Syphilis management for primary and secondary stages: Difference between revisions

Jump to navigation Jump to search
No edit summary
 
(41 intermediate revisions by 10 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{CMG}}
{{CMG}}{{AE}}{{AA}}
{{Syphilis}}
{{Syphilis}}


==Overview==
==Overview==
[[Penicillin#Benzylpenicillin (penicillin G)|Parenteral penicillin G]] has been used effectively for more than 50 years to achieve clinical resolution (i.e., the healing of lesions and prevention of sexual transmission) and to prevent late sequelae. However, no comparative trials have been adequately conducted to guide the selection of an optimal penicillin regimen (i.e., the dose, duration, and preparation). Substantially fewer data are available for non-penicillin regimens.
[[Penicillin#Benzylpenicillin (penicillin G)|Parenteral penicillin G]] has been an effective regimen to achieve clinical resolution and to prevent late [[sequelae]] of [[syphilis]].


==Management of Primary and Secondary Stages==
==Management for Primary and Secondary Syphilis==
* Penicillin G is effectively used to achieve clinical resolution.
* [[Penicillin G]] is effectively used to achieve clinical resolution and to prevent late sequeale.<ref name=cdc2015>http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016</ref>
*Available data demonstrate that additional doses of [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin G]], [[amoxicillin]], or other antibiotics in ([[Syphilis pathophysiology#Primary syphilis|primary]], [[Syphilis pathophysiology#Secondary syphilis|secondary]], and [[Syphilis pathophysiology#Latent syphilis|early latent syphilis]] do not enhance efficacy, regardless of HIV status.
* Additional doses of [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin G]], [[amoxicillin]], or other antibiotics are not known to enhance efficacy of the recommended regimen in the management of [[Syphilis pathophysiology#Primary syphilis|primary]] and [[Syphilis pathophysiology#Secondary syphilis|secondary]], regardless of [[Human Immunodeficiency Virus (HIV)|HIV]] status.


*Infants and children aged more than 1 month diagnosed with syphilis should have a [[Syphilis laboratory tests#CSF analysis|CSF examination]] to detect [[Neurosyphilis#Clinical presentation: Four clinical types|asymptomatic neurosyphilis]], and birth & maternal medical records should be reviewed to assess whether such children have congenital or acquired syphilis. Children with acquired [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis should be evaluated (e.g., through consultation with child-protection services) and treated by using the following pediatric regimen.
===CDC Recommendations: Pharmacotherapy for Adults<ref name="urlSexually Transmitted Diseases Treatment Guidelines, 2010">{{cite web|url=http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm |title=Sexually Transmitted Diseases Treatment Guidelines, 2010 |format= |work= |accessdate=2012-12-19}}</ref>===


==CDC Recommendations: Pharmacotherapy [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm]==
{| style="background: #FFFFFF;"
{{cquote|
| valign=top |
====Recommended Regimen for Adults====
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
'''1.''' [[Penicillin#Benzylpenicillin (penicillin G)|Benzathine penicillin G]] 2.4 million units IM in a single dose.
! 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|Primary Syphilis}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''Preferred Regimen'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ Benzathine [[Penicillin G]] (Bicillin L-A) 2.4 million units IM 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 | ▸ [[Doxycycline]] 100 mg po bid x 14 days
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | OR
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ [[Tetracycline]] 500 mg po qid x 14 days
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | OR
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ ''[[Ceftriaxone]] 1 gm IM/IV q24h x 10 -14 days''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |OR
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ [[Azithromycin]]2 gm po x 1 dose
|-


====Recommended Regimen for Infants and Children====
|}
'''1.''' [[Penicillin#Benzylpenicillin (penicillin G)|Benzathine penicillin G]] 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose.}}
|}


==Other Management Considerations==
*'''Infants and children aged >/= 1 month'''
====HIV-infection====
** Upon diagnosis with syphilis, birth and maternal medical records should be reviewed for assessment of congenital or acquired syphilis.
*All persons who have syphilis '''''should be tested''''' for [[HIV|HIV infection]].  
** Those with [[Syphilis pathophysiology#Primary syphilis|primary]] and [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis should also be evaluated for sexual abuse, through consultation with child-protection service.
 
===CDC Recommendations: Pharmacotherapy for Infants and Children===
 
{| 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|Primary Syphilis}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''Preferred Regimen'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ Benzathine [[Penicillin G]] (Bicillin L-A) 50,000 units/kg body weight IM, up to the adult dose of 2.4 million units x 1 dose
|-
 
|}
|}
 
===Other Management Considerations===
====HIV Infection====
*All persons who have syphilis should be tested for [[HIV|HIV infection]].  


*In geographic areas in which the prevalence of HIV is high, persons who have [[Syphilis pathophysiology#Primary syphilis|primary syphilis]] should be retested for HIV after 3 months if the first HIV test result was negative.
*In geographic areas in which the prevalence of HIV is high, persons who have [[Syphilis pathophysiology#Primary syphilis|primary syphilis]] should be retested for HIV after 3 months if the first HIV test result was negative.


====Neurosyphilis====
====Neurosyphilis====
*Patients who have syphilis and [[Neurosyphilis#Clinical presentation: Four clinical types|symptoms or signs suggesting neurologic disease]] (e.g., [[meningitis]] and [[hearing loss]]) or ophthalmic disease (e.g., [[uveitis]], [[iritis]], [[neuroretinitis]], and [[optic neuritis]]) should have an evaluation that includes [[Syphilis laboratory tests#CSF analysis|CSF analysis]], [[Syphilis physical examination#Ophthalmic examination|ocular slit-lamp ophthalmologic examination]], and otologic examination. Treatment should be guided by the results of this evaluation.
*Patients who have syphilis and [[Neurosyphilis#Clinical presentation: Four clinical types|symptoms or signs suggesting neurologic disease]] (e.g., [[meningitis]] and [[hearing loss]]) or signs of [[Syphilis natural history, complications and prognosis#complications|ocular syphilis]] (e.g., [[uveitis]], [[iritis]], [[neuroretinitis]], and [[optic neuritis]]) should have an evaluation that includes [[Syphilis laboratory findings#CSF analysis|CSF analysis]], thorough cranial nerve examination, ocular slit-lamp and ophthalmologic examination. Treatment should be guided by the results of this evaluation.


*Invasion of [[CSF]] by T. pallidum accompanied by [[Syphilis laboratory tests#CSF analysis|CSF laboratory abnormalities]] is common among adults who have [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis.<ref name="pmid3056164">Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH (1988) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3056164 Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment.] ''Ann Intern Med'' 109 (11):855-62. PMID: [http://pubmed.gov/3056164 3056164]</ref> Therefore, in the absence of clinical neurologic findings, no evidence exists to support variation from the recommended treatment regimen for early syphilis.  
*Invasion of [[CSF]] by ''T. pallidum'' accompanied by CSF laboratory abnormalities is common among adults who have [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis.<ref name="pmid3056164">Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH (1988) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3056164 Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment.] Ann Intern Med 109 (11):855-62. PMID: [http://pubmed.gov/3056164 3056164]</ref> Therefore, in the absence of clinical neurologic findings, no evidence exists to support variation from the recommended treatment regimen for early syphilis.  


*[[Neurosyphilis#Clinical presentation: Four clinical types|Symptomatic neurosyphilis]] develops in only a limited number of persons after treatment with the penicillin regimens recommended for [[Syphilis pathophysiology#Primary syphilis|primary]] and [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis. Therefore, unless clinical signs or symptoms of neurologic or ophthalmic involvement are present or treatment failure is documented, routine [[Syphilis laboratory tests#CSF analysis|CSF analysis]] is not recommended for persons who have [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]].
*[[Neurosyphilis#Clinical presentation: Four clinical types|Symptomatic neurosyphilis]] develops in only a limited number of persons after treatment with the penicillin regimens recommended for [[Syphilis pathophysiology#Primary syphilis|primary]] and [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis. Therefore, unless clinical signs or symptoms of neurologic or ophthalmic involvement are present or treatment failure is documented, routine [[Syphilis laboratory findings#CSF analysis|CSF analysis]] is not recommended for persons who have [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis.


==Special considerates==
===Special Considerations===
====Penicillin Allergy: Alternative regimen====
====Penicillin Allergy: Alternative Regimen====
*Data to support the use of alternatives to [[penicillin]] in the treatment of [[Syphilis pathophysiology#Primary syphilis|early syphilis]] are limited. However, several therapies might be effective in non-pregnant, penicillin-allergic patients who have [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis.  
*Data to support the use of alternatives to [[penicillin]] in the treatment of [[Syphilis pathophysiology#Primary syphilis|early syphilis]] are limited. However, several therapies may be effective in non-pregnant, penicillin-allergic patients who have [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis.  


*'''[[Doxycycline]]''' 100 mg orally twice daily for 14 days <ref name="pmid16477545">Ghanem KG, Erbelding EJ, Cheng WW, Rompalo AM (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16477545 Doxycycline compared with benzathine penicillin for the treatment of early syphilis.] ''Clin Infect Dis'' 42 (6):e45-9. [http://dx.doi.org/10.1086/500406 DOI:10.1086/500406] PMID: [http://pubmed.gov/16477545 16477545]</ref><ref name="pmid18823862">Wong T, Singh AE, De P (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18823862 Primary syphilis: serological treatment response to doxycycline/tetracycline versus benzathine penicillin.] ''Am J Med'' 121 (10):903-8. [http://dx.doi.org/10.1016/j.amjmed.2008.04.042 DOI:10.1016/j.amjmed.2008.04.042] PMID: [http://pubmed.gov/18823862 18823862]</ref> and '''[[tetracycline]]''' (500 mg four times daily for 14 days) are regimens that have been used for many years.  
*[[Doxycycline]] 100 mg orally twice daily for 14 days<ref name="pmid16477545">Ghanem KG, Erbelding EJ, Cheng WW, Rompalo AM (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16477545 Doxycycline compared with benzathine penicillin for the treatment of early syphilis.] Clin Infect Dis 42 (6):e45-9. [http://dx.doi.org/10.1086/500406 DOI:10.1086/500406] PMID: [http://pubmed.gov/16477545 16477545]</ref><ref name="pmid18823862">Wong T, Singh AE, De P (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18823862 Primary syphilis: serological treatment response to doxycycline/tetracycline versus benzathine penicillin.] Am J Med 121 (10):903-8. [http://dx.doi.org/10.1016/j.amjmed.2008.04.042 DOI:10.1016/j.amjmed.2008.04.042] PMID: [http://pubmed.gov/18823862 18823862]</ref> and [[tetracycline]] (500 mg four times daily for 14 days) are regimens that have been used for many years.  


*Compliance is likely to be better with [[doxycycline]] than [[tetracycline]], because tetracycline can cause gastrointestinal side effects.  
*Compliance is likely to be better with [[doxycycline]] than [[tetracycline]], because tetracycline can cause gastrointestinal side effects.  


*Although limited clinical studies, along with biologic and pharmacologic evidence, suggest that '''[[ceftriaxone]]''' (1 g daily either IM or IV for 10-14 days) is effective for treating [[Syphilis pathophysiology#Primary syphilis|early syphilis]], the optimal dose and duration of ceftriaxone therapy have not been defined.<ref name="pmid3171231">Hook EW, Roddy RE, Handsfield HH (1988) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3171231 Ceftriaxone therapy for incubating and early syphilis.] ''J Infect Dis'' 158 (4):881-4. PMID: [http://pubmed.gov/3171231 3171231]</ref>  
*Clinical studies, though limited, along with biologic and pharmacologic evidence suggest that [[ceftriaxone]] (1 g daily either IM or IV for 10-14 days) is effective for treating [[Syphilis pathophysiology#Primary syphilis|early syphilis]]; the optimal dose and duration of ceftriaxone therapy have not been defined.<ref name="pmid3171231">Hook EW, Roddy RE, Handsfield HH (1988) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3171231 Ceftriaxone therapy for incubating and early syphilis.] J Infect Dis 158 (4):881-4. PMID: [http://pubmed.gov/3171231 3171231]</ref>  


*'''[[Azithromycin]]''' as a single 2-g oral dose is effective for treating [[Syphilis pathophysiology#Primary syphilis|early syphilis]].<ref name="pmid16177249">Riedner G, Rusizoka M, Todd J, Maboko L, Hoelscher M, Mmbando D et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16177249 Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis.] ''N Engl J Med'' 353 (12):1236-44. [http://dx.doi.org/10.1056/NEJMoa044284 DOI:10.1056/NEJMoa044284] PMID: [http://pubmed.gov/16177249 16177249]</ref><ref name="pmid12172535">Hook EW, Martin DH, Stephens J, Smith BS, Smith K (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12172535 A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis.] ''Sex Transm Dis'' 29 (8):486-90. PMID: [http://pubmed.gov/12172535 12172535]</ref><ref name="pmid20402591">Hook EW, Behets F, Van Damme K, Ravelomanana N, Leone P, Sena AC et al. (2010) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=20402591 A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis.] ''J Infect Dis'' 201 (11):1729-35. [http://dx.doi.org/10.1086/652239 DOI:10.1086/652239] PMID: [http://pubmed.gov/20402591 20402591]</ref> However, T. pallidum chromosomal mutations associated with azithromycin resistance and treatment failures have been documented in several geographical areas in the United States.<ref name="pmid15247355">Lukehart SA, Godornes C, Molini BJ, Sonnett P, Hopkins S, Mulcahy F et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15247355 Macrolide resistance in Treponema pallidum in the United States and Ireland.] ''N Engl J Med'' 351 (2):154-8. [http://dx.doi.org/10.1056/NEJMoa040216 DOI:10.1056/NEJMoa040216] PMID: [http://pubmed.gov/15247355 15247355]</ref><ref name="pmid16392078">Mitchell SJ, Engelman J, Kent CK, Lukehart SA, Godornes C, Klausner JD (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16392078 Azithromycin-resistant syphilis infection: San Francisco, California, 2000-2004.] ''Clin Infect Dis'' 42 (3):337-45. [http://dx.doi.org/10.1086/498899 DOI:10.1086/498899] PMID: [http://pubmed.gov/16392078 16392078]</ref> As such, the use of [[azithromycin]] should be used with caution only when treatment with [[penicillin]] or [[doxycycline]] is not feasible. [[Azithromycin]] should not be used in MSM or pregnant women.  
*[[Azithromycin]] as a single 2-g oral dose is effective for treating [[Syphilis pathophysiology#Primary syphilis|early syphilis]].<ref name="pmid16177249">Riedner G, Rusizoka M, Todd J, Maboko L, Hoelscher M, Mmbando D et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16177249 Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis.] N Engl J Med 353 (12):1236-44. [http://dx.doi.org/10.1056/NEJMoa044284 DOI:10.1056/NEJMoa044284] PMID: [http://pubmed.gov/16177249 16177249]</ref><ref name="pmid12172535">Hook EW, Martin DH, Stephens J, Smith BS, Smith K (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12172535 A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis.] Sex Transm Dis 29 (8):486-90. PMID: [http://pubmed.gov/12172535 12172535]</ref><ref name="pmid20402591">Hook EW, Behets F, Van Damme K, Ravelomanana N, Leone P, Sena AC et al. (2010) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=20402591 A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis.] J Infect Dis 201 (11):1729-35. [http://dx.doi.org/10.1086/652239 DOI:10.1086/652239] PMID: [http://pubmed.gov/20402591 20402591]</ref> However, ''T. pallidum'' chromosomal mutations associated with azithromycin resistance and treatment failures have been documented in several geographical areas in the United States.<ref name="pmid15247355">Lukehart SA, Godornes C, Molini BJ, Sonnett P, Hopkins S, Mulcahy F et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15247355 Macrolide resistance in Treponema pallidum in the United States and Ireland.] N Engl J Med 351 (2):154-8. [http://dx.doi.org/10.1056/NEJMoa040216 DOI:10.1056/NEJMoa040216] PMID: [http://pubmed.gov/15247355 15247355]</ref><ref name="pmid16392078">Mitchell SJ, Engelman J, Kent CK, Lukehart SA, Godornes C, Klausner JD (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16392078 Azithromycin-resistant syphilis infection: San Francisco, California, 2000-2004.] Clin Infect Dis 42 (3):337-45. [http://dx.doi.org/10.1086/498899 DOI:10.1086/498899] PMID: [http://pubmed.gov/16392078 16392078]</ref> As such, the use of [[azithromycin]] should be used with caution only when treatment with [[penicillin]] or [[doxycycline]] is not feasible. [[Azithromycin]] should not be used in MSM or pregnant women.  


*Close follow-up of persons receiving any alternative therapies is essential.
*Close follow-up of persons receiving any alternative therapies is essential.


*Persons with a [[Syphilis medical therapy#Pencillin allergy|penicillin allergy]] whose compliance with therapy or follow-up cannot be ensured should be [[desensitized]] and treated with [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin]].  
*Persons with a [[Syphilis medical therapy#Pencillin allergy|penicillin allergy]] whose compliance with therapy or follow-up cannot be ensured should be [[desensitize]]d and treated with [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin]].  


*'''[[Syphilis medical therapy#Pencillin allergy: Penicillin skin test|Skin testing]]''' for penicillin allergy might be useful in some circumstances in which the reagents and expertise are available to perform the test adequately.
*[[Syphilis medical therapy#Pencillin allergy: Penicillin skin test|Skin testing]] for penicillin allergy may be useful in some circumstances in which the reagents and expertise are available to perform the test adequately.


====Pregnancy====
====Pregnancy====
Pregnant patients who are allergic to penicillin should be [[desensitized]] and treated with [[penicillin]].
Pregnant patients who are allergic to penicillin should be [[desensitize]]d and treated with [[penicillin]].


==Follow-Up==
===Follow-Up===
*'''''Treatment failure''''' can occur with any regimen. However, assessing response to treatment frequently is difficult, and definitive criteria for cure or failure have not been established.  
*Treatment failure can occur with any regimen. However, assessing response to treatment frequently is difficult, and definitive criteria for cure or failure have not been established.  
:*In addition, [[Syphilis laboratory tests#Nontreponemal test|nontreponemal test titers]] might decline more slowly for persons who previously have had syphilis.<ref name="pmid16943224">Ghanem KG, Erbelding EJ, Wiener ZS, Rompalo AM (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16943224 Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted diseases clinics.] ''Sex Transm Infect'' 83 (2):97-101. [http://dx.doi.org/10.1136/sti.2006.021402 DOI:10.1136/sti.2006.021402] PMID: [http://pubmed.gov/16943224 16943224]</ref>  
:*[[Syphilis laboratory findings#Nontreponemal test|Nontreponemal test titers]] may decline more slowly for persons who previously had syphilis.<ref name="pmid16943224">Ghanem KG, Erbelding EJ, Wiener ZS, Rompalo AM (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16943224 Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted diseases clinics.] Sex Transm Infect 83 (2):97-101. [http://dx.doi.org/10.1136/sti.2006.021402 DOI:10.1136/sti.2006.021402] PMID: [http://pubmed.gov/16943224 16943224]</ref><ref name="pmid23118269">{{cite journal| author=Seña AC, Wolff M, Behets F, Van Damme K, Martin DH, Leone P et al.| title=Response to therapy following retreatment of serofast early syphilis patients with benzathine penicillin. | journal=Clin Infect Dis | year= 2013 | volume= 56 | issue= 3 | pages= 420-2 | pmid=23118269 | doi=10.1093/cid/cis918 | pmc=3590030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23118269  }} </ref>  


:*[[Syphilis physical examination#Physical examination|Clinical]] and [[Syphilis laboratory tests#Serology|serologic]] evaluation should be performed 6 months and 12 months after treatment; more frequent evaluation might be prudent if follow-up is uncertain.
:*[[Syphilis physical examination#Physical examination|Clinical]] and [[Syphilis laboratory findings|serologic]] evaluation should be performed 6 months and 12 months after treatment; more frequent evaluation may be prudent if follow-up is uncertain.


:*Patients who have [[Syphilis physical examination#Physical examination|signs]] or [[Syphilis history and symptoms|symptoms]] that persist or recur or who have a sustained fourfold increase in [[Syphilis laboratory tests#Nontreponemal test|nontreponemal test titer]] (i.e., compared with the maximum or baseline titer at the time of treatment) probably failed treatment or were reinfected. These patients should be retreated and reevaluated for [[HIV|HIV infection]].  
:*Patients who have [[Syphilis physical examination#Physical examination|signs]] or [[Syphilis history and symptoms|symptoms]] that persist or recur or who have a sustained fourfold increase in [[Syphilis laboratory tests#Nontreponemal test|nontreponemal test titer]] (i.e. compared with the maximum or baseline titer at the time of treatment) probably failed treatment or were reinfected. These patients should be retreated and reevaluated for [[HIV|HIV infection]].  


:*Because treatment failure usually cannot be reliably distinguished from reinfection with T. pallidum, a [[Syphilis laboratory tests#CSF analysis|CSF analysis]] also should be performed.
:*Because treatment failure usually cannot be reliably distinguished from reinfection with ''T. pallidum'', a [[Syphilis laboratory findings#CSF analysis|CSF analysis]] also should be performed.


*Although failure of [[Syphilis laboratory tests#Nontreponemal test|nontreponemal test titers]] to decline fourfold within 6-12 months after therapy for [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis might be indicative of treatment failure.
*Failure of [[Syphilis laboratory findings#Nontreponemal test|nontreponemal test titers]] to decline fourfold within 6-12 months after therapy for [[Syphilis pathophysiology#Primary syphilis|primary]] or [[Syphilis pathophysiology#Secondary syphilis|secondary]] syphilis may be indicative of treatment failure.


:*Clinical trial data have demonstrated that greater than 15% of patients with early syphilis treated with the recommended therapy will not achieve the two dilution decline in [[Syphilis laboratory tests#Nontreponemal test|nontreponemal titer]] used to define response at 1 year after treatment.<ref name="pmid9235493">Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M et al. (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9235493 A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group.] ''N Engl J Med'' 337 (5):307-14. [http://dx.doi.org/10.1056/NEJM199707313370504 DOI:10.1056/NEJM199707313370504] PMID: [http://pubmed.gov/9235493 9235493]</ref>
:*Clinical trial data have demonstrated that greater than 15% of patients with early syphilis treated with the recommended therapy will not achieve the two dilution decline in [[Syphilis laboratory findings#Nontreponemal test|nontreponemal titer]] used to define response at 1 year after treatment.<ref name="pmid9235493">Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M et al. (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9235493 A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group.] N Engl J Med 337 (5):307-14. [http://dx.doi.org/10.1056/NEJM199707313370504 DOI:10.1056/NEJM199707313370504] PMID: [http://pubmed.gov/9235493 9235493]</ref>


:*Persons whose titers do not decline should be reevaluated for [[HIV|HIV infection]].  
:*Persons whose titers do not decline should be reevaluated for [[HIV|HIV infection]].  
Line 72: Line 112:
:*Optimal management of such patients is unclear.  
:*Optimal management of such patients is unclear.  


:*At a minimum, these patients should receive additional [[Syphilis physical examination#Physical examination|clinical]] and [[Syphilis laboratory tests#Serology|serologic]] follow-up.  
:*At a minimum, these patients should receive additional [[Syphilis physical examination#Physical examination|clinical]] and [[Syphilis laboratory findings#Serology|serologic]] follow-up.  


:*If additional follow-up cannot be ensured, [[Syphilis medical therapy#Pharmacotherapy|retreatment]] is recommended.  
:*If additional follow-up cannot be ensured, [[Syphilis medical therapy#Pharmacotherapy|retreatment]] is recommended.  


:*Because treatment failure might be the result of unrecognized CNS infection, [[Syphilis laboratory tests#CSF analysis|CSF examination]] can be considered in such situations.
:*Because treatment failure may be the result of unrecognized CNS infection, [[Syphilis laboratory findings#CSF analysis|CSF examination]] can be considered in such situations.


*For '''''retreatment''''', weekly injections of [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin G]] 2.4 million units IM for 3 weeks is recommended, unless [[Syphilis laboratory tests#CSF analysis|CSF examination]] indicates that [[neurosyphilis]] is present.  
*For retreatment, weekly injections of [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin G]] 2.4 million units IM for 3 weeks is recommended, unless [[Syphilis laboratory findings#CSF analysis|CSF examination]] indicates that [[neurosyphilis]] is present.  


*In rare instances, [[Syphilis laboratory tests#Serology|serologic titers]] do not decline despite a negative [[Syphilis laboratory tests#CSF analysis|CSF examination]] and a repeated course of therapy. In these circumstances, the need for additional therapy or repeated CSF examinations is unclear, but is not generally recommended.
*In rare instances, serologic titers do not decline despite a negative [[Syphilis laboratory tests#CSF analysis|CSF examination]] and a repeated course of therapy. In these circumstances, the need for additional therapy or repeated CSF examinations is unclear, but is not generally recommended.


==References==
==References==
Line 90: Line 130:
[[Category:Disease]]
[[Category:Disease]]
[[Category:Gynecology]]
[[Category:Gynecology]]
[[Category:Infectious disease]]
[[Category:Bacterial diseases]]
[[Category:Bacterial diseases]]
[[Category:Sexually transmitted diseases]]
[[Category:Sexually transmitted diseases]]
[[Category:Emergency mdicine]]
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Urology]]
[[Category:Neurology]]

Latest revision as of 17:30, 12 August 2021

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]

Sexually transmitted diseases Main Page

Syphilis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Syphilis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Primary and Secondary Syphilis
Latent Syphilis
Tertiary Syphilis
Neurosyphilis
HIV-Infected Patients
Pregnancy
Management of Sexual Partners

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Syphilis management for primary and secondary stages On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Syphilis management for primary and secondary stages

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Syphilis management for primary and secondary stages

CDC on Syphilis management for primary and secondary stages

Syphilis management for primary and secondary stages in the news

Blogs on Syphilis management for primary and secondary stages

Directions to Hospitals Treating Syphilis

Risk calculators and risk factors for Syphilis management for primary and secondary stages

Overview

Parenteral penicillin G has been an effective regimen to achieve clinical resolution and to prevent late sequelae of syphilis.

Management for Primary and Secondary Syphilis

CDC Recommendations: Pharmacotherapy for Adults[2]

Primary Syphilis
Preferred Regimen
▸ Benzathine Penicillin G (Bicillin L-A) 2.4 million units IM x 1 dose
Alternative Regimen
Doxycycline 100 mg po bid x 14 days
OR
Tetracycline 500 mg po qid x 14 days
OR
Ceftriaxone 1 gm IM/IV q24h x 10 -14 days
OR
Azithromycin2 gm po x 1 dose
  • Infants and children aged >/= 1 month
    • Upon diagnosis with syphilis, birth and maternal medical records should be reviewed for assessment of congenital or acquired syphilis.
    • Those with primary and secondary syphilis should also be evaluated for sexual abuse, through consultation with child-protection service.

CDC Recommendations: Pharmacotherapy for Infants and Children

Primary Syphilis
Preferred Regimen
▸ Benzathine Penicillin G (Bicillin L-A) 50,000 units/kg body weight IM, up to the adult dose of 2.4 million units x 1 dose

Other Management Considerations

HIV Infection

  • All persons who have syphilis should be tested for HIV infection.
  • In geographic areas in which the prevalence of HIV is high, persons who have primary syphilis should be retested for HIV after 3 months if the first HIV test result was negative.

Neurosyphilis

  • Invasion of CSF by T. pallidum accompanied by CSF laboratory abnormalities is common among adults who have primary or secondary syphilis.[3] Therefore, in the absence of clinical neurologic findings, no evidence exists to support variation from the recommended treatment regimen for early syphilis.
  • Symptomatic neurosyphilis develops in only a limited number of persons after treatment with the penicillin regimens recommended for primary and secondary syphilis. Therefore, unless clinical signs or symptoms of neurologic or ophthalmic involvement are present or treatment failure is documented, routine CSF analysis is not recommended for persons who have primary or secondary syphilis.

Special Considerations

Penicillin Allergy: Alternative Regimen

  • Data to support the use of alternatives to penicillin in the treatment of early syphilis are limited. However, several therapies may be effective in non-pregnant, penicillin-allergic patients who have primary or secondary syphilis.
  • Doxycycline 100 mg orally twice daily for 14 days[4][5] and tetracycline (500 mg four times daily for 14 days) are regimens that have been used for many years.
  • Compliance is likely to be better with doxycycline than tetracycline, because tetracycline can cause gastrointestinal side effects.
  • Clinical studies, though limited, along with biologic and pharmacologic evidence suggest that ceftriaxone (1 g daily either IM or IV for 10-14 days) is effective for treating early syphilis; the optimal dose and duration of ceftriaxone therapy have not been defined.[6]
  • Azithromycin as a single 2-g oral dose is effective for treating early syphilis.[7][8][9] However, T. pallidum chromosomal mutations associated with azithromycin resistance and treatment failures have been documented in several geographical areas in the United States.[10][11] As such, the use of azithromycin should be used with caution only when treatment with penicillin or doxycycline is not feasible. Azithromycin should not be used in MSM or pregnant women.
  • Close follow-up of persons receiving any alternative therapies is essential.
  • Skin testing for penicillin allergy may be useful in some circumstances in which the reagents and expertise are available to perform the test adequately.

Pregnancy

Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin.

Follow-Up

  • Treatment failure can occur with any regimen. However, assessing response to treatment frequently is difficult, and definitive criteria for cure or failure have not been established.
  • Clinical and serologic evaluation should be performed 6 months and 12 months after treatment; more frequent evaluation may be prudent if follow-up is uncertain.
  • Patients who have signs or symptoms that persist or recur or who have a sustained fourfold increase in nontreponemal test titer (i.e. compared with the maximum or baseline titer at the time of treatment) probably failed treatment or were reinfected. These patients should be retreated and reevaluated for HIV infection.
  • Because treatment failure usually cannot be reliably distinguished from reinfection with T. pallidum, a CSF analysis also should be performed.
  • Clinical trial data have demonstrated that greater than 15% of patients with early syphilis treated with the recommended therapy will not achieve the two dilution decline in nontreponemal titer used to define response at 1 year after treatment.[14]
  • Persons whose titers do not decline should be reevaluated for HIV infection.
  • Optimal management of such patients is unclear.
  • At a minimum, these patients should receive additional clinical and serologic follow-up.
  • If additional follow-up cannot be ensured, retreatment is recommended.
  • Because treatment failure may be the result of unrecognized CNS infection, CSF examination can be considered in such situations.
  • In rare instances, serologic titers do not decline despite a negative CSF examination and a repeated course of therapy. In these circumstances, the need for additional therapy or repeated CSF examinations is unclear, but is not generally recommended.

References

  1. http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016
  2. "Sexually Transmitted Diseases Treatment Guidelines, 2010". Retrieved 2012-12-19.
  3. Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH (1988) Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Ann Intern Med 109 (11):855-62. PMID: 3056164
  4. Ghanem KG, Erbelding EJ, Cheng WW, Rompalo AM (2006) Doxycycline compared with benzathine penicillin for the treatment of early syphilis. Clin Infect Dis 42 (6):e45-9. DOI:10.1086/500406 PMID: 16477545
  5. Wong T, Singh AE, De P (2008) Primary syphilis: serological treatment response to doxycycline/tetracycline versus benzathine penicillin. Am J Med 121 (10):903-8. DOI:10.1016/j.amjmed.2008.04.042 PMID: 18823862
  6. Hook EW, Roddy RE, Handsfield HH (1988) Ceftriaxone therapy for incubating and early syphilis. J Infect Dis 158 (4):881-4. PMID: 3171231
  7. Riedner G, Rusizoka M, Todd J, Maboko L, Hoelscher M, Mmbando D et al. (2005) Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med 353 (12):1236-44. DOI:10.1056/NEJMoa044284 PMID: 16177249
  8. Hook EW, Martin DH, Stephens J, Smith BS, Smith K (2002) A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sex Transm Dis 29 (8):486-90. PMID: 12172535
  9. Hook EW, Behets F, Van Damme K, Ravelomanana N, Leone P, Sena AC et al. (2010) A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis 201 (11):1729-35. DOI:10.1086/652239 PMID: 20402591
  10. Lukehart SA, Godornes C, Molini BJ, Sonnett P, Hopkins S, Mulcahy F et al. (2004) Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med 351 (2):154-8. DOI:10.1056/NEJMoa040216 PMID: 15247355
  11. Mitchell SJ, Engelman J, Kent CK, Lukehart SA, Godornes C, Klausner JD (2006) Azithromycin-resistant syphilis infection: San Francisco, California, 2000-2004. Clin Infect Dis 42 (3):337-45. DOI:10.1086/498899 PMID: 16392078
  12. Ghanem KG, Erbelding EJ, Wiener ZS, Rompalo AM (2007) Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted diseases clinics. Sex Transm Infect 83 (2):97-101. DOI:10.1136/sti.2006.021402 PMID: 16943224
  13. Seña AC, Wolff M, Behets F, Van Damme K, Martin DH, Leone P; et al. (2013). "Response to therapy following retreatment of serofast early syphilis patients with benzathine penicillin". Clin Infect Dis. 56 (3): 420–2. doi:10.1093/cid/cis918. PMC 3590030. PMID 23118269.
  14. Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M et al. (1997) A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group. N Engl J Med 337 (5):307-14. DOI:10.1056/NEJM199707313370504 PMID: 9235493


Template:WikiDoc Sources