healthmedicinet

This study was aimed to investigate ESBL-producing E. coli among Enterobacteriaceae isolates and sensitivity pattern of isolates toward various
chemotherapeutic agents. Organisms producing ESBLs are clinically relevant and remain
an important cause of failure of therapy with cephalosporins. ESBLs are primarily
produced by the Enterobacteriaceae family, in particular K. pneumoniae and E. coli. Bacteria harbouring ESBLs may also acquire and most often exhibit additional resistances
to other antimicrobial classes such as the quinolones, tetracyclines, cotrimoxazole,
trimethoprim, and aminoglycosides, which further limits therapeutic options and thus
pose a therapeutic dilemma 13].

Significant growth was obtained in 31.33 % urine culture samples. The majority of
urine specimens showed no growth (68.67 %). The possible cause of low rate of growth
positivity might be due to urine samples obtained from patients on antibiotics therapy,
infection due to slow growing organisms or due to those organisms that were not able
to grow on the routine media used 1], 14]. Number of female patients requesting for urine culture was higher than the male
patients. Significant microbial growth was higher in case of female than in male.
Urethral opening in females, short urethra and complicated physiology especially during
pregnancy can be considered as reason 15]. Female patients requesting for urine culture was higher, than the male patients,
in age group of 21–40 years this may be because this age group consists sexually active
women. Frequent or recent sexual activity is the most important risk factor for UTIs
in young women. Nearly 80 % of all UTIs in premenopausal women occur within 24 h of
intercourse. UTIs are very rare in celibate women. Certain types of contraceptives
can also increase the risk of UTIs 16].

Numbers of gram negative organisms isolated were much higher than the gram positive.
Similar predominance of gram negative organism in urine sample has been observed by
other researchers too 17], 18]. Staphylococcus aureus, Coagulase-negative staphylococci (CoNS) and Enterococcus spp. were the gram positive organisms isolated. E. coli, Klebsiella spp., Proteus spp., Citrobacter spp., Pseudomonas spp. and Neisseria spp. were the gram negative organisms isolated. Among the gram negative organisms,
Enterobacteriaceae were most frequent, 95 out of 100 gram negative organisms. Members
of Enterobacteriaceae are more likely to cause UTIs than other organisms. In various
studies predominant organisms isolated in UTI cases is Enterobacteriaceae 17], 19], 20].

Antibiotic susceptibility pattern shown by the Enterobacteriaceae isolates were variable.
Imipenem was the most effective antibiotic as 92.63 % of isolates were susceptible,
followed by amikacin (82.11 %). Isolates were comparatively less susceptible to cephalosporins
than other antibiotics. Resistance to ?-lactams in Enterobacteriaceae is mainly due
to the production of ?-lactamases, which may be encoded either chromosomally or on
plasmids 4]. Out of 14 antibiotics used, 11 were found effective to only less than half of the
isolates. Majority (96.84 %) of Enterobacteriaceae isolates were found to be MDR.
Thakur et al. 21] has observed 64.04 % MDR Enterobacteriaceae and 73.68 % MDR E. coli isolates. The widespread use of antibiotics could be associated with the selection
of antibiotic resistance mechanisms in pathogenic and non pathogenic isolates of E. coli22]. MDR isolates were more in females than in males and common in age group ??61 years.

Over the past few years, the prevalence of ESBL producing strains among clinical isolates
varies greatly with different geographic regions and rapidly changing over time 23]. In this study, phenotypically 18 (26.87 %) isolates were confirmed as ESBL producers
E. coli isolates. ESBL positive E. coli was distributed equally among male and female. Highest number of ESBL producers E. coli was obtained from the patients of age above 60 years. Other studies have also shown
that ESBL isolates are encountered more frequently in the elderly, according to Roshan
et al. 24], Shah et al. 25] and Rajan and Prabavathy 26] majority of isolates were from patients between 40 to 70 years, 50 to 60 years and
51 to 70 years respectively. The ESBLs-producing E. coli were most frequent in older age group in this study; it can be due to the reason
that older patients are immunocompromised and more prone to infections by resistant
organisms 27]. Nosocomial infections caused by ESBL producing pathogens are associated with risk
factors such as elderly age, prolonged hospitalization, previous antibiotic use, and
presence of invasive devices 28].

All ESBL positive E. coli strains were resistant to cefotaxime, ceftazidime and ceftriaxone. This outcome is
in agreement with the study done by Islam et al. 29]. Similarly all E. coli isolates were resistant to cefotaxime and ceftriaxone in a study by Sompolinsky et
al. 30] and to ceftazidime and ceftriaxone in a study by Chander and Shrestha 6]. High percentage of resistance to cefotaxime (99.2 %), ceftazidime (99.2 %) and ceftriaxone
(99.5 %) was observed by Wani et al. 31]. ESBL positive isolates also showed high degree of resistance to other antibiotics
like cefalexin, norfloxacin, cefixime, nalidixic acid, ciprofloxacin and ofloxacin.
Aminoglycosides have good activity against clinically important gram negative bacilli
32]. Aminoglycosides are very important group of antibiotics with activity against many
gram-negative rods and the most common mechanism of aminoglycoside resistance is enzymatic
modification of antibiotic molecule. All ESBL positive isolates were sensitive to
the amikacin (100 %) followed by imipenem (94.44 %) and nitrofurantoin (72.22 %).
Antimicrobial resistance surveillance done Nepal Public Health Laboratory (NPHL) found
that ESBL E. coli were susceptible to imipenem (98.5 %), amikacin (96.1 %) followed by nitrofurantoin
(89.2 %) and chloramphenicol (90.8 %) 33]. Amikacin and nitrofurantoin can therefore be used effectively against ESBL producing
isolates but these antibiotics have many limitations. High percentage of isolates
were susceptible to the carbapenem. The study done by Kader and Angamuthu 34] revealed more than 89 % of the ESBL producers were susceptible to imipenem and meropenem,
whereas Mekki et al. 35] found 100 % isolates sensitive to the carbapenems. The production of ?-lactamase
may be of chromosomal or plasmid origin 4], 36]. Plasmid mediated production is often acquired by transfer of genetic information
from one organism to another. Such transferable plasmid also codes for resistant determinants
to antimicrobial agents other than ?-lactams 37]. Hence multidrug resistance is expected to be more common in ESBL producing organisms.

The production of ESBL pathogens like E. coli has an important clinical importance. It has been well recognized that poor outcome
occurs when patients with serious infections due to ESBL-producing organisms are treated
with antibiotics like cephalosporins and penicillins to which the organisms are resistant.
The mortality rate in such patients is significantly higher than in patients treated
with antibiotics to which the organism is susceptible. All patients with antibiotics
failure either die or have continued sign of infections, which necessitates change
in antibiotic 38]. Microbiology laboratories can play an important role in detecting and promptly reporting
the isolation of ESBL-positive bacteria, since drug susceptibility data are important
for the clinical management of patients infected by these organisms 39]. Clinicians, whose laboratories do not perform tests for detection of ESBLs, and
report ESBL producers as resistant to cephalosporins, risk poor outcome for their
patients infected with ESBL producing organisms. The detection of ESBLs in any clinical
isolate has great potential significance from the point of view of infection control
38].

This study also has some limitations; the study was carried out in a hospital. The
picture of the study does not necessarily reveal the picture of the whole country,
therefore systematic prospective surveillance should be carried covering wide geographical
region in order to obtain information on seasonal, geographical and ethnic variation
of pathogens and their antibiotic susceptibility profile. Moreover, characterization
of ESBL strains should be performed genotypically, so that the information can be
used in fighting with increasing resistance to antimicrobials.