PHARMACOTHERAPY OF SYPHILIS

PROF. DR SYED AZHAR SYED SULAIMAN

 Syphilis is a sexually transmitted disease with varied and often subtle
clinical manifestations.

 Primary syphilis typically presents as a solitary, painless chancre

 secondary syphilis can have a wide variety of symptoms, especially fever,

lymphadenopathy, rash, and genital or perineal condyloma latum.

 In latent syphilis, all clinical manifestations subside, and infection is

apparent only on serologic testing.

 Late or tertiary syphilis can manifest years after infection as gummatous

disease, cardiovascular disease, or central nervous system involvement.

 Neurosyphilis can develop in any stage of syphilis.

Sign and symptoms of syphilis
 The symptoms of syphilis are the same for men and
women, and can be difficult to recognise.

 They are often mild, which means you can pass on

the infection without knowing you have it.
Primary syphilis
 The initial symptoms of syphilis can appear any time from 10 days to
three months after you have been exposed to the infection.

 The most common symptom is the appearance of a small, painless sore

or ulcer called a chancre. The sore will appear on the part of your body
where the infection was transmitted, typically the penis, vagina, or
around the anus.

 The sores can also appear in the mouth or on the lips, tonsils, fingers or
buttocks. Most people only have one sore, but some people have more.

 The sore will then disappear within two to six weeks. If the condition is
not treated, syphilis will move into its second stage.
Secondary syphilis
 The symptoms of secondary syphilis will begin a few weeks after the
disappearance of the sore.
 Symptoms can include:
 a non-itchy skin rash appearing anywhere on the body, but commonly on the
palms of the hands or soles of the feet
 small skin growths, often mistaken for genital warts – on women these
appear on the vulva and for both men and women they appear around the
anus
 flu-like symptoms – such as tiredness, headaches, joint pains and fever
 swollen lymph glands
 weight loss
 patchy hair loss

 These symptoms may disappear within a few weeks, or come and go

over a period of months.
Latent phase
 Without treatment, syphilis will then move into its latent (hidden)
phase, will experience no symptoms, even though remain
infected.

 Latent syphilis can still be passed on during the first year of this
stage of the condition, usually through sexual or close physical
contact.

 The latent stage can continue for many years (even decades) after
you first become infected.

 However, without treatment, there is a risk that latent syphilis will

move on to the third, most dangerous stage – tertiary syphilis.

Tertiary syphilis
The symptoms of tertiary syphilis can begin years or even decades after initial
infection

 The symptoms of tertiary syphilis will depend on what part of the body the infection
spreads to. For example, it may affect the brain, nerves, eyes, heart, bones, skin or
blood vessels, potentially causing any of the following symptoms:
 stroke
 dementia
 loss of co-ordination
 numbness
 paralysis
 blindness
 deafness
 heart disease
 Skin rashes

 At this stage, syphilis can be dangerous enough to cause death.

 Parenterally administered penicillin G is considered
first-line therapy for all stages of syphilis.

 Alternative regimens for non-pregnant patients with no

evidence of central nervous system involvement include
doxycycline, tetracycline, ceftriaxone, and
azithromycin.

 In pregnant women and patients with neurosyphilis,

penicillin remains the only effective treatment option; if
these patients are allergic to penicillin, desensitization is
required before treatment is initiated.
Stages of Syphilis
 Primary syphilis most often manifests as a solitary, painless chancre that
develops at the site of infection an average of three weeks after exposure
to T. pallidum.

 Without treatment, blood-borne spread of T. pallidum over the next

several weeks to months results in secondary syphilis, which has
numerous clinical manifestations. The most common features are fever,
lymphadenopathy, diffuse rash, and genital or perineal condyloma latum.

 During the latent stage of syphilis, skin lesions resolve, and patients are
asymptomatic. However, serologic tests are positive for T. pallidum.

 Tertiary or late syphilis develops years after the initial infection and can
involve any organ system. The most dreaded complications are
neurosyphilis and involvement of the aortic valve and root.
PHARMACOTHERAPY
 The goal of pharmacotherapy is to eradicate the causative
organism of syphilis, T pallidum.

 Penicillin is the mainstay of treatment, the standard by which

other modes of therapy are judged, and the only therapy that
has been used widely for :
o neurosyphilis,
o congenital syphilis, or
o syphilis during pregnancy.
Penicillin
 The drug of choice is parenteral penicillin G for all stages of
syphilis.

 CDC STD treatment guidelines, penicillin G is the only therapy

that is clinically documented to be effective against syphilis during
pregnancy.

 Since the dividing time of T pallidum is slow (days), penicillin G

benzathine is the only penicillin effective for single-dose therapy
because it is in depo form and levels remain therapeutic in the
blood for up to 30 days.

 Avoiding Bicillin C-R (combination procaine and benzathine),

which remains in blood for only 7 days, is essential.
Syphilis Treatment and Care
 Syphilis can be cured with the right antibiotics. However, treatment will
not undo any damage that the infection has already caused.

 A single intramuscular injection of long acting Benzathine penicillin

G (2.4 million units administered intramuscularly) will cure a person
who has primary, secondary or early latent syphilis.

 Three doses of long acting Benzathine penicillin G (2.4 million units

administered intramuscularly) at weekly intervals is recommended for
individuals with late latent syphilis or latent syphilis of unknown
duration.

 Treatment will kill the syphilis bacterium and prevent further damage,
but it will not repair damage already done.
Syphilis Treatment and Care
 Selection of the appropriate penicillin preparation is important to
properly treat and cure syphilis. Combinations of some penicillin
preparations (e.g., Bicillin C-R, a combination of benzathine
penicillin and procaine penicillin) are not appropriate
treatments for syphilis, as these combinations provide inadequate
doses of penicillin.

 Although data to support the use of alternatives to penicillin is limited,

options for non-pregnant patients who are allergic to penicillin may
include doxycycline, tetracycline, and for neurosyphilis, potentially
probenecid.

 These therapies should be used only in conjunction with close clinical

and laboratory follow-up to ensure appropriate serological response and
cure.
Penicillins
 Penicillin G benzathine (Bicillin L-A)
 Benzathine penicillin G is the first-line agent for primary and
secondary syphilis infection. It is a spirocheticide with in vivo
activity against T pallidum. It interferes with cell wall
mucopeptide synthesis during replication.

 Penicillin G procaine
 Penicillin G procaine is the first-line agent for treating late
latent syphilis.
Alternatives
 Doxycycline
 Doxycycline is used as alternative therapy for syphilis
infection.

 Tetracycline
 Tetracycline is used as alternative therapy for syphilis
infection. It inhibits bacterial growth by binding to the 30S
ribosomal unit, preventing protein synthesis.
Alternatives
 Ceftriaxone (Rocephin)
 Ceftriaxone is an alternative agent for penicillin-allergic patientsit
has lower efficacy against gram-positive organisms and higher
efficacy against resistant organisms. It arrests bacterial growth by
binding to one or more penicillin binding proteins.

 Azithromycin (Zithromax)
 Azithromycin acts by binding to the 50S ribosomal subunit of
susceptible microorganisms and blocks dissociation of peptidyl
tRNA from ribosomes, causing RNA-dependent protein synthesis
to arrest. Nucleic acid synthesis is not affected
Alternatives to penicillin
 The efficacy of ceftriaxone and azithromycin in treating syphilis. -
Central nervous system (CNS) penetration and its similarity to penicillin
support the use of ceftriaxone in the treatment of syphilis dictates a 5-
to 7-day course of treatment for early syphilis.

 The long half-life of azithromycin and its clinical efficacy in vitro against
syphilis support its use in treating early syphilis. At present, however,
clinical data remain insufficient to recommend its use.

 No good evidence indicates that the non–beta-lactam antibiotics, which

are used as alternatives to penicillin, are clinically effective in syphilis.
Erythromycin has been associated with high failure rates. Doxycycline
may be an option for patients who refuse parenteral therapy.