feature of these strains is that they carry specific genes that enable them to produce enzymes that destroy a large number of common antibiotics, making the infection they
cause very difficult to treat. In many instances, only two oral and a very limited group of intravenous antibiotics remain effective. ESBL-producing strains E coli were first noted in
2003 when East and West Midlands region of England reported.
E. coli as the constant influx of community isolates colonizing patients at hospital admission is highly significant in the epidemiology of these organisms within hospitals,
understanding the complex epidemiological behavior of E. coli in the community is a key to adequate interpretation of studies addressing the epidemiology of E. coli in hospitalized
patients. The extra-intestinal pathogenic strain are the predominant strains in 20 of individual and harbor the typical virulence factors causing extra-intestinal infections when
reaching the appropriate site from the bowel, which serve as their primary reservoir. Transmission of extra-intestinal pathogenic E. coli in the community is thought to occur by
person to person transmission, either through direct contact or by means of faecal-oral route through or by contaminated food andor water. Johnson JR et al. 2010
2.3. Klebsiella species
There have been several rescent studies of the epidemiology of K. pneumonia as a nosocomial pathogen. Cross-transmission via H
CWs‟hands seems to be important in the nosocomial spread of K pneumonia strains. However in a recent study, an outbreak
caused by contaminated food was described, indicating that transmission may also occur via the food chain.
2.4. Detection
The clinical laboratory acts as an early warning system, alerting the medical community to new resistance mechanism present in clinically important bacteria. The methods for
detection of ESBLs can be broadly devided into two groups: phenotypic methods that use non-molecular techniques, which detect the ability of the ESBL enzymes to hydrolyse
different cephalosporins and genotypic method, which use molecular techniques to detect the gene responsible for the production of the ESBL. Clinical diagnostic laboratories use
mostly phenotypic methods because these tests are easy to do, are cost effective and have been incorporated in most automated susceptibility systems, making them widely
accessible.
2.5. Treatment
This multiple drug resistance has major implications for the selection of adequate empirical therapy regimens. Empirical therapy is prescribed at the time when an infection is clinically
diagnosed, while the results of cultures and antimicrobial susceptibility profiles are awaited. Multiple studies in a wide range settings, clinical syndromes, and organisms have
shown that failure or delay in adequate therapy results in an adverse mortality outcome, which is also true of infections cause by ESBL-producing bacteria. A major challenge
when selecting an empirical regimen is to choose an agent that has adequate activity against the infecting organisms. Empirical antibiotic choices should be individualized
based on institutional antibiograms, which tend to be quite different from hospital to hospital, from city to city, and from country to country. Pitout J.D., et al. 2008
The next issue surrounding the therapy of ESBL-producing infections is that even if an agent is selected that has activity against the bacteria in vitro, clinical efficacy in patients is
not always guaranteed. Although in vitro tests ESBLs are inhibited by ß-lactamase inhibitors such as clavulanic acid, other study has shown the activity of ß-lactamß-
lactamase inhibitor combination agent e.g. piperacillin-tazobactam is influenced by the bacterial inoculums, dose administration regimen and specific type of ESBL present. The
other consideration treatment of ESBL-producing bacteria are cephamycins e.g. cefoxitin, cefotetan and Cefepime. This is widely believe to occur as a result of the so-called
inoculums effect that occurs when the minimum inhibitory concentration of the antibiotic rises i.e. the antibiotic looses activity with the increasing size of the inoculums or
number of bacteria tested. This effect has been described for cephalosporins,
β-lactam-β lactamase inhibitor combinations piperacillin, tazobactam and to a lesser extent with the
quinolones. Tigecycline is also one of the drugs in the pipeline which can be considered for treatment. Pitout J.D., et al. 2008; Perez et al. 2007
The carbapenems imipenem, meropenem, ertapenem, doripenem are still the first choice of treatment for serious infections with ESBL-producing E coli and K pneumonia. It
has been reported that 98 of the ESBL-producing E coli, K pneumonia and P. mirabilis are still susceptible to these drugs. This agents are highly stable to hydrolysis by ESBLs,
are distributed into body tissues in high concentration and there is no inoculums effect. Perez et al, 2007; Pitout J.D., et al. 2008. But with the emergence of the carbapenem
– resistant Enterobateriaceae, the “magic bullet” is actually difficult to find. There are some
older drugs which can be used to treat the ESBL-producing E. coli or K. pneumonia infections. Fosfomycin was reported of having admirable in vitro activity against the ESBL-
producing E. coli or K. pneumonia. In HongKong, most of the ESBL-producing E coli isolates were reported to be sensitive to fosfomycin. Ho et al., 2010. Colistin is another
choice which we can consider for the treatment of these organisms. Although once considered as quite a toxic antibiotic, it is a last resort that we can consider at the present
moment as there is no new anti gram negative antibiotics available for the treatment of these multidrug resistant organisms. Perz et al. 2007
To reduced the problem of antimicrobial resistance, action should be taken along to tracks; promotion of prudent use of antibiotics and prevention of the spread of resistant bacteria.
Improving antibiotic use can be achieved by changing the prescribing behavior of doctors, education, guideline and clinical pathway, antimicrobial cycling, antimicrobial order form,
combination therapy streamlining or de-escalation, dose optimization, intravenous or oral therapy.
