Part I: Antibiotic resistance - Local scenario
1.4 ESBL-producing Enterobacteriaceae
- ESBLs are enzymes capable of hydrolysing penicillin, first-, second- and third-generation (extended-spectrum) cephalosporins and aztreonam (except the cephamycins and carbapenems). Most ESBLs can be inhibited by ß-lactamase inhibitors such as clavulanic acid and tazobactam (41) (Table 1.7). TEM, SHV and CTX-M are the three most common families of ESBLs seen worldwide.
- In HK (Figure 1.2), >90% of strains with an ESBL phenotype produced CTX-M type enzymes (42–43). There is a high rate of resistance towards non-ß-lactam antibiotics, particularly fluoroquinolones, cotrimoxazole and aminoglycosides (42–43). The high rate of resistance to non-ß-lactam antibiotics therefore limits the choice for management of patients in outpatient setting.
- ESBL-producing Enterobacteriaceae has been considered to be a hospital pathogen in the past. However, community-onset infection has been described in different countries including HK in the recent years. Most of the patients presented with lower urinary tract infection, other presentations includes bacteraemia and intra-abdominal infection (44–47).
- Rectal colonisation with ESBL-producing Enterobacteriaceae has been increasingly seen in healthy individuals (48), and this has been postulated to be a risk factor for community-onset ESBL-producing Enterobacteriaceae infection. Food animals are a major reservoir of ESBL-producing E. coli (49–50).
- In HK, the burden of ESBL is highest among the elderly population, especially those aged 75 years and above (51).
- For two decades, ESBL-producing Enterobacteriaceae were considered to be clinically resistant to all cephalosporins. Accordingly, all laboratories are advised to edit the results for ceftazidime, ceftriaxone and cefepime to resistant, irrespective of the in vitro inhibition zone diameters or MIC values.
- Recently, the laboratory testing advisory bodies in the United States and Europe have revised their advice and argued that with the lowered cephalosporin breakpoints that both organisations now adopted, it is unnecessary to edit susceptibility categories if an ESBL is found (52–53). A group of international experts in this field considered such advice is misguided (54). Therefore it is prudent to continue to test for the presence of ESBLs directly and to avoid cephalosporins as treatment.
- In HK, if we apply the new ceftazidime breakpoint, three-quarters of the ESBL-producing isolates would be re-classified from resistant to susceptible to ceftazidime (55). Caution with this approach is necessary whilst clinical data are limited (54).
Figure 1.2 Burden for ESBL-producing E. coli bacteraemia in a regional hospital in HK. Incidence density, number of episodes per 100,000 patient days was used as an indicator (51). R square for fitted line = 0.89 (p<0.001)
Table 1.7 Characteristics of ESBL and AmpC ß-lactamases
|Bush-Jacoby-Medeiro functional class||2be||1|
|Ambler molecular classification||A||C|
|Plasmid mediated||Almost always (responsible for the spread)||Most are chromosomal plasmid increasingly reported|
|ß-lactamase inhibitor||Inhibited||Not inhibited|
|Carbapenem||Not hydrolysed||Not hydrolysed|
|Examples||TEM, SHV and CTX-M||Enterobacter, Citrobacter and Serratia possess inducible AmpC
ß-lactamase encoded in their chromosomes