Update on Infections

Update on Infections
By:Mark A. Lassoff, MD, MBA, MPH
September 18, 2007

Malacoplakia
* “malako” – soft, “plakos” – plaque
* Rare granulomatous disease
* Michaelis – Gutmann bodies: basophilic lamellar inclusion bodies
* Associated with other autoimmune diseases
o Sarcoidosis, Chedak-Higashi syndrome
* Incidence: 1 in 10,000
* Female: Male – 4:1
* Peak incidence is in patients ≥ 50 yrs old
* 75% of cases occur in GU system, most commonly in the bladder (2nd – kidney)
* Predilection for those with immunodeficiency, systemic dz, carcinoma or chronic UTI with coliform organisms (E Coli – up to 75%, Enterobacter, Klebsiella, Proteus and Pseudomonas)
* Etiology – unknown
o Theory: acquired immunodeficiency interfering with normal intracellular function of the monocyte’s phagolysosome. Residual undigested bacterial components become mineralized by Ca++ & Fe
o Cause appears to be related to imbalance in the intracellular cGMP/cAMP
* Dx made by biopsy
o Lesion: large histiocytes  von Hansemann cells and small intracytoplasmic calculospherules  Michaelis-Gutmann bodies
o Immunohistochemical staining for α1-antitrypsin useful for early and accurate differential dx
* Clinical findings
o Bladder
+ Irritability and hematuria
+ Mucosal plaques or nodules  fungating, firm, sessile masses
o Renal
+ Bilaterality in up to 50%; multifocal is more common
+ Fever, flank pain or mass on PE
+ Cause loss of function via direct invasion or obstruction
+ E Coli infxn in up to 93%
+ Bilateral dz  mortality rate approaches 100% w/i 6 mos of dx w/o intervention
+ IVP: unifocal – may displace calyces vs. multifocal – nephromegaly and poor renal fxn; multiple filling defects
* Management
o Lower tract:
+ Initial treatment with medications
# Bethanecol (↑ cGMP), Ascorbic acid (↓ cAMP)
# Fluoroquinolones (DOC)
# Others: Bactrim, Rifampin, Cipro
+ TUR prn for plaque removal
o Upper tract:
+ Unilateral renal dz: most often requires nephrectomy
o In immunodeficient pts and those with multifocal dz, surgical tx is essential to survival

Sexually Transmitted Infections
Syphilis
* Treponema pallidum (spirochete)
* Spread: infectious lesions, body fluids, in utero, blood transfusions
* Primary
o Single painless, indurated ulcer appearing 3 wks after inoculation (@ site of inoculation) and remains for 4 – 6 wks
o Often with bilateral, non-tender inguinal or regional lymphadenopathy
o Can heal w/o treatment; often goes unnoticed
o Presence of chancres increases risk of HIV acquisition 2-5x
* Latent
o Seroreactivity w/o clinical evidence of dz
o Early: within the last year
o Late latent vs. latent syphilis of unknown duration
* Secondary
o Begins 4 – 10 wks after the appearance of the ulcer but may present up to 24 mos after initial infection
o Mucocutaneous, constitutional and parenchymal signs and symptoms
+ Maculopapular rash (trunk and arms)
+ Generalized non-tender lymphadenopathy
+ Papular rash (may accompany first rash)
# Becomes necrotic and pustular
# Affects palms and soles
# Intertriginous areas: enlarge and erode  condyloma lata (infectious)
+ Less commonly: hepatitis and immune-complexed glomerulonephritis
* Tertiary
o One third of untreated pts
o Rare in industrialized countries, except for pts w/ HIV
o Cardiovascular, skeletal, CNS, skin
+ Aortitis, meningitis, uveitis, optic neuritis, general paresis, tabe dorsalis, gummas of skin/skeleton
* Screening
o Rapid Plasma Reagin (RPR) & Venereal Disease Research Laboratory (VDRL)
+ Correlate with disease activity
+ Become negative one year after treatment
o T. pallidum particle agglutination (TP-PA) or Fluorescent Treponemal Antibody Absorbed (FTA-ABS)
+ Antibody tests remain positive for life; do not correlate w/ active disease
o HIV can cause FN results by treponemal & non-treponemal methods
* Treatment
o Benzthiazide penicillin G (2.4 million units IM x 1)
o Jarisch – Herxheimer rxn
+ Headaches, myalgia, fever, tachycardia, increased resp rate within first 24 hrs after tx w/ PCN
+ Managed with bed rest and NSAIDs
o PCN allergy: Doxycycline (100mg BID x 14d)
o Latent: PCN IM weekly x 3 doses or doxycycline for a total of 4 wks
o Tertiary: Aqueous crystalline PCN G (IV q4h) x 10-14 d or PCN G procaine IM + probenecid (po QID) x 10-14 d
o Pregnancy: desensitization to PCN

Herpes Simplex Virus
* Genital herpes: HSV-2 (85-90%), HSV-1 (10-15%)
* Silent infection may account for >75% of transmission
* Primary
o Painful ulcers of genitalia or anus
+ Group of vesicles on an erythematous base that does not follow a neural distribution is pathognomonic
o Bilateral painful inguinal adenopathy
o Often associated with constitutional flu-like symptoms
o Urethral lesions may cause transient urinary retention in women
o Asx viral shedding can happen up to 3 mos after clinical presentation
* Recurrent episodes are usually less severe
* Severe dz and complications:
o Pneumonitis, disseminated infxn, hepatitis, meningitis, encephalitis
* Dx: viral culture with subtyping (gold standard)
o Not on clinical suspicion alone, classic presentation occurs in a small percentage of pts
o Can see abrasions, fissures or itching
o Subtyping is important for prognosis and counseling
+ HSV-2: ave of 4 recurrences in 1st yr vs. 1 for HSV-1
o Sensitivity: 30 – 95% depending on stage of lesion and whether it is primary or recurrence
* Treatment
o Oral acyclovir, valacyclovir and famciclovir
o Topical meds are not effective
o Recurrences: episodic or suppressive approach
+ Suppressive: decreases frequency/duration and viral shedding
Chancroid
* Haemophilus ducreyi
* Men: Women – 3:1
* Painful, non-indurated ulcer on penis or vulvovaginal area
o Friable base covered with a gray or yellow purulent exudate and a shaggy border
* Inguinal adenopathy is typically unilateral and tender with tendency to become suppurative and fistulize
* Dx: culture media not widely available so gram stain often helpful (short, fine, GN streptobacilli in short, parallel chains)
* Approximately 10% are co-infected w/ HSV or syphilis
* Treatment
o Single dose
+ Azithromycin 1gm po or Ceftriaxone 250mg IM
o Other tx: Cipro x 3d or Erythromycin x 7d

Lymphogranuloma Venereum
* Chlamydia trachomatis – L1, L2, L3
* Single, painless ulcer on the penis, anus or vulvovaginal area that goes unnoticed
* Painful unilateral suppurative inguinal adenopathy and constitutional symptoms that occur 2 – 6 wks after resolution of ulcer
* Significant tissue injury and scarring can occur leading to labial fenestration, urethral destruction, anorectal fistulas and elephantiasis of penis, scrotum or labia
* Dx: mainly clinical
o Complement fixation or indirect fluorescence antibody titers can confirm
* Tx: Doxycycline BID or erythromycin QID x 3 wks

Genital Warts
* Condylomata acuminata
* Human papillomavirus (HPV) – DNA virus
* Types 6 and 11 are most often responsible for visible external genital warts
o Cervix, vagina, urethra, anus, mucous membranes
* Types 16, 18, 31, 33, 35, 39, 45 and 51: associated with cervical dysplasia and neoplasm in women and squamous intraepithelial neoplasia in men
o >99% of cervical cancers and 84% of anal cancers are associated with HPV (16 & 18)
o Cervical cancer is considered an AIDS defining illness
* Most are subclinical and asx
* In women HPV may be associated with nonspecific symptoms such as vulvodynia or pruritis; malodorous vaginal discharge
* Dx: usually inspection or palpation
* Bx: not routinely needed
o Atypical, pigmented, indurated, fixed or ulcerated
o Lesions persist/worsen after tx; immunocompromised pts
* Treatment
o Depends on size, number, location, and patient and physician preference
o Observation (spontaneously resolve with time)
o Patient applied (less expensive)
+ Podofilox 0.5% solution or gel (3d on, 4d off, may repeat x 4)
+ Imiquod 5% cream (3/wk qhs for up to 16 wks)
# Needs to be washed off, can cause ulceration
o Provider applied
+ Cryotherapy with liquid nitrogen
+ Electrosurgery
+ Laser therapy (CO2)
+ Podophyllin resin (20 – 25%)
+ Trichloracetic acid (TCA) or bichloracetic acid (BCA)
+ Surgical excision
* Lesions around the meatus may herald presence of urethral or bladder condyloma
* Urethral or bladder lesions should be cystoscopically excised
* Intraurethral 5% FU cream 2/wk
* Vaccine containing 8 of the most common HPV types associated with cancer could potentially prevent 95% of cervical cancer
* Topical BCG: promising preliminary results

Sexually Transmitted Infections
Chlamydia
* Chlamydia trachomatis: most common bacterial STD in the US and worldwide
* Majority of men and women are asx
* 50% of men experience LUTS attributed to urethritis, epididymitis or prostatitis; may see clear or white urethral discharge
* 75% of women are asx and 40% of those untreated will have PID
* May be transmitted during vaginal birth
o Ocular, oropharyngeal, respiratory, urogenital or rectal infxn
Chlamydia
* Women should be screened annually until 25 yo or if risk factors such as new sexual partner are present
o Nucleic acid amplification test (NAAT) on endocervical swab or urine specimen
o Unamplified nucleic acid hybridization test, enzyme immunoassay or direct fluorescence antibody test
o Culture
* Treatment
o Azithromycin 1gm po x 1 or Doxy BID x 7d
o Refrain from sex until treatment completed or 7d after single dose therapy
o Re-culture recommended 3 wks later if treated with erythromycin, in pregnant women or if symptoms persist
o Re-screened 3 – 4 mos after tx as are high risk for re-infxn

Gonorrhea
* Neisseria gonorrhoeae (GN diplococcus)
* Men usually experience LUTS attributed to urethritis, epididymitis, proctitis or prostatitis w/ associated mucopurulent urethral discharge
* Women may have vaginal and pelvic discomfort, dysuria or abnormal vaginal discharge but are usually asx
* Same screening recs as for Chlamydia
* Treatment
o Ceftriaxone 125mg IM x 1
o Single dose oral regimen
+ Cipro, Levaquin, Ofloxacin (growing resistance to FQs)
o Simultaneous treatment for Chlamydia






Trichomoniasis

* Trichomonas vaginalis (flagellated protozoan)
* Increased incidence in developing countries and those with multiple sexual partners
* Can inhabit the vagina, urethra, Bartholin glands, Skene’s glands and prostate (not rectum/mouth)
* Men: usually asx but can produce short-term urethral discharge, dysuria and urgency
* Women: asx in 50%, otherwise can see sudden onset of frothy white or green, foul-smelling vaginal discharge, pruritis, and erythema
o Dyspareunia, suprapubic discomfort, urgency
Trichomoniasis
* Examination: frothy discharge and “strawberry vulva” or “strawberry cervix”
* Vaginal discharge has increased pH
* Motile protozoa on vaginal wet-mount smear or microscopic examination of urine
* Men: urethral cx or microscopic exam of urine
* Treatment
o Metronidazole 2gm po x 1 (ok in 2nd trimester)
+ GI side effects common
o Abstain from Etoh consumption
o Prolonged Metronidazole for failure

Vaginitides / Urethritides
* Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium
o Implicated in chronic prostatitis and urgency frequency symptoms in women and in up to 40% of NGU
o Tx: Azithromycin po x 1 or doxycycline x 2 wks
* Bacterial vaginosis
o Gardnerella vaginalis, anaerobic orgs, Mycoplasma and/or inhibition of normal vaginal flora
o 10% KOH with vag secretions  fishy odor secondary to release of amines
o Microscopic exam (3 of 4 necessary): (1) thin, white vag d/c (2) vag pH >4.5 (3) clue cells (4) pos whiff test
o Tx: Metro po BID x 7d, Clinda cream x 7d, Metro gel x 5d
* Candida albicans
o Thick, cheesy vaginal discharge usually associated with vulvar irritation and itching
+ Vaginal discomfort, burning, dyspareunia and external dysuria
o Dx: yeast or pseudohyphae on wet prep or gram stain
o Tx: single oral dose of fluconazole (150mg) or OTC antifungal vaginal creams, tablets or suppositories x 1-7 days (butoconazole, clotrimazole, miconazole and terconazole)
References

Update on Infections .ppt