For instance, over 850 β-lactamases,
92
which inactivate β-lactam antibiotics, have been described.2
Individual
species or strains of resistant bacteria may incorporate single or multiple resistance mechanisms. Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to:1
• penicillin through β-lactamase production; • •
• tetracycline through increased efflux.
Acinetobacter baumanii, a highly resistant Gram-negative rod, incorporates:3,4
• drug inactivation (it has β-lactamases, carbapenemases and aminoglycoside-modifying enzymes);
• efflux pumps (making β-lactams, glycylcyclines, aminoglycosides, fluoroquinolones, macrolides and co-trimoxazole (trimethoprim/ sulfamethoxazole [TMP/SMX]) ineffective);
• •
membrane permeability changes (preventing the penetration of carbapenems and polymyxins); and
target alteration (making it resistant to tetracycline and also fluoroquinolones).
Thus, antimicrobial resistance mechanisms for a given organism may be complex and are often multiple and therefore redundant.
Development of resistance by previously susceptible bacteria occurs following the acquisition of DNA with resistance elements from other bacteria, or the induction of pre-existing resistance genes following antimicrobial exposure and mutation. Resistance genes are transferred
© TOUCH BRIEFINGS 2011 methicillin due to target alteration of penicillin-binding protein 2a;
linezolid, vancomycin and aminoglycosides through target alteration; and
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