Extended Spectrum B-Lactamases in Haemophilus? Stephen Tristram

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Transcript Extended Spectrum B-Lactamases in Haemophilus? Stephen Tristram

Normal Microbial Flora
“ Microbiota”
Prof. Khaled H. Abu-Elteen
Microbial Habitats
Sources of infection
SELF
Person
Animal
Environment
Normal flora: microorganisms normally living on or in the body
without normally causing disease.
Your body is a home to 1 x 1014 microbial cells (bacteria)
Outline
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Definitions
Interactions between humans and bacteria
Changes in normal flora
Benefits of normal flora
Why care about the normal flora?
Normal flora
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Throat and mouth
Skin and nose
Adult female genital tract
Large bowel
Harmful effects of gut flora
Harmful alterations in gut flora
Key Terms
Resident
Transient
Contaminant
• Commensalism:
microbe benefits, host unaffected.
• Mutualism:
microbe benefits, host benefits.
• Opportunism:
change in host circumstance.
Normal flora is a significant cause of both minor AND
serious life threatening infections.
Definitions
• Pathogen
– an organism that can cause infection in individuals with normal
host defences, e.g., Salmonella enteritidis, Vibrio cholerae
• Commensal
– an organism that is found normally on those parts of the body that
are exposed to, or communicate with, the external environment, eg.
Bacteroides fragilis, Staphylococcus epidermidis; the 'normal flora'
• Opportunistic pathogen ('opportunist')
– an organism that can cause infection in individuals with abnormal
host defences. Commensals may be opportunistic pathogens.
Microbes and humans
Very few microbes are
always pathogenic
Many microbes are
potentially pathogenic
Most microbes are
never pathogenic
Acquisition of normal flora
• Sterile at birth, but from then on we are continually
exposed to microorganisms, some of which become
established as normal flora.
• During birth
• After birth
maternal
dietary sources and direct contact
• NOT static, but continually changing….
- may reflect your environment
Location, Location, Location
NOT all body sites have normal flora
• Sterile sites
- inaccessible
- unsuitable
- protected
“Most external body sites have normal flora”
• Skin, mouth, URT, GIT, genitourinary tract
• Nature of body SITE has a major influence on TYPE of
normal flora - TROPISM
NORMALLY STERILE SITES IN THE
HUMAN BODY
Colonization of one of these sites generally involves a defect
or breach in the natural defenses that creates a portal of entry
Brain; Central nervous system, CSF
Blood; Tissues; Organ systems
Sinuses; Inner and Middle Ear
Lower Respiratory Tract: Larynx; Trachea;
Bronchioles (bronchi); Lungs; Alveoli
Kidneys; Ureters; Urinary Bladder; Posterior Urethra
Uterus; Endometrium (Inner mucous membrane of
uterus ); Fallopian Tubes;
Skin Flora
• Relatively inhospitable
• Location ?
- dry
- low pH and temperature
- inhibitory secretions
- surface or subsurface
- dry or moist body site
Handwashing: resident, transient, contaminant flora
• Body odour
staphylococci
- role of microbes and anti-perspirant
propionibacterium
yeasts
Upper Respiratory Tract Flora
• Sterile below larynx (bronchi and lungs are sterile)
• Common organisms
- streptococci
- Neisseria
- haemophilus
SPECIAL CONSIDERATION
•Streptococcus pyogenes
•Streptococcus pneumoniae
•Neisseria meningitidis
•Haemophilus influenzae
All are potentially
serious pathogens at
this and other body
sites.
The normal flora
mouth and throat
• saliva has approx. 108
bacteria/ml
• 'viridans streptococci'
– Strep. mutans, Strep.
mitior, Strep. salivarius
• Neisseria spp.
– N. lactamica, N.
flavescens, N.
meningitidis
• Haemophilus influenzae
• Streptococcus pneumoniae
• Corynebacterium spp.
– inc. C. diphtheriae toxigenic and nontoxigenic strains
• Spirochaetes
• Bacteroides
melaninogenicus
• Fusobacteria
• anaerobic cocci
• Actinomyces spp.
Gastronitestinal flora 1
Various parts of organ system – pH, O2 tension, nutrients
MOUTH
- paradoxically is quite anaerobic
- 100 billion per gram tissue
(clenched fist injuries)
- plaque and tooth decay
STOMACH
- ? Sterile site (microbes in transit)
- What about Helicobacter?
Gastrointestinal flora 2
• Small versus large bowel
• 1011-12 bacteria per gram of bowel contents.
- most are anaerobic bacteria (1000:1)
- E. coli is a well known aerobic component.
E. coli as a faecal
indicator organism.
The bowel is an important source of organisms for infection.
The normal flora
large bowel
• Density
– Upper: Medium 108 - 1010/g
– Lower: High >1010/g
• Organisms
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Bacteroides spp.
Enterobacteriaceae, esp E. coli
Enterococci
Clostridium spp.
Candida spp.
Genitourinary tract flora
Urinary tract
Vaginal flora
• Pre-pubescent
• Post-pubescent
- sterile site ? (transient / protected)
- distal urethra
- pH 7
- skin and bowel flora
- pH 5
- hormone / epithelial changes
- lactobacilli
LOSS of normal vaginal flora: CAUSE and EFFECT
Age is a strong predictor for nature of infection
The normal flora
adult female genital tract
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Lactobacilli
Diphtheroids
Staphylococcus epidermidis
Streptococci
enterobacteriaceae
Summary
• Normal flora is not present at all body sites.
• The types of normal flora vary with the nature of the body
site.
• Normal flora is continually changing to reflect your
environment and biological state.
• Normal flora is primarily bacterial with occasional yeasts
(fungi), but no viruses, moulds (fungi) or parasites.
• Important to distinguish between resident, transient and
contaminating flora.
Microbes and humans
Disease can come about in several overlapping ways
1. Some bacteria are entirely adapted to the pathogenic way of life in humans. They are
never part of the normal flora but may cause subclinical infection, e.g. M .
tuberculosis
2. Some bacteria which are part of the normal flora acquire extra virulence factors
making them pathogenic, e.g. E. coli
3. Some bacteria which are part of the normal flora can cause disease if they gain
access to deep tissues by trauma, surgery, lines, e.g. S. epidermidis
4. In immunocompromised patients many free-living bacteria and components of the
normal flora can cause disease, especially if introduced into deep tissues, e.g.
Acinetobacter
How do we know that a given pathogen causes a specific disease?
Diagnosis and effective treatment of
infection depends not just on isolating an
organism, but in establishing a plausible
link between the laboratory findings,
recognised syndromes and the patient's
clinical condition
potential pathogen
isolated from or
detected in clinical
samples
Recognised syndromes
e.g.
septicaemia, endocarditis,
osteomyelitis meningitis,
UTI, pneumonia
pharyngitis
patient's clinical
condition
Microbes and humans
• Evidence for a potential pathogen being clinical significant
(particularly for bacteria)
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Isolated in abundance
Isolated in pure culture
Isolated on more than one occasion
Isolated from deep tissues
Evidence of local inflammation
Evidence of immune response to pathogen
Fits with clinical picture
Changes in normal flora
• with changes in hormal physiology and development
– female genital tract and lactobacilli
• when antibiotics select for a 'resistant flora’
– Candida overgrowth in mouth, vagina
– Clostridium difficile (antibiotic-associated colitis)
• new organisms may be acquired
– neonate from maternal genital tract during birth
– Gram-negative colonisation of gut and URT in hospitalised patients
– Cross-infection with C. difficile, MRSA, VRE etc
Why care about the normal flora?
it may be good for you!
• colonization resistance:
– competition for space and nutrients with pathogens
• release of bacteriocins and colicins (antibacterial substances) to
prevent pathogen growth
• vitamin K production in gut
• continued antigenic stimulation from commensals
– cross-reacting protective immunity against pathogens
– commensal neisseriaceae and Neisseria meningitidis
Why care about the normal flora?
• commensal bacteria may cause disease at their site of carriage or
nearby, e.g.
– Streptococcus mutans (mouth)
• causes dental caries
– Streptococcus pneumoniae (upper airways)
• causes otitis media, sinusitis
• Some members of the normal flora can become pathogenic if they
acquire additional virulence factors (e.g. E. coli) or are introduced into
normally sterile sites (e. g. Staphylococcus aureus)
Harmful effects of gut bacteria
• escape of normal flora to abnormal sites
– perforated appendix leads to peritonitis with
– Bacteroides spp. and facultative aerobes inc. E. coli
• cholecystitis and cholangitis
– often mixed infection, E. coli predominant, also including enterococci
• urinary tract infection
– most frequent organism in normal urinary tract is E. coli
• vaginal candiosis
Harmful effects of alterations in normal gut flora
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antibiotic use
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sensitive gut flora killed
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overgrowth with resistant flora inc.
Clostridium difficile
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C. difficile toxin production
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Diarrhoea, pseudomembraneous
colitis
• Treatment
– stop precipitating antibiotic
– give oral metronidazole or
vancomycin
– recovery requires reestablishment of normal flora
• ? probiotics