• Information
  1. Urethritis
  2. Pelvic Inflammatory Disease
  3. Endometritis
  4. Vaginitis
  5. Bacterial Vaginitis
  6. Vulvovaginal Candidiasis
  7. Trichomonas
  8. Mycoplasma and Ureaplasma

A. Urethritis [1]

1. Transmission
   1. Sexually Transmitted: >50%
   2. Non-STD: iatrogenic, frequent douching, bacterial vaginosis
   3. Other Risk Factors: Age < 25, Multiple sex partners
   4. Primarily symptomatic in women
   5. May also be symptomatic in men
2. Etiology
   1. N. gonorrhea ~30%
   2. C. trachomatis ~40%
   3. Ureaplasma urealyticum ~10%
   4. Trichomonas vaginalis
   5. Mycoplasma genitalium
   6. Herpes Simplex Virus (non-ulcerating)
3. Characteristics
   1. Asymptomatic chlamydial infection occurs substantial number of young women
   2. ~6% of asymptomatic sexually active girls 14-18 screened positive for chlamydia [24]
   3. Gonorrhea is usually symptomatic in women and men
   4. Either infection may progress to pelvic inflammatory disease (PID, see below)
4. Comparison of Two Main Types of Urethritis in Women

   Urethritis	Gonococcal	Chlamydial
   Incubation	1-5d	5-21d
   Onset	Abrupt	Gradual
   Symptoms	Prominent	Milder
   Dysuria Only	2%	15%
   Discharge Only	27%	47%
   Dysuria & Discharge	71%	38%
   Discharge	Purulent 91%	Mucoid 58%

5. Gonococcal Detection is simply by gram stain and/or culture (Thayer-Martin Plates)
6. Detection of Chlamydia
   1. Culture is gold standard with specificity ~100%; sensitivity is now questionable
   2. Culture is expensive, requires animal cells, and is not routinely available
   3. Enzyme immunoassays and direct fluorescent antibody tests are now available
   4. Specificity is 95-99% (sensitivity ~80%) so that positive tests require culture
   5. Ligase Chain Reaction (LCR) is more sensitive than culture with good specificity [3]
   6. LCR use on urine and genital swab will lead to increased incidence [3]
7. Screening for Chlamydia [8]
   1. Screening sexually active women is generally recommended
   2. General screening in high risk populations reduce PID incidence
   3. Annual screening is probably adequate
   4. Positive screening should prompt eradication with azithromycin or doxycycline
   5. Sexual partners currently and in previous 60 days should be tested or empirically treated
8. Treatment Overview [1,5,6]
   1. In general, patients should be treated for both gonococci and chlamydia
   2. This is because these organisms frequently track together
   3. Sexual partners of affected persons should be treated as well
   4. Some low grade pelvic inflammatory disease (PID) may be treated as outpatient
   5. Treatment is generally the same in HIV+ and HIV- women
   6. Patients with gonorrhea should be treated empirically for chlamydia [27]
9. Treatment of Gonococcal Infection
   1. Ceftriaxone (Rocephin®) 125mg im x 1
   2. Cefixime (Suprax®) 400mg po qd x 1
   3. Ofloxacin 400mg po x 1
   4. Ciprofloxacin 500mg po x 1
   5. Spectinomycin 2gm im x 1
10. Treatment of Chlamydial Infection
    1. Azithromycin 1gm po x 1 (safety in pregnancy is unknown)
    2. Doxycycline - 100mg po bid (contraindicated in pregnancy) x 7 days
    3. Azithromycin is more cost effective (fewer complications) than doxycycline [9]
    4. Ofloxacin 400mg po x 1 then 300mg bid x 7 days (also kills gonorrhea)
11. Treatment in Pregnant Women
    1. Quinolones and tetracyclines must not be used
    2. Cephalosporins are recommended for gonococcal coverage
    3. Spectinomycin 2gm single dose alternative for gonococcal coverage
    4. Chlamydia: Erthromycin (non-estolate) 500mg po qid x 7 days OR
    5. Amoxicillin 500mg po tid x 7 days
    6. Azithromycin may be safe in pregnancy, but data are not currently sufficient
12. Recurrent or Persistent Urethritis [8]
    1. Metronidazole 2gm po x1 with erythromycin 500mg qid x 7 days
    2. Azithromycin or clarithromycin could probably replace erythromycin
13. Treatment of Other Organisms
    1. Ureaplasma urealyticum - doxycycline or azithromycin
    2. Trichomonas vaginalis - metronidazole (Flagyl®) 2gm po x 1
14. Nonoxynol-9 gel does not reduce urogenital gonococcal or chlamydial infection [10]

B. Pelvic Inflammatory Disease [1]

1. Also called Salpingitis
2. Organisms
   1. N. gonorrhea ~50%
   2. Chlamydia trachomatis ~25%
   3. Pyogenic Organisms - E. coli, S. viridans, Enterococci, B. fragilis
   4. Mycoplasma hominis, Ureaplasma urealyticum
   5. Mycobacterium tuberculosis
   6. Most commonly sexually transmitted
3. Symptoms
   1. May be asymptomatic, particularly initially
   2. Pelvic or Lower Abdominal Pain - dull, constant, <2 weeks duration
   3. Abnormal vaginal discharge
   4. Postcoital bleeding, spotting between menstrual periods
   5. Gastrointestinal symptoms not uncommon
   6. Signs of Bacteremia / Sepsis (Nausea/Vomiting/Fever/Chills)
   7. Arthritis - disseminated gonococcal infection
   8. Reiter's Syndrome - following chlamydia, ureaplasma, or other organisms
4. Diagnosis
   1. Direct abdominal tenderness on examination
   2. Cervical motion and adnexal tenderness
   3. T > 38°C (102°F) and/or White blodd cells (WBC) >10.5K/µL
   4. Leukocytes and/or G- Diplococci on smear
   5. ESR elevation
   6. Positive Chlamydia antigen test followed up with culture
   7. Sonography may be indicated to rule out Tubo-ovarian abscess
   8. Specificity may only be ~50% with above criteria; sensitivity probably >80%
   9. Screening for cervical chlamydia infection reduces risk of PID
5. Complications
   1. Infertility and Ectopic Pregnancy
   2. Tubo-ovarian Abscess
   3. Peri-oophoritis
   4. Fitz-Hugh-Curtis Syndrome (rare perihepatitis from GC infection)
   5. Disseminated Gonococcemia
   6. Gonococcal arthritis
6. Disseminated Gonococcemia
   1. Rash and Arthralgias (true arthritis may occur)
   2. Pelvic Pain ± Discharge
   3. High Fever
   4. Waterhouse-Friedrickson Syndrome: Adrenal Destruction
   5. Treat with 1-2gm ceftriaxone iv x 7-10 days (usually with doxycycline)
   6. Metronidazole and ampicillin or clindamycin can be added for broad spectrum coverage
7. Parenteral Treatment
   1. Hospitalization should be strongly considered (see below)
   2. Parenteral regimens used for moderate to severe disease
   3. Cefotetan 2gm IV q12 h OR cefoxitin 2gm IV q6 h AND Doxycycline 100mg IV q12 h
   4. Alternative: clindamycin 900mg IV q8 h + gentamicin 5mg IV qd
   5. Gentamicin qd dosing has less toxicity than q8-12 hour dosing with equal efficacy [11]
   6. Alternative: ofloxacin 400mg IV q12 h OR levofloxacin 500mg IV qd AND doxycycline
   7. Metronidazole (500mg IV q8 h) or Ampicillin/Sulbactam (Unasyn®) 3gm IV q6 h may be added for improved anaerobic control in patients receiving fluoroquinolones
   8. Continue IV for at least 48 h after patient's condition improves
   9. Then use doxycycline 100mg bid po OR clindamycin 450mg po qid for 14 days
   10. Improvement should occur within 3-5 in hospital (follow fever, WBC, ESR)
   11. In general, an Intrauterine Device (IUD) should be removed 2-3 after starting antibiotics
   12. For outpatient trial, ceftriaxone 250mg IM x 1 may be used with oral doxycycline
   13. If no improvement as outpatient within 3 days, admit for parenteral therapy
   14. Note: IUD does NOT increase the risk of upper genital-tract infection [12]
8. Hospitalization strongly recommended:
   1. Diagnosis is uncertain and surgical emergencies cannot be ruled out
   2. Pelvic abscess suspected
   3. Failure to take adequate fluids (severe nausea and vomiting)
   4. Pregnancy
   5. HIV infection
   6. Failed response to outpatient therapy (progression on oral antibiotics)
   7. Unable to followup after 48-72 hours of outpatient therapy
9. Oral Treatment
   1. Clinical proof of efficacy not as strong as for parenteral therapy
   2. If no response to oral therapy within 72 hours, administer parenteral therapy
   3. Ofloxacin 400mg po bid x 14 days OR levofloxacin 500mg qd x 14 days
   4. Metronidazole 500mg po bid x 14 days may be added for improved anaerobic coverage

C. Endometritis [5]

1. Causes
   1. Post-abortion or post-partum
   2. Septic Abortion: C. perfringes infection (gas gangrene)
   3. Puerperium
   4. Chlamydia trachomatis
2. Pathology
   1. Edema with neutrophils in uterine tissue
   2. Hyperemia
   3. Parametritis (inflammation of broad ligament)
3. Differential Diagnosis
   1. Acute Pyelonephritis
   2. Acute Appendicitis
   3. Pelvic Inflammatory Disease
4. Extension of Infection
   1. Ovarian Involvement (Peri-oophoritis, Tubo-ovarian Abscess)
   2. Local Peritonitis
   3. Cul-de-sac Abscess Formation
   4. Pelvic Abscess
   5. Fitz-Hugh-Curtis Syndrome

D. Vaginitis [2,13]

1. Common, especially in sexually active young women
   1. Usually related to alterations of vaginal pH in sexually active women
   2. Concern for transmission of other STDs
2. Common Types
   1. Bacterial (~30%) - usually Gardnerella, other species such as Bacteroides
   2. Fungal (~25%) - usually Candida albicans called "vulvovaginal candidiasis"
   3. Protozoan (~15%) - trichomonas
   4. Atrophic vaginitis
   5. Each of these is discussed in more detail below
3. Uncommon, Noninfectious
   1. Chemical irritant
   2. Allergic: hypersensitivity or contact dermatitis
   3. Traumatic
   4. Desquamative inflammatory vaginitis (steroid-responsive)
   5. Erosive lichen planus
   6. Behcet's Syndrome
   7. Pemphigus
4. Overview of Main Symptoms
   1. Can vary depending on type of vaginitis, but unreliable for definitive diagnosis
   2. Infectious vaginitis associated with increased discharge (white, yellow, thick, thin)
   3. Pain - mainly with candida and trichomonas
   4. Itching - especially with candida; occasionally with trichomonas
   5. Unpleasant vaginal odor
   6. Dyspareunia (painful intercourse)
5. Diagnosis (see below) [13]
   1. Wet mount microscopic examination of vaginal discharge is most effective
   2. Bacterial: clue cells, amine odor after adding potassium hydroxide (KOH), increased cocci
   3. Candida: hyphae or spores; hyphae withstand KOH, can be mixed infection with baacterial
   4. Trichomonas: mobile trichomonads, increased white cells, foul odor
6. Atrophic Vaginitis [14]
   1. Usually due to low estrogen
   2. Major symptom is vaginal dryness; tissue atrophy may also occur
   3. Dryness leads to vaginal pain, especially during intercourse (dyspareunia)
   4. Bleeding may occur, particularly after intercourse
   5. Treat with topical, oral, or patch estrogens

G. Bacterial Vaginitis (BV) [1,2,13]

1. Most common cause of vaginitis in women of childbearing age (~30%)
2. Clinical syndrome due to replacement of normal peroxide-producing Lactobacillus species
3. Common Associated Bacteria
   1. Gardnerella vaginalis is most commonly found
   2. Anaerobes: Prevotella, Mobiluncus, Bacteroides
   3. Mycoplasma hominis
   4. Molecular identification of bacteria associated with BV has shown different organisms
4. Molecular Idenitification of Bacteria in BV [29]
   1. Women without BV have 1-6 bacterial species, primarily lactobacillus
   2. Women with BV have greater bacterial diversity with 9-17 (mean 12) phylotypes
   3. 35 unique bacterial species were detected in BV patients
   4. Gardnerella found most commonly (in all patients with BV, and 1 of 8 without BV)
   5. Prevotella and Atopobium next most common
   6. Leptotrichia, Megasphaera and Eggerthella also found
   7. These are mainly anaerobes
5. Risk Factors
   1. Multiple sex partners
   2. Douching
   3. Lack of vacinal lactobacilli
6. Symptoms
   1. "Fishy" vaginal odor with homogeneous discharge
   2. Vaginal irritation, redness, pain
   3. Up to 50% of women do not report symptoms
   4. Increased risk for pregnancy complications and preterm birth
7. Diagnosis
   1. Clinical criteria and Gram stain are used
   2. Gram stain to detect relative concentrations of bacterial morphotypes
   3. Vaginal or cervical culture no longer recommended as it is nonspecific
   4. DNA probe test (Affirm® VP III)
   5. Testing for BV prior to surgical abortion or hysterectomy is recommended
   6. Women testing positive for BV should be treated prior to these surgeries
8. Clinical Criteria (3 required for diagnosis; 2 may be sufficient [13])
   1. Homogeneous white, noninflammatory discharge, smoothly coats vaginal walls
   2. Clue cells - bacteria coating leukocytes, are seen on microscopic exam
   3. Vaginal pH is >4.5
   4. Fishy odor of vaginal discharge before or after addition of 10% KOH ("Whiff Test")
9. Treatment [1]
   1. Metronidazole (Flagyl®) 500mg po bid x 7 days
   2. Alternative: Metronidazole gel (MetroGel®) 0.75%, 5gm intravaginally qd x 5 days
   3. Alternative: Clindamycin (Cleocin®) cream 2%, 5gm intravaginally qhs x 7 days
   4. Single Dose Alternative: Extended Release Clindamycin Cream (Clindesse®): apply once
   5. Alternative: Metronidazole 2gm po single dose less effective than 7 days
   6. Alternative: Clindamycin 300mg po bid x 7 days
   7. Alternative: Tinidazole (Tindamax®) 2gm po qd x 2 days or 1gm po qd x 5 days [4]
   8. Tinidazole likely as effective and is better tolerated, shorter course than metronidazole [4]
   9. Active yogurt cultures (with lactobacillus) may help reduce risk of BV
10. Treatment Efficacy
    1. Reduces symptoms and risk for other infectious complications
    2. Clindamycin cream less effective than metronidazole
    3. Amoxicillin prophylaxis for women with group B strep infections has reduced disease [26]
    4. Recurrent BV is common and requires treatment with standard agents for 10-14 days
    5. Use of lactobacillus with standard therapy may be beneficial in recurrent BV
11. BV in Pregnancy [2]
    1. Risk factor for premature labor and perinatal infection
    2. Lower genital tract infections associated with increased risk of preterm delivery
    3. Treatment recommended for high risk persons only
    4. High risk is defined as women with prior preterm delivery
    5. Randomized trial data recommend against routine screening for bacterial vaginosis in asymptomatic women at low risk for preterm delivery [30,]
12. Treatment in Pregnancy
    1. Clindamycin 300mg po bid x 5 days (probably preferred)
    2. Alternative: Metronidazole 250mg po tid x 7 days
    3. All pregnant women at high risk for preterm delivery should be treated
    4. Clindamycin 300mg bid x 5 days in women with bacterial vaginosis or abnormal bacterial flora 12-22 weeks' gestationreduced preterm delivery/miscarriages by >60% [25]
    5. Metronidazole treatment of asymptomatic pregnant women 23-24 weeks' gestation with bacterial vaginosis has shown conflicting effects on rate of preterm delivery [22,23]

F. Vulvovaginal Candidiasis (VVC) [1,2,7,13]

1. Most common female fungal genital infection
   1. Typically seen in healthy, sexually active females
   2. Uncomplicated or complicated forms
2. Uncomplicated
   1. Sporadic or infrequent OR
   2. Mild to moderate OR
   3. Likely to be Candida albicans OR
   4. Non-immunocompromised
3. Complicated
   1. Recurrent (>3 episodes / year) OR
   2. Severe OR
   3. Non-albicans candidiasis OR
   4. Uncontrolled diabetes, debilitation, immunocompromise, pregnancy
   5. Diabetics have increased incidence of all candidal infections
   6. Very high incidence in patients with HIV, particularly women
4. Symptoms and Signs
   1. Marked itching; burning on urination
   2. Creamy, thick white discharge
   3. Marked erythema
   4. Vaginal pH <4.5 (that is, normal vaginal pH)
   5. Pseudohyphae seen easily on 10% potassium hydroxide preparations
5. Non-Prescription Treatment for Uncomplicated Disease [13,15]
   1. Acutely, various over-the counter medications are available
   2. One to 14 days of topical therapy is usually used
   3. Butoconazole (Femstat3®, Mycelex3®) 2% cream, 5gm intravaginally (IVA) x 3 days
   4. Clotrimazole 1% cream, 5gm IVA x 7-14 days
   5. Miconazole 2% cream, 5gm IVA x 7 days
   6. Miconazole 200mg vaginal suppository, 1 suppository qd x 3 days
   7. Tioconazole (Vagistat-1®, Monistat1®) 6.5% ointment, 5gm x 1 dose
6. Prescriptions for Uncomplicated Disease [1]
   1. Butoconazole Sustained Release, 2% cream, 5gm IVA x 1
   2. Clotrimazole 100mg vaginal tablet, 2 tablets qd x 3 days
   3. Clotrimazole 500mg vaginal tablet, 1 tablet x 1
   4. Nystatin 100,000 unit vaginal tablet, 1 tablet qd x 14 days
   5. Terconazole 0.8% cream, 5gm IVA x 3 days
   6. Terconazole 80mg vaginal suppository, one suppository x 3 days
   7. Tioconazole and terconazole have activity against non-albicans Candidal strains
   8. Oral fluconazole (Diflucan®) 150mg x 1
   9. Itraconazole (Sporanox®) 200mg bid x 1 day or qd x 3 days is effective
7. Treatment of Recurrent VVC
   1. Fluconazole 150mg on day 1 and day 4 OR
   2. Prescription topical therapy x 7 -14 days
   3. Recurrent VVC may be reduced by using maintenance prophylactic therapy
   4. Maintenance: fluconazole 150mg once weekly or 200mg once monthly [16]
   5. Maintenance: itraconazole 400mg once monthly
   6. Maintenance: clotrimazole 500mg vaginal tablet weekly
   7. Lactobacillus acidophilus (in 8oz of yogurt) reduces recurrence of candidal vaginitis [17]
   8. Fluconazole 200mg weekly reduces oropharyngeal and vaginal candidiasis [16]
   9. In patients with recurrent candidiasis, fluconazole 150mg weekly for 6 months reduces recurrence from 72% with placebo to 10% [21]
   10. Fluconazole prophylaxis should be strongly considered in patients with recurrent VVC
8. Severe VVC treated as for recurrent VVC
9. Non-Albicans Candidiasis
   1. Treatment with non-fluconazole azole first line
   2. If recurrent, 600mg boric acid in gelatin capsule IVG daily x 14 days
   3. Topical 4% flucoytosine may be used (refer to specialist)
   4. Maintenance: 100,000 units nystatin daily IVG
10. Treatment in HIV+ patients similar to HIV- patients [1,7]

G. Trichomonas [2,5]

1. Flagellated Protozoan
2. Symptoms
   1. Itchy
   2. Thick, green discharge (seen usually in severe cases only)
   3. Foul odor
   4. Vaginal pH 5-6.0
3. Diagnosis [18]
   1. Organisms are often seen on wet preparation or Pap smear
   2. Positive Pap smear in areas where trichomonas prevalance <10% requires confirmation
   3. Large, motile, "tennis racquet" shaped organisms seen in 60% of cases
   4. Very large numbers of neutrophils
   5. Microscopy is negative in ~50% of culture confirmed cases
   6. Therefore, culture if microscopy is negative
4. Treatment [1,19]
   1. Metronidazole (Flagyl®) single dose 2gm po (HIV- or HIV+)
   2. Tinidazole (Tindamax®) single dose 2gm po is also effective
   3. Partner must be treated as well
   4. Two 2gm doses of metronidazole (for trichomonas) during pregnancy at weeks 16-23 is safe [20]
   5. Metronidazole treatment of trichomonas vaginalis infection does not prevent preterm delivery [20]
   6. Centers for Disease Control recommend treatment of symptomatic pregnant women with single 2gm oral dose metronidazole [2]

H. Mycoplasma and Ureaplasma

1. Generally asymptomatic in women
2. Causes mild to severe urethritis in men and sometimes in women
3. Usual part of standard screening for gynecologic examinations
4. Appear to be a risk factor for preterm delivery in pregnant women
5. Treatment
   1. Doxycycline100mg po bid x 7 days
   2. Some strains are resistant to doxycycline, especially M. hominis)
   3. Recommend azithromycin 1gm po x 1 dose

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