Phenotypic screening of ESBL producing Enterobacteriaceae is essential for understanding and proper management of the development of resistance mechanisms as well as very important for epidemiology purposes [13]. In Ethiopia various fragmented studies have been conducted on ESBL producing Enterobacteriaceae in different parts of the country [10–11]. The present study was conducted at National Clinical Bacteriology and Mycology reference laboratory which is the only laboratory that gives reference service for the country. The data we obtained from the study may indicate the level of ESBL burden and its impact on antimicrobial resistance management in the country.
In current findings, ESBL production was detected in different genera of Enterobacteriaceae with overall prevalence of 64.7% in the strains tested and Klebsiella sp and E. coli were among the majority in the strains. This finding is comparable to that was reported in Addis Ababa (57.7%) [14], in Pakistan (60%) [15] and reported from Nigeria (65%) [16].
However, the current result was higher than of the study findings reported from Jima Ethiopia (51%) [17] and of study conducted in Algeria (47.6%) [18] and lower than reported from a tertiary care hospital in Riyadh capital Saudi Arabia (72%) [19]. These indicate that the distribution of ESBL producing organisms vary from region to region and may be higher in certain geographic areas [20].
Regarding the clinical samples analyzed in this study, higher rate of ESBL producers were identified from blood samples with most common isolates being klebsiella sp followed by E. coli and Enterobacter sp. Similar findings have been reported from Bahirdar Ethiopia [21], Pakistan [22] and Iran [23] and showed these organisms as the major Gram negative bacteria responsible for bloodstream infections. The incidence of these organisms was particularly very high among pediatrics population with age group of ≤ 1 year. This finding was in agreement with studies in Ethiopia [24] and other counties [25]. This suggests that the risk of children in acquiring bloodstream infections is greater due to different factors. These included undeveloped in immune system in the young children, poor skin integrity, frequent visit to health care facility, and the parents’ socioeconomic status, poor hygiene practices and high incidence of delivery at home particularly in developing country[25]. High rate of the ESBL producing Eneterobacteriaceae were identified from elderly patients greater than 60-year-old group. This may be explained by the longer exposure of these individuals to extended spectrum cephalosporins drugs which has been well described as the age of the patients are one of the factors for antimicrobial resistance [26].
Bacteria characterized in present study showed varied degree of susceptibility with high level of resistance to all tested antimicrobial agents. These are especially very high level in ESBL positive organisms. In addition to their ability to hydrolyze the activity of common beta-lactams antimicrobial ages such as penicillins, cephalosporins and aztreonam, ESBLs producing organisms are also associated with resistance to other antimicrobial classes and as a result they manifest a multidrug resistance trait [27].
Based on the present findings, ESBL producing Enetrobacteriaceae showed high resistance rate to amoxicillin-clavulanate, the drug that are proved to inhibit the action of ESBL. This may be explained by production of chromosomal beta-lactamases (AmpC) with serine active sites which have the ability to hydrolyze cphalosporins and also resistant to beta-lactamases inhibitors including clavulanate, sulbactam and tazobactam [28].
In comparison to amoxicillin-clavulanate, piperacillin-tazobactam was relatively active against ESBL producing organisms in in present study. This was justified in study conducted by Drawz and Bonomo in that they indicated piperacillin in combination with beta-lactamases inhibitors was resistant to the hydrolysis of some plasmid mediated beta-lactamses as compared with amoxicillin or ampicillin combination with bata-lactamases inhibitors [29].
Fluoroquinolones such as ciprofloxacin and norfloxacin are used for treatment of various bacterial infections and are among the therapeutic options for infections caused by ESBL positive organisms [30]. The resistance rate of ESBL producing Enterobacteriaceae to fluoroquinolones is reported in different studies [31].These support our finding in which 75% and 92.5% of ESBL positive isolates were resistant to ciprofloxacin and norfloxacin, respectively as compared with 47.3% and 50.4% of resistance rates for non ESBL producers. This is described in that, plasmids encode ESBL genes also carry plasmid mediated quinolone resistance genes. As resistance plasmids with ESBLs encoding genes are transferred among different species of Enterobacteriaceae by conjugation, this helps for dissemination of plasmid mediated quinolones resistance genes in these group of organisms [32]. Moreover, plasmid mediated quinolones resistance genes facilitate the chromosome-encoded quinolones resistance. The chromosome-encoded quinolones resistance is the most known mechanisms of quinolones resistance due to chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) genes [33].
Plasmid-mediated quinolone resistance genes play also an important role in resistance to aminoglycosides [34]. This justify our study results in that the resistance rate of the ESBL positive isolates to aminoglycoside (gentamicin and tobramycin) was very high when comparing with non ESBL strains. There were also studies those identified the co-existence of as extended-spectrum beta-lactamase with qnr, aac(6′)-Ibcr genes and genes encoding 16S rRNA methylases in the same ESBLs-producing strain to mediate multidrug resistance [35–36].
Similarly, the resistance rates to trimethoprim-sulfamethoxazole in ESBLs-producing strains in this study were very high. This is not surprising among ESBL positive organisms and it was well described in various studies [37]. This indicates the coexistence of trimethoprim-sulfamethoxazole associated resistant genes such as sul1 and sul2 encoded on ESBL plasmids which facilitate the transmissions of the determinants [38].
ESBL positive isolates tested in this study showed relatively lower resistance to Nitrofurantoin, a relatively active agent against both ESBL positive and ESBL negative. Similar study results were reported from Kenya [39] and Brazil [40]. This may be due to low prescription of this drug by physicians and therefore, nitrofurantoin remains active for treatment of non-life-threatening urinary tract infections [39].
Carbapenems, such as imipenem, meropenem and ertapenem, are the most effective antibiotics for the treatment of infections caused by ESBL producing Enterobacteriaceae [41]. The rising in the prevalence of ESBL producing organisms directly associated with the increase in consumption of carbapenems led to the emergency of resistant organisms to this last generation antimicrobial agents which in turn limit the treatment option for infections caused by ESBL producing organisms [41]. In the current study, we reported high prevalence of carbapenems resistant in ESBL positive isolates. This may indicate that using carbapenems for treatment bacterial infections is widely spread in the country.