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Prognosis:  Related to promptness of treatment/adequacy of drainage if tuboovarian abscess. . Late complications of PID/salpingitis include tubal scarring/infertility..

Empiric Therapy of Sexually Transmitted Diseases

Urethritis/Cervicitis

	Usual
Subset	Pathogens	IM Therapy	PO Therapy
Gonococcal	N.. gonorrhoeae	Ceftriaxone	Cefixime† 400 mg (PO) × 1 dose†
(GC)		250 mg (IM)	or
		× 1 dose	Cefpodoxime† 400 mg (PO) × 1 dose†
		plus either	or
		Azithromycin 1–2 gm	Azithromycin† 2 gm (PO) × 1 dose†
		(PO) × 1 dose
		or
		Doxycycline 100 mg
		(PO) of q12h × days
Non-	C.. trachomatis	Not applicable	Doxycycline 100 mg (PO) q12h × 7 days ‡
gonococcal	U.. urealyticum		or
(NGU)	M.. genitalium		Quinolone*† (PO) × 7 days
			or
			Azithromycin 1 gm (PO) × 1 dose
			or
			Erythromycin 500 mg (PO) q6h × 7 days
	Trichomonas	Not applicable	Tinidazole 2 gm (PO) × 1 dose
	vaginalis		or
			Metronidazole 2 gm (PO) × 1 dose

*Levofloxacin 500 mg q24h or Moxifloxacin 400 mg q24h or Ofloxacin 300 mg q12h..

†Increased resistance oral regimens should be considered alternate (second line) therapy and test of cure essential..

‡(Doxycycline may be given as a 200 mg (PO) of q24h × 7 days..

Gonococcal Urethritis/Cervicitis (Neisseria gonorrhoeae)

Clinical Presentation:  Purulent penile/cervical discharge with burning/dysuria 3–5 days after contact.. Diagnostic Considerations:  Rapid diagnosis in males by Gram stain of urethral discharge showing gramnegative diplococci; urethral cultures also positive.. In females, diagnosis requires identification of organism by culture or DNA probe, not Gram stain.. Rapid diagnosis in males/females by DNA probe.. Obtain throat/rectal culture for N.. gonorrhoeae.. Co-infections are common; obtain syphilis and HIV serologies..

Pitfalls:  Gram stain of cervical discharge showing gram-negative diplococci is not diagnostic of N.. gonorrhoeae; must confirm by culture or nucleic acid amplification.. N.. gonorrhoeae infections are asymptomatic in 10% of men and 70% of women..

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115

Therapeutic Considerations:  Failure to respond suggests re-infection or relapse.. Treat all GC with ceftriaxone.. Because of frequent coinfection with agents of NGU, add oral azithromycin.. Because of increasing resistance, consider using azithromycin 2 gm for dual therapy in patients with GC..

Prognosis:  Good even with disseminated infection..

Non-Gonococcal Urethritis/Cervicitis (Chlamydia/Ureaplasma/Mycoplasma)

Clinical Presentation:  Mucopurulent penile/cervical discharge ± dysuria ~ 1 week after contact.. Diagnostic Considerations:  Diagnosis by positive chlamydial NAAT/Ureaplasma or Mycoplasma NAAT of urethral/cervical discharge.. Evaluate urethral/cervical discharge to rule out N.. gonorrhoeae.. Coinfections are common; obtain syphilis and HIV serologies..

Pitfalls:  C.. trachomatis infections are asymptomatic in 25%..

Therapeutic Considerations:  Failure to respond to doxycycline therapy suggests re-infection or Trichomonas/Ureaplasma/Mycoplasma infection.. Failure to respond to azithromycin suggests trichomoniasis, or infection due to a resistant Mycoplasma (consider quinolone therapy)..

Prognosis:  Tubal scarring/infertility in chronic infection..

Trichomonas Urethritis/Cervicitis (Trichomonas vaginalis)

Clinical Presentation:  Frothy, pruritic vaginal discharge..

Diagnostic Considerations:  Trichomonas by wet mount/culture on special media.. Pitfalls:  Classic “strawberry cervix” is infrequently seen..

Therapeutic Considerations:  Use week-long regimen if single dose fails.. Resistance now recognized as a cause of treatment failure..

Prognosis:  Excellent if partner is also treated..

Vaginitis/Vaginosis

Subset	Usual Pathogens	PO Therapy
Bacterial	Polymicrobial (Gardnerella	Tinidazole 1 gm (PO) ×5 days or 2 gm (PO) ×2
vaginosis/	vaginalis, Mobiluncus,	days or Clindamycin 300 mg (PO) q12h ×7 days or
vaginitis	Prevotella, M.. hominis, etc..)	Metronidazole 500 mg (PO) q12h ×7 days
Candida	Candida	Fluconazole 150 mg (PO) × 1 dose†
vaginitis/balanitis

†Those failing to respond should be treated with Fluconazole 200 mg (PO) ×1 dose then 100 mg (PO) q24h × 1 week..

Bacterial Vaginosis/Vaginitis

Clinical Presentation:  Non-pruritic vaginal discharge with “fishy” odor..

Diagnostic Considerations:  Diagnosis by “clue cells” in vaginal fluid wet mount.. Vaginal pH ≥ 4..5.. Pitfalls:  “Fishy” odor from smear of vaginal secretions intensified when 10% KOH solution is added (positive “whiff test”).

Therapeutic Considerations:  As an alternative to oral therapy, clindamycin cream 2% intravaginally qHS × 7 days (avoid in pregnancy) or metronidazole gel 0..075% 1 application intravaginally q12h × 5 days can be used..

Prognosis:  Complications include premature rupture of membranes, premature delivery, increased risk of PID.. Recurrences very common..

116	A n t i b i o t i c E s s e n t i a l s

Candida Vaginitis/Balanitis

Clinical Presentation:  Pruritic white plaques in vagina/erythema of glans penis.. Diagnostic Considerations:  Diagnosis by gram stain/culture of whitish plaques.. Pitfalls:  Rule out Trichomonas, which also presents with pruritus in females..

Therapeutic Considerations:  Uncomplicated vaginitis (mild sporadic infections in healthy individuals) responds readily to single-dose therapy.. Complicated vaginitis (severe, recurrent, or in difficult-to- control diabetes) often requires ≥ 7 days of therapy (daily topical therapy or 2 doses of fluconazole 150 mg given 72h apart).. Non-albicans infections respond poorly to azoles.. Topical boric acid (600 mg/d in a gelatin capsule × 14 days) is often effective in this setting..

Prognosis:  Good with systemic therapy.. Diabetics/uncircumcised males may need prolonged therapy..

Genital Vesicles (Genital Herpes) (HSV-2/HSV-1)

Subset	PO Therapy
Initial therapy	Acyclovir 200 mg (PO) 5×/day × 10 days or Famciclovir 500 mg (PO) q12h ×
	7–10 days or Valacyclovir 1 gm (PO) q12h × 3 days
Recurrent/	Acyclovir 200 mg (PO) 5×/day × 5 days or Valacyclovir (normal host:
intermittent therapy	500 mg [PO] q24h × 5 days; HIV positive: 1 gm [PO] q12h × 7–10 days)** or
(< 6 episodes/year)	Famciclovir (normal host: 125 mg [PO] q12h × 5 days or 1 gm [PO] q12h × 1
	day*; HIV-positive: 500 mg [PO] q12h × 7 days)
Chronic suppressive	Acyclovir 400 mg (PO) q12h × 1 year or Valacyclovir (normal host:
therapy (> 6	1 gm [PO] q24h × 1 year; HIV-positive: 500 mg [PO] q12h × 1 year) or
episodes/year)	Famciclovir 250 mg (PO) q12h × 1 year

*Patient initiated therapy to be started immediately when recurrence begins..

**Short-course therapy with Valaciclovir 500 mg (PO) q12h ×3 days or Acyclovir 800 mg (PO) q8h ×2 days also effective..

Clinical Presentation:  Painful vesicles/ulcers on genitals with painful bilateral regional adenopathy ± low-grade fever..

Diagnostic Considerations:  Diagnosis by clinical presentation may be misleading..

Pitfalls:  70% of newly acquired gential herpes is due to HSV-1.. Elevated IgG HSV-2 titer indicates past exposure, not acute infection.. HSV-2 IgM titers may be negative..

Therapeutic Considerations:  If concomitant rectal herpes, increase acyclovir to 800 mg (PO) q8h × 7 days.. For recurrent genital herpes, use acyclovir or valacyclovir (dose same as primary infection) for 7 days after each relapse.. Recurrent episodes of HSV-2 are less painful than primary infection, and inguinal adenopathy is less prominent/painful..

Prognosis:  HSV-2 tends to recur, especially during the first year.. HSV-1 recurrences less frequent..

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117

Genital Ulcers

	Usual
Subset	Pathogens	IM Therapy	PO Therapy
Primary	Treponema	Benzathine penicillin 2..4 mu	Doxycycline
syphilis	pallidum	(IM) × 1 dose	100 mg (PO) q12h × 2 weeks
			or
			Azithromycin 2 gm (PO) × 1 dose**
Chancroid	Hemophilus	Ceftriaxone 250 mg (IM) ×	Azithromycin 1 gm (PO) × 1 dose
	ducreyi	1 dose or Any 3rd generation	or Quinolone* (PO) × 3 days or
		cephalosporin 250–500 mg	Erythromycin base 500 mg (PO) q8h
		(IM) × 1 dose	× 7 days

*Ciprofloxacin 500 mg q12h or Levofloxacin 500 mg or Moxifloxacin 400 mg q24h..

**Resistance increasing (careful followup essential)..

Primary Syphilis (Treponema pallidum)

Clinical Presentation:  Painless, indurated ulcers (chancres) with bilateral painless inguinal adenopathy.. Syphilitic chancres are elevated, clean and indurated, but not undermined..

Diagnostic Considerations:  Diagnosis by spirochetes on darkfield examination of ulcer exudate. . Elevated non-treponemal (VDRL/RPR) titers after 1 week..

Pitfalls:  Non-treponemal (VDRL/RPR) titers fall slowly within 1 year; failure to decline suggests treatment failure/HIV.. Even after effective treatment some patients remain VDRL/RPR positive for life (serofast).. Therapeutic Considerations:  Parenteral penicillin is the preferred antibiotic for all stages of syphilis.. If treatment fails and VDRL/RPR titers do not decline, obtain HIV serology..

Prognosis:  Good with early treatment..

Chancroid (Hemophilus ducreyi)

Clinical Presentation:  Ragged, undermined, painful ulcer(s) + painful unilateral inguinal adenopathy.. Diagnostic Considerations:  Diagnosis by streptobacilli in “school of fish” configuration on gramstained smear of ulcer exudate/culture of H.. ducreyi/NAAT..

Pitfalls:  Co-infection is common; obtain Syphilis and HIV serologies..

Therapeutic Considerations:  In HIV, multiple dose regimens or azithromycin is preferred.. Resistance to erythromycin/ciprofloxacin has been reported..

Prognosis:  Good with early treatment..

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Suppurating Inguinal Adenopathy

Subset	Pathogens	IV Therapy	PO Therapy
Lympho-	Chlamydia	Not applicable	Doxycycline 100 mg (PO) q12h × 3 wks or
granuloma	trachomatis (L1–3		Erythromycin base 500 mg (PO) q6h × 3
venereum (LGV)	serotypes)		weeks
Granuloma	Klebsiella	Not applicable	Azithromycin 1 gm (PO) q week until
inguinale	(Calymmato-		cured.. Doxycycline 100 mg (PO) q12h until
(Donovanosis)	bacterium)		cured or Erythromycin 500 mg (PO) q6h
	granulomatis		until cured or TMP–SMX 1 DS (PO) q12h
			until cured or Ciprofloxacin 750 mg (PO)
			q12h until cured

Lymphogranuloma Venereum (Chlamydia trachomatis) LGV

Clinical Presentation:  Unilateral inguinal adenopathy ± discharge/sinus tract..

Diagnostic Consideration:  Diagnosis by very high Chlamydia trachomatis L1–3 titers.. Do not biopsy site (often does not heal and may form a fistula).. May present as FUO..

Pitfalls:  Initial papule not visible at clinical presentation.. Biopsy shows granulomas; may be confused with perianal Crohn’s disease..

Therapeutic Considerations:  Rectal LGV may require additional courses of treatment.. Prognosis:  Fibrotic perirectal/pelvic damage does not reverse with therapy..

Granuloma Inguinale (Klebsiella [Calymmatobacterium] granulomatis) Donovanosis

Clinical Presentation:  Pseudolymphadenopathy with painless inguinal ulcers..

Diagnostic Considerations:  Donovan bodies (“puffed-wheat” appearance) in tissue biopsy.. Pitfalls:  No true inguinal adenopathy, as opposed to LGV infection..

Therapeutic Considerations:  Doxycycline or azithromycin preferred.. Continue therapy until lesions are healed..

Prognosis:  Good if treated early..

Genital/Perianal Warts (Condylomata acuminata)

Subset	Pathogens	Therapy
Genital/	Human	Podophyllin 10–25% in tincture of benzoin or podofilox
perianal warts	papilloma virus	or imiquimod (patient applies) or surgical/laser removal/
	(HPV)	cryotherapy with liquid nitrogen or cidofovir gel (1%) QHS
		× 5 days every other week for 6 cycles or trichloracetic acid
		(TCA)/bichloracetic acid (BCA) or intralesional interferon..
		Sinecatechins (15% ointment) q8h × 4 months

Clinical Presentation:  Single/multiple verrucous genital lesions ± pigmentation, without inguinal adenopathy..

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119

Diagnostic Considerations:  Diagnosis by clinical appearance.. Genital warts are usually caused by HPV types 6, 11.. Anogenital warts caused by HPV types 16,18,31,33,35 and others are associated with cervical neoplasia.. Females with anogenital warts need serial cervical PAP smears to detect cervical dysplasia/ neoplasia..

Pitfalls:  Most HPV infections are asymptomatic..

Therapeutic Considerations:  Cidofovir cures/halts HPV progression in 50% of cases..

Prognosis:  Related to HPV serotypes with malignant potential (HPV types 16,18,31,33,35).. Preventative (not therapeutic) vaccines now available..

Syphilis

Subset	Pathogen	IV/IM Therapy	PO Therapy
Primary,	Treponema	Benzathine penicillin 2..4 mu (IM) × 1 dose	Doxycycline 100 mg
secondary, or	pallidum		(PO) q12h × 2 weeks
early latent			or
(duration < 1			Azithromycin 2 gm
year) syphilis			(PO) × 1 dose*
Late latent	Treponema	Benzathine penicillin 2..4 mu (IM) weekly ×	Doxycycline 100 mg
(duration	pallidum	3 weeks	(PO) q12h × 4 weeks
> 1 year)
or tertiary
syphilis
Neurosyphilis	Treponema	Penicillin G 3–4 mu (IV) q4h or continuous	Doxycycline 100 mg
	pallidum	infusion × 10–14 days	(PO) q12h × 4 weeks
		or	or Minocycline 100
		Alternate: Procaine penicillin 2..4 mu (IM)	mg (PO) q12h × 4
		q24h × 10–14 days plus probenecid 500 mg	weeks
		(PO) q6h × 10–14 days
		or
		Ceftriaxone 2 gm (IV) q24h × 10–14 days

*Resistance increasing (careful follow up essential)..

Duration of therapy represents total time IV, IM, or PO.. All stages of syphilis in HIV patients usually respond to therapeutic regimens recommended for normal hosts.. Syphilis in pregnancy should be treated according to the stage of syphilis; penicillin-allergic pregnant patients should be desensitized and treated with penicillin..

Primary Syphilis (Treponema pallidum)

Clinical Presentation:  Painless, indurated ulcer(s) (chancre) with bilateral painless inguinal ­adenopathy.. Diagnostic Considerations:  Diagnosis by spirochetes on darkfield or DFA examination of ulcer exudate.. Reactive non-treponemal (VDRL/RPR) or treponemal (TPPA, others) test after 1 week.. Patients with ↑ low titers of VDRL/RPR and − treponemal test may be BFP, e..g.., SLE..

Pitfalls:  VDRL/RPR titers fall slowly within 1 year; failure to decline suggests treatment failure.. Therapeutic Considerations:  Parenteral penicillin is the preferred antibiotic for all stages of syphilis; if treatment fails and VDRL/RPR titers do not decline, obtain HIV serology.. Some effectively treated patients remain VDRL/RPR positive in low titers eg 1:4 (serofast) for years..

Prognosis:  Good with early treatment..

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Secondary Syphilis (Treponema pallidum)

Clinical Presentation:  Facial/truncal macular, papular, papulosquamous, non-pruritic, non-tender, symmetrical rash which may involve the palms/soles.. Usually accompanied by generalized adenopathy.. Typically appears 4–10 weeks after primary chancre, although stages may overlap.. Alopecia, condyloma lata, mucous patches, iritis/uveitis may be present.. Renal involvement ranges from mild proteinuria to nephrotic syndrome.. Without treatment, spontaneous resolution occurs after 3–12 weeks..

Diagnostic Considerations:  Diagnosis by clinical findings and VDRL/RPR in high titers (≥ 1:64).. After treatment, RPR/VDRL titers usually ↓ × 4 < 6 months..

Pitfalls:  If only undiluted serum is tested, prozone phenomenon may render VDRL/RPR falsely negative.. Therapeutic Considerations:  Parenteral penicillin is the preferred antibiotic for all stages of ­syphilis.. Prognosis:  Excellent with early treatment..

Latent Syphilis (Treponema pallidum)

Clinical Presentation:  Patients are asymptomatic with elevated non-treponemal titers and reactive treponemal tests..

Diagnostic Considerations:  Diagnosis by positive serology ± prior history, but no signs/symptoms of syphilis. . Asymptomatic syphilis < 1 year in duration is termed “early” latent syphilis; asymptomatic syphilis > 1 year/unknown duration is termed “late” latent syphilis.. Secondary syphilis may relapse in up to 25% of patients with early latent syphilis, but relapse is rare in late latent syphilis.. Evaluate patients for neurosyphilis..

Pitfalls:  Treponemal tests (FTA-ABS, MHA-TP, TPPA, others) usually remain positive for life, even after adequate treatment..

Therapeutic Considerations:  Parenteral penicillin is the preferred antibiotic for all stages of syphilis.. Repeat VDRL/RPR titers at 6, 12, and 24 months; therapeutic response is defined as a 4-fold reduction in RPR/VDRL titers (2 tube dilutions)..

Prognosis:  Excellent even if treated late..

Tertiary Syphilis (Treponema pallidum)

Clinical Presentation:  May present with aortitis, neurosyphilis, iritis, or gummata 5–30 years after initial infection..

Diagnostic Considerations:  Diagnosis by history of syphilis plus positive serological tests with signs/ symptoms of late syphilis..

Pitfalls:  Treat for signs of neurosyphilis on clinical exam or LP, even if VDRL/RPR are non-reactive.. Therapeutic Considerations:  Parenteral penicillin is the preferred antibiotic for all stages of syphilis.. Prognosis:  Related to extent of end-organ damage..

Neurosyphilis (Treponema pallidum)

Clinical Presentation:  Patients are often asymptomatic, but may have ophthalmic/auditory symptoms, cranial nerve abnormalities, tabes dorsalis, paresis, psychosis, or signs of meningitis/dementia.. Diagnostic Considerations:  Diagnosis by elevated CSF VDRL titers; no need to obtain CSF FTA-ABS titers.. Diagnosis confirmed if CSF has pleocytosis (> 5 WBCs/hpf ) or increased protein (> 50 mg/dL), and positive VDRL..

Pitfalls:  Persistent CSF abnormalities suggest treatment failure.. CSF VDRL (60% sensitive) may be negative in neurosyphilis..