Extended-Spectrum Beta-Lactamase (ESBL) in Bacteria

This assignment delves into the growing concern of Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae. It examines various aspects, including epidemiological factors associated with ESBL infections, genetic mechanisms behind ESBL production, and strategies to combat their spread. The provided research papers shed light on CTX-M enzymes, trends in ESBL prevalence, and the resurgence of old antibiotics as potential solutions. This comprehensive analysis aims to understand the complexities surrounding ESBL resistance and its implications for public health.

0Escherichia coli that produces Extended Spectrum β lactamases
Escherichia coli that produces Extended Spectrum β lactamases
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1Escherichia coli that produces Extended Spectrum β lactamases
Table of contents
History and importance of Escheria coli.........................................................................................3
Evolution of Ecoli............................................................................................................................4
Taxonomy and classification...........................................................................................................5
Characteristics of E. coli..................................................................................................................5
Natural Habitats...............................................................................................................................6
E. coli genome.................................................................................................................................7
Pathogenesis....................................................................................................................................8
Virulentfactors.................................................................................................................................8
Epidemiology of E. coli.................................................................................................................10
Treatment of E. coli.......................................................................................................................12
Sources of E.coli............................................................................................................................13
β lactam antibiotics........................................................................................................................13
Resistance of βlactam antibiotics...................................................................................................15
β lactamase.....................................................................................................................................17
Extended spectrum βlactamase [ESBLs].......................................................................................18
The Plasmids gene transfer............................................................................................................20
ESBL –E. coli infection.................................................................................................................20
Treatment of E. coli that produces ESBLEs..................................................................................22
Risk factors....................................................................................................................................23
Individuals mostly at risk...............................................................................................................23
Epidemiology of ESBL E. coli......................................................................................................25
Conclusion.....................................................................................................................................28

2Escherichia coli that produces Extended Spectrum β lactamases
History and importance of Escheria coli.
The study of microbes in the infant gut began in 1884 by a German paediatrician and
scientist known as Theodor Escherich; he discovered a fastidious bacterium, Bacteria coli
commune, while conducting his studies. The bacteria are presently Escheria coli[2]. In his 1885
publication, Theodor Escherich reported for the first time, bacterial characterization and
isolation of thin short rods in infants and named them “Bacteria coli commune.” Escheria coli
were fully recognized 125 years later in 1954 after description by several names and synonyms
[8].
The first harmful strain of E. coli was discovered in 1982 by scientists at the Disease
Control and Prevention. The bacteria caused diarrhea, chronic illnesses and death. The E.
coli,0157:H7 produces powerful toxins that cause severe illnesses in humans. Furthermore, it is
resistant to antibiotics [1, 17]. The bacteria were previously detected in the United States. A large
outbreak of the bacterial disease was witnessed in Wales and England in 1983. Many people
contracted the disease and visited hospitals for treatment and the doctors diagnosed patients by
observing symptoms and conducting tests to ascertain the origin of the disease [7].
After a close examination of the genetic and biochemical characteristics of the bacteria
evolution of the bacteria was proposed. In phylogenetics, E coli O157:H7 was determined to
have evolved from E. coli ancestors of serotype 055:H7 [1]. Scientists such as Bordet and
Werkman (1927) performed early studies on viruses, bacterial physiology and genetics and
established it as good lab organism to work with. This started molecular biology revolution of
the 1950s. Moreover, E. coli was the organism with the most appropriate life aspects for instance
transcription, genetic code, replication and translation [2].

3Escherichia coli that produces Extended Spectrum β lactamases
E. coli was beneficial in studies involving biochemistry, genetics and pathway
inferences; it facilitated well studied topics such as genomics. These studies formed the basis for
E. coli studies for example bio-fuel engineering, production of chemicals, recombinant protein
expression, binary fission, DNA replication and clinically relevant strains. The molecular
methods and knowledge of manipulation and investigating E. coli biology have facilitated the
prominence of E. coli in fields of academics, pharmaceutical production, academics and biotech
companies .Therefore, E. coli is the most important model organism in biology [2, 7].
Evolution of Ecoli
The use of E. coli in biology is attributed to its availability. Fastidious hardy, non
pathogenic and versatile strains can be easily isolated from humans.These characteristics made it
the most appropriate model in microbiology teaching and it was the most appropriate model
organism for early 20th century microbiologists [2]. Some rare mutations can be attributed to this
prolonged and unique evolution in function. Moreover, an ordinary mutation with phenotypic
expression or physical occurrence might have happened to early mutation of the population [3].
Taxonomy and classification
Enterobacteriaceae is an important family in human medicine, it has genera and species
that cause nosocomial infections and well known diseases. The family has rod shaped, non
sporulating, Gram negative bacteria which ferments glucose [26]. The first report on Escheria
genus was published by Theodore Escherich in 1886, in his dissertation at the University of
Munich. Castellani and Chalmers later proposed the name E. coli in honour of Theodor
Escherich. The name was adopted by the Botanical Commission in 1958. Furthermore, it was
listed as bacterial name in 1980 [6].

4Escherichia coli that produces Extended Spectrum β lactamases
Lipo- polysaccharides and flagellar antigens define the serotype and groups of pathogenic
E. coli [6, 12]. The Multilocus Sequencing Typing (MLST) is a commonly used method in
typing E. coli that is pathogenic. Furthermore, it establishes relationships of the strains. House
keeping genes are assigned to a distinct allele after sequencing. The profile of these alleles give a
sequencing type to an isolate. Furthermore, the types of sequence are organized into clonal
complexes based on their similarities. Therefore, genetic typing in high resolution is needed to
provide more insight on evolutionary relationships [8].
Characteristics of E. coli.
It a rod shaped, bacillus and Gram negative bacteria. Its size varies depending on the
bacterial strain and conditions and it is a facultative anaerobe. The bacteria can either be motile
or non-motile because of the flagella or pilli [2, 28]. Furthermore, it grows both aerobically and
anaerobically at temperatures of 10 0 C and 45 0 C and a pH range of 5.5 – 8.0. Nevertheless, it
cannot grow in extreme temperatures or ph. It produces gases that ferment lactose, glucose and
other carbohydrates [28]. E. coli has a relationship with Salmonella, Serratia, Yersinia Pestis and
Klebsiella pathogens [2, 28].
Natural Habitats
E. coli is the most studied microorganism due to its versatility, hardiness and broad
palate. Moreover, it has a complex multifaceted niche. Wild E. coli studies have provided a lot of
information regarding its habitat in the natural world, genomic evolution and its role in human
pathogenicity. These findings have elaborated its biological ecology that had many unanswered
questions hence illustrating how appreciation of the natural history of E. coli has expanded its
value as a model organism [2].

5Escherichia coli that produces Extended Spectrum β lactamases
Most Enterobacteriaceae are gastrointestinal flora though many are wide spread in the
environment [26]. E. coli’s habitat is the mammalian gut. Furthermore, it can be located in the
gut of birds, fish and reptiles [2, 26]. Furthermore, it is the most common species of facultative
anaerobes. Its important habitat is the human intestine [9]. It is found in faecal flora of healthy
adults and it is harmless [1, 9]. It plays an important role in digestion as it absorbs vitamin in
foods. Furthermore, it prevents the growth of other harmful microorganisms [1].
E. coli population has short-term transients and strains that reside on the long term, which
vary in diet, health and antibiotic exposure. Interaction with other microbes also determines
population and vast host viromes to defend itself against restriction enzymes. This has become a
significant approach to molecular biology [2].
E. coli genome.
The size of E. coli genome vary in size by a million base pairs between extra genetic
elements, pathogenic variants and commensals. The genome is divided into a set of divided
genes called the core genome, which is created by the genetic loss and gain of material in
genome hotspots in the genome [8]. Virulent pathotypes have larger genomes as compared to
non- pathogenic E. coli. Furthermore, virulence factors encoded in plasmids, chromosomes and
bacteriophages are also present.
Virulent pathotypes of E.coli have larger genomes than nonpathogenic pathotypes.
Furthermore, virulent factors are always encoded in plasmids, chromosomes and
bacteriophages[13]. The public health sector faces challenges from the extended spectrum beta
lactamases ESBLs. ESBLs spread through bacteria producing clones, plasmids that carry genes

6Escherichia coli that produces Extended Spectrum β lactamases
or mobile elements. Therefore, identification of transmission routes and bacterial sources is not
easy [13, 46].
The common clusters size of isolates was reduced when E. coli definition included
ESBLs types, phylogenetic grouping and antimicrobial susceptibility data. Nonetheless,
quantities of similar subtypes were found in livestock isolates, study animals and human.
Therefore, indicating a bacterial exchange of genes in the populations.Moreover, the result
showed a correlation between properties of bacterial isolates and ESBL genes in different
populations. This method examines clusters specific to the populationwhich can be used to select
ESBL producing isolates from clusters for a detailed characterization [46].
Pathogenesis.
E. coli is a gastrointestinal organism that is harmless and it is ever used in the laboratory.
However, an alternative side of E.coli describes it as a highly adapted pathogen.It is virulent and
it tolerates dry conditions. Furthermore, it can be fatal by causing kidney or brain damage and
few strains can cause illnesses. Pathogenic E.coli cause a wide array of infections in various
body sites such as the nervous system or the blood stream. The pathogen mostly affects young
ones below five years and older people.
Its environmental presenceis of importance because it causes diarrheal infections,
peritonitis, colitis, bacteremia, infant mortalityand urinary tract infectionsin humans.These
diseasesare costly. Furthermore, some strains cause cancer.Opportunistic infections are
associated with the beneficial or harmless strains when inoculated in a sick host or another part
of the body apart from the gastrointestinal tract. Moreover, pathogenic strains are classified
according to how and where they cause diseases and they are grouped into pathotypes

7Escherichia coli that produces Extended Spectrum β lactamases
enteroaggregative E.coli, enterohaemorragic E.coli, enteropathogenic E.coli, enterotoxigenic
E.coli and meningitis associated E.coli [2].
E coli has a reservoir in the gastrointestinal tract of cattle.It enters the food chain through
cattle since it is a food borne pathogen.Furthermore, it is a harmful life threatening human
pathogen that causes gastro intestinal illnesses in humans [2].
Virulentfactors.
Each E. coli that is virulent shares virulent strategies with another one. All pathovars
attach to host cells except EIEC which achieves this by long appendages called fimbriae. It stops
cell processes of the host using secreted proteins. Furthermore, it hijacks the host cell, grows
within it, hence affecting the signaling pathway of the host. Therefore, cell invasion is facilitated
Moreover, it evades the host cell immune system and colonizes the cell hence disease
occurs.Each pathovar has its own mechanism of entry into ahost cell despite the fact that they
target similar host machinery [7].
Recently, main interactions between virulent factors and host proteins have resulted in
the understanding of how they contribute to diseases.Verocytotoxins or Shiga-like toxins are
produced by this serotype and some non O- 157 serotypes of E. coli .These toxins resemble those
produced by the Shigella dysenteriaceae.The symptoms produced by these toxins lead to names
such as VTEC (Veroxytotoxin-producing E.coli), STEC (Shiga toxin producing E.coli), and
EHEC(enterohemmorrhagicE.coli)[7].

8Escherichia coli that produces Extended Spectrum β lactamases
E. coli diseases.
E.coli is a harmless organism before it acquires a combination of mobile genetic elements
that makes it a highly virulent pathogen. It then causes a wide range of diseases from the
gastrointestinal tract to the central nervous system. The disease burden in the world is extreme as
it kills hundreds of people annually. Eight pathovars have been determined to cause diseases and
they use several virulence factors to destroy the host cell mechanism and initiate virulence.
E. coli is one of the leading cause of urinary tract infections in humans that can progress
to more serious blood poisoning which is life threatening[12].ESBLs producing E.coliare
commonly associated with urinary tract infections (UTI) rather than food poisoning[12].
Furthermore, they causediverse intestinal and extra intestinal diseases by virulence factors that
affect cellular process[5].
Some E. colihave been identified in animal and human diseases. Studies have identified
eight pathovars up to date which can be divided into diarrhea genic and extra intestinal
pathovars. Six diarrheagenicpathovars include enteropathogenic,
enterohaemorrhagic,enterotoxigenicand diffusely inherent E. coli. Two extraintestinalpathovars
include neonatal meningitis and uropathogenicpathovars. Other pathovars lack a well-defined
mechanism of pathogenesis [5].
Several toxin producing E. coli are present and they cause diarrhea, but most of these
cause the onset UTI infections in women and adolescents.Meningitis, septicaemia, pneumonia,
intraabdominal, and gynaecologcalinfections are also caused by infection.The UK Protection
Agency in 2003, reported that E. coli that produces ESBL was causing diseases. The most

9Escherichia coli that produces Extended Spectrum β lactamases
common type was CTX –M -15.Most of the strains were resistant to β lactams and other
antibiotics, in some cases, only carbapenems and aminoglycosides could treat infections [5].
Epidemiology of E. coli.
E.coli causes significant extra intestinal diseases.Furthermore, its pathovars cause
significant illnesses and death in the population.Therefore, is widely studied.The onset, course
and complication from the pathovars vary significantly eventhough the pathotypes employ
various features to cause diseases by colonizing the intestinal mucosa. Outbreaks of diseases
mostly occur in developed countries and developing countries.Furthermore,they are always
transmitted by omnipresent mediums such as food and water.The dedicated national surveillance
programs is a clear indication of the complexity of pathogenic Ecoli.The programs monitor and
track disease outbreaks.Nevertheless, most developing countries lack these surveillance
programs.All pathotypes have a huge potential to cause diseases although they do not carry
similar public health profiles [8, 34].
Hemolytic Uremic Syndrome or (HUS) is caused by E. coli strain O157:H7 It leads to
kidney and heart failure,they also destroy a person’serythrocytes thus force the person to seek
blood transfusion.Approximately 5 % HUS cases cause death. Furthermore, it leads to more
health complications. HUS affects any age group but it mostly affects young children and older
adults [17].
E. coli O157:H7 is mostly reported in developed countries possibly due to the lack of
sophisticated laboratories in developing countries .Nevertheless, it is isolated from sick people
worldwide[4].73, 500 morbidity cases and 60 cases of mortality are caused in the United States,
while others such as non- O157 VTEC led to 37, 000 cases of morbidity yearly[4].

10Escherichia coli that produces Extended Spectrum β lactamases
Epidemiological studies on outbreak of foodborne diseases describe less than 40 cells that
cause disease in humans. Outbreaks of waterborne diseases indicate low infections dose due to a
great dilution factor in large water bodies.People with VTEC may have symptoms such as
diarrhea, HUS or colitis based on their age health, immunity and virulence factors.
Studies have indicated an increase in risk of HUS with antibiotic use.Patients who have
higher temperatures,high leukocytes, or long diarrheal periods are likely to develop HUS [4,
28].Antibiotic resistance is evident as VTEC bacteria evolves during infections.CDC reports that
10.8 of O157: H7 patients have developed resistance to antibiotics.The evidence reveals that
many non 0157:H7strains are linked to cattle and ruminants. Nevertheless, they vary in ability to
cause severe diseases. Ten states in the U.S recorded 110 O157VTEC infections with new
groups 0111, 0103, and 026 frequently identified in 2004 [28].
The E. coli O157: H7 strain caused a disease outbreak in Australia one associated with
sausage while the other was associated with a person to person spread. Other types caused by
contact with cattle have been explained. Several countries in Europe have been affected by the
strain O157: H7 [28].
Diarrheal diseases mostly affect children under the age of five especially in developing
countries.Pathogenic E. coli is the main contributorof diarrheal illnesses.ShigellaandE.coliare
reported to be the major causes of diarrhea in young children which has led to an increase in
mortality. Therefore, it is important to study E.coli while outlining the impact of diarrheal
diseases in the society.Advances made by the scientific and clinical communities on
microbiology pathogens, ecology and interaction with cost are important for vaccines and
treatment that prevent complication associated with E. coli induced diarrheal diseases [8, 34].

11Escherichia coli that produces Extended Spectrum β lactamases
Treatment of E. coli.
Multiplex PCR of ESBLs andphenotypic antibiotic therapy can do early detection of E.
coli. Many E. colithat produce ESBLs are resist drugs for examplecephalosporins,
penicillin, ,tetracycline and trimethoprim. Therefore, a limited number of antibiotics such as
nitrofurantoin and fosfomycin, are left for treatment [10].
The choice of treating Urinary Tract Infections caused by E. coli is reducing. Severe
infections are being treated by broad spectrum agents such as carbapenemsand novel
combination of antibiotics.Reports in the U.Kreveal organisms that produce enzyme
carbapenemase therefore indicating widespread resistance[14]. Furthermore, the resistance has
led to the use of carbapenemswhich unfortunately has increased selectionpressure and antibiotic
resistance, agents that spare carbapenems are required in hospitals. Old drugs used to treat E. coli
such as Fosfomycin and Temocilinare being used to treat ESBL producing bacteria [15].
Sources of E.coli.
Slaughterhouses are sources of E.coliand meat is contaminatedon the surface especially
when it is being slaughtered.Meat processors can also spread the bacteria through the mechanical
process.Raw fruits and vegetables are also reputable sources of the bacteria therefore they should
be washed thoroughly. Furthermore, contaminated water, poor hygiene and animals are also
sources of the bacteria.E. colican be disseminated from one person to the other and infected
people can be carriers [8].
Enteric bacterial pathogens originated from animals either directly or indirectly.The
several sources and routes of exposure complicate management of E coli. Since humans share

12Escherichia coli that produces Extended Spectrum β lactamases
the same environment with commensal bacteria, interaction between humans and animals
facilitates the dissemination of E. coli [8]
β lactam antibiotics.
They are the most commonly used antibiotics worldwide. They are distinguished by a
βlactam ring in their structures.The antibiotics have four groups based on the ring structure on
the β –lactam ring.These include penicillin, carbapenems, monolactamand β lactamase inhibitors
[9].The β lactam antibiotics show good tolerability.Bacteria that have extended spectrum β
lactamases [ESBLs], cephalosporins and enzymes hydrolyzing penicillinmay not be effective
towards these antibiotics.Furthermore, the bacteria have resistance to other antibiotics
thereforelimiting treatment options [9].
βlactams inhibits cell wall synthesisby attaching to thepenicillin binding protein[PBP],
which catalyzes the final stages in the formation of a cell wall.Furthermore, its hydroxyl radicals
destroy the cell wall. Moreover, effect and range of β lactamsis identified by PBPs that the
antibiotics bind [25].
β lactams becoming less effective in treatment against enterobacteria due to production of
extended spectrum βlactamases(ESBLs)[20].Β lactam antibiotics block the trans-peptidation of
peptidoglycan by inhibiting PBPs.Toxicity of βlactams is low because animal cells lack PBPs.
Beta lactams originate from environmental fungi and bacteria .They are over 80
differentβlactams in clinical uses which have a narrow spectrum [25].

13Escherichia coli that produces Extended Spectrum β lactamases
Figure1: β-lactam antibiotics classification
Resistance of βlactam antibiotics
Healthcare providers and their patients face the issue of drug resistance.Selecting
antibiotic regimen has become more complex than ever due to changes in resistance patternsand
rising costs of antibiotics [26].The repeated use of antibiotics results in antibiotic resistance [25,
26].Resistance has led to untreatableinfections whichlead to high costs of healthcareand rise in
mortality.The last resort antibiotics during resistance are expensive and cannot be easily accessed
[25].
E.colihas also developed resistance to antibiotics such as cephalosporins.In 17 to 22
European countries,E. coli isolates ranging from 85 to 100 percent were ESBL positive in a 2013

14Escherichia coli that produces Extended Spectrum β lactamases
study.In sub Saharan Africa, the resistance ranged upto 47 %.In Latin America, resistance in
Klebsiella pneumonia ranged from 19% to 87% in Bolivia [25].
New beta lactamantibiotics have been developed in the last twenty years,specifically built
to resist the hydrolytic action of beta lactamase.However for each developed, a new βlactamase
emerges that causes resistance to that class of drugs [23].Resistance by beta lactams is caused by
various mechanisms suchas change in structure of PBPs which results in a low drug affinity or
production of enzymes that cleave β lactam ring [9]. For instance the UTI E. coli produces
ESBLs thatresist antibiotics[13].
Resistance has been increasing especially in Gram negative bacteria because strains that
produce ESBL have been spreading. ESBL producing bacteria are resistant to quinolones and
trimethoprim because resistance mechanisms are characterized by plasmid
expression[14].Resistance is a global issue that requires proper interventions [15].

15Escherichia coli that produces Extended Spectrum β lactamases
β lactamase.
These enzymes open the βlactam ring by hydrolyzing the β lactam bond [4]. Abraham
and Chain first observed thehydrolyzationin 1940in an E. coli strain. The clinical effect of
hydrolyzationwas noted in early 1950s when hospitals received first βlactam resistant βaureus
[25]. The most significant resistance mechanism to antimicrobials is βlactamase production by
bacteria [23]. βlactamaseshydrolyse beta lactam antibiotics. The bacteria breaks up nitrogen
carbonyl bond in the βlactam ring [46].
βlactamasesare classified according to the amino acid levels.The mode of classification
was introduced by Ambler in 1980 from Class A to D. Serine enzymes belong to A, C,D while
zinc dependent enzymes are class B[48]. Substrates and inhibitor profiles define four functional
groups proposed by Bush, Jacoby, and Medeiros in 1995 namely: Group 1 are
cephalosporines;Group 2 are penicilllinases, cephslosporinases and broad spectrum β

16Escherichia coli that produces Extended Spectrum β lactamases
lactamases;Group 3 are metallo beta lactamases that hydrolyze penicillins and Group 4 are
penicillinases[48].
Plasmid encoded βlactamases first hydrolyzed the extended spectrum cephalosporinsgene
encoding the beta lactamase. Gene encoding βlactamase indicated single nucleotide mutation as
more than gene coding. Lactamases that were able to elucidate resistance to extended
cephalosporins, later termed as extended spectrum β lactamases (ESBLs) represented first
example in which resistance mediated by β lactam antibioticsarose from basic changes in the
spectrum of enzyme substrates[35].
Extended spectrum βlactamase [ESBLs]
Gram-positive bacteria produce an enzyme, β lactamase that breaks down antibiotics
thusenable resistance.E. coli and pneumoniaare common examples of ESBL producing bacteria
[40].The enzyme changes the susceptibility to antibiotics.ESBLs inactivate and hydrolyze a wide
range of β lactam antimicrobials for instance penicillin, cephalosporinsand aztreonam.
Nevertheless, they are inhibited by clavulanic acid. Furthermore, ESBL producing bacteria have
reduced susceptibility to non-βlactamase antimicrobials such as amino glycosides and
nitrofurantoin. Therefore, limiting an array of treatment options[41].
β lactamases induce resistance and hydrolyzescephalosporins such as ceftriaxone,
cefotaxime and monobactams.ESBLs hydrolyze antimicrobials and they can be inhibited. A
classification system by Bush, Jacoby and Medeiros categorizes the enzyme into three groups
that include:TEM,(about 200 variants), SHV (140 variants) and CTX M enzymes(about 130
variants)[26].

17Escherichia coli that produces Extended Spectrum β lactamases
The CTX- M group is the most common ESBL presently; it was described in a study by
Matsumoto et al. (1986) in the study of βlactam antibiotics.Bauernfeind obtained a cefotaxime
resistant E. coli isolate in 1989 to produce an enzyme that was non-SHV and non TEM. It was
named CTX – M -1 due to its increased activity against cefotaxime.The βlacatamases produced
by Kluyvera spp., are found in bacterial chromosomes. Furthermore, they have been moved to a
plasmid that carries the enzymes. Five main groups for the CTX enzymes include: CTX-M-1,
CTX-M-2, CTX-M-9,and CTX - 25 [26].
SHV and TEM ESBLs began spreading in 1980.These enzymes were encountered in
nosocomical infections for two years because of ESBL producing K. pneumonia.Enzymatic
background in ESBL infections began to change in late 1990 and early 2000, ever since CTX-M
enzymes have dominated. The worrying trendisspread of CTX into E. coli [9].
ESBLs are causing major disease burden in healthcare facilities[10] .Many studies have
investigated presence of ESBLs in clinical isolates resistance by ESBL producing E. coli. The
studiesdeveloped a simple method for detecting and sub-typing common ESBL genes
[11].Plasmid mediated ESBLsare resistant to cephalosporins.The spread of ESBLS IS
successfully associated with genes encoding ESBLs, which are located in broad range self-
transmissible or mobile plasmids.The activity of an enzyme is determined by the change in type
of ESBL genes [10].
ESBLs hydrolyze penicillin, early cephalosporins, or oxyimino beta lactams such as
aztreonam andcefepime. Furthermore, they exhibit in vitro inhibition by clavunic acid and
belong to Ambler group of classification A.Nevertheless, somehave extended cephalosporinase
activity that belongs to Ambler group D andare not inhibited by clavulanic acid [9].

18Escherichia coli that produces Extended Spectrum β lactamases
SHV-2 was the first ESBL to be encountered in the mid-1980s.There are over 180 TEM
and over 100SHV whichare known presently.CTX – M β lactamases are believed to have
originated from Kluyverra spp. chromosomal genes, they are exclusively found in functional
group 2be.180 variants have been sequenced in its protein up to today. CTX-M are divided into
five groups depending on the sequences in their amino acids[9.31].
ESBL genes are foundin plasmids. Both M and CTX genes are found on mobile
elements.SHV genes are foundin K. pneumonia and can be found in mobile E.coli[9].Clinical
laboratories face a problem of distinguishing different enzymes of different origins [9]. CTM –X
isolates are also resistant to antibiotics.
ESBLs cause infection or colonisation.Colonisation is the presence of bacteria in a bowel
but this does not make the carrier sick.Infection means that the bacterial burden in the body leads
to sickness [18].
The Plasmids gene transfer.
Plasmids are replicons of the DNA in the cell of bacteria. They play a role in evolution of
bacteria.Plasmids spread several traits such as drug resistance or virulence that facilitate
adaptationof bacteria to any environment. Moreover, they vary in size and are self-transferrable
[26].
Plasmids spread ESBLs. Gene transfer in microorganisms happens through mechanisms
such as Transformation, Conjugation and Transduction[26].The coding of ESBLs on plasmids
has made it easier for them to be transferred from one species to another. Ecoli and Klebsiella
have a high potential of acquiring these enzymes, they could be responsible for infection
outbreaks in hospital patients[23].

19Escherichia coli that produces Extended Spectrum β lactamases
ESBL –E. coli infection
Global increase in infection by CTX- M ESBL producing bacteriahas been experienced
in last fifteen years. They have led to increase in mortality, morbidity, healthcare costs and the
need for broadspectrum antibiotics.ESBLs bacteria cause a common infection known as the
Community Acquired Urinary Tract Infectio [37]. CTX- Mtype ESBL can worsen standard
infection control measures [39]. A previous use of fluoroquinolone and healthcare associated
infections has been associated to ESBLs in E.coli especially at infections that originate from the
community [38].
Table 2: Antimicrobial susceptibility and ESBL types

20Escherichia coli that produces Extended Spectrum β lactamases
Most patients diagnosed with UTIs have community onset infections. Limited
information regarding the epidemiology of ESBL E. coli that onsets within the community are
available. Previous studies have concentrated on UTIs [38].
Treatment of E. coli that produces ESBLEs
ESBLs exhibit antibiotic resistance. Nevertheless, they are treatable. Treatment needs
toxic and broad spectrum antimicrobials 19]. ESBLs production by gram-negative bacteria is a
rising health concern worldwide. ESBLs are resistant to B- lactam antibiotics apart from
cephamycins and carbapenems Furthermore, they also resist antibiotic classes such as
fluoroquinolones. Therefore, limited treatment options for these multidrug resistant bacteria
Figure 5: A graph of CTX-M-1 genes against time

21Escherichia coli that produces Extended Spectrum β lactamases
exists leads to increase in mortality. Early detection is important to guide empirical treatment and
effect measures in prevention [39].
The most appropriate treatment is the use of carbapenem antibiotics. In most,
cases the patients might be assymptomatic carriers who do not need treatment [19]. The
pathogenic significance and incidence of ESBL organisms is increasing. Therefore, more data is
needed on the risk factors associated with the bacteria. Mecilliam is a pro-drug can be used in
treatment since it is stable as compared to other antimicrobials [37]. The study has examined the
epidemiology and clinical features of E .coli that produces ESBLs identified its risk factors
infections [38].
Risk factors.
Recent hospitalization, long term or short term residency in a care facility and recent
antibiotics use. The reported risk factors are sex, functional status, use of gastric modifying

22Escherichia coli that produces Extended Spectrum β lactamases
drugs, age and cormobid conditions. Furthermore, risk factors are also evident in the community.
Nonetheless, emergence of CTX-M type beta lactamases may complicate strategies based on
traditional risk factors in the community [26, 39].Clinical information on community onset
infections that are caused by ESPL E. coli is limited [38].A major significant risk factor for CA-
UTI is international travel [37].
Individuals mostlyat risk.
Risk factor that lead to infection of a patient infection include prolonged stay in the
hospital, poor antimicrobial therapy, the strain of bacteria, immunosuppression, wounds,
increasing age or underlying medical conditions.[19, 28].Another independent risk factor for
ESBLUTI is recreational swimming in freshwater since the bacteria have been identified in
water.

23Escherichia coli that produces Extended Spectrum β lactamases
Moreover, UTI infections may be caused by strains in water. Environmental pollution can
therefore be linked to antimicrobial resistance.
Hospital admissions,antibiotic usage are risk factors for UTI. Furthermore, another risk
factor is travelling to disease endemic countries. Contact with pets is associated with the E.
coli.Spread of the disease is mainly facilitated by human to human interaction.Sources of
colonization are foods and meat .ESBL genes carrying plasmids could be detected in farmers and
their animals [46].
Epidemiology of ESBL E. coli.
E. coli bacteria have managed to spread worldwide since its identification bya German
scientist. The early nosocomical outbreaks occurred in the early 1990s [23, 26]. ESBL E. coli is
an important community acquired pathogen [38]. Levels of epidemiology that should be
considered include the geographical areas, country, the hospital, community, the host and
bacterial plasmids[25, 26].
The last decade witnessed an increase in β lactamase, CTX –M bacteria.The bacteria
have replaced TEM and SHV variants. Concurrently, E. coli is the most common ESBL
producing pathogen globally. CTX –M genes migrate to highly transmissible plasmids that have
facilitated the spread of ESBLs in the community.
ESBL producing bacteria causes community acquired infections because they have been
found in domestic animals, food products and stool samples [39]. High risk areas include Africa,
Asia and the Middle East had a high rate of colonization in travelers who visited those countries
[37, 39].

24Escherichia coli that produces Extended Spectrum β lactamases
K. pneumonia and E. coli incidences vary in different Asian countries. Korea has a 4.8 %
prevalence rate, 12.6% in Hong Kong and 12.6 to 68 % in India [23].A recent study has revealed
that E. Coli clone ST131 that has CTX-M- 15 and resists quinolone has facilitated spread of
ESBL bacteria globally [23, 26]. In the Middle East, 38 % of people were resistant to cephalo
sporins in a study conducted in five hospitals between 1999 – 2000 [111].Furthermore, another
study in the same region revealed that 61 % of E. coli had ESBLs of CTM –M -14, M-15 and
CTM- M 27 types. Moreover, the stains had the TEM enzyme [26].
A study in Saudi Arabia revealed that 26% of K. pneumonie isolates produced ESBLs, 36
% were CTX-M-15. A study undertaken in 2004- 2005 revealed ESBL producers in 10% urinary
isolates from inpatients and 4% in outpatients[26, 32].Faecal samples analyzed in Lebanon in
2003reported differences in ESBL carriage between healthcare workers[3%], patients[16%] and
healthy subjects who had 2%.The CTX – M – 15 enzyme was more predominant at 83%.Another
interesting study compared proportion of ESBL producing isolates in patients and out patients
and it revealed that in patients had 15.4% while outpatients had 4.5%.Data collected in Kuwait
reported low prevalence in the community [25].
The world has been experiencing an increase in ESBL producing E. coli [30] The
detection of ESBL carriers in the early stage could facilitate control measures, prevent spread of
isolates and appropriate facilitate selection of antimicrobials [21].Producers of ESBL express
resistance to antimicrobial drugs, therefore therapeutic options are limited[30].
Since ESBLs resist third generation cephalosporinswhich are commonly used in various
hospitals, this leads to failures in treatment.Despite the fact that ESBL can be produced by many

25Escherichia coli that produces Extended Spectrum β lactamases
Enterobacteriaceae, the study detected the presence of E.coli and K. pneumonia isolates [23].
Appropriate use of drugs is needed to address resistance [22].
CTX –M enzymes are the most common ESBLs worldwide.Nonetheless, the enzymes
differ between countries.Success of the genes has been facilitated by spreadof the isolates since
humans, animals and food are ever moving [9].
ESBLs producing bacteria had a low prevalence in Ostergotland at below one percent.
Nevertheless, the prevalence is increasing.ESBL E. coli have also increased from 5 to 47
annually.Prevalence of K. pneumonia remain one to four annually.The dominant genes were the
CTX- M group at 67 %. Primary cares report a 10.7 -12.1 DID consumption of antimicrobial
agents yearly while hospital care report a 14.1 -1,30 DID yearly[9].Community Acquired
Urinary Tract Infections is a predominant infection caused by ESBL producing
bacteria .Nevertheless,its clinical epidemiology is unknown in low prevalence countries [37].

26Escherichia coli that produces Extended Spectrum β lactamases
Conclusion.
The most common problem in hospitals and health facilities is ESBL producing
Ecoli.The investigation has studied this microorganism because of its importance in controlling
ESBL producing bacteria[22]. Limited molecular characterization is present for ESBL genes in
Saudi Arabia.The study isolated ESBL producing bacteria strains of Ecoliat King Abdulaziz
University Hospital in Jeddah. The study objective was to use tests in molecular biology to
characterize genes encoding the enzyme.
A major crisis of antimicrobial resistance by these organisms has been reported by the
government, international bodies and pharmaceutical companies.Antibiotic stewardship
programs have failed to address drug resistant bacteria. It is important to consider the
significance of beta lactams as antibiotics.Few studies have analyzed the impact of beta lactam
resistance depending on the phenotype features. Molecular genotyping of ESBL is not widely

27Escherichia coli that produces Extended Spectrum β lactamases
known .Consequently, the study determined beta lactam resistant genotype ofE. coli isolates
from Jeddah.

28Escherichia coli that produces Extended Spectrum β lactamases
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