Examples of bacterial infections

and their interaction with the host

Weaskthelabforadiagnosis,
expectingayesorno,butoften
endupwithjustamaybe

Microbes and humans

Very few microbes are
always pathogenic

Many microbes are

potentially pathogenic

Most microbes are

never pathogenic

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

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?
Koch's postulates

the pathogen must be present in every case of the

disease
the pathogen must be isolated from the diseased host &
grown in pure culture
the specific disease must be reproduced when a pure
culture of the pathogen is inoculated into a healthy
susceptible host
the pathogen must be recoverable from the
experimentally infected host

The iceberg concept of infectious disease

poliomyelitis in a child
0.1-1% of infections are
clinically apparent

classical
clinical disease
less severe
disease

rubella
50% of infections are
clinically apparent
asymptomatic infection

Spectrum
of virulence

rabies
100% of infections
are clinically apparent

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

Recognised syndromes
e.g.
septicaemia, endocarditis,
osteomyelitis meningitis,
UTI, pneumonia
pharyngitis

patient's
clinical
condition

potential pathogen
isolated from or
detected in
clinical samples

Microbes and humans

Evidence for a potential pathogen being clinical significant
(particularly for bacteria)

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

The Normal Flora

A New Year Greeting

After an article by Mary J. Marples

in Scientific American, January, 1969
On this day tradition allots
to taking stock of our lives,
my greetings to all of you, Yeasts,
Bacteria, Viruses,
Aerobics and Anaerobics:
A Very Happy New Year
to all for whom my ectoderm
is as Middle-Earth to me.

For creatures your size I offer

a free choice of habitat,
so settle yourselves in the zone
that suits you best, in the pools
of my pores or the tropical
forests of arm-pit and crotch,
in the deserts of my fore-arms,
or the cool woods of my scalp.
Build colonies: I will supply
adequate warmth and moisture,
the sebum and lipids you need,
on condition you never
do me annoy with your presence,
but behave as good guests should,
not rioting into acne
or athlete's-foot or a boil..

W.H. Auden

Relevance of normal flora

(1) Diagnostic microbiology

Which microorganism is a pathogen?

(2) Opportunistic Infections

Normal flora can cause disease

Even organisms not normally considered invasive or pathogenic
Occur in compromised hosts
E.g., immunocompromised, skin breaches,
other infections
Can be medically induced (iatrogenic),
e.g., urinary catheters, venous catheters

The Normal Flora

Our bodies are like mobile warm-blooded

coral reefs, rich in microbial biodiversity and
home to vast numbers of bacterial cells

What are they?

Bacteria, Protozoa, Fungi, Archaea

Metazoa? Viruses?

Where are they?

more bacterial cells (1014) associated with the

human body than there are human ones (only
1013)!

External surfaces (not internal!)

composition of normal flora varies from

individual to individual

some bacterial species carried only transiently

most fairly permanent
difficult to alter composition of the normal flora
of gut in a healthy individual

Microbial Loads on External Surfaces

Large intestine
Skin
Vagina
Mouth
Nose
Throat

1014
1012
1010
1010
1010
1010

Anaerobic Normal Flora

Site

Ratio of Anaerobes:
Aerobes

skin

~ 1:1

large intestine

1000:1

vagina

10:1

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

Normal flora at
various body
sites
Mims C et al.
Medical Microbiology
Textbook. 2004.

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)

Why care about the normal flora?

Normal flora as contaminants

To allow interpretation of

Skin flora in blood cultures

Perineal flora in urine

Throat flora in sputum

Gram stains on clinical samples

Culture results
BUT coagulase-negative staphylococci can be pathogens in deviceassociated sepsis, so can be hard to interpret
Take an MSU!
Mixed culture=contamination
Need to assess whether
Heavy pure growth
Obtained repeatedly
Fits clinical picture

Normal gut
flora
Mims C et al.
Medical Microbiology
Textbook. 2004.

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

antibiotic use
leads to

sensitive gut flora killed

leads to

overgrowth with resistant

flora inc. Clostridium difficile
leads to

C. difficile toxin production

leads to

Diarrhoea,
pseudomembraneous colitis

Treatment
stop precipitating
antibiotic
give oral metronidazole
or vancomycin
recovery requires reestablishment of normal
flora
? probiotics

Bacterial infections & clinical

syndromes
Syndromes caused by bacterial infection can be
classified into two basic types:

those defined on basis of pathogen, where a given species

of bacterium causes a clearly defined syndrome
those defined on the basis of anatomical site of infection
caused by many different sorts of bacteria, individually or
even in combination.

There is overlap between these types of syndrome

because some bacteria cause characteristic
infections at several sites (e.g. Haemophilus
influenzae meningitis and epiglotitis).

The top 7 killers

Mims C et al.
Medical Microbiology. 2004.

Some syndromes defined by

pathogen

typhoid fever
legionnaires disease
tuberculosis
diphtheria

Some syndromes defined by

site

urinary tract infection

pharyngitis
pneumonia
septicaemia
endocarditis
meningitis
osteomyelitis

Urinary tract infection

Definitions
infection of urinary tract

lower UTI (cystitis) of

bladder alone
upper UTI (pyelonephritis)
of kidney & bladder

Signs & Symptoms

Dysuria
Frequency
Tender bladder and/or
kidneys

Samples

Mid-stream urine (MSU)

Meningitis
Definition

Infection of meninges &

adjacent brain

Signs & Symptoms

Headache
Photophobia
Malaise
Neck stiffness
Coma

Samples

Cerebrospinal fluid,
Blood cultures

Septicaemia
Definition

Infection of the blood

("blood poisoning")
Bacteria multiply in the
blood

Signs & Symptoms

Fever
Malaise
Hypotension ( "septic
shock")
Tachycardia

Samples

Blood cultures

Endocarditis
Definition
Infection of the heart valves

Signs & Symptoms

Fever
Malaise
Weight loss
Heart failure

Samples
Blood cultures

Osteomyelitis
Definition
Infection of bone

Signs & Symptoms

Fever
Malaise
Local pain & tenderness

Samples
Blood culture
Bone chippings

Gastroenteritis
Definition

Infection of gut

Signs & Symptoms

Nausea
Vomiting
Diarrhoea

Samples
faeces

Pneumonia
Definition

Infection of lungs

Various clinical syndromes

Bronchopneumonia

Signs & Symptoms

Dyspnoea
Cough
Chest pain

Samples

sputum

Diffuse patchy consolidation

S. pneumoniae, H. influenzae

Lobar pneumonia
Typically S. pneumoniae

Interstitial pneumonia
Characteristically viral

Lung abscess
Atypical pneumonia

Pharyngitis
Definition
throat infection

Signs & Symptoms

sore throat
malaise

Samples
throat swab

Pyrexia of unknown origin

Definition
varies - a common
definition is that of a
fever of more than 2-3
weeks duration, with no
cause that be ascertained
from initial tests.

Signs & Symptoms

various

Samples
many & varied