STDs, UTIs, Protein Synthesis Inhibitors, Intro to Eye (Week 4) Flashcards
Bacterial STDs
Most are curable!
Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum (syphilis), Klebsiella granulomatis, Haemophilus ducreyi
However, complications if untreated (PID; epididymitis; syphilis becomes chronic)
Reporting STDs
Syphilis: report and try to track down partners
Chlamydia and gonorrhea: report (?) but don’t track down partners
Sequelae of N. gonorrhoeae and C. trachomatis
Urethritis (urethral inflammation): dysuria, discharge, WBCs, leukocyte esterase positive
Cervicitis (cervical inflammation): asymptomatic; vaginal bleeding, discharge, friable cervix
Most common bacterial STD
Chlamydia trachomatis
(reportable)
Chlamydia
Requires columnar epithelial cells
Young people more prone, because have more columnal epithelial cells
Beefy red cervical mucosa, follicular changes “cobblestoning”
Women: Cervicitis, urethritis, conjunctivitis (auto-inoculation) –> PID, peri-hepatitis (Fitz-Hugh-Curtis)
Men: Urethritis, proctitis, conjunctivitis (auto-inoculation) –> epididymitis, reactive arthritis
Pelvic inflammatory disease (PID)
Can be acute or silent
A result of untreated chlamydia or gonorrhea
Infection of entometrium (endometriosis), fallopian tubes (salpingitis), pelvic peritoneum (Fitz-Hugh-Curtis syndrome w/violin strings)
Adnexal pain, easily provoked cervical bleeding, elevated ESR or CRP
Diagnose with imaging or laparoscopy
Leads to ectopic pregnancy because of scarring, infertility because of fallopian tube occlusion, chronic pelvic pain
Reiter’s syndrome (reactive arthritis)
Complication of chlamydia
Oligoarthritis (swelling and tenderness in mult joints)
Circinate balantis (scaling erythematous plaques on penis)
Autoimmune reaction associated with HLA B27
Lymphogranuloma venereum (LGV)
Serotypes L1, L2, L3 of chlamydia causes this
Enters lymphatics, replicates in macrophages –> inguinal lymphadenitis –> proctocolitis
Groove sign: enlarged inguinal and femoral nodes separated by ligament of Poupart
Neonatal chlamydia
Note: not one of “ToRCHeS” but mother can still give to child during birth
Conjunctivitis, pneumonia
Diagnostic tests for chlamydia
Chlamydia is INTRACELLULAR organism, so need to culture cells
However, now we can do nucleic acid amplification testing (NAAT) just using urine specimens: PCR, LCR, TMA, SDA
Treatment for chlamydia
Azithromycin 1g PO x 1
Doxycycline 100mg PO BID x 7 days
Patient delivered partner therapy
Gonorrhea
Facultative intracellular (can be inside or out of cells)
Infects noncornified epithelium
Formation of submucosal abscesses and accumulation of exudate in lumen
Women: cervicitis, urethritis, proctitis, pharyngitis, skene/bartholin gland infection –> PID, Fitz-Hugh-Curtis, disseminated infection
Men: urethritis, epididymitis/seminal vesiculitis, proctitis, conjunctivitis, abscess of Cowper’s/Tyson’s glands, pharyngitis –> disseminated gonococcal infection (DGI), urethral stricture, penile edema
Disseminated gonococcal infection (DGI)
Gonococcal bacteremia
Symptomatic or asymptomatic infection of pharynx, urethra, cervix
<5% of GC infected people
Complement deficiency (C7, 8, 9) means higher risk for this
“Arthritis-dermatitis syndrome” with polyarthritis and sterile tenosynovitis and skin lesions
Neonatal gonorrhea
Not one of “ToRCHeS” but vertical transmission during birth (30%) if no prophylaxis
Ophthalmia neonatorum, DGI, vaginal/rectal/pharyngeal infections
Diagnostic tests for gonorrhea
Gram stain, culture, DNA probe, NAATs using urine
Treatment for gonorrhea
Ceftriaxone IM (injection) x 1
PLUS
Azithromycin 1g PO x 1 or doxycycline 100mg PO BID x 7d (same as chlamydia, but also enhanced activity against gonorrhea!)
DON’T use fluoroquinolones (resistance) or cefixime (anaphylactic shock)
Epididymitis
Complication of gonorrhea or chlamydia in men; also from UTI
Unilateral testicular pain/swelling, usually accompanied by urethritis
Genital ulcer disease
STD causes: herpes simplex, syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale
Non-STD causes: Candida balanitis, impetigo, trauma, Bechet’s syndrome, fixed drug eruption, malignancy, contact dermatitis
Vaginitis
Trichomonas vaginalis (parasite)
Related to sexual activity, but not clearly transmitted sexually
Tetracyclines mechanisms of resistance
1) Bacteria alter outer membrane porin proteins so decreased influx of drug into bacteria
2) Bacteria do active transport out of cell by pump proteins
Tetracycline considerations regarding food, etc
Do not take tetracycline with dairy (calcium) because will form chelates so cannot be absorbed
Do not give tetracycline to pregnant women (bc of effect on fetus) or children under 8 whose teeth have not formed because will stain teeth brown
Take with full glass of water because can cause gastric discomfort if stuck in esophagus
Causes phototoxicity, dizziness, liver failure
Can cause superinfection (because broad spectrum)
Tigecycline
Clycylcycline class of protein synthesis inhibitors
IV administration only
Very broad spectrum (gram +, gram -, anaerobes MRSA, VRE, MDR acinetobacter)
Good for intra-abdominal infection (Enterococci, E. coli, Klebsiella, Bacteroides fragilis)
NOT Pseudomonas aeruginosa
Mechanisms of resistance to aminoglycosides
Bacteria can:
1) Alter uptake mechanisms to decrease influx of drug into bacteria
2) Alter target (mutate 30S ribosome)
3) Enzymatic modification to phosphorylate, adenylate, acetylate the drug to make it inactive
Dosing of aminoglycosides
Exhibit concentration dependent killing: bactericidal activity proportional to peak concentration (so want peak conc as high as possible)
Have post-antibiotic effect (drug works even after levels are below MIC)
Toxicity less with once daily dosing
Give one single high dose per day
Pharmacokinetics and toxicities of aminoglycosides
Only used IV, IM or topically (poor absorption in GI)
Polar, bad CSF penetration
High levels in urine because excreted there so good for treating UTIs
Also get into blood so good for gram - septic shock
Toxicities: nephrotoxicity and ototoxicity
Adverse effects of macrolides
Epigastric distress (worst with erythromycin)
Cholestatic jaundice
Ototoxicity (rare)
QT prolongation
Adverse drug interactions because interfere with CYP450 clearance
Mupirocin
AKA Bactroban, pseudomonic acid A
Active against gram + bacteria including MRSA
Used topically only
Used before surgery to prevent MRSA into open would
Drugs for anaerobic infections
Clindamycin
Chloramphenicol
Tigecycline
Penicillins
Piperacillin/tazobactam
Ampicillin/sulbactam
Amoxicillin/clavulanate
2nd generation cephalosporins (cefoxitin, cefotetan)
Carbapenems
Moxifloxacin
Treatments for specific anaerobic infections
Anaerobic streptococci: penicillin
Oropharyngeal GI infections (head and neck abscess): clindamycin, penicillin, penicillin + beta lactamase inhibitor
Intestinal GI infections (ruptured appendix): metronidazole, cefoxitin, cefotetan, carbapenem, penicillin + beta lactamase inhibitor, clindamycin
Abscesses: metronidazole, chloramphenicol
Causative organisms for UTI in women
E. Coli
S. saprophyticus
P. mirabilis, Klebsiella, Pseudomonas, Serratia, Enterococcus, yeast
Uropathogenic E. coli (UPEC)
A few serotypes of E. coli cause UTI
Virulence factors specific/important to UPEC: adhesins (type 1 fimbriae, P fimbriae)
Contains pathogenicity-associated islands (PAIs) which contain clusters of virulence factor genes
Pathogen has to stick in order to infect you (or else you’d pee it out)
Type 1 Fimbriae
One of two adhesins important to UPEC
Rod-like polymer of FimA with one FimH on the tip which adheres to mannose-containing uroplakin proteins on bladder uroepithelial cells
Cystitis
P Fimbriae
Adhesin that helps E. coli (UPEC, specifically) bind to uroepithelial cells
Pyelonephritis-associated pilus (pap) gene cluster has 11 genes
PapG adhesin subunit at tip binds glycolipids on uroepithelial cells of kidney –> causes pyelonephritis
P fimbriae is important vaccine target
Pyelonephritis
Host defense mechanisms against UTI
Unobstructed flow of urine (flush out anything that tries to colonize)
Normal urine characteristics (osmolality, urea concentration, pH, etc)
Tamm-Horsfall glycoprotein (THP) produced by ascending loop of Henle and DCT, mannose rich residue secreted into urine
Host susceptibility to UTI
Obstruction to urine flow
Neurogenic bladder (incomplete emptying)
Renal calculi
Sexual activity
Antibiotic therapy (altered flora)
Diabetes (glucose in urine)
Low estrogen (post-menopause) makes it easier for bacteria to attach to cells
Urinalysis for UTI
10 WBC/high power field = pyuria = evidence for inflammatory response
RBCs = evidence for damage to uroepithelium
Gram stain = evidence for bacteria in urine
2 lab tests used together to diagnose UTI
Leukocyte esterase (suggests WBCs in urine)
Nitrite (suggests bacteria in urine)
Cystitis vs. pyelonephritis
Cystitis: bladder infection
Pyelonephritis: kidney pelvis infection (have abscess formation in kidney; costovertebral-angle tenderness; fevers, chills, nausea) and can lead to sepsis or death
What else can present with burning on urination?
Urethritis due to N. gonorrhoeae, chlamydia, HSV
This is NOT a UTI
Should you get a culture when you suspect UTI?
Only if you suspect pyelonephritis since that is dangerous
No need to culture for uncomplicated cystitis
What can cause kidney stones?
Bacteria produces urease –> splits urea into ammonium hydroxide –> raises urinary pH –> precipitation of struvite and apatite stones in bladder and kidney –> obstruction of urine flow
Intervention to relieve pressure in order to preserve renal function
Urease +: Proteus mirabilis, S. saprophyticus, K. pneumoniae, C. urealyticum
Asymptomatic bacteriuria
Positive bacterial culture from appropriately collected sample in patient with no symptoms
Only treat pregnant women (reduce risk of pyelonephritis which would be bad because hard to treat pregnant women!)
Drugs to treat uncomplicated UTI
Trimethoprim-sulfamethoxazole BID x 3 days
Nitrofurantoin 100mg BID x 5 days
Nitrofurantoin
AKA Macrobid 100mg
No tissue penetration, so use only for cystitis
Proteus and Klebsiella resistant
Safe in pregnancy
Can cause severe lung injury: acute presenting like allergy, or chronic interstitial fibrosis
Fosfomycin
To treat uncomplicated UTIs
Activity against VRE, ESBL producing E. coli, some MDR Pseudomonas aeruginosa, few MDR Acinetobacter baumanii
Fluoroquinolones for UTI
Don’t use them for uncomplicated UTIs because you need them for more serious infections (pyelonephritis)
Risk of “collateral damage” or producing resistance by using these drugs
High: TMP-SMX, fluoroquinolones, beta-lactams
Low: nitrofurantoin, fosfomycin, pivmecillinam
Inpatient treatment of pyelonephritis
3rd generation cephalosporin +/- aminoglycoside
Extended spectrum penicillin +/- aminoglycoside
Carbapenem +/- aminoglycoside
Outpatient treatment of pyelonephritis
PO fluoroquinolone +/- IV aminoglycoside one time
Ciprofloxacin better than TMP-SMX
How to deal with pyelonephritis
Get a urinalysis and culture for all patients with pyelonephritis
CT scan for anyone with history of renal colic
If fever persists after 72 hours, reculture because might be missing a pathogen and do radiological studies
Mechanisms of resistance to fluoroquinolones
Mostly due to alteration in subunits of DNA gyrase or topoisomerase IV
Less commonly decreased outer membrane permeability, activation of efflux pumps
Adverse effects of fluoroquinolones
GI upset is most prominent side effect
Dizziness with moxifloxacin, tendinopathy (achilles tendon rupture), hepatotoxicity, hyper/hypoglycemia
Contraindicated in pregnancy and in children due to cartilage toxicity
Pharmacokinetics of fluoroquinolones
Well absorbed but don’t give with Ca2+, Fe, Mg2+ because it will inhibit absorption
Concentration in kidney and urine is high (good for UTIs!), CSF levels lower than plasma
Hepatic metabolism clears 20% and the rest excreted in urine (good for UTIs!)
Adverse effects of methenamine
GI distress
Contraindicated in patients with renal dysfunction, hepatic dysfunction
Don’t give with sulfonamides because will inactivate both agents
Daptomycin
Inserts K+ channel into bacterial cell membrane to disrupt electrochemical gradient –> bactericidal
Active against many gram +, MRSA, VRE
NOT active against gram -
Used for skin infection, bacteremia, right sided endocarditis; NOT for pneumonia bc inactivated by surfactant
Doesn’t break open bacteria like beta-lactams do so might use this if worried about that
Chlamydiaecea
Chlamydia trachomatis
Chlamydophila pneumoniae, Chlamydophila psittaci
Obligate intracellular
Gram - but LPS does not cause cytokine storm!
No peptidoglycans of cell wall so beta lactams don’t work!
Treatment for chlamydia
Azithromycin (macrolide) 1g PO x 1 day
Doxycycline (tetracycline) 100mg BID x 7 days
Quinolones x 7 days
Chlamydophila pneumoniae
Pharyngitis, bronchitis
Atypical pneumonia (interstitial infiltrates, non-productive cough)
Otitis media, endocarditis (rare)
Mycoplasma and Ureaplasma
M. pneumoniae, M. hominis, M. genitalium, U. urealyticum
Smallest bacteria
Lack rigid cell wall
Diagnosis: NAAT, serology, cold hemagglutinin
Treatment: tetracyclines, macrolides, quinolones (NOT cell wall agents!)
M. hominis, M. genitalium, U. urealyticum
Cause of non-gonococcal urethritis
Rickettsiae
Rickettsia, Orientia, Coxiella, Anaplasma
Infect vascular endothelial cells, and other cells
Arthropod vector transmission for Rickettsia, Orientia, Anaplasma
Goats, sheep etc transmission for Coxiella
Anaplasmosis (Ehrlichiosis)
Tick vector
Similar to RMSF without a rash (headache and fever)
Infects leukocytes; monocytic, granulocytic; doesn’t infect vascular endothelium so no rash!
Treatment: doxycycline/chloramphenicol
Endemic (murine) typhus
Rickettsia typhi
Rats with fleas are reservoir –> fleas bite humans accidentally
Abrupt onset fevers, chills, headaches, myalgias
Milder than RMSF and resolves without treatment
Treatment: doxycycline or chloramphenicol, if necessary
Tpr membrane proteins
Proteins on surface of Treponema pallidum that change variable region so immune system cannot catch them!
Stages of syphilis
Incubation: 21 days
Primary syphilis: 3-6 weeks; painless chancre w/raised borders
Secondary syphilis: 2-8 weeks after chancre appeared; dissemination, condyloma lata, maculopapular rash on palms and soles, meningitis, hepatitis, arthritis
Latent syphilis: early or late (1 year cutoff)
Tertiary (late) syphilis: gummas, cardiovascular (aortitis, aortic aneurysm), neurosyphilis (meningiovascular, general paresis, tabes dorsalis, Argyll Robertson pupil)
Serodiagnosis of syphilis
Nonspecific (nontreponemal) tests: VDRL, RPR; used as screening, titer measures disease activity, response to therapy; antibody to cardiolipin (lipid found in normal tissues); false positive reactions in SLE
Specific (treponemal) tests: FTA-ABS, MHA-TP; antibody to specific antigens of T. pallidum; used to confirm positive VDRL or RPR
How do you treat syphilis if patient is allergic to penicillin?
Desensitize to penicillin (especially if patient is pregnant)
Doxycycline, ceftriaxone, chloramphenicol
Interaction between syphilis and HIV
Patients with syphilitic lesions more susceptible to acquiring HIV
Co-infected patients more likely to transmit both HIV and syphilis
Co-infected patients have more malignant course of syphilis
Syphilis relapses after adequate therapy in co-infected individuals
Nonvenereal treponematoses
Yaws: T. pallidum (pertenue) in humid tropics, transmitted skin to skin, papules, gummas of bone and skin
Pinta: T. carateum in arid Americas, transmitted skin to skin, papules, achromic macules
Bejel: T. pallidum (endemicum) in arid Africa, transmitted mouth to mouth, oral lesions, gummas of bone and skin
Borrelia vsp expression
vsp = variable surface protein
Moves antigenic genes around by recombination to produce different vsp proteins to evade immune response!
Borrelia recurrentis, Borrelia hermsii
Relapsing fever
Borrelia recurrentis spread by lice; higher fatality
Borrelia hermsii and others spread by ticks; lower fatality
Fever, chills, headache, myalgias, sweats, febrile relapses
OspA
OspA = outer surface protein
On Borrelia burgdorferi (in tick midgut)
OspA helps bacteria stay attached to tick midgut but as tick sucks blood from mouse, temperature rises and that causes OspA to be downregulated
Also increase in temperature upregulates OspC which is important for Borrelia burgdorferi life in the mouse
Do we have a vaccine for B. burgdorferi?
No
Tried to give antibodies to OspA because it kills B. burgdorferi before it can get into humans and infect them, but was shown to induce autoimmune arthritis (very bad side effect!)
Stages of Lyme disease
Stage 1: localized infection; erythema chronicum migrans (target) around bite location, flu-like symptoms
Stage 2: disseminated infection; secondary annular skin lesions, pain in joints, tendons, lymphocytic meningitis, cranial neuritis (Bell’s palsy), radiculoneuropathy, AV nodal block
Stage 3: persistent infection; intermittent attacks of joint swelling and pain primarily in large joints (knee; 1 or 2 joints at a time)
Indications for testing for Lyme disease
Migratory pain in joints, tendons, brief attacks of arthritis
Lymphocytic meningitis, cranial neuritis (facial palsy), radiculoneuropathy
AV nodal block
All the serious symptoms…
How do you prevent Lyme disease
Can wear clothing with permetherine in it
Check for ticks! Early detection and removal of tick within 24 hours can prevent disease
Prophylactic doxycycline 200mg if engorged tick is found
Leptospira weilii
Spirochete wound in thin tight coil
Lives in renal tubules of host (rodent, dog, fish, bird), shed in animal urine, transmitted to humans via contaminated water (surfers get this)
First/septicemic (leptospiremic) phase: 3-7 days; bacteria invade blood and CSF; high fever, headache, malaise, myalgia, abdominal pain, conjunctival suffusion (red), photophobia
Second (immune) phase if ANICTERIC: 0-1 month; milder fever, headache, vomiting, aseptic meningitis
Second (immune) phase if ICTERIC (Weil’s Syndrome): jaundice, renal failure, hypotension, hemorrhagic pneumonitis, mortality 5-40%
Do spirochetes have toxins?
No!
Which innate immune response mechanism recognizes leptospiral LPS?
TLR-2
Usually LPS recognized by TLR-4, but leptospiral LPS is different!
3 layers of tear film
1) Lipid layer
2) Aqueous layer (composed of proteins)
3) Glycocalyx (covers surface of cornea)
Where do lipids come from?
Meibomian oil at the meibomian orifice
Where do tears come from?
Lacrimal gland
Note: tears protect you because they contain immunoglobulins
Dry eye disease
Most common eye disease
Conjunctiva
Conjoins cornea to eyelid at the limbus
Non-keratinized stratified squamous epithelium with goblet cells (which produce mucin 5AC which goes into tear film and is very protective)
Clear so you can’t see it, but contains blood vessels that you can see
Squamous carcinoma of the eye
Gelatinous layer that covers surface of cornea (so can’t see well)
Most common malignant disease
Cornea
Central visual axis, must remain clear for good vision
Key refractive surface
5 layers
5 layers of the cornea
1) Epithelium
2) Bowman’s layer
3) Stroma (most of the thickness of cornea)
4) Descemet’s membrane
5) Endothelium
Infectious corneal ulcer
Most common disease of cornea
Most common reason for this disease is contact lens wearing
Can perforate through eye, through stroma and can lose eye if not treated rapidly
Lens
Behind iris
Grows for your entire life
Lens fibers surrounded by thin capsule
Most common disease of lens is cataract
Cataract
Precipitation of aggregation of lens crystalline proteins
Opaque, so can’t see through it
Anterior chamber
Bounded by cornea anteriorly, iris posteriorly, scleral spur, ciliary body
Key structures for aqueous drainage: Schlemm’s canal and trabecular meshwork
Uvea
Contains iris, ciliary body and choroid
Contains melanocytes to absorb scattered light and give you a good view
Iris
Anterior border layer
Stroma
Constrictor muscle
Dilator muscle
Posterior pigmented epithelium
Ciliated body
Produces aqueous (non-pigmented layer)
2 layers: pigmented layer and non-pigmented layer
Muscle for accommodation
Important blood vessel that can rupture during trauma
Malignant melanoma of eye
Most common malignant disease of uvea
Slower growing than melanoma on the skin, but still can kill you
Retina
Thin membrane that covers entire posterior compartment, contiguous with optic nerve
Joins ciliary body
Processes light, modulates, and sends to lateral geniculate ganglion
3 major cellular layers: ganglion cell layer (will form optic nerve), inter-nuclear layer (electrical modulation system), photoreceptors, retinal pigment epithelium (integrated with photoreceptors and keeps them alive)
Macular degeneration
Causes decrease in central vision
Fibrous tissue grows between retina, from choroid
Doesn’t cause complete blindness
Optic nerve
At posterior part of eye
Tubular structure containing numerous axons of ganglion cells and glial cells arranged in columns which are separated by fibrous sheaths
Optic atrophy
Final common pathway of most optic disease
