ESKAPE
pathogens with strains the are multi drug resistant, responsible for
majority of HAI
E (ESKAPE)
Enterococcus faecium
S (ESKAPE)
Staphylococcus aureus
K (ESKAPE)
Klebsiella pneumoniae
A (ESKAPE)
Acinetobacter baumanii
P (ESKAPE)
Pseudomonas aeruginosa
E (ESKAPE)
Enterobacter species
Genera of Gram Positive Bacteria w/ Pathogenic Representatives
Staphylococcus, Streptococcus, Enterococcus, Bacillus, Clostridium,
Listeria, Mycoplasmas, Corynebacterium, Mycobacterium,
Propionibacterium, Nocardia and Actinomyces
Structure of Staphyloccocus
Facultative anaerobes, cells occur in grape like clusters, nonmotile,
salt-tolerant (halo tolerant - tolerate salt on human skin), tolerant
of desiccation, radiation and heat (survive of environmental surfaces)
Common Staphylococcus associated with diseases in humans
Staphylococcus aureus and Staphylococcus epidermidis
Staphylococcus aureus
more virulent strain
variety of conditions depending on site of infection
primarily found only in moist skin folds
Staphylococcus epidermidis
normal microbiota of human skin
opportunistic infections
Staphylococcus diseases
normal microbial flora of skin and upper respiratory tract
opportunistic pathogen
endo and exotoxins
pyrogenic and pus forming
exotoxin a-superantigen, t-cell response (diarrhea/vomit)
MRSA, VISA, VRSA
Source of Exotoxins
Mainly gram-positive and gram-negative bacteria
Relation to bacteria (Exotoxins)
Metabolic product secreted from living cell
Chemical Nature (Exotoxins)
Protein or Short Peptide
Toxicity of Exotoxins
high
Heat Stability of Exotoxins
typically unstable at temp. above 60oC
Exotoxin Effect on Host
Variable depending on source, may be cytotoxin, neurotoxin, enterotoxin
Are Exotoxins fever producing?
No
Antigenicity of Exotoxins
Strong: stimulates antitoxin (antibody) production
Exotoxins: Toxid Formation for immunisation?
By treatment with heat or formaldehyde
Representative Diseases
Botulism, tetanus, gas gangrene, diphtheria, cholera, plague,
staphylococcal food poisoning
Source of Endotoxins
Gram-negative bacteria
Relation to Bacteria (Endotoxins)
portion of outer (cell wall) membrane released upon cell death
Chemical Nature (Endotoxins)
Lipid portion of lipopolysaccharide (Lipid A) of outer (cell wall) membrane
Toxicity (Endotoxins)
Low but may be fatal in high doses
Heat Stability of Endotoxins
Stable for up to 1 hour at autoclave temp. (121oC)
Effect on Host (Endotoxins)
Fever, lethargy, malaise, shock, blood coagulation
Do Endotoxins produce fever?
Yes
Antigenicity of Endotoxins
Weak
Toxoid formation for immunisation (Endotoxins)
Not feasible
Representative diseases of endotoxins
Typhoid fever, tularemia, endotoxic shock, urinary tract infections,
meningococcal meningitis
Superantigen
group of powerful antigens occurring in various microbes that bind
outside of the normal T cell receptor site. They are able to react
with multiple TCR, thus activating T cells nonsepcficially
Pathogenicity of Staphylococcus
Results from:
Structures that enable it to evade phagocytosis
production of enzymes
production of toxins
(Pathogenicity) Structural defences against phagocytosis:
Protein A Coats the cell of Surface
Binds to IgG and inhibits opsonisation and the complement cascade
(Pathogenicity) Structural defences against phagocytosis:
Bound coagulase
Converts fibrinogen into fibrin molecules, fibrin clots hide the
bacteria from phagocytic cells
(Pathogenicity) Structural defences against phagocytosis:
Synthesize polysaccharide slime layers (capsules)
inhibit leukocyte chemotaxis and phagocytosis, facilitate attachment
of Staphylococcus to surfaces
(Pathogenicity) Enzymes (exotoxins):
Cell-free coagulase
triggers blood clotting
(Pathogenicity) Enzymes (exotoxins):
Hyaluronidase
breaks down hyaluronic acid, enables the bacteria to spread between cells
(Pathogenicity) Enzymes (exotoxins):
Staphylokinase
dissolves fibrin threads in blood clots, allows S. aureus to free
itself from clots
(Pathogenicity) Enzymes (exotoxins):
Lipases
digest lipids, allow staphylococcus to grow on skin and in oil glands
(Pathogenicity) Enzymes (exotoxins):
Beta-lactamase
antibiotic resistance, breaks down penicillin, allows bacteria to
survive treatment with beta-lactam antimicrobial drugs (penicillin,
oxacillin, nafcillin and methicillin)
(Pathogenicity) Toxins:
produced by S. aureus and less frequently by S. epidermidis
(Pathogenicity) Toxins:
Cytolytic Toxins
disrupt the cytoplasmic membrane of a variety of cells, leukocidin
can lyse leukocytes specifically
(Pathogenicity) Toxins:
Exfoliative toxins
cause skin cells to separate and slough off
(Pathogenicity) Toxins:
Toxic-shock syndrome toxin
superantigen, causes toxic-shock syndrome
(Pathogenicity) Toxins:
Enterotoxins
stimulate symptoms associated with food poisoning
Both S. epidermidis and S. aureus
grow in the upper respiratory, gastrointestinal, and urogenital
tracts of humans
Staphylococcal Disease: Noninvasive Disease
Food Poisoning
- due to ingestion of enterotoxin-contaminated food
Staphylococcal Disease: Cutaneous Disease
various skin conditions, scalded skin syndrome, impetigo, folliculitis
Staphylococcal Disease: Systemic Disease:
Toxic-Shock Syndrome (nonsteptococcal)
some Staphylococcus strains produce TSS toxin
Causes of Systemic Staphylococcal Diseases
primarily tampon usage (abrasive), skin infections and surgery
Treatment for Systemic Staphylococcal Disease
Treatment: antibiotics (IV), dialysis, fluids, IV gamma globulins
Staphylococcal Disease: Systemic Disease:
Endocarditis
damage to the lining of the heart
Staphylococcal Disease: Systemic Disease:
Pneumonia
Inflammation of the lungs, empyema occurs when pus fills the lungs
Staphylococcal Disease: Systemic Disease:
Bacteremia
presence of bacteria in the blood
Staphylococcal Disease: Systemic Disease:
Osteomyelitis
inflammation of the bone and bone marrow
Staphylococcal Disease:
Septicemia
presence of any microbial infection of the blood that produces illness
Staphylococcal Disease:
Bacteremia
bacterial septicaemia that is often harmless
Staphylococcal Disease:
Toxemia
release of bacterial toxins into the blood
Diagnosis of Staphylococcus
detect gram-positive bacteria in grape like arrangements
Treatment of Staphylococcus
methicillin, vancomycin used to treat MRSA infections
Prevention of Staphylococcus
Hand antisepsis
Some Pathogenic Gram-Negative Bacteria
Neisseria, Pseudomonas, Enterobacteriaceae, Pasteurellaceae
Enterobacteriaceae
Coliform, Noncoliform, True Pathogens
Enterobacteriaceae: Coliform
Escherichia coli, Klebsiella
Enterobacteriaceae: Noncoliform
Proteus
Enterobacteriaceae: True Pathogens
Salmonella, Shigella, Yersinia
Enterobacteriaceae: Pasteurellaceae
Pasteurella, Haemophilus
Coliforms - Structure
aerobic or faculatative anaerobic, gram-negative, rod-shaped bacteria
that ferment lactose to form gas in lactose broth
Coliforms - Found where...
in soil, on plants and on decaying vegetation,
Coliforms - Colonizes...
intestinal tracts of animals and humans
Coliform are indicators of...
Sanitary quality of foods and water
Indicates the potential presence of a health risk
not necessarily pathogens but easily detected
Characteristics of Coliforms
- Gram-negative rods
- 35-37oC ferment lactose: acid and gas
Sources of Coliform
feces, nonpathogenic and pathogenic microbes.
Coliform: Escherichia coli
most common/important
have genese for fimbraie, adhesions and exotoxins
causes several diseases
Most common E. coli disease
gastroenteritis
produces diarrhoea, cramps, nausea and vomitting, often mediated
by enterotoxins, major cause of pediatric diarrhoea in developing countries
E. coli is the most common cause of...
non-nosocomial urinary tract infections
(more in women)
E. coli O157:H7
- most prevalent pathogenic E.Coli in developed countries, associated
with consumption of undercooked ground beef or contaminated milk/fruit
juice, produces type III secretion system and Shiva-like toxin, causes
diarrhoea, hemorrhagic colitis, haemolytic ureic syndrome
Klebsiella
found in digestive and respiratory systems of humans and animals,
capsule protects the bacteria from phagocytosis, can cause
opportunistic infections
Klebsiella pneumoniae
most commonly isolated pathogenic species, causes pneumonia, may be
involved in bacteria, meningitis, wound infections, UTIs
Serratia
produce a red pigment when grown at room temp. , can grow on
catheters, in saline solutions and on other hospital supplies, can
cause life-threatening opportunistic infections in immunocompromised
patients, frequently resistant to antimicrobial drugs
Enterobacter, Hafnia, and Citrobacter is found in...
soil, water, decaying vegetation and sewage
Enterobacter, Hafnia, and Citrobacter resides...
digestive tracts of animals and humans
Enterobacter
can contaminate diary products
Enterobacter, Hafnia, and Citrobacter can cause...
opportunistic pathogens like nosocomial infections in
immunocompromised patients
(difficult to treat due to resistance to antimicrobial drugs)
Gram-Negative Bacteria
breach skin or mucous membranes, grow at 37oC and evade the immune
system can cause disease in humans
Gram- Negative Bacteria
largest group of human bacterial pathogens
produces endotoxins and also some exotoxins
Gram-Negative Endotoxin
Lipid A in the bacterial cell wall that triggers fever, vasodilation,
inflammation, shock, DIC
Structure and Physiology of Neisseria
only genus of Gram-negative cocci that regularly causes disease in
humans, aerobic, nonmotile, arranged as diplocci,
How does Neisseria different from other Gram-negatives
oxidase positive
Pathogenic strains of neisseria
have fijmbraie, a polysaccharide capsule and a cell wall containing
lipid A
2 pathogenic species of Neisseria to Humans
N. gonorrhoea, N. meningitidis
Meningococcus
Neisseriai meningitidis
Neisseria meningitidis
most common cause of meningitis in <20 years old, can be normal
microbiota of the upper respiratory tract, transmitted by respiratory droplets
Meningitis can cause death within...
6 hours of symptoms
Meningococcal septicemia
can be life threatening
Diagnosis: Neisseria meningitidis
critical, gram-negative diplococci in phagocytes of the CNS
Treatment: Neisseria meningitidis
immediate administration o intravenous penicillin
Prevention: Neisseria meningitidis
asymptomatic carriers make eradication unlikely, vaccine against some
meningococcal strains is available
Gonococcus is caused by
Neisseria gonorrhoeae
causes gonorrhea
Gonorrhea
only occurs in humans, STD, gonococci adhere to the genital, urinary,
and digestive tract
How does Neisseria gonorrhoeae evade the immune system
secrete protease that cleaves secretory IgA, survive within
neutrophils, antigenic switching
Epidemiology
occurs more in females, most occur in adolescents
Gonorrhea in Men
inflammation causes painful urination and puss-filled discharge
Gonorrhea in Women
often asymptomatic, can trigger pelvic inflammatory disease
Infection of Gonococcus
outside the reproductive tract (proctitis, pharyngitis, gingivitis)
cornea or respiratory tract of newborns can occur during childbirth
Diagnosis: Neisseria gonorrhoeae
asymptomatic cases identified with genetic probes, gram-negative
diplococci in pus from inflamed penis
Treatment: Neisseria gonorrhoeae
complicated due to antibiotic resistant strains, broad-spectrum
intramuscular cephalosporins
Prevention: Neisseria gonorrhoeae
sexual abstinence, monogamy, and proper condom use
eye infections in newborns prevent with antimicrobials
Transmission of DHH STIs
nonsexual, sexual, vertical transmission to offspring, horizontal transmission
Gonorrhea: Neisseria gonorrhoeae
Properties
Gram-negative, diplococcus, sensitive to environmental conditions
(UV, sunlight - drying out)
Gonorrhea: Neisseria gonorrhoeae
Drug Resistance
Penicillin, increasing drug resistance
Gonorrhea: Neisseria gonorrhoeae
Immunity
no acquired immunity (antigenic switching), oral contraceptives
alters vagina, more suitable for N. gonorrhoeae.
Syphilis: genera and species
Treponemia Pallidum
Syphilis
gram-negative, extremely sensitive to environmental conditions,
highly invasive, few surface proteins, multistage infection
Primary Syphilis
localised lesion (chanc??) infection
clears up
Secondary Syphilis
Mucous membranes, eyes, joints, bones and CNS,
general skin rash
1/2 clears up
Tertiary Syphilis
mild skin infection,
serious/fatal degeneration of cardiovascular or CNS
Chlamydia: genus, species
Chlamydia trachomatis
Properties of Chlamydia
obligate intracellular, asymptomatic 3/4 in females and 1/2 in males
Chlamydia if untreated can cause, in females,
can lead to pelvic inflammatory disease, or worst, sterility
Chlamydia and Gonorrhoeae
An infection that usually falls gonorrhea
there are antibiotics that are coupled with treatment for Neisseria gonorrhoeae
In the U.S., about _ people acquire bacterial infections in U.S.
hospitals each year.
2 million
_ die as result of bacterial infections
90,000
Approximately, _ of those infections are resistant to at least one antibiotic.
70%
Mechanisms of Drug Resistance
Alteration of target (enzymes/ribosomes), Inactivation of drug by
pathogen, Degrading the drug, Chemical modification of drug,
Alteration of membrane permeability, alteration of Metabolic Pathway,
Efflux pumps
Origin and Spread of Drug Resistance Genes
Rare mutations of bacterial chromosomes, horizontal gene transfer,
mobile genetic elements
Horizontal Gene Transfer
Transformation, Transduction, Conjugation
Mobile Genetic Elements
R Plasmid (resistance) can carry multiple resistance genes, transposons
Carbapenem- Resistant Enterobacteriaceae in Healthcare Settings
Klebsiella sp. & Escherichia coli
Klebsiella sp. & Escherichia coli
� KPC (Klebsiella pneumoniae carbapenemase)� NDM (New Delhi
Metallo-beta-lactamase)� VIM (Verona Integron-Mediated Metallo-?-lactamase)
Antibiotics
antimicrobial agents produced naturally by organisms
Alexander Fleming 1928
penicillin and antibiotics
Ernst Chain and Howard Florey
doctors could cure diseases
U.S. Surgeon General William H. Steward
the idiot that thought that infectious diseases were gone
Origin of Antibacterial Chemotherapeutic agents
antibiotics (natural products and semi-synthetic compounds)
Synthetic compound s
Spectrum of Action
Narrow and Broad
Consideration of Chemotherapeutic Agents
Allergic, Disruption of Normal Microbiome, Toxicity
Consideration of Chemotherapeutic Agents: Toxicity
Selective Toxicity
ability of drug to kill or inhibit pathogen while damaging host as
little as possible
Consideration of Chemotherapeutic Agents: Toxicity
Therapeutic Dose
drug level required for clinical treatment
Consideration of Chemotherapeutic Agents: Toxicity
Toxic Dose
drug level at which drug becomes too toxic for patient (therefore,
side effects)
Therapeutic Index =
Toxic Dose / Therapeutic Dose
Farm animals get _ of antibiotics sold in the US.
80%