GU / STI

    . Ref: "Infectious Diseases: A Clinical Short Course" by Frederick Southwick

    UTI

    Reference: MKSAP 16

    • Inflammation of the uroepithelium of:
      • Lower urinary tract: cystitis
      • Upper urinary tract: pyelonephritis
    • Women >> Men  (1 in 3 women will have UTI by 20, recurrence 45%)
    • Nosocomial UTI's: develop bacteremia 2-4% of patients, 13% mortality.
      • High antimicrobial resistance

    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.

     

    Acute Pyelonephritis

    • Inflammation of the renal parenchyma from an ascending bladder infection.
    • Symptoms:
      • Flank pain radiating to groin, fever, chills, nausea, vomiting.
      • Concurrent or antecedent symptoms of lower UTI.
    • Labs/Diagnosis:
      • Urine Culture
    • Treatment:
      • If don't require hospitalization:
        • ciprofloxacin 500mg PO BID x7d. (Can also give loading dose cipro 400mg IV)
          • Appropriate in areas where fluoroquinolones resistance rates < 10%.
          • If higher resistance rates, initial single parenteral dose of long-acting cephalosporin (i.e. ceftriaxone 1g) or 24hr dose of aminoglycoside is recommended prior to oral fluoroquinolone therapy
        • Oral Beta-Lactams are less effective than other IV agents in pyelonephritis
      • If require hospitalization, any of:
        • fluoroquinolone (except moxifloxacin doesn't penetrate kidney)
        • aminoglycoside (+/- ampicillin) 
        • extended-spectrum cephalosporin (+/- aminoglycoside)
        • extended-spectrum penicillin (+/- aminoglycoside)
        • Carbapenem

     

    Asymptomatic Bacteuria

    • Defined as presence of bacteria in an ansymptomatic patient.
      • Screening/Treatment is not indicated except in:
        • Screening/treatment for asymptomatic bacteuria indicated ONLY for:
          • Pregnant women
          • Women/men undergoing invasive urologic procedures

     

    Acute Prostatitis

    • In men often bladder symptoms (acute UTI) associated with acute bacterial prostatitis.
    • Symptoms:
      • Sudden febrile illness, chills, low back pain, perineal pain.
      • Symptoms of lower UTI.
    • Diagnosis:
      • Clinical Findings + DRE (edematous tender prostate)
      • Urinalysis: Pyuria + bacteuria.
    • Cause:
      • Enteric gram negative pathogens
    • Treatment:
      • SMX/TMP
      • Alternative: fluoroquinolone (cipro or levo)
      • Treat for 4-6 weeks (important!!!)

    Syphilis

    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!
    • Syphilis Chart.png

    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.

     

     

    Traveller's Diarrhea

    • Definition:

      Occurrence ≥3 unformed stools/day AND

      - abdominal pain or cramps

      - nausea or vomiting

      - bloody stools

      - OR fever and is the most common travel-related infection. 

    • Mild traveller's diarrhea (above), does not require treatment (use fluids, etc..)
    • SEVERE traveller's Diarrhea defined by:
      • > 4 unformed stools/day
      • + fever
      • + blood, pus, or mucus in the stool.
    • Antibiotic treatment may also be a reasonable option in patients with milder illness if it is markedly disruptive to travel plans.
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