Pharmacotherapy of gonorrhoea & syphilis

1. PRESENTED BY: ANOOP UNIYAL
PHARM. D (PB) 1ST YEAR
DIVISION OF PHARMACY PRACTICE
SGRR UNIVERSITY

3.  Gono-seeds, rhoea-flow.
so, gonorrhoea means abnormal flow of semen.
 Caused by gram-negative diplococcus Neisseria
gonorrhoeae.
 Gonorrhea can cause infections in the genitals, rectum,
and throat.
 Vaginal, anal, or oral sex with someone who has
gonorrhea.
 Humans are the only known host of this intracellular
parasite.

4. In the U.S.
 2nd most common disease that is required to be
reported.
 718,000 new cases per year.
 Adolescent women (ages 15 to 19) currently have the
highest rates of infection.
 High risk of single episode of vaginal intercourse with
an infected male & increases with multiple exposures
(50%-70%).
 Risk of transmission from infected female to an
uninfected male is not as great following a single
episode(20%).

5.  Multiple & new sex partners
 Inconsistent condom use
 Urban residence
 Adolescents, females particularly
 Lower socio-economic status
 Drug addicts
 Exchanging of sex for drugs & money

6.  Efficiently transmitted by sexual contact
-Male to female via semen
-Female to male urethra
-Anal intercourse
-Oro-genital sex (pharyngeal infection)
-Peri-natal transmission (mother to infant)
 Gonorrhea associated with increased transmission &
susceptibility to HIV infection

7.  On contact with a mucosal surface lined by columnar,
cuboidal, or noncornified squamous epithelial cells, the
gonococci attach to cell membranes by means of surface
pili and are then pinocytosed.
 The virulence of the organism is mediated primarily by
the presence of pili and other outer membrane proteins.
After mucosal damage is established, polymorphonuclear
(PMN) leukocytes invade the tissue, submucosal
abscesses form, and purulent exudates are secreted.
 Most common sites of inoculation:
• Cervix (cervicitis) or vagina in the female
• Urethra (urethritis) or penis in the male

8. Differences Between Men
& Women with Gonorrhea

9. IN MEN:
 Urethritis; Epididymits
 Most infections among men are acute and symptomatic
with purulent discharge & dysuria (painful urination) after
2-5 day incubation period
 Male host seeks treatment early preventing serious
sequelae, but not soon enough to prevent transmission to
other sex partners
 The two bacterial agents primarily responsible for
urethritis among men are N. gonorrhoeae and Chlamydia
trachomatis

10. IN WOMEN:
 Cervicitis; Vaginitis; Pelvic Inflammatory
Disease (PID); Disseminated Gonococcal
Infection (DGI)
 Women often asymptomatic or have atypical
indications (subtle, unrecognized S/S); Often
untreated until PID complications develop
 Pelvic Inflammatory Disease (PID)
• May also be asymptomatic, but difficult diagnosis
accounts for many false negatives
• Can cause scarring of fallopian tubes leading to
infertility or ectopic pregnancy

11. IN WOMEN:
 Disseminated Gonococcal Infection (DGI):
• Result of gonococcal bacteremia
• Often skin lesions
• Petechiae (small, purplish, hemorrhagic spots)
• Pustules on extremities
• Arthralgias (pain in joints)
• Tenosynovitis (inflammation of tendon sheath)
• Septic arthritis
• Occasional complications: Hepatitis; Rarely
endocarditis or meningitis

12. Men Women
General Incubation period 1–14 days
Symptom onset in 2–8 days
Incubation period 1–14 days
Symptom onset in 10 days
Site of infection Most common—urethra
Others—rectum (usually due to
rectal intercourse in men who have
sex with men), oropharynx, eye
Most common—endocervical canal
Others—urethra, rectum (usually due
to perineal contamination)
oropharynx, eye
Symptoms May be asymptomatic or minimally
symptomatic
Urethral infection—dysuria and
urinary frequency
Anorectal infection—asymptomatic
to severe rectal pain
Pharyngeal infection asymptomatic
to mild pharyngitis
May be asymptomatic or minimally
symptomatic
Endocervical infection—usually
asymptomatic or mildly symptomatic
Urethral infection—dysuria, urinary
frequency
Anorectal and pharyngeal infection—
symptoms same as for Men
Signs Purulent urethral or rectal discharge
can be scant to profuse
Anorectal—pruritus, mucopurulent
discharge, bleeding
Abnormal vaginal discharge or
uterine bleeding; purulent urethral
or rectal discharge can be scant to
profuse
Complications Rare (epididymitis, prostatitis,
inguinal lymphadenopathy, urethral
stricture)
Disseminated gonorrhea
Pelvic inflammatory disease and
associated complications (ie,
ectopic pregnancy, infertility)
Disseminated gonorrhea (3 times
more common than in men)

13.  Gram-stained smears, culture, or methods based
on the detection of cellular components of the
gonococcus
 Alternative methods of diagnosis, including
1. Enzyme immunoassay (EIA),
2. DNA probe techniques, and
3. Nucleic acid amplification techniques (NAATs)

14.  NOTE: Importance of
Sensitivity vs. Specificity
for any Diagnostic Test

15. Sensitivity = Measure of True Positive Rate (TPR)
TPR = No. of True Pos. = No. of True Positive .
No. of Actual Pos. No. of (True Pos. + False Neg.)
Specificity = Measure of True Negative Rate (TNR)
TNR = No. of True Neg. = No. of True Neg. .
No. of Actual Neg. No. of (True Neg. + False Pos.)

16.  All gonorrhoea treatment regimens recommended
by the Centers for Disease Control and Prevention
(CDC) consist of various oral or parenteral
cephalosporins and fluoroquinolones given as a
single dose.
 Ceftriaxone, the only parenteral agent included in
CDC recommended first-line agents for the
treatment of gonorrhoea, is administered IM as a
single 125 mg dose.
 Some clinicians advocate that a single 2g dose of
azithromycin should be treatment of choice for
gonorrhoea because it is also effective in
eradicating concomitant chlamydial infection.

17. Type of Infection Recommended Regimens Alternative Regimens
Uncomplicated infections of
the cervix, urethra, and
rectum in adults,
Ceftriaxone 250 mg IM once
plus
Azithromycin 1 g orally once
Cefixime 400 mg orally once
Plus
Azithromycin 1 g orally once, or
doxycycline 100 mg PO twice daily
for 7 Days, or
Gemifloxacin 320 mg orally once
or gentamicin 240 mg IM
plus
Azithromycin 2 g orally
Once
Uncomplicated infections of
the pharynx
Ceftriaxone 250 mg IM once
plus
Azithromycin 1 g orally once
Consult with infectious
disease expert
Disseminated gonococcal
infection in adults (>45 kg)
Ceftriaxone 1-2 g IM or IV every 12-
24 hours
Plus
Azithromycin 1 g orally once
Cefotaxime 1 g IV every 8 hours or
ceftizoxime 1 g IV every 8 hours
Plus
Azithromycin 1 g orally
Once
Uncomplicated infections of
the cervix, urethra, and
rectum in children (<45 kg)
Ceftriaxone 25-50 mg/kg IV or IM
once (not to exceed 125 mg)

18. Type of Infection Recommended Regimens Alternative Regimens
Disseminated gonococcal
infection in children (<45 kg)
Ceftriaxone 50 mg/kg IV or IM once daily
(not to exceed 1 g)
Gonococcal conjunctivitis in
adults
Ceftriaxone 1 g IM once
Ophthalmia neonatorum Ceftriaxone 25–50 mg/kg IV or IM once
(not to exceed 125 mg)
Disseminated gonococcal
infection in neonates
Ceftriaxone 25-50 mg/kg/day IV or IM once
daily or cefotaxime 25 mg/kg IV or IM twice
daily for 7 days, or 10-14 days if
meningitis is suspected
Infants born to mothers with
gonococcal infection
(prophylaxis)
Erythromycin (0.5%) ophthalmic ointment
in a single application
Ceftriaxone 25-50 mg/kg IM or IV once (not
to exceed 125 mg)
 Tetracyclines are contraindicated during pregnancy. Pregnant women should be treated with
recommended cephalosporin-based combination therapy.
 Patients who are treatment failures with alternative regimens should be treated with
ceftriaxone 250mg IM once plus azithromycin 1 g PO once in consultation with an infectious
disease expert.
 Caution should be taken when administering ceftriaxone to hyperbilirubinemic neonates.

19. Treponema pallidum

20.  The causative organism of syphilis is Treponema pallidum,
a spirochete.
 Syphilis usually is acquired by sexual contact with infected
mucous membranes or cutaneous lesions, although on
rare occasions it can be acquired by nonsexual personal
contact, accidental inoculation, or blood transfusion.
 Syphilis has been known as "the great imitator" as it may
cause symptoms similar to many other diseases.

21.  In 2015, about 45.4 million people were infected with
syphilis, with 6 million new cases. During 2015, it caused
about 107,000 deaths, down from 202,000 in 1990.
 Of these newly diagnosed cases, 91% were reported in
men, the majority of whom were reported as MSM.

22.  The signs and symptoms of syphilis vary depending in
which of the four stages:
1. Primary syphilis,
2. Secondary syphilis,
3. Latent syphilis, and
4. Tertiary syphilis.

23.  The primary stage classically presents with a single
chancre (a firm, painless, non-itchy skin ulceration) but there
may be multiple sores.
 Typically disappear after a few weeks without treatment (still
progresses to next stage)
 Acquired by direct sexual contact with the infectious lesions of
another person.
 Incubation period- 9-90 days (mean, 21 days)
 Sharp borders- 0.3–3.0 cm in size
 The most common location in women is the cervix (44%),
the penis in heterosexual men (99%), and anally
and rectally relatively commonly in men who have sex
with men (34%).

24. Primary syphilis - chancre

25.  Develops 2-8 weeks after initial infection in untreated or
inadequately treated Individuals.
 In secondary syphilis a diffuse rash occurs, which frequently
involves the palms of the hands and soles of the feet.
 There may also be sores in the mouth or vagina.
 There may be a symmetrical, reddish-pink, non-itchy rash on
the trunk and extremities, including the palms and soles.
 Other symptoms may include fever, sore throat , malaise
, weight loss, hair loss, and headache.
 Rare manifestations include liver inflammation
, kidney disease, joint inflammation, periostitis , inflammation
of the optic nerve, uveitis, and interstitial keratitis.

26. SECONDARY SYPHILIS

27.  Latent syphilis is defined as having serologic proof of
infection without symptoms of disease.
 In latent syphilis, which can last for years, there are few
or no symptoms.
 It is further described as-
1. Early (less than 1 year after secondary syphilis)
2. Late (more than 1 year after secondary syphilis)
 Early latent syphilis may have a relapse of symptoms.
Late latent syphilis is asymptomatic, and not as
contagious as early latent syphilis.

28. Late syphilis

29.  In tertiary syphilis there are gummas (soft non-cancerous
growths), neurological, or heart symptoms.
 Tertiary syphilis may occur approximately 3 to 15 years after
the initial infection
 It may be divided into three different forms:
1. Gummatous syphilis (15%)
2. Late neurosyphilis (6.5%), and
3. Cardiovascular syphilis (10%)
 Gummatous syphilis or late benign syphilis usually occurs 1-
46 years after the initial infection, with an average of 15 years.
 Typically affect the skin, bone, and liver, but can occur
anywhere.

30. Cardiovascular syphilis -
narrowing of coronary ostia
in aortus
Neurosyphilis - spirochetes in
neural tissue

31.  In pregnant women with syphilis, T. pallidum can cross
the placenta at any time during pregnancy.
 Transmission of syphilis during pregnancy occurs
primarily transplacentally and can result in fetal death,
prematurity, or congenital syphilis.
 Symptoms can be seen during the first months of life
(early congenital syphilis) or later in childhood or
adolescence (late congenital syphilis)

32. Clinical presentation of Syphilis
General
Primary Incubation period 10-90 days (mean, 21 days)
Secondary Develops 2-8 weeks after initial infection in untreated or
inadequately treated Individuals
Latent Develops 4-10 weeks after secondary stage in untreated or
inadequately treated individuals
Tertiary Develops in approximately 30% of untreated or inadequately
treated individuals 10-30 years after initial infection
Site of Infection
Primary External genitalia, perianal region, mouth, and throat
Secondary Multisystem involvement secondary to hematogenous and
lymphatic spread
Latent Potentially multisystem involvement (dormant)
Tertiary CNS, heart, eyes, bones, and joints

33. Signs and Symptoms
Primary Single, painless, indurated lesion (chancre) that
erodes, ulcerates, and eventually heals (typical);
regional lymphadenopathy is common; multiple,
painful, purulent lesions possible but uncommon
Secondary Pruritic or nonpruritic rash, mucocutaneous lesions,
flu like symptoms, lymphadenopathy
Latent Asymptomatic
Tertiary Cardiovascular syphilis (aortitis or aortic
insufficiency), neurosyphilis (meningitis, general
paresis, dementia, tabes dorsalis, eighth cranial
nerve deafness, blindness), gummatous lesions
involving any organ or tissue

34.  Serologic test
 Dark-field microscopic examination
 Direct fluorescent-antibody (test) for T. pallidum (DFA-TP),
 Common nontreponemal tests include:
1. Venereal Disease Research Laboratory (VDRL) slide test,
2. Rapid plasma reagin (RPR) card test,
3. Unheated serum reagin (USR) test, and
4. Toluidine red unheated serum test (TRUST).

35. Stage/Type of Syphilis Recommended Regimens Follow-up Serology
Primary, secondary, or early
latent syphilis (<1 year’s
duration)
Adults: Benzathine penicillin G 2.4
million units IM in a single dose
Children: Benzathine penicillin G
50,000 units/kg IM in a single dose,
up to 2.4 million units
Quantitative nontreponemal tests at
6 and 12 months for primary and
secondary syphilis; at 6, 12, and 24
months for early latent syphilis
Late latent syphilis (>1 year’s
duration) or latent syphilis of
unknown duration or tertiary
syphilis or retreatment
Adults: Benzathine penicillin G 2.4
million units IM once a week for 3
successive weeks (7.2 million units
total)
Children: Benzathine penicillin G
50,000 units/kg IM once a week for 3
successive weeks, up to 7.2 million
units total
Quantitative nontreponemal tests at
6, 12, and 24 months
Neurosyphilis Aqueous crystalline penicillin G 18-
24 million units IV (3-4 million units
every 4 hours or by continuous
infusion) for 10-14 days
or
Aqueous procaine penicillin G 2.4
million units IM daily, plus
probenecid 500 mg orally four times
daily, both for 10-14 days
CSF examination every 6 months
until the cell count is normal; if it
has not decreased at 6 months or is
not normal by 2 years, retreatment
should be considered

36. Stage/Type of Syphilis Recommended Regimens Follow-up Serology
Congenital syphilis (infants with
proven or highly probable
disease)
Aqueous crystalline penicillin G
50,000 units/kg/dose IV every
12 hours during the first 7 days
of life and every 8 hours
thereafter for a total of 10 days
or
Procaine penicillin G 50,000
units/kg IM daily for 10 days
Serologic follow-up only
recommended if antimicrobials
other than penicillin are used
Penicillin-Allergic Patients:
Primary, secondary, or early
latent syphilis
Doxycycline 100 mg orally two
times daily for 14 days, or
Tetracycline 500 mg orally four
times daily for 14 days
or
Ceftriaxone 1-2 g IM or IV daily
for 10-14 days
Same as for non–penicillin-
allergic patients
Late latent syphilis (>1 year’s
duration) or syphilis of unknown
duration
Doxycycline 100 mg orally twice
a day for 28 days
or
Tetracycline 500 mg orally four
times daily for 28 days
Same as for non–penicillin-
allergic patients

37.  Health promotion, education & counseling
 Increased access to condoms
 Early detection through screening in selected high
risk populations
 Effective diagnosis & treatment
 Partner management
 Risk reduction counseling

38.  For women:
 If you are age 24 or younger and having sex = once every year
 If you are age 25 or older = if you have more than one sex partner
or a new sex partner.
 If you have had sex with someone who tested positive for gonorrhea.
 For men:
 Talk with a doctor about getting tested if you have had sex with
someone who tested positive for gonorrhea.

39.  Get tested for syphilis if you:
 are pregnant.
 are a man who has sex with men.
 have sex for drugs or money.
 have HIV or another STD.
 have had sex with someone who tested positive for syphilis.