Clinical Scenario # 1Getachew, a 22 year old man, comes to your office

complaining of pain when he urinates for the past 3 days. This morning he noticed a “drip” from the tip of his penis.

He has had unprotected sex with four new female partners in the past 4 weeks, most recently 6 days ago.

a. What is your diagnosis?

b. What are the pathogens responsible for the disease?

c. How do you treat him?

urethritisLearning Objectives:

Upon completion of this content you will be able to:

1. List the etiologic agents of urethritis.

2. Describe the clinical manifestations and sequelae of urethritis.

3. State the clinical and laboratory criteria for the diagnosis of urethritis. 4. Summarize the clinical management of patients with urethritis to

include: recommended diagnostic tests , treatment, follow-up, Patient counseling and partner management.

urethritis Definition:

- Clinical syndrome:

- Inflammation of the urethra, manifested by 1. urethral discharge or without UD, UD can be mucoid, mucopurulent or purulent

2. dysuria, urethral pruritus or meatal erythema

- Microscopic definition: Presence of >4 PMNs/oil immersion field ( x 1000) on a smear

Etiology A. Gonococcal Urethritis: ~ 20% of urethritis are caused by Neisseria gonorrhoeae.

B. Nongonococcal Urethritis (NGU): ~80% of cases of urethritis

Etiologic Agents of NGU Based on Culture Chlamydia trachomatis 15- 40%

Ureaplasma urealyticum 10---40%

Mycoplasma genitalium 15---25%

Trichomonas vaginalis Up to 13%

HSV Rare Candida albicans < 1%

Miscellaneous bacteria < 1% Other (E. Coli, Haemophilus species,Gm positives) ? Unknown 20—30%

clinical features GU NGU

Incubation period 2-8 days 7-14 days

Onset Abrupt Gradual

Dysuria Severe Mild

Discharge quality Purulent Mucoid

Discharge quantity More Less

NB: a considerable overlap may exist between these presentations

General features of GU and NGU

III. Clinical Manifestations

Remember the following

- Distinguishing on clinical ground alone GU from NGU is not reliable ( at best, 50% accurate)

- It does not also distinguish CT positive NGU from CT negative NGU

- 15-40 % of GU also harbor CT.

Therefore Rx for GU should always include TX for CT

Gonnorhea and chlamydia Trachomatis

Sites of infection local complication general complications

Classi Sites Local general General

In Men 1.Tysonitis 1. arthritis

2.paraurethral 2. anterior uveitis duct infection 3. Littritis 3 Myocarditis Anterior 4. Periurethral 4. Endocarditis urethra abscess 5. Cowperitis 5. Pericarditis

6. Cowper ‘s gland 6. meningitis Abscess 7. Ureth. Stricture 7. DGI

Gonorrhea ( cont.)

Sites Local General Prostatitis 2.Posterior acute/ chronic

urethra Prostatic Abscess Same Vesiculitis Epididymitis TrigonitisIn women:

Parametritis Myocarditis 1.cervix Uteri Salpingo-oophoritis Pericarditis Endocarditis

Pelvic abscess Meningitis Pelvic peritonitis DGI Perihepatitis Arthritis Anterior uveitis

2.Urethra Skenitis Bartholinitis

In both sex

1. Anorectum Proctitis 2. Conjuctivae Conjuctivitis 3. Oropharynx Pharyngitis

In Children

1. Vulvovagina Vulvovaginitis 2. Anorectum Proctitis 3.Conjuctivae Conjuctivitis, Suppurative Panophthalmitis and Blindness

Clinical Manifestations (cont”d) B. complications of urethritis: 1. Epididymitis is an infrequent (<3%) complication.

2. Reiter’s syndrome complicates 1-2% of NGU (Chlamydia Infections). 3. DGI occurs very rarely as a result of GU. dermatitis-arthritis syndrome

Asymptomatic urethritis: ~ 1/3 of men with NGU 10-15% of men with GU

4.Conjuctivitis: uni- or bi-lateral ocular involvement as a result of self-

inoculation a) Chlamydial: follicular conjunctivitis with onset 1-2

wks following an exposure.

b) Gonococcal: mucopurulent with copious discharge and conjuctival swelling occurring 24-48 hrs after exposure.

How to test

DEFINITELY NOT THIS WAY

Diagnosis

Diagnosis is based onDiagnosis is based on (Documentaion Of Any ONE OF the followings)

1. History : Symptoms: UD, Dysuria, Meatal itching

2. Physical examination: confirmation of the presence of UD a. Optimally, exam should occur two or more hrs post-

urination.

b. Examine urethra for discharge:

if no UD, stripping/milking of the urethra may increase the yield of the examination.

3. Laboratory findings:

A. Gram stain: urethral swab specimen 1. look for 5 or more WBC/oil-immersion field (x1000) , qualifies as urethritis.

PMNs ≥ 5PMNs ≥ 5

Diagnosis cont‘d2. Look for presence of Gram-negative intracellular diplococci (GNID), the presence of which is suggestive of GU

B. First-catch Urine (FVU): 1. 10 or more WBC/high powered field (400) qualifies as urethritis on sediment of first 10-15 ml of urine.

2. Leukocyte esterase test (LET) is less sensitive than FVU testing, but easier to perform on fresh-spun urine.

Diagnosis ( cont’d )

C . Test for GC and Chlamydia (CT) with : 1. Culture: For GC-Non selective media-Chocolate-Agar media Selective media-Thayer-martin, NY modified media

If possible do culture for CT using McCoy cells Specimen collection: e For GC : Okay to culture urethral exudates. For CT insert swab 2-4 cm for optimal results.

2. Non culture method: DNA amplification testing Assays Include: NAAT : PCR, LCR, specimens: urethral exudates, Urine For urine based test, collect the first 10-15 ml of urine.

Diagnosis cont’d

D. If diagnosis is equivocal (e.g., symptoms but no signs), the decision to empirically treat vs. treat based on test results

is made on an individual basis (i.e., high-risk pts unlikely to return for follow up, etc.).

Treatment

A. Gonococcal urethritis( treat for co-existent chlamydial infection):

Recommended regimens to cover GC; 1. cefixime 400 mg po x1 2. ceftriaxone 125 mg IM x1 3. Ciprofloxacin 500 mg pox1 4. Ofloxacin 400 mg po x1 5. Levofloxacin 250 mg po x1 6. Spectinomycin 2 gm IM x 1

Quinolones should be avoided whose infection may have originated from an area where quinolone resistance is common (e.g., Asia , the Pacific Islands, Hawaii).

B. Chlamydial Urethritis and NGU : 1. Recommended regimens: a) Azithromycin 1 gm orally x 1 b) Doxycycline 100 mg b.i.d. x7 days efficacy of rx for CT urethritis 95-100%, and non-CT

NGU 60-80%

2. Alternative regimens:

a) Erythromycin Base 500 mg qid x 7 days b) Erythromycin ethylsuccinate 800 mg qid x7

days c) Ofloxacin 300 mg bid x 7 days d) levofloxacin 500 mg q.d. po x 7 days

Rx of Gonococcal infections at selected Sites

Pharyngitis : Preferred regimens are: Ceftriaxone, 125 mg IM or Ciprofloxacin,500 mg po both with doxycycline 100 mg po bid x 7 days Or Azithromycin,1 gm po ) Conjuctivitis: Ceftriaxone, 1 gm IM x 1 PLUS lavage

of infected eyes x 1 DGIs: a. Hospitalization may be needed b.Recommended Rx: Cefttiaxone 1 gm IV or IM daily

DDuurraattiioonn

Treatment of DGIAlternative regimens:

cefotaxime, 1 gm IV q8h or Ceftizoxime, 1 gm IV q8h or Spectinomycin, 2 gm IM q12h ( allergy to betalactam drugs)

Duration of Parenteral rx: 24-48 hr after symptoms resolve, then : cefixime, 400 mg po bid or Ciprofloxacin, 500 mg, po bidDuration of oral Rx : to complete a full week of antibiotic Rx

Meningitis : Ceftriaxone, 1-2 gm IV q12h X 10-14 days Endocarditis: Ceftriaxone, 1-2 gm IV q12h x4 wk

Salpingitis:

Treatment cont’d

C. Other management considerations

1. Follow-up: pts should be instructed to return for evaluation if symptoms persist or recur after completion of therapy.

2. Referral Partner: ● Chlamydia can be isolated from 30-60%. ● Pts should refer all sexual partners of the past 60 days for evaluation and Rx. ● Testing for gonorrhea and chlamydia is encouraged.

3. Recurrent or persistent urethritis

Recurrent or persistent urethritis after standard 1st-line pharmacotherapy:

Pts should be evaluated for a) Possible causes of persistent urethritis: 1) Re-infection : a. Re-exposure to untreated partner b. Infection acquired from new partner 2) Medication not taken correctly / not completed 3) Persistent infection due to: a) Inadequate drug tissue levels( prostatic involvement ?) b) Resistant pathogen( quinolone-resistant gonorrhea; tetracycline resistant ureaplasma / mycoplasma. c) HSV d) trichomoniasis e) Non-infectious etiologies. f) Intraurethral growth( e.g., condyloma)

Treatment ( cont’d )

b) Approach to the patient:

1) Question pt closely regarding: re exposure during or after Rx, compliance with oral regimen, and concurrent Rx of partner (s) . 2) Re-examine and establish objective evidence of urethritis

by urethral Gram stain, urine sediment or LET.

3) Examine for trichomonas with saline wet mount,

4) Culture if wet mount negative on spun urine or urethral swab.

Presumptive therapy may be warranted even in the face of normal wet mount.

C) Treatment of persistent/ recurrent urethritis:

1) Pts should be treated with the initial regimen if: - they failed to comply with the Rx regimen or - they were re-exposed to an treated sex partner.

2) If pt has been compliant and not re-exposed, consider: a) Metronidazole 2 gm po single dose PLUS b) Erythromycin base 500 mg po 4 times a day for 7 days OR c) Erythromycin ethyl succinate 800 mg po qid for 7 days 3) Pts with s/s of persistent urethritis following re-treatment,

where re-infection is unlikely, should be referred to a urologist for further evaluation and management

Prevention

A. Partner management: 1. all sex partners within the preceding 60 days should be

evaluated and treated. 2. Testing for gonorrhea and chlamydia is encouraged.

B. Patient counseling/ education: Nature of the infection: 1. Explain urethritis as a syndrome vs. an infection, specific

disease etiology if known, routes of transmission and acquisition.

2) Explain to pt why they are being treated, including possible sequelae to self and partners (e.g., increased HIV susceptibility, PID/infertility/ectopic pregnancy in female partners).

3) Explain need for referral/ treatment of sex partners to establish etiology an possible treatment. A specific diagnosis of STD should prompt treatment of partners