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					Gynecological infections

     Gebre K. Tseggay, M. D.
       Normal Vaginal Flora
   Dominated by lactobacilli
   Lactobacilli convert glucose to lactic acid, to maintain an
    acidic vaginal pH of 3.8 to 4.2. This acidic environment
    inhibits the overgrowth of bacteria and other organisms
    with pathogenic potential.
   Some lactobacilli also produce hydrogen peroxide (H2O2), a
    potential microbicide.
   After onset of sexual activity, increase in Gardnerella
    vaginalis, lactobacilli, mycoplasmas, ureaplasmas is seen.
   BACTERIA ENDOGENOUS TO THE LOWER
             GENITALTRACT

GRAM POSITIVE                GRAM NEGATIVE
Lactobacillus acidophilus    Escherichia coli
Corynebacterium spp          Enterobacter cloacae
                             Gardnerella vaginalis
Staphylococcus epidermidis   Klebsiella
Streptococci                 Morganella
Enterococcus faecalis        Proteus
Peptococcus                  Bacteroides
Peptostreptococcus           Fusobacterium
Prevotella
                                       modified from Schlossberg,CTID 2001
                      Vaginitis
Most common causes include:
     Vulvovaginal Candidiasis (VVC)
     Bacterial Vaginosis (BV)
     Trichomoniasis
   *In some cases the etiology may be mixed
               VAGINITIS
              SYMPTOMS
   Often non-specific:
     Abnormal discharge

     Vulvovaginal irritation

     Vulvar itching

     Odor
                       VAGINITIS
                       DIAGNOSIS
   History
   Visual inspection
   Appearance of vaginal discharge: color, viscosity,
    adherence to vaginal walls, odor
   Collection of specimen
   Diagnostic tests:
       Vaginal pH: determine vaginal pH with narrow-range pH paper
       Whiff test: assessment of a fishy odor after application of 10% KOH
        to wet mount
       KOH (wet mount): wet mount of discharge with 10% KOH
       NaCl (wet mount): wet mount of discharge with 0.9% normal saline
                   VAGINITIS
                   DIAGNOSIS
Other tests:
   Cultures: not used routinely, but are available for
       both T. vaginalis and Candida spp.
      New tests for BV (commercially available) :
          Fem Exam Test Card™: pH and amines
          Fem Exam vaginalis PIP Activity Test Card™: detects enzyme
           breakdown from G. vaginalis
      DNA probe for 3 organisms (T. vaginalis, C. albicans,
       and G. vaginalis): sensitivity, specificity, and clinical
       utility are under investigation.
VULVOVAGINAL CANDIDIASIS

   Not considered to be STD
   Caused by overgrowth of Candida species
    (Candida species are normal flora of vagina)
   80-90% caused by C. albicans.
   Non-albicans candida play increasing role
           VULVOVAGINAL CANDIDIASIS
                RISK FACTORS

   Uncontrolled DM                        Sponge
   Corticosteroid therapy                 Nonoxynol-9 (?)
   Antimicrobial therapy (oral,           Diaphragm (?)
    parental, topical)
                                           Increased frequency of coitus
   Poor hygiene
                                           "Candy binge―
   Estrogen therapy
   High-dose estrogen contraceptives      Women frequenting STD clinics
   Pregnancy                              Tight-fitting synthetic underclothing
   IUD
   HIV infection
                                        But, most episodes of vulvovaginal
                                          candidiasis occur in the absence
                                          of a recognizable precipitating
                                          factors
    VULVOVAGINAL CANDIDIASIS
             CLASSIFICATION
Uncomplicated          Complicated
Sporadic, infrequent   Recurrent
Mild-to-moderate       Severe
Likely C albicans      Non-albicans
Non-immunocomprised    Diabetes, pregnancy,
                       immunosuppression
      VULVOVAGINAL CANDIDIASIS
                        MANIFESTATIONS


   Vulvar pruritis is most common
    symptom
   Thick, white, curdy vaginal discharge
    ("cottage cheese-like")
   Erythema, irritation, occasional erythematous
    "satellite" lesion
   External dysuria and dyspareunia
    VULVOVAGINAL CANDIDIASIS
                   DIAGNOSIS
 Clinical
 pH normal (<4.5)

 Whiff test negative

 Fungal stain positive
      30% may have a negative fungal stain
     Severity does not depend on No. yeasts present
         Regimens for the Treatment of Vulvovaginal Candidiasis
    Intravaginal agents:
       Butoconazole 2% cream, 5 g intravaginally for 3 days†
       Butoconazole 2% sustained release cream, 5 g single intravaginally application
       Clotrimazole 1% cream 5 g intravaginally for 7-14 days†
       Clotrimazole 100 mg vaginal tablet for 7 days
       Clotrimazole 100 mg vaginal tablet, 2 tablets for 3 days
       Clotrimazole 500 mg vaginal tablet, 1 tablet in a single application
       Miconazole 2% cream 5 g intravaginally for 7 days†
       Miconazole 100 mg vaginal suppository, 1 suppository for 7 days†
       Miconazole 200 mg vaginal suppository, 1 suppository for 3 days†
       Nystatin 100,000-unit vaginal tablet, 1 tablet for 14 days
       Tioconazole 6.5% ointment 5 g intravaginally in a single application†
       Terconazole 0.4% cream 5 g intravaginally for 7 days
       Terconazole 0.8% cream 5 g intravaginally for 3 days
       Terconazole 80 mg vaginal suppository, 1 suppository for 3 days
    Oral agent:
       Fluconazole 150 mg oral tablet, 1 tablet in a single dose


Note: The creams and suppositories in this regimen are oil-based and may weaken latex condoms and diaphragms. Refer to condom
     product labeling for further information.
† Over-the-counter (OTC) preparations
              RECURRENT
        VULVOVAGINAL CANDIDIASIS
  Four or more symptomatic episodes/year
 Usually NOT from resistance to antifungals
 Diabetes mellitus or immunosuppression should be considered in refractory/
   recurrent cases
 Simultaneous Rx of sex partners has no effect on recurrence (but 3-10% of sex
   partners may have balanitis)
 Vaginal culture useful to confirm diagnosis and identify unusual species

Treatment
   Initial regimen of 7-14 days topical therapy
   Fluconazole 150 mg (repeat 72 hrs)
   Maintenance regimens- clotrimazole, ketoconazole, fluconazole, itraconazole
   For Non-albicans VVC:
      Longer duration of therapy

      Non-azole regimen may even be needed

      600 mg boric acid in gelatin capsule vaginally once a day for 14 days
VULVOVAGINAL CANDIDIASIS
    Treatment in Pregnancy

   Only topical intravaginal regimens
    recommended (usually for 7 days)
        VULVOVAGINAL CANDIDIASIS
          Management of Sex Partners

   Treatment not recommended
   Treatment of male partners does not reduce
    frequency of recurrences in the female
       But, male partners with balanitis may benefit from
        treatment
       BACTERIAL VAGINOSIS
   Not a classical STD
   Overgrowth of vaginal normal flora with anaerobic bacteria and
    decrease or loss of protective lactobacilli (Disturbed vaginal ecosystem)
   Gardrenella vaginalis (GV) & other microrganisms in high titers
   But, GV found in 50% of vaginal cultures in asymptomatic
    women too.
   BV linked to: premature rupture of membranes, premature
    delivery and low birth-weight delivery, acquisition of HIV,
    development of PID, and post-operative infections after
    gynecological procedures
   Male sex partners may be colonized but asymptomatic
          BACTERIAL VAGINOSIS
   Gray, homogenous discharge
    w foul (fishy) odor reported mostly
    after vaginal intercourse and after
    completion of menses
   Without obvious vaginal
    inflammation
   Clue cells present
   pH>4.5
   Positive Whiff test (KOH)
 NOT a clue cell


        Clue cells




NOT a clue cell
     BV Diagnosis: Amsel Criteria
                            Vaginal pH >4.5

                            Presence of >20% per HPF of
Amsel Criteria:              "clue cells" on wet mount
Must have at least           examination
three of the following      Positive amine or "whiff" test
findings:
                            Homogeneous, non-viscous,
                             milky-white discharge adherent
                             to the vaginal walls
          BACTERIAL VAGINOSIS
           Other Diagnostic Tools
   Culture not recommended; Do not Rx a positive GV
    vaginal culture in asymptomatic women
   Newer diagnostic modalities include:
        FemExam™
        PIP Activity TestCard™
   DNA probe
           BACTERIAL VAGINOSIS
                  TREATMENT
Metronidazole    500 mg twice daily x 7 days
Metronidazole gel 0.75%, 5 g intravaginally once daily x 5 days
Clindamycin cream 5%, 5 g intravaginally qhs x 7 days



                   Alternative regimens
Metronidazole 2 gm in a single dose
Clindamycin 300 mg twice daily x 7 days

Clindamycin ovules 100 g intravaginally qhs x 3 days
            BACTERIAL VAGINOSIS
              Treatment in Pregnancy
   Symptomatic pregnant women should be treated
    due to association with adverse pregnancy
    outcomes
   Do not use of topical agents in pregnancy
   Some experts recommend screening and
    treatment of asymptomatic women at high risk for
    preterm delivery (previous preterm birth) at the
    first prenatal visit; optimal regimen not
    established
   BACTERIAL VAGINOSIS
     Treatment in Pregnancy

 Metronidazole 250 mg three times
          daily for 7 days
                 or
Clindamycin 300 mg twice daily for 7
                days
      BACTERIAL VAGINOSIS
      Management of Sex Partners

Not   recommended
     Woman’s response to therapy and the
      likelihood of relapse or recurrence not
      affected by treatment of sex partner
             TRICHOMONIASIS

   Etiologic agent
       Trichomonas vaginalis – a
        flagellated protozoa
        Trichomoniasis and other vaginal infections
        — Initial visits to physicians‘ offices: United
                       States, 1966–2003
Visits (in thousands)
      4,500

                                          Trichomonal
     3,600                                Other Vaginitis

     2,700


     1,800


       900


          0

               1966       69        72        75        78        81          84   87   90   93   96   99   2002



                SOURCE: National Disease and Therapeutic Index (IMS Health)
             TRICHOMONIASIS
   Estimated 7.4 million cases annually in the U.S.
   Almost always sexually transmitted
   Causes urethritis in men (usu. asymptomatic)
   Transmission between female sex partners has been
    documented
   Fomite transmission rare
   Possible association with
       Pre-term rupture of membranes and pre-term delivery
       Increased risk of HIV acquisition
                  TRICHOMONIASIS
                     DIAGNOSIS
   Copious, yellow-green or gray frothy
    discharge, adherent to vaginal walls, w
    foul odor.
   Vulvovaginal erythema
   Punctate cervical microhemorrhages
    seen in 25%: ‗strawberry cervix‘
   Saline smear 80% sensitive, highly
    specific (motile trichomonads)
   Liquid culture, Diamond’s medium, done
    in persistent cases
   Gram stain & Pap smear are not
    sensitive or specific
   Whiff test (KOH) +/-
          TRICHOMONIASIS
            TREATMENT
Recommended regimen
  Metronidazole 2 gm orally in a single dose
Alternative regimen
  Metronidazole 500 mg twice a day for 7 days
Pregnancy
  Metronidazole 2 gm orally in a single dose
                   TRICHOMONIASIS
                 TREATMENT FAILURE
   Re-treat with metronidazole 500 mg twice daily for 7 days
   If above fails, Rx with metronidazole 2 gm single dose x 3-5 days
   In repeated failure:
        Confirm diagnosis with culture
        consider metronidazole susceptibility testing through the
         CDC
        Trial of tinidazole
           TRICHOMONIASIS
         Other management issues

   No alcohol for the duration of treatment and
    for at least 24 h after the last dose.
   Trich is an STD, so:
     GC and Chlamydia testing should be done, &
     Syphilis, HIV, and hepatitis B serologic testing
      should be considered
        TRICHOMONIASIS
     Management of Sex Partners
   Sex partners should be treated, even
    if asymptomatic
   Avoid intercourse until therapy is
    completed and patient and partner
    are asymptomatic

.
          VAGINITIS DIFFERENTIATION
                                                                            Bacterial
                    Normal       Trichomoniasis         Candidiasis
                                                                            Vaginosis

                                  discharge, itch,    Itch, discomfort,
Symptom                                                                   Odor, discharge,
                                                        dysuria, thick
presentation                    50% asymptomatic                                itch
                                                          discharge
                                                                          Homogenous,
                                  Frothy, gray or      Thick, clumpy,     adherent, thin,
                    Clear to
Vaginal discharge                 yellow-green;        white ―cottage      milky white;
                     white
                                   malodorous             cheese‖          malodorous
                                                                           ―foul fishy‖
                                 Cervical petechiae Inflammation and
Clinical findings
                                ―strawberry cervix‖      erythema
Vaginal pH          3.8 - 4.2          > 4.5           Usually < 4.5           > 4.5

KOH ―whiff ‖ test   Negative      Often positive          Negative            Positive
                                 Motile flagellated                         Clue cells (>
                     Lacto-
NaCl wet mount                   protozoa, many         Few WBCs           20%), no/few
                     bacilli
                                      WBCs                                     WBCs
KOH wet mount                                          Pseudohyphae
NON-INFECTIOUS VAGINITIS
   Vaginal foreign bodies, especially in prepubescent
    girls, may present with a heavy white discharge but
    would be unaccompanied by vulvar erythema or the
    microscopic appearance of hyphae.
   Atrophic vaginitis is commonly found in
    postmenopausal women and is distinguished from
    candidal vaginitis by mucosal dryness, atrophy,
    dyspareunia, minimal discharge, and itching.
   Contact dermatitis, local irritation secondary to tight-
    fitting underwear, and contact dermatitis from toiletry
    items, latex condoms, diaphragms, spermicides
              MUCOPURULENT
                CERVICITIS

   Largely caused by
    Chlamydia trachomatis and
    Neiserria Gonorrheae
Chlamydia trachomatis
     Chlamydia — Rates: United States, 1984–2003


Rate (per 100,000 population)
   350


   280


   210


   140


    70


     0

           1984        86       88   90   92   94   96   98   2000   02
          Chlamydia — Rates by sex: United States,
                       1984–2003

Rate (per 100,000 population)
   500


   400


   300
                                                                      Men
                                                                      Women
   200


   100


     0

           1984        86       88   90   92   94   96   98   2000   02




                                                                          CDC
           Chlamydia trachomatis
   Estimated 3 million cases in the U.S. annually
   Women: bartholinitis, cervicitis, urethritis, PID,
    perihepatitis, conjunctivitis
         Men: urethritis, epididymitis
         M&W: LGV
         Infants: conjunctivitis, pneumonia
   Complications: PID, perihepatitis, Reiter’s syndrome,
    infertility, ectopic pregnancy, chronic pelvic pain,
    increased risk for HIV
   Incubation period is 7-21 days.
        Chlamydia trachomatis
            Risk factors

   Adolescence
       Cervical epithelial cells are developmentally immature (ectopy) making them
        more susceptible to infection.
       Risky behaviors also contribute to susceptibility.
   New or multiple sex partners
   History of past STD infection
   Presence of another STD
   Oral contraceptive use (contributes to cervical ectopy, &
    OCP users less likely to use barrier protection)
   Lack of barrier contraception
                 Chlamydia trachomatis
Cervicitis
   Majority of cervical infections are asymtpomatic-70% to 80%.
   When symptomatic, S+S may be non-specific:
         spotting, or mucopurulent cervicitis, with mucopurulent endocervical
          discharge, edema, erythema, and friability w easily induced bleeding within
          the endocervix or any zones of ectopy.
Urethritis
       50% of infected women yield chlamydia from both
        urethra and cervical sites
       Usually asymptomatic
       May cause the ―dysuria-pyuria‖ syndrome mimicking
        acute cystitis. On urinalysis, pyuria present but few
        bacteria.
               Chlamydia trachomatis
                        DIAGNOSIS
Culture: high specificity BUT
        labor-intensive, expensive,
        variable sensitivity (50%-80%),
        not suitable for widespread screening


Non-culture methods:
  Serology: not very useful
  EIA, DFA, DNA probe : less sensitive(50-75%), nonspecific
  Nucleic acid amplification tests (NAAT): PCR, LCR:
          more sensitive than culture (>80%-90%)
          highly specific (>99%)
          can use first void urine
          can use self-obtained vaginal swab
 Chlamydia trachomatis
      Treatment

Azithromycin 1 gm single dose
             or
Doxycycline 100 mg bid x 7d
      Chlamydia trachomatis
            Alternative regimens

    Erythromycin base 500 mg qid for 7 days
                       or
Erythromycin ethylsuccinate 800 mg qid for 7 days
                       or
     Ofloxacin 300 mg twice daily for 7 days
                       or
     Levofloxacin 500 mg for 7 days
        Chlamydia trachomatis
             Treatment in Pregnancy
Recommended regimens
  Erythromycin base 500 mg qid for 7 days
                             or
  Amoxicillin 500 mg three times daily for 7 days
Alternative regimens
   Erythromycin base 250 mg qid for 14 days
                              or
   Erythromycin ethylsuccinate 800 mg qid for 14 days
                              or
   Erythromycin ethylsuccinate 400 mg qid for 14 days
                              or
   Azithromycin 1 gm in a single dose
         Chlamydia trachomatis
              Screening
   Annual screening of sexually active women
    < 25 yrs
   Annual screening of sexually active women
    > 25 yrs with risk factors
   Sexual risk assessment may indicate need for
    more frequent screening for some women
   Screen pregnant women in the first trimester
   Re-screen women 3-4 months after treatment
    due to high prevalence of repeat infection
GONORRHEA
      Gonorrhea — Rates: United States, 1970–2003
          and the Healthy People 2010 target

Rate (per 100,000 population)
   500
                                                                                     Gonorrhea
                                                                                     2010 Target
   400


   300


   200


   100


     0

           1970       73        76   79      82      85      88      91      94      97       2000   03


               Note: The Healthy People 2010 target for gonorrhea is 19.0 cases per 100,000
               population.
                   GONORRHEA
   Caused by Neisseria gonorrhoeae, a gram-neg intracellular
    diplococcus.
   Estimated 700,00-800,000 persons infected annually in
    the US.
   Manifestations in women may include:
      cervicitis, PID, urethritis, pharyngitis, proctitis,
       disseminated (bacteremia,arthritis, tenosynovitis)
      Accessory gland infection (Bartholin’s glands,
       Skene’s glands)
       Fitz-Hugh-Curtis Syndrome (Perihepatitis)
              Gonorrhea Cervicitis
              Clinical Manifestations
   Symptoms are non-specific : abnormal vaginal
    discharge, intermenstrual bleeding, dysuria, lower
    abdominal pain, or dyspareunia
   Clinical findings: mucopurulent or purulent
    cervical discharge, easily induced cervical bleeding
   50% of women with clinical cervicitis are
    asymptomatic
   Incubation period unclear, but symptoms may
    occur within 10 days of infection
Gonorrhea Cervicitis   Bartholin’s Abscess
                     GONORRHEA
                     LAB DIAGNOSIS
   Culture (selective media-Thayer Martin, needs CO2)

   Non-culture tests: DNA probe, nucleic acid
    amplification

   Gram-stain, less sensitive in cervicitis (most sensitive for
    symptomatic urethritis in men)
Gonorrhea: Gram Stain of
  Urethral Discharge




            Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides
Neisseria gonorrhoeae (Cervix, Urethra, Rectum)
                           Cefixime 400 mg
                                  or
                         Ceftriaxone 125 IM
                                  or
                        1Ciprofloxacin 500 mg

                                  or
                          1Ofloxacin 400 mg

                                   or
                        1Levofloxacin    250 mg

        PLUS Chlamydial therapy if infection not ruled out

    1 Contraindicatedin pregnancy and children. Not recommended for infections
      acquired in California, Asia, or the Pacific, including Hawaii.
         Neisseria gonorrhoeae
         (Cervix, Urethra, Rectum)

Alternative regimens
 Spectinomycin 2 grams IM in a single dose
                         or
 Single dose cephalosporin (cefotaxime 500 mg)
                         or
 Single dose quinolone (gatifloxacin 400 mg,
 lomefloxacin 400 mg, norfloxacin 800 mg)
PLUS Chlamydial therapy if infection not ruled out
               Neisseria gonorrhoeae
                Treatment in Pregnancy
   Cephalosporin regimen
   Women who can’t tolerate cephalosporin regimen may
    receive 2 g spectinomycin IM
   No quinolone or tetracycline regimen


    PLUS Erythromycin or amoxicillin for presumptive or
    diagnosed chlamydial infection
             Gonococcal Isolate Surveillance Project (GISP) —
          Percent of Neisseria gonorrhoeae isolates with resistance or
            intermediate resistance to ciprofloxacin, 1990–2003

Percent
  7.5
                 Resistance
  6.0            Intermediate resistance


  4.5


  3.0


  1.5


  0.0
          1990       91       92     93    94   95    96     97    98     99    2000    01   02   03


                  Note: Resistant isolates have ciprofloxacin MICs ≥ µg/ml. Isolates with
                  intermediate resistance have ciprofloxacin MICs of 0.125 - 0.5 µg/ml.
                  Susceptibility to ciprofloxacin was first measured in GISP in 1990.
              Neisseria gonorrhoeae
              Antimicrobial Resistance

   Surveillance is crucial for guiding therapy
    recommendations
   No significant resistance to ceftriaxone
   Fluoroquinolone resistance in SE Asia, Pacific,
    Hawaii, California, Washington.
   FQ resistance 15% in MSM.
                  GONORRHEA
               TREATMENT ISSUES
   Fluoroquinolones are no longer recommended for
    therapy for gonorrhea acquired in Asia, the Pacific
    Islands (including Hawaii), and California.
   CDC no longer recommends fluoroquinolones as a
    first-line therapy for gonorrhea in MSM
   If symptoms persist, perform culture for N. gonorrhoeae.
   Any gonococci isolated should be tested for
    antimicrobial susceptibility
   Co-infection with Chlamydiae in up to 50% of pts,
    hence anti-Chlmydia Rx added.

Note : A test of cure is not recommended, if a
       recommended regimen is administered.
                   GONORRHEA
                Partner Management
   Evaluate and treat all sex partners for N. gonorrhoeae and
    C. trachomatis infections if contact was within 60 days of
    symptoms or diagnosis.
   If a patient’s last sexual intercourse was >60 days
    before onset of symptoms or diagnosis, the patient’s
    most recent sex partner should be treated.
   Avoid sexual intercourse until therapy is completed and
    both partners no longer have symptoms.
PELVIC INFLAMMATORY DISEASE
            (PID)
    PELVIC INFLAMMATORY DISEASE
   Estimated about 1 million annual cases in the US
   Endometritis, salpingitis, tuboovarian abscess, & pelvic
    peritonitis.
   Ascending infection from or via cervix
   Most cases of PID are polymicrobial: Chlamydia, GC,
    vaginal organisms, anaerobes, enteric GNR, GPC).
    May be unrelated to STD.
   Most common pathogens:
      N. gonorrhoeae: recovered from cervix in 30%-80% of
       women with PID
      C. trachomatis: recovered from cervix in 20%-40% of
       women with PID
      N. gonorrhoeae and C. trachomatis are present in
       combination in approximately 25%-75% of patients
        PELVIC INFLAMMATORY DISEASE
              RISK FACTORS
   Adolescence (in sexually active teens 3x more than 25-29 yr olds)
   History of PID
   GC or chlamydia, or a history of GC or chlamydia
   Male partners with GC or chlamydia
   Multiple partners
   Current douching
   Insertion of IUD (especially within 4 mos after insertion)
   Bacterial vaginosis
   Demographics (lower socioeconomic status)
   Oral contraceptive use, in some cases (by avoidance of barrier precautions?)
               PID Classification
                                Mild to
Subclinical/                  moderate
  silent                      symptoms
   60%                           36%

                                          Overt
                                          40%


                                 Severe
                               symptoms
                                   4%



                                             CDC
   PELVIC INFLAMMATORY
          DISEASE
        Minimum Diagnostic Criteria
Uterine/adnexal tenderness or cervical motion
  tenderness

        Additional Diagnostic Criteria
Oral temperature >38.3 C        Elevated ESR
Cervical Chlamydia or GC        Elevated CRP
WBCs/saline microscopy          Cervical Discharge
       Pelvic Inflammatory Disease
               More Specific Criteria

   Endometrial biopsy: histopathologic evidence of
    endometritis
   Imaging Studies: Transvaginal sonography or MRI
    (showing thickened fluid-filled tubes)
   Laparoscopy: abnormalities consistent with PID
    PELVIC INFLAMMATORY DISEASE
            MANAGEMENT
   Antibiotics
   Bed rest
   Reevaluation within 72 hrs of treatment
   All male sex partners should be evaluated for STD
    and empirically treated with regimen effective for
    GC/Chlmydia
       PELVIC INFLAMMATORY DISEASE
                MANAGEMENT
Hospitalize, if:
   Surgical emergencies not excluded (e.g., appendicitis, ectopic
    pregnancy..)
   Pregnant patient
   Pelvic abscess is suspected
   Adolescent
   Severe illness
   If unable to tolerate outpt regimen
   If f/up within 72 hrs after starting abx cannot be arranged
   Non-response to oral therapy
   HIV infection with low CD4 count
Pelvic Inflammatory Disease
     Parenteral Regimen A

    Cefotetan 2 g IV q 12 hours
                 or
     Cefoxitin 2 g IV q 6 hours

              PLUS
   Doxycycline 100 mg orally/IV
             q 12 hrs
PELVIC INFLAMMATORY DISEASE
      Parenteral Regimen B

          Clindamycin 900 mg IV q 8 hours
                       PLUS
Gentamicin loading dose IV/IM (2 mg/kg) followed by
 maintenance dose (1.5 mg/kg) q 8 hours. Single daily
             dosing may be substituted.
PELVIC INFLAMMATORY DISEASE
  Alternative Parenteral Regimens

     Ofloxacin 400 mg IV q 12 hours
                    or
    Levofloxacin 500 mg IV once daily
         WITH OR WITHOUT
    Metronidazole 500 mg IV q 8 hours
                    or
    Ampicillin/Sulbactam 3 g IV q 6 hrs

                  PLUS
   Doxycycline 100 mg orally/IV q 12 hrs
PELVIC INFLAMMATORY DISEASE
         Oral Regimen A

     Ofloxacin 400 mg twice daily for 14 days
                     or
  Levofloxacin 500 mg once daily for 14 days
           WITH OR WITHOUT
  Metronidazole 500 mg twice daily for 14 days
PELVIC INFLAMMATORY DISEASE
         Oral Regimen B
       Ceftriaxone 250 mg IM in a single dose
                           or
 Cefoxitin 2 g IM in a single dose and Probenecid 1 g
              administered concurrently
                         PLUS
     Doxycycline 100 mg twice daily for 14 days

              WITH or WITHOUT
    Metronidazole 500 mg twice daily for 14 days
SUSPECTED TUBOOVARIAN ABSCESS

   Cultures
   Broad spectrum antibiotics
       85% of abscesses w a diameter of 4-6 cm (& only
        40% of those >10 cm) respond to abx alone
   Surgery for failure to respond to abx.
PELVIC INFLAMMATORY DISEASE
                               SEQUELAE
   Ectopic pregnancy
       7-fold increase in risk after a single episode of PID

   Infertility:
       13% of women after one episode of PID
       25-35% after 2 episodes, 50-75% after 3 or more episodes
       2/3 unable to conceive after Rx for TOA

   Dyspareunia
   Pelvic adhesions
   Chronic pelvic pain
PELVIC INFLAMMATORY DISEASE
    Management of Sex Partners

   Male sex partners of women with PID should
    be examined and treated for sexual contact 60
    days preceding pt’s onset of symptoms
   Sex partners should be treated empirically with
    regimens effective against CT and GC
       Genital herpes — Initial visits to physicians‘
             offices: United States, 1966–2003

Visits (in thousands)
    250


   200


   150


   100


    50


      0

           1966         69      72        75         78        81        84   87   90   93   96   99   2002



                SOURCE: National Disease and Therapeutic Index (IMS Health)
             Genital HSV Infection
   More than one in five Americans (45 million people)-are estimated infected
    with genital herpes
   more common in women than men, infecting approximately one out of four
    women, versus one out of five men.
   In a national house-hold survey, less than 10 percent of people who tested
    positive with herpes knew they were infected (Fleming, 1997). ---Silent
    epidemic---
   Genital herpes is a recurrent, lifelong viral infection.
   Asymptomatic shedding occurs (Most sexual transmission occurs while
    source case is asymptomatic).
   Incubation period is 2-12 days (average is 4 days).
   Can be transmitted between sex partners, from mothers to newborns, and can
    increase a person's risk of becoming infected with HIV
     Estimated Annual Incidence of
     Selected STDs in the U.S. , 2000
   Trichomoniasis 7.4 million
   Human Papillomavirus (HPV) 6.2 million
   Chlamydia 2.8 million
   Herpes Simplex Virus (HSV) Type 2 : 1.6
    million
   Gonorrhea 718,000
   Syphilis 37,000
          HSV Serologic Tests
                Type-Specific
   HSV-specific glycoprotein G2 for HSV 2
    infection and glycoprotein G1 for HSV 1
   Available gG type-specific assays- POCkit
    HSV-2, HerpeSelect HSV1/2 IgG ELISA
    and HerpeSelect 1/2 immunoblot IgG
   Sensitivity 80-98%, Specificity > 96%
   Confirmatory testing may be indicated in
    some settings
     Genital Herpes
  First Clinical Episode
   Acyclovir 400 mg tid
             or
   Famciclovir 250 mg tid
             or
   Valacyclovir 1000 mg bid

Duration of Therapy 7-10 days
         Genital Herpes
        Episodic Therapy
Acyclovir 400 mg three times daily x 5 days
                   or
Acyclovir 800 mg twice daily x 5 days
                   or
Famciclovir 125 mg twice daily x 5 days
                   or
Valacyclovir 500 mg twice daily x 3-5 days
                   or
Valacyclovir 1 gm orally daily x 5 days
     Genital Herpes
    Daily Suppression

   Acyclovir 400 mg bid
               or
  Famciclovir 250 mg bid
               or
Valacyclovir 500-1000 mg daily
              Genital Herpes
              in HIV Infection

   May have prolonged or severe episodes with
    extensive genital or perianal disease

   Episodic or suppressive antiviral therapy
    often beneficial

   For severe cases, acyclovir 5-10 mg/kg IV q 8
    hours may be necessary
        Genital Herpes
HIV Infection/Episodic Therapy
  Acyclovir 400 mg three times daily
                 or
  Famciclovir 500 mg twice daily
                 or
  Valacyclovir 1 gm twice daily


   Duration of Therapy 5-10 days
              Genital Herpes
   HIV Infection/Daily Suppression

Acyclovir 400-800 mg twice to three times daily
                       or
Famciclovir 500 mg twice daily
                       or
Valacyclovir 500 mg twice daily
                 Genital Herpes
                Antiviral Resistance
   Persistent or recurrent lesions on antivirals
   Obtain viral isolate for viral susceptability
   5% immunocomprised patients
   Acyclovir resistant isolates-resistant to
    valacyclovir, most resistant to famciclovir
   Alternatives: Foscarnet 40 mg/kg IV q 8 or
    topical cidofovir gel 1% (daily x 5 days)
             Herpes in Pregnancy
Risk for transmission to neonate from infected mother is :
 high (30%-50%) among women who acquire genital herpes near
   the time of delivery, but low (<1%) in women with histories of
   recurrent herpes at term or who acquire genital HSV during the
   first half of pregnancy.
 Prevention of neonatal herpes depends on avoiding acquisition
   of HSV during late pregnancy and avoiding exposure of the
   infant to herpetic lesions during delivery.
 Women without symptoms or signs of genital herpes or its
   prodrome can deliver vaginally
                   Genital Herpes
              Treatment in Pregnancy
   Acyclovir may be used with first episode or severe
    recurrent disease
   Available data do not indicate an increased risk of
    major birth defects (first trimester)
   The safety of acyclovir, valacyclovir, and famciclovir
    therapy in pregnant women has not been established.
                 Genital Herpes
                     Counseling
   Natural history of infection, recurrences,
    asymptomatic shedding, transmission risk
   Individualize use of episodic or suppressive
    therapy
   Abstain from sexual activity when lesions or
    prodromal symptoms present
   Risk of neonatal infection
      HUMAN PAPILLOMAVIRUS
    6.2 million Americans get a new genital HPV infection each year   .
     May cause cancer of cervix, vulva, vagina, or anus
         the most common sources of genital warts--HPV types 6 and 11--are
          rarely associated with malignancy
          the high-risk HPV types 16 and 18 have been found in more than 90%
          of cervical cancers
     They appear an average of 3 months after exposure, the latency period can
      be much longer.
     Infection can be clinically apparent, subclinical, or latent
     Frequency of spontaneous regression is unclear. A few studies indicate a
      regression rate of 10%-30% within 3 months.
     Persistence of infection occurs, but frequency and duration is unknown.
     Recurrences after treatment are common (20%-50% recurrence rate at 3-6
      months).
     Symptoms
     Genital warts usually cause no symptoms other than the warts themselves.
     Vulvar warts can cause dyspareunia, pruritis, and burning discomfort.
     Urethral meatal warts occasionally cause hematuria or impairment of
      urinary stream.
     Vaginal warts occasionally cause discharge, bleeding, or obstruction of
      birth canal (due to increased wart growth in pregnancy).
       HUMAN PAPILLOMAVIRUS
              Risk for Malignancy
   Externa genital warts
     HPV types 6, 11.
     Minimal risk for malignancy
   Flat warts
     HPV 16,18, 31, 45…
     Associated with cancer of cervix, vagina, vulva, anus, penis
     Most women with persistent HPV infection do not develop
       cervical cancer precursors or cervical cancer.
     Over 99% of cervical cancers have HPV DNA detected
       within the tumor.
     Persistent infection with a high-risk HPV type is necessary
       but not sufficient for the development of cervical cancer.
    HUMAN PAPILLOMAVIRUS
         DIAGNOSIS
 Inspection usually diagnostic of external warts:,
  biopsy if in doubt
 Pap smear, biopsy for flat warts of cervix
 HPV-DNA studies, PCR, hybrid capture
 HPV cannot be cultured, and serologic tests are not
  available to test for HPV antibodies
 Subclinical infections may be detected by applying
  3% to 5% acetic acid solution for 5 to 10 minutes.
  The lesions then become visible, and can be further
  visualized via colposcopy.
HUMAN PAPILLOMAVIRUS
                  Treatment

   Primary goal for treatment of visible warts
    is the removal of symptomatic warts
   Therapy may reduce but probably does not
    eradicate infectivity
   Difficult to determine if treatment reduces
    transmission
     No laboratory marker of infectivity

     Variable results utilizing viral DNA
    HUMAN PAPILLOMAVIRUS
   Choice of therapy guided by preference of patient,
    experience of provider, resources
   No evidence that any regimen is superior
   Locally developed/monitored treatment algorithms
    associated with improved clinical outcomes
   Acceptable alternative may be to observe; possible
    regression/uncertain transmission
PAPILLOMAVIRUS
Patient-applied
   Podofilox 0.5% solution or gel
   Imiquimod 5% cream

Provider-administered
   Cryotherapy
   Podophyllin resin 10-25%
   Trichloroacetic or Bichloroacetic
    acid 80-90%
   Surgical removal
    HUMAN PAPILLOMAVIRUS
            Treatment in Pregnancy
   Imiquimod, podophyllin, podofilox should not be
    used in pregnancy
   Many specialists advocate wart removal due to
    possible proliferation and friability
   HPV types 6 and 11 can cause respiratory
    papillomatosis in infants and children
   Preventative value of cesarean section is unknown;
    may be indicated for pelvic outlet obstruction
                 CHORIOAMNIONITIS
                   RISK FACTORS

   Nulliparity                       Underlying Host Factors
   Length of labor                     No. of lactobacilli,
   Preterm labor                       IgA,
   PROM                               Chronic diseases

   Meconium stained amniotic fluid    Immunosuppression

   Internal fetal or uterine          Nutritional disorders
    monitoring                         Drug abuse.
   Presence of GU pathogens
    (GBS, GC,BV)
   No of vag exams in women w
    ruptured membrane
                  CHORIOAMNIONITIS
                        DIAGNOSIS
   Maternal fever >38C(>100.4) AND at least 2 of the following:
      Maternal leukocytosis (>15,000 cells/cubic mm)
      Maternal tachycardia (>100 beats/min)
      Fetal tachycardia (>160 beats/min)
      Uterine tenderness
      Foul odor of the amniotic fluid
   AMNIOTIC FLUID ANALYSIS:
      Gram stain: bacteria & leukocytes (> 6 leukocytes/hpf)
      Glucose (<15mg/dl abnormal)
      WBC (Abnormal >30 cells/cc)
      Leukocyte esterase (strips) +
    Abnormal glu + wbc + Leuk/esterase= sensitivity 90%, specificty 80%
    for pos culture

MICROBIOLOGY:
 Organisms from vaginal flora, anaerobes, mycoplasma, GBS, E.coli.
 Usually polymicrobial
               CHORIOAMNIONITIS
                     MANAGEMENT
1.    Antibiotics
           Amp/gent/clinda.
           Other broad-spectrum regimen


2.    Delivery

     (Note: C-section should be performed only for accepted
        obstetric indications)
         POSTPARTUM ENDOMETRITIS
                          DIAGNOSIS
   Fever, usually on 1st or 2nd postpartum day.
   Lower abdominal pain
   Uterine tenderness
   Leukocytosis

   Bimanual exam should be done

Microbiologic diagnosis:
     Transvaginally obtained cultures are controversial (contaminants)
     Blood cultures should be done (10-20% have bacteremia)
     Chlamydia testing (culture, antigen, PCR) should be done for high
      risk pts & with late-onset PPE.
        POSTPARTUM ENDOMETRITIS
         PREDISPOSING FACTORS
   C-section, especially after labor or rupture of membranes is
    the main predictor
      Incidence after vaginal delivery 0.9-3.9 %
      Incidence after C-section 10-50%
   Other predictors:
      Duration of labor
      Rupture of membranes
      Presence of BV
      Number of vag. Exams during labor
      Use of internal fetal monitoring.
         POSTPARTUM ENDOMETRITIS (PPE)
                       MICROBIOLOGY

   Polymicrobial (GBS, enterococci, G. vaginalis, E. coli, Prevotella
    bivia, Bacteroides spp, peptostreptococci, Ureoplasma
    urealyticum, Mycoplasma hominis)
   Chlamydia trachomatis may cause a late form of PPE (>2days
    to 6 wks postpartum, after vag delivery)
   Group A Strep PPE is rare
         of exogenous source, usually caregiver.
         Major epidemiologic significance: HCW screening (all at the delivery
         & those who did vag exam before delivery should be screened w
         cultures of nares, throat, vagina, rectum, skin. If culture + should
         refrain from patient care for the 1st 24h of abx therapy)
        POSTPARTUM ENDOMETRITIS
             MANAGEMENT
   Antibiotics (broad-spectrum)
       until pt is afebrile, pain-free, & with normal wbc count.

FAILURE TO RESPOND may indicate:
 multi-drug resistant bacteria,
 inadequate regimen,
 abscess,
 puerperal ovarian vein thrombosis,
 non-infectious fever (e.g., drug-fever, breast engorgement)


PROPHYLAXIS:
 Abx prophylaxis for any c-section after labor or rupture of
    membranes of any duration
         PUERPERAL OVARIAN VEIN
              THROMBOSIS
   Acute postpartum thrombosis of ovarian veins
   Rare, incidence 1/2000 deliveries or 1-2/100 pts w postpartum infection
   Can occur after c-section or vaginal delivery.
   Usually associated with post-c-section endometritis. Previously diagnosed
    w ―PPE failing to respond to abx‖
   Onset mostly 2-4 days after delivery.
   Acute onset, pt appears ill, febrile/chills, lower abd pain (usually rt sided),
    tachycardia disproportionately elevated c/w temp.
   EXAM: tenderness, tender sausage-shaped mass may be palpable (1/2-
    2/3).
   If PE has occurred may have respiratory complaints too.
   Usually a diagnosis of exclusion.
   Sono, CT, or MRI may confirm diagnosis
   Rx: Abx, anticoagulation ( usually x 7-10d, in absence of PE)

				
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