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Extended spectrum beta-lactamases
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download a lecture on ESBL
- ß-lactamases capable of hydrolysing extended spectrum cephalosporins and
penicillins and aztreonam
- plasmid mediated
- aminoglycoside and trimethoprim-sulfamethoxazole resistance often
transferred on same plasmid
- often associated with fluoroquinolone resistance
- some ESBL-producing organisms have also acquired an AmpC-type ß-lactamase
- this is distinct from from ESBL
- most often associated with E. coli or Klebsiella pneumoniae
but can be transferred to Proteus mirabilis, Citrobacter, Serratia
and other enteric bacilli
- >170 different ESBLs
Detection
- difficult
- organisms appear sensitive to certain antibiotics (eg 3rd and 4th
generation cephalosporins) at standard innoculum but have significantly
elevated MIC at higher innoculums. As a result it is necessary to screen all
E. coli and Klebsiella pneumoniae with reduced susceptibility
to these drugs or aztreonam
- no current recommendations for screening for ESBL in other organisms which
may lead to more widespread dissemination of the problem in other species
before microbiological detection
- all ESBL producing organisms should be considered resistant to all
penicillins, cephalosporins and aztreonam. If the organism is sensitive to
ß-lactam/ß-lactamase inhibitor combinations it is suggested that the
organism is reported as being susceptible although use of these combinations
to treat patients is not ideal
Epidemiology
Prevalence
- probably underestimated. Significant proportion of laboratories do not
perform tests specifically designed to detect ESBLs
- increasing
- considerable geographical variation.
Risk factors
- central venous or arterial catheter, gastrostomy or jejunostomy tube,
urinary catheter
- emergency intra-abdominal surgery
- GI colonization
- prolonged ICU or hospital stay
- prior antibiotics (including 3rd generation cephalosporins)
- number and duration of antibiotics probably most important factors
- prior nursing home stay
- severity of illness
- mechanical ventilation
Treatment
- difficulty exacerbated by associated resistance to aminoglycosides and
trimethoprim-sulfamethoxazole as well as high frequency of co-existence of
fluoroquinolone resistance
- decreased susceptibility to 3rd and 4th generation cephalosporins seen in
vitro at higher innoculums associated with clinically significant
reductions in efficacy in vivo
- although cefamycins (cefoxitin and cefotetan) not hydrolyzed by
majority of ESBLs but are hydrolyzed by associated AmpC-type ß-lactamase
- similarly ß-lactam/ß-lactamase inhibitor combinations may not be
effective against organisms that produce AmpC-type ß-lactamase. In vivo studies
have yielded mixed results against ESBL-producing K. pneumoniae
- carbapenems are agents of choice
- highly stable against ß-lactamase hydrolysis
- emergence of carbapenemase-producing organisms is a potential problem
Infection control
- antibiotic selection pressure for resistance plasmid dissemination and
genetic mutation important in spread of resistance
- clonal strain transmission reported as primary mechanism for ESBL
outbreaks indicating that patient-to-patient spread is a significant problem
- contact precautions (gloves, gowns) important
- notification by institutions when transferring patients may help limit
spread (inter-hospital transfer of ESBL-producing organisms has been
described)
- restrict use of antibiotics, especially cephalosporins
Further reading
Patterson JE. Extended-spectrum beta-lactamases. Sem Respir
Crit Care Med, 2003;24(1):79-87
Rupp ME and Fey PD. Extended spectrum beta-lactamase (ESBL)-producing
Enterobacteriaceae. Considerations for diagnosis, prevention and drug treatment.
Drugs, 2003;63(4):353-65
Potential conflict of interest
The Dept of Anaesthesia & Intensive Care, The Chinese
University of Hong Kong received sponsorship for educational activities from
Merck Sharp & Dohme and AstraZeneca in 2002 and 2003
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