Urethritis medical therapy: Difference between revisions

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{{CMG}}; {{AE}}{{CZ}}
{{CMG}}; {{AE}} {{MehdiP}}, {{CZ}}, {{SR}}
 
==Overview==
[[Treatment]] is based on the causative [[pathogen]]. Presumptive [[treatment]] should be initiated while waiting for the [[diagnostic]] confirmation. Once the diagnosis is confirmed, the appropriate [[antibiotic]] regimen should be initiated to reduce the risk of complications. [[Doxycycline]] 100 mg PO bid for 7 days is administered to treat [[Non-gonococcal urethritis|Non-gonococcal Urethritis]], as an alternative therapy [[azithromycin]] 1 g PO in a single dose or [[azithromycin]] 500 mg orally in a single dose; then 250 mg orally daily for 4 days is recommended. For gonococcal urethritis, [[ceftriaxone]] 500 mg IM in a single dose (for [[patients]] weighing ≥150 kg (300 lbs) [[ceftriaxone]] 1 g IM in a single dose), for alternate therapy [[gentamicin]] 240 mg PO in a single dose plus [[azithromycin]] 2 g PO in a single dose, or cefixime 800 mg PO in a single dose is recommended. [[Metronidazole]] 2 g PO in a single dose is used for patients with recurrent and persistent urethritis. Following treatment, patients should be instructed to return for evaluation if symptoms persist or recur after completion of therapy. Providers should be alert to the possibility of chronic [[prostatitis]]/chronic pelvic pain syndrome in male patients experiencing persistent pain ([[perineal]], penile, or [[pelvic]]), discomfort, irritating voiding symptoms, pain during or after ejaculation, or new onset premature ejaculation lasting for >3 months. All sex partners within the preceding 60 days should be referred for evaluation, testing, and empiric treatment with a drug regimen effective against [[Chlamydia]]. Clinicians must report both [[chlamydia]] and [[gonorrhea]] to health departments.


==Medical Therapy==
==Medical Therapy==
Treatment should be initiated as soon as possible after diagnosis.
*Presumptive [[treatment]] should be initiated while waiting for the [[diagnostic]] confirmation.
===Pharmacotherapy===
*Once the diagnosis is confirmed, the appropriate [[antibiotic]] regimen should be initiated to reduce the risk of complications.<ref name="pmid7629982">{{cite journal |vauthors=Stamm WE, Hicks CB, Martin DH, Leone P, Hook EW, Cooper RH, Cohen MS, Batteiger BE, Workowski K, McCormack WM |title=Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men. A randomized double-blind study |journal=JAMA |volume=274 |issue=7 |pages=545–9 |year=1995 |pmid=7629982 |doi= |url=}}</ref>
A variety of drugs may be prescribed based on the cause of the patient's urethritis. Some examples of medications based on causes include:
*[[Erythromycin]] is no longer considered as an alternative choice for [[non-gonococcal urethritis|non-gonococcal urethritis]] due to its [[gastrointestinal]] [[side effect]] and number of doses required.
 
*Due to its lower efficacy [[levofloxacin]] is no longer alternatively used for [[non-gonococcal urethritis|non-gonococcal urethritis]].
*[[Clotrimazole]] (Mycelex) - Trichomonas
*The standard of choice is described below.<ref>{{cite book |last = Bennett |first = John |title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases |publisher = Elsevier/Saunders |location = Philadelphia, PA |year = 2015 |isbn=9781455748013}}</ref><ref name="pmid26042815">{{cite journal |vauthors=Workowski KA, Bolan GA |title=Sexually transmitted diseases treatment guidelines, 2015 |journal=MMWR Recomm Rep |volume=64 |issue=RR-03 |pages=1–137 |year=2015 |pmid=26042815 |doi= |url=}}</ref><ref name="pmid20353145">{{cite journal |vauthors=Brill JR |title=Diagnosis and treatment of urethritis in men |journal=Am Fam Physician |volume=81 |issue=7 |pages=873–8 |year=2010 |pmid=20353145 |doi= |url=}}</ref>
*[[Doxycycline]] (Vibramycin) - [[Chlamydia]]
===Antibiotic Therapy===
*[[Fluconazole]] (Diflucan) - Monilial
*[[Metronidazole]] (Flagyl) - Trichomonas
*[[Nitrofurantoin]] - Bacterial Infection
*[[Nystatin]] (Mycostatin) - Monilial
*[[Co-trimoxazole]], which is a combination of Sulfamethoxazole and Trimethoprim in a ratio of 5 to 1 (Septrin, Bactrim) - Bacterial Infection
 
==Antimicrobial Therapy==


 
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
 
|+
*1. '''Nongonococcal Urethritis'''
! style="background: #4479BA; width: 180px;" | {{fontcolor|#FFFFFF|Disease}}
:* Preferred regimen: [[Azithromycin]] 1 g PO in a single dose {{or}} [[Doxycycline]] 100 mg PO bid for 7 days
! style="background: #4479BA; width: 500px;" | {{fontcolor|#FFFFFF|Treatment}}
:* Alternative regimen (1): [[Erythromycin]] base 500 mg PO qid for 7 days
:* Alternative regimen (2): [[Erythromycin ethylsuccinate]] 800 mg PO qid for 7 days
:* Alternative regimen (3): [[Levofloxacin]] 500 mg PO qd for 7 days
:* Alternative regimen (4): [[Ofloxacin]] 300 mg PO bid for 7 days
 
*2. '''Gonococcal Urethritis'''
 
:* Preferred regimen: [[Ceftriaxone]] 250 mg IM in a single dose {{and}} [[Azithromycin]] 1 g PO in a single dose
:* Alternative regimen: [[Cefixime]] 400 mg PO in a single dose {{and}} [[Azithromycin]] 1 g PO in a single dose (if ceftriaxone is not available)
 
*3. '''Recurrent and Persistent Urethritis'''
:* Preferred regimen: [[Metronidazole]] 2 g PO in a single dose {{or}} [[Tinidazole]] 2 g PO in a single dose {{and}} [[Azithromycin]] 1 g PO in a single dose for 7 days
 
===Gonococcal Urethritis Treatment===
{| style="background: #FFFFFF;"
| valign=top |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center |{{fontcolor|#FFF|Gonococcal Urethritis Treatment}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Preferred Regimen‡'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ceftriaxone]]  250 mg IM x 1 dose'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
| style="padding: 7px 7px; background: #DCDCDC;" |'''[[Non-gonococcal urethritis|Non-gonococcal Urethritis]]'''
| style="padding: 7px 7px; background: #F5F5F5;" |Recommended:
:::::[[Doxycycline]] 100 mg PO bid for 7 days
Alternatives:
:::::[[Azithromycin]] 1 g PO in a single dose 
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''[[Azithromycin]] 1 gm PO x 1 dose for 7 days'''''<br>OR<br>'''''[[Doxycycline]] 100 mg po q12h for 7 days '''''
| style="padding: 7px 7px; background: #DCDCDC;" | '''Gonococcal Urethritis'''
| style="padding: 7px 7px; background: #F5F5F5;" |Recommended:
:::::[[Ceftriaxone]] 500 mg IM in a single dose
:::::For [[patients]] weighing ≥150 kg (300 lbs) [[ceftriaxone]] 1 g IM in a single dose
Alternative:
:::::[[gentamicin]]  240 mg PO in a single dose
:::::::::'''PLUS'''
:::::[[Azithromycin]] 2 g PO in a single dose
:::::::::'''OR'''
:::::[[cefixime]] 800 mg PO in a single dose
|-
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Alternative Regimen'''''
| style="padding: 7px 7px; background: #DCDCDC;" | '''Recurrent and Persistent Urethritis'''
|-
| style="padding: 7px 7px; background: #F5F5F5;" |
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Azithromycin]] 2 gm po x 1 dose'''''
:::::[[Metronidazole]] 2 g PO in a single dose
|-
:::::::::''or''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | OR '''[[Cephalosporins]]''' single dose
:::::[[Tinidazole]] 2 g PO in a single dose
|-
:::::::::'''PLUS'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ceftizoxime]] 500 mg IM''''' <BR> OR <BR> ▸ '''''[[Cefotaxime]] 500 mg IM''''' <BR> OR <BR> ▸ '''''[[Cefoxitin]] 2 gm IM + [[Probenecid]] 1 gm po'''''<BR> OR <BR> ▸ '''''[[Cefixime]] 400 mg po¶''''' 
:::::[[Azithromycin]] 1 g PO in a single dose
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Azithromycin]] 1 gm PO x 1 dose'''''OR'''''[[Doxycycline]] 100 mg po q12h x 7 days'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | OR
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Spectinomycin]]<sup>NUS</sup> 2 gm IM x 1 dose'''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Failure of treatment†
 
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ceftriaxone]] 500 mg IM x 1 dose'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |  ▸ '''''[[Azithromycin]] 2 gm po x 1dose'''''
|-
|-
|}
|}
|}
‡Use combination therapy even if NAAT test is negative for Chlamydiae.<br>
†Treat sex partner, repeat NAAT test after 1 week of cure.<br>
¶If IM cephalisporins are not available.
Proper perineal hygiene should be stressed.  This includes avoiding use of vaginal deodarant sprays and proper wiping after urination and bowel movements.  Intercourse should be avoided until symptoms subside.


===Follow-Up===
===Follow-Up===
*[[HIV]] and [[syphilis]] should be tested in men with [[non-gonococcal urethritis|non-gonococcal urethritis]]. [[HIV]] transmission is facilitated by co-existing [[non-gonococcal urethritis|non-gonococcal urethritis]], however treatment of NGU is the same in [[HIV]] negative or positive [[patients]].
*[[Patients]] should be instructed to return for evaluation if [[symptoms]] persist or recur after completion of [[therapy]]. these [[patients]] should also be tested for [[Mycoplasma genitalium]] and [[Trichomonas vaginalis]]. <ref name="pmid26042815">{{cite journal |vauthors=Workowski KA, Bolan GA |title=Sexually transmitted diseases treatment guidelines, 2015 |journal=MMWR Recomm Rep |volume=64 |issue=RR-03 |pages=1–137 |year=2015 |pmid=26042815 |doi= |url=}}</ref>
*It is recommended for [[male]] [[ patients]] to return after three months for re-testing to rule out [[re-infection]] especially if [[urethritis]] was due to [[chlamydia]], [[gonorrhea]], or [[trichomoniasis]].
*[[Symptoms]] without  [[signs]] or [[laboratory]] evidence of [[urethral inflammation]] are not sufficient for re-treatment.
*Possibilities of [[chronic prostatitis]]/[[chronic]] [[pelvic pain syndrome]] in [[male]] [[patients]] demonstrating persistent [[pain]] ([[perineal]], [[penile]], or [[pelvic]]), discomfort, irritating [[voiding]] [[symptoms]], [[pain]] during or after [[ejaculation]], or new onset [[premature ejaculation]] lasting for >3 months should be evaluated and if present, a [[[urology]] consult should be made.<ref name="pmid26042815">{{cite journal |vauthors=Workowski KA, Bolan GA |title=Sexually transmitted diseases treatment guidelines, 2015 |journal=MMWR Recomm Rep |volume=64 |issue=RR-03 |pages=1–137 |year=2015 |pmid=26042815 |doi= |url=}}</ref><ref name="pmid20353145">{{cite journal |vauthors=Brill JR |title=Diagnosis and treatment of urethritis in men |journal=Am Fam Physician |volume=81 |issue=7 |pages=873–8 |year=2010 |pmid=20353145 |doi= |url=}}</ref>
*[[Clinicians]] must report both [[chlamydia]] and [[gonorrhea]] to [[health]] departments.


Patients should be instructed to return for evaluation if symptoms persist or recur after completion of therapy. Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not a sufficient basis for retreatment. Providers should be alert to the possibility of chronic prostatitis/chronic pelvic pain syndrome in male patients experiencing persistent pain (perineal, penile, or pelvic), discomfort, irritative voiding symptoms, pain during or after ejaculation, or new-onset premature ejaculation lasting for >3 months.
===Treatment of Sexual Partners===
 
*If expedited [[treatment]] is required and permissible by state law for the partner then, in [[chlamydia]] negative partners single 800 mg oral dose of [[cefixime]] is recommended. In [[patients]] where [[chlamydia]] is not excluded recommended [[therapy]] is single 800 mg oral dose of [[cefixime]] plus oral doxycycline 100 mg twice daily for 7 days.
Unless a patient’s symptoms persist or therapeutic noncompliance or reinfection is suspected by the provider, a test-of-cure (i.e., repeat testing 3–4 weeks after completing therapy) is not recommended for persons with documented chlamydia or gonococcal infections who have received treatment with recommended or alterative regimens. However, because men with documented chlamydial or gonococcal infections have a high rate of reinfection within 6 months after treatment (251,252), repeat testing of all men diagnosed with chlamydia or gonorrhea is recommended 3–6 months after treatment, regardless of whether patients believe that their sex partners were treated (251).
*All sex partners within the preceding 60 days should be referred for evaluation, testing, and [[empiric treatment]] with a [[drug]] regimen effective against [[Chlamydia]].
 
*A specific [[diagnosis]] might facilitate partner referral. Therefore, testing for [[gonorrhea]] and [[chlamydia]] [[infection]] is encouraged. A substantial proportion of [[female]] partners of males with non-chlamydial, [[non-gonococcal urethritis]] are [[infected]] with [[chlamydia]].
===Partner Referral===
*Partner [[treatment]] is recommended for [[males]] with [[non-gonococcal urethritis]] regardless of whether a specific [[etiology]] is identified.<ref name="pmid26042815">{{cite journal |vauthors=Workowski KA, Bolan GA |title=Sexually transmitted diseases treatment guidelines, 2015 |journal=MMWR Recomm Rep |volume=64 |issue=RR-03 |pages=1–137 |year=2015 |pmid=26042815 |doi= |url=}}</ref><ref name="pmid20353145">{{cite journal |vauthors=Brill JR |title=Diagnosis and treatment of urethritis in men |journal=Am Fam Physician |volume=81 |issue=7 |pages=873–8 |year=2010 |pmid=20353145 |doi= |url=}}</ref>
 
A specific diagnosis might facilitate partner referral. Therefore, testing for gonorrhea and chlamydia is encouraged. Because a substantial proportion of female partners of males with nonchlamydial NGU are infected with chlamydia, partner management is recommended for males with NGU regardless of whether a specific etiology is identified. All sex partners within the preceding 60 days should be referred for evaluation, testing, and empiric treatment with a drug regimen effective against chlamydia. Expedited partner treatment and patient referral are alternative approaches to treating partners (71).
 
===Recurrent Urethritis===
Objective signs of urethritis should be present before the initiation of antimicrobial therapy. In persons who have persistent symptoms after treatment without objective signs of urethritis, the value of extending the duration of antimicrobials has not been demonstrated. Persons who have persistent or recurrent urethritis can be retreated with the initial regimen if they did not comply with the treatment regimen or if they were reexposed to an untreated sex partner. Persistent urethritis after doxycycline treatment might be caused by doxycycline-resistant U. urealyticum orM. genitalium. T. vaginalis is also known to cause urethritis in men; a urethral swab, first void urine, or semen for culture or a NAAT (PCR or TMA) on a urethral swab or urine can be performed. If compliant with the initial regimen and re-exposure can be excluded, the following regimen is recommended while awaiting the results of the diagnostic tests.
 
{| style="background: #FFFFFF;"
| valign=top |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Recurrent Non-gonococal Urethritis }}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Preferred Regimen'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[ Metronidazole]] 2 gm po single dose'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Azithromycin]] 1 gm po x 1 dose'''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Alternative Regimen'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Tinidazole]] 2 gm po x 1 dose'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Azithromycin]] 1 gm po x 1 dose'''''
|-
|}
|}
 
Studies involving a limited number of patients who experienced NGU treatment failures have demonstrated that Moxifloxacin 400 mg orally once daily for 7 days is highly effective against M. genitalium (253,254). Men with a low probability of T. vaginalis (e.g., MSM) are unlikely to benefit from the addition of metronidazole or tinidazole.
 
Urologic examinations usually do not reveal a specific etiology for urethritis. A four-glass Meares-Stamey lower-urinary-tract localization procedure (or four-glass test) might be helpful in localizing pathogens to the prostate (255). A substantial proportion of men with chronic nonbacterial prostatitis/chronic pelvic pain syndrome have evidence of urethral inflammation without any identifiable microbial pathogens. Estimates vary considerably depending on the source and sensitivity of the assay, but one study demonstrated that in 50% of men with this syndrome, ≥5 WBCs per high-power field were detected in expressed prostatic secretions (256). Referral to a urologist should be considered for men who experience pain for more than 3 months within a 6-month period.
 
If men require treatment with a new antibiotic regimen for persistent urethritis and a sexually transmitted agent is the suspected cause, all partners in the past 60 days before the initial diagnosis and any interim partners should be referred for evaluation and appropriate treatment.
 
===Special Considerations===
 
'''HIV Infection'''
 
Gonococcal urethritis, chlamydial urethritis, and nongonococcal, nonchlamydial urethritis might facilitate HIV transmission. Patients who have NGU and also are infected with HIV should receive the same treatment regimen as those who are HIV negative.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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Latest revision as of 15:57, 27 August 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2], Cafer Zorkun, M.D., Ph.D. [3], Sujit Routray, M.D. [4]

Overview

Treatment is based on the causative pathogen. Presumptive treatment should be initiated while waiting for the diagnostic confirmation. Once the diagnosis is confirmed, the appropriate antibiotic regimen should be initiated to reduce the risk of complications. Doxycycline 100 mg PO bid for 7 days is administered to treat Non-gonococcal Urethritis, as an alternative therapy azithromycin 1 g PO in a single dose or azithromycin 500 mg orally in a single dose; then 250 mg orally daily for 4 days is recommended. For gonococcal urethritis, ceftriaxone 500 mg IM in a single dose (for patients weighing ≥150 kg (300 lbs) ceftriaxone 1 g IM in a single dose), for alternate therapy gentamicin 240 mg PO in a single dose plus azithromycin 2 g PO in a single dose, or cefixime 800 mg PO in a single dose is recommended. Metronidazole 2 g PO in a single dose is used for patients with recurrent and persistent urethritis. Following treatment, patients should be instructed to return for evaluation if symptoms persist or recur after completion of therapy. Providers should be alert to the possibility of chronic prostatitis/chronic pelvic pain syndrome in male patients experiencing persistent pain (perineal, penile, or pelvic), discomfort, irritating voiding symptoms, pain during or after ejaculation, or new onset premature ejaculation lasting for >3 months. All sex partners within the preceding 60 days should be referred for evaluation, testing, and empiric treatment with a drug regimen effective against Chlamydia. Clinicians must report both chlamydia and gonorrhea to health departments.

Medical Therapy

Antibiotic Therapy

Disease Treatment
Non-gonococcal Urethritis Recommended:
Doxycycline 100 mg PO bid for 7 days

Alternatives:

Azithromycin 1 g PO in a single dose
Gonococcal Urethritis Recommended:
Ceftriaxone 500 mg IM in a single dose
For patients weighing ≥150 kg (300 lbs) ceftriaxone 1 g IM in a single dose

Alternative:

gentamicin 240 mg PO in a single dose
PLUS
Azithromycin 2 g PO in a single dose
OR
cefixime 800 mg PO in a single dose
Recurrent and Persistent Urethritis
Metronidazole 2 g PO in a single dose
or
Tinidazole 2 g PO in a single dose
PLUS
Azithromycin 1 g PO in a single dose

Follow-Up

Treatment of Sexual Partners

References

  1. Stamm WE, Hicks CB, Martin DH, Leone P, Hook EW, Cooper RH, Cohen MS, Batteiger BE, Workowski K, McCormack WM (1995). "Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men. A randomized double-blind study". JAMA. 274 (7): 545–9. PMID 7629982.
  2. Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.
  3. 3.0 3.1 3.2 3.3 Workowski KA, Bolan GA (2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR Recomm Rep. 64 (RR-03): 1–137. PMID 26042815.
  4. 4.0 4.1 4.2 Brill JR (2010). "Diagnosis and treatment of urethritis in men". Am Fam Physician. 81 (7): 873–8. PMID 20353145.