ESBL is an enzyme that is resistant to most beta-lactam antibiotics including penicillins, cephalosporins and monobactam aztreonam. ESBL-secreting bacterial infections are associated with poor treatment outcomes.
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Beta-lactamase is an enzyme that opens the beta-lactam ring, causing antibiotic inactivation. ESBL has different effects on the oxyimino-beta-lactam ring structure (ceftriaxone, cefotaxime and ceftazidime) but does not inactivate cephamycins (cefoxitin, cefotetan and cefmetazol) and carbapenems (imipenem, meropenem, doripenem and ertapenem).
Figure 1. Structure of the oxyimino-aminothiazolyl cephalosporin. The C=N-OR group makes the beta-lactam ring stable to beta-lactamase enzymes, but the above structure is not stable to ESBL.
ESBL is present on gram-negative bacteria, mainly Klebsiella pneumonia, Klebsiella oxytoca and Escherichia coli and some other bacteria such as Acinetobacter, Burkholderia, Citrobacter, Enterobacter, Morganella, Proteus, Pseudomonas, Salmonella, Serratia and Shigella spp.
2. Risk factors for infections caused by ESBL .-secreting bacteria
The gastrointestinal tract is a reservoir for ESBL-producing Enterobacteriaceae, and the presence of such bacteria is a risk factor for infection with ESBL-producing bacteria.
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Risk factors in the community |
Risk factors in hospital |
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Recurrent urinary tract infections |
Length of hospital stay |
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Previous use of antibiotics (especially cephalosporins and fluoroquinolones) |
Severe disease progression |
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Using corticosteroids |
Length of stay in the intensive care unit |
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History of hospitalization |
Intubation |
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Living in a nursing home |
Urinary catheterization and arterial catheterization |
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Old |
Previous use of antibiotics (especially cephalosporin antibiotics) |
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Diabetes |
Central venous catheter or arterial catheter |
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Background liver or kidney disease |
Open the stomach to the skin/open the jejunum to the skin |
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Skin feeding tubes |
Re-insertion of urinary catheter |
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Travel (especially in Asia or North Africa) |
Hemodialysis |
3. KYnew borntreatment ESBL .-secreting bacteria
3.1. Carbapenem antibiotics
Carbapenem is the antibiotic of choice in the treatment of invasive infections caused by ESBL-producing bacteria. Treatment of ESBL-secreting bacteria with carbapenem antibiotics often improves patient survival. There was no clear difference in the therapeutic effect between imipenem and meropenem. The choice of antibiotic is mainly based on the toxicity of the drug in the patient. Meropenem is preferred for use in epileptic patients or pregnant women because imipenem’s potential for CNS toxicity and safety have not been established in pregnant women. Meropenem is easily divided in dose in the case of patients with renal impairment or changes in renal function.
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Since Doripenem is a relatively new antibiotic, clinical data on its use in infections caused by ESBL-producing bacteria are limited, but overall efficacy is comparable to that of meropenem or imipenem.
Ertapenem has the advantage of once-daily dosing and good activity in vitro, and clinical data on the use of ertapenem are increasing. However, some ESBL-producing isolates are resistant to ertapenem and this resistance may occur during treatment.
3.2. Piperacillin/Tazobactam
The use of piperacillin-tazobactam is not recommended in the treatment of severe infections caused by ESBL-producing bacteria. However, piperacillin-tazobactam may be an effective and reasonable choice for urinary tract infections because urinary drug concentrations are much higher than plasma drug concentrations.
Although some ESBL-producing isolates had MICs within the sensitivity range for piperacillin-tazobactam, treatment of severe infections with piperacillin-tazobactam resulted in poorer clinical outcomes compared with the carbapenem group.
3.3. Other drugs
Cefepim can be effective in the treatment of ESBL-producing bacteria in cases of antibiotic-susceptible bacteria and when used in high doses (2g every 8 hours). Plazomicin remains active against ESBL-producing bacteria and is effective in the treatment of complicated urinary tract infections despite resistance to other aminoglycoside antibiotics. Ceftolozan-tazobactam, ceftazidim-avibactam and eravacycline are promising, but more clinical data are needed to determine the efficacy of these agents compared with carbapenems. Clinical evidence for the use of cephamycin is limited and its use is associated with the development of resistance. ESBL-producing bacteria are normally resistant to fluoroquinolone antibiotics.
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REFERENCES
1. https://www.uptodate.com/contents/extended-spectrum betalactamases?source=history_widget
2. https://www.uspharmacist.com/article/the-pharmacists-role-in-treating-extendedspectrum-betalactamase-infections
3. DMlivermore, (2018), Difining an extended-spectrum β-lactamase, Clinical Microbiology and Infection, 14 (1), pp. 3-10.
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