Escherichia coli is a common opportunistic pathogen in nosocomial infections. Increasing use of beta-lactam antibiotics has led to antibiotic resistance in this bacterium, which is usually due to the production of beta-lactamase enzymes. The production of beta-lactamase enzyme in bacteria, especially in Escherichia coli, has caused many problems for the treatment of patients.
Organisms that carry these genes increase morbidity and mortality among individuals, which will pose a serious threat to society as the growing trend of resistance develops. (10).
In all efforts to reduce antibiotic resistance, three main factors should be considered, namely the timely identification of isolates producing beta-lactamase and broad-spectrum enzymes, appropriate treatment measures.
Arbitrary, improper, and excessive use of antibiotics in medicine has caused resistant strains. In the present study, Escherichia coli 100 isolates collected from patients with urinary tract infections. Out of 100 isolates, 53% had ESBLs and 19% had MBL.
77% of isolates contained TEM gene and 23% contained Ampc gene and 38% contained KPC gene. 15% of isolates contained both TEM and Ampc genes, 15% of isolates contained both TEM and KPC genes, and 15% of isolates contained all three TEM, Amp, and KPC genes.
21% of isolates contained IND gene, 21%of isolates contained GIM gene and 37% of isolates contained SIM gene. 11% of isolates contained both GIM and SIM genes and 11%of isolates contained all three genes IND, GIM, and SIM.
According to the results of the present study, the highest and lowest antibiotic resistance was observed against cefotaxime (52%), ceftazidime (27%), and imipenem (2%), respectively.
In a study conducted by Mobasher and colleagues in Tabriz, it was found that out of 41 isolates of Escherichia coli, 98% reported the isolates as ESBL (11).
In the study of Manouchehri et al. In 1994, 200 urine samples were collected from the infectious and nephrology wards of Razi hospitals in Ghaemshahr and Imam Khomeini hospitals in Sari, and only 120 Escherichia coli isolates were isolated. Of these, 55% were broad-spectrum beta-lactamase-producing strains. The prevalence of antibiotic resistance is very high compared to the present study.
In a 2013 study by Mahmoud Asaf Habib in Pakistan, he noted an increase in ESBL in Escherichia coli from 34% in 2005 to 60% in 2009, with resistance to cefotaxime and ceftazidime above 85%, especially in urine samples. The increase is significant and has increased from 10–65%. (12) The study of Manouchehri and Asf Habib is in line with our study in terms of the frequency of isolated ESBLs. But in terms of resistance to cefotaxime and ceftazidime antibiotics, they show high resistance compared to the present study.
In a study conducted by Shahcheraghi in 2007, 45% of ESBL positive samples were resistant to cefotaxime and 48% to ceftazidime (13). In the study of Mashouf et al. In 2013, resistance to ciprofloxacin 17% and imipenem 0%: was reported (14).
In a 2005 study by Kadder et al. sensitivity to imipenem antibiotics was 92% and ciprofloxacin was 59% (15).
In a study conducted between March 2012 and December 2012 at Al-Zahra Hospital in Isfahan by Reza Moayedtia et al., Escherichia coli isolates 0.3% contained MBL (16).
The frequency of MBL genes in the study of Lozaro et al. was reported to be 0.7%. (17). In a study conducted in 2011 by Sara Abdollahi Khairabadi, et al. 87% were identified as sensitive to imipenem (18).
In a study conducted between 2009 and 2011 by Fereshteh Shahcheraghi et al. In Tehran, out of 244 isolates of Escherichia coli, 9 isolates (4%) to meropenem, 1 isolate (0.4%) to imipenem, two isolates (0.8%) were reported to be resistant ertapenem (19). In a study conducted between March 2012 and December 2012 in Al-Zahra Hospital in Isfahan by Moayednia et al., 1% were reported to be resistant to imipenem (20).
The prevalence of antibiotic resistance of imipenem in our studies and others is almost equal. According to similar studies with the present studies, the prevalence of isolated ESBLs and antibiotic resistance of cefotaxime and ceftazidime in Escherichia coli is increasing. They are important in infections. They require strict therapeutic supervision in the use of antibiotics. The frequency of MBL isolates in our study compared to other studies indicates an increase in the prevalence, which is very worrying in the antibiotic treatment of Escherichia coli infection.
In the study of Yazdi et al. In 1989, out of 246 isolates studied, 47% were ceftazidime resistant isolates and 39% were cefotaxime resistant isolates. Also, 44% of isolates were ESBL. The blaTEM gene was found in 87% of ESBL isolates (21). Mohammad Mehdi Sultan Dalal in 2010 showed that out of 200 Escherichia coli isolates, 64% were ESBL, of which 58% contained TEM gene (22). In 2007 in Valiasr Hospital of Tehran, among 76 clinical samples of E. coli, 60% of isolates contained TEM gene (23). Masjedian showed that out of 148 strains E.coli 85% of the isolates contained the TEM gene (24). In a study by Mir Salehian, it was found that out of 33 isolates of Escherichia coli, 39% of the isolates contained beta-lactamase TEM gene (25).
Similar studies in Turkey showed that 53% of Escherichia coli isolates had the TEM plasmid (26).
Comparison of the results of the present study with the other studies indicates the high prevalence of beta-lactamase genes, especially TEM type in Escherichia coli isolates, so it is necessary to identify this type of resistance using molecular methods along with phenotypic methods. In the study of Dokht Shamstalab et al. in 1995, 100 clinical isolates of Escherichia coli were collected from hospitals in Kermanshah. After further examination of these 44 isolates by multiplex PCR, it was determined that 44% of them had the AmpC beta-lactamase gene.
In a 2010 study of 909 gram-negative bacteria by Manoharan et al. in India, 312 isolates were resistant to cefoxitin and used the combined disk method for phenotypic confirmation, which considered 36% AmpC producer. After PCR, 42% had the AmpC gene (27). In 2012, Tanja et al. conducted a study on 100 Escherichia coli isolates in India, which showed that 59 AmpC-producing isolates were considered to have 57% AmpC gene after PCR (28).
In 2013, Hackman and colleagues tested 400 isolates of the bacterium in the country, 50 of which were resistant to cefoxitin. Of the 50 cefoxitin-resistant isolates, 10% produced AmpC beta-lactamase, meaning that only 1% of the 400 isolates produced AmpC beta-lactamase (29).
The differences between the results of this study and other studies may be due to differences in the geographical area and genetics of individuals, differences in bacterial strains, as well as differences in the type of antibiotics prescribed or how they are used.
In the researches of Soltan Dallal et al and Mansouri (30) which were performed on Escherichia coli isolates in Tehran in 2010 and 2007, the prevalence of AmpC genes was 3% and 6%, respectively. It was reported that their results are significantly different from the present study and it can be concluded that the prevalence of resistance genes in these bacteria is increasing over the years and this issue should be further investigated. In addition to the difference in the geographical area, the reason is that doctors mistakenly prescribe patients with arbitrary and unprincipled consumption or other reasons.
ESBLs genes are associated with the development of multiple resistances to other antibiotics, so that the occurrence and spread of various antibiotic genes, especially as multidrug, due to the increased resistance of ESBLs, has created many problems for the treatment of infections caused by them. According to our research and others, this increase in ESBL-producing strains is worrying and the need for the annual review of such research will change the treatment aid of patients and the treatment strategy in hospitals.
Based on the results of this study and other studies, it seems that the widespread and uncontrolled use of broad-spectrum beta-lactam antibiotics and transmission by hospital staff and patient-to-patient transmission has led to an increasing number of ESBL-producing strains in the community. Extensive use of beta-lactam antibiotics, especially cephalosporins, has increased the prevalence of broad-spectrum beta-lactamase (ESBL) enzymes in Escherichia coli. It is effective in treating resistant infections and preventing the increase of antibiotic resistance, as well as performing antibiogram tests before prescribing antibiotics to prevent the indiscriminate use of beta-lactam antibiotics.
In a study conducted by Tawfik Abd Motaleb from 2011 to 2012 on 105 isolates containing metallo-beta-lactamase isolated from the ICU of Shams Teaching Hospital. Eleven isolates belonged to Escherichia coli: 1 isolate (9%) contained blaGIM and 2 isolates (18%) contained bla SIM (31).
In a 2013 study of 230 clinical isolates from 2007 to 2011, 50 clinical isolates including Pseudomonas spp., Enterobacteriaceae (Enterobacter cloacae), Klebsiella oxytoca, Serratia marcescens, Escherichia coli were positive for the blaGIM-1 gene. Of these, only one Escherichia coli isolate isolated from blood culture had the blaGIM-1 gene (32).
A 2019 study was performed on 88 patients with sepsis. E. coli isolates were detected by gram staining and biochemically. The polymerase chain reaction was performed for E. coli genes producing ESBL and carbapenemase. Of 88 patients with sepsis, 49 and 30 strains had ESBL and carbapenemase. Of 30 carbapenemase-producing genes in E. coli had 2 isolates (7%) bla SIM and 1 isolate (3%) blaGIM and no isolates were bla KPC and 2 isolates (7%) had both bla SIM and blaGIM genes (33).
There are few studies about the prevalence of IND GIM, SIM, the gene in Escherichia coli. However, these studies show that these genes are more prevalent in Escherichia coli. Infection control measures are needed, including management of antibiotic use and rapid identification of resistant isolates. The genes encoding MBLs are located on class I integrons and transmissible plasmids; therefore, the study of these enzymes is essential to rapidly identify resistant strains to prevent their spread.
The frequency of different prevalence is probably due to differences in the type of clinical isolates, geographical location according to the results of the present study, and comparison with other similar studies. The frequency and prevalence of antibiotic resistance are different according to geographical areas, so maybe this is the reason for the differences between the results of this study and the other studies. The differences between the results of this study and other studies are evidence of differences in the frequency and prevalence of antibiotic resistance between different countries, different hospitals and hospital wards, and even between individuals. It can be related to the rate of antibiotic use in these areas, the emergence of different mechanisms of resistance, the selection, and spread of resistant clones under antibiotic use. Perhaps this is another reason for such studies to be a model identify the resistance of each region and hospital, and in line with that, the methods of infection control and prevention of the spread of resistance and, most importantly, help in choosing appropriate treatment methods to rid patients of infections caused by this important and highly resistant "Escherichia coli" pathogen (34–36).