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
