Community and hospital acquired bacterial infections

Question 1

Describe the different shapes of bacteria

Answer 1

Cocci
Baccili
Budding and appendaged bacteria- hypha and stalk
Virbio, comma’s form, club rod, helical form, corkscrew’s form, filamentous, spirochete

Question 2

What is meant by a secretion system

Answer 2

How bacteria transfer their virulent factors to the human cells

Question 3

Define virulence factor

Answer 3

Molecules produced by pathogens that contribute to the pathogenicity of the organism

Question 4

Describe some important bacterial virulence factors

Answer 4

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.

Question 5

What is meant by facultative intracellular organisms

Answer 5

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.

Question 6

What are exotoxins

Answer 6

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.

Question 7

Describe neurotoxins

Answer 7

Neurotoxins are exotoxins that act on the nerves or motor endplates to cause paralysis – Tetanus toxin and botulinum toxin are examples

Question 8

Describe enterotoxins

Answer 8

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.

Question 9

Describe infectious diarrhoea caused by enterotoxins

Answer 9

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

Question 10

Describe food poisoning caused by enterotoxins

Answer 10

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

Question 11

Describe pyrogenic exotoxins

Answer 11

Pyrogenic exotoxins stimulate the release of cytokines and can cause rash, fever and toxic shock syndrome

i.e. Staphylcoccus aureus or Streptococcus pyogenes

Question 12

Describe tissue invasive exotoxins

Answer 12

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

Question 13

Describe miscellaneous exotoxins

Answer 13

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

Question 14

What are endotoxins

Answer 14

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.

Question 15

Describe how endotoxins differ from exotoxins

Answer 15

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.

Question 16

Define bacteraemia

Answer 16

Simply bacteria in the blood

Can trigger the immune system, leading to sepsis and possibly death.

Question 17

Describe sepsis

Answer 17

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.

Question 18

Describe septic shock/endotoxin shock

Answer 18

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.

Question 19

Describe the sequelae of events in septic shock

Answer 19

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.

Question 20

Describe treatment and management of septic shock

Answer 20

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).

Question 21

What is meant by an outbreak

Answer 21

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.

Question 22

How can an outbreak be identified

Answer 22

Surveillance provides an opportunity to identify outbreaks

Good and timely reporting systems are instrumental to identify outbreaks

Question 23

Describe the key features of the E.Coli outbreak in Germany 2011

Answer 23

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

Question 24

Describe Haemolytic-Uremic syndrome

Answer 24

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

Question 25

Describe the time scale of the German E.Coli outbreak in 2011

Answer 25

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

Question 26

Describe a possible epidemic case

Answer 26

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.

Question 27

Describe a probable epidemic case

Answer 27

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.

Question 28

Describe a confirmed epidemic case

Answer 28

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

Question 29

Ultimately, what is the difference between a possible, probable and confirmed epidemic case

Answer 29

§ 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.

Question 30

Describe how PCR can be used to detect the outbreak strain

Answer 30

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.

Question 31

Describe the information gained from genome sequencing of the outbreak strain

Answer 31

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

Question 32

What family does the Shiga/ Vero toxin belong to

Answer 32

Shiga toxin family members have an AB5 subunit composition

Question 33

Describe the Shiga toxin

Answer 33

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

Question 34

Describe the Shiga toxin on the move

Answer 34

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

Question 35

Describe the different types of E.coli and where they colonise

Answer 35

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

Question 36

Summarise the action of aggregative adhesive fimbriae - the virulence factor of EAEC

Answer 36

``` 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

Question 37

Describe the virulence of EAEC

Answer 37

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

Question 38

Describe how the EAEC adhered to the intestinal mucosa

Answer 38

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

Question 39

State 6 groups of communicable diseases in Europe

Answer 39

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

Question 40

State some respiratory tract infections

Answer 40

Influenza Animal influenzas, including avian influenza SARS - Severe acute respiratory syndrome ``` Legionnaires’ disease (legionellosis) Legionella pneumophila (Gram -) ``` ``` Tuberculosis Mycobacterium tuberculosis (Gram +) ```

Question 41

Summarise legionella pneumophila

Answer 41

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

Question 42

Describe the role of the type IV secretion System in Legionella pneumophila

Answer 42

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)

Question 43

Describe the virulent features of mycobacterium tuberculosis

Answer 43

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

Question 44

Describe the epidemiology of mycobacterium tuberculosis

Answer 44

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%

Question 45

State the sexually transmitted infections

Answer 45

``` Chlamydia trachomatis infection Gonorrhoea (Neisseria gonorrhoeae) Hepatitis B virus infection Hepatitis C virus infection HIV/AIDS Syphilis (Treponema pallidum) ``` All three are gram negative

Question 46

What is the causative agent of Syphillis

Answer 46

Treponema pallidum the causative agent of Syphilis is a Gram-negative bacterium and it is a spirochete/

Question 47

Summarise chlamydia trachomatis

Answer 47

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

Question 48

Summarise Neisseria gonorrhoea

Answer 48

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 ```

Question 49

State the food- and waterborne diseases and zoonoses

Answer 49

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)

Question 50

Summarise Campylobacter sp (mostly C.Jejuni)

Answer 50

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

Question 51

Summarise Salmonella sp.

Answer 51

``` 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

Question 52

Summarise Vibrio Cholerae

Answer 52

``` 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

Question 53

Describe the actions of the cholera toxin

Answer 53

      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

Question 54

Describe how vibrio cholerae developed its virulence

Answer 54

Infected by a TCP phage- leading to the expression of adhesive pili Further infection with CTX phage- leading to production of cholera toxin

Question 55

Summarise listeria monocytogenes

Answer 55

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

Question 56

Describe the impact of research on Listeria

Answer 56

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 ```

Question 57

State the emerging and vector-borne diseases

Answer 57

``` 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 ```

Question 58

State the vaccine preventable diseases

Answer 58

``` 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 +) ```

Question 59

Describe the impact of vaccine preventable diseases

Answer 59

Smallpox and poliomyelitis have been eradicated | Other diseases virtually eradicated (98-99% reduction)

Question 60

Define antimicrobial

Answer 60

Antimicrobial | interferes with growth & reproduction of a ‘microbe’

Question 61

Define antibacterial

Answer 61

Antibacterial | commonly used to describe agents to reduce or eliminate harmful bacteria

Question 62

What is the difference between antimicrobial and antibacterial

Answer 62

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.

Question 63

What is meant by hospital-acquired infections

Answer 63

Healthcare-associated infections (HAI) are infections that occur after exposure to healthcare Infections starts > 48 after admission to the hospital

Question 64

Describe the epidemiology of hospital acquired infections

Answer 64

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.

Question 65

Describe the socio-economic burden of hospital-acquired infections

Answer 65

estimated extra cost £1 billion By increasing the length of stay longer hospital stays increased healthcare costs increased mortality

Question 66

Describe hospital intervention as a cause of hospital-acquired infection

Answer 66

``` Lines Intravenous Central Arterial CVP/Pulmonary artery ``` Catheterisation Intubation Chemotherapy- immunosuppression Prophylactic antibiotics Inappropriate prescribing Prosthetic material

Question 67

Describe some other factors that increase the risk of hospital acquired infections

Answer 67

Dissemination by healthcare staff Concentration of ill patients

Question 68

Describe the original ESKAPE pathogens

Answer 68

``` Enterococcus faecium Staphylococcus aureus Klebsiella pneumoniae Acinetobacter baumanii Pseudomonas aeruginosa Enterobacter species ```

Question 69

What are the ESCAPE pathogens

Answer 69

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

Question 70

Describe the issue of the ESCAPE pathogens with antibiotic resistance

Answer 70

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)

Question 71

Why is antibiotic resistance such an issue for clinicians

Answer 71

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,

Question 72

Summarise pathogenic E.coli

Answer 72

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

Question 73

Describe cephalosporins

Answer 73

``` are a class of b-lactam antibiotics ``` Target pathway Inhibit peptidoglycan synthesis Target protein Inhibit the activity of penicillin binding proteins (PBPs)

Question 74

Describe resistance to cephalosporins

Answer 74

Extended spectrum b-lactamase (ESBL) encoded on a plasmid Mobile ESBL enzyme cleaves cephalosporin

Question 75

Describe carbapenems

Answer 75

``` are a class of b-lactam antibiotics ``` Target pathway Inhibit peptidoglycan synthesis Target protein Inhibit the activity of penicillin binding proteins (PBPs)

Question 76

Describe resistance to carbapenems

Answer 76

carbapenemase enzyme, blakpc encoded on a tranposon mobile genetic element enzyme cleaves carbapenem

Question 77

Summarise Klebsiella pneumoniae

Answer 77

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

Question 78

Summarise pseudomonas aeringuosa

Answer 78

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%

Question 79

Summarise MRSA

Answer 79

MRSA is the most important cause of antimicrobial resistant infection worldwide

Question 80

Describe Methicillin

Answer 80

Is a b-lactam antibiotics Target pathway Inhibit peptidoglycan synthesis Target protein Inhibit the activity of penicillin binding proteins (PBPs)

Question 81

Describe resistance to Methicillin

Answer 81

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

Question 82

Summarise Vancomycin resistant Enterococcus faecium

Answer 82

Third most frequently identified cause of nosocomial blood stream infections (BSI) identified in the US Vancomycin resistance is around 60%

Question 83

Describe the action of vancomycin

Answer 83

Target pathway Inhibit PG synthesis Target binds to PG precursor

Question 84

Describe resistance to Vancomycin

Answer 84

multiple proteins genes encoded on plasmid or transposon Results in the synthesis of a different PG precursor

Question 85

Summarise the gram negative antibiotic resistance infections

Answer 85

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.

Question 86

Summarise the gram positive antibiotic resistance infections

Answer 86

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.