Antimicrobial Resistance
between bacteria of similar or different species through recombination or via transposons. Most of these genes are located on plasmids, but occasionally they may be transferred from the plasmid to the chromosome. Simultaneous resistance to more than one antimicrobial is often acquired through genetic transfer of transposons.1
Inducible
resistance is usually chromosomal. Derepressed mutants of Enterobacter cloacae with inducible chromosomal AmpC β-lactamases5 are reported to occur in 10–19 % of infected patients following exposure to broad-spectrum β-lactams.6
Resistance to first-line antituberculosis
drugs is attributable to the intrinsic frequency of mutations arising in drug-susceptible populations - this is estimated to be 10-6 for isoniazid, 10-8 for rifampin and 10-15.5 for simultaneous resistance to both agents.7
Epidemiology
Clinically-important antimicrobial resistance that compromises therapeutic management is now widespread in both community- and healthcare-acquired infections (see Table 2). MRSA was initially considered an organism limited to healthcare infections, but epidemic community-acquired strains have subsequently emerged, with widespread reports of both minor and severe infections.8
These
community strains have subsequently been introduced into and caused outbreaks in healthcare facilities.
Streptococcus pneumoniae has acquired resistance to penicillin G as well as macrolides and fluoroquinolones.9
In Europe, the prevalence
of penicillin-non-susceptible S. pneumoniae varies from 1–5 % in northern countries to 25–50 % in Mediterranean countries.10 Macrolide resistance varies from 1–5 % in Latvia and Sweden to 15–50 % in France, Italy and Greece.10
Salmonella species causing typhoid and paratyphoid fever in some parts of the world have high levels of resistance to fluoroquinolones – previously a drug of choice for therapy.11
Escherichia coli isolated from acute cystitis has repeatedly acquired resistance to first-line therapies – ampicillin, sulphonamides, and trimethoprim – and now to fluoroquinolones as extended-spectrum β-lactamase (ESBL)-producing strains have emerged globally.12
Streptococcus pyogenes (group A streptococcus) and Neisseria meningitidis have both remained susceptible to penicillin G. Despite this, resistance to macrolides is widespread in the former and sulphonamide prophylaxis was abandoned for the latter because of resistance development.
Antimicrobial resistance may be an even greater problem in Asia and Africa than Europe or North America.13,14
Over 90 % of strains of
Vibrio cholera in some parts of Africa are reported to be resistant to tetracycline, chloramphenicol, TMP/SMX or ampicillin.14
In the community, antimicrobial-resistant organisms are acquired by direct or indirect human contact, as is usually the case for MRSA and most respiratory pathogens. These resistant strains may also be acquired from food, where resistance is attributed to widespread agricultural use of antibiotics,15–17 food production17
or from contact with companion animals.18
Globalisation and widespread travel also provide opportunities for the acquisition and transmission of resistant organisms.19 of CTX-M extended-spectrum beta-lactamase (ESBL) E. coli from
Isolation EUROPEAN INFECTIOUS DISEASE
Risk factors for colonisation or infection with resistant organisms in patients in healthcare settings include the number and type of pre-existing comorbidities, invasive procedures (surgical interventions, central lines, urinary catheters, ventilators) and prolonged length of hospital stay.24
for antimicrobial resistance.25–27 by contact with animals raised for
Despite this, antimicrobial exposure is the main driver Hospitalised patients acquire resistant
organisms directly from contact with other patients or indirectly from the hands of healthcare workers or from the environment. Resistant strains are also frequently derived endogenously through de novo mutation when the patient is treated with antibiotics or via antibiotic-induced selection of pre-existing low-level resistant bacteria.26
A recent Dutch
study from two intensive care units in one hospital reported that most resistant organisms were acquired endogenously.26
93
Some clinically-important resistant organisms, particularly MRSA, are a problem for both healthcare- and community-acquired infections. However, there is generally a different spectrum of resistant organisms in the healthcare setting. Vancomycin-resistant S. aureus, vancomycin-resistant enterococci (VRE), ESBL-producing Enterobacteriaceae, carbapenamase-producing Klebsiella pneumoniae and non-fermenters such as P. aeruginosa and A. baumanii22,23
are all
examples of important resistant organisms isolated in healthcare settings (see Table 2).
The emergence of bacteria resistant to all available therapies is a concern. Vancomycin-resistant S. aureus is considered a particular danger, given the frequency and potential severity of S. aureus infections. Multidrug-resistant Gram-negative organisms such as the non-fermenters P. aeruginosa4
resistant to virtually all antibiotics.3,4
and Burkholderia cepacia, may be Carbapenemase-producers
enterobacteriaceae, including New Delhi metalloprotease-1 (NDM-1)-producing K. pneumoniae with K. pneumoniae carbapenemases (KPC), are also becoming common. Some of these strains23
have
acquired multidrug-resistant plasmids and are resistant to all β-lactams, aminoglycosides, fluoroquinolones, TMP/SMX and tetracyclines.
Table 1: Mechanisms of Resistance of Bacteria to Antimicrobial Agents
Mechanism
Drug inactivation ↓Cell entry
• outer membrane permeability Target site modification
Examples of Antimicrobials Affected β-lactams, aminoglycosides
β-lactams
• cytopasmic membrane transport fluoroquinolones, aminoglycosides Increased efflux
Fluoroquinolones, macrolides
Macrolides, fluoroquinolones, β-lactams, glycopeptides
community infections in Calgary in Canada was significantly associated with recent travel, with a risk 145 times greater for recent travellers to India and 18 times greater for travellers to the Middle East.20
Whatever the mode of exposure, current or recent antimicrobial use is a major risk for acquisition of resistance. In a systematic review of primary care studies, an antimicrobial prescription given to an infected patient within the previous two months was associated with an increased risk of resistance in urinary isolates (odds ratio [OR] 2.5, 95 % confidence interval [CI] 2.1–2.9) and respiratory isolates (OR 2.4, 95 % CI 1.4–3.9]. The likelihood of isolation of a resistant organism also correlated with the number of antimicrobial courses and duration of therapy.21
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