Community and hospital acquired bacterial infections Flashcards
Describe the different shapes of bacteria
Cocci
Baccili
Budding and appendaged bacteria- hypha and stalk
Virbio, comma’s form, club rod, helical form, corkscrew’s form, filamentous, spirochete
What is meant by a secretion system
How bacteria transfer their virulent factors to the human cells
Define virulence factor
Molecules produced by pathogens that contribute to the pathogenicity of the organism
Describe some important bacterial virulence factors
Diverse secretion systems
Flagella (movement, attachment)
Pili (important adherence factors)
Capsule (protect against phagocytosis)
i.e. Streptococcus pneumoniae
Endospores (metabolically dormant forms of bacteria)- form spores when their is a shortage of nutrients or in unfavourable conditions
heat, cold, desiccation and chemical resistant
i.e. Bacillus sp. and Clostridium sp.
Biofilms (organized aggregates of bacteria embedded
in polysaccharide matrix – antibiotic resistant)
i. e. Pseudomonas aeruginosa
i.e. Staphylococcus epidermidis- normally commensal on the skin- but can form a biofilm on an intravenous catheter- and leaches out to cause bacteraemia and catheter related sepsis- like a biological bunker to protect attack from the immune system and antibiotics- they can’t penetrate the prosthetic device.
What is meant by facultative intracellular organisms
Many bacteria are phagocytksed by the host’s macrophages and neutrophils, yet survive within these white blood cells unharmed.
These bacteria inhibit phagosome-lysosome function, thus escaping the host’s deadly hydrogen peroxide and superoxide radicals. inside these cells, these bacteria are safe from antibodies and other immune defences.
Yersinia
Listeria monocytogenes.
What are exotoxins
Exotoxins are proteins released by both gram-negative and gram-positive bacteria. They may cause many disease manifestations. Exotoxins are released by most of the major gram-positives.
Gram-negative bacteria such as Vibrio Cholera, E.coli and others also secrete exotoxins.
Severe diseases caused by bacterial exotoxins include anthrax, botulism, tetanus and cholera.
Describe neurotoxins
Neurotoxins are exotoxins that act on the nerves or motor endplates to cause paralysis – Tetanus toxin and botulinum toxin are examples
Describe enterotoxins
Are exotoxins that act on the G.I tract to cause diarrhoea. They inhibit NaCl resorption, activate NaCl secretion, or kill intestinal epithelial cells. The common end result is the osmotic pull of fluid into the intestine, which causes diarrhoea.
Describe infectious diarrhoea caused by enterotoxins
Bacteria colonise and bind to the G.I tract, continuously releasing their enterotoxin locally.
The diarrhoea will continue until the bacteria are destroyed by the immune system, antibiotics, or the patient dies secondary to dehydration).
NEED TO HAVE THE LIVE ORGANISM
i.e. Vibrio cholera, Escherichia coli, Shigella dysenteriae
and Campylobacter jejuni
Describe food poisoning caused by enterotoxins
Bacteria grow in food and release enterotoxin into the fiood.
DON’T NEED LIVE ORGANISM- CAUSED BY ENTEROTOXINS.
The enterotoxin is ingested resulting in diahrrea and vomiting for less than 24 hours.
i.e. Bacillus cereus or Staphylcoccus aureus
Describe pyrogenic exotoxins
Pyrogenic exotoxins stimulate the release of cytokines and can cause rash, fever and toxic shock syndrome
i.e. Staphylcoccus aureus or Streptococcus pyogenes
Describe tissue invasive exotoxins
Tissue invasive exotoxin (allow bacteria to destroy
and tunnel through tissue)
enzymes that destroy DNA, collagin, fibrin, NAD,
red or white blood cells
i.e. Staphylococcus aureus, Streptococcus pyogenes
Clostridium perfringens
Describe miscellaneous exotoxins
Miscellaneous exotoxin (specific to a certain bacterium and/or function not well understood)
i.e. Bacillus anthracis and Corynebacterium diphtheriae
principle virulence factor for that bacteria
What are endotoxins
Endotoxin is lipid A, which is a piece of the outer membrane of LPS of gram-negative bacteria.
LipidA/endotoxin is very toxic and is released when the bacteria undergoes lysis (destruction).
Endotoxin is also shed in steady amounts from living bacteria.
Sometimes, treating a patient who has gram-negative infection with antibiotics can worsen the patient’s condition because all the bacteria are lysed, releasing large quantities of endotoxin.
Endotoxins pathogenic to humans have only been confirmed in gram negative bacteria.
Describe how endotoxins differ from exotoxins
Endotoxin differs from exotoxin in that it is not a protein excreted from bacterial cells, but rather it is a normal part of the outer membrane that sort of sheds off, especially during lysis.
Define bacteraemia
Simply bacteria in the blood
Can trigger the immune system, leading to sepsis and possibly death.
Describe sepsis
Sepsis refers to bacteraemia that causes a systemic immune response to the infection. This response can include low or high temperature, elevation of the WBC, and fast heart rate or low breathing rate. Septic patients are described as looking sick.
Describe septic shock/endotoxin shock
Sepsis that results in dangerous drops in blood pressure and organ dysfunction is called septic shock. It is also referred to as endotoxin shock because endotoxin often triggers the immune system that results in sepsis and shock.
Since gram-positive bacteria and fungi can also trigger this adverse immune response, the term septic shock is more appropriate and inclusive.
Describe the sequelae of events in septic shock
Often begins with a localised site of infection of gram-positive or negative bacteria or fungi.
From this site or from the blood, the organism releases structural components (such as endotoxin and/or exotoxin) that circulate in the bloodstream and stimulate immune cells such as macrophages and neutrophils. These cells, in response to the stimulus, release a host of proteins that are referred to as endogenous mediators of sepsis.
TNF- cachexia and hypotension
IL-1
Prostaglandins
Vasodilation, hypotension and organ system dysfunction.
Describe treatment and management of septic shock
The most effective treatment – find the site of infection the microbe responsible and eradicate it. Lung, abdomen and urinary tract are commune places
Use broad-spectrum antibiotics
Blood pressure must be supported with fluids and drug (dopamine and norepinephrine are commonly used) and oxygenation maintained (intubation and mechanical ventilation).
What is meant by an outbreak
An outbreak is a greater-than-normal or greater-than-expected number of individuals infected or diagnosed with a particular infection in a given period of time, or a particular place, or both.
How can an outbreak be identified
Surveillance provides an opportunity to identify outbreaks
Good and timely reporting systems are instrumental to identify outbreaks
Describe the key features of the E.Coli outbreak in Germany 2011
Causative agent: Outbreak was caused by an entero-aggregative
Shiga-toxin producing E. coli O104:H4 strain
Illness: gastroenteritis and hemolytic-uremic syndrome (HUS)
Source: The consumption of sprouts was identified as the most likely vehicle of infection
Time frame: 1 May 2011- 4 July 2011
Scale: Total of 3816 Cases (54 death) in Germany
845 (22%) of these were with hemolytic-uremic syndrome
Smaller outbreak in France
Incubation period was around 8 days with a medium of 5 days from the onset of diarrhea to development of the hemolytic-uremic syndrome
Describe Haemolytic-Uremic syndrome
first described in children in the 1950th
characterized by a triad of acute renal failure, hemolytic anemia and thrombocytopenia
usually found in children and usually caused by the Shiga toxin producing E. coli strain O157:H7
EHEC strains - enterohemorrhagic E. coli
reservoir are normally ruminants – mostly cattle
human infection occurs through the inadvertent ingestion of fecal matter and secondary through contact with infected humans
usually the hemolytic-uremic syndrome is very rare in adults
Describe the time scale of the German E.Coli outbreak in 2011
May 19th 2011: First report to German’s national-level public health authority of three cases of the hemolytic-uremic syndrome in children admitted on the same day to a hospital in Hamburg.
May 20th 2011: a team arrived to investigate
Other authorities (i.e. food safety) were also contacted and involved to find source in order to prevent further disease
May 22th 2011 – public informed
Describe a possible epidemic case
Any person who developed on or after May 1, 2011:
STEC diarrhoea defined as
- Acute onset of diarrhoea or bloody diarrhoea
AND
- At least one of the following laboratory criteria:
o Isolation of an E. coli strain that produces Shiga toxin 2 (Stx2) or harbors
stx2 gene;
o Direct detection of stx2 gene nucleic acid in faeces without strain isolation.
STEC HUS defined as
Haemolytic Uremic Syndrome (HUS) defined as acute renal failure and
at least one of the following clinical criteria:
Microangiopatic haemolytic anaemia,
Thrombocytopenia.
Describe a probable epidemic case
PROBABLE EPIDEMIC CASE
Any person meeting the criteria for a possible case of STEC diarrhoea or STEC HUS
AND
During the exposure period of 14 days before the onset of illness, meeting at least one of the following epidemiological criteria:
- Stay in Germany or any other country where a confirmed case has probably
acquired infection;
- Consumption of food product obtained from Germany;
Close contact (e.g., in a household) with a confirmed epidemic case.
Describe a confirmed epidemic case
Any person meeting the criteria for a possible case,
AND
Isolation of a STEC strain of serotype O104:H4
OR
Isolation of a STEC strain of serotype O104 AND fulfilling epidemiological criteria for a
probable case
Ultimately, what is the difference between a possible, probable and confirmed epidemic case
§ Possible epidemic case:
o Any person that has developed the symptoms AND has met a laboratory criteria (e.g. isolation of agent).
§ Probable epidemic case:
o Any person that has met the above criteria AND has been in epidemic country, consumed possibly contaminated food, been in close contact with a confirmed epidemic case.
§ Confirmed epidemic case:
o Any person meeting criteria for a possible case AND has had strain isolated.
Describe how PCR can be used to detect the outbreak strain
Isolates can be screened
by multiplex PCR for characteristic features
of the outbreak strain
(rfbO104, fliCH4, stx2, terD)
Can be done on
stool samples
Can for instance use PCR to define if an infection is caused by the outbreak strain or not – different countries have different regulations what is accepted and what is not accepted for diagnosis.
Describe the information gained from genome sequencing of the outbreak strain
Isolate is most similar to the enteroaggregative E. coli (EAEC)
Contains 2 plasmids:
pAA-type plasmids of EAEC strains, which contains the
aggregative adhesion fimbrial operon
ESBL plasmid: harbors the genes encoding for extended- spectrum b-lactamases. This type of plasmid is widely distributed in pathogenic E. coli strains- confers to antibiotic resistance to beta-lactams
Main significant difference of the outbreak strain to those of EAEC strains is the presence of a prophage encoding the Shiga toxin, which is characteristic for enterohemorrhagic E. coli (EHEC) strains- gained by Six phage of EHEC
What family does the Shiga/ Vero toxin belong to
Shiga toxin family members have an AB5 subunit composition
Describe the Shiga toxin
Subunit a (StxA) is non-covalently associated with a
pentamer of protein B (StxB)
StxA is enzymatically active domain (A1 and A2)
StxB pentamer is responsible for binding to host cell receptors
StxA is an enzyme that cleaves the 28S ribosomal RNA in eukaryotic cells
leads to inhibition of protein synthesis
Bacterial ribosomes are also a substrate for StxA and this will result in decreased proliferation of susceptible bacteria
might affect the commensal microflora in the gut
Shiga toxin does not only block protein synthesis in eukaryotic cells but also affects several other cellular processes
Describe the Shiga toxin on the move
Shiga toxins are encoded
on a bacteriophage
highly mobile genetic
elements and contributes
to horizontal gene transfer
Toxins are highly expressed when
the lytic cycle of the phage is activated
Describe the different types of E.coli and where they colonise
Pathogenic Escherichia coli colonize various sites in the human body. Enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC) and diffusely adherent E. coli (DAEC) colonize the small bowel and cause diarrhoea, whereas enterohaemorrhagic E. coli (EHEC) and enteroinvasive E. coli (EIEC) cause disease in the large bowel; enteroaggegrative E. coli (EAEC) can colonize both the small and large bowels. Uropathogenic E. coli (UPEC) enters the urinary tract and travels to the bladder to cause cystitis and, if left untreated, can ascend further into the kidneys to cause pyelonephritis. Septicaemia can occur with both UPEC and neonatal meningitis E. coli (NMEC), and NMEC can cross the blood–brain barrier into the central nervous system, causing meningitis.
Depends on their virulence factors
Summarise the action of aggregative adhesive fimbriae - the virulence factor of EAEC
genes encoding for AAF are on a plasmid mobilized between strains AAF required for adhesion to enterocytes AAF stimulate a strong IL-8 response allowing biofilm formation
Additional virulence factors
lead to the disruption of actin cytoskeleton exfoliations
Describe the virulence of EAEC
Enteroagreggative E. coli (EAEC) attaches to enterocytes in both the small and large bowels
through aggregative adherence fimbriae (AAF) that stimulate a strong interleukin-8 (IL-8) response, allowing biofilms to
form on the surface of cells. Plasmid-encoded toxin (Pet) is a serine protease autotransporter of the Enterobacteriaceae
(SPATE) that targets α-fodrin (also known as SPTAN1), which disrupts the actin cytoskeleton and induces exfoliation
Describe how the EAEC adhered to the intestinal mucosa
First, the bacteria adhere to the intestinal
mucosa using aggregative adherent fimbriae (AAF). Second,
these fimbriae cause autoaggregative adhesion, by
which the bacteria adhere to each other in a ‘stacked-brick’
configuration producing a mucous-mediated biofilm on the
enterocyte surface. Third, the bacteria release toxins that
affect the inflammatory response, intestinal secretion, and
mucosal cytotoxicity. Aspects of each of these steps
involve plasmid-encoded traits but also chromosomal encoded
virulence factors
State 6 groups of communicable diseases in Europe
1) Respiratory tract infections
2) Sexually transmitted infections, including HIV and blood-borne viruses
3) Food- and waterborne diseases and zoonoses
4) Emerging and vector-borne diseases
5) Vaccine-preventable diseases
6) Antimicrobial resistance and healthcare-associated infections
State some respiratory tract infections
Influenza
Animal influenzas, including avian influenza
SARS - Severe acute respiratory syndrome
Legionnaires’ disease (legionellosis) Legionella pneumophila (Gram -)
Tuberculosis Mycobacterium tuberculosis (Gram +)
Summarise legionella pneumophila
Gram-negative bacterium
Lives in amoeba in ponds, lakes, air conditioning units, whirlpools,…
Infection route: inhalation of contaminated aerosols
In humans L. pneumophila will infect and grow in aveolar macrophages
Human infection is “dead end” for bacteria
Important virulence factor type IV secretion system
Describe the role of the type IV secretion System in Legionella pneumophila
Type IV secretion system allows L. pneumophila
to infect and replicate in human macrophages
Secretion of effector proteins
by the type IV secretion system
allow Legionella to replicate in a
Legionella containing vacuole (LCV)
Describe the virulent features of mycobacterium tuberculosis
Groups with
Gram-positive
bacteria
very different cell wall – extra lipid layer makes treatment more difficult- It has a mycolic acid outer membrane – this prevents normal antibiotics from getting into the cell
M. tuberculosis can enter a dormant state
Latent TB - evidence of infection by immunological tests but no clinical signs and symptoms of active disease
Describe the epidemiology of mycobacterium tuberculosis
Around 60,000 cases reported in EU in 2016
Treatment of infections: with antibiotics
BUT TAKES at least 6 months
72% success rate of treatment of new cases
Treatment success rate for second infection is 54%- as a result of resistance to the previous treatment
Multi drug resistant (MDR) treatment success rate in is 32%
State the sexually transmitted infections
Chlamydia trachomatis infection Gonorrhoea (Neisseria gonorrhoeae) Hepatitis B virus infection Hepatitis C virus infection HIV/AIDS Syphilis (Treponema pallidum)
All three are gram negative
What is the causative agent of Syphillis
Treponema pallidum the causative agent of Syphilis is a Gram-negative bacterium and it is a spirochete/
Summarise chlamydia trachomatis
obligate intracellular pathogen
cannot culture it outside host cell
Most frequent STI in Europe 410.000 cases/year
Infection likely higher due to underreporting
Other parts of the world Eye infection:
84 million people infected and about 8 million visually impaired.
It is responsible for more
than 3% of the world’s blindness
Summarise Neisseria gonorrhoea
Gram- negative diplococcus
Establishes infection in the urogenital tract by interacting with non-ciliated epithelical cells
Important virulence factors and traits:
pili and antigenic variation escape detection and clearance by the immune system
State the food- and waterborne diseases and zoonoses
Anthrax (+ Bacillus anthracis -hoofed animals i.e. sheep, cattle, and goats,
but humans who come into contact with infected animals can get sick )
Botulism (+ Clostridium botulinum - through wounds, canned/preserved food)
Brucellosis (– Brucella spp. caused by ingestion of unsterilized milk or meat)
Campylobacteriosis (Campylobacter sp. mostely C. jejuni)
Cholera (- Vibrio cholera)
Infection with Vero/shiga toxin-producing Escherichia coli (Gram negative)
Leptospirosis (- Leptospira spp.)
Listeriosis (+ Listeria monocytogenes)
Salmonellosis (- Salmonella sp.)
Shigellosis (- Shigella sp.)
Tularaemia (- Francisella tularensis)
Typhoid/paratyphoid fever (- Salmonella typhi and S. Paratyphi)
Yersiniosis (- Yersinia enterocolitica)
Summarise Campylobacter sp (mostly C.Jejuni)
Most commonly reported infectious GI disease in the EU
Usually sporadic cases and not outbreaks
Small children 0-4 years – highest risk group
Infection most likely through undercooked poultry
Virulence factor:
Adhesion and Invasion factors,
Flagella motility,
Type IV Secretion system, Toxin
Summarise Salmonella sp.
One of the most common GI infections in the EU Undercooked poltry Outbreaks Highest infection rate in small children (0-4 years) Important virulence determinant Type III secretion systems encoded on pathogenicity islands (SPI)
Salmonella enterica
Type III secretion system
SPI1: is required for invasion
SPI2: intracellular accumulation
Summarise Vibrio Cholerae
Cholera is an acute, severe diarrheal disease Without prompt rehydration, death can occur within hours of the onset of symptoms Latest epidemic in Haiti Oct 2010 – Jan. 2019 As of 2018 > 800.000 cases with ca.10.000 death Important virulence factor: type IV fimbria cholera toxin carried on a phages
Gram positive
Describe the actions of the cholera toxin
When cholera toxin is released from the bacteria in the infected intestine, it binds to the intestinal cells known as enterocytes (epithelial cell in above diagram) through the interaction of the pentameric B subunit of the toxin with the GM1 ganglioside receptor on the intestinal cell, triggering endocytosis of the toxin. Next, the A/B cholera toxin must undergo cleavage of the A1 domain from the A2 domain in order for A1 to become an active enzyme. Once inside the enterocyte, the enzymatic A1 fragment of the toxin A subunit enters the cytosol, where it activates the G protein Gsa through an ADP-ribosylation reaction that acts to lock the G protein in its GTP-bound form, thereby continually stimulating adenylate cyclase to produce cAMP. The high cAMP levels activate the cystic fibrosis transmembrane conductance regulator (CFTR), causing a dramatic efflux of ions and water from infected enterocytes, leading to watery diarrhoea.
One area of anti-diarrhoea treatment lies in the stimulation of enkephalins, which regulate intestinal secretion by acting directly on enterocytes. Enkephalins bind to the opioid receptors on enterocytes, which act through G proteins to inhibit the stimulation of cAMP synthesis induced by cholera toxin, thereby directly controlling ion transport.
Belongs to the AB5 family
Describe how vibrio cholerae developed its virulence
Infected by a TCP phage- leading to the expression of adhesive pili
Further infection with CTX phage- leading to production of cholera toxin
Summarise listeria monocytogenes
Risk group immuno-compromised, elderly, pregnant and their fetus
Listeria can enter non-phagocytic cells and cross three tight barriers
Intestinal barrier, Blood / brain barrier and Materno / fetal barrier
They can enter non-phagocytic cells and cross tight barriers (e.g. BBB and maternal-foetal barrier)
actin-based cell motility
pregnant women should not eat unpasteurised cheese
Describe the impact of research on Listeria
Instrumental for our current understanding of fundamental concepts in cell biology such as actin based cell mobility
Great importance in the field of immunology MHC class I presentation
State the emerging and vector-borne diseases
Malaria Plague (Yersinia pestis; Gram-) Q fever (Coxiella burnetti; Gram –) Severe acute respiratory syndrome (SARS) Smallpox Viral haemorrhagic fevers (VHF). West Nile fever Yellow fever
State the vaccine preventable diseases
Diphtheria (Clostridium diphtheriae Gram +) Invasive Haemophilus influenzae disease (Gram -) Invasive meningococcal disease (Neisseria meningitidis Gram -) Invasive pneumococcal disease (IPD) (Streptococcus pneumoniae Gram +) Measles Mumps Pertussis (Bordetella pertussis Gram -) Polio, Rabies, Rubella Tetanus (Clostridium tetani Gram +)
Describe the impact of vaccine preventable diseases
Smallpox and poliomyelitis have been eradicated
Other diseases virtually eradicated (98-99% reduction)
Define antimicrobial
Antimicrobial
interferes with growth & reproduction of a ‘microbe’
Define antibacterial
Antibacterial
commonly used to describe agents to reduce or eliminate harmful bacteria
What is the difference between antimicrobial and antibacterial
Antibiotic is a type of antimicrobial
used as medicine for humans, animals
originally referred to naturally occurring compounds
may wipe out gut microbiota too
some antibiotics are synthesised- research now looking at unexplored environmental antibiotics.
What is meant by hospital-acquired infections
Healthcare-associated infections (HAI) are infections that occur after exposure to healthcare
Infections starts > 48 after admission to the hospital
Describe the epidemiology of hospital acquired infections
3.2 million patients acquire a healthcare-associated infection in the EU each year (1 in 18 patients acquires an health care associated infection every day)
About 37.000 of them die as the direct consequence of the infection.
The most frequent types of HAI are surgical site infections, urinary tract infections, pneumonia, bloodstream infections and gastrointestinal infections.
Describe the socio-economic burden of hospital-acquired infections
estimated extra cost £1 billion
By increasing the length of stay
longer hospital stays
increased healthcare costs
increased mortality
Describe hospital intervention as a cause of hospital-acquired infection
Lines Intravenous Central Arterial CVP/Pulmonary artery
Catheterisation
Intubation
Chemotherapy- immunosuppression
Prophylactic antibiotics
Inappropriate prescribing
Prosthetic material
Describe some other factors that increase the risk of hospital acquired infections
Dissemination by healthcare staff
Concentration of ill patients
Describe the original ESKAPE pathogens
Enterococcus faecium Staphylococcus aureus Klebsiella pneumoniae Acinetobacter baumanii Pseudomonas aeruginosa Enterobacter species
What are the ESCAPE pathogens
Enterococcus faecium
Staphylococcus aureus
Clostridium difficile
Acinetobacter baumanii
Pseudomonas aeruginosa
Enterobacteriaceae
(E.coli, Klebsiella pneumoniae, Enterobacter sp.)
NOTE:
ESC are Gram-positive
APE are Gram-negative
Describe the issue of the ESCAPE pathogens with antibiotic resistance
Enterococcus faecium (vancomycin resistance)
Staphylococcus aureus (methicillin resistant - MRSA)
Clostridium difficile (can establish infection
because of previous antibiotic treatment)- wipes out gut microbiota- leading to reduced competition for colonisation
Acinetobacter baumanii (highly drug resistant)
Pseudomonas aeruginosa (multi drug resistant
i.e fluoroquinolone-resistant)
Enterobacteriaceae
pathogenic E. coli (multi drug resistant)
Klebsiella pneumoniae (multi drug resistant)
Enterobacter species (multi drug resistant)
Why is antibiotic resistance such an issue for clinicians
Clinicians are forced to use older, previously discarded drugs, such as colistin, that are associated with significant toxicity and for which there is a lack of robust data to guide selection of dosage regimen or duration of therapy
Our therapeutic options for these pathogens are so extremely limited that clinicians are forced to use older, previously discarded drugs, such as colistin,
Summarise pathogenic E.coli
Most frequent cause of bacteraemia by a Gram-negative bacterium
Most frequent cause of community and
hospital acquired UTI
Increase in multi-drug resistant strains
Occurrence of resistance to 3rd generation cephalosporsins as high as 20% in some countries
Most isolates that are resistance to cephalosporin express the extended spectrum beta lactamase (ESBL)
Still sensitive to carbapenems
Describe cephalosporins
are a class of b-lactam antibiotics
Target pathway
Inhibit peptidoglycan
synthesis
Target protein
Inhibit the activity
of penicillin binding
proteins (PBPs)
Describe resistance to cephalosporins
Extended spectrum
b-lactamase (ESBL)
encoded on a plasmid
Mobile
ESBL enzyme cleaves cephalosporin
Describe carbapenems
are a class of b-lactam antibiotics
Target pathway
Inhibit peptidoglycan
synthesis
Target protein
Inhibit the activity
of penicillin binding
proteins (PBPs)
Describe resistance to carbapenems
carbapenemase enzyme,
blakpc
encoded on a tranposon
mobile genetic element
enzyme cleaves carbapenem
Summarise Klebsiella pneumoniae
Important cause of UTI and respiratory tract infections
Risk group: immuno compromised
High proportion of resistance to 3rd generation cephalosporins, fluroquinolones and aminoglycosides
carbapenem-resistant Klebsiella pneumoniae (CRKP) is the species of CRE most commonly encountered in the United States
Summarise pseudomonas aeringuosa
Important cause of infection in immuno-compromised
High proportions of strains are resistant to several antimicrobials
In ½ of EU countries resistance to carbapenems is above 10%
Summarise MRSA
MRSA is the most important cause of antimicrobial resistant infection worldwide
Describe Methicillin
Is a b-lactam antibiotics
Target pathway
Inhibit peptidoglycan
synthesis
Target protein
Inhibit the activity
of penicillin binding
proteins (PBPs)
Describe resistance to Methicillin
Expression of additional
penicillin binding protein
PBP2A has low affinity for methicillin and can still function
in the presence of the antibiotic
MRSA strains can synthesis peptidoglycan and survive in the presence of methicillin
Summarise Vancomycin resistant Enterococcus faecium
Third most frequently identified cause of nosocomial blood stream infections (BSI) identified in the US
Vancomycin resistance is around 60%
Describe the action of vancomycin
Target pathway
Inhibit PG
synthesis
Target
binds to PG precursor
Describe resistance to Vancomycin
multiple proteins
genes encoded on plasmid or transposon
Results in the synthesis of a different PG precursor
Summarise the gram negative antibiotic resistance infections
Pseudomonas aeruginosa: hospital acquired pneumonia, UTI, particularly affects immune compromised hosts (e.g. chemotherapy, individuals with cystic fibrosis). Survives on abiotic surfaces.
ESBL: Extended spectrum beta-lactamase producers. E. coli, Klebsiella.
Acinetobacter baumanii: ITU infections, Survives on abiotic surfaces.
Summarise the gram positive antibiotic resistance infections
Methicillin Resistant Staphylococcus aureus: colonises skin and nasopharynx, causes line associated sepsis, urinary tract infections, bloodstream infections, disseminated spread.
Enterococcus faecium: commensal of gastrointestinal tract. Causes line and urinary tract infection.
