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342 Cards in this Set

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haemophilus influenzae
most common cause of bacterial meningitis in children under 4 years
haemophilus influenzae
name is misnomer. was once through to be cause of flu epidemics (which in fact were viral in origin; although they may have been a secondary invader)
haemophilus influenzae
small, gran-negative, non-motile, non-spore-forming bacillus (or coccobacillus) with complex nutritional requirements
H. influenzae type b (Hib) and other encapsulated strains
as a natural disease, occurs only in humans, experiementally in monkeys/rodents
H. influenzae type b (Hib) and other encapsulated strains
no known edotoxin (anti-endotoxin Abs not protective, but anti-capsular Abs are)
H. influenzae type b (Hib) and other encapsulated strains
produces IgA protease
H. influenzae type b (Hib) and other encapsulated strains
portal into humans is via respiratory tract generally by aerosols between children; often live there harmlessly, 30-50% carrier rate in children who may harbor unencapsulated strains
H. influenzae type b (Hib) and other encapsulated strains
disease starts as a nasopharyngitis (with otitis media--infection of the middle ear--or sinusitis)
H. influenzae type b (Hib) and other encapsulated strains
bacteremia with involvement of meninges
H. influenzae type b (Hib) and other encapsulated strains
less common but serious: epiglottitis and obstructive laryngitis, sudden onset, fatal within 24 hours, treatment must be prompt and airway ensured if necessary by tracheotomy
H. influenzae type b (Hib) and other encapsulated strains
sometimes bacteria spread to face (causing cellulitis)
H. influenzae type b (Hib) and other encapsulated strains
sometimes bacteria spread to joints, causing childhood pyarthrosis (pus in a joint)
H. influenzae type b (Hib) and other encapsulated strains
causes pneumonia
meningitis, epiglottitis
medical emergencies
H. influenzae type b (Hib) and other encapsulated strains
possesses a polysaccharide capsule that is antiphagocytic
H. influenzae type b (Hib) and other encapsulated strains
capsular carbohydrates provoke protective antibodies, capsule is basis for serotyping, six types a-f identified by agglutination, precipitation, or quellung (capsular swelling) tests with specific antisera
H. influenzae type b (Hib) and other encapsulated strains
most important. unlike a,c,d,e,f, which have hexose in polysaccharide capsular structure, this has ribose (5-carbon sugar)
H. influenzae type b (Hib) and other encapsulated strains
not known if or how unusual ring structure relates to pathogenicity of this type
H. influenzae type b (Hib) and other encapsulated strains
antigens and endotoxin exist, but not much known
encapsulated virulent strains of Hib
grow as smooth colonies
encapsulated virulent strains of Hib
spontaneously give rise to "rough" unencapsulated variants
H. influenzae type b (Hib) and other encapsulated strains
facultative anaerobe, requires 2 growth factors in blood.
X growth factor
growth factor present in blood, heat-stable;
hemin (precursor of heme groups of respiratory enzymes)
V growth factor
growth factor present in blood, heat-labile;
NAD or NADP
staphylococcus
secretes sufficient V factor so can promote growth of H. influenzae
on agar plates with no other source of V factor, such as blood agar plates, these colonies will be surrounded by small "satellite" colonies of H. influenzae
detection of satellites cumberson and not used in hospital diag labs
X and V factors
released from RBC by action of hemolysins secreted by some species of Staphylococci and Streptococci;
released when mild heat used in preparation of chocolate agar
H. influenzae type b (Hib) and other encapsulated strains
chocolate agar used for culture
H. influenzae type b (Hib) and other encapsulated strains
sugar ferminentation reactions are not of diagnostic use
H. influenzae type b (Hib) and other encapsulated strains
very susceptible to disinfectants and drying
H. influenzae type b (Hib) and other encapsulated strains
passive immunity acquired from mother lasts only a few months
H. influenzae type b (Hib) and other encapsulated strains
after 3-4 years, most children have acquired active immunity from asymptomatic infections, and incidence of disease falls off--although some cases found in older children and, uncommonly, in adults
H. influenzae type b (Hib) and other encapsulated strains
conjugate capsular vaccine has been very effective.
vaccine is capsule (PRP=polyribosyl phosphate) linked to diphtheria toxoid so as to have inccreased dependence of "T cells and memory , as compared to previous formulation composed only of capsule. more immunogenic in very young children than previous versions
H. influenzae type b (Hib) and other encapsulated strains
conjugate vaccine wherein the carbohydrate moiety is synthetic
H. influenzae type b (Hib) and other encapsulated strains
Diagnosis: history and age of patient most important
meningitis from Hib
blood and spinal fluid are cultured (spinal fluid centrifuged and sediment examined by gram stain)
Diagnosis of Hib
spinal fluid specimen streaked on chocolate agar and incubated in CO2 incubator or candle jar
H. influenzae type b (Hib) and other encapsulated strains
diagnosis: requirement of colonies for X and V factors demonstrated
H. influenzae type b (Hib) and other encapsulated strains
detection of capsular Ag in spinal fluid by immunofluorescence or immunoelectrophoresis (sensitive and accurate measure) establishes diagnosis
H. influenzae type b (Hib) and other encapsulated strains
diagnosis: latex-agglutination testq
Hib meningitis
ampicillin is drug of choice, 3rd generation cephalosporin for ampicillin-resistant;
Augmentin (ampicillin+clavulanate (B lactamase inhibitor)) renders ampicillin-resistant stains sensitive to antibiotic.
if B-lactamase-negative, treatment switched to ampicillin
H. influenzae type b (Hib) and other encapsulated strains
moratality rate low if treated early.
1/3 used to havve resideual neurological damage but decreased with use of corticosteroids during antibiotic treatment to reduce inflammationa nd cytokine production due to LPS reelased as a result of lysis of bacteria
rifampin or single dose of cirprofloxacin or ceftraixone
for prophylaxis of Hib in contacts
non-typeable H. influenzae
structure doesn't possess polysaccharide capsule
non-typeable H. influenzae
structure utilizes cell-surface adhesions and LPS to colonize cell surfaces
non-typeable H. influenzae
no known role for toxins
non-typeable H. influenzae
growth and metabolism identical to typeable strains
typeable H. influenzae strains
become systemic
non-typeable H. influenzae
generally restricted to respiratory tract and infections of the ear
non-typeable H. influenzae
2nd most common cause of otitis media (after S. pneumoniae) most common in children b/c iummune system of children doesn't fight infections of respiratory tract as effectively and structure of eustachian tube in young children is felt to make fluid and infections more likely due to a straighter angle and shorter length
non-typeable H. influenzae
typically causes respiratory tract infectiosn in pateitns with underlying respiratory issues (COPD, chronic bronchitis, CF), sinusitis, conjunctivitis, and otitis media (middle ear infections)
non-typeable H. influenzae
colonization starts in nasopharynx with preferential adhesion to respiratory mucus, non-ciliated cells and damaged epithelium
-peritrichous pili
-cell-surface adhesions: Hap; Hia; HMW1/2; P2 and P5 porins, OapA OM protein; LPS
Hap adhesion, non-typeable H. influenzae
found among typeable and non typeable
HMW1/2 adhesion, non-typeable H. influenzae
expressed by most non-typeable (but not typeable) strains
Hia adhesion, non-typeable H. influenzae
expressed in most non-typeable strains lacking HMW1/2
Hsf adhesion, non-typeable H. influenzae
homologue of Hia found in typeable strains
LPS adhesions, non-typeable H. influenzae
may bind to platelet activating factor (PAF) receptor
non-typeable H. influenzae
invasion via 3 routes: macropinocytosis, paracytosis, LPS binding to PAF
macropinocytosis, non-typeable H. influenzae
can manipulate host cell biology to surround bacteria with host cell membrane projections, formation of a vacuole and internalization of the bacterium. normal host cell behavior but the bacteria manipulates pathway
paracytosis, non-typeable H. influenzae
can pass between cells (via tight junctions?) to invade sub-epithelial space. unknown OM protein required for this process
non-typeable H. influenzae
any passive immunity acquired from mother lasts only a few months

adults are susceptible to infection - not clear that long term immunity develops

immunity appears to be strain specific - variation in OM proteins
non-typeable H. influenzae
no vaccine
non-typeable H. influenzae
requirement for X and V factors demonstrated
non-typeable H. influenzae
typing not typically performed unless isolates are from invasive infections, such as meningitis
non-typeable H. influenzae
treatment includes:
oral amoxicillin for out-patients for otitis media and sinusitis

20-35% isolates resistant to amoxicillin

alternative: use amoxicillin with B-lactamase inhibitor (i.e., clavulanate) or ceftriaxone

infections can be persistent and recurrent, can form antibiotic resistant biofilm OR can invade host cells and thus avoid antibiotics--controversial
otits media and sinusitis, non-typeable H. influenzae
one of top reasons antibiotics are prescribed in the US
H. ducreyi
emerging sexually transmitted disease in the U.S.
cause of chancroid ("soft chancre" appearing as ragged ulcer on genitalia). venereal disease.
H. ducreyi
uncommon in US but beginning to increase especially around cities that serve as major seaports; occurs more commonly in parts of Africa and Asia
H. ducreyi
type of haemophilus sensitive to sulfonamides, tetracycline, streptomycin
H. aegypticus
Koch-Weeks bacillus
H. aegypticus
tyep of haemophilus that produces purulent conjunctivitis.
H. aegypticus
type of haemophilus common in hot climates
H. parainfluenzae
type of haemophilus that is occasional cause of pharyngitis and bacterial endocarditis
bordetella pertussis
cause of whooping cough, a severe childhood disease
whooping cough, bordetella pertussis
begins with mild upper respiratory symptoms, followed by acute inflammation of trachea, bronchi, and bronchioles with paroxysmal cough, lasting 1-4 weeks. cough usually has characteristic sound
bordetella pertussis
small, gram-negative cocco-bacillus. similar in appearance to H. influenzae
bordetella pertussis
strict aerobe
bordetella pertussis
no requirement for X and V factors
bordetella pertussis
requires very fresh media for growth, so most clinical labs have switched to PCR based method to detect organism from washes of nasal cavity
bordetella pertussis, neisseria meningitidis (meningococcus), Neisseria gonorrhoeae (gonococcus)
found only in humans. no natural animal reservoir known
pertussis toxin, bordetella pertussis
ADP-ribosylating toxin that catalyzes transfer of ADP-ribose from NAD to inhibitory G protein that normally inhibits adenylate cyclase- this causes increased accumulation of cAMP

also affects control of phospholipase C and ion channels

combined actions responsible for lymphocytosis, sensitization to histamine, enhancement of insulin secretion
cholera toxin
ADP ribosylates stimulatory G protein also resulting in increased adenylate cyclase activity and cAMP level
calmodulin-stimulated adenylate cyclase toxin, bordetella pertussis
catalyzes production of cAMP from ATP, activated by endogenous calmodulin. results in supraphysiologic concentrations of cAMP that may impair leukocyte functions and even cause cell death
dermonecrotic toxin, bordetella pertussis
aka mous elethal toxin or heat-labile toxin

discovered when necrotic lesions developed following intradermal injection into suckling mice
dermonecrotic toxin, bordetella pertussis
causes vascular smooth muscle contraction resulting in ischemic necrosis of lung tissue
tracheal toxin, bordetella pertussis
causes ciliostasis, inhibits DNA synthesis and ultimately kills tracheal epithelial cells
pili, bordetella pertussis
mediate attachment to ciliated epithelial cells of upper respiratory tract, cause diminished ciliary activity

also filus-like filmamentous hemagglutinin (FHA)
pertactin, bordetella pertussis
surface molecule
acute local inflammation, increased mucous secretions, patchy ulceration of respiratory epithelium

may result in diminished oxygen supply or pneumonia
bordetella pertussis
do not invade blood stream but remain in respiratory tract
bordetella pertussis
expression of genes encoding virulence factors regulated at level of transcription by two-component system--composed of bacterial transmembrane sensor protein that responds to host environmental cues to phosphorylate cytoplasmic response regulator protein that binds DNA to activate transcription from appropriate promotors
bordetella pertussis
incubation period ~7-10 days
2 stages
catarrhal stage, bordetella pertussis
runny nose, sneezing, low-grade fever, mild occasional cough (similar to cold)
paroxysmal stage, bordetella pertussis
bursts of coughing (probably to dislodge mucus), followed by high-pitched whoop and occasional vomiting
paroxysmal stage, bordetella pertussis
patients become cyanotic during cought attacks, which occur more frequently at night

infants don't make whooping sound
bordetella pertussis
immunization in latter half of 20th century produced dramatic decline in disease
120,000 cases by 1950 but only 2,000 in 1977
bordetella pertussis
neither immunization nor disease produces lifelong immunity
bordetella pertussis
until recently, immunization was through one component of trivalent DTP (diphtheria toxoid + tetanous toxoid + heat killed pertussis organisms).
bordetella pertussis
potential side effects including encephalopaty and permanent neurological sequelae led to less infants receiving vaccine from late 80's into 90's, so disease cases actually began increasing

incidence rising since mid 1980's with nearly 9,000 cases reported in 1999
bordetella pertussis
acellular vaccines recently licsensed. each incorporated into one of several DTaP trivalent vaccines that are now the recommended vaccines DTP is essentially phased out
bordetella pertussis
transmitted by aerosolized droplets during sneezing or coughing. very contagious
bordetella pertussis
following prolonged series of coughs, inspiration through narrowed glottis produces whoop
bordetella pertussis
deaths have occurred mostly in infants, who are susceptible to disease b/c quantity of Ab crossing placenta is not adequate for protection by passive immunity
bordetella pertussis
antibodies in children found only after several weeks
bordetella pertussis
diagnosis includes history of contact, classic cough, marked lymphocytosis
bordetella pertussis
diagnosis includes isolation of organism by cough plate. colonies grow very slowly. identify by appearance of colony, gram stain, biochemical reactions
bordetella pertussis
rapid direct fluorescein-labeled antibody test for nasopharyngeal specimens
bordetella pertussis
erythromycin is drug of choice (alternatives: tetracycline, chloramphenicol).
bordetella pertussis
not sensitive to penicillin or ampicillin
B. parapertussis
other species of bordetella

produce a number of virulence factors similar to those of B. pertussis, but don't carry genes for pertussis toxin

causes sporadic cases of whooping cough
B. bronchiseptica
other species of bordetella

produce a number of virulence factors similar to those of B. pertussis, but don't carry genes for pertussis toxin

causes respiratory illness in animals and only occasionally in humans
H. influenzae type B
major infection: meningitis, epiglottitis, pneumonia, otitis media
H. influenzae type B
less common infection: arthirtis, osteomyelitis
H. influenzae type B
B. pertussis
Neisseria meningitidis
Neisseria gonorrhoaea
reservoir: humans
H. influenzae type B
B. pertussis
Neisseria meningitidis
transmission: droplet
H. influenzae type B
B. pertussis
Gm-, coccobacilli
H. influenzae type B
growth requires X (hemin) and V (NAD) factors
H. influenzae type B
virulence: capsule, pili, IgA protease
H. influenzae type B
no exotoxins
H. influenzae type B
Diagnostics: Gram stain blood and spinal fluid; culture chocolate agar demonstrate XV req's confirm type b antigen
H. influenzae type B
treatment: 3rd generation cephalosporin, then amoxicillin if sensitive; contacts-rifampin, ciprofloxacin, or ceftraxone
H. influenzae type B
Hib vaccine
B. pertussis
major infection: pertussis (whooping cough)
B. pertussis
less common infection: pneumonia
B. pertussis
growth: Bordet-Gengou complex medium
B. pertussis
Virulence: FHA, pili, pertactin numerous toxins
B. pertussis
pertussis toxin, adenylate cyclase toxin, tracheal cytotoxin, dermonecrotic toxin
B. pertussis
Gram stain nasopharyngeal swab; direct antibody test; culture on B-G
B. pertussis
erythromycin and treat household contacts
B. pertussis
new acellular vaccine with PT, FHA, pertactin, pilli
Neisseria meningitidis
major infection: meningitis, septicemia
Neisseria meningitidis
less common infection: arthritis
Neisseria meningitidis
Neisseria gonorrhoeae
Gm-, diplococci, with adjacent sides slightly flattened
Neisseria meningitidis
Neisseria gonorrhoeae
+ oxidase

addition of drop of 1% solution of dye (dimethyl- or tetramethyl-p-phenylenediamine) to colony causes a pink and then a black color to appear within seconds. however, non-pathogenic also react positively.
Neisseria meningitidis
Fermentation:
Glu+ Mal+ Lac- Suc-
Neisseria meningitidis
virulence: capsule, meningitis usually assoc. with type B; IgA protease; pili
Neisseria meningitidis
Neisseria gonorrhoeae
toxins: LOS (LPS)-endotoxin; no exotoxins

in contrast to LPS, LOS has no O side chains
Neisseria meningitidis
meningitis-fever, stiff neck, vomiting, lethargy, petechial rash
septicemia-fever, petechial rash, hypotension, W-F syndrome
Neisseria meningitidis
Gram stain, spinal fluid, blood, nasopharyngeal or free-living and internalized bacteria; culture on chocolate agar and Thayer Martin.
Neisseria meningitidis
treatment with Penicillin G, ceftriaxone; rifampin prophylactically for close contacts b/c efficiently secreted into saliva, or ciprofoloxacin b/c so potent
Neisseria meningitidis
vaccine available epidemics or military for capsule types A, C, Y and W-135; but not for type B

type B capsule composed of sialic acid not recognized by C3b component of complement, so doesn't stimulate recruitment of phagocytes
Neisseria gonorrhoeae
major infection: gonorrhea, PID
Neisseria gonorrhoeae
less common infection: arthritis, conjunctivitis
Neisseria gonorrhoeae
transmission: direct, STD
Neisseria gonorrhoeae
fermentation:
Glu+ Mal- Lac- Suc-
Neisseria gonorrhoeae
virulence:
pili, IgA protease, Omp's?; Opa?
Neisseria gonorrhoeae
men-urethritis
women-cervical gonorrhea, PID
neonates-opthalmia neonatorum
Neisseria gonorrhoeae
Gram stain urethral pus, fresh exudate for bacteria within WBC's
Neisseria gonorrhoeae
treatment: ceftriaxone and doxycycline for chlamydia trachomatis
Neisseria gonorrhoeae
no vaccine
Neisseria meningitidis
agent of meningococcal meningitis, also called meningococcus
meningococcus
gonococcus
require rich medium for isolation; grow better in 5-10% CO2
Thayer-Martin selective medium
permits recognition of N. meningitidis and N. gonorrhoeae from materials contaminated with other bacteria

contains chocolate agar, with vancomycin (to inhibit gram-positives) and colistin (to inhibit gram-negative enterics) and nystatin (anti-fungal)

non-pathogenic Neisseria fail to grow on this media

pathogenic species require blood products in medium, while nonpathogenic species do not
meningococcus
gonococcus
readily killed by drying, heat, disinfectants
non-pathogenic Neisseria
ferment all the sugars except sucrose
Neisseria meningitidis
multiplies outside of cells, but not once phagocytized (although bacteria can be seen within leukocytes)
Neisseria meningitidis
endotoxin from organism damages walls of small vessels
Neisseria meningitidis
lives in nasopharynx. carrier rate varies; 5% in general population, higher in households where there has been a case of meningococcal meningitis
Neisseria meningitidis
differencies in composition of polysaccharide capsule are basis for classification into serogroups: bacteria of A, B, and C are most important

within each serogroup, there may be serotypes (e.g. group B has a dozen serotypes) based on differences between outer membrane proteins
Neisseria meningitidis
encapsulated, Neisseria
Neisseria gonorrhoeae
not encapsulated, Neisseria
Neisseria meningitidis
virulent strains are encapsulated and have smooth colonies

on artificial media, rough colonies (unencapsulated, relatively avirulent) are often produced
Neisseria meningitidis
carrier state may last from days to many months
Neisseria meningitidis
in some, mild pharyngitis and fever are all that occur
Neisseria meningitidis
transmission most often in crowded conditions (day care centers, military barracks)
Neisseria meningitidis
in small % of infected humans, bacteria progress from nasopharynx to bloodstream

incidence of severe disease--1 in 50,000 per years
Neisseria meningitidis
incubation period: matter of days to a week
Neisseria meningitidis
predilection for children below 5. highest incidence in 1st year (but after protective maternal antibodies are gone; i.e. not neonates)
group B Strep or E. coli K1
most common meningitis in neonates due to this
Neisseria meningitidis
without treatment, mortality about 85%

with early treatment mortality <1% in otherwise healthy patients
Neisseria meningitidis
capsule has antiphagocytic properties, contributing to virulence
Neisseria meningitidis
bacteria have organotropism, and localize in meninges preferentially. skin, eyes, lungs also sites in which bacteria localize
Waterhouse-Friderichsen syndrome, Neisseria meningitidis
uncommon: may cause adrenal failure, circulatory collapse, and shock, with rapid death
Neisseria meningitidis
most adults have antibodies that confer immunity. evoked within a week by the carrier state. when diverse groups are brought together--as in military camps--there is exposure to serotypes of bacteria not encountered before, hence outbreaks may occur
Neisseria meningitidis
clinical picture of upper respiratory infection followed by high fever and signs of meningitis

petechiae (small purplish-reddish spots caused by munte hemorrhages) may appear in skin, followed by large areas of ecchymosis (black and blue spots caused by leakage of blood from small vessels)
Neisseria meningitidis
specimens from blood, spinal fluid, nasopharyngeal secretions cultured and examined for gram-negative diplococci

further identify organ by sugar fermentation test (4 hrs), and/or latex agglutination test (10 min) based on capsule antigen in CSF
Neisseria meningitidis
clinical picture is critical
presence of patechial rash in case of adult or child with neurological symptoms is indicative
meningitis caused by H. influenzae and S. pneumoniae
hardest meningitis to diagnose in children
Neisseria gonorrhoeae
can be seen by gram stain in fluid of purulent exudate (pus)
Neisseria gonorrhoeae
can be seen inside of epithelial and phagocytic cells
Neisseria gonorrhoeae
lives primarily in genitourinary tract
Neisseria gonorrhoeae
endotoxin activity not major factor in disease state
Neisseria gonorrhoeae
more than 100 serotypes based on antigenicity of pilus protein
Neisseria gonorrhoeae
common mode of transmission: STD, direct genital contact, resulting in genitourinary tract infection
Neisseria gonorrhoeae
another mode of transmission through rectal and pharyngeal mucosa (non-pathogenic Neisseria also found in pharynx)
Neisseria gonorrhoeae
another mode of transmission in conjunctiva of newborns' eyes during passage of newborn through birth canal--ophthalmia neonatorium
Neisseria gonorrhoeae
infection established within hour of exposure.

bacteria anchor to surface fo epithelial cells using pili (which also impair phagocytosis by PMN's, non-piliated are non-virulent), then penetrate thru surface cells (intracellularly) and reach sub-epithelial CT in a few days. followed by inflammation and yellow purulent urethral discharge (with burning sensation on urination).

symptoms in males typically appear in 2-3 days

more variable and less well-defined in females. usually within 10 days; however high percentage of infected females remain asymptomatic in contrast to males.

infection occasionally spreads to epididymis or prostrate in males and, more often, to Fallopian tubes in femails
Neisseria gonorrhoeae
this disease--and infection with venereally-transmitted Chlamydia trachomatis--are probably the 2 most prevalent communicable bacterial diseases of humans

worldewide pandemic of this disease, not appreciably lessened by introduction of chemotherapy
Neisseria gonorrhoeae
asymptomatic carrier states common. carriers can transmit infection
Neisseria gonorrhoeae
for males it is estimated that 1-10% of infected and able to transmit disease are asymptomatic.

higher for females
Neisseria gonorrhoeae
complications of disseminated disease: arthritis-dermatitis syndrom, with spread to one of more joints, and with skin lesions; joint infection may occur in absence of prior overt genito-urinary symptoms
Neisseria gonorrhoeae
complication of disseminated disease: chronic pelvic inflammatory disease in females
Neisseria gonorrhoeae
clinical picture of discharge, plus history of exposure
Neisseria gonorrhoeae
stained smears of fresh exudate often show G- diplococci within PMN
Neisseria gonorrhoeae
culture should be done before treatment is started, if possible. colonies show oxidase-positive, gram- diplococci

chronic disease, diagnosis more difficult
3 major forms of gonococcal resistance
drug resistant is major problem. recommended regimens have changed several times in past 10 years

a. plasmid-mediated penicillinase producing N. gon (PPNG)
b. plasmid-mediated tetracycline resistant N. gon (TRNG)--TetR plasmid is conjugatieve and can mobilize PenR plasmid
c. chromosome-mediated resistant N. gon (CMRNG). CMRNG is a broad based resistance--includes Pen, Tet, and some cephalosporins--related to mutations affecting permeability; level of resistance low; treatment failure rate
Neisseria gonorrhoeae
b/c of widespread resistance, single-dose penicillin therapy no longer recommended
chlamydia trachomatis
IM ceftriaxone and 10day oral tetracycline or doxycycline

this is STD of highest incidence, so one assumes it's present in cases of gonorrhea
opthalmia neonatorum, Neisseria gonorrhoeae
once the cause of 50% of blindness in children

prophylactic treatment of newborn required by law
tetracycline or erythromycin ointment, or dilute (1%) silver nitrate from standardized ampules to prevent damaging effects of overdosing with silver nitrate
Neisseria gonorrhoeae
immune response, although can be demonstrated after infection, is weak, for unknown reasons. hence repeated attacks are common. high degree of antigenic variation of surface components (for ex, 100's of antigenic pilus variants) may contribute to this
Koch's postulate
1. pathogen should be found in all cases of disease, with corresponding tissue distribution
2. microorganism should be grown in pure culture in vitro
3. a pure culture, inoculated into susceptible animals, the typical disease would ensue. the microorganism must be re-isolated from the lesion of such experimentally induced disease
Molecular Koch postulate
1. the phenotype or molecular properties (e.g. DNA) should be associated with pathogenic strains and not with nonpathogenic strains
2. specific inactivation of the gene (or genes) associated with virulence trait should lead to a measurable decrease in pathogenicity
3. reversion or replacement of mutated gene with "wild type" should lead to restoration of pathogenicity or virulence
adherence and colonization
invasion
evasion of host defenses
production of extracullular substances to facilitate bacterial spread
bacterial infection is a multistep process
toxin mediated disease
tetanus
anthrax
staphylococcal food poisoning
nosocomial infections, gram-negative opportunistic bactera
hospital-acquired infections
carry multiple antibiotic resistances, making them difficult to treat
lack of washing hands
virulence factors, gram-negative opportunistic bactera
toxins and cell surface structures, contribute to disease caused by bacterium
pathogenecis or virulence determinants, gram-negative opportunistic bactera
factors or pathways required for organism to cause disease

may not be specific to bacterium-host interactions
LPS, gram-negative opportunistic bactera
immune response to this gram-negative cell component causes symptoms
biofilms, gram-negative opportunistic bacteria, gram-negative opportunistic bactera
surface-attached microbial communities

65% nosocomial infections related to this
device-related infections

increased resistance to range of antimicrobial agents, associated with production of large quantities of extracellular polysaccharides
Escherichia coli
part of our normal flora and most common opportunistic pathogen
Escherichia coli
most common cause of Gram-negative infections.
Escherichia coli
gastrointestinal infections
UTI
bacteremia
meningitis
neonatal meningitis
capsular antigen of E. coli causes this disease
UTI, GI tract infections
pili of E. coli and other G- bacteria cause invasive and cell adhesive behavior, cause this disease
exotoxin
principal cause of GI tract symptoms, proteins produced by E. coli
E. coli
pathogenicity:
capsular antigen--neonatal meningitis
pili-UTI, GI tract infecitons
exotoxin--GI tract symptoms
uropathogenic E. coli (UPEC)
95% of all non-hospital acquired UTI
60% women in U.S. will have one UTI during lifetime, 11% one per year
uropathogenic E. coli (UPEC)
correlation between expression of certain virulence factors and site/type UTI. cell surface adhesins
Many UTI bacteria can bind mannosides that are common constituents of uroepithelial cells and urinary tract mucus. adhesion blocked by mannose, so mannose-sensitive
bacteriurial infection
at least 10^5 bacteria/ml present in urine
cystitis
describes syndrome involving dysuria (burning feeling during urination), frequency, urgency, and occasionally suprapubic tenderness. typically involves infection of lower urinary tract but may include upper
acute pyelonephritis
results from UTI that has disseminated to kidney
clinical syndrome characterized by flank pain, tenderness and fever, dysuria, frequency and urgency
uropathogenic E. coli (UPEC)
invasion and spread of bacteria into urinary tract almost always associated with ascending route of infection. urethra usually colonized with bacteria
UTI, uropathogenic E. coli (UPEC)
persistent infections due to formation of "pods" or biofilm-like structures that form within epithelial cells of urinary tract

can invade epithelial cells and replicate within cells
hemagglutination
assay that uses RBC and series of dilution in microtiter dish or set of tubes to assay adherence or senstivity to mannose
adhesins
play role in colonization of urinary catheters. almost 100% catheters colonized with bacteria within 3 days
P pili
pili on E. coli strains associated with pylenonephritis

mediate attachment of bacteria to ( ) blood group globoseries Gal-Gal constituent of glycolipids present on uroepithelial cells and erythrocytes

chromosomally located operon (pap genes) encodes functions necessary for biogenesis and function of this pilus system
phase variation
stochastic switching of phenotypic trait to provide phenotypic diversity inside and outside host

controlled by variety of mechanisms: strand slippage, methylation, recombination

influenced by environmental factors
uropathogenic E. coli (UPEC)
virulence factors: LPS, capsule, motility, exotoxins including hemolysin
E. coli
major cause of bacteremia, leading cause of nosocomial bacteremia
E. coli
majority of isolates are noninvasive, but 2 routes that promote invasion are UTI and indwelling devices like intravenous catheters
E. coli
maybe ability to invade host cells allows crossing into bloodstream
E. coli
serum resistance is critical trait of strains and correlated with production of K1 capsule
gram-negative bacteremia
hallmark is systemic reaction to endotoxin or LPS
LPS
most toxic component of most bacteremic isolates of E. coli and is life-threatening
management of bacterial sepsis and accompanying endotoxic shock is difficult
E. coli
most common neonatal pathogen, one of leading causes of neonatal meningitis
E. coli K1
isolated from 20-40% of healthy individuals including newborns. generally can colonize newborns ithin hours of birth via vertical transmission from mother or nursery staff
neonatal meningitis caused by E. coli K1
pathogenesis:
colonize host mucosal surfaces
translocate across surfaces into bloodstream
survive transport through bloodstream, serum resistance
cross blood-brain barrier and survive in CSF
proliferate and cause tissue damage
E. coli
virulence determinants: K1 polysialic acid capsule (major) and S fimbriae, siderophores
E. coli capsule
outmost structure on bacterial surface
typically glycoconjugates
allows it to evade nonspecific host immune defenses
primarily anti-phagocytic mechanism
Klebsiella pneumoniae
capsule can be used to help identify it based on mucoid colony

capsule allows reduced phagocytosis, reduced complement susceptibility
Enterobacter cloacae
formerly lumped into Aerobacter and Klebsiella
differs from Klebsiella in that it is motile and generally less heavily encapsulated
Enterobacter cloacae
infection occurs in hospital setting secondary to antibiotic therapy

associated with burn, wound, respiratory, urinary infectionws
Enterobacter cloacae and E. agglomerans
associated with intravenous tubing contamination affecting hundreds of patients in 25 hospitals
Proteus vulgaris; proteus mirabilis
frequent cause of UTI
flagella, urease synthesis contribute to pathogenicity

urea, urease>NH3+CO2> alkaline urine> salt crystalization and stone formation> chronic infection
serratia marcesens
infections seen secondary to broad spectrum antigbiotic therapy or secondary to instrumentation (tracheostomy, indwelling catheters, renal dialysis, etc.)

infections can involve most itssues

pneumonia often contracted after use of contaminated respirator
serratia marcesens
different from other enterobacteriaceae in that it is less likely to colonize GI tract, and is more associated with respiratory and urinary tract.

GI tract is important reservoir among neonates
serratia marcesens
ouside hospital, associated with heroin addicts
serratia marcesens
outpatient setting, associated with septic arthritis
serratia marcesens
can produce Ig-specific protease that may influence pathogenicity
Pseudomonas aeruginosa
can cause both acute and chronic infections
Pseudomonas aeruginosa
acute infections:
bacteremia in immunocompromised patients
eye infections
burn infections
Pseudomonas aeruginosa
chronic infections:
in lung in association with respiratory diseases like cystic fibrosis or implanted medical devices
people with CF, chronic bacterial infection can't be cleared by current antimicrobial therapies, pt usually die of respiratory failure in mid-30's. bacteria grow in biofilms
Pseudomonas aeruginosa
can't ferment sugars, so detection in blood culture requires aerobic incubation
Pseudomonas aeruginosa
can grow via anaerobic respiration with nitrate as electron acceptor, or ferment arginine
Pseudomonas aeruginosa
few nutritional requirements for growth and ability to grow at low temps 4degC

widespread distribution and great potential for contamination of many environments
Pseudomonas aeruginosa
plasmid content. resistance to many antibiotics leads to its frequent overgrowth after antibiotic treatment. high natural resistance to many antibiotics for other Gram-
ExoA, Pseudomonas aeruginosa
ADP-ribosylates EF-2, stops protein synthesis, elicits apoptosis of affected cells
ExoS and ExoT
ADP-ribosylating enzymes that target host regulatory proteins
ExoU
cytotoxic, phospholipase activity; causes irreversible damage to cellular membranes and rapid necrotic death
Pseudomonas aeruginosa
elastases break down elastin, CT protein in lung, leads to tissue damage in lung

phospholipases break down phospholipids in lung surfactant and host cell membranes
Pseudomonas aeruginosa
in chronic infections associated with CF, produces alginate capsule that makes strains appear mucoid. alginate thought to block phagocytosis
Pseudomonas aeruginosa
model organism for study of biofilm formation
Legionella pneumophila
elderly or immunocompromised most at risk
Legionella pneumophila
very strict growth requirements and grows slowly, rarely isolated from patients
E. coli
LPS (O-antigen)
Peritichous flagella (H-antigen)
Capsule (K antigen)
heat labile toxin (LT) and heat stable toxin (ST), E. coli
encoded on plasmids
Shiga-like toxin
encoded on lysogenic phage similar in many ways to phage lambda
virulence factors, E. coli
Adhesions: fimbrial including colonization factor antigens (CFAs) and bundle forming pili (BFP); and nonfimbrial
Toxins LT and ST; Shiga-like toxins
Endotoxin (LPS)
Nutrient uptake systems like sideropores
hemolysins and cytotoxins
K1 capsule
Enterohemorrhagic E. Coli O157:H7
from contaminated farm products:
cattle feces
ground beef: under-cooked hamburger
leafy vegetables
unpasteurized apple cider/juice, raw milk/dairy products, vegetables (spinach)
large centralized processing facilities
secondary person to person spread or contaminated wading pools, etc.
petting zoos
Enterohemorrhagic E. Coli O157:H7
asymptomatic carrier
diarrhea, frequently bloody
severe, cramping abdominal pain
vomiting in about 50% of the cases
HUS (hemolytic uremic syndrome). hemolytic anemia, thrombocytopenia, acute renal failure.
Enterohemorrhagic E. Coli O157:H7
preschool children and elderly are especially susceptible
Enterohemorrhagic E. Coli O157:H7
specific serogoup based on LPS and flagellar antigens
other serogoups: O111, O26, O157:H-
Enterohemorrhagic E. Coli O157:H7
additional factors encoded on genetic elements:
intimin/Tir
delivered by the TypeIII secretion system
attaching and effacing lesion
Enterohemorrhagic E. Coli O157:H7
Toxins: shiga-like toxin, hemolysin encoded on plasmid
secretion, Enterohemorrhagic E. Coli O157:H7
moving bacterial proteins from cytoplasm across cytoplasmic membrane
type III secretion system, Enterohemorrhagic E. Coli O157:H7
specialized form, where protein moves across bacterial cytoplasmic and outer membrane AND across the host cell membrane through an injection needle
type III secretion system, Enterohemorrhagic E. Coli O157:H7
allows bacterium to deliver proteins to host cytoplasm
type III secretion system, Enterohemorrhagic E. Coli O157:H7
genes often found together with other virulence genes in pathogenicity islands
LEE (locus for enterocyte effacement), Enterohemorrhagic E. Coli O157:H7
pathogenicity island that encodes T3SS, intimin, and tir
type III secretion systems, Enterohemorrhagic E. Coli O157:H7
secretion apparatus to deliver proteins to host cell

effector proteins delivered into host cell via secretion apparatus, alter host cell biology
Tir, type III secretion systems, Enterohemorrhagic E. Coli O157:H7
T3ss-secreted bacterial that is delivered to surface of epithelial cell to allow for E. coli attachment
Intimin, type III secretion systems, Enterohemorrhagic E. Coli O157:H7
Tir binding protein on surface of E. coli
type III secretion systems, Enterohemorrhagic E. Coli O157:H7
toxin, proteins can recruit host cell actin, causing altered morphology, impact signal transduction pathways in host cell to form A/E lesions
Shiga-like toxin, Enterohemorrhagic E. Coli O157:H7
toxin, also called verotoxin
encoded on a phage
comprised of 2 subunits
Shiga-like toxin, Enterohemorrhagic E. Coli O157:H7
toxin, interferes with protein synthesis via its RNA cleavage activity (subunit A) and may impact cytoskeleton (subunit B)
Hemolysin, Enterohemorrhagic E. Coli O157:H7
toxin, nutrient acquisition
cytotoxic-pore formation in cells
Enterohemorrhagic E. Coli (EHEC)
large inestine (food borne pathogen)
moderately invasive, produces Shiga toxin, forms A/E lesions

complicated by hemolytic uremia
Enterophathogenic E. coli (EPEC)
small intestine (major cause of infantile diarrhea)

forms A/E lesions, no known hemolysin, no shiga-like toxin or other toxins identified
Enteroaggregative E. coli (EAEC)
small intestine

no A/E lesions, non-invasive, produces heat stable-like toxin, produces hemolysin, causes persistent diarrhea in children
enteroinvasive E. coli (EIEC)
large intestine (important cause of diarrhea)
non-fimbrial adhesins, replicate within enterocytes leading to lysis, no Shiga toxin
enterotoxigenic E. coli (ETEC)
small intestine (major cause of diarrhea world wide)

fimbrial adhesins, non-invasive, produce LT and/or ST, watery diarrhea, no inflammation
Enterohemorrhagic E. Coli O157:H7
biochemical identification based on carbohydrate fermentation patterns and other reactions

Lac+, discerned on EMB or MacConkey agar
Enterohemorrhagic E. Coli O157:H7
sorbitol-negative (colorless)
commensal strains are positive

direct or latex agglutination tests to identify antigen

biochemical tests to confirm ID

serology and toxin analysis
diagnosis of other diarrheagenic E. coli:
serotyping-pulsed field gel electrophoresis
PCR analysis of virulence factors
Enterobacteriaceae family (enterics)
normally as part of human gut flora
gram negative rods, including E. coli, salmonella, shigella, etc
facultative anaerobes, ferment glucose, oxidase negative (no cytochrome oxidase)
Salmonella
gram negative rods, non-spore-forming, facultative anaerobes

ferment glucose under anaerobic conditions

DO NOT FERMENT LACTOSE (distinguishing characteristic

PRODUCE H2S
Salmonella
more than 1500 species
antigenic analysis of O antigen, sugar part of LPS
analysis of H antigen, part of flagella, two types, phase I and phase II antigens
Salmonella typhi
unique antigen called Vi antigen
Salmonella typhi, S. choleraesuis
typhoid fever or enteric (typhi)

one serotype
salmonella enteriditis
many serotypes, named by city in which microorganism discovered
Salmonella
feces, blood, urine
primary isolation from feces on media containing lactose (EMB and MacConkey agar)

biochemical and serological tests to identify organism for diagnostic and epidemiologic purposes, using type specific sera against O, H, Vi antigens
Salmonella
requires high inoculum for disease (10^5 CFU)
Salmonellosis, 3 distinguishable syndromes
enteric fevers, septicemias, acute gastroenteritis (most)
typhoid fever, Salmonella
prototype of enteric fevers, caused by S. typhi/paratyphi (facultative intracellular organisms)
typhoid fever, Salmonella
acquired by ingestion of contaminated food or water, common in developing countries

many infections subclinical, 7-14 day incubation
malaise, anorexia, headache, onset of fever with stepwise increase to 104 F
diarrhea usually absent but abdominal tenderness and distention present, due to enlarged liver and spleen, sepsis
skin rash on trunk called rose spots, lasting few days
leukopenia is common
fever subsides after third week
severe intestinal hemorrhages in later stages
osteomyelitis in patients with sickle cell anemia
typhoid fever, Salmonella
ingested organisms survive gastric acid, reach small intestine, multiply within mononuclear cells of Peyer's patches, enter intestinal lymphatics, travel via thoracic duct to blood where disseminated into spleen, bone marrow, gall bladder.
endotoxin (lipid A of LPS) released into bloodstream causes some of symptoms
typhoid fever, Salmonella
stool cultures positive very early in course of infection. culture may be missed b/c no GI symptom, becomes negative after 1st week
blood cultures positive after 7-14 days
stool cultures positive again when excreted into intestine from gall bladder where it resides in late stage of disease or in carrier state, particularly in pateints with gallbladder diseases
typhoid fever, Salmonella
3% patients excrete large number of oragnisms from suppurative focus in biliary tract over extended periods
important sources for spreading infection if sewage disposal is incorrect or compromised
typhoid fever, Salmonella
isolate from blood, stool, or urine
test for elevated or rising O and H agglutinins between 1st and 3rd week--febrile agglutinins
test rise in Ab to Vi antigen to diagnose
typhoid fever, Salmonella
fluoroquinolones (ciprofloxacin or 3rd generation cephalosporins

chloramphenicol, ampicillin, tremethoprim plus sulfa

chronic: ampicillin or cipro, cholecystectomy
typhoid fever, Salmonella
only infects man, not animals

vaccination only for those at high risk: deficiency in gastric acid, defects in cell-mediated immunity, HIV patients, patients with splenectomy, sickle cell disease
typhoid fever, Salmonella
old vaccine is saline suspension of heat/phnol-killed S. typhi, 51-67% vaccine efficacy

two available currently: oral live (4 doses), attenuated not for children less than 6 years

Vi capsular polysaccharide vaccine (ViCPS) for intramuscular use, 2 weeks prior to exposure, 50-80% of recipients protected
Salmonella choleraesuis, septicemia
high fever and bacteremia usually without GI involvement

may occur in patients with sickle cell anemia, cancer, or young childre. osteomyelitis due to bacteria in child with sickle cell anemia
Salmonella choleraesuis, septicemia
suppurative lesions during bacteremia almost anywhere in body: local abscesses, cholecystitis, pericarditis, meningitis, osteomyelitis. extra-intestinal infection in association with underlying chronic diseases or impairment of host defense
Salmonella typhimurium, enterocolitis
confined to GI tract, blood cultures positive in 5-10% patients

most common form of Salmonella infections

8-48 hrs after contaminated food consumption

sudden onset with headache, chills, abdominal pain, nausea, vomiting, diarrhea, accompanied by fever. endotoxin release upon invasion of epithelial tissues of small and alrge intestins 6-8 hr after ingestion

lasts 1-4 days, selflimited
S. typhi (enteric fever) and S. choleraesuis (septicemia)
blood cultures positive in these types of Salmonella
Salmonella typhimurium, enterocolitis
almost all of 1500 seotypes cause gastroenteritis
transmission patterns differ from typhpoid fever, reservoir determined by serotypes in domestic animals
Salmonella typhimurium, enterocolitis
domestic nanimals fed bacteria-laden meat scraps
poultry, eggs, pork, dog food, domestic turtles, pork sausage are common sources of contamination
Salmonella typhimurium, enterocolitis
Salmonella common in developed and developing countries
Salmonella typhi
Salmonella common in developING countries
Salmonella enteritidis
Salmonella serotype most frequently involved in egg contamination
Salmonella typhimurium, enterocolitis
fruits when contaminated in field by animal or human fecal matter, spread this type of Salmonella
Salmonella typhimurium, enterocolitis
diagnosis dependent on finding organism in feces or fecal swab
H and O agglutinins useful at late stage, for species ID
Salmonella typhimurium, enterocolitis
mostly self limiting
replace fluid and electrolytes
treatment with antibiotics where underlying predisposing conditions
type of salmonella
shigella and salmonella
doesn't ferment lactose
Shigella (contrast with Salmonella)
non-motile
Shigella (contrast with Salmonella)
do not produce gas from glucose
Shigella (contrast with Salmonella)
doesn't produce H2S
Shigella (contrast with Salmonella)
LPS polysaccharide O antigens only, no H antigents (no flagella)
Shigella
more difficult to recover from feces
Shigella
produces disease only in humans, inhabits human intestinal tract, no animal reservoir
spread by Food, Feces, Fingers, Flies, especially in overcrowded conditions
once ingested, invades intestinal epithelial cells after 1-4 days incubation
Shigella
facultative intracellular organism, growing within host cells during infection
Shigella
penetration beyond submucosa rare, rarely cause bacteremia
Shigella (contrast with Salmonella)
inoculum needed to initiate disease is low, easily transmitted by fecal-oral route in daycare and mental hospitals

can resist killing by stomach acid, can infect at low numbers
Shigella (contrast with Salmonella)
produces bloody diarrhea by invading cells in terminal ileum and colon )mucosal ulcerations with PMN and bacteria enmeshed in fibrin)
S. dysenteriae
exotoxin, cytotoxin called Shiga toxin
contains A/B polypeptide subunits
B=receptor binding subunit to bind to intestinal epithelial cells, A enters cell to inactivate 60S ribosome, stopping protein synthesis
Shiga toxin, Shigella
causes fluid secretion
blocks fluid absorption in intestine
kills absorptive epithelial cells, bloody diarrhea from invasion of epithelial cells and blockage of lfuid absorption (in cholera there is active fluid secretion)
Bacillary dysentery, S. dysenteriae
characterized by sudden onset of abdominal cramps, diarrhea and fever following incubation of 1-4 days. diarrhea watery at first but later contains blood and mucus

diarrhea may occasionally be severe; may cause dehydration and electrolyte imbalance, particularly in infants and young children
diarrhea usually self-limiting last a few days
mucus and blood and PMN in stool are common, blood cultures usually negative
send stool for PMN's, indicator of invasive disease
Bacillary dysentery, S. dysenteriae
identification of organism from feces, Gram- rods, non lactose fermenting, no gas, no H2S, nonmotile
clinical symptom difficult to differentiate from other GI diarrheal diseases. get stool culture for diagnosis
Bacillary dysentery, S. dysenteriae
most important therapy is fluid and electrolyte replacement

antibiotics effect not dramatic (cipro, trimethoprim-sulfa) no antibiotics for mild cases. many strains carry R factors for ampicillin resistance
Bacillary dysentery, S. dysenteriae
caused by Food, Fingers, Feces, Flies
Bacillary dysentery, S. dysenteriae
vaccine: little immunity, not very effective. organisms clear in week but small % people have more persistent carriabge

live avirulent oral vaccines not successful
Rickettsia and Chlamydia
small, 300nm
obligate intracellular growth

NOT viruses
contain both DNA and RNA
binary fission
susceptible to antibiotics, esp tetracyclines
own protein synthetic machinery
bacteria-like cell walls, related to gram neg
Rickettsia and Chlamydia, Mycobacterium leprae
only obligate intracellular bacteria (others are facultative intracellular)

intracellular during infection but can grow extracellularly both in vivo and in vitro