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Infections of the Lower and Upper Genital Tracts Pelvic Tuberculosis Actinomycosis

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OUTLINE
INFECTIONS OF THE VULVA
Acute Bacterial Cystitis Infections of Bartholins Glands Pediculosis Pubis and Scabies Molluscum Contagiosum

Condyloma Acuminatum
Genital Ulcers
Genital Herpes Granuloma Inguinale (Donovanosis) Lymphogranuloma Venereum Chancroid Syphilis
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VAGINITIS

OUTLINE Bacterial Vaginosis


Trichomonas Vaginal Infection

Candida Vaginitis

TOXIC SHOCK SYNDROME CERVICITIS


Neisseria Gonorrhoeae Chlamydia Trachomatis

PELVIC TUBERCULOSIS ACTINOMYCOSIS

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ACUTE BACTERIAL CYSTITIS


HOMEWORK

Risk Factors for UTI


Clinical, diagnostic and distinguishing features

Etiologic agent
Diagnostic work up Management of first episode acute uncomplicated cystitis Management of recurrent cystitis
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BARTHOLINS ABSCESS
HOMEWORK Causes of Bartholins gland enlargement Diagnosis and differentials of Bartholins gland cyst Diagnosing Bartholins gland abscess

Management of Bartholins gland infection & enlargement


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PEDICULOSIS PUBIS
Crab louse or pubic louse Phthirus pubis

hairy areas of the vulva, occasionally in the eyelids


travels slowly Major nouroshment is the human blood Life cycle has 3 stages: egg (nit), nymph, and adult. Eggs deposited at the base of the hair follicle Adult parasite - dark gray when alimentary tract empty Predominant clinical symptom of infestation: constant itching in the pubic area due to allergic sensitization Pruritus may occur within 24 hrs after a reinfection
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PEDICULOSIS PUBIS
Transmitted by direct sexual contact
Non-sexual transmission also documented

Most contagious of all STDs


>90% of sexual partners infected after single exposure

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PEDICULOSIS PUBIS
Diagnosis

Examination of the vulvar area without magnification demonstrates eggs and adult lice, and pepper grain feces adjacent to the hair shaft Definitive diagnosis: microscopy (obtain specimen by scratching the skin papule with a needle and placing the crust under a drop of mineral oil)
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Microscopy
Adult louse and nit containing larvae

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PEDICULOSIS PUBIS
Treatment: kill both the adult parasite and eggs
Permethrin 1% cream rinse (Nix crme) applied to affected areas and washed off after ten minutes Lindane 1% shampoo(Kwell)applied for 4 minutes then washed off Pyrethrins with piperonyl butoxide
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SCABIES
Parasitic infection of the itch mite Sarcoptes scabiei Transmitted by close contact Infection is widespread over the body without a predilection for hairy areas

the mite travels rapidly over the skin and may move up to 2.5 cm in 1 minute.
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SCABIES
Predominant clinical symptom: severe but intermittent itching; pruritus is more intense at night papules, vesicles or burrows Burrows pathognomonic sign of scabies infection; appears as a twisted line on the skin surface, with a small vesicle at one end May involve the hands, wrists, breasts, vulva, and buttocks
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Rashes Short, wavy rashes in the buttocks and interdigits

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SCABIES
Note the burrows Laboratory work up: microscopy using scratch technique; mites lack lateral claw legs but have 2 triangular hairy buds Differential diagnosis: virtually all dermatologic diseases causing pruritus

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Microscopy

Adult mite

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SCABIES
Treatment: kill both the adult parasite and the eggs

Permethrin cream 5% applied to all areas of the body from the neck down and washed off after814 hours Ivermectin 02 mg/kg orally, repeated in 2 weeks if necessary
Lindane 1% 1 oz of lotion or 30g of cream applied thinly to all areas of the body from the neck down and thoroughly washed after 8 hours.
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Etiologic Agent

Phthirus pubis

Sarcoptes scabiei

Site of Infection

Hairy body parts

Non-hairy areas

Movement

Slow

Rapid

Lesions

Pepper grain feces, tiny rough spots constant itching

Papules, vesicles, burrows Intermittent itching, more intense at night

S/Sx

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PEDICULOSIS PUBIS OR SCABIES


Prevention of reinfection
Treatment should be prescribed for sexual contacts within the previous 6 weeks and other close household contacts Clothing and bedding should be decontaminated

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MOLLUSCUM CONTAGIOSUM
Pox virus Chronic localized infection Spread by skin to skin contact, autoinoculation or by fomites Widespread infection closely related to underlying cellular immunodeficiency (HIV infection, chemotherapy or corticosteroid administration)
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MOLLUSCUM CONTAGIOSUM
Characteristic appearance of lesion: fleshcolored small nodules or domed papules usually 1-5 mm in diameter with umbilicated center
Complication - superinfection

Diagnosis:
Microscopy of the white waxy material from inside the nodule: intracytoplasmic molluscum bodies with Wright or Giemsa stain Clinical
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MOLLUSCUM CONTAGIOSUM
Treatment
Self-limiting infection Individual papules
injection of local anesthetic evacuation of caseous material excision of nodule with a sharp dermal curette base of the papule chemically treated with ferric subsulfate (Monsel solution) or 85% TCA
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CONDYLOMA ACUMINATUM
Genital, venereal, or anogenital warts

Most common viral STD of the vulva, vagina, rectum and cervix caused by Human Papilloma Virus (HPV virus) 30% of infected women - clinically recognizable macroscopic lesion
70% - unrecognized subclinical infection
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CONDYLOMA ACUMINATUM
Sexual transmission

Autoinoculation
Conditions that predispose women to HPV infection: Immunosuppression, Diabetes, pregnancy, local trauma Signs & symptoms: Asymptomatic Pain, itching, tendency to bleed when friable, (+) odor when secondarily infected
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HPV Type 6, 11 40, 42, 53, 54, 57, 66, 84 16, 18, 31, 33, 35, 39 45, 51, 52, 56, 58, 59 68, 73, 82 61, 62, 67, 69, 70

Morphology Genital warts, LSIL, RRP LSIL LSIL HSIL Cancer ?

Potential for Cancer Low (negligible) Low (negligible)

High

Uncertain

HPV 16 & 18 aneuploid, premalignant and malignant lesions HPV 6 & 11 benign, euploidus intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion;
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Raised warty lesions 2mm to 2 cm in diameter Bigger pedunculated lesions

Pigmented, indurated, fixed or ulcerated Cauliflower-like lesions

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Male Partner

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Cervical inspection - whitish lesions

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CONDYLOMA ACUMINATUM
Diagnosis:
Direct inspection Biopsy:
When lesions do not respond to standard therapy

When condition accelerates during therapy


Immunocompromised woman Pigmented, indurated, fixed or ulcerated growths

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Microscopy:
Biopsy - koilocytes

Electron microphotograph causative agent

Koilocytes
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CONDYLOMA ACUMINATUM
Management:
Depends on the location, size, and extent of the condyloma and whether the woman is pregnant

Treatment: Chemical, Cautery, Immunologic therapy , surgery

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Treatment of Warts: Patient-Administered

Podofilox 0.5% Solution or Gel (Condylox)

Imiquimod 5% Cream (Aldera)

Dose

Bid for 3 days, 4 days Daily and qhs, 3 off up to 4 cycles times/week up to 16 weeks, wash 610 min after Rx Antimitotic Immune enhancer Mild to moderate pain, Mild to moderate local local irritation inflammation NO NO

Mode of action Side effects Pregnancy


MMWR 55(RR-11), 2006.

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Treatment of Warts: Provider-Administered Trichloroacetic Podophyllin Resin Acid (TCA) Weekly, frosting

Cryotherapy Dose

Weekly every 12 Weekly weeks (no cryoprobe in vagina) Thermal-induced cytolysis Pain, necrosis + blistering OK Antimitotic

Mode of action

Chemical coagulation of proteins Pain, adjacent damage [use soap, soda] OK

Side effects

Local irritation

Pregnancy
MMWR 55(RR-11), 2006.

NO

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Another chemical alternatives: topical 5 Fuorouracil, epinephrine, bovine collagen gel

GENITAL ULCERS

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Clinical Features of Genital Ulcers


Syphilis
Incubation period Primary lesion Number of lesions 24 weeks (112 weeks) Papule Usually one

Herpes
27 days Vesicle Multiple, may coalesce 12

Chancroid
114 days Papule or pustule

LGV
3 days6 weeks Papule, pustule, or vesicle

Donovanosis
14 weeks (up to 6 months) Papule Variable

Usually multiple, may Usually one coalesce 220 210

Diameter (mm) Edges

515

Variable Elevated, irregular

Sharply demarcated Erythematous Elevated, round or oval

Undermined, ragged, Elevated, round irregular or oval irregular

Depth
Base Induration Pain Lymphadenopathy

Superficial or deep Superficial


Smooth, nonpurulent Firm Unusual Firm, nontender, bilateral Serous, erythematous None Common

Excavated
Purulent Soft Usually very tender

Superficial or deep
Variable

Elevated
Red and rough (beefy)

Occasionally firm Firm Variable Uncommon

Firm, tender, often Tender, may bilateral suppurate, usually unilateral

Tender, may Pseudoadenopathy suppurate, loculated, usually unilateral

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GENITAL HERPES
Recurrent, incurable, highly contagious and one of the most frequently encountered STD Transmitted by asymptomatic shedding Not a debilitating physical disease, but may present an overwhelming psychological burden

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GENITAL HERPES
HERPES SIMPLEX VIRUS
TYPE 1 infection above the waist but may cause LGT infections; most commonly acquired genital herpes in women younger than 25; does not protect against HSV-2 TYPE 2 infection below the waist; offers some protection against HSV-1

(definite sexual transmission)


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GENITAL HERPES
Signs & Symptoms of Primary Infection:
Paresthesia of the vulvar skin Papule and vesicle formation
Multiple vesicles become shallow then develop as superficial ulcers over a large area of the vulva

Severe vulvar pain, tenderness and inguinal adenopathy General malaise and fever
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GENITAL HERPES
Recurrences
Related to the onset of menstrual period or emotional stress
May be asymptomatic; most are half as severe as primary infection Prodrome: sacroneuralgia, vulvar burning, tenderness and pruritus vor a few hours to 5 days before vesicle formation HSV resides in a latent phase in the dorsal root ganglia of S2, S3 and S4
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GENITAL HERPES
Diagnosis:
Clinical inspection

Viral culture positive in primary episodes


Polymerase Chain Reaction (PCR) Test most accurate and sensitive technique for identifying HSV Western blot assay for antibodies to HSV- most specific method for diagnosing recurrent, unrecognized or subclinical herpes

Prevention: vaccine
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Erythematous labia with vesicular lesions and sores

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Multiple cervical erosions

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Male Partner

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Microscopy:
Tzanck
Electron microphotograph

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Antiviral Treatment for HSV-Nonpregnant Patient Indication First clinical episode Recurrent episodes Valacyclovir Acyclovir Famciclovir

GENITAL HERPES

1000 mg bid for 7 200 mg five times a 250 mg tid for 710 10 days day or 400 mg tid days for 710 days 1000 mg daily or 500 mg bid for 5 days (or 3 days) 500 mg daily (8 recurrences per year) or 1000 mg/day or 250 mg bid (>9 recurrences/year) 400 mg tid for 5 125 mg bid for 5 days or 800 mg bid days 1000 mg bid for 5 days or 800 for 1 day mg tid for 3 days 400 mg bid 250 mg bid

Daily suppressive therapy

MMWR 55(RR-11), 2006.

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GRANULOMA INGUINALE (DONOVANOSIS)


Chronic, slowly progressive,ulcerative, bacterial infection of the skin and subcutaneous tissue of the vulva Common in tropical climates Calymmatobacterium granulomatosis a gram negative, non-motile, encapsulated rod Spread both sexually and through close, non-sexual contact Not highly contagious, and chronic exposure is necessary to contract the disease
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GRANULOMA INGUINALE
Initially appears as asymptomatic nodule which ulcerates (beefy-red ulcer with fresh granulation tissue), coalesce and if untreated eventually destroy the normal vulvar architecture
Subcutaneous involvement- pseudobubo

Secondary bacterial infection

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GRANULOMA INGUINALE

(DONOVANOSIS)
Diagnosis: Donovan bodies (clusters of dark-staining bacteria with a bipolar or safety-pin appearance) in smears and specimen taken from the ulcers; special Silver stain is used to identify the Donovan bodies

Differential Diagnosis: Lymphogranuloma venereum, vulvar carcinoma, Syphilis, chancroid, genital herpes, amebiasis

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GRANULOMA INGUINALE (DONOVANOSIS)


Treatment:
Doxycycline 100 mg twice daily
Alternative regimen:
Ciprofloxacin 750 mg twice daily or Erythromycin base 500 mg four times daily or Azithromycin 1 gm orally weekly or Trimethoprim-sulfamethoxazole 800 mg/160 mg BID

Minimum treatment duration three weeks and until lesions have completely healed
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LYMPHOGRANULOMA VENEREUM (LGV)


Chronic infection of lymphatic tissue produced by Chlamydia trachomatis

Majority of cases - men


Affect the vulva (most frequent site), urethra, rectum and cervix

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LGV-Three Phases
Primary infection shallow painless ulcer of the vestibule or labia, resolves spontaneously

Secondary infection painful adenopathy in inguinal and perirectal areas when untreated becomes enlarged, tender and matted Groove sign
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LGV- Three Phases


Tertiary infection
formation of multiple draining sinuses and fistula

extensive destruction of the external genitalia and anorectal region leading to secondary extensive scarring elephantiasis, multiple fistulas, stricture formation of the anal canal and rectum
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LYMPHOGRANULOMA VENEREUM (LGV)


Diagnosis:

Culture of pus or aspirate from an infected mode


Complement fixation antibody titer = 1:64 is indicative of infection
Treatment

Doxycycline 100 mg twice daily for at least 21 days

Alternative:
Azithromycin 1g oraly 1x per week for 3 weks Erythromycin base 500 mg4x daily for 21 days
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CHANCROID
Sexually transmitted, acute, ulcerative disease of the vulva painful and tender ulcer Tender suppurative inguinal adenopathy (buboes) Genital ulcers of chancroid facilitate the transmission of HIV infection

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CHANCROID
Haemophilus ducreyi highly contagious small gram-negative rod non-motile, facultative anaerobe Tissue trauma or excoriation must precede initial infection since H. Ducreyi is unable to penetrate and invade normal skin

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Chancroid: Diagnosis
Gram stain
school of fish

Culture of purulent material by aspiration of tender lymph nodes

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CHANCROID
Treatment:
Azithromycin 1 gm orally Ceftriaxone 250 mg IM in a single dose

Ciprofloxacin 500 mg twice daily x 3 days


Erythromycin base 500 mg tid x 7 days H. ducreyi is resistant to multiple antibiotics Susceptibility of bacterial isolates should be performed

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SYPHILIS
Chronic complex systemic disease cause by Treponema pallidum T. pallidum- anaerobic, elongated, tightly wound spirochete; can penetrate the skin or mucous membrane Patients are contagious during the primary, secondary and probably the 1st year of latent syphilis
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Microscopy:
Darkfield - thin, silvery spiral motile organism

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SYPHILIS Transmission is by sexual contact, or by kissing or touching a person who has an active lesion on the lips, oral cavity, breast or genitals. Case transmission can occur with oralgenital contact.

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SYPHILIS
Diagnosis:
VDRL( Venereal Disease Research Laboratories) or RPR (Rapid Plasma Reagin)
Screening test Index for response to treatment

Treponema Immobilization Test FTA-ABS (Fluorescent-labeled Treponema antibody absorption)

MHA-TP (Microhemagglutination assay for antibodies to T. pallidum)


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SYPHILIS
Primary Syphilis
Solitary, painless ulcer (chancre); heals spontaneously

Secondary
Result of hematogenous dissemination of the spirochetes and is a systemic disease Rashes red macules and papules over the palms of the hands and the soles of the feet Vulvar lesions mucous patches and condyloma latum associated with painless adenopathy
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SYPHILIS
Latent Stage
Follows secondary stage Positive serology without symptoms or signs of her disease

Tertiary
Potentially destructive effects on the central nervous, cardiovascular, and musculoskeletal systems

Late syphilis: optic atrophy, tabes dorsalis, generalized paresis, aortic aneurysm, gummas (similar to a cold abscess with a necrotic center and the obliteration of small vessels by endarteritis) of the skin and bones
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Primary Syphilis
Small ulcerated lesion on the labia majora Q-tip probing - hard, non-tender ulcer base Non-tender nodulations in the inguinal areas

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Male partner

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Secondary stage
Hyperpigmented skin eruptions-pink to dull coppery-red

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Secondary stage
Condylomata lata - pale brown or pale pinky gray 5-20 mm diameter
Slightly raised surface, flat, clean, moist from exudates

Highly infectious

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Tertiary Syphilis

Gumma: area of tissue necrosis resulting to ischemia caused by endarteritis and surrounded by granulation tissue

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SYPHILIS
Treatment:
Primary, Secondary and Early Latent Phase
Benzathine Penicillin G, 2.4 million units IM Penicillin Allergy / non-pregnant Doxycycline 100 mg twice daily x 14 days or Ceftriaxone 1 gm IM/IV daily x 8-10 days (limited) or Azithromycin 2 gm single oral dose (preliminary data)

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SYPHILIS
Latent Phase
Benzathine penicillin G 2.4 million units IM at one week intervals x 3 doses Penicillin allergy / non-pregnant Doxycycline 100 mg orally twice daily Tetracycline 500 mg orally four times daily

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SYPHILIS
Neurosyphilis
Aqueous crystalline penicillin G, 18-24 million units administered 3-4 million units IV every 4 hours for 10-14 days Alternative regimen Procaine penicillin 2.4 million units IM daily plus probenecid 500 mg po 4 x daily for 10-14 days

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SYPHILIS
Some experts administer benzathine penicillin 2.4 million units IM wkly x 3 after completion of these regimens to provide comparable duration of treatment with latent syphilis
Management of Sex Partners
Sexual partners of women with syphilis at any stage should be evaluated both clinically and serologically

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SYPHILIS
Management of Sex Partners
Time intervals used to identify an at-risk sex partner are:
3 months plus duration of symptoms for primary sy 3 months plus duration of symptoms for secondary sy 1 year for early latent syphilis

Individuals who are exposed within the 90 days preceding the diagnosis of primary, secondary, or early latent syphilis in their sexual partners should be treated presumptively because they may be infected even if seronegative

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VAGINITIS
Normal physiologic vaginal discharge:
cervical and vaginal epithelial cells, normal bacterial flora, water, electrolytes, other chemicals pH 4.0 Lactobacilli, S. epidermidis, E.coli, diphtheroids, streptococci

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VAGINITIS
Three common infections infections of the vagina are produced by: Fungus (candidiasis) Protozoon (trichomonas) Synergistic bacterial infection (bacterial vaginosis) Symptoms associated with vaginal infection: Vaginal discharge, superficial dyspareunia, dysuria, odor, vulvar burning

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Typical Features of Vaginitis


Symptoms and Signs[*] Increased discharge (white, thin) Findings on Examination[*]

Condition Bacterial vaginosis[]

pH

Wet Mount

Comment

Thin, whitish gray >4.5 homogeneous discharge, sometimes frothy

Clue cells (>20%) shift in Greatly decreased flora lactobacilli

Increased odor

Amine odor after adding potassium hydroxide to wet mount Thick, curdy discharge <4.5 Hyphae or spores

Greatly increased cocci, bacilli small curved rods Can be mixed infection with bacterial vaginosis, T. vaginalis, or both, and have higher pH

Candidiasis

Increased discharge (white, thick)[]

Pruritus
Dysuria Burning Trichomoniasis[] Increased discharge (yellow, frothy) Increased odor Pruritus Dysuria JTC2007

Vaginal erythema

Yellow, frothy discharge >4.5 with or without vaginal or cervical erythema

Motile trichomonads

More symptoms at higher vaginal pH

Increased white cells

BACTERIAL VAGINOSIS
Reflects a shift in vaginal flora from lactobacilli-dominant to mixed flora (genital microplasmas, G.vaginalis, and anaerobes, such as peptostreptococci, and Prevotella, and Mobiluncus species)

No causative agent has been identified


not classified as an STD (more of sexually associated infection) Absence of inflammation in biopsies hence the term vaginosis rather than vaginitis

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BACTERIAL VAGINOSIS
Risk factors New or multiple sexual partners Women who have sex with women Douching at least monthly or within the prior 7 days Social stressors Associated with Upper tract infections (endomyometritis, PID) Vaginal cuff cellulitis In pregnancy preterm rupture of the membranes and endomyometritis; decreased success of IVF and increased pregnancy loss <20 weeks gestation
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BACTERIAL VAGINOSIS
Criteria: Amsels Clinical Criteria
Homogenous vaginal discharge pH 4.5 Amine-like odor when mixed with KOH (whiff test) Wet smear demonstrates clue cells greater in number than 20% of the of vaginal epithelial cells *** 3 out of 4 criteria is sufficient for diagnosis
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Wet Prep: Bacterial Vaginosis


Saline: 40X objective

NOT a clue cell

Clue cells

NOT a clue cell


Source: Seattle STD/HIV Prevention Training Center at the University of Washington
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Microscopy:

Gram stain - clue cells, decreased number of lactobacilli

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Vaginal Gram stain (Nugent criteria)


Score Lactobacillus morphotypes
4+ 3+ 2+ 1+ 0

Gardnerella & Bacteroides sp morphotypes


0 1+ 2+ 3+ 4+

Curved Gram variable rods


0 1+ or 2+ 3+ or 4+

0 1 2 3 4

0, no morphotypes; 1, <1 present; 2, 1-4 present; 3, 5-30 present; 4, 30 or > present

Classification: Normal (0-3 points)


Intermediate (4-6 points) Bacterial vaginosis (7-10 points)
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Nugent evaluation of Gram's stained vaginal smears A, Normal smear; score 0. B, Normal smear; score 2. C, Intermediate smear; score 4. D, Intermediate smear; score 6. E, Bacterial vaginosis smear; score 8. F, Bacterial vaginosis smear; score 10. (Nugent RP, Krohn MA, Hillier SL: Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J Clin Microbiol 1991, 9:297-301.)
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BACTERIAL VAGINOSIS
Treatment:
Metronidazole 500 mg twice daily for 7 days Metronidazole gel 0.75%, 5 g intravaginally once daily for 5 days Clindamycin cream 5%, 5 g intravaginally qhs for 7 days
Alternative regimen
Clindamycin 300 mg BID daily for 7 days Clindamycin ovules 100 g intravaginally at HS for 3 days

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TRICHOMONAS VAGINAL INFECTION


Trichomonas vaginalis unicellular intracellular, anaerobic, flagellated protozoon
sexually transmitted inhabits the vagina and lower urinary tract, Skenes ducts in the female

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TRICHOMONAS VAGINAL INFECTION


Signs & symptoms:
Profuse frothydischarge with unpleasant odor Erythema and edema of the vulva and vagina strawberry cervix and upper vagina Vulvar pruritus

dysuria

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Diagnosis:

TRICHOMONAS VAGINAL INFECTION

NSS smear / wet smear visualization of the trichomonas organism

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TRICHOMONAS VAGINAL INFECTION


Treatment
Metronidazole 2 gm orally in a single dose Tinidazole 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

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CANDIDA VAGINITIS
Produced by a ubiquitous, airborne, grampositive fungus (Candida albicans, C.glabrata, C.tropicalis)
commensal saprophytic organisms on the mucosal surface of the vagina, which become opportunistic when the vaginal ecosystem is disturbed.
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CANDIDA VAGINITIS
Predisposing factors:
Hormonal Menstrual period Pregnancy Depressed cell-mediated immunity AIDS Diabetes mellitus, obesity and debilitating disease Antibiotic use Broad spectrum antibiotics (penicillin, tetracycline, cephalosporins)
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CANDIDA VAGINITIS
Classification:
Uncomplicated: Sporadic, infrequent, Mild-tomoderate, Likely C albicans Complicated or Recurrent: Severe, Non-albicans, DM, Pregnancy, Immunosuppression

Signs & Symptoms:


Pruritus, vulvar burning, external dysuria, dyspareunia

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Intense vaginal pruritus exacerbated by menstruation

Vulvar edema and erythema

Intertrigo extending to the perianal region

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Shallow erosions on the labia and perineum

Plaques of white cheesy discharge

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Male Partner

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CANDIDA VAGINITIS
Diagnosis:
KOH (10-20%) smear filamentous forms, mycelia, hyphae, pseudohyphae Culture with Nickerson or Saboraud medium (useful when KOH smear is negative or when a woman has recently treated herself with an antifungal)

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Microscopy

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CANDIDA VAGINITIS
Treatment:
Intravaginal regimens
Butoconazole, clotrimazole, miconazole, nystatin, tioconazole, terconazole

Oral regimen
Fluconazole 150 mg in a single dose

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Disease

Drug

Dose

Bacterial vaginosis

Metronidazole (Flagyl)
0.75% Metronidazole gel (Metrogel) 2% Clindamycin cream (Cleocin vaginal) 2% Extended-release clindamycin cream (Clindesse)

500 mg orally twice a day for 7 days


One 5-g application intravaginally daily for 5 days One 5-g application intravaginally every night for 7 days One application intravaginally

Vulvovaginal candidiasis uncomplicated Intravaginal therapy Azoles 2% Butoconazole cream (Mycelex-3) 2% Sustained-release butoconazole cream (Gynazole) 1% Clotrimazole cream (Mycelex-7) Clotrimazole (Gyne-Lotrimin 3) 5 g per day for 4 days One 5-g dose 5 g for 714 day Two 100-mg vaginal tablets per day for 3 days One 500-mg vaginal tablet 5 g per day for 7 days One 100-mg vaginal suppository per day for 7 days One 200-mg vaginal suppository per day for 3 days

2% Miconazole cream Miconazole (Monistat-7) Miconazole (Monistat-3) Miconazole (Monistat-1) 6.5% Tioconazole oinment (Monistat 1-day) 0.4% Terconazole cream (Terazol 7) 0.8% Terconazole cream (Terazol 3) Terconazole vaginal Nystatin vaginal Oral therapy Intravaginal therapy Oral therapy[] Trichomoniasis Fluconazole (Diflucan) Azole Fluconazole (Diflucan) Metronidazole (Flagyl)

One 5-g dose 5 g per day for 7 days 5 g per day for 3 days One 80-mg vaginal suppository per day for 3 days One 100,000-U vaginal tablet per day for 14 days One 150-mg dose orally 714 days Two 150-mg doses orally 72 hr apart One 2-g dose orally 500 mg orally twice daily for 7 days

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Tinidazole (Tindamax)

One 2-g dose orally

TOXIC SHOCK SYNDROME


ASSIGNS READING AND WRITTEN REPORT Identify the etiology of TSS Explain the pathophysiology of TSS Three requirements for development of classical TSS Case definition of TSS Management of TSS

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CERVICITIS
Inflammatory process associated with trauma, inflammatory systemic disease, neoplasia, and infection Ectocervicitis or endocervicitis Ectocervicitis - viral (HSV) or from a severe vaginitis (e.g., strawberry cervix associated with T. vaginalis infection) or C. albicans Endocervicitis - C. trachomatis or N. gonorrhoeae
Bacterial vaginosis and M. genitalium have also been associated with endocervicitis

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MUCOPURULENT CERVICITIS
Criteria:
gross visualization of yellow mucopurulent material on a white cotton swab

presence of 10 or more PMN leukocytes per microscopic field (magnification 1000) on Gram-stained smears obtained from the endocervix

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MUCOPURULENT CERVICITIS
Alternative clinical criteria:
erythema and edema in an area of cervical ectopy or associated with bleeding secondary to endocervical ulceration friability when the endocervical smear is obtained

increased vaginal discharge and intermenstrual vaginal bleeding


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MUCOPURULENT CERVICITIS
Signs & symptoms:
hypertrophic and edematous cervix

vaginal discharge, deep dyspareunia, and postcoital bleeding.

Pathogens: Chlamydia trachomatis and Neisseria gonorheae


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NEISSERIA GONORRHOEAE
gram-negative diplococci - epithelium of the genitourinary tract, rectum, pharynx or the eye localized acute infection resulting to bacteremia / disseminated infection

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Purulent urethral discharge with edema of the meatus

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Reddish and edematous cervix with mucopurulent exudation

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NEISSERIA GONORRHOEAE
Diagnosis:

Culture Gram stain Enzyme immunoassay sensitivity 50 100% Nucleic Acid Amplification test: GOLD STANDARD
sensitivity 91 100%; specificity 97 100%

Nucleic Acid Hybridization test: sensitivity 91 100%; specificity 97 100%

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Microscopy
Gram - stained smear of the endocervical swab: gram negative intracellular diplococci

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NEISSERIA GONORRHOEAE
Treatment:
Priorities when choosing an antibiotic:
single-dose efficacy and simultaneously treating coexisting CT infection

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NEISSERIA GONORRHOEAE
Recommended Regimens (CDC 2006)
Ceftriaxone 125 mg IM in a single dose OR Cefixime 400 mg orally in a single dose OR Ciprofloxacin 500 mg orally in a single dose OR Ofloxacin 400 mg orally in a single dose OR Levofloxacin 250 mg orally in a single dose PLUS TREATMENT FOR CHLAMYDIA IF NOT RULED OUT

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NEISSERIA GONORRHOEAE
Treatment: April 2007 Cefixime 400 mg po or Ceftriaxone 125mg IM

PLUS Chlamydial therapy if not ruled out

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NESSERIA GONORRHOEAE
Alternative regimens (CDC 2006)
Spectinomycin 2 grams IM in a single dose or Ceftizoxime 500 mg IM; or Cefoxitin 2 g IM, administered with probenecid 1 g orally; or Cefotaxime 500 mg IM Single dose quinolones - Norfloxacin 800mg, Lomefloxacin 400mg, Gatifloxacin 400mg

PLUS Chlamydial therapy if infection not ruled out


JTC2007

NESSERIA GONORRHOEAE
Alternative regimens (April 2007)
Spectinomycin 2 grams IM in a single dose or Ceftizoxime 500 mg IM; or Cefoxitin 2 g IM, administered with probenecid 1 g orally; or Cefotaxime 500 mg IM Some evidence indicates that cefpodoxime 400 mg and cefuroxime axetil 1 g might be oral alternatives

PLUS Chlamydial therapy if infection not ruled out

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CHLAMYDIA TRACHOMATIS INFECTION


Obligatory intracellular organism Empiric therapy- recommended in women at increased risk of this common STD (young age 25 years, new or multiple sex partners, unprotected sex)

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Cervical edema and ectopy with mucopurulent exudation

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Male Partner

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CHLAMYDIA TRACHOMATIS INFECTION


Diagnosis:
NAAT (Nucleic acid amplification testing)
sensitivity 98% / specificity 99%

GOLD STANDARD Cell culture - sensitivity 70-80% Direct fluorescent antigen (DFA)
sensitivity 90% / specificity 98%

Enzyme Immunoassay (EIA)


sensitivity 92%-97% / specificity 67%-91%

Rapid enzyme tests low sensitivity / specificity

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Microscopy
Direct immunoflourescence test - elementary bodies

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CHLAMYDIA TRACHOMATIS INFECTION


Treatment:
Azithromycin 1 gm single dose
Doxycycline 100 mg bid x 7days

Alternative regimen:
Erythromycin base 500 mg qid for 7 days Erythromycin ethylsuccinate 800 mg qid for 7 days

Ofloxacin 300 mg twice daily for 7 days


Levofloxacin 500 mg for 7 days

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Infection in the upper genital tract not associated with pregnancy or intraperitoneal pelvic operations. Include infection of any or all of the following anatomic locations:
endometrium (endometritis) oviducts (salpingitis) most characteristic and common componenet of PID, ovary (oophoritis), uterine wall (myometritis), uterine serosa broad ligaments (parametritis)
pelvic peritoneum
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ASCENDING INFECTION
> 99% of cases result from ascending infection from the bacterial flora of the vagina and cervix
Infection occurs along the mucosal surface bacterial colonization and infection of the endometrium and fallopian tubes may extends to the surface of the ovaries and nearby peritoneum (rarely into the adjacent soft tissues, such as the broad ligament and pelvic blood vessels)
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Less than 1 % - from transperitoneal spread of infectious material from a perforated appendix or intraabdominal abscess Hematogenous and lymphatic spread to the tubes or ovaries - rare

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Polymicrobial infection
Two classic sexually transmitted organisms, N. gonorrhoeae and C. trachomatis are involved

coexist in the same individual 25% to 50% of the time.


Endogenous aerobic and anaerobic bacteria from the normal vaginal flora are cultured from tubal fluid in approximately 50% of cases BV-associated microorganisms have been isolated laparoscopically from the fallopian tubes of women with BV and and PID
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gonococci ascends to the fallopian tube and selectively adheres to nonciliated mucus-secreting cells majority of damage occurs to the ciliated cells, ( acute complement-mediated inflammatory response with migration of polymorphonuclear leukocytes, vasodilation, and transudation of plasma into the tissues ) cell death and tissue damage

The process of repair with removal of dead cells and fibroblast scarring and tubal adhesions

JTC2007

may remain in the tubes for months after initial colonization of the upper genital tract Cell-mediated immune mechanisms appear to be important in tissue destruction Primary infection appears to be self-limited with mild symptoms and little permanent damage

Antibodies to chlamydial heat shock protein severe tubal scarring and Fitz-HughCurtis syndrome
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Atypical or Silent PID (Chlamydia)


Asymptomatic (or mild symptoms) despite ongoing inflammation of upper genital tract
Sequelae:
tubal factor infertility ectopic pregnancy

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M. Hominis and U. urealyticum


M. hominis - commensal organism

Rate of isolation of genital mycoplasmas from the cervix is approximately 75% and similar in populations of women who are sexually active both with and without PID.
Direct tubal cultures demonstrated M. hominis in 4% to 17% and U. urealyticum in 2% to 20% of women with acute PID. Pathology is in the parametria and the tissue surrounding the tubes, not in the tubal lumen
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M. Hominis and U. urealyticum


Not highly pathogenic and the presence of genital mycoplasmas does not change the clinical presentation and clinical course of acute PID Both M. hominis and U. urealyticum may colonize or persist in the endometrial cavity after complete recovery from acute PID

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RISK FACTORS

Age at first intercourse

Multiple partners Lack of contraception

Oral contraceptive use


IUD the increase in risk for PID occurs only at the time of insertion of the IUD and in the first 3 weeks after placement.
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RISK FACTORS
Previous tubal ligation rare and less severe
Previous PID - 25% subsequently develop another episode Transcervical penetration with instrumentation - iatrogenic

Virulence factors

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Acute Salpingitis: Clinical Criteria for Diagnosis


Abdominal direct tenderness, with or without rebound tenderness Tenderness with motion of cervix and uterus All 3 necessary for diagnosis

Adnexal tenderness
Plus Gram stain of endocervixpositive for gramnegative intracellular diplococci Temperature (>38 C) Leukocytosis (>10,000) Purulent material (white blood cells present) from peritoneal cavity by culdocentesis or laparoscopy Pelvic abscess or inflammatory complex on bimanual examination or on sonography
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1 or more necessary for diagnosis

CDC Guidelines for Diagnosis of Acute PID Clinical Criteria for Initiating Therapy
Minimum Diagnostic Criteria
Uterine tenderness or Adnexal tenderness or

Cervical motion tenderness or

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Additional Diagnostic Criteria


Oral temperature >38.3 C, Cervical CT or GC

WBCs/saline microscopy
Elevated ESR Elevated CRP Cervical discharge

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Definitive Diagnostic Criteria


Endometrial biopsy with histopathologic evidence of endometritis

Transvaginal sonography or MRI showing thick fluidfilled tubes


Laparoscopic abnormalities consistent with PID GOLD STANDARD

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MANAGEMENT OBJECTIVES
SHORT TERM- elimination of signs and symptoms and eradication of infecting organisms LONG TERM- reduction of tubal damage and preservation of fertility capacity

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CDC 2006 Outpatient Management of Acute PID


Regimen A - OPD
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

Regimen B - OPD
Ceftriaxone 250 mg IM SD (or cefoxitim 2 g IM + probenecid 1 g PO SD) OR

Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) PLUS Doxycycline 100 mg twice daily for 14 days WITH or WITHOUT Metronidazole 500 mg twice daily for 14 days
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ORAL REGIMEN
Ceftriaxone 250 mg IM SD (or cefoxitim 2 g IM + probenecid 1 g PO SD) Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) PLUS Doxycycline 100 mg twice daily for 14 days WITH or WITHOUT Metronidazole 500 mg twice daily for 14 days

ALTERNATIVE REGIMEN
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

Test is negative for gonorrhea (April 2007)


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Outpatient Therapy
Reexamine women within 48 to 72 hours of initiating outpatient therapy Hospitalization warranted if not responding

Reevaluate 4 to 6 weeks after therapy to assess resolution of clinical symptoms and establish post therapy baseline

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Indications for Hospitalizing Patients with Acute Pelvic Inflammatory Disease


Surgical emergencies (e.g., appendicitis) cannot be excluded. The patient is pregnant. The patient does not respond clinically to oral antimicrobial therapy. The patient is unable to follow or tolerate an outpatient oral regimen. The patient has severe illness, nausea and vomiting, or high fever. The patient has a tuboovarian abscess.

JTC2007

CDC 2006 Inpatient Management of Acute PID


Parenteral Regimen A
Cefotetan 2 g IV every 12 hours OR Cefoxitin 2 g IV every 6 hours PLUS Doxycycline 100 mg PO or IV every 12 hours

Parenteral Regimen B
Clindamycin 900 mg IV every 8 hours PLUS Gentamicin loading dose IV or IM (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kd) every 8 hours. Single daily dosing may be substituted

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Regimen A
excellent for community-acquired infection
Doxycycline and cefoxitin provide excellent coverage for N. gonorrhoeae, C. trachomatis, and also penicillinaseproducing N. gonorrhoeae. Cefoxitin Peptococcus, Peptostreptococcus, and E. coli Disadvantage less ideal for pelvic Doxycycline should be included in the regimen of followup oral therapy (2 weeks)

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Regimen B
Excellent coverage for anaerobic infections and facultative gramnegative rods. For patients with an abscess, IUD-related infections, and pelvic infections after a diagnostic or operative procedure

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Alternative Parenteral Regimens


Levofloxacin 500 mg IV once daily OR

Ofloxacin 400 mg IV every 12 hours


WITH or WITHOUT Metronidazole 500 mg IV every 8 hours OR Ampicillin/Sulbactam 3 g IV every 6 hours PLUS

Doxycycline 100 mg PO or IV every 12 hours

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In-Patient: Reassess
After three days of treatment Continue regimen if improving With no improvement, consider
wrong diagnosis
resistant organism (e.g. enterococcus) mixed abscess, or rupture septic thrombophlebitis
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With 24 hours of Therapeutic Response.


Shift to Oral Doxycycline 100 mg BID x 14 days
Alternative:
Clindamycin 450 mg QID x 14 days

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Operative Treatment
Indications:
life-threatening infections ruptured tuboovarian abscesses laparoscopic drainage of a pelvic abscess persistent masses in older women for whom future childbearing is not a consideration removal of a persistent symptomatic mass.

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Operative Treatment
Procedures:
Drainage of a cul-de-sac abscess via percutaneous drainage or a culpotomy incision Unilateral Salpingooophorectomy TAHBSO

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Short-term Sequelae
Perihepatitis (Fitz-Hugh-Curtis syndrome)

Tubo-ovarian abscess

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Long-term Sequelae
Infertility Ectopic pregnancy
10% to 15% of pregnancies will be ectopic after laparoscopically mild-to-moderate PID 50% after severe PID

Recurrent PID
approximately 25% of women

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Long-term Sequelae
Chronic pelvic pain
hydrosalpinx (end-stage of a pyosalpinx develops in a woman with normal pelvic examination 4 to 8 weeks following acute infection

adhesions and the resultant fixatio


may benefit from laparoscopy to establish the diagnosis and rule out other diseases, such as endometriosis conservative surgery for this sequela via either laparoscopy or celiotomy
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PARTNER
Examine and treat sex partners

Health education
Culture discharge Empiric treatment:
Cefixime 400 mg SD or
Ceftriaxone 250 mg SD Doxycycline 100 mg BID for 7 days or

Azithromycin 1 gm SD

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Method
Behavioral Monogamy Reducing number of partners Avoiding certain sexual practices Inspecting and questioning partners Barriers Condom

Mechanism

Efficacy in Prevention of STDs

Decreases likelihood of exposure to infected Not well studied; theoretic efficacy persons Decreases likelihood of contact with infectious agents

Protects partner from direct contact with semen, urethral discharge, or penile lesion Protects wearer from direct contact with partner's mucosal secretions

Effective in vitro barrier to chlamydiae, CMV, and HIV, partial protection HSV Appears to decrease risk of acquiring urethral/cervical GC, PID, and male urethral Ureaplasma colonization; partial HPV protection Effect on risk of acquiring NGU not established Nonvaginal use has not been studied Inactivates gonococci, syphilis spirochetes, trichomonads, HSC, ureaplasmas, and HIV in vitro. In vivo studies disappointing. 100 mg gel dose and contraceptive sponge associated with epithelial ulcers and abrasiors

Spermicide

Chemically inactivates infectious agents

Diaphragm/spermicide

Mechanical barrier covers cervix Used with spermicides

Diaphragm alone has not been studies Appears to decrease risk of acquiring cervical GC and PID

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Vaccines

Induce antibody response that renders Commercially available hepatitis B host immune to disease vaccine is safe and effective Results of clinical trials of gonococcal and herpes simplex vaccines ongoing Gonococcal, HIV, and HSV vaccines research in progress Effective guardravalent HPV vaccine safe and effective

Oral Antibiotics Penicillin Sulfathioazole Tetracycline analogues Kill infectious agent on or shortly after No studies among women or civilian exposure before infection is men established Appears to decrease risk of acquiring GC and hard and soft chancres, but use not recommended

Local Postcoital urination Postcoital washing Flushes infectious agents out of Poorly studied urethra and washes infectious agents of genital skin and mucous membrane Inactivates and washes infectious agents out of vagina Poorly studied. Not recommended. Increases risk of endometritis

Postcoital antiseptic douching

JTC2007

PELVIC TUBERCULOSIS
HOMEWORK
Clinical features of pelvic TB Diagnostic work-up for pelvic TB Differential diagnosis PTB treatment - Directly Observed Treatment Strategy (short course) Sequelae of pelvic TB Preventive strategies

JTC2007

ACTINOMYCOSIS
HOMEWORK
Describe the etiologic agent Clinical manifestations Explain the relationship of actinomycosis with IUD use Management

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