Syphilis medical therapy: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: Removing from Primary care)
 
(48 intermediate revisions by 13 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{CMG}}
{{CMG}}{{AE}}{{AA}}; {{NRM}}
{{Syphilis}}
{{Syphilis}}
==Overview==
==Overview==
[[Penicillin#Benzylpenicillin (penicillin G)|Penicillin G]], administered parenterally, is the preferred drug for treating all stages of syphilis. If allergic, then [[tetracycline]] or [[doxycycline]] may also be used. During pregnancy, [[Penicillin#Benzylpenicillin (penicillin G)|parenteral penicillin G]] is the only therapy with documented efficacy for syphilis.  
[[Penicillin#Benzylpenicillin (penicillin G)|Penicillin G]], administered [[parenterally]], is the preferred drug for treating all stages of syphilis. If the patient is allergic, then [[Tetracycline]] or [[doxycycline]] may also be used. During pregnancy, [[Penicillin#Benzylpenicillin (penicillin G)|parenteral penicillin G]] is the only therapy with documented efficacy for syphilis.  The [[Jarisch-Herxheimer reaction]] is an acute adverse febrile reaction that may occur after initiation of therapy for syphilis.


==Medical Therapy==
==Medical Therapy==
*[[Penicillin#Benzylpenicillin (penicillin G)|Penicillin G]], administered parenterally, is the preferred drug for treating all stages of syphilis.  
*[[Penicillin#Benzylpenicillin (penicillin G)|Penicillin G]], administered [[parenterally]], is the preferred drug for treating all stage of syphilis.<ref name=cdcsyphilis>http://www.cdc.gov/std/tg2015/syphilis.htm Accessed on September 26, 2016</ref>


:*The preparation used (i.e., benzathine, aqueous procaine, or aqueous crystalline), the dosage, and the length of treatment depend on the stage and clinical manifestations of the disease.  
:*The preparation used (i.e., [[Benzathine penicillin G|benzathine]], aqueous [[Procaine penicillin G|procaine]], or [[Penicillin G potassium|aqueous crystalline]]), the dosage, and the length of treatment depend on the stage and clinical manifestations of the disease.  


:*Selection of the appropriate [[Penicillin#Benzylpenicillin (penicillin G)|penicillin preparation]] is important, because T. pallidum can reside in sequestered sites (e.g., the CNS and aqueous humor) that are poorly accessed by some forms of penicillin.  
:*Treatment for longer duration is required in patients with late latent, latent with unknown duration and tertiary syphilis.


:*Combinations of benzathine penicillin, procaine penicillin, and oral penicillin preparations are not considered appropriate for the treatment of syphilis.  
:*Selection of the appropriate [[Penicillin#Benzylpenicillin (penicillin G)|penicillin preparation]] is important, because ''T. pallidum'' can reside in sequestered sites (e.g., the [[CNS]] and [[aqueous humor]]) that are poorly accessed by some forms of penicillin.


*During pregnancy, [[Penicillin#Benzylpenicillin (penicillin G)|parenteral penicillin G]] is the only therapy with documented efficacy for syphilis. Pregnant women with syphilis in any stage who report penicillin allergy should be desensitized and treated with penicillin
:*Combinations of benzathine penicillin, procaine penicillin, and oral penicillin preparations are not considered appropriate for the treatment of syphilis.<ref name=BCR>http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5409a1.htm</ref> 
 
*The [[Herxheimer reaction|Jarisch-Herxheimer reaction]] is an acute febrile reaction
 
:*Frequently accompanied by [[headache]], [[myalgia]], [[fever]], and other symptoms that usually occur within the first 24 hours after the initiation of any therapy for syphilis.  
 
:*Patients should be informed about this possible adverse reaction.  
 
:*The Jarisch-Herxheimer reaction occurs most frequently among patients who have early syphilis, presumably because bacterial burdens are higher during these stages.  
 
:*[[Antipyretics]] can be used to manage symptoms, but they have not been proven to prevent this reaction.
 
:*The Jarisch-Herxheimer reaction might induce early labor or cause [[fetal distress]] in pregnant women, but this should not prevent or delay therapy.


===Pharmacotherapy===
===Pharmacotherapy===
*The first-choice treatment for all manifestations of syphilis remains [[penicillin]] in the form of [[Penicillin#Benzylpenicillin .28penicillin G.29|penicillin G]].<ref name=CDC>{{cite journal | author=Centers for Disease Control | title=Sexually Transmitted Diseases Treatment Guidelines, 2006 | journal=MMWR | volume=55 | date=08-04-2006 | issue=RR-11 | pages=24-32}}</ref>  
:'''Syphilis Among non-HIV-Infected Persons'''<ref name="pmid26042815">{{cite journal |vauthors=Workowski KA, Bolan GA |title=Sexually transmitted diseases treatment guidelines, 2015 |journal=[[MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control]] |volume=64 |issue=RR-03 |pages=1–137 |year=2015 |pmid=26042815 |doi= |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm |issn=}}</ref>
 
::'''Primary and Secondary Syphilis'''
*The effect of penicillin on syphilis was widely known before randomized clinical trials were used; as a result, treatment with penicillin is largely based on case series, expert opinion, and years of clinical experience.  
::*Preferred regimen: [[Benzathine penicillin G]] 2.4 MU IM single dose
 
::*Pediatric regimen: [[Benzathine penicillin G]] 50,000 U/kg (Maximum, 2.4 MU) IM single dose
*[[Penicillin#Benzylpenicillin (penicillin G)|Parenteral penicillin G]] is the only therapy with documented effect during pregnancy. For early syphilis, one dose of penicillin is sufficient.
::'''Latent Syphilis'''
 
:::Early Latent Syphilis:
=====Late latent and Infections of Unknown Duration=====
:::*Preferred regimen: [[Benzathine penicillin G]] 2.4 MU IM in a single dose
*Late latent syphilis is defined as latency for greater than one year.
:::*Pediatric regimen: [[Benzathine penicillin G]] 50,000 U/kg (Maximum, 2.4 MU) IM single dose
 
:::Late Latent Syphilis or Latent Syphilis of Unknown Duration:
*If [[Syphilis laboratory tests#CSF analysis|CSF examination]] yields no evidence of [[neurosyphilis]], then [[Penicillin#Benzylpenicillin (penicillin G)|penicillin G]] is recommended as weekly doses for 3 weeks.
:::*Preferred regimen: [[Benzathine penicillin G]] 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
 
:::*Pediatric regimen: [[Benzathine penicillin G]] 50,000 U/kg IM (Maximum, 2.4 MU), administered as 3 doses at 1 week intervals (total 150,000 U/kg up to the adult total dose of 7.2 MU)
*If allergic, then [[tetracycline]] or [[doxycycline]] may also be used for this stage, but for 28 days instead of the normal 14. As with before, the data to support use of [[tetracycline]] and [[ceftriaxone]] are limited.
::'''Tertiary Syphilis'''
 
::*Preferred regimen: [[Benzathine penicillin G]] 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
=====Neurosyphilis=====
::'''Ocular syphilis'''
*For patients diagnosed with [[neurosyphilis]] including ocular or auditory syphilis with or without [[Syphilis laboratory tests#CSF analysis|positive CSF results]], [[Penicillin#Benzylpenicillin (penicillin G)|aqueous crystalline penicillin G]] is the treatment of choice.  
:::Pathogen-directed antimicrobial therapy:<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 = 978-1455748013 }}</ref>
 
:::*Preferred regimen (1): [[Penicillin]] 4 MU IV q4h for 10-14 days {{and}} [[Benzathine penicillin G]] 2.4 MU IM once weekly for 3 weeks
*The recommended regimen is intravenous treatment every 4 hours or continuously for 10-14 days.
:::*Note (1): [[Corticosteroids]] (Prednisone 60-80 mg PO qd) are co-administered to decrease intraocular inflammation and prevent rebound inflammation from [[Jarisch-Herxheimer reaction]].
 
:::*Note (2): All patients with presumed ocular syphilis should be tested for [[Human Immunodeficiency Virus (HIV)|HIV]], and all should have a [[lumbar puncture]] before starting therapy to exclude concurrent [[neurosyphilis]].
*If intravenous administration is not possible, then [[Penicillin#Procaine benzylpenicillin|procaine penicillin]] is an alternative (administered daily with [[probenecid]] for two weeks). Procaine injections are painful, however, and patient compliance may be difficult to ensure.
:'''Syphilis Among HIV-Infected Persons'''
 
::'''Primary and Secondary Syphilis Among HIV-Infected Persons'''
*To approximate the 21-day course of therapy for late latent disease and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin G]] after the completion of a 14-day course of aqueous crystalline or aqueous procaine penicillin G for [[neurosyphilis]].  
::*Preferred regimen: [[Benzathine penicillin G]] 2.4 MU IM single dose<ref name="pmid9235493">{{cite journal| author=Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M et al.| title=A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group. | journal=N Engl J Med | year= 1997 | volume= 337 | issue= 5 | pages= 307-14 | pmid=9235493 | doi=10.1056/NEJM199707313370504 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9235493  }} </ref>
 
::'''Latent Syphilis Among HIV-Infected Persons'''
*No oral antibiotic alternatives are recommended for the treatment of [[neurosyphilis]]. The only alternative that has been studied and shown to be effective is intramuscular [[ceftriaxone]] daily for 14 days.
:::Early latent:
 
:::*Preferred regimen: [[Benzathine penicillin G]] 2.4 MU IM single dose<ref name="pmid25286091">{{cite journal| author=Yang CJ, Lee NY, Chen TC, Lin YH, Liang SH, Lu PL et al.| title=One dose versus three weekly doses of benzathine penicillin G for patients co-infected with HIV and early syphilis: a multicenter, prospective observational study. | journal=PLoS One | year= 2014 | volume= 9 | issue= 10 | pages= e109667 | pmid=25286091 | doi=10.1371/journal.pone.0109667 | pmc=4186862 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25286091  }} </ref>
=====HIV-infected patients=====
:::Late latent:
*Alternative regimens such as [[tetracyclines]] are not well studied in HIV infection and a careful follow-up is recommended. Tetra-cyclines are contraindicated in pregnancy.
:::*Preferred regimen: [[Benzathine penicillin G]] 2.4 MU once a week for 3 weeks
 
::'''Neurosyphilis Among HIV-Infected Persons'''
*HIV-infected patients with early syphilis may have a higher risk of neurological complications and a higher rate of treatment failure with currently recommended regimens.
::*Preferred regimen: [[Aqueous crystalline penicillin G]] 18-24 MU per day, administered as 3-4 MU IV q4h or continuous infusion, for 10-14 days
 
::*Alternative regimen: [[Procaine penicillin]] 2.4 MU IM q24h {{and}} [[Probenecid]] 500 mg PO qid  for 10-14 days
*The magnitude of these risks, however, although not precisely defined, is probably small.
:'''Syphilis During Pregnancy'''
 
:*Pregnant women should be treated with the [[penicillin]] regimen appropriate for their stage of infection.
*Skin testing or [[desensitization]] is recommended in latent syphilis and neurosyphilis in other patients with HIV infection.
:*[[Penicillin#Benzylpenicillin (penicillin G)|Parenteral penicillin G]] is the only therapy with documented efficacy for syphilis. Pregnant women with syphilis in any stage who report penicillin allergy should be desensitized and treated with penicillin
 
:*The [[Herxheimer reaction|Jarisch-Herxheimer reaction]] is an acute febrile reaction.  
===Pencillin Allergy===
::*Frequently accompanied by [[headache]], [[myalgia]], [[fever]], and other symptoms that usually occur within the first 24 hours after the initiation of any therapy for syphilis.  
Although [[penicillin]] is still the most commonly reported allergy, less than 20% of all patients who believe that they have a penicillin allergy are truly allergic to penicillin.<ref>{{cite journal|author=Salkind AR, Cuddy PG, Foxworth JW|title=Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy|journal=JAMA|year=2001|volume=285|issue=19|pages=2498&ndash;2505|url=http://jama.ama-assn.org/cgi/content/abstract/285/19/2498}}</ref> Nevertheless, penicillin is still the most common cause of severe allergic drug reactions.
::*Patients should be informed about this possible adverse reaction.
 
::*The Jarisch-Herxheimer reaction occurs most frequently among patients who have early syphilis, presumably because bacterial burdens are higher during these stages.
[[Allergy|Allergic]] reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent. [[Anaphylaxis]] will occur in approximately 0.01% of patients. There is about a 5% cross-sensitivity between penicillin-derivatives, [[cephalosporins]] and [[carbapenems]].<ref>{{cite journal |author=Gruchalla RS, Pirmohamed M |title=Clinical practice. Antibiotic allergy |journal=N. Engl. J. Med. |volume=354 |issue=6 |pages=601-9 |year=2006 |pmid=16467547 |doi=10.1056/NEJMcp043986}}</ref> This risk warrants extreme caution with all β-lactam antibiotics in patients with a history of severe allergic reactions ([[urticaria]], [[anaphylaxis]], [[interstitial nephritis]]) to any β-lactam antibiotic.
::*[[Antipyretics]] can be used to manage symptoms, but they have not been proven to prevent this reaction.  
 
::*The Jarisch-Herxheimer reaction might induce early labor or cause [[fetal distress]] in pregnant women, but this should not prevent or delay therapy.
====Jarisch-Herxheimer reaction====
:'''Congenital Syphilis in Neonates'''
*Before administering any treatment, clinicians should warn all patients about the possibility of a [[Jarisch-Herxheimer reaction]], which occurs most often in secondary syphilis and with penicillin therapy, and may be more common in HIV-infected patients.<ref>{{cite journal |author=Rolfs RT, Joesoef MR, Hendershot EF, et al |title=A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group |journal=N. Engl. J. Med. |volume=337 |issue=5 |pages=307-14 |year=1997 |pmid=9235493 |doi=}}</ref>
::'''Condition 1''': Infants with proven or highly probable disease and (1) an abnormal physical examination that is consistent with congenital syphilis;（2）a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer; or （3）a positive darkfield test of body fluid(s).
 
::*Preferred regimen (1): [[Aqueous crystalline penicillin G]] 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days
*This reaction is characterized by fever, fatigue, and transient worsening of any mucocutaneous symptoms, and usually subsides within 24 hours.  
::*Preferred regimen (2): [[Procaine penicillin G]] 50,000 U/kg/dose IM q24h for 10 days
 
::*Note: If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., [[ampicillin]]). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with ''T. pallidum'' and treatment for syphilis must be considered when evaluating and treating the infant.
*These symptoms can be alleviated with [[acetaminophen]] (paracetamol) and should not be mistaken for drug allergy.
::'''Condition 2''': Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was not treated, inadequately treated, or has no documentation of having received treatment; (2) mother was treated with [[erythromycin]] or another non-penicillin regimen; or (3) mother received treatment <4 weeks before delivery.
 
::*Preferred regimen (1): [[Aqueous crystalline penicillin G]] 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days
*In addition, clinicians should inform HIV-infected patients that currently recommended regimens may be less effective for them than for patients without HIV infection and that close serologic follow-up is therefore essential.
::*Preferred regimen (2): [[Procaine penicillin G]] 50,000 U/kg/dose IM q24h for 10 days
 
::*Preferred regimen (3): [[Benzathine penicillin G]] 50,000 U/kg/dose IM single dose
====Penicillin Skin Test====
::*Note: If the mother has untreated early syphilis at delivery, 10 days of parenteral therapy can be considered
*[[Penicillin skin testing]] with the major and minor determinants of penicillin can reliably identify persons at high risk for penicillin reactions.<ref name="pmid3300459">{{cite journal |author=Saxon A, Beall GN, Rohr AS, Adelman DC |title=Immediate hypersensitivity reactions to beta-lactam antibiotics |journal=[[Annals of Internal Medicine]] |volume=107 |issue=2 |pages=204–15 |year=1987 |month=August |pmid=3300459 |doi= |url= |accessdate=2012-02-18}}</ref><ref name="pmid18589051">{{cite journal |author=Yates AB |title=Management of patients with a history of allergy to beta-lactam antibiotics |journal=[[The American Journal of Medicine]] |volume=121 |issue=7 |pages=572–6 |year=2008 |month=July |pmid=18589051 |doi=10.1016/j.amjmed.2007.12.005 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9343(08)00037-5 |accessdate=2012-02-18}}</ref> Although these reagents are easily generated and have been available for more than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen which is the major determinant) and penicillin G have been available commercially. These two tests identify an estimated 90%-97% of the currently allergic patients. However, because skin testing without the minor determinants would still miss 3%-10% of allergic patients and because serious or fatal reactions can occur among these minor-determinant--positive patients, caution should be exercised when the full battery of skin-test reagents is not available.  
::'''Condition 3''': Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery; and (2) mother has no evidence of reinfection or relapse.
 
::*Preferred regimen: [[Benzathine penicillin G]] 50,000 U/kg/dose IM single dose
*Patients with history of penicillin reaction and negative skin-test negative can receive conventional penicillin therapy.  
::'''Condition 4''': Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother's treatment was adequate before pregnancy; and (2) mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).
 
::*No treatment is required
*Skin-test-positive patients should be desensitized before initiating treatment.
::*[[Benzathine penicillin G]] 50,000 U/kg IM single dose might be considered, particularly if follow-up is uncertain.
 
:'''Congenital Syphilis in infants and children'''
*All patients with a history suggesting IgE- mediated reactions to penicillin (e.g., [[anaphylaxis]], [[angioedema]], [[bronchospasm]], or [[urticaria]]) should be desensitized in a hospital setting. In patients with reactions not likely to be IgE-mediated, outpatient-monitored test doses can be considered.
:*Preferred regimen: [[Aqueous crystalline penicillin G]] 50,000 U/kg q4–6h for 10 days
 
=====Indication:=====
*Patients at high risk for [[anaphylaxis]], including those who have:
:*a history of [[penicillin]]-related anaphylaxis, [[asthma]], or other diseases that would make anaphylaxis more dangerous (or)
:*are being treated with [[Beta blockers|beta-adrenergic blocking agents]], should be tested with 100-fold dilutions of the full-strength skin-test reagents before being tested with full-strength reagents.
 
*In these situations, patients should be tested in a monitored setting in which treatment for an anaphylactic reaction is available. If possible, the patient should not have taken [[antihistamines]] recently (e.g., [[chlorpheniramine|chlorpheniramine maleate]] or [[fexafenadine]] during the preceding 24 hours, [[diphenhydramine|diphenhydramine HCl]] during the preceding 4 days, or [[hydroxyzine]] or [[phenathiazines]] during the preceding 3 weeks).
 
=====Procedures:=====
*Dilute the [[antigens]] either 100-fold for preliminary testing (if the patient has had a life-threatening reaction to [[penicillin]]) or 10-fold (if the patient has had another type of immediate, generalized reaction to penicillin within the preceding year).


*Epicutaneous (Prick) Tests:
==Approach to Diagnosis and Management of Syphilis==
:*Duplicate drops of skin-test reagent are placed on the volar surface of the forearm. The underlying epidermis is pierced with a 26-gauge needle without drawing blood.
:*An epicutaneous test is positive if the average wheal diameter after 15 minutes is greater than or equal to 4 mm larger than that of negative controls; otherwise, the test is negative.
:*The [[histamine]] controls should be positive to ensure that results are not falsely negative because of the effect of [[antihistaminics|
antihistaminic drugs]].


*Intradermal Test:
{{Family tree/start}}
:*If epicutaneous tests are negative, duplicate 0.02-mL intradermal injections of negative control and antigen solutions are made into the volar surface of the forearm by using a 26- or 27-gauge needle on a syringe.
{{Family tree | | | | | | | | | | | | | | A01 | | | | | | | | | | | | |A01=Positive syphilis screening test}}
:*The margins of the wheals induced by the injections should be marked with a ball point pen.
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | |}}
:*An intradermal test is positive if the average wheal diameter 15 minutes after injection is greater than 2 mm larger than the initial wheal size and also is greater than 2 mm larger than the negative controls. Otherwise, the tests are negative.
{{Family tree | | | | | | | | | | | | | | B01 | | | | | | | | | | | | |B01=Perform treponemal-specific test}}
 
{{Family tree | | | | | | | |,|-|-|-|-|-|-|^|-|-|-|-|-|-|.| | | | | | | }}
===Management of Patients with History of Penicillin Allergy===
{{Family tree | | | | | | | C01 | | | | | | | | | | | | C02 | | | | | |C01=Positive treponemal-specific test|C02=Negative treponemal-specific test}}
=====CDC Recommendations [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm]=====
{{Family tree | | | | | | | |!| | | | | | | | | | | |,|-|^|-|.| | | | |}}
{{cquote|
{{Family tree | | | | | | | D01 | | | | | | | | | | D02 | | D03 | | | |D01=Establish stage of infection; obtain quantitative nontreponemal test titres|D02=Primary syphilis suspected|D03=False-positive test result suspected}}
1. If the full battery of skin-test reagents is available, including both major and minor determinants, patients who report a history of penicillin reaction and who are skin-test negative can receive conventional [[penicillin]] therapy. Skin-test positive patients should be [[desensitized]] before initiating treatment.
{{Family tree | | |,|-|-|-|-|+|-|-|-|-|-|.| | | | | |!| | | |!| | | | |}}
 
{{Family tree | | E01 | | | E02 | | | | E03 | | | | E04 | | E05 | | | |E01=Signs or symptoms of primary or secondary syphilis|E02=No clinical signs or symptoms (latent syphilis)|E03=Signs or symptoms of tertiary (late) syphilis, or patient is HIC positive or otherwise immunocompromised|E04=Obtain quantitative nontreponemal test titres|E05=Consider other causes}}
2. If the full battery of skin-test reagents, including the minor determinants, is not available, the patient should be skin tested using benzylpenicilloyl poly-L-lysine (i.e., the major determinant) and [[Pencillin|penicillin G]]. Patients who have positive test results should be [[desensitized]].
{{Family tree | | |!| | |,|-|^|-|.| | | | | | | | | |!| | | | | | | | |}}
:*One approach suggests that persons with a history of allergy who have negative test results should be regarded as possibly allergic and desensitized.
{{Family tree | | |!| | F01 | | F02 | | F03 | | | | F04 | | | | | | | |F01=Early latent syphilis|F02=Late latent syphilis|F03=Lumbar puncture|F04=Penicillin G benzazthine, 2.4 million units IM (single dose)<sup>*</sup>}}
:*Another approach in those with negative skin-test results involves test-dosing gradually with oral penicillin in a monitored setting in which treatment for anaphylactic reaction can be provided.
{{Family tree | | |!| |!| | | | |!| | | |!| | | | | |!| | | | | | | | |}}
 
{{Family tree | | | G01 | | | | G02 | | |!| | | | | G03 | | | | | | |G01=Penicillin G benzazthine, 2.4 million units IM (single dose)*|G02=Penicillin G benzazthine, 2.4 million units IM once a week for 3 weeks (three doses)<sup>**</sup>|G03=Signs, symptoms, or CSF findings consistent with neurosyphilis}}
3. If the major determinant (Pre-Pen) is not available for skin testing, all patients with a history suggesting [[IgE|IgE]]-mediated reactions to [[penicillin]] (e.g., [[anaphylaxis]], [[angioedema]], [[bronchospasm]], or [[urticaria]]) should be [[desensitized]] in a hospital setting. In patients with reactions not likely to be IgE-mediated, outpatient-monitored test doses can be considered.}}
{{Family tree | | | | | | | | | | | | | |!| | | | | | | | | | | | | | }}
 
{{Family tree | | | | | | | | | |,|-|-|-|^|-|-|-|.| | | | | | | | | |}}
=====Pencillin Allergy: Non-pregnant Individuals=====
{{Family tree | | | | | | | | | H01 | | | | | | H02 | | | | | | | | |H01=Yes|H02=No}}
*No proven alternatives to [[penicillin]] are available for treating [[neurosyphilis]], [[congenital syphilis]], or [[Syphilis management during pregnancy|syphilis in pregnant women]]. [[Penicillin]] also is recommended for use, whenever possible, in HIV-infected patients.
{{Family tree | | | | | | | |,|-|^|-|.| | | | | |!| | | | | | | | |}}
 
{{Family tree | | | | | | | I01 | | I02 | | | | I03 | | | | | | | |I01=No penicillin allergy|I02=Penicillin allergy|I03=Unvolve appropriate subspecialists. Penicillin G benzazthine, 2.4 million units IM once a week for 3 weeks (three doses)<sup>**</sup>}}
*Of the adult U.S. population, 3%-10% have experienced an [[IgE|immunoglobulin E (IgE)]]-mediated allergic response to [[penicillin]]<ref name="pmid3300459">{{cite journal |author=Saxon A, Beall GN, Rohr AS, Adelman DC |title=Immediate hypersensitivity reactions to beta-lactam antibiotics |journal=[[Annals of Internal Medicine]] |volume=107 |issue=2 |pages=204–15 |year=1987 |month=August |pmid=3300459 |doi= |url= |accessdate=2012-02-18}}</ref><ref name="pmid18589051">{{cite journal |author=Yates AB |title=Management of patients with a history of allergy to beta-lactam antibiotics |journal=[[The American Journal of Medicine]] |volume=121 |issue=7 |pages=572–6 |year=2008 |month=July |pmid=18589051 |doi=10.1016/j.amjmed.2007.12.005 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9343(08)00037-5 |accessdate=2012-02-18}}</ref>, such as [[urticaria]], [[angioedema]], or [[anaphylaxis]] (i.e., upper airway obstruction, [[bronchospasm]], or [[hypotension]]). Readministration of [[penicillin]] to these patients can cause severe, immediate reactions.
{{Family tree | | | | | | | | |!| | |!| | | | | | | | | | | | | | |}}
 
{{Family tree | | | | | | | | |!| | J01 | | | | | | | | | | | | | |J01=Desensitization}}
*Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., [[anaphylaxis]]) may be treated with oral [[tetracycline]] or [[doxycycline]] although data to support this is limited. [[Ceftriaxone]] may be considered as an alternative therapy, although the optimal dose is not yet defined. However, cross-reactions in penicillin-allergic patients with [[cephalosporin]]s such as ceftriaxone are possible. [[Azithromycin]] was suggested as an alternative. However, there have been reports of treatment failure due to resistance in some areas.<ref name=Azith>{{cite journal | author=Lukehart SA, Godornes C, Molini BJ, et al | title=Macrolide resistance in Treponema pallidum in the United States and Ireland | journal=N Engl J Med. | volume=351 | pages=154-8 | date=2004 | PMID=15247355}}</ref>
{{Family tree | | | | | | | | |!| |!| | | | | | | | | | | | | | | |}}
 
{{Family tree | | | | | | | | | K01 | | | | | | | | | | | | | | | |K01=Aqueous crystalline penicillin G, 3 to 4 million units IV every 4 hours for 10 to 14 days; or penicillin G procaine, 2.4 million units once daily, plus 500 mg of probenecid orally four times daily for 10 to 14 days}}
*Because anaphylactic reactions to penicillin can be fatal, every effort should be made to avoid administering penicillin to penicillin-allergic patients, unless they undergo [[Pencillin desentization|acute desensitization]] to eliminate anaphylactic sensitivity.
{{Family tree/end}}
 
*Although an estimated 10% of persons who report a history of severe allergic reactions to [[penicillin]] continue to remain allergic their entire lives, with the passage of time, most persons who have had a severe reaction to penicillin stop expressing penicillin-specific [[IgE]].<ref name="pmid3300459">{{cite journal |author=Saxon A, Beall GN, Rohr AS, Adelman DC |title=Immediate hypersensitivity reactions to beta-lactam antibiotics |journal=[[Annals of Internal Medicine]] |volume=107 |issue=2 |pages=204–15 |year=1987 |month=August |pmid=3300459 |doi= |url= |accessdate=2012-02-18}}</ref><ref name="pmid18589051">{{cite journal |author=Yates AB |title=Management of patients with a history of allergy to beta-lactam antibiotics |journal=[[The American Journal of Medicine]] |volume=121 |issue=7 |pages=572–6 |year=2008 |month=July |pmid=18589051 |doi=10.1016/j.amjmed.2007.12.005 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9343(08)00037-5 |accessdate=2012-02-18}}</ref> These persons can then be treated safely with [[penicillin]].
 
=====Pencillin Allergy: Pregnant Individuals=====
All pregnant women with syphilis should be desensitized and treated with penicillin. Follow-up includes clinical evaluation at 1 to 2 weeks followed by clinical and serologic evaluation at 3, 6, 9, 12, and 24 months after treatment.
 
=====Pencillin Allergy: Desensitization=====
[[Desensitization (medicine)#Pencillin desentization|click here]]


==References==
==References==
Line 142: Line 108:
[[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:Infectious Disease Project]]
[[Category:Emergency mdicine]]
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Urology]]
[[Category:Neurology]]

Latest revision as of 00:23, 30 July 2020

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

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 medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Syphilis medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Syphilis medical therapy

CDC on Syphilis medical therapy

Syphilis medical therapy in the news

Blogs on Syphilis medical therapy

Directions to Hospitals Treating Syphilis

Risk calculators and risk factors for Syphilis medical therapy

Overview

Penicillin G, administered parenterally, is the preferred drug for treating all stages of syphilis. If the patient is allergic, then Tetracycline or doxycycline may also be used. During pregnancy, parenteral penicillin G is the only therapy with documented efficacy for syphilis. The Jarisch-Herxheimer reaction is an acute adverse febrile reaction that may occur after initiation of therapy for syphilis.

Medical Therapy

  • The preparation used (i.e., benzathine, aqueous procaine, or aqueous crystalline), the dosage, and the length of treatment depend on the stage and clinical manifestations of the disease.
  • Treatment for longer duration is required in patients with late latent, latent with unknown duration and tertiary syphilis.
  • Selection of the appropriate penicillin preparation is important, because T. pallidum can reside in sequestered sites (e.g., the CNS and aqueous humor) that are poorly accessed by some forms of penicillin.
  • Combinations of benzathine penicillin, procaine penicillin, and oral penicillin preparations are not considered appropriate for the treatment of syphilis.[2]

Pharmacotherapy

Syphilis Among non-HIV-Infected Persons[3]
Primary and Secondary Syphilis
Latent Syphilis
Early Latent Syphilis:
Late Latent Syphilis or Latent Syphilis of Unknown Duration:
  • Preferred regimen: Benzathine penicillin G 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
  • Pediatric regimen: Benzathine penicillin G 50,000 U/kg IM (Maximum, 2.4 MU), administered as 3 doses at 1 week intervals (total 150,000 U/kg up to the adult total dose of 7.2 MU)
Tertiary Syphilis
  • Preferred regimen: Benzathine penicillin G 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
Ocular syphilis
Pathogen-directed antimicrobial therapy:[4]
Syphilis Among HIV-Infected Persons
Primary and Secondary Syphilis Among HIV-Infected Persons
Latent Syphilis Among HIV-Infected Persons
Early latent:
Late latent:
Neurosyphilis Among HIV-Infected Persons
Syphilis During Pregnancy
  • Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection.
  • Parenteral penicillin G is the only therapy with documented efficacy for syphilis. Pregnant women with syphilis in any stage who report penicillin allergy should be desensitized and treated with penicillin
  • The Jarisch-Herxheimer reaction is an acute febrile reaction.
  • Frequently accompanied by headache, myalgia, fever, and other symptoms that usually occur within the first 24 hours after the initiation of any therapy for syphilis.
  • Patients should be informed about this possible adverse reaction.
  • The Jarisch-Herxheimer reaction occurs most frequently among patients who have early syphilis, presumably because bacterial burdens are higher during these stages.
  • Antipyretics can be used to manage symptoms, but they have not been proven to prevent this reaction.
  • The Jarisch-Herxheimer reaction might induce early labor or cause fetal distress in pregnant women, but this should not prevent or delay therapy.
Congenital Syphilis in Neonates
Condition 1: Infants with proven or highly probable disease and (1) an abnormal physical examination that is consistent with congenital syphilis;（2）a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer; or （3）a positive darkfield test of body fluid(s).
  • Preferred regimen (1): Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days
  • Preferred regimen (2): Procaine penicillin G 50,000 U/kg/dose IM q24h for 10 days
  • Note: If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant.
Condition 2: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was not treated, inadequately treated, or has no documentation of having received treatment; (2) mother was treated with erythromycin or another non-penicillin regimen; or (3) mother received treatment <4 weeks before delivery.
  • Preferred regimen (1): Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days
  • Preferred regimen (2): Procaine penicillin G 50,000 U/kg/dose IM q24h for 10 days
  • Preferred regimen (3): Benzathine penicillin G 50,000 U/kg/dose IM single dose
  • Note: If the mother has untreated early syphilis at delivery, 10 days of parenteral therapy can be considered
Condition 3: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery; and (2) mother has no evidence of reinfection or relapse.
Condition 4: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother's treatment was adequate before pregnancy; and (2) mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).
  • No treatment is required
  • Benzathine penicillin G 50,000 U/kg IM single dose might be considered, particularly if follow-up is uncertain.
Congenital Syphilis in infants and children

Approach to Diagnosis and Management of Syphilis

 
 
 
 
 
 
 
 
 
 
 
 
 
Positive syphilis screening test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Perform treponemal-specific test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive treponemal-specific test
 
 
 
 
 
 
 
 
 
 
 
Negative treponemal-specific test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Establish stage of infection; obtain quantitative nontreponemal test titres
 
 
 
 
 
 
 
 
 
Primary syphilis suspected
 
False-positive test result suspected
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signs or symptoms of primary or secondary syphilis
 
 
No clinical signs or symptoms (latent syphilis)
 
 
 
Signs or symptoms of tertiary (late) syphilis, or patient is HIC positive or otherwise immunocompromised
 
 
 
Obtain quantitative nontreponemal test titres
 
Consider other causes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Early latent syphilis
 
Late latent syphilis
 
Lumbar puncture
 
 
 
Penicillin G benzazthine, 2.4 million units IM (single dose)*
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Penicillin G benzazthine, 2.4 million units IM (single dose)*
 
 
 
Penicillin G benzazthine, 2.4 million units IM once a week for 3 weeks (three doses)**
 
 
 
 
 
 
 
 
Signs, symptoms, or CSF findings consistent with neurosyphilis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No penicillin allergy
 
Penicillin allergy
 
 
 
Unvolve appropriate subspecialists. Penicillin G benzazthine, 2.4 million units IM once a week for 3 weeks (three doses)**
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Desensitization
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aqueous crystalline penicillin G, 3 to 4 million units IV every 4 hours for 10 to 14 days; or penicillin G procaine, 2.4 million units once daily, plus 500 mg of probenecid orally four times daily for 10 to 14 days
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

References

  1. ↑ http://www.cdc.gov/std/tg2015/syphilis.htm Accessed on September 26, 2016
  2. ↑ http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5409a1.htm
  3. ↑ Workowski KA, Bolan GA (2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 64 (RR-03): 1–137. PMID 26042815.
  4. ↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
  5. ↑ 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.
  6. ↑ Yang CJ, Lee NY, Chen TC, Lin YH, Liang SH, Lu PL; et al. (2014). "One dose versus three weekly doses of benzathine penicillin G for patients co-infected with HIV and early syphilis: a multicenter, prospective observational study". PLoS One. 9 (10): e109667. doi:10.1371/journal.pone.0109667. PMC 4186862. PMID 25286091.


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Syphilis_medical_therapy&oldid=1643802"