GU / STI

Pathogens:

• 85% - E.coli
• 10% - Coag Negative Staphylocci (i.e. Staph saprophyticus) 
• 5% - Other Gram Negatives
• Other:
  • Proteus, Pseudomonas, Klebsiella, Enterobacter (frequent pathogens in recurrent UTI's and structural UI abnormalities).
  • Fungi (Diabetes, Chronic indwelling urinary catheters, Antibiotics)
• Multi-Drug Resistant pathogens more common in hospitalizations, kidney transplants, underlying UI abnormalities, previous UTIs, recent use of abx, or immunocompromised.

Diagnosis

• Classify as:
  • Uncomplicated
    • Infected normal urinary tract.
    • Uncompliated UTI's respond well to antimicrobial treatment.
    • Generally don't need culture, just treat --> improves before culture comes back.
  • Complicated
    • Pregnant Women, or any Men
    • Structural or functional UI abnormalities
      • Often in Infants, older patients, indwelling UI cathers, renal calculi.
    • Patients with spinal cord injuries, DMII, MS, AIDs --> more likely to develop complicated UTI's
    • Complicated UTI's associated with multi-drug resistant pathogens, often require imaging.
• Symptoms
  • Dysuria, Frequency, Nocturia, Enuresis, Urgency, Hematuria, Low back pain, Suprapubic/ flankpain
  • Systemic: fevers, chills, rigors
  • Elderly: Decreased LOC or altered mental status.
• Labs:
  • Microscopic urinalysis
  • Urine Dip for Leukocyte Esterase (pyruia) and Bacterial nitrites
    • Helpful, esp if both positive and patient has signs/symptoms of UTI
    • Regardless may need C&S
  • Uncomplicated UTI: Generally don't need culture, just treat.
  • CT/Ultrasound not necessary, but indicated for pyelonephritis with persistent flank pain or fever after 72hrs of antimicrobial therapy to exclude perinephritc or intra-renal abscess. 
  • Older men with recurrent UTI's: Urologic assessment for tract defects and prostatitis.
• Diagnosis:
  • >10^5 CFU of bacteria / mL of mid-stream clean catch sample => diagnostic
  • >10^2 CFU/mL in women with dysuria and pyuria => diagnostic
  • Contamination if mixed bacteria.
  • Presence of pyuria is enough to diagnose cystitis in young sexually active women (culture only if dx unclear, pregnant or recurred)

Management

• Asymptomatic bacteriuria does not require treatment, EXCEPT: 
  • 1. Pregnant Women
  • 2. Traumatic urologic interventions that result in mucosal bleeding
• Uncomplicated:
  • TMP/SMX (Double Strength 160/800mg BID for 3 days)
    • Avoid if local resistance >20% or previously used in last 3 months to treat UTI.
  • Nitrofurantoin (100mg BID x5d) - fails in pyelonephritis
  • Fosfomycin (3g oral single dose) RARE!!!, but in guidelines.  Lower efficacy, fails in pyelonephritis.
  • NOTE: Fruoroquinolone and B-lactams not recommended as first-line agents.  Alternative agents (worried about resistance, reserve!)
• Pregnant:
  • Amoxycillin
  • Nitrofurantoin
• Recurrent UTI's
  • Often in young healthy women with normal urinary tract, 25% of first-time UTI can recur in 1 month.
  • Often two types of recurrence:
    • Relapse - Same pathogen, recurs in 2 weeks after initial therapy
    • Re-infection - Different strain, or urine culture was sterile between two episodes. (MOST)
  • Risk Factors:
    • Young: vaginal colonization, genetic (non-secreted ABO), frequent sexual activity, spermicide use, new sexual parter, history of UTI's <15y, family history of mother with recurrent UTI.
    • Post-menopausal: incontinence, cystocele, post-void urine residual, history of UTI's before menopause.
  • Management:
    • Avoid spermicides
    • Other Factors (not studied, but recommended)
      • post-coital voiding
      • high fluid intake
      • cranberry juice

    • Post-coital antimicrobial prophylaxis considered for: ≥2 symptomatic infections within 6mo OR ≥3 episodes in 12 months. Initial Duration: 6 months (50% recur in 3mo after d/c prophylaxis) If this occurs, restart prophylaxis x1-2 years with reassessment after that time. Self-diagnosis and self-treatment can be done alternatively (decreases abx use)

    • Can give abx for patient to take.
    • Intra-vaginal extrogen cream (for post-menopausal women with UTI's). 
    • Proteus can be suspected if associated with nephrolithiasis.
    • Generally urologic workup not required for recurrent UTI's; Indications for urologic workup:
      • Suspect structural abnormalities
      • Multiple recurrences with same pathogen

Urinary Catheters 

• Indications:
  • Diagnose pathologic findings of lower UI tract.
  • Urinary retention
  • Monitor fluid status of ill patients if it affects management
  • Manage Stage III-IV pressure ulcers on buttocks.
• Help decrease catheter-related UTI:
  • Sterile catheter insertion, unobstructed urine flow, washing hands.
  • Closed sterile drainage.
  • Maintain collecting bag below level of bladder. (prevent back-flow of contaminated urine)
  • Minimize catheter use
  • DO NOT USE if just "convenient". --> increases risk of UTI.
• NOT HELPFUL:
  • Meatal area clensing
  • Ruotine changing urinary catheters not necessary or effective
  • Do not treat asymptomatic bacteuria!
  • Antiseptic coated UI catheters:
    • Has not been demonstrated to decrease incidence of UTI yet (2014)
    • Only shown to decreases colonization rates, or colonization density of UI catheters.

Intro

• Syphilis spirochete T. pallidum
  • Fragile bacterium 5-20 um long and 0.1um thin.. spirochete.
  • Cannot be visualized by light microscopy (too thin), but can be seen by darkfield or phase microscopy (angles light).
  • Cannot be grown in vitro, hence difficult to detect.  Need to grow in rabbit tissue.
  • Divides slowly.. doubles 30hrs (most pathogenic bacteria is 60min).
  • Natural History of Infection:
    • 1. Primary syphilis
    • 2. Secondary syphilis
    • 3. Latent syphilis
       
• Spread person-to-person:
  • Sexual Intercourse (#1)
  • Placenta passage (congenital disease)
  • Close contact of active lesion (kissing)
  • Blood transfusions
• Risk Factors:
  • Recent epidemiologic study: MSM have 140-fold risk of syphilis than heterosexual.
    • Most common misconception is that unprotected oral sex is safe.
• History
  • Appeared in Europe: called "The Great Pox" - in 16th century.
  • By late 19th century 10% of population infected with syphilis, 575000 cases/year.  With penicillin: dropped to 6500.
  • Infected many historic figures:
    • Henry VIII, Frederick the Great, Pope Alexander VI, Oscar Wilde, Ludwig von Beethoven, Franz Schubert.
  • Homosexual promiscuity in 1970s and 80's: 50% of new cases: homosexual men, many w/ HIV.
  • In 1992 -- aggressive public health measures, and education --> 50,000 cases/year --> 28,000 cases/y.
  • With ART vs. HIV, may men believe HIV is treatable... stoped using condoms.
    • Rates of syphilis climbing!
• 

Primary Syphilis

• Following sexual intercourse --> penetrates skin --> multiples at site of entry
• PMNs and T-lymphocytes penetrate --> inflammation and antibodies --> Skin ulceration --> Painless chancre
• Painless chancre appears ~3 weeks after exposure.

Secondary Syphilis

• Treponemes penetrate skin, and in 30% of pts gain access to lymphatics and blood stream.
• Happens 2-8 weeks post-exposure.  Can be found in blood, skin, CNS, aqueous humor of eye.
• Symptoms
  • 1. Skin rash (pink to red macular, maculopapular, papular or pustular lesions).
    • Often on trunk and spread to extremities. (Proximal to distal)
    • In areas of moisture (groin, axilla) vesicles can coalesce into painless, gray-white, erythematous highly infections plaques "condyloma lata".
    • Patches of alopecia on eyebrows and beard (moth-eaten appearance).
  • 2. Diffuse lymphadenitis 
    • Enlargement of epitrochlear lymph nodes (inside of elbow) is characteristic.
  • 3. Others:
    • Basilar meningitis (CN III, VI, VII, and VIII) - pupils, diplopia, facial weakness, hearling loss, tinnitus.
    • Anterior uveitis
    • Immune complex GN
    • Other organs: hepatitis, synovitis, periostitis, etc....
• Known as "The Great Imitator" !!!
  • Always order syphilis serology in pts with unexplained rash, lymphadenopathy, lymphocytic meningitis, neuro deficits, bone/joint problems, GN, hepatitis.

Latent Syphilis

• After dissemination is controlled by immune system, organisms persist w/o symptoms.
• Spirochets "slow" their metabolism, and doubling time.  Can be latent x20-30yrs.
• "Latent Syphilis" defined as >1yr after primary infection.
• During latent period --> can detect via fluorescent treponemal antibody absorption assay (FTA-ABS).

Tertiary or Late Syphilis

• Pts with syphilis who are untreated have 40% risk of developing late syphilis.
• Three syndromes:
  • 1. Late Neurosyphilis
    • A. Arteritis  (CVA-like)
      • Arteritis in meninges, brain, spinal cord --> multiple small infarcts.
        • Hemiparesis, generalized/focal seizures, aphasia.
      • "Neurosyphilis" also called "Meningovascular syphilis"
      • ALWAYS consider in young patient with CVA.
    • B. Direct damage  (called "General Paresis") - usually 15-20yrs after primary infection
      • 1. Personality Disorder (emotional libaility, paranoia, carelessness, lost judgement etc..)
      • 2. Psychiatric Disturbances (delusions, hallucinations, megalomania)
      • 3. Distinct Neurologic Abnormalities
        • abnormal pupils, Argyll Robertson pupils (no light response, but dilate on convergence). 
        • Hyperactive reflexes, tremors, seizures, aphasias, optic atrophy, etc...
    • C. Demyelination - aka "tabes dorsalis"  (Lower Motor Neuro findings)
      •  Demyelination of Posterior Column, Dorsal roots, and doral root ganglia
      • aka "tabes dorsalis"
      • Ataxic, loss vibration/pain/temp sens, lightning-like pains, reflex loss, impotence, lost bladder, fecal incontinence, Neuropathy -- Charcot's joints.
  • 2. Cardiovascular Syphilis  (10%)
    • Arteritis -  involving feeding vessels of aorta (vasa vasorum) - necrosis of media of vessels, and dilatation of artoa --> aortic regurg, CHF, coronary stenosis (angina).
    • Aneurisms
  • 3. Late benign gummas
    • Granulomatous-like lesions on skin, bone, mucous membranes (less commonly other organs)
    • Chronic non-healing ulcers, bony tenderness/destruction, visceral gummas (on organs).

Diagnosis

• Complicated!!! Cannot culture in vitro (only in animals i.e. Rabits).
• Dark Field Microscopy
  • Primary and Secondary disease only.
  • Often not available... needs skilled technitian.
• Non-Treponemal Tests
  • Two available:
    • VDRL (Venereal Disease Research Laboratory)
    • RPR Titre (Rapid Plasma Reagin)
      • Frequently negative in primary syphilis.
  • Measure levels of antibody to cardiolipin-cholesterol-lecithin antigen. (called "reagin").
  • VDRL and RPR both measure highest dilution of serum that causes antigen to flocculate (clump) on a slide.
  • Prozone phenomenon observed in 2% of cases (Too many antibodies to antigen.. no flocculate observed)
    • Need to keep diluting until flocculate observed.
  • VDRL and RPR usually highest in secondary or early latent disease.
  • With treatment titre decreases to less than 1:4 and in 1/4 becomes negative.
    • Late syphilis --> slower decline in VDRL/RPR titre.
    • In small number of pts, test stays positive permanently. (False positive)
    • False positives especially likely in HIV+ and connective tissue diseases (Many antibodies?).
  • False negatives possible in late syphilis (i.e. neurosyphilis, etc..)
• Specific Treponemal Tests
  • SPECIFIC antibodies to T. pallidum spirochete.
  • FTA-ABS
  • Specific + Sensitive, but persist for life (cannot track treatment).
  • Used to verify positive VDRL or RPR
  • Positive indicates was exposed to syphilis in past.
  • Other tests (TPHA - T. pallidum hemagglutination assay, MHATP micro-hemagglutin).
  • Useful for neurosyphilis, and negative VDRL
  • If CSF taken --> CSF VDRL positive (50%), but FTA-ABS is always reactive.
• Treponemal PCR/DNA (UNDER DEVELOPMENT) - not available.

Treatment

• Penicillin!!  if allergic--> tetracyclines
• Optimal dose/length never been proven
• Slow growth rate --> 2 weeks.
• Jarisch-Herxheimer reaction  (70-90% for 2ndary syphilis, and 10-25% at any stage).
  • After initiation of abx for syphilis
  • Fever, chills, muscle aches, headache,
  • Hyperventilation, tachycardia, flushing, mild hypotension.
  • Lasts 12-24hrs.
  • Can abort with:
    • 1. Prednisone (recommended for pregnant women, cardiovascular syphilis, neurosyphilis)
    • 2. Aspirin q4h for 24-48hrs helps with symptoms.

• Type of Syphilis	Treatment
  Primary or  Secondary	IM Benzathine Penicillin x 1 dose OR (if Penicillin allergy): Doxycycline x 2 weeks.  (if pregnant -> desensitize + tx w/ penicillin)
  Early Latent (within 1yr of exposure)	IM Benzathine Penicillin X1 dose OR (if pen-allergy) Doxycycline x4 weeks.
  Late Latent	IM Benzathine Penicillin x 3 doses? or 3 weeks? OR (if pen-allergy) Doxycycline x4 weeks
  Neurosyphiilis OR Ocular OR HIV + any stage	IV Penicillin G q4h x 10-14d OR IM Procaine Penicillin + Probenecid x 2 weeks.
  Late Syphilis (NOT neurosyphilis. Only if gumma or cardio)	IM Benzathine Penicillin x 3 weeks. OR (if pen-allegic) Doxycycline x 4 weeks.

  
   

• Need to re-examine in 6 months - 1 year.  Treatment failure/re-infection if:
  • Symptoms persist or recur
    OR
  • If VDRL or RPR titres increase by factor of 4.
• If treatment failure: need to test for HIV and LP for neurosyphilis.