Sexually Transmitted Infections and Vaginitis Flashcards

Question 1

Q

Sexually Transmitted Infections

Epidemiology

Question 2

Q

STI’s

Transmission Risk

Question 3

Q

Treponema pallidum

Morphology and General Characteristics

Answer

A

Slender, helical or coiled spirochete
Cannot be cultured in vitro
Visualized by silver stain or dark field microscopy
- Too thin to be seen by Gram’s stain or Giemsa
Fresh wet mount ⇒ corkscrew movement and flexion
Microaerophilic or anaerobic
- Extremely sensitive to oxygen
Sensitive to drying, disinfectants and heat
Subspecies of Treponema that cause tropical diseases: yaws, pinta and bejel

Question 4

Q

Treponema pallidum

Transmission / Epidemiology

Answer

A

Transmission 1° through sexual contact and congenital
Transmission via transfusion possible but rare
Treponemes cross the placenta from mother → fetus by unknown mech
Humans are the only host
Disease occurs worldwide w/ no seasonal incidence
Incidence is ↑, particularly in MSM

Question 5

Q

Treponema pallidum

Pathogenesis

Answer

A

Sexual exposure to ⊕ individual ⇒ high probability of acquisition w/ subsequent disease
Enters host via mucous membranes or small abrasions in the skin which commonly occur during sexual intercourse
Incubation is 4-6 wks
Initially replicate locally
Spread via lymphatic and circulatory systems

Question 6

Q

Treponema pallidum

Virulence Factors

Answer

A

Limited knowledge of virulence factors that promote disease
Lack of species-specific surface Ag helps organism evade the immune system
Resists phagocytosis
Binds fibronectin allowing them to bind cells

Question 7

Q

Primary Syphilis

Answer

A

Immune cells → site of entry where treponemes are replicating
Battle between immune cells and bacteria ⇒ lesion of primary syphilis (chancre)
- Painless w/ a raised border
- Heals spontaneously in ~ 6 months
Organisms that spread via bloodstream ⇒ 2° Syphilis

Question 8

Q

Secondary Syphilis

Answer

A

~3-6 wks after chancre heals, 2°form of syphilis appears in ~50% of individuals
Systemic spread of treponemes ⇒ replication in LNs, tissues and skin
Lesions ass. w/ secondary syphilis varied ⇒ “the great imitator”
Rash may be maculopapular, pustular, or scaly
Raised lesions called condyloma lata may appear in skin folds and mucous membranes
Clinical signs of disseminated disease include HA, fever, myalgia, LAD
Rash and sx resolve within a few wks but may recur

Question 9

Q

Tertiary Syphilis

Answer

A

~ ⅓ ⇒ organisms disappear and person is cured
⅔ ⇒ remain latent for yrs or even decades after 1° infection
- ~½ of these ⇒ manifestation of tertiary syphilis
Most sx due to immune destruction of tissue due to presence of treponemal Ag
Chronic inflammation may manifest as:
- Gummas: soft masses composed of few organisms and many inflammatory cells, frequently granulomatous lesions
  - May destroy bone and soft tissue
  - May involve vital organs such as the liver, brain etc.
- Neurosyphilis
  - Characterized by some or all of the following:
  - Tabes dorsalis: loss of positional sensation ⇒ staggering
  - Charcot joint: trauma to the knee and ankle joints
  - General paresis
  - Gradual loss of higher integrative functions and personality
  - Argll Robertson pupil: pupil does not react to light but contracts when object is moved from far to near

Question 10

Q

Congenital Syphilis

Answer

A

Premature birth, intrauterine growth retardation
Most infected
Infants don’t initially show sx until ~ 2 y/o
- Facial and tooth deformities
- Hutchinson incisors and mulberry molars
- Deafness, arthritis and CV disease are common

Question 11

Q

Treponema pallidum

Diagnosis

Answer

A

Fragile & fastidious ⇒ cannot be cultured
Darkfield microscopy or special stains
- Visualize organisms in wet mounts from chancre or skin lesions
- No longer performed
Non-Treponemal Serological Tests
- Reaginic Ab
  - Measure IgM and IgG vs cardiolipin from damaged cells
  - Inexpensive and easy to use but can result in false ⊕s
  - Recommended for screening
  - May be ⊖ in 1° syphilis
  - ⊕ at 2-3 wks after infection, 30% ⊕ after 1 wk
  - ⊕ in 2° disease
  - ⊖ or ⊕ during latent and 3° disease
  - Titers ∆ w/ disease activity
- Most commonly used tests:
  - Venereal Disease Research Laboratory (VDRL)
    - Slide micro-flocculation, cardiolipin Ag suspension
    - Specimen: CSF
    - Qualitative or semi-quantitative
  - Rapid plasma regain (RPR)
    - IgG and IgM vs cardiolipin Ag-coated particles
    - Rapid dx in clinical settings
Treponemal Specific Tests
- Use T. pallidum as Ag
- Specific and sensitive
  - False ⊕ of 1-2%
- ⊕ specific serology remains ⊕ for life
  - Cannot be used to track efficacy of tx
- Most commonly used tests:
  - Fluorescent treponemal Ab-absorption test (FTA-ABS)
    - Indirect IF test
  - Treponema pallidum particle absorption test (TP-PA)
    - Agglutination assay
  - EIA/CIAs
Lumbar puncture
For pts w/ ocular or neurologic sx, treatment failure (non-treponemal titers not declining appropriately)

Question 12

Q

Treponema pallidum

Treatment

Answer

A

Penicillin G ⇒ abx of choice in all stages of syphilis
- Spirochete exquisitely sensitive to PCN despite almost a century of use
Sex partner(s) should be evaluated and treated
Adults w/ primary, secondary and early latent (less than 1 year) syphilis:
- Benzathine PCN G IM (single dose)
Latent syphilis over 1 year, unknown duration, or tertiary sx:
- 3 wks of Benz. PCN G IM (once weekly)
Evidence of Neurosyphilis (including ocular syphilis):
- Aqueous crystalline PCN G IV
  - Dosed q4 hrs or continuous infusion, for 10-14 days

Question 13

Q

Benzathine Penicillin G

Answer

A

Repository PCN: PCN G + ammonium base
Depot injections ⇒ low but detectable serum concentrations of PCN G for up to 1 month
Bicillin C-R: combo of benzathine and procaine PCN which is not appropriate for syphilis
Bicillin L-A: benzathine PCN alone which is appropriate

Question 14

Q

Aqueous Crystalline Penicillin G

Answer

A

Used for IV therapy

When given in large dose it can penetrate the CNS

Question 15

Q

Treponema pallidum

Treatment Reactions

Answer

A

Jarisch-Herxheimer reaction
- Acute febrile rxn w/ headache and myalgia
- Occurs within first 24 hrs after tx
- Not a drug allergy or adverse event to PCN
PCN allergy
- Pts w/ established PCN allergy may need to be desensitized to PCN if alternative drug (doxycycline) cannot be used
  - Ex. pregnant women w/ a true penicillin allergy
- Takes ~ 4 hrs and should be done in a hospital setting

Question 16

Q

Treponema pallidum

Immunity and Prevention

Answer

A

Immune response is largely unknown
- CMI important b/c HIV pts have a rate of tx failures
- CMI also contributes to pathology ass. w/ disease manifestations
No vaccine
Condoms are effective barrier method

Question 17

Q

Neisseria gonorrhoeae

Morphology and General Characteristics

Answer

A

Gram ⊖ diplococci, coffee bean shaped
Frequently visualized by gram stain inside of neutrophils
Cell wall contains outer membrane proteins and lipooligosaccharide (LOS), not LPS
- LOS acts like endotoxin
Fragile organisms and do not survive long outside the human host

Question 18

Q

Neisseria gonorrhoeae

Transmission / Epidemiology

Answer

A

Sexually transmitted in men and women
- Both can have asymptomatic carriage
  - Greater in women ⇒ less likely to be dx and receive tx
Transmission from mother → infant during passage through birth canal
Disease is most common in 15-24 age group and those w/ multiple sexual partners

Question 19

Q

Neisseria gonorrhoeae

Pathogenesis

Answer

A

Gonococci enter the vaginal or urethral mucosa
Attach to epithelial cells of the cervix or distal urethra ⇒ local replication
Pili and other surface proteins ⇒ facilitate attachment to host cells
Exhibit both phase variation and Ag variation
- Pili and OSPs recognized by immune system but highly variable in structure ⇒ immune responses do not protect vs repeated infections
Important OSPs are called colony opacity associated proteins (Opa)
- Bacteria w/o these proteins are not engulfed by neutrophils
- Commonly ass. w/ PID, disseminated gonococcal infections (DGI) and arthritis
Damage to tissues caused by LOS ⇒ ⊕ TNF-alpha and causes other inflammatory processes

Question 20

Q

Neisseria gonorrhoeae

Urethritis

Answer

A

Occurs after 2-5 day incubation
Purulent discharge, thick, greenish-yellow, accompanied by pain
Usually subsides within a few wks w/o tx
Repeated infections can lead to scarring and strictures of the urethra

Question 21

Q

Neisseria gonorrhoeae

Cervicitis

Answer

A

Frequently asymptomatic (30% of women)
Sx can include dysuria, dyspareunia, discharge and genital discomfort
Lack of tx ⇒ ± local spread and inflammation ⇒ fallopian tube inflammation ⇒ ± long term sequalae:
- Chronic pain, ectopic pregnancy, infertility
- Pelvic Inflammatory Disease (PID)
  - Disorder that includes cervix, uterus, fallopian tubes and adjacent pelvic structures
- May spread to the abdomen
  - Most common chief complaint is lower abd pain
- May also cause tubo-ovarian abscesses
- Can spread and cause peritonitis and perihepatitis (Fitz-Hugh Syndrome)

Question 22

Q

Disseminated Gonococcal Infections (DGI)

Answer

A

Most gonococci killed by nl human serum (IgG, IgM, complement activation) ⇒ don’t spread via the bloodstream
Serum resistant strains can spread
- Lack colony opacity associated proteins (Opa)
Cause pustular skin lesions, septicemia and septic arthritis

Question 23

Q

Ophthalmia Neonatorum

Answer

A

Conjunctivitis seen in the newborn delivered via the birth canal in an infected mother.

Caused by Neisseria gonorrhoeae.

Question 24

Q

Neisseria gonorrhoeae

Diagnosis

Answer

A

Smear and culture
- Gram stain of gonococci in PMNs
- Samples from cervical or urethral secretions
- Very sensitive in men w/ purulent discharge but not in asymptomatic men or in women (w/ or w/o sx)
- Organisms can be cultured on chocolate agar or Thayer Martin medium
Nucleic acid assays (NAA)
- Direct detection of organisms in clinical specimens
- Rapid, sensitive and specific
Combination tests are available for Gonococci and chlamydia to screen asymptomatic individuals

Question 25

Q

Neisseria gonorrhoeae

Resistance

Answer

A

Resistant to PCN
- Due to beta lactamase or altered affinity of penicillin binding proteins
Resistant to tetracycline
- Ass. w/ Tet-m ⇒ ∆ ability to block binding and/or displace tetracycline from 30S subunit of ribosome
Quinolone resistance also widespread
Gonorrhea has shown resistance to every single class of abx

Neisseria gonorrhoeae now 1 of 3 resistant organisms CDC has categorized as “Urgent”

Question 26

Q

Neisseria gonorrhoeae

Treatment

Answer

A

Uncomplicated gonococcal infections of the cervix, urethra, and rectum
Ceftriaxone 500 mg IM single dose
If Chlamydia infection has not been ruled out ⇒ dual therapy
- Add Doxycycline 100 mg BID for 7 days
  - Azithromycin no longer recommended b/c of developing resistance
Sex partner(s) should also be evaluated and treated

Question 27

Q

Ceftriaxone

Answer

A

3^rd gen cephalosporin
- Resistant to cephalosporinases
Binds transpeptidase & other binding proteins ⇒ ⊗ cell wall synthesis
All beta lactams can cause hypersensitivity reactions
At high doses, beta lactams can cause seizures

Question 28

Q

Doxycycline

Answer

A

Same class tetracycline
Binds 30S subunit ⇒ blocks AA-linked tRNA from binding to the “A” site of the ribosome ⇒ ⊗ protein synthesis
GI upset and photosensitivity are most common AEs
Can cause esophageal irritation
- Should be administered w/ water
- Pts instructed to sit upright for 30 mins after admin
All tetracyclines can cause discoloration of the teeth
- Contraindicated in pregnant women and children under 8
Tetracyclines can chelate ions
- Should not be administered w/ calcium, iron, antacids, or multivitamins
No dose ∆ for renal or hepatic function

Question 29

Q

Neisseria gonorrhoeae

Immunity and Prevention

Answer

A

Immune response is Ab mediated
PMNs effective at killing many strains
Long-term immunity and cross-reactive immunity to other strains does not exist
- Reinfection is common
Condoms are effective barrier method

Question 30

Q

Chlamydia trachomatis

Morphology and General Characteristics

Answer

A

Intracellular bacteria w/ a complex lifecycle
Two biovars: trachoma and lymphogranuloma vereum
- LGV w/ further subdivides into serovars based on Ag differences
Ass. w/ different clinical syndromes

Question 31

Q

Chlamydia trachomatis

Lifecycle

Answer

A

Elementary body (EB) and reticulate body (RB)

EB resistant to environmental conditions much like a spore.

Question 32

Q

Chlamydia trachomatis

Transmission / Epidemiology

Answer

A

Found worldwide w/ no seasonal incidence
- Different serovars ⇒ different types of disease ⇒ different prevalence rates depending on region
Diseases include:
- Trachoma
- Urogenital infections (STDs)
  - 1.4 million infections in the US
- Adult inclusion conjunctivitis
- Newborn inclusion conjunctivitis
- Lymphogranuloma venereum (LGV)

Question 33

Q

Chlamydia trachomatis

Pathogenesis

Answer

A

Bacteria target columnar epithelial cells ⇒ acute → chronic inflammatory response
- Infection freq. remains sub-acute ⇒ unnoticed and untreated
- Trachoma ⇒ limited health resources
Unique life cycle protects from immune response

Question 34

Q

Trachoma

(Chronic keratoconjunctivitis)

Answer

A

Caused by the trachoma biovar of Chlamydia trachomatis
Leading cause of preventable blindness in the world (60 mil cases)
Endemic in Africa, Middle East, South Asia and parts of South America
Eye to eye transmission via droplet, hands, flies, fomites
Repeated infections from childhood
Chronic inflammation → eyelids turn inward ⇒ eyelashes abrade cornea ⇒ scarring, pannus (vessel formation in cornea) and loss of vision

Question 35

Q

Acute Follicular Conjunctivitis

Answer

A

Occurring in adults w/ genital infections caused by C. trachomatis
Probably auto-inoculation
Muco-purulent discharge, keratitis
Can result in scarring if not treated

Question 36

Q

Newborn Inclusion Conjunctivitis

Answer

A

C. trachomatis acquired by passage through infected birth canal
Occurs 1-2 wks after birth
Swelling of eyelids, purulent discharge
Untreated may lead to interstitial PNA

Question 37

Q

Chlamydia trachomatis

Urogenital Infections

Answer

A

In woman, up to 80% asymptomatic
- Can become symptomatic and include cervicitis, salpingitis, endometritis
In men, 25% are asymptomatic
- Urethritis characterized by discharge not quite as mucopurulent as that of N. gonorrhoeae but cannot be distinguished from it
  - These Infections frequently occur together

Question 38

Q

Reiters Syndrome

Answer

A

Urethritis, conjunctivitis, arthritis and lesions
Occurs in some men
Probably initiated by sexual transmission of Chlamydia

Question 39

Q

Lymphogranuloma Venereum (LGV)

Answer

A

Chronic STD that occurs mostly in tropical, developing countries
Chlamydia trachomatis serovars L1-3
Primary lesion on genitals of man or woman, small painless, often unnoticed, heals spontaneously
Followed by inguinal lymphadenopathy w/ formation of “bubos” ⇒ inflamed painful LNs, inguinal most common, containing the organism
Bubos contain infected, purulent material that must be aspirated or they may rupture
Includes fever, myalgias, systemic sx

Question 40

Q

Chlamydia trachomatis

Diagnosis

Answer

A

Gram stain
- In symptomatic pts, look for PMNs but no gonocci present (presumptive)
Ag detection
- Usually EIA or immunofluorescence from direct specimen
- Most effective w/ symptomatic urethral specimen in males
- Also LGV, neonatal PNA
NAAT
- Test of choice for STIs
- First void urine or urethral or cervical specimens

Question 41

Q

Chlamydia trachomatis

Treatment, Immunity and Prevention

Answer

A

Intracellular organisms that require CMI
- Also causes the pathology
No long-lasting immunity
- Reinfection leads to more vigorous immune response and pathology
Need abx that penetrate cells
Macrolides
- 7 day course of tetracycline or usu. doxycycline
- Or a single dose of Azithromycin
- Dual-therapy w/ Ceftriaxone for Gonorrhea
Condoms can protect against STD
ID sex partners and f/u
Screen high risk populations

Question 42

Q

Haemophilis ducreyi

Morphology, Transmission, Epidemiology

Answer

A

Small pleomorphic gram ⊖ rods
Sexually transmitted
Usually dx in men because women are asymptomatic
Endemic in many parts of the world but uncommon in developed countries
Frequently seen in HIV infected men

Question 43

Q

Haemophilis ducreyi

Pathogenesis and Clinical Disease

Answer

A

Chancroid

5-10 days incubation
Tender raised lesion w/ erythematous base develops in the genital area
Lesion ulcerates and becomes painful within a few days
Has soft ragged margins in contrast to the lesion of syphilis
Lesion resolves in 1-3 months

Question 44

Q

Haemophilis ducreyi

Diagnosis

Answer

A

Specimen from base of lesion
Visualized by gram stain and microscopy
Cultured on specialized agar, but organism is fastidious so not always successful

Question 45

Q

Haemophilis ducreyi

Treatment, Immunity and Prevention

Answer

A

Several abx options including azithromycin or ceftriaxone

Drain involved nodes

Question 46

Q

Herpes Simplex Virus

Epidemiology

Answer

A

Infection w/ HSV is life-long
HSV type 1
- ~60% sero-prevalence overall
- Close to 90-100% in middle-aged adults
HSV type 2
- ~20% sero-prevalence
- ↑ w/ higher number of sexual partners and hx of other STIs
- ↑ w/ age
- More common in women
> 50 mil in the US have genital HSV 1/2

Question 47

Q

Herpes Simplex Virus

Morphology

Answer

A

HSV-1/2 are double-stranded DNA human herpesviruses

Question 48

Q

Herpes Simplex Virus

Transmission

Answer

A

Direct contact w/ mucosal surfaces
- Oropharynx, vagina, rectum, cervix, and conjunctivae
Asymptomatic transmission possible

Question 49

Q

Herpes Simplex Virus

Clinical Diseases

Answer

A

HSV 1 and 2 cause a variety of clinical presentations and can have overlap:
Most people are asymptomatic
HSV-1 usually causes herpes labialis (cold sores)
- However, increasingly seen in anogenital disease
HSV-2 usually causes genital herpes
Stages of HSV infection include: primary, latent, and recurrent

Question 50

Q

Herpes Simplex Virus

Natural History

Answer

A

Primary genital HSV
- Classic sx is painful genital ulcers or vesicles – generally multiple
- Local lymphadenopathy
- ± Fever and headache
Oral HSV can include gingivostomatitis and pharyngitis
- Sx can range from very mild to severe
Latent HSV
- Can have no further episodes after 1° infection
Recurrent HSV
- Can have over 3 reactivations per year
- Usually recurrence sx are milder than 1° infection sx
- Complications can include meningitis and proctitis

Question 51

Q

Herpes Simplex Virus

Diagnosis

Answer

A

Usually diagnosed clinically based on appearance of lesions
Can directly swab lesion for HSV-1/2
- HSV DNA by PCR – sensitivity higher than culture and more rapid
- Viral culture – only 50% sensitivity
- ↓ Viral detection as lesion heals and lower in recurrence
- HSV shedding can be intermittent
  - ⊖ PCR or culture does not mean HSV infection is not present
Serologic blood tests
- Type-specific glycoprotein (gG) ⇒ assay of choice
- ⊖ Serology w/ active HSV lesion ⇒ consistent w/ new infection
Serology not recommended for routine screening (helpful in specific settings)
- HSV-1 serology can reflect oral or genital infection
- HSV-2 serology is consistent w/ genital infection

Question 52

Q

1° Herpes Simplex Virus

Treatment

Answer

A

Acyclovir 400 mg PO TID for 7-10 days
Acyclovir 200 mg PO 5x/day for 7-10 days
Valacyclovir 1 g PO BID for 7-10 days
Famciclovir 250 mg PO TID for 7-10 days

Question 53

Q

HSV

Suppressive Therapy

Answer

A

Acyclovir 400 mg PO BID
Valacyclovir 500 mg or 1 g PO qDay
Famciclovir 250 mg PO BID

Question 54

Q

Acyclovir, Valacyclovir, Famciclovir

Answer

A

Nucleoside analogues
℗ by viral thymidine kinase
- Affinity is 200x greater for viral thymidine kinase vs. mammalian thymidine kinase
After acyclovir-monophosphate formed, cellular kinases ℗ further → acyclovir triphosphate
Compound acts as a substrate and an inhibitor of viral DNA polymerase
- Acyclovir-℗³ incorporated into DNA ⇒ terminates chain elongation
Generally safer drugs
Important to stay hydrated to avoid crystalluria

Question 55

Q

Genital Ulcer Disease

Answer

A

Can be seen in multiple STIs
- Syphilis, HSV, chancroid, lymphogranuloma venereum, (and Granuloma Inguinale [donovanosis])
Generally classify based on:
- Pain
  - Painful ⇒ HSV or chancroid
  - Painless ⇒ syphilis
- Number of lesions
  - Single ⇒ syphilis or chancroid
  - Multiple or grouped ⇒ HSV

Question 56

Q

Urethritis / Cervicitis

Answer

A

Infections characterized by dysuria, burning, and urethral /cervical discharge
- Discharge can range from minimal to frank pus
Usually categorized as:
- Gonococcal ⇒ caused by Neisseria gonorrhoeae
- Can be seen on Gram stain
- Nongonococcal ⇒ Chlamydia trachomatis is a major one
- Others: Mycoplasma genitalium, HSV, T. pallidum, adenovirus, Ureaplasma urealyticum
  - M. genitalium is 15-25% of cases of nongonococcal urethritis in men in U.S.
Generally treat symptomatic urethritis empirically (for gonorrhea and chlamydia) while waiting for results

Question 57

Q

Pelvic Inflammatory Disease

Characteristics

Answer

A

Spectrum of inflammatory disorders of upper female genital tract
Endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis
Basic pathogenesis is an ascending infection from cervix → uterus → fallopian tubes and ovaries
Can spread outside the reproductive organs ⇒ pelvic peritonitis and rarely inflammation of the liver capsule w/ development of adhesions (Fitz-Hugh-Curtis syndrome)

Question 58

Q

Pelvic Inflammatory Disease

Etiologies

Answer

A

Implicated causes:

Gonorrhea and Chlamydia
Normal vaginal flora (anaerobes, G. vaginalis, H. influenzae, enteric GNRs, S. agalactiae)
CMV, M. hominis, U. urealyticum, M. genitalium

Question 59

Q

Pelvic Inflammatory Disease

Diagnosis

Answer

A

All women w/ PID should have gonorrhea, Chlamydia and HIV testing
Dx can be difficult
- Wide variation in sx
- May have mild sx
Clinical dx depends on pre-test suspicion
- Abnl bleeding, dyspareunia, vaginal d/c
- Pelvic or lower abd pain
Laparoscopy may be helpful
Sexually active women at risk for PID should be treated empirically if they have:
- Pelvic or lower abdominal pain w/ no other cause identified as one or more:
  - Cervical motion tenderness
  - Uterine TTP
  - Adnexal TTP
- One or more of these ↑ specificity:
  - Fever > 101°F
  - Abnl cervical or vaginal mucopurulent d/c, ↑ WBCs in vaginal fluid
  - ↑ ESR or CRP
  - Cervical infection w/ gonorrhea or Chlamydia

Question 60

Q

Pelvic Inflammatory Disease

Treatment

Answer

A

Sexually active women at risk for PID should be treated empirically
- PID usu. caused by Gonorrhea, Chlamydia and bacterial vaginosis organisms predominantly
- Treatment should cover Gonorrhea, Chlamydia, anaerobes, GNRs and strep
Parental tx recommended for emergencies, in pregnant women, pts unable to tolerate oral therapy
- IV therapy used until sx abate then pt switched to PO therapy
  - Cefotetan 2 gram IV every 12 hours + Doxycycline 100 mg orally or IV every 12 hours
- Or
  - Cefoxitin 2 gram IV every 6 hours + Doxycycline 100 mg orally or IV every 12 hours
Intramuscular and oral therapy
- PO therapy can be considered for women w/ mild to moderately severe acute PID, or after sx abate w/ IV therapy
- Several possibilities including:
  - Ceftriaxone 250 mg IM in a single dose PLUS
  - Doxycycline 100 mg PO BID for 14 days
  - ± Metronidazole 500 mg orally twice a day for 14 days
    - Add if you suspect anaerobes, but also good for bacterial vaginosis which very often accompanies PID
- or
  - Cefoxitin 2 g IM in a single dose PLUS
  - Probenecid 1 g orally administered concurrently in a single dose
    - Prolongs action of cefoxitin by ⊗ secretion via renal anion transporter
  - Doxycycline 100 mg orally twice a day for 14 days
  - ± Metronidazole 500 mg orally twice a day for 14 days

Question 61

Q

Cefotetan and Cefoxitin

Answer

A

2^nd gen cephalosporins
- Categorized as cephamycins
  - Similar activity as 2^nd gen cephalosporins except for activity vs anaerobes in the GI tract
- Used for surgical prophylaxis in abd surgery and abd and pelvic infections
Adverse effects:
- AE similar to the beta lactams
- Thrombophlebitis after IV injection
- Cefotetan has a methylthiotetrazole group
  - Disulfiram like reaction w/ ethanol
  - ⊗ Vitamin K production ⇒ prolonged bleeding time

Question 62

Q

Vaginitis

Overview

Answer

A

Disorder of the vagina characterized by inflammation or irritation of the vulva w/ abnl vaginal discharge.

Frequent cross contamination of nl and pathogenic flora b/t vaginal, urinary, and GI tracts
In pregnant women, vaginitis ass. w/ ↑ risk of miscarriage, pre-term delivery, and infections post-delivery
- ↑ Likelihood of acquiring a STI upon exposure including HIV

Question 63

Q

Vaginal Tract

Innate Defenses

Answer

A

Vaginal tract lacks a cleansing mech. to flush out microbes
- Mucus from cervix, cycle dependent
Main defense is low pH (4-4.5) and high numbers of normal flora
- Predominant genus is Lactobacillus spp
  - Gram ⊕ rods, facultative or microaerophilic
  - Bacterial fermentation of glycogen → lactic acid ⇒ low pH
    - Glycogen deposited in vaginal epithelial cells in response to estrogen
  - Produce hydrogen peroxide
    - Defense vs pathogens

Question 64

Q

Vaginal

Normal Flora

Answer

A

Pre-puberty and post-menopausal
- Scant flora
- Some lactobacilli and other orgnaisms derived from skin and GI tract
Child-bearing years
- Predominantly lactobacilli
- Some yeast
- Bacteria that tolerate low pH
- Some aneaerobes

Answer 63

A

Most common causes of vaginitis__:
- Trichomonas vaginalis ⇒ Trichomoniasis
- Candida albicans ⇒ Candida vulvovaginitis
Most common causes of bacterial vaginosis:
- Gardnerella vaginalis
- Mobiluncus spp (anaerobic)
- Prevotella spp (anaerobic)

Answer 64

A

Vaginitis is the inflammation of the vagina
Ass. w/ itching, burning, painful urination, odor, and vaginal discharge
Odor and discharge vary in amount and type depending on etiologic agent
Discharge may consist of inflammatory cells, epithelial cells, cell debris, and microbes
Different from urethritis, but overlap of sx and micro

Answer 65

A

Most common vaginal infection in women of child bearing age
- ~ 29% of women in the US are affected
Results from overgrowth of normal flora in the vagina ⇒ polymicrobial
Risk factors: multiple or new sexual partners, IUD, recent abx use, vaginal douching, and cigarette smoking
Role of sexual intercourse is poorly understood
- Not thought to be sexually transmitted and celibate women may contract it
- While not contagious, there may be a spread of bacteria between sexual partners that may predispose to the condition

Answer 66

A

~85% of women are asymptomatic
Most common sx are fishy odor and thin gray-white discharge
- Both are more noticeable after sexual intercourse

Answer 67

A

↓ Lactobacilli (gram ⊕ rods, aerobes)
- Usually present in high numbers in vaginal flora
Concomitant ↑ in anaerobes
- Previously ass. w/ ↑ Gardnerella spp (gram variable, facultative anaerobe)
- Now ass. w/ overgrowth of multiple anaerobic organisms including Mobiluncus and Prevotella spp (gram ⊖)

Answer 68

A

Pelvic exam w/ ⊕ Whiff test
- When KOH comes into contact w/ discharge fluid, a “fishy” or amine odor is detected
Laboratory detection of “Clue Cells” (epithelial cells covered w/ gram variable organisms)

Answer 69

A

Polymicrobial syndrome resulting from replacement of normal H₂O₂ producing bacteria in the vagina w/ high concentrations of anaerobic bacteria
Many cases resolve on their own
May be treated by metronidazole PO or clindamycin cream
- Benefits of therapy include relief of sx, ↓ risk of infectious complications s/p abortion/hysterectomy, ↓ risk of other infections (HIV and other STIs)
50% experience recurrent sx within 12 months and need a 2^nd course of abx
Recommended regimen:
- Metronidazole 500 mg PO BID for 7 days
Or
- Metronidazole gel 0.75% one full applicator (5g) intravaginally for 5 days
Or
- Clindamycin cream 2% one full applicator (5g) intravaginally for 7 days

Answer 70

A

Derivative of lincomycin
Effective against anaerobes that participate in mixed infections
MOA similar to erythromycin
Clindamycin cream tx may have fewer adverse effects vs metronidazole PO
Tx w/ creams is not recommended in pregnant women

Answer 71

A

Clinical manifestations
- Often asymptomatic
- Minimal discharge; usually has a fishy odor
- May have mild vulvar irritation
Risk factor
- Most often occurs in sexually active women
Physical exam
- Gray to white, adherent, thin discharge
- May have minimal vulvar erythema
Vaginal pH
- 4.5-6
Wet mount
- Large number of clue cells
“Whiff test”
- ⊕
Treatment
- Metronidazole (7 days)

Answer 72

A

Motile protozoan parasite
Exists in flagellated trophozoite form w/ short undulating membrane
Anaerobic
Multiplies by longitudinal binary fission
Placed in vagina or urethra primarily by sexual intercourse, transmission by fomites possible
Infects ~ 3.7 million but only ~30% are symptomatic
- Presentation may be related to overall status of host
- Older women more likely to be symptomatic

Answer 73

A

Men
- Primarily asymptomatic carriers
- May experience urethritis or prostatitis
Women
- May be asymptomatic
- Can have a scant, watery discharge
- ± Extensive inflammation ⇒ erosion of vaginal epithelial lining
  - Purulent discharge (white or yellow)
  - Vaginal itching and burning
  - Painful urination
  - Discomfort during intercourse

Answer 74

A

Organisms may be visualized in discharge fluid or in PAP smears

Nucleic acid probe assay is also available

Answer 75

A

Metronidazole is drug of choice for male and females
Sex partners must be treated to avoid reinfection
Prevention achieved through good hygiene, safe sexual practices and avoiding sharing of intimate apparel
Recommended regimen:
- Metronidazole 2 gram orally single dose
Or
- Tinidazole 2 gram orally single dose

Answer 76

A

Members of the nitroimidazole family
Nitro group is reduced in anaerobic bacteria and sensitive protozoans
- Reactive products responsible for antimicrobial activity
The only useful drugs for trichomoniasis
No alcohol for 24 hrs after metronidazole and 72 hrs after tinidazole
Metronidazole AE: nausea, headache, anorexia, and metallic taste
- Class B for pregnancy ⇒ no adverse events in animal studies
Tinidazole has fewer side effects
- Class C ⇒ some adverse events

Answer 77

A

Clinical manifestations
- Purulent vaginal discharge
- Usually has a bad odor
- Vulvar irritation
Risk factor
- Sexually transmitted
Physical exam
- Purulent discharge; can be yellow-green or frothy
- Vulvar erythema
Vaginal pH
- 4.5-6
Wet mount
- Neutrophils
- May see motile trichomonads
- Can also do NAAT testing
“Whiff test”
- May be ⊕
Treatment
- Metronidazole (single or 7 day)

Answer 78

A

Numerous species, most important is C. albicans
- Long term fluconazole tx ⇒ appearance of other Candida species (especially C. glabrata and C. krusei)
Candida albicans:
- Unicellular ovoid organism
- Adheres well to mucosal surfaces
- Reproduces asexually by budding
- Forms pseudohyphae ⇒ new budding cells → filamentous elongated form → true hyphae
- Can also form sprout-like hyphae called germ tubes (in the presence of serum) → hyphae

Answer 79

A

C. albicans are nl flora of the mouth, intertriginous skin folds, GI tract and vagina
Immunocompetent individuals have high resistance to Candida & other fungal infections
Mucosal infections, particularly of the vagina
Due to disruptions in the normal flora (abx use) ⇒ microbial imbalance ⇒ allows Candida to overgrow

Answer 80

A

Pruritis (burning and itching)
± Cheesy discharge
Not a typical STD (endogenous transmission)
Often recurrent
More common in 3^rd trimester of pregnancy and users of estrogen contraceptives

Answer 81

A

Usually clinical dx
Confirmed by microscopic exam of tissue (w/ or w/o KOH) for yeast and pseudohyphae
- Gram ⊕, size in between bacteria and host cell
C. albicans: germ tube formation in 1-2 hrs at 37__°__C in serum, chlamydospores on corn meal agar

Answer 82

A

Eliminate predisposing factor(s)

Topical antifungals

Answer 83

A

Clinical manifestations
- Vulvar pruritis/irritation
- May have mild discharge
Risk factor
- Immune suppression, DM, ↑ estrogen, abx
Physical exam
- Vulvar erythema
- Thick, white, “cottage-cheese” like discharge
Vaginal pH
- 3.8-4.5 (normal)
Wet mount
- Pseudohyphae (also seen w/ KOH exam)
“Whiff test”
- ⊖
Treatment
- Fluconazole or topical antifungal agents

Answer 84

A

Papovavirus
Small non-enveloped, isosohedral capsid
dsDNA genome
~70 types, classified into 16 groups
Classified as cutaneous or mucosal HPV based on target tissues

Answer 85

A

Episomal genome
8 early genes: E1 to E8
- Expression of E1 and E2 important for lytic cycle
- Expression of E6 and E7 important for oncogenesis
2 late or structural genes: L1 and L2

Answer 86

A

Found worldwide, no seasonal incidence
20 million individuals in the US
10-20% of women may be infected
HPV 16 and 18 directly linked to cervical CA
- 2^nd leading cause of CA mortality in women

Answer 87

A

Requires close contact for transmission:
- Direct contact (breaks in skin)
- Sexual contact
- Passage through the birth canal
⊕ Asymptomatic transmission
Capsid confers environmental resistance
- Survives on inanimate objects (fomites

Answer 88

A

Enters via skin breaks
Incubation 3-4 months
Lytic infection in a permissive cell
- Cutaneous and mucosal forms
  - Wart appearance related to HPV type and site of infection
- Common, plantar and flat warts ⇒ children and young adults
  - Resulting acquired immunity may limit disease in adults
- Genital warts ⇒ sexually active individuals
- Wart resolution in ~ 2 yrs
- Viral persistence, asymptomatic shedding
± Oncogenic transformation of a non-permissive cell
- Usu. by integrating viral genome into host genome
- Some HPV types ass. w/ oral and genital cancers

Answer 89

A

Viral replication linked to skin cell differentiation:

Infection of basal cells
HPV early genes ⇒ ⊕ host cell growth & viral genome replication using host DNA polymerase
- Expression of E1 and E2 important for lytic cycle
Cell division ⇒ basal and prickle layer thickens
Basal layer differentiation ⇒ ⊕ expression of nuclear factors ⇒ ⊕ transcription of viral proteins
HPV late genes expression in terminally differentiated keratin layer
Assembled virion shed along w/ dead cells
Warts usu. spontaneously regress after months to years
± Persistent or latent viral infections in the basal layer
Virus remains in plasmid form

Answer 90

A

Strain specific (HPV 16, 18)

Integration of viral genome into host DNA ass. w/ oncogenic events
- ~85% of cervical CA contain HPV DNA in integrated form
Integration limits viral replication (inactivation of E1 and E2 genes)
Allows expression of viral oncogenes (E6 and E7)
E6 and E7 ⇒ ⊗ cellular growth suppressor proteins (p53 and p105 or pRb)
- Uncontrolled cell proliferation
- ↑ Susceptibility to mutations and other cancer-causing events

Answer 91

A

Tobacco use
OCPs
Other STIs, chronic inflammation
Certain HLD-DR alleles

Answer 92

A

Infection of keratinized surfaces
May result in common, flat or plantar wart
- Depending on HPV type (HPV 1-4, 10) and site of infection
Usually results from infection in childhood or adolescence

Answer 93

A

Occurs in young children or adults > 40 y/o
- In children, HPV acquired through birth canal
Ass. w/ HPV 6, 11
Two types:
- Oral papillomas ⇒ benign epithelial tumors in the oral cavity,
  - Usually solitary and rarely recur
- Laryngeal papillomas ⇒ benign epithelial tumors of the larynx
  - Frequently recur

Answer 94

A

“Condyloma acuminata”

Occurs on external genitalia and perianal areas as a result of sexual contact
90% are caused by HPV 6 and 11
Rarely become malignant (10%)
Risk factors:
- Sexual activity before 16 y/o
- Multiple sexual partners
- Partner w/ multiple sexual partners

Answer 95

A

STI of female genital tract w/ HPV 16 or 18

± Progressive cellular changes: dysplasia → neoplasia → carcinoma

Answer 96

A

Virus sequestered in skin cells ⇒ limits exposure to immune system
CMI important for wart regression
Persistent infection ass. w/ transformation
- AIDS, lymphoproliferative d/o, immunosuppressive therapy ⇒ ↑ risk

Answer 97

A

Visual dx by appearance
Confirmed by PAP smear
- Koilocytes
- Hyperplasia of prickle cells
- Excessive production of keratin (hyperkeratosis)
Molecular probes and PCR
- Used to ID virus in cervical swabs and tissue specimens
- HPV 16, 18

Answer 98

A

Dx cervical changes by Papanicolaou smears
- Koilocytotic squamous epithelial cells
  - Contain vacuolated cytoplasm and occur in rounded clumps

Answer 99

A

Warts usually spontaneously regress but are frequently surgically excised
- Removal ass. w/ high recurrence rate
Papillomas and cervical dysplasia and neoplasia must be surgically removed
Pharmacologic agents:
- Skin warts ⇒ salicylic acid
- Anogenital warts ⇒ podophyllin, imiquimode (INF inducer) tricloracetic acid
- Laryngeal warts ⇒ intralesion interferon
Condoms ↓ but cannot completely prevent sexual spread

Answer 100

A

Quadrivalent vaccine
- HPV 6, 11, 16, 18
Gardasil 9
- HPV 6, 11, 16, 18, 31, 33, 45, 52, 58
3 shot series
- Targeted to adolescent girls
- Recently approved and recommended for boys
Will not prevent all genital warts but provides significant (not complete) protection vs cervical cancer