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"Isolation of klebsiella spp. From urinary tract infection"
.Although this type of pili is called "mannose-resistant Klebsiella-like hemagglutination" (MR/K-HA),later studies demonstrated that this type can be found in many enteric bacteria, not just Klebsiella . These pili can bind to endothelial cells, respiratory tract epithelia, and uroepithelial cells. In the kidneys, type 3 pili mediate bacterial adhesion to tubular basement membranes, Bowman's capsules, and renal vessels . However, the exact pathogenic role of these pili remains unclear [23] 2-11-2-2. Serum Resistance in Klebsiella and Lipopolysaccharide (LPS): Many Klebsiella strains exhibit serum resistance, meaning they are able to resist the bactericidal effect of human serum, which is primarily mediated by complement proteins. This resistance is thought to be an important factor in the onset and severity of infection. Most non-pathogenic gram-negative bacteria are sensitive to the bactericidal effect of serum, whereas pathogenic strains often exhibit serum resistance, mainly due to surface proteins like CPS and LPS. LPS, in particular, can protect the bacteria from complement-mediated damage by forming a barrier that isolates the complement components from the bacterial cell membrane, thus preventing the formation of the membrane attack complex (C5b-C9) [24] 2-11-2-3- New Adhesins in Klebsiella: Recent studies have identified several new adhesins in Klebsiella, such as CF29K, a protein encoded by an R-plasmid that mediates adherence to human intestinal cells. This adhesin appears to be related to CS31-A, a protein found in diarrheal Escherichia coli strains. Additionally, a new fimbria called KPF-28 was identified in Klebsiella pneumoniae strains producing Extended-Spectrum Beta-Lactamases (ESBLs). However, further studies are needed to understand the distribution, frequency, and pathogenic significance of these adhesins in Klebsiella species .[25]
Fig(2-3) Resistance in Klebsiella
2-12-VaccinAtion Effort
Klebsiella infections, primarily acquired in hospital settings, represent 5 to 7.5% of all nosocomial infections and are associated with high morbidity and mortality rates. Severe systemic infections, such as bacteremia and pneumonia caused by Klebsiella, exhibit fatality rates ranging from 20 to 50% for bacteremia and over 50% for pneumonia. The prevalence of Klebsiella infections is particularly concerning in pediatric wards, where it ranks among the top pathogens in neonatal intensive care units, especially affecting premature neonates who are more susceptible to developing an intestinal flora rich in Klebsiella spp. The emergence of extended-spectrum beta-lactamase (ESBL)-producing multiresistant strains underscores the urgent need for immunological strategies to control Klebsiella infections. Potential approaches include immunoprophylaxis through active vaccination of at-risk patients and immunotherapy via passive immunization with hyperimmune sera. Current research is focusing on two surface components, lipopolysaccharides (LPS) and capsular polysaccharides (CPS), as promising candidates for the development of an anti-Klebsiella vaccine. Hart C. A. Klebsiellae and neonates J. Hosp. Infect. 23 1993 83 -86
2-12-1-polysaccharides (LPS) Due to their endotoxic properties, LPS are considered important in the pathology of septicemia. Until recently, Klebsiella LPS O antigens were generally considered to be masked by the capsule polysaccharides and thus not to be exposed on surface, leaving them inappropriate as vaccine candidates. Recent studies, however, demonstrated surface exposure of O-antigens in strains expressing particular capsular serotypes (Tomas J. M., Camprubi S., and Williams P. Surface exposure of the O-antigen in Klebsiella pneumoniae O1:K1 serotype strains Microb. Pathog. 5 1988 141 -147)
The small number of different Klebsiella O-types is a great advantage with respect to their applicability as vaccines. In contrast to the K antigens, only eight O types are known, O1 being the most commonly found O type in clinical isolates. A multivalent LPS vaccine composed of these eight O antigens or at least the inclusion of the common O1 antigen in a broad spectrum capsular polysaccharide vaccine might be a promising approach. Recently, the administration of monoclonal antibodies to the Klebsiella O1 antigen has been reported to be protective in a mouse model of lethal endotoxemia (Mandine E., Salles M. F., Zalisz R., Guenounou M., and Smets P. Murine monoclonal antibodies to Klebsiella pneumoniae protect against lethal endotoxemia and experimental infection with capsulated K. pneumoniae Infect. Immun. 58 1990 2828 -2833). Moreover, the inclusion of O antigens in a multivalentKlebsiella vaccine formulation might be of additional benefit due to strong adjuvant action, as has been demonstrated for theKlebsiella O3 lipopolysaccharide (Yokochi T., Inoue Y., Kato Y., Sugiyama T., Jiang G. Z., Kawai M., Fukada M., and Takahashi K. Strong adjuvant action of Klebsiella O3 lipopolysaccharide and its inhibition of systemic anaphylaxis FEMS Immunol. Med. Microbiol. 10 1995 181 -184). A great drawback of active immunization with LPS-containing vaccines, however, is adverse toxic reactions, which must be expected because of the endotoxin content. Thus, each Klebsiella vaccine composed of O antigens has to be rendered safe by sufficient. detoxification of the LPS)Capsular Polysaccharides )CPS 2-12-2-
CPS have been the obvious vaccine candidates for several reasons. Capsules are produced by almost all Klebsiella strains; they represent the outermost layer of surface structures in contact with the host milieu, and they have been proven to be highly immunogenic and nontoxic (Cryz S. J. Jr., Furer E., and Germanier R. Safety and immunogenicity of Klebsiella pneumoniae K1 capsular polysaccharide vaccine in humans J. Infect. Dis. 151 1985 665 -671). A serious disadvantage of aKlebsiella CPS vaccine is the great number of K antigens (77 different antigens). However, in a study of the incidence of the capsule types among bacteremic Klebsiella isolates, Cryz et al. observed that only 25 serotypes made up 70% of all bacteremic strains (Cryz S. J., Mortimer P. M., Mansfield V., and Germanier R. Seroepidemiology of Klebsiella bacteremic isolates and implications for vaccine development J. Clin. Microbiol. 23 1986 687 -690). Based on their seroepidemiological findings, they formulated a 24-valent Klebsiella CPS vaccine that subsequently was proven to be safe and immunogenic ( Cryz S. J. Jr., Mortimer P., Cross A. S., Furer E., and Germanier R. Safety and immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine in humans Vaccine 4 1986 15 -20). To date, this vaccine seems to be the most promising approach for preventing sepsis caused by Klebsiella and has already passed phase I human trials (Edelman R., Taylor D. N., Wasserman S. S., Mcclain J. B., Cross A. S., Sadoff J. C., Que J. U., and Cryz S. J. Phase 1 trial of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered simultaneously Vaccine 12 1994 1288 -1294). The most recent study of the 24-valent Klebsiella CPS vaccine demonstrated an excellent antibody response after active immunization in patients with acute blunt or penetrating trauma (Campbell W. N., Hendrix E., Cryz S., and Cross A. S. Immunogenicity of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered to victims of acute trauma Clin. Infect. Dis. 23 1996 179 -181)
2-13-Diagnosis and Testing
2-13-1- Medical History and Clinical Examination
Symptoms of a Klebsiella urinary tract infection (UTI) may include frequent urination, a burning sensation while urinating, blood in the urine, and lower abdominal or pelvic pain. If the infection has reached the kidneys, symptoms may also include fever or back pain. 2-13-2-Urine Tests
2-14-Treatment Guidelines for Klebsiella Infections The treatment for a Klebsiella infection varies based on the type of infection and the results from the antibiotic sensitivity test. Commonly prescribed antibiotics include: Cephalosporins (e.g., ceftriaxone) Carbapenems (e.g., meropenem) for severe infections Fluoroquinolones (e.g., ciprofloxacin), particularly for uncomplicated urinary tract infections (UTIs), though rising resistance is a concern Important Notes: o Klebsiella pneumoniae* is a significant pathogen known to cause urinary tract infections, which can lead to severe complications, particularly in individuals with weakened immune systems. o Some strains of Klebsiella pneumoniae may be resistant to standard antibiotics. Those that produce Extended-Spectrum Beta-Lactamases (ESBLs) or are classified as Carbapenem-Resistant Klebsiella pneumoniae (CRKP) may require more intensive treatment with stronger antibiotics. Surgery When the condition worsens and progresses, and abscesses appear, it is necessary to remove them through surgery. Depending on the locations of the abscesses, the doctor will determine the significance and location of the procedure, deciding whether it should take place in a hospital or a private clinic, especially if the required surgical procedure is simple.[35] 2-15- How to Protect Yourself from Exposure to Klebsiella Infection
MATERIALS AND METHODS
Design and setting Our review was a multi-centric retrospective study done from November 2008 to January 2011. ???? ?????? ???? ??????? . Samples were collected from routine patients
Clinical isolates A total of 1,617 mid-stream clean catch urine samples yielding K. pneumoniae were included in the study. Isolates were identified by standard protocol and API-20 E system (Biomerieux) and subjected to Kirby-Bauer disk diffusion sensitivity. MICs were also estimated by Enephlometry. Clinical isolates were tested for their sensitivity; resistance or intermediate response to these 20 locally available drugs using Oxoid discs: amikacin, gentamicin, amoxicillin, amoxiclav (Augmentin), imipenem, piperacillin.tazobactum, cephradine, cefuroxime, cefixime, cefotaxime, ceftazidime, ceftriaxone, fosfomycin, pipemidic acid, oflaxacin, ciprofloxacin, doxycycline, cotrimoxazole, nitrofurantoin and cefoperazone-sulbactam. Zone diameters for each antibiotic were interpreted as Resistant, Intermediate or Sensitive. The antibiotics were from Oxoid. The zone diameters were estimated using calipers and according to the method recommended
by the National Committee for Clinical Laboratory Standards (NCCLS, 1987) and the WHO. Patient data Subjects were either self-referrals or referred by physicians. Data of age, sex, date of investigation and any history of antibiotic usage were recorded from patients presenting with suggestive UTI. Data was analyzed using SPSS version 16.0. In case of missing values in records, the reported percentage in results is the valid percentage, ignoring missing values. Chapter four Results & Discussions
Isolation of Klebsiella spp. from Urinary Tract Infection (UTI)
Results 4-1- As presented in the table and figure below, most of patient in this study were females (52%). Table (1)The distribution of patients according to gender Gender frequency Percent
Male 29 48% Female 31 52% Total 60 100% Gender Figure The distribution of patients according to gender
As presented in the table and figure below, most of patients in this study were those aged between 20- to 40-years old (53%). The mean age of patients was 33.55+-17.26 years, with ranged between 5- to 74 years old. Table ( 4-2)The distribution of patients according to Age Categories
Age Categories Frequency Percent <20yrs 10 17% 20-40yrs 32 53% 40-60yrs 12 20% >60yrs 6 10% Total 60 100%
Age (years) Mean+-SD 33.55+-17.26 SEM 2.23 Minimum 5 Maximum 74
Age Categories Figure (4-2)The distribution of patients according to Age Categories
As presented in the table and figure below, most of patients in this study were males who those aged between 20- to 40-years old (28%). Table( 4-3)The Cross-distribution of patients according to Gender and Age Categories
Figure(4-4) The Cross-distribution of patients according to Gender and Age Categories ??? ????? 4-4 ?? ?????? As presented in the table and figure below, most of the susceptible antibiotics against K. pneumonia in this study were MEM, VA, and AK as (88%, 80%, and 65%, respectively) while the most resistance were TE, RA, DXT, CFM, and AMC as (90%, 88%, 88%, 85%, and 82%, respectively)
Table (4-3)The activity of Antibiotics against K. pneumoniae in this study
Figure (4-5)The activity of Antibiotics against K. pneumoniae in this study
DISCUSSION 4-2- Clinically, UTI is said to exist when 105 bacteria or more per ml of urine are found in a mid-stream specimen, a common baseline which was adhered to in our retrospective data. K. pneumoniae, an important uropathogen, is also said to be the most common cause of illness in humans after respiratory tract infections, thereby demanding tailored treatment. In our study, imipenem with an efficacy of 97.7% was found to be the most effective drug against K. pneumoniae isolates as has been reported by Shah et al. and Mehrgan et al.. Our results are also consistent with those observed recently on the efficacy of the drug and was more than the 92.5% sensitivity to carbapenems reported in Islamabad and 85.1% in Egypt. One study in India showed only 46.66% antibiotic efficacy for imipenem , while another study also in India considered imipenem efficacy to be as high as 99.2% although Klebsiella isolates have been showing increased resistances the world over . Amoxicillin had efficacy of 0.1%, which was consistent with findings in other studies such as that of Ullah et al. Incidentally, our data revealed that only one patient was sensitive to this antibiotic. In addition, the first generation cephalosporin, cephradine, showed low (40.3%) sensitivity in our study, the second generation, cefuroxime, showed 55.9% efficacy, while the third generation cephalosporins; cefixime, ceftriaxone, ceftazidime and cefotaxime showed 57.7%, 66.2%, 66.4 and 66.6% efficacy respectively. In Egypt, cefotaxime, which along with ceftazidime is a potential marker for ESBL production, was reported to be significantly less effective than in our study . The same study reported ceftazidime sensitivity of 52% compared with our 66.4%, ceftriaxone sensitivity of 35.3% as opposed to our 66.2%, cefuroxime sensitivity of 32.7% compared with our 55.9%, indicating the variation of drug effects in different geographical areas. Furthermore, a study done in Iran revealed significantly higher resistance (86.6%) to ceftriaxone than that observed in our study in Karachi and also as reported in Egypt . Combination antibiotics showed varying efficacies: piperacillin.tazobactam: 95.7%; cefoperazone.sulbactam: 95.8% and cotrimoxazole (Septran): 43.1 %. The results of cotrimoxazole effectiveness were noted to be currently improved as compared to the previously reported 6.52% by Ullah et al. . Our study also underlined the current efficacy of piperacillin.tazobactam on our isolates for years 2009-2010 to have only 2.1% resistance, compared to the resistance (66.8%) for years 2005-2007 reported
2-7-Antibiotic Resistance Extended-spectrum ?-lactamase (ESBL)-producing Klebsiella strains represent a serious threat in healthcare environments due to their resistance to extended-spectrum cephalosporins.SHV-5, TEM-10, and TEM-12 extended-spectrum beta-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli.3_??????2.3.4.5.6.?????????????????????????21/ ???????????(1991).
“Isolation of klebsiella spp.
From urinary tract infection”
.
Chapter one
Introduction
Introduction:-
Klebsiella Urinary Tract Infections (UTIs)
Klebsiella is a type of Gram-negative bacteria that belongs to the Enterobacteriaceae family. It is commonly found in the human gut, where it does not usually cause harm. However, when it spreads to other parts of the body, such as the urinary or respiratory tract, it can cause serious infections.
Klebsiella pneumoniae is one of the most common Klebsiella species responsible for urinary tract infections (UTIs). The infection occurs when the bacteria travel from the gastrointestinal tract to the urinary system, leading to inflammation and discomfort.(1)
Risk Factors for Klebsiella UTIs
Several factors increase the risk of developing a Klebsiella UTI, including:
Weakened immune system, such as in diabetes, cancer, or immunosuppressive treatments.
Use of urinary catheters, which can introduce bacteria into the bladder.
Prolonged hospital stays, particularly in intensive care units (ICUs).
Advanced age, as elderly individuals are more susceptible.
Excessive antibiotic use, which can contribute to antibiotic resistance.
Klebsiella bacteria can cause serious urinary tract infections, [2]
particularly in individuals with weakened immune systems or those in hospital settings. Early diagnosis and appropriate antibiotic treatment are crucial to prevent complications. Preventive measures, such as good hygiene and responsible antibiotic use, can help reduce the risk of infection.
Klebsiella is not transmitted in the air, [3]
but it is possible to catch the infection if you are in nursing homes or hospitals, or
through direct contact with the bacteria and then touching open wounds
Fig (1) klebsiella
Chapter two
Literature review
klebsiella It's a type of bacteria that belongs to a family Intestinal bacteria It is a non
motile bacteria on Short Gram negative bacilli form Surrounded by a capsule.
klebsiella bacteria usually live in the intestines Naturally The presence of klebsiella in
the stool is normal, but if it spreads to Other parts of the body They cause serious
infection. Klebsiella is usually spread in Healthcare Environments Like nursing homes
Intensive[4]
2-1 Types of klepsella
exist Three types Of the strains of Klebsiella that cause infection, they are Klebsiella Pulmonary Causes Klebsiella Pulmonary (from Klebsiella Pneumoniae) In the lung infection that may result PneumoniaAlso, it may cause Urinary tract infection, bacterial
meningitis, or endophthalitis, as well as Purulent liver abscessAnd maybe klepsila
circulating in the blood, causing it Bacteremia.
2-1-1-Klebsiella pulmonary
is also Causes of urinary tract infection in pregnancyIt may
result from the effect of Klebsiella bacteria on pregnancy Premature birth, neonatal
sepsisIf not treated, the bacteria can cause delayed fetal growth within the uterus
and low birth weight.
2-1-2-Klepsila Oxytoka
Live Klebsilla Oxytoka Klebsiella Oxytoca Nose, mouthIn addition to the intestines,
it causes some kind of infection, its symptoms are similar to pneumonia, and it can
also lead to Urinary tract infection, or Infection of wounds.
2-1-3-Klepsila Granular
Causes kalbsiella granular (from Klebsiella Granulomatis) Genital infection.
Do you cause symptoms of Klebsiella bacteria in urine
The importance of obtaining medical advice as soon as possible if you notice a
symptom of a urinary tract infection. [5]
To get the appropriate treatment early in order to avoid any unexpected problems.
Symptoms of urinary tract infections caused by Klebsiella bacteria include the
following :
1-Note that there is blood in the urine .
2-Pain and burning during urination .
3-Feeling of pain in the area below the
4-pubic bone .
5-Frequent urination
6-incontinence .
7-high body temperature, abdominal pain
The period of receiving antibiotic treatment varies from one case to another, but in
most cases it lasts from two days to two weeks only, depending on what the doctor
deems appropriate.[6]
2-2-Nosocomial infections
are among the most significant challenges faced by modern healthcare systems. Among the pathogens associated with these infections, Klebsiella spp., particularly Klebsiella pneumoniae, stand out due to their capacity for colonization and resistance to antimicrobial treatments.[7]
2-3-Distribution and Habitats
Klebsiella spp. are widely distributed in nature, commonly found in surface water, soil, and on plants. They also colonize mucosal surfaces of mammals, including humans, where they are part of the normal flora in the gastrointestinal and upper respiratory tracts.[8]
2-4-Colonization in Humans and Hospital Environments
Although Klebsiella may be present in healthy individuals with variable carriage rates (5–38% in fecal samples and 1–6% in the nasopharynx), these rates increase significantly in hospital settings. Studies have reported colonization rates as high as 77% in stool, 19% in the pharynx, and 42% on patients’ hands during hospitalization, particularly among those receiving antibiotic treatments.[9]
2-5-Role of Antibiotics in Colonization
The use of antibiotics, especially broad-spectrum agents, is strongly associated with increased colonization by Klebsiella. Evidence indicates a direct link between prior antibiotic use and elevated colonization rates, emphasizing that antimicrobial policy within hospitals is a major determinant of colonization patterns.[10]
2-6-Transmission in Healthcare Settings
Klebsiella transmission in hospitals primarily occurs through contaminated medical equipment or the hands of healthcare workers. The gastrointestinal tract of patients is considered the principal reservoir. Multiple outbreaks, particularly in neonatal intensive care units, have been documented, highlighting the organism's capacity for rapid spread.[11]
2-7-Antibiotic Resistance
Extended-spectrum β-lactamase (ESBL)-producing Klebsiella strains represent a serious threat in healthcare environments due to their resistance to extended-spectrum cephalosporins. The prevalence of these strains varies globally, with rates around 5% in the United States and up to 25–40% in some European hospitals.[12]
2-8-Taxonomy and Differentiation of Klebsiella Species
The genus Klebsiella, part of the Enterobacteriaceae family, has undergone a complex taxonomic evolution. Initially, the genus was divided into three species based on the diseases they caused: K. pneumoniae, K. ozaenae, and K. rhinoscleromatis. As microbiological techniques advanced, including numerical taxonomy, the species classification within Klebsiella was refined, with key contributions from scientists such as Cowan, Bascomb, and Ørskov.
In the 1980s, environmental isolates of Klebsiella, previously classified as "Klebsiella-like" organisms, led to the identification of new species: K. terrigena, K. ornithinolytica, K. planticola, and K. trevisanii. Later, K. planticola and K. trevisanii were merged due to their DNA sequence homology . While initially considered non-pathogenic, these species, particularly K. planticola, have been increasingly reported in human clinical infections, with a high frequency observed in respiratory tract and urinary infections .
Despite these advances, the taxonomy of Klebsiella has been complicated by differing nomenclature practices. The United Kingdom and Commonwealth countries typically adhere to Cowan’s classification, while the United States and Europe generally follow Ørskov’s classification, leading to regional discrepancies in species identification .
The differentiation of Klebsiella species is primarily based on biochemical tests. These gram-negative, nonmotile, encapsulated rods are characterized by their ability to produce lysine decarboxylase and test positive for the Voges-Proskauer reaction. However, K. terrigena and K. planticola require more specialized biochemical testing, such as the ability to utilize m-hydroxybenzoate or grow at low temperatures, for accurate identification .[19]
2-10-Typing of Klebsiella Isolates
The determination of clonality in Klebsiella strains is crucial from an epidemiological perspective, especially in the context of endemic and epidemic hospital outbreaks. Identifying the clonal relationship among isolates helps improve the management of such outbreaks. Several typing methods, each with varying success rates, are employed to categorize Klebsiella strains, including[20]
2-11- Pathogenicity Factors of Klebsiella
The term "pathogenicity" refers to the ability of a bacterium to cause disease, while "virulence" refers to the degree of pathogenicity of a bacterial species. Nosocomial infections caused by Klebsiella most commonly affect the urinary and respiratory tracts, with different virulence factors involved depending on the infection site. Animal models have been essential for understanding how Klebsiella interacts with the host and the factors that contribute to disease development.[21]
2-11-1-Capsular Antigens
Capsular polysaccharides are a major virulence factor in Klebsiella. The capsule, composed of complex acidic polysaccharides, plays a key role in protecting the bacterium from phagocytosis and complement-mediated killing. This is achieved by inhibiting the activation of complement components, especially C3b, which helps the bacterium avoid immune destruction. There are 77 known capsular serotypes, with types K1 and K2 being particularly virulent in animal models of peritonitis and skin lesions The virulence of these serotypes is often linked to the absence of certain sugar sequences, such as mannose or rhamnose, which help macrophages target and kill bacteria.
Fig(2-2) Capsular Antigens
2-11-2-Pili (Fimbriae)
Pili are essential for the initial adhesion of Klebsiella to host tissues. The most studied pili are Type 1 and Type 3. Type 1 pili are mannose-sensitive and facilitate bacterial adherence to mucosal surfaces in the urinary, respiratory, and intestinal tracts. These pili play a significant role in the development of lower urinary tract infections (Traglia et al., 2017). Type 3 pili, while less understood, are involved in bacterial adhesion to various cells, including endothelial cells and uroepithelial cells. They are particularly important in persistent infections, such as those associated with indwelling catheters.[22]
2-11-2-1-Pili Types and Their Effects in Klebsiella Bacteria:
2-11-2-1-1. Pili Types and Their Role in Agglutination and Cell Interaction:
Pili are surface proteins in Klebsiella bacteria that contribute to bacterial interaction with host cells. Among these, type 3 pili are distinctive for their ability to agglutinate tannin-treated red blood cells. Although this type of pili is called "mannose-resistant Klebsiella-like hemagglutination" (MR/K-HA),later studies demonstrated that this type can be found in many enteric bacteria, not just Klebsiella . These pili can bind to endothelial cells, respiratory tract epithelia, and uroepithelial cells. In the kidneys, type 3 pili mediate bacterial adhesion to tubular basement membranes, Bowman’s capsules, and renal vessels . However, the exact pathogenic role of these pili remains unclear [23]
2-11-2-2. Serum Resistance in Klebsiella and Lipopolysaccharide (LPS):
Many Klebsiella strains exhibit serum resistance, meaning they are able to resist the bactericidal effect of human serum, which is primarily mediated by complement proteins. This resistance is thought to be an important factor in the onset and severity of infection. Most non-pathogenic gram-negative bacteria are sensitive to the bactericidal effect of serum, whereas pathogenic strains often exhibit serum resistance, mainly due to surface proteins like CPS and LPS. LPS, in particular, can protect the bacteria from complement-mediated damage by forming a barrier that isolates the complement components from the bacterial cell membrane, thus preventing the formation of the membrane attack complex (C5b–C9) [24]
2-11-2-3- New Adhesins in Klebsiella:
Recent studies have identified several new adhesins in Klebsiella, such as CF29K, a protein encoded by an R-plasmid that mediates adherence to human intestinal cells. This adhesin appears to be related to CS31-A, a protein found in diarrheal Escherichia coli strains. Additionally, a new fimbria called KPF-28 was identified in Klebsiella pneumoniae strains producing Extended-Spectrum Beta-Lactamases (ESBLs). However, further studies are needed to understand the distribution, frequency, and pathogenic significance of these adhesins in Klebsiella species .[25]
Fig(2-3) Resistance in Klebsiella
2-12-VaccinAtion Effort
Klebsiella infections, primarily acquired in hospital settings, represent 5 to 7.5% of all nosocomial infections and are associated with high morbidity and mortality rates. Severe systemic infections, such as bacteremia and pneumonia caused by Klebsiella, exhibit fatality rates ranging from 20 to 50% for bacteremia and over 50% for pneumonia. The prevalence of Klebsiella infections is particularly concerning in pediatric wards, where it ranks among the top pathogens in neonatal intensive care units, especially affecting premature neonates who are more susceptible to developing an intestinal flora rich in Klebsiella spp. The emergence of extended-spectrum beta-lactamase (ESBL)-producing multiresistant strains underscores the urgent need for immunological strategies to control Klebsiella infections. Potential approaches include immunoprophylaxis through active vaccination of at-risk patients and immunotherapy via passive immunization with hyperimmune sera. Current research is focusing on two surface components, lipopolysaccharides (LPS) and capsular polysaccharides (CPS), as promising candidates for the development of an anti-Klebsiella vaccine. Hart C. A. Klebsiellae and neonates J. Hosp. Infect. 23 1993 83 -86
2-12-1-polysaccharides (LPS) Due to their endotoxic properties, LPS are considered important in the pathology of septicemia. Until recently, Klebsiella LPS O antigens were generally considered to be masked by the capsule polysaccharides and thus not to be exposed on surface, leaving them inappropriate as vaccine candidates. Recent studies, however, demonstrated surface exposure of O-antigens in strains expressing particular capsular serotypes (Tomás J. M., Camprubi S., and Williams P. Surface exposure of the O-antigen in Klebsiella pneumoniae O1:K1 serotype strains Microb. Pathog. 5 1988 141 -147)
The small number of different Klebsiella O-types is a great advantage with respect to their applicability as vaccines. In contrast to the K antigens, only eight O types are known, O1 being the most commonly found O type in clinical isolates. A multivalent LPS vaccine composed of these eight O antigens or at least the inclusion of the common O1 antigen in a broad spectrum capsular polysaccharide vaccine might be a promising approach. Recently, the administration of monoclonal antibodies to the Klebsiella O1 antigen has been reported to be protective in a mouse model of lethal endotoxemia (Mandine E., Salles M. F., Zalisz R., Guenounou M., and Smets P. Murine monoclonal antibodies to Klebsiella pneumoniae protect against lethal endotoxemia and experimental infection with capsulated K. pneumoniae Infect. Immun. 58 1990 2828 -2833). Moreover, the inclusion of O antigens in a multivalentKlebsiella vaccine formulation might be of additional benefit due to strong adjuvant action, as has been demonstrated for theKlebsiella O3 lipopolysaccharide (Yokochi T., Inoue Y., Kato Y., Sugiyama T., Jiang G. Z., Kawai M., Fukada M., and Takahashi K. Strong adjuvant action of Klebsiella O3 lipopolysaccharide and its inhibition of systemic anaphylaxis FEMS Immunol. Med. Microbiol. 10 1995 181 -184). A great drawback of active immunization with LPS-containing vaccines, however, is adverse toxic reactions, which must be expected because of the endotoxin content. Thus, each Klebsiella vaccine composed of O antigens has to be rendered safe by sufficient.
detoxification of the LPS)Capsular Polysaccharides )CPS 2-12-2-
CPS have been the obvious vaccine candidates for several reasons. Capsules are produced by almost all Klebsiella strains; they represent the outermost layer of surface structures in contact with the host milieu, and they have been proven to be highly immunogenic and nontoxic (Cryz S. J. Jr., Fürer E., and Germanier R. Safety and immunogenicity of Klebsiella pneumoniae K1 capsular polysaccharide vaccine in humans J. Infect. Dis. 151 1985 665 -671). A serious disadvantage of aKlebsiella CPS vaccine is the great number of K antigens (77 different antigens). However, in a study of the incidence of the capsule types among bacteremic Klebsiella isolates, Cryz et al. observed that only 25 serotypes made up 70% of all bacteremic strains (Cryz S. J., Mortimer P. M., Mansfield V., and Germanier R. Seroepidemiology of Klebsiella bacteremic isolates and implications for vaccine development J. Clin. Microbiol. 23 1986 687 -690). Based on their seroepidemiological findings, they formulated a 24-valent Klebsiella CPS vaccine that subsequently was proven to be safe and immunogenic ( Cryz S. J. Jr., Mortimer P., Cross A. S., Fürer E., and Germanier R. Safety and immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine in humans Vaccine 4 1986 15 -20). To date, this vaccine seems to be the most promising approach for preventing sepsis caused by Klebsiella and has already passed phase I human trials (Edelman R., Taylor D. N., Wasserman S. S., Mcclain J. B., Cross A. S., Sadoff J. C., Que J. U., and Cryz S. J. Phase 1 trial of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered simultaneously Vaccine 12 1994 1288 -1294). The most recent study of the 24-valent Klebsiella CPS vaccine demonstrated an excellent antibody response after active immunization in patients with acute blunt or penetrating trauma (Campbell W. N., Hendrix E., Cryz S., and Cross A. S. Immunogenicity of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered to victims of acute trauma Clin. Infect. Dis. 23 1996 179 -181)
2-13-Diagnosis and Testing
2-13-1- Medical History and Clinical Examination
Symptoms of a Klebsiella urinary tract infection (UTI) may include frequent urination, a burning sensation while urinating, blood in the urine, and lower abdominal or pelvic pain. If the infection has reached the kidneys, symptoms may also include fever or back pain.
2-13-2-Urine Tests
Fig(2- 4) Cultur media of klebsiella
2-14-Treatment Guidelines for Klebsiella Infections
The treatment for a Klebsiella infection varies based on the type of infection and the results from the antibiotic sensitivity test. Commonly prescribed antibiotics include:
Cephalosporins (e.g., ceftriaxone)
Carbapenems (e.g., meropenem) for severe infections
Fluoroquinolones (e.g., ciprofloxacin), particularly for uncomplicated urinary tract infections (UTIs), though rising resistance is a concern
Important Notes:
• Klebsiella pneumoniae* is a significant pathogen known to cause urinary tract infections, which can lead to severe complications, particularly in individuals with weakened immune systems.
• Some strains of Klebsiella pneumoniae may be resistant to standard antibiotics. Those that produce Extended-Spectrum Beta-Lactamases (ESBLs) or are classified as Carbapenem-Resistant Klebsiella pneumoniae (CRKP) may require more intensive treatment with stronger antibiotics.
Surgery When the condition worsens and progresses, and abscesses appear, it is necessary to remove them through surgery. Depending on the locations of the abscesses, the doctor will determine the significance and location of the procedure, deciding whether it should take place in a hospital or a private clinic, especially if the required surgical procedure is simple.[35]
2-15- How to Protect Yourself from Exposure to Klebsiella Infection
Chapter three
Material & Methods
MATERIALS AND METHODS
Design and setting Our review was a multi-centric retrospective study done from
November 2008 to January 2011. تغير الفترة لجمع العينات
. Samples were collected from routine patients
Clinical isolates A total of 1,617 mid-stream clean catch urine samples yielding K.
pneumoniae were included in the study. Isolates were identified by standard protocol
and API-20 E system (Biomerieux) and subjected to Kirby-Bauer disk diffusion
sensitivity. MICs were also estimated by Enephlometry. Clinical isolates were tested
for their sensitivity; resistance or intermediate response to these 20 locally available
drugs using Oxoid discs: amikacin,
gentamicin, amoxicillin, amoxiclav (Augmentin), imipenem, piperacillin.tazobactum,
cephradine, cefuroxime, cefixime, cefotaxime, ceftazidime, ceftriaxone, fosfomycin,
pipemidic acid, oflaxacin, ciprofloxacin, doxycycline, cotrimoxazole, nitrofurantoin
and cefoperazone-sulbactam. Zone diameters for each antibiotic were interpreted as
Resistant, Intermediate or Sensitive. The antibiotics were from Oxoid.
The zone diameters were estimated using calipers and according to the method recommended
by the National Committee for Clinical Laboratory Standards (NCCLS, 1987) and the
WHO.
Patient data Subjects were either self-referrals or referred by physicians. Data of age,
sex, date of investigation and any history of antibiotic usage were recorded from
patients presenting with suggestive UTI. Data was analyzed using SPSS version 16.0.
In case of missing values in records, the reported percentage in results is the valid
percentage, ignoring missing values.
Chapter four
Results & Discussions
Isolation of Klebsiella spp. from Urinary Tract Infection (UTI)
Results 4-1-
As presented in the table and figure below, most of patient in this study were
females (52%).
Table (1)The distribution of patients according to gender
Gender frequency Percent
Male 29 48%
Female 31 52%
Total 60 100%
Gender
Figure The distribution of patients according to gender
As presented in the table and figure below, most of patients in this study were those
aged between 20- to 40-years old (53%). The mean age of patients was 33.55±17.26
years, with ranged between 5- to 74 years old.
Table ( 4-2)The distribution of patients according to Age Categories
Age Categories
Frequency Percent
60yrs
6 10%
Total
60 100%
Age (years)
Mean±SD 33.55±17.26
SEM
2.23
Minimum
5
Maximum
74
Age Categories
Figure (4-2)The distribution of patients according to Age Categories
As presented in the table and figure below, most of patients in this study were males
who those aged between 20- to 40-years old (28%).
Table( 4-3)The Cross-distribution of patients according to Gender and Age Categories
Figure(4-4) The Cross-distribution of patients according to Gender and Age Categories
فصل الشكل 4-4 عن الجدول
As presented in the table and figure below, most of the susceptible antibiotics
against K. pneumonia in this study were MEM, VA, and AK as (88%, 80%, and 65%,
respectively) while the most resistance were TE, RA, DXT, CFM, and AMC as (90%,
88%, 88%, 85%, and 82%, respectively)
Table (4-3)The activity of Antibiotics against K. pneumoniae in this study
Figure (4-5)The activity of Antibiotics against K. pneumoniae in this study
DISCUSSION 4-2-
Clinically, UTI is said to exist when 105 bacteria or more per ml of urine are found
in a mid-stream specimen, a common baseline which was adhered to in our
retrospective data. K. pneumoniae, an important uropathogen, is also said to be the
most common cause of illness in humans after respiratory tract infections,
thereby demanding tailored
treatment. In our study, imipenem with an efficacy of 97.7% was found to be the
most effective drug against K. pneumoniae isolates as has been reported by Shah et
al. and Mehrgan et al.. Our results are also consistent with those observed recently
on the efficacy of the drug and was more than the 92.5% sensitivity to carbapenems
reported in Islamabad and 85.1% in Egypt. One study in India showed only 46.66%
antibiotic efficacy for imipenem ,
while another study also in India considered imipenem efficacy to be as high as 99.2% although Klebsiella isolates
have been showing increased resistances the world over . Amoxicillin had efficacy of
0.1%, which was consistent with findings in other studies such as that of Ullah et al. Incidentally, our data revealed that only one patient was sensitive to this antibiotic.
In addition, the first generation cephalosporin, cephradine, showed low (40.3%)
sensitivity in our study, the second generation, cefuroxime, showed 55.9% efficacy,
while the third generation cephalosporins; cefixime, ceftriaxone, ceftazidime and
cefotaxime showed 57.7%, 66.2%, 66.4 and 66.6% efficacy respectively. In Egypt,
cefotaxime, which along with ceftazidime is a potential marker for ESBL
production, was reported to be significantly less effective than in our study . The
same study reported ceftazidime sensitivity of 52% compared with our 66.4%,
ceftriaxone sensitivity of 35.3% as opposed to our 66.2%, cefuroxime sensitivity of
32.7% compared with our 55.9%, indicating the variation of drug effects in
different geographical areas.
Furthermore, a study done in Iran revealed significantly higher resistance (86.6%)
to ceftriaxone than that observed in our study in Karachi and also as reported in
Egypt .
Combination antibiotics showed varying efficacies: piperacillin.tazobactam: 95.7%;
cefoperazone.sulbactam: 95.8% and cotrimoxazole (Septran): 43.1 %. The results of
cotrimoxazole effectiveness were noted to be currently improved as compared to the
previously reported 6.52% by Ullah et al. . Our study also underlined the current
efficacy of piperacillin.tazobactam on our isolates for years 2009-2010 to have only
2.1% resistance, compared to the resistance (66.8%) for years 2005-2007 reported
Chapter five
Conclusion & Recommendations
Conclusions 5-1
1-Klebsiella is an opportunistic pathogen that can cause severe diseases such as sepsis, pneumonia, urinary tract infections, and soft tissue infections.
2-The infection is mostly nosocomial (hospital-acquired) and primarily affects immunocompromised patients, making it a key model for hospital-acquired infections.
3-Klebsiella infections account for 5-7% of all hospital-acquired infections, ranking it among the most significant nosocomial pathogens.
4-Increased outbreaks have been reported in children’s wards, particularly in neonatal intensive care units (NICUs), where Klebsiella causes sepsis and meningitis in newborns.
5-Many of these outbreaks involve multidrug-resistant (MDR) strains, posing a growing concern for pediatricians.
6-Repeated isolation of MDR Klebsiella expressing serotype K55 has been observed, but its significance remains unclear.
7-Hospital outbreaks are often caused by extended-spectrum β-lactamase (ESBL)-producing strains, leading to limited treatment options.
8-The incidence of ESBL-producing strains has been steadily increasing, reaching up to 40% in some areas, highlighting the urgent need for infection control measures.
9- Previously, only K. pneumoniae and K. oxytoca were considered pathogenic, but new Klebsiella species may also be emerging as potential threat
5-2- Recommendations
Supporting research on alternative treatments, such as bacteriophage therapy and immunotherapy.
Strengthening cooperation between hospitals, laboratories, and universities to share data on Klebsiella infections and update treatment protocols based on research findings.
Developing national surveillance programs to monitor infection trends and enable rapid interventions to control outbreaks.
Chapter six
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