Infectious diseases and tumours
Lecture 1: Introduction
Antimicrobial peptides: found in tears, the liver, and the
intestine. They are broad-spectrum, immunomodulators with
little resistance. They are amphipathic, meaning the red are
charged residues (= hydrophilic) and the green hydrophobic
parts.
Preventing a disease can be done by nutrition, personal
hygiene and resistance. Also with vaccination, hygiene
protocols in hospital, and general antimicrobial compounds
(disinfectants, antiseptica)
Disinfectants – sterilants
- Alcohol: vegetative bacterial > denaturation of proteins
- Phenols > denaturation of proteins, disruption of membranes, inactivation of enzymes
- Chlorhexidine: pore formation in membranes (gram+, spores)
- Ammonia: inactivation of enzymes by denaturation
- Aldehydes: alkylation of proteins and nucleic acids
Hospital hygiene: ozone machines > ozone fog > cell lysis
Zoonosis:
- Direct: via air/saliva/bit
- Indirect: via vector (viral diseases, bacterial diseases, protozoan diseases,
helmithoses, mycoses like ringworm, arthropoda like mites)
Ebola: average EVD case fatality rate around 50%, case fatality rates have varied from 25%
to 90% in past outbreaks.
Q fever: Coxiella burnetiid, small, gram-, obligate intracellular, aerosols
Because of the pH, more bacteria are present later in the intestine.
Out of balance: good intestine bacteria can be killed by drugs, making it possible for bad
bacteria to overgrow.
Opportunistic infects: only pathogenic in case of weakened immune system:
- Systemic: neutropenia (HIV, chemotherapy), diabetes, malicious lymphoma (Hodgkin
disease, non-Hodgkin lymphoma)
- Local: skin damage (burn wound, cut, catheter, needle etc), defect in lung mucous layer
Pseudomonas aeruginosa – an opportunistic pathogenic bacterium
It is omnipresent and grows easily. It is already resistant against many antibiotics. 11% of all
hospital infections are from pseudomonas aeruginosa: nosocomial pneumonia, burn wound
infections, urinary tract infections, gram-negative sepsis (bloedvergiftiging), endocarditis,
bone/joint infections, hot tub folliculitis. The infection is green.
Bacterial biofilm:
Attachment > micro colony > early biofilm > mature biofilm > dispersion.
Biofilm-forming communities cause refractory chronic infections. 60% of all the infections
treated by physicians are related to bacteria organized in biofilms. Biofilms have high tolerance
against antibiotics.
,Surface derived biofilm associated infections:
Between 15-25% of hospitalized patients receive urinary catheters during their hospital stay.
13,000 deaths each year are associated with healthcare-associated UTIs. 8.1% risk increase
each subsequent day for the first 7 days. Ventrial hernia repair mesh infection rates range from
1-10%. The cost for a surgical site infection of a total knee replacement exceeds 15,000
dollars.
Quorum sensing:
Bacterial sends out signal (virulence factors) > when many bacteria are around > signal
strength increases > cell will show reaction > biofilm production.
Gram+ vs gram- bacteria
Bactericidal vs bacteriostatic
Bactericidal drugs kills bacteria, bacteriostatic drugs only gives the bacterial grow a rest.
Therefore, for bacteriostatic drugs, a functional immune system is required. Meaning, allergies,
age, kidney function, liver function, pregnancy/lactation, genetic factors, and immunological
response are important.
Infections treated by general practitioner:
1. Airways infections 65%
2. Urinary tract infections 15%
3. Skin infections 10%
4. STDs 5%
5. Intestinal infections 5%
Hospital-antibiotics:
In the hospital are always special situations (low
defence), special pathogens (e.g. Pseudomonas),
problem of resistance (e.g. MRSA).
Pharmacotherapy always on the bases of a culture
(antibiogram)
,Spreading of resistance
Bad bugs, no drugs: no ESKAPE – the
nosocomial ESKAPE pathogens (know these!)
- Enterococcus faecium
- Staphylococcus aureus
- Klebsiella pneumoniae
- Acinetobacter baumanni
- Pseudomonas aeruginosa
- Enterobacter species
Superbugs:
- MRSA (methicillin resistant)
- ESBL (E. Coli and klebsiella) > extended spectrum β-lactamase
- Iraqibacter (multidrug resistant Acenotobacter) > MDRAB
- VRE (vancomycin resistant)
- CRE (carbapenem resistant)
- Multidrug resistant pseudomonas aeruginosa
Transfer to antibiotic resistance:
- Vertical gene transfer ‘’mother-daughter’’
- Horizontal gene transfer ‘’across the boundaries’’
Mechanisms of resistance
Target of the antibiotic:
- Change of structure
- Overproduction
- Bypass
Antibiotic:
- Inactivation by: degradation, modification
- Lowering of conc by: lowered uptake, enhanced
secretion > proton-/ATP-driven pumps
Antibiotic resistance will be the #1 death in 2050 (10 million deaths)
, How to solve problem of resistance?
New investigations like non-explore biotopes in the ocean/desert, symbiotic communititis,
unexplored micro-organisms, activating ‘sleeping’ gene-clusters, or lantibiotics.
Treatment options for biofilms by destroying the signals (quorum quenching, PvdQ).
Bacteriophages (viral therapy) > kill bacteria (bactericidal), replication, specific, disruption of
biofilms, low toxicity. Little research, neutralising ab, not for intracellular pathogens, exchange
of toxins against phages between bacteria, can not be patented.
Use and policy – actions to fight problem of resistance
Quantitative reduction of infections and qualitative improvement of care, novel scientific
research.
Identification of infectious organism:
Diagnosis of disease > microbial culture > microscopy > biochemical test (enzymes,
metabolism) > molecular diagnosis > specific antigen tests.
Approach:
Good diagnostics (antibiogram) > antibiotic (optimal antibiotic/dosing/administration) >
treatment (length/dose, finish the treatment).
Lecture 1: Introduction
Antimicrobial peptides: found in tears, the liver, and the
intestine. They are broad-spectrum, immunomodulators with
little resistance. They are amphipathic, meaning the red are
charged residues (= hydrophilic) and the green hydrophobic
parts.
Preventing a disease can be done by nutrition, personal
hygiene and resistance. Also with vaccination, hygiene
protocols in hospital, and general antimicrobial compounds
(disinfectants, antiseptica)
Disinfectants – sterilants
- Alcohol: vegetative bacterial > denaturation of proteins
- Phenols > denaturation of proteins, disruption of membranes, inactivation of enzymes
- Chlorhexidine: pore formation in membranes (gram+, spores)
- Ammonia: inactivation of enzymes by denaturation
- Aldehydes: alkylation of proteins and nucleic acids
Hospital hygiene: ozone machines > ozone fog > cell lysis
Zoonosis:
- Direct: via air/saliva/bit
- Indirect: via vector (viral diseases, bacterial diseases, protozoan diseases,
helmithoses, mycoses like ringworm, arthropoda like mites)
Ebola: average EVD case fatality rate around 50%, case fatality rates have varied from 25%
to 90% in past outbreaks.
Q fever: Coxiella burnetiid, small, gram-, obligate intracellular, aerosols
Because of the pH, more bacteria are present later in the intestine.
Out of balance: good intestine bacteria can be killed by drugs, making it possible for bad
bacteria to overgrow.
Opportunistic infects: only pathogenic in case of weakened immune system:
- Systemic: neutropenia (HIV, chemotherapy), diabetes, malicious lymphoma (Hodgkin
disease, non-Hodgkin lymphoma)
- Local: skin damage (burn wound, cut, catheter, needle etc), defect in lung mucous layer
Pseudomonas aeruginosa – an opportunistic pathogenic bacterium
It is omnipresent and grows easily. It is already resistant against many antibiotics. 11% of all
hospital infections are from pseudomonas aeruginosa: nosocomial pneumonia, burn wound
infections, urinary tract infections, gram-negative sepsis (bloedvergiftiging), endocarditis,
bone/joint infections, hot tub folliculitis. The infection is green.
Bacterial biofilm:
Attachment > micro colony > early biofilm > mature biofilm > dispersion.
Biofilm-forming communities cause refractory chronic infections. 60% of all the infections
treated by physicians are related to bacteria organized in biofilms. Biofilms have high tolerance
against antibiotics.
,Surface derived biofilm associated infections:
Between 15-25% of hospitalized patients receive urinary catheters during their hospital stay.
13,000 deaths each year are associated with healthcare-associated UTIs. 8.1% risk increase
each subsequent day for the first 7 days. Ventrial hernia repair mesh infection rates range from
1-10%. The cost for a surgical site infection of a total knee replacement exceeds 15,000
dollars.
Quorum sensing:
Bacterial sends out signal (virulence factors) > when many bacteria are around > signal
strength increases > cell will show reaction > biofilm production.
Gram+ vs gram- bacteria
Bactericidal vs bacteriostatic
Bactericidal drugs kills bacteria, bacteriostatic drugs only gives the bacterial grow a rest.
Therefore, for bacteriostatic drugs, a functional immune system is required. Meaning, allergies,
age, kidney function, liver function, pregnancy/lactation, genetic factors, and immunological
response are important.
Infections treated by general practitioner:
1. Airways infections 65%
2. Urinary tract infections 15%
3. Skin infections 10%
4. STDs 5%
5. Intestinal infections 5%
Hospital-antibiotics:
In the hospital are always special situations (low
defence), special pathogens (e.g. Pseudomonas),
problem of resistance (e.g. MRSA).
Pharmacotherapy always on the bases of a culture
(antibiogram)
,Spreading of resistance
Bad bugs, no drugs: no ESKAPE – the
nosocomial ESKAPE pathogens (know these!)
- Enterococcus faecium
- Staphylococcus aureus
- Klebsiella pneumoniae
- Acinetobacter baumanni
- Pseudomonas aeruginosa
- Enterobacter species
Superbugs:
- MRSA (methicillin resistant)
- ESBL (E. Coli and klebsiella) > extended spectrum β-lactamase
- Iraqibacter (multidrug resistant Acenotobacter) > MDRAB
- VRE (vancomycin resistant)
- CRE (carbapenem resistant)
- Multidrug resistant pseudomonas aeruginosa
Transfer to antibiotic resistance:
- Vertical gene transfer ‘’mother-daughter’’
- Horizontal gene transfer ‘’across the boundaries’’
Mechanisms of resistance
Target of the antibiotic:
- Change of structure
- Overproduction
- Bypass
Antibiotic:
- Inactivation by: degradation, modification
- Lowering of conc by: lowered uptake, enhanced
secretion > proton-/ATP-driven pumps
Antibiotic resistance will be the #1 death in 2050 (10 million deaths)
, How to solve problem of resistance?
New investigations like non-explore biotopes in the ocean/desert, symbiotic communititis,
unexplored micro-organisms, activating ‘sleeping’ gene-clusters, or lantibiotics.
Treatment options for biofilms by destroying the signals (quorum quenching, PvdQ).
Bacteriophages (viral therapy) > kill bacteria (bactericidal), replication, specific, disruption of
biofilms, low toxicity. Little research, neutralising ab, not for intracellular pathogens, exchange
of toxins against phages between bacteria, can not be patented.
Use and policy – actions to fight problem of resistance
Quantitative reduction of infections and qualitative improvement of care, novel scientific
research.
Identification of infectious organism:
Diagnosis of disease > microbial culture > microscopy > biochemical test (enzymes,
metabolism) > molecular diagnosis > specific antigen tests.
Approach:
Good diagnostics (antibiogram) > antibiotic (optimal antibiotic/dosing/administration) >
treatment (length/dose, finish the treatment).
