midterm 2 Flashcards
prevalence of UTIs
one of the most common reasons for visiting primary care physician
50% of women have one by 30
incidence decreases with age
about 25% of women will experience a second episode within 6 months of their first UTI = recurrent UTI
Bacteriuria
presence of bacteria in urine - does not mean infection
asymptomatic bacteriuria
presence of bacteria in urinary tract + absence of symptoms
usually clinically insignificant unless woman is pregnant or has undergone invasive procedure in urinary tract
normal mechanisms that maintain sterility of urine
adequate urine volume
free flow from kidneys through urinary meatus
complete bladder emptying
normal acidity of urine
peristaltic activity of ureters
increased intra-vesicular pressure preventing reflux
in males: antibacterial effect of zinc in prostatic fluid
how are UTIs classified
based on location:
- upper: pyelonephritis
- lower: cystitis + urethritis
based on condition of the urinary tract or patient:
- uncomplicated
- complicated
based on evolution:
- acute
- chronic (symptoms persist over time)
- recurring (relapse or reinfection)
Cystitis
UTI confined to bladder
symptoms: dysuria (painful peeing) urinary frequency urinary urgency supra-pubic pain hematuria ( blood in urine) nocturia (peeing at night) bladder tenesmus absence of vulvar/vaginal discharge or irritation
absence of symptoms or physical signs suggests inflammation at other sites in urinary tract
differential diagnosis (UTI)
acute lower UTI (cystitis)
acute urethritis ( chlamydia or gonorrhoeae)
vulvitis - contact dermititis, allergic rxn, yeast infection, HSV infection
vaginitis/ bacterial vaginosis
pyelonephritis
clinical diagnosis that implies a more invasive infection
Symptoms:
- fever
- flank pain
- nausea
- chills
- malaise
- headache
symptoms indicate: inflammation of the kidney and renal pelvis
prostatitis
inflammation/infection of prostate gland - acute or chronic
intrarenal /perinephric abscess: collection of pus in kidney or in the soft tissue surrounding the kidney
uncomplicated vs complicated UTIs
uncomplicated:
- occurs in patients with normal genitourinary tracts
- usually non- pregnant, premenopausal women of childbearing age
complicated:
- structural or functional abnormality of the gentiourinary tract
- pregnant women, elderly, men, children
- chronic symptoms
- comorbid illness or immuno-compromised
- upper tract disease
complicated UTI infection definition
underlying abnormality that predisposes patient UTI or makes UTI more difficult to treat effectively
recurrent infections : relapse vs re-infection
relapse:
- recurrence of infection by the same organism after treatment ends (possibly resistance)
reinfection: recurrence of infection by a different organism after discontinuation of treatment
pathogenesis of UTIs
UTI usually due to patients own intestinal flora: ascending route of infection (organisms enter the urinary tract in a retrograde fashion via the urethra)
complicating factors (catheters, nephrostomy tubes, surgery, urinary stones) results in:
- allows organisms to enter and persist in urinary tract
- alter the typical spectrum of organisms
- may have multiple etiologies
UTI Risk Factors
- aging (increased incidence of diabetes mellitus/risk of urinary stasis, incontinence, impaired immune response)
- female: short urethra, sex, contraceptives that alter normal flora, pregnancy
- male: prostatic hypertrophy, anal sex
- urinary tract obstruction: tumor or calculi, strictures
- impaired bladder innervation
- hematogenous spread
Etiology of UTIs
majority of UTIs are caused by single pathogen
enterobacterales are responsible for 90% of UTIs: gram neg bacilli, facultative anaerobes, common intestinal flora
E.coli is most commonly isolated (70%)
features of Uro-pathogenic E. coli
Adherence
- uropathogenic E.coli have P fimbria which bind to P blood group antigen present on uro-epithelial cells (99% of population)
hemolysins, colinin V: resistance to complement in serum
K antigen: assoc. with upper tract infections
Type 1 fimbria: interbacterial binding and biofilm formation
common characteristics of uro-pathogens + examples
proteus, morganella, providencia (classical UTI pathogens)
produce urease - increases urinary pH = crystal/ struvite stone formation = obstructs flow - provides matrix
formation of biofilms: colonization of catheters
highly motile, produce fimbria for attachment
staphylococcus saprophyticus
typically associated with younger, sexually active females
1-5% of cystitis
Lab ID: resistance to novobiocin
UTI diagnosis via rapid in-office lab testing
dipstick testing
looks for nitrites and leukocytes produced by infection
leukocyte detection is sensitive but not specific
nitrite is sensitive for gram negative but highly specific
RBC detection is not sensitive or specific
quantitative culture for UTI diagnosis
urine culture: significant bacteriuria defined as 10^5/ ml
can use SBA, MacConkey agar, chromogenic agars
lower numbers may be significant in children or catheter collected specimens
urine specimen collection
clean catch mid stream specimens:
- most frequently used method
- urethra cleaned prior to collection
- first void urine allowed to pass to clear urethra
- mid-stream collected in sterile container
collection bags (children):
- used in young children
- often contaminated
- most meaningful result is a negative culture
indwelling catheters:
- urine obtained by inserting needle into catheter or through diaphragm
- preferable to obtain specimen from new catheter rather than old catheter
suprapubic aspiration/straight catheters:
- invasive
- specimen obtained directly from bladder
urine specimen transport
sent to and processed by lab ASAP
requires method of collection and time/date of collection on specimen
after 1-2hrs must be refrigerated
unless transported in boric acid tube urine not received in 24 hrs or not refrigerated will be rejected
antimicrobial therapy for UTIs
empiric therapy:
- based on most probable pathogens
- lower vs upper tract infection
- local rates of resistance
- acute infection vs relapse/re-infection
patient management is becoming more difficult due to increasing resistance to oral first line drugs
typical treatment regimes for UTIs
uncomplicated cystitis: - nitrofurantoin - fosfomycin - TMP/SMX (24% res) pyelonephritis: - ciprofloxacin - beta lactam + aminoglycoside
common RTIs (bacteria)
pneumonia - community acquired, nosocomial
AECB (AE -COPD)
sinusitis
otitis media
pharyngitis - sore throat
RTI specimen
sputum
BAL/ bronchial washing
nasopharyngeal aspirates / swabs
endotracheal aspirates
sinus aspirates
typanocentesis - takes pain away right away = therapeutic + you get a specimen
throat swabs = diagnosis of group A strep
common bacterial RTI pathogens
strep pneumo
h. influenzae
moraxella catarrhalis
mycoplasma pneumoniae - no cell wall
chlamydia pneumoniae – atypical cell wall
legionella pneumophila - strict intracellular susceptibility doesnt match vitro and in vivo
s. aureus
B. pertussis
gram neg/ anaerobes
s. pyogenes - primarily pharyngitis
what is pneumonia
an inflammatory condition of the lung primarily affecting the alveoli
typical signs/symptoms:
fever, cough (productive or dry), chest pain, shortness of breath
severity of disease and mortality vary considerably
CAP, HAP, VAP
S. pneumoniae - RTI
most common cause of of bacterial RTI
sm. gram positive diplococci
alpha hemolytic, bile soluble, optochin sensitive
growth often enhanced in CO2 atmosphere
most are encapsulated- most important virulence factor
colonizes the nasopharynx in 5-10% of adults and 20-40% of children
incidence increases in winter months
predisposition to pneumococcal infection
defective Ab formation insufficient number of PMNs day cares, military, prisons, shelters (close quarters) chronic respiratory disease (COPD) infancy and aging diabetes, alcoholism, liver diseases
S. pneumoniae virulence factors
capsule most important virulence factor
- aids in escape from phagocytic cells
- aids in adherence - essential for colonization
pneumolysin (hemolysin)
- destroys ciliated epithelial cells
- activates classical complement pathway
- suppress oxidative burst by phagocytic cells
secretory IgA protease
vaccines for pneumococcus
pneumovax
- 23 different serotypes that account for 90% of invasive strains protection wanes with time and age
prevnar
- conjugate vaccine
- indicated for use in infants less than 2 years old and adults
conditions under which someone should get a pneumococcal vaccine
advanced age splenectomy HIV/AIDS lymphoma myeloma alcoholism diabetes
antibiotic treatment of . pnumoniae
penicillins cephalosporins macrolides fluoroquinolones vancomycin
relationship between patient types, pulmonary function, and likely pathogens in COPD
as lung function goes down you get more gram negative infections and more complicated infections such as chronic bronchitis
also get more resistant bacteria
COPD
chronic obstructive pulmonary disease
characterized by breathlessness
umbrella term used to describe progressive lung diseases including: emphysema chronic bronchitis refractory (nonreversible) asthma some forms of brochiectasis
H. influenzae - RTIs
most common cause of AE- COPD
small gram negative bacilli
requires X and V factors for growth
will grow on chocolate agar (5% CO2)
may be encapsulated
type b (Hib) responsible or majority of invasive disease (meningitis, epiglottitis)
introduction of Hib vaccine - now we hardly see this
majority of mucosal disease due to non-encapsulated strains
haemophilus species
see notes for table with x factor v factor and catalase results
porphyrin test
determines and isolates X factor requirement
if it turns red = does not require x factor
no colour = requires exogenous source of X
treatment of H. influenzae RTIs
approx. 18% produce beta lactamase
1% have altered PBP
2nd and 3rd generation of cephalosporins effective
newer macrolides have reasonable activity
flouroqinolones very active , but contraindicated in children
amoxicillin-clavulualante very effective
moraxella catarrhalis -RTIs
sm. gram negative cocco-bacilli
otitis media, sinusitis, AECB
carriage rate = 50%
DNase +, asacchrolytic
90% of strains are resistant to ampicillin/amoxicillin
other than tmp/smx it will be susceptible to most oral antibiotics
Legionella pneumophila - RTI
gram neg bacilli
intracellular pathogen
common in environment
widespread spectrum of illness
culturing legionella
requires L-cysteine for growth
stimulated by 5% CO2
asaccharolytic
they are motile
fastidious, BCYE agar
best ways to ID legionella
Culture
urinary Ag - excrete legionella antigens in your urine
treatment of legionella
predictably susceptible to fluoroquinolones: cipro and levo
macrolides are excellent alternative
morphology and physiology of mycoplasma
smallest free-living bacteria
small genome size: require complex media for growth
facultative anaerobes except M. pneumoniae
lack a cell wall
clinical syndrome assoc with M. pneumoniae
tracheobronchitis:
- 50% of infections
- prolonged post-infectious cough
pneumonia:
- approx 20-30% of infections
- mild disease but long duration
- most common cause of atypical pneumonia
antibiotics to treat atypical pathogens in RTIs
mycoplasma/chlamydia pneumoniae
not susceptible to cell wall active agents
highly susceptible to doxycycline, macrolides, and fluoroquinolones
bordetella pertussis -RTI
causes pertussis sm. gram neg, cocci-bacilli strictly aerobic, fastidious requires growth on media containing charcoal, blood, or starch BG or RL medium
classical course of pertussis disease
see notes
3 phases
lab diagnosis of pertussis RTI
naso-pharyngeal specimens are best yield
typically culture on BG agar and then do PCR
treatment = macrolides: azithromicin or clarithromicin
bacterial pharyngitis
caused by S. pyogenes
- gram +, catalse (-), beta haemolytic (grp A), PYR+, susceptible to TaxoA
treatment: pen/ amoxicillin
non-suppurative complications of bacterial pharyngitis (S. pyogenes)
rheutmatic heart disease
- treat patients to prevent this from happening
post-streptococcal glomerulonephritis:
- going to get this wether you you receive treatment or not ( don’t always get it)
arcanobacterium hemolyticum
pharyngitis in teens and young adults
- rash similar to scarlet fever
- invasive disease occurs but rare
usually doesn’t respond well to pen but disease is self limiting
culturing arcanobacterium hemolyticum
if doctor suspects this then incubate plate for 72hrs with CO2
usually weakly beta hemolytic - best seen on rabbit blood
anaerobically= slower growth
reasons for treating bacterial pharyngitis
only speeds up disease resolution by 18-24 horus so this is not why
eradication of the organism and stop the spread is a reason
most important reason is that it prevents complications - but you have 10 days to treat after onset so no need for empiric treatment
reasons to look for respiratory viruses
discontinuation of antibiotics
reduce unnecessary investigations
initiation of specific antiviral therapy
interventions = vaccine (flu)
how are viral RTIs transmitted?
droplet (not aerosol)
- tend to be enveloped
contact
sporadic cases
- outbreaks are common
specimen collection for viral RTIs
nasopharyngeal (NP) swab or aspirates
- need transport media (keeps nucleic acids stable) - does not support growth
bronchial alveolar lavages
what factors does viral RTI
clinical illness timing of collection (most important): preferably within 48hr host factors type of specimen specimen transport diagnostic test
diagnostic methods for viral RTIs
EM - not good for diagnostics
culture + direct fluorescent antibody (DFA) - poor sensitivity
rapid antigen testing - poor sensitivity
molecular methods - high sensitivity + specificity (expensive)
- examples:
multiplex PCR and RT-PCR
Rhinovirus
most common viral RTI
number 1 cause of common cold
ssRNA+
coronavirus
2nd most common viral RTI
common cold (typically)
some strains linked t severe disease such as SARS
enterovirus
mild respiratory illness
aspectic meningitis
rash - hand, foot and mouth
EV-D68 = viral RTI linked to acute flaccid paralysis (similar to polio)
adenovirus
more than 60 types
spectrum of disease: RTIs, conjunctivitis (eye), hemorrhagic cystitis
types 40 and 41 cause GI illness
parainfluenza viruses
common cause of upper RIT in children
approx. 2% get croup:
inflammation of upper airway
narrowing subglotic region
barking cough
tends to go away on its own
respiratory syncytial virus (RSV)
most common cause of bronchiolitis in children
can also infect adults
severe infections can be fatal
antiviral = ribavirin for severe cases only
no vaccine YET
influenza virus
3 types: A, B, C (rare)
A and B cause seasonal pandemics
Flu A is the most important: causes more severe disease compared to B and has pandemic potential
sub typing based on hemagglutinin (HA) and neuraminidase (NA)
influenza symptoms
onset is abrupt
congestion/sneezing/sore throat = rare
cough = common (dry but severe)
headache
fever
fatigue/malaise - common/lasts for weeks
muscle pain - often severe
antiviral treatment for influenza
adamantanes = M2 channel inhibitor
neurominidase inhibitors:
oseltamivir or zanamivir
antiviral resistance
immunocompromised host:
- virus shed for long periods of time
- predisposes for development of resistance
amantidine is no longer an option bc mutations in the M2 channel amino acids = all fluA resistant
fluB doesn’t have M2 channel
resistance to neuraminidase inhibitors = mutations in surface proteins HA and NA
influenza vaccines
quadruvalent vaccine:
Flu A: pH1N1, H3N2
flu B: 2 lineages
antigenic drift
viral RNApol makes mistakes
mutations over time in surface glycoproteins (HA and NA)
mutations in vaccine-antibody epitope = mismatches
may lead to vaccine ineffectiveness
when do influenza pandemics arise?
no existing immunity
FluA becomes well adapted to human replication and spread
antigenic shift (result of genetic reassortments)
flu reservoirs
aquatic birds - direct transmission can occur but not common
only some flu strains are adapted to humans
pigs have receptors for both avian and human lineages = mixing species
antigenic shift
influenza has segmented genome (8 rna segments)
genetic reassortments between avian/swine/human flu
new viruses emerge with different HA and NA combinations
avian influenza A
poultry birds can also carry flu
transmission = direct contact with infected birds or objects contaminated but their feces
doesn’t have efficient human to human spread but they are usually fatal or very severe
example = H7H9
40% mortality but no sustained human-to-human transmission
CNS infections
life threatening - associated with mortality and morbidity
acute, sub-acute, chronic
clinical findings determined by anatomic sites, infecting pathogen, host response
vulnerability of CNS to effects of inflammation and edema mandates prompt diagnosis with appropriate therapy if consequences are going to be minimized
types of acute CNS infections
meningitis (bacteria/viral)
menigoencephephalitis (usually viral)
brain abscess
subdural empyema (pus)
epidural abscess
septic venous sinus thrombophlebitis
meningitis definition
an infection that causes inflammation of the membranes covering the brain and spinal cord
non-bacterial meningitis = aseptic meningitis
causes of meningitis
bacterial infections
viral infections
fungal infections
inflammatory diseases
cancer
trauma to head or spine
viral meningitis
generally benign, rarely fatal
enterovirus = 80% of cases
other viruses = mumps, EBV
HSV = rare but serious
most clear in 3-8 days
HSV/VZV - require systemic antivirals
causes of bacterial meningitis based on age range
less than 3 months old: grp B strep L. monocytogenes E.coli S. pneumoniae
3 months -18yrs
N. meningitidis
S. pneumoniae
H. influenzae
18-50yrs
S. pneumoniae
N. meningitidis
H. influenzae
50+
S.pneumoniae
L. monocytogenes
gram neg bacilli
steps in meningococcal infection
nasopharyngeal colonization
invasion of epithelium
invasion of blood
further dissemination into cerebrospinal fluid
meningitis symptoms
see notes for bacterial vs bacteria + shared symptoms
goals for managing a patient with acute CNS infection
quickly recognize the acute CNS infection
initiate empiric therapy asap:
- ideal to get CSF before antimicrobials but if there is going to be any delay - initiate drugs
quickly ID causative organism - adjust management if needed
optimize management for complicating features
diagnostic test for meningitis
lumbar puncture:
collects CSF
spinal needle is inserted between the 3rd and 4th lumbar vertebrae
allows for the urgent distinction between viral and bacterial meningitis
typical CSF findings in viral vs bacterial meningitis
see notes
neisseria meningitidis
gram neg diplococci
polysaccharide capsule
13 sero-groups classified by their capsule - 5 accoutn for disease: A/B/C/Y/W-135
appear intracellular in gram stain
catalase +
oxidase +
grows on chocolate and blood agar
clinical presentations of meningitis
fever + headache (flu like symptoms)
stiff neck
nausea
altered mental status
seizures
up to 40% fatality
clinical presentations of meningococcemia
rash
vascular damage
DIC
multi-organ failure
shock
death can occur in under 24hrs
fatality rate = 3-10%
transmission of meningitis
humans only
asymptomatic pharyngeal carriage can occur in 10-30% of the population
transmission by saliva, most often by aerosol effect (coughing, sneezing), kissing
incubation period varries between 2-10days
prevention of meningitis caused by N. meningitidis
monovalent serogroup C
quadrivalent serogroups: A/C/Y/W-135
monovalent serogroup B
listeria monocytogenes
gram postive
CAMP+
catalase +
tumbling motility at 25 degrees
umbrella motility in semi-soft agar
beta hemolytic
clinical manifestations of L. monocytogenes
meningitis
abortion
perinatal septicemia:
- infant dies shortly after birth
- symptoms = disturbance of respiratory, circulatory, central nervous system
- if infant survives = meningitis or permanent mental deficiency
others = influenza like/ GI
L. monocytogenes virulence
listeriolysin O = most significant virulence factor
responsible for beta hemolysis on RBCs
destruction of phagocytic
aids in escape from the phagosome
present in all strains
management of meningitis
if possible obtain CSF before antibiotic treatment
in adults 3rd gen cephalosporin and vancomycin are empirically given
ampicillin added if patient is at risk for L. monocytogenes (50+)
steroids often added concomitantly
C. Difficile
anaerobic, spore forming, gram positive rod
major cause of nosocomial infectious diarrhea
pathogenesis: C diff colonization
see notea
C. diff pathogenesis: disruption of microflora
antibiotic exposure disrupts flora = selection for c. diff
c diff colonizes and then starts to produce toxins
C.difficile toxins
without the toxins they are unable to produce disease
paloc pathogenecity locus: 2 toxins = TcdA and TcdB
inflammation caused by C. diff
inflammation of the colon = colitis
neutrophil infiltration
intestinal damage
impaired permeability
fluid secretion
overall result = diarrhea and inflammation
C. difficile associated disease (CDAD)
spectrum of disease: asymptomatic (colonization) antibiotic assoc, diarrhea (AAD) psuedomembranous colitis (PMC) toxic megacolon (rare)
lab diagnosis of C.diff (pathogenic)
- detection of C. diff
- do an EIA for C. diff by looking for glutamatedehydrogenase (GDH) common to all c. diff
then:
- detection of toxins:
- cell culture cytotoxicity neutralization assay (CCCNA)
- EIA for toixin
- nucleic acid amp test (PCR)
toxin enzyme immunoassays
toxin B alone or toxin A and B
never do just toxin A bc it is sometimes deficient
sometimes do this in combination with GDH
management and prevention of C. difficile
barrier precauaitons and envrionmental cleaning in hospitals
stop unnecessary antimicrobial use
new approaches to treating C.diff
biotherapuetics - microflora restoration
fecal transplants: repopulation had successes in clinical trials
indications of viral gastroenteritis
incubation period is longer than toxigenic disease
no warning signs of bacterial infection like high fever, bloody diarrhea, sever abdominal pain
vomiting is often prominent
duration: entire illness is usually over in 24-72 hours
no epidemiological clues to suggest alternative diagnosis
common viruses associated with gastroenteritis
caliciviruses
adenoviruses (40and 41)
astroviruses
rotavirus
Hep a and E
caliciviruses
4 genera, 2 cause human disease:
norovirus = most common cause of actue viral gastroenteritis in adults
saporovirus = rare cause of human disease
clinical presentaiton: projectile vommiting/ explosive diarrhoea
epidemiology of norovirus
highly infectious - low infectious dose (1-10 partcicles)
transmission = fecal-oral or contact/fomites
viral shedding
detection of norovirus
real time RT-PCR
sequencing for genotyping
rotavirus
looks like a wheel
non-enveloped
3 capsids: outer, inner, intermediate
7 groups: A-C cause human disease
detected by RT-PCR or EIA from stool
transmission of rotavirus
low infectious dose: 10-100
by age 3 majority of children have been infected
transmission = fecal-oral, food/waterborne
clinical features of Rotavirus in children
low grade fever
vomiting for 2-4 days
explosive, non-bloody diarrhea
hospitalized for dehydration
- treat with IV fluids + electrolytes
epidemiology of rotavirus
25-65% of severe gastroenteritis is in children
6% of deaths among children under the age fo 5
current rotavirus vaccines
rotarix: IV and monovalent
RotaTeq: oral and pentavalent
enteric adenoviruses
linear DNA, non-enveloped
serogroup F, serotypes 40 and 41 cause gastroenteritis
enteric adenoviruses vs noro/rotavirus
longer incubation period: 3-10 days
less fever and dehydration
more prolonged sickness
more likely to infect children than adults (like rota)
diarrhea +, no vomiting
transmission = fecal-oral
detected by RT-PCR or EIA testing on stool
astrovirus
ssRNA +, non-enveloped
infections mainly in childhood
decal oral spread, low infectious dose
similar to rotavirus but less vomiting, fever, and nausea
detected by RT PCR
waterborne vs bloodborne hepatitis
see notes
hepatitis A
in developing countries: usually contracted in childhood
developed countries: adutls who travel to endemic countries or out breaks in food/water
usually self limiting
no chronic disease
risk of symptoms increases with age
hepatitis A symptoms
fatigue
nausea/vomiting
abdominal pain
jaundice (yellow skin and eyes)
dark amber urine
diagnosis of HAV
serology
early in disease HAV is excreted in stool so pcr is possible
diagnosis usually made by serology: IgM = acute infection vs IgG = immunity
prevention of hep A
natural infection confers life long immunity
vaccination: HAV or can get HAV and HBV
diagnosis of viral gastroenteritis
EM- nope
culture of enteric adenoviruses is possible but not sensitive (noro cant be cultured)
antigen detection (EIA) - sensitivity = only 60%
molecular testing - much more sensitive
serology = not typical for GI viruses except for HAV
prevention of gastroenteritis
hand washing
removal of source of infection
decontamination of environment (bleach)
vaccines
neisseria classification
see notes
N. gonorrhoeae
aerobic gram negative diplococci (Ox+, Cat+, superoxol+)
often appear intracellular on gram stain
fastidious
- grow on TM media (chocolate agar with antibiotics)
epidemiology of N. gonorrhoeae
risk factors : less than 25 yrs street youth/homeless new sexual partners (more than 2/year) non-barrier contraception
clinical manifestations of N. gonorrhoeae
acute urethritis/cervicitis ano-rectal gonorrhea pharyngeal gonorrhea pelvic inflammaotry disease (PID) septic arthritis
transmission/epidemiology of N. gonorrhoeae
risk of transmission of GC from infected woman to male =1/5
risk of transmission from male to female =1/2
perinatal transmission occurs during vaginal delivery and typically involves the eyes
risk during anal sex is high too
virulence factors associated with N. gonorrhoea
pili:
- adherence to mucosal surfaces
- inhibit killing by neutrophils
outer membrane:
- proteins (OMPs) facilitate invasion of epithelial cells
- lipooligosaccharides possess endotoxin activity, results in ciliary death
pathogenesis of N. gonorrhoeae
primarily infects columnar or cuboidal epithelium - found in cervix
attachment mediated by pili and OMPs
epithelial cells penetrated within 20-24hrs
vigorous neutrophil response follows with sloughing of epithelium and exudation of pus (neutrophils)
infection may spread - proximal genital tract, blood stream and joints
culture/diagnosis of gonorrhoea
does not grow on SBA
for culture used to take urethral of cervical swabs
now we use PCR
- vaginal swabs
- voided urine for males
sensitivity vs specificity
sensitivity = the percentage of sick people who are correctly identified as being sick
specificity = the percentage of healthy people who are correctly identified as negative for disease
positive vs negative predictive value
positive: proportion of patients with positive test results who are correctly diagnosed. its value is dependent on the the prevalence of the disease
negative: proportion of patients with negative test results who are correctly diagnosed
antimicrobial resistance treatment options for gonorrhoea
plasmid mediated beta lactamases
tetracycline resistance is common
fluoroquinolone resistance common
current recomendation: 800 mg cefixime or 250mg ceftriaxone intramuscular
chlamydia classification
c. trachomatis
c. pneumoniae
c. psittaci
biphasic life cycle (notes)
chalmydia infections
urethritis in men:
- incubation period = 7-21 days
- 25% of men are asymptomatic
cervicitis in women:
- 80% are asymptomatic + have normal cervical exam -this makes control of PID complicated
urethritis in women
laboratory diagnosis of chlamydia
antigen detection
immuno-fluorescence
cell culture
PCR(male urine, vaginal swab)
treatment of chlamydia
1st line: 1g azithromycin (single dose)
2nd line: 100mg BID doxycycline (10 days)
haemophilus ducreyi
cause chancroid ulcers/ bubos (STI)
morphology:
- intracellular or extracellular
- pleomorphic cocco bacilli or short rods
- gram variable
- bipolar staining
- arranged in parallel chains
cultural characteristics and growth requirements of haemophilus ducreyi
fastidious organism
grows slowly on chocolate agar
use of two medias is optimal
gonococcal agar or mueller hinton based medium
treatment of haemophilus ducreyi (chanchroid)
1g azithromyci (single dose) or 250 mg ceftriaxone intramuscular
molluscum contagiosum diagnosis
clinical appearance:
- dome shaped with dimpled center
- smooth waxy or pearly surface
- core = curd like (cheese/waxy)
electron microscopy (insensitive)
PCR in reference labs only
symptoms of molluscum contagiosum
not painful but sometimes itchy
scratching can cause irritation + scarring
secondary bacterial infections
shaving = bleeding risk+spread
molluscum contagiosum transmission
contact:
- affects skin/mucosal membranes
- sexual or scratching/touching skin
indirect = fomites such as clothes or towels
molluscum contagiosum treatment
chemical or surgical removal
herpes simplex virus (HSV)
HSV-1 +HSV-2= enveloped, icosahedral capsid, dsDNA
two important enzymes: thymidine kinase and DNA polymerase
HSV epidemiology
HSV2 = second most common sti
HSV1 causes cold sores - 80% of the population
40% of genital herpes is caused by HSV-1
most people dont know theyve been infected bc primary infections are usually asymptomatic
first symptoms = usually reactivation
HSV spectrum of disease
encephalitis
ocular infections
muco-cutaneous lesions
HSV latency and reactivation
primary infection = local replication and viral entry into neurons - migration along the axons to ganglia = latency
replication (triggered by stress or immunosuppression) - migration to epidermis = reactivation
reactivation of HSV-1 vs HSV-2
HSV-2: reactivation is frequent
- asymptomatic shedding on 28% of days
HSV-1: reactivation is less frequent, less than once a year
- asymptomatic shedding occurs less frequently
acyclovir mechanism of action
it is a pro-drug that blocks viral DNA polymerase by acting as a nucleotide analogue
requires phosphorylation by viral thymidine kinase - then gets phosphorylated by host enzymes
acyclovir resistance
less frequent in immunocompetent hosts
resistance mechanism = thymidine kinase mutats (95%) viral DNApol (5%)
alternative treatments for HSV
cidofivir = phosphorylated nucleotide analog (doesn't need TK) foscamet = pyrophosphate analog (blocks viral DNApol)
diagnosis of HSV
molecular testing: RT-PCR or other NAAT
human papilloma virus (HPV)
non-enveloped, dsDNA circular
most common sti (80% of adults)
cannot be grown in culture
-pap test are best for ID
high risk vs low risk HPV strains and what they cause
high risk: 16 and 18 - cause cancer - low or high grade pap smear abnormalities
low risk: 6 and 11 - cause anogential warts and recurrent respiratory papillomatosis
respiratory papillomatosis
benign warts in the upper airway
- may cause obstruction
surgical removal
caused by hp 6 and 11
childhood - normally aquired at birth
adult - oral intercourse
how to treat genital warts
treatment is usually for aesthetic reasons
- clearnence rate = 30-90%
available treatments:
- podophyllin resin
- trichloroacetic acid (TCA)
cryotherapy
HPV acquisition
hpv is acquired shortly after onset of sexual intercourse
coninfection with multiple strains is common
38% of females get hpv after one year of being sexually active
HPV infection
individual episodes last between 4-20 months
for most people = transient infection (nothing happens)
body’s immune system eliminates hpv infection
for infections that clear, reappearance of same type is common
why are only some HPV strains oncogenic?
high risk strains integrate into the host DNA as linear - disrupts E2 (transcriptional repressor) = increase in expression of E6andE7
drives cell growth = cancer
development of cervical cancer from HPV infection
hpv infects basal layer cells
hpv replicates and infects squamous epithelial cells = squamous intraepithelial lesion
abnormalities arise as E6/E7 are produced
proceeds to invasive cancer
detection of the development of cervical cancer
do a primary screen (pap test)
detection of patients with cervical cell abnormalities = atypical squamous cells of unknown significance (ASCUS)
do follow up
HPV prevention
vaccines
gardasil = types 16,18, 6, 11
ceravix = 16 and 18 only
epidemiology of bacterial GI infections
developed countries:
- waterborne/foodborne outbreaks
- overall burden not well established
- attack reate: 1-3 illnesses per child/year
developing countries:
- major cause of morbidity and mortality in children
- 10/18 illnesses/child/year
- 4-6 million deaths/year (asia, latin America, africa)
ID of bacterial GI based on incubation periods
really short time span (hours): toxin mediated
really long time (2-8 days): E. coli 0157
lab diagnosis/ appropriate specimens
1g of feces contains approx. 10^11 bacteria therefore selective media must be used
most bugs present in 3 days so if stool is from patient admitted to hospital more than 3 days ago sample is rejected
formed stool should also be rejected
on requiest use TCBS agar for virbio
routine agars: XLD, Campy, MacConkey, sorbitol MacConkey, chromogenic
camplyobacter
gram neg, highly motile, spiral rod
C. jejuni & C. coli
thermophillic (25-44)
microaerophilic
isolation on blood/charcoal containing agar + antibiotics
C. fetus occasionally associated with disease
campylobacter infection
incubation period: usually 2-4 days
infective dose= large
prodrome of fever, myalgia
diarrhoea (occasionally bloody) - abdominal pain and malaise
usually self limiting, resolves within 7 days - only treat if bacteremic or immunosuppressed
occasionally assoc. with guillain barre syndrome
salmonella species
only 2 species: s. enterica (most relevant) and s. bongori
over 2000 serovars such as S. typhimurium
salmonella antigenic structure
kauffmann-white antigenic scheme: agglutination reactions with specific antisera against salmonella antigens
O antigens:
- O polysaccharide of LPS
H antigens:
- flagellar antigens (protein)
Vi antigens (S.typhi only) - capsular polysaccharide
salmonella gastroenteritis
incubation period depends on dose (infectious dose = 1million+)
symptoms (within 48-72hrs)
- nasuea/vomiting
- diarrhoea
- abdominal pain
- myalgia + headache
- fever
duration = 2-7days
usually self limiting
only fatal in elderly/immunocompromised
salmonella enteric fever
caused by S. typhi
incubation period = 10-14 days
bacteraemic illness:
- myalgia and headache
- fever
- splenomegaly
- abdominal pain
- leukopenia
- rose spots/ rash
blood, bone marrow, stool and urine cultures are positive
potential consequence: intestinal hemorrhage and perforation
isolation of salmonella
pre-enrichment broths:
-selenite or tetrathionate
selective and differential media
-XLD, HE. SS agar, Bismuth-sulfite agar
XLD
selective and differential medium designed for the isolation of gram negative enteric pathogens from clinical specimens
contains xylose, lysin, sodium desoxycholate, sodium thiosulfate, and ferric ammonium citrate
prinicple of XLD selection
all enterics ferment glucose except shigella
salmonella rapidly uses xylose and the decarboxylates lysine (mimics the shigella rxn) - reverts to alkaline conditions
(lactose and sucrose are added in excess to prevent lactose fermenters from doing same thing)
production of hydrogen sulfide under alkaline conditions results in black colonies (salmonella)
E.coli 0157 infection
incubation period = 3-9 days
infectious dose= 10 bugs
diarrhoea: mild to grossly bloody (haemorrhagic colitis)
severe abdominal cramping
HUS in up to 10% of cases:
-anemia, thrombocytopenia, kidney damage
significant mortality (1-5%)
shiga-like toxin on E.coli 0157
a distinguishing virulence factor
subunit toxin:
A: inhibits protein synthesis by acting on ribosomes
B: binds glycolipid receptor in mammalian cells (renal endothelium)
E.coli 0157
virtually all 0157 stains do not ferment sorbitol (most non-0157 strains do)
- use a sorbitol-MacConkey agar where lactose is replaced with sorbitol
0157 strains are beta-gluconidase neg
latex agglutination to confirm 0157 strains
ID is important bc:
- antibiotics/antimotility agents are a risk factor for HUS
- want to know if you’re dealing with an outbreak
shigella species
S.dysenteriae (grp A)
S. flexneri (grpB)
S boydii (grpC)
S. sonnei (grpD)
tests: Urea - motility - TSI K/A - no gas all ferment mannitol except s.dysenteriae
clinical significance of shigella
shigellosis or bacillary dysentery
infectious dose = low
fecal-oral route (may be person to person)
2-4day incubation
fever, cramping, abdominal pain, watery diarrhea
may be followed by frequent scan stools with blood, mucous, and pus (invasion of intestinal muscosa)
disease severity depends on infecting species
shigella antigenic structure and virulence factors
A, B, C, D grouping is based on O antigen serotyping
- similar O antigen to E.coli so need to ID as shigella first
shiga toxin = virulence factor
- produced by dysenteriae and in smaller amounts from S. felxneri and S.sonnei
yersinia enterocolitica
infection can mimic appendicitis
virulence = result of tissue invasiveness by the organism
main pathogenic strains from swine but also get it from:
beef, lamb, seafoods, veg milk, cake, vaccum packaged meet
grown on MacConkey agar
vibrio, aeromonas and plesiomonas: similarities and differences compared to enterobacteriaceae
similarities:
- gram negative
- facultative anaerobes
- fermentative bacilli
differences:
- polar flagella
- oxidase positive
the three used to be vibrionaceae:
- primarily found in water sources + cause GI disease
morphology and physiology of vibrio
shaped like commas
v.cholerae, v. parahaemolyticus, V. vulnificus = significant
broad temp/pH range
grow on MacConkey and TCBS
V.cholerae grow without salt, most other vibrios are halophilic
taxonomy of vibrio cholerae
over 200 serogroups based on somatic O antigen
O1 and 0139 = epidemic cholera
O1 subdivded into El Tor and classical
some O1 strains dont produce cholera enterotoxin
pathogenesis of V. cholerae
incubation period: 2-3 days
high infectious dose > 10^8 CFU
- lower if you have reduced stomach acid
abrupt onset of vomiting and life threatening diarrhea (15-20L a day)
as more fluid s lost, feces streaked stool changes to rice water stool
encephalitis
inflammation of the brain itself
meningitis symptoms + mental status changes
seizures, decreased consciousness, confusion, hallucination
indications of viral CNS infection
gram stain does not show bacteria
WBCs are less than 300 and mainly lymphocytes
occasionally increased RBCs (HSV)
normal to mid-high protein
normal glucose
etiology of viral CNS infections
enterovirus
HSV 1 and 2
arboviruses
rabies
enterovirus epidemiology
RTIs
myocarditis, exanthems (rash), acute flaccid paralysis
causes 30-50% of viral meningitis = aseptic meningitis
people at risk: anyone
seasonal outbreaks are common
enterovirus aseptic meningitis
usually RTI symptoms
sometimes vomiting
severe headaches
photophobia
no longterm sequelae
will go away on its own
diagnosis, treatment, prevention of enterovirus CNS infection
diagnosis
- clinical suspicion: RTI, meningitis, photophobia
- CSF profile (high WBC (lymphocytic), mod-high protein)
- CSF rt-pcr
prevention: no vaccine available
treatment: supportive as needed
- antivirals are no longer available/effective
HSV - encephalitis epidemiology
most common cause of sporadic viral encephalitis in north america
no seasonal distribution
high morbidity/mortality without treatment
pathogenesis of HSV encephalitis
rare to occur from primary infection
often a reactivation from latency
clinical manifestations of HSV encephalitis
fever/headache
progressive neurological symptoms
mental status changes are frequent (temporal lobe)
seizures = common
long term neurological sequelae are possible
immunodeficiency can lead to systemic spread = often fatal
diagnosis of HSV encephalitis
clinical suspicion (mental status changes)
CSF profile (high wbc, mod/high protein, high rbc)
CSF pcr for hsv 1/2
diagnostic imagaing (MRI or CT) - temporal lobe involvement
prevention and treatment fo HSV encephalitis
no vaccines
treat empirically with acyclovir
rabies virus epidemiology
common in developing countries but rare in north america
rabies virus transmission
transmission through saliva of infected animals
reservoir in north america = bats, skunks, raccoons and foxes
infected animals show no fear of humans and are agitated
bat bites often go unnoticed
rare form domestic pets
pathogenesis of rabies virus
rabies is neurotropic = affinity for nerve cells/tissue
has a long incubation descending on the location of the bite - will infect other things on the way to the brain
clinical manifestations of rabies
fever agitation hydrophobia = fear of water painful spasms - infecting muscles on way to brain excessive saliva
lab diagnosis of rabies virus
clinical suspicion with exposure history
CSF profile not helpful
post-mortem exam of the animal or human is best
post-mortem on CSF/saliva/tissue
DFA on neck skin biopsies - specifically need the skin with hair follicles
treatment and prevention of rabies virus infection
prevention = vaccine
- only covered for people at risk (vets)
treatment = rabies immunoglobulin and vaccine
- was cute/bite with soap and water then add Ig directly to opening
- administer vaccine at same time
arboviruses
transmitted through vectors
-insect that can transmit an infection - transmits from one infect animal to another
zika virus
association with microcephaly
arboviruses that cause encephalitis
west nile virus (WNV)
Japanese encephalitis virus
eastern equine encephalitis virus
la crosse virus
clinical manifestations of arboviruses
most are asymptomatic
mild, non-specific viral syndrome
meningoencephalitis (fever, headache, seizures)
severity varies with virus and host
longer term neurological sequelae are possible
epidemiology of arboviruses
seasonal bc of mosquitos
geographically distributed - need vector and reservoir
transmission cycles of arboviruses
epidemic cycle
endemic cycle
enzoonotic cycles
and all of these cycles can overlap
epidemic transmission cycle of arboviruses
reservoir = humans (high level of viremia)
vector readily transmits virus between humans
examples: dengue, yellow fever, chickungunya
enzootic transmission of arboviruses
reservoir = vertebrae host (has virus without showing symptoms)
vector = mosquito
humans are incidental hosts (there is no human to human spread and low viremia)
example = west nile virus
epizooic cycle (rural cycle)
virus amplification in animal (gets visibly sick)
possible spillover into humans
diagnosis, treatment, and prevention of arboviruses
diagnosis:
- clinical suspicion: exposure/travel
- CSF profile: high wbc (lymphocytic, mod-high protein
- pcr on CSF + serology
treatment: supportive
prevention: no vaccine for most
but have things like: nets, insect repellent, clothing
CA-MRSA
serious community acquired infections
necrotizing skin and soft tissue infections
several clonal groups/PVL positve
treat with: TMP/SMX, doxycycline, and clindamycin
definition of MRSA
novel PBP
PBP-2a has reduced affinity for beta-lactam agents- can perform essential functions for other pbp
encoded on the mecA gene - acquired via transposition but is now chromosomal
homogenous vs heterogeneous expression
homogenous - all bugs have the resistance
heterogenous - see a haze after about 24hrs around the disk because the resistant organisms start to move in
detection of MRSA
muller hinton agar with salt and oxicillin
or chromogenic agar with cefoitin (better at inducing mrsa)
risk factors for CA-MRSA
younger age groups (us) IV drug users lower economic status MSM crowded conditions
factors that cause spread of CA-MRSA
-skin to skin contact
-cuts and abrasions
-shared contaminated items/surfaces
-poor hygiene
crowded living conditions
clinical manifestations of CA-MRSA
halmark = pus
boils or draining pimples
sores that won’t heal
red areas of the skin that feel warm
systemic infections
MRSA genetics
MecA gene complex is carried on specific integrated genetic element = staphylococcal cassette chromosome (SCC)
5 types of SCC-mec
HA-MRSA mec has types 1,2,3
CA-MRSA strains have type 4 (don’t carry multiple resistance genes) - usually only resistant to beta lactams and erythromycin
panton-valentine leucocidin (PVL) toxin
cytotoxin present in less than 5% of MRSA
rare in HA
capable of destroying WBC
severe tissue damage and associated with necrotic skin lesions
severe necrotizing pneumonia
vancomycin resistant enterococci (VRE)
intrinsic glycopeptide resistance in gallinarum and casselifavus but chromosomal
faeciuma and faecalis have transferable resistnance
ID of enterococcus
motility
E. faecium/faecalis = non.motile
gallinarurm = motile (mostly)
pigment:
E.casselifavus = yellow pigment (not visible on plate)
glucopyranoside
gallinarium/casselifavus = +
faecium/faecalis = -
CRE
carbapenem resistant enterobacterales
KPC = K. pneumoniae cabapenemase (first discovered in kp but exists in other organisms)
NDM = bad one
modified carbapenem inactivation method mCIM
fill tubes with broth
inoculate with bug of interest
put in merepenem disks - incubate
inoculate pate with susceptible E.coli strain
takes the disks out and put them on the plate
if the organism produced a carbapenemase then the disks will not work against e coli
classifications of SSTIs
related to the depth fo the infection
uncomplicated = superficial wound
complicated = deep wound
cellulitis
acute
infection of dermis and epidermidis
inflammation but little/no necrosis or edema
lymphatic involvement
fever, chills, leukocytosis
bacteremia (30% of cases)
s.aueus and strep pyogenes
bugs that infect surgical wounds
s. aureus enterococci coag neg staph e.coli p. aeruginosa
bacteria that infect traumatic woulds
S.aureus and enterobacterales
streptococci/clostridia
vibrio vulnificus (salt water wounds)
vibrio vulneificus
infection results when skin lacerations or abrasions come in direct contact with seawater
infections begin with swelling, redness, and intense pain around the infected site
develop and progress to tissue necrosis in a rapid process
50% require surgical intervention
bacteria that infect burns
s.aureus enterobacter clocacae coag-neg staphylococci p.eruginosa e.coli enterococcus spp
bacteria that infect bites
pasteurella maltocida capnocytophaga canimorsus eikenlla corrodens peptostreptococci alpha and beta strep
staph enzymes
coagulase:
fibrin coagulum
sets up localized infection
hylauronidase:
hydrolyzes hyaluronic acids in the intracellular matrix of connective tissue - facilitates spread of s.aureus through tissues
staph toxin: exfoliative toxin
exfoliative toxin genes are carried on plasmids
mechanism of action is unknown
leads to disturbance of the adherence of cells in the stratum granulosum layer of the epidermis
neutralizing antibodies develop after infection, protecting older children and adults
staphylococcal scalded skin syndrome
abrubt onset of a localized peri-oral erythema (redness and inflammation around the mouth) - covers entire body in 2 days
large bullae or cutaneous blisters form - then sequamation of the epithelium
caused by exfoliative toxin
toxic shock toxin
responsible for toxic shock syndrome
this is a super antigen - causes massive polyclonal t ell stimulation
usually associated with s.aureus and occasionally in coagulase negative staph
toxic shock syndrome
initially described in women on their periods or ppl with localized staph infections
systemic absorption TssT-1
TSS produces fever, blood vessel dilation, and a sunburn-like rash
cytokine stimulation: hypotension and multi-organ failure
fatality rate =15%
S.pyogenes (SSTIs)
cellulitis
toxic shock
necrotizing fasciitis
pasteurella multocida
sm. fastidious gram negative rod
facultative anaerobe
catalase/oxidase +
MacConkey rarely supports growth
characteristic odor
intrinsically resistant to oral cephalosporins
50% of infections caused by dog bite wounds
capnocytophaga
capno = co2 loving
gram neg
dogs and cats
oxidase/catalase +
serious disease in asplenic and immuno compromised
cat bites
serological diagnostics
pasteurella/capnocytophaga
bartonella henselae
aerobic, fastidious gram negative cocco-bacilli
hemin dependent:
- cat scratch fever
- endocarditis
rarely cultured
eikenella
e. corrodens
small gram neg rod
catalse - / oxidase +
no growth on MacConkey
no acid on TSI slant
bleach odour
human bites
clenched fist injuries
rat bites
streptobacillus monoliformis
rat bit fever
pleomorphic facultative gram negative rod
catalase/oxidase -
biochemically inert
bone infections
osteomyelitis = inflammation of the bone caused by an infecting organism
remain localized or may spread from bone to marrow to cortex, periosteum and then soft tissue surroundings
3 ways organisms may reach the bone
skin wound communicating with bone - open fracture
direct spread form neighbouring soft tissue infection
indirectly via the blood stream
septic arthritis
infection of joint spaces
hematogenous or contiguous
caused by s. aureus, step, gram negative bacilli
osteomyelitis
infection of the bone
hematogenous or contiguous
s.aureus, s.pyogenes
CNS H influenzae, gram neg bacilli
diabetic foot infection
cellulitis - deep soft tissue infection and then osteomyeltis
risk factors:
- vascular disease
- peripheral neuropathy
- poor foot care
