Gonorrhea

Gonorrhea is a sexually transmitted infection Sexually Transmitted Infection Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections ( STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections) caused by the gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis, or pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis. Without antibiotic treatment, complications can occur. Complications for men may include epididymitis Epididymitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis, prostatitis Prostatitis Prostatitis is inflammation or an irritative condition of the prostate that presents as different syndromes: acute bacterial, chronic bacterial, chronic prostatitis/chronic pelvic pain, and asymptomatic. Bacterial prostatitis is easier to identify clinically and the management (antibiotics) is better established. Prostatitis, balanitis, and periurethral abscess. Women may develop pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease, which can cause perihepatitis and fertility issues. Disseminated gonococcal infection is associated with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, dermatitis, tenosynovitis, septic arthritis Septic arthritis Septic arthritis is an infection of the joint due to direct inoculation, contiguous extension, or hematogenous spread of infectious organisms into the joint space. This process causes an acute, inflammatory, monoarticular arthritis. Septic Arthritis, and (rarely) endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis or meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis. Gonorrhea diagnosis is made by microscopy, culture, or nucleic acid amplification tests. Management generally involves ceftriaxone, but treatment with doxycycline should be pursued if a coinfection with Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis (C. trachomatis) is not excluded.

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Epidemiology and Etiology

Epidemiology

  • 2nd most common bacterial STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections (chlamydia is the most common)
  • Worldwide annual incidence: approximately 80–100 million people:
    • Higher incidence in developing countries, including Africa and the Western Pacific
    • United States new cases in 2018: approximately 600,000
    • Incidence appears to be increasing globally.
  • Gender differences: men > women (particularly in men who have sex with men (MSM))
  • Most common age groups:
    • Men: 20–29 years old
    • Women: 15–24 years old
  • Factors sustaining gonorrhea in the population:
    • A recent reversing trend in safe sexual practices
    • Asymptomatic cases
    • Antibiotic-resistant strains
  • Gonorrhea is a notifiable disease.

Etiology

Gonorrhea is caused by the pathogen Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae (N. gonorrhoeae):

  • Gram-negative, nonmotile, nonspore-forming bacterium
  • Diplococcus (grows in pairs)
  • Culture and biochemical characteristics:
    • Grows best in aerobic conditions, but can grow in anaerobic conditions
    • Medium: modified Thayer-Martin (MTM) agar in 5% CO2 atmosphere:
      • Enriched chocolate agar 
      • Antimicrobial agents are used to selectively favor Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria growth by inhibiting the growth of fungi Fungi Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi. Mycology: Overview and other bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview.
    • Oxidase and catalase positive: 
      • Only oxidizes glucose 
      • Produces acid, not gas (nonfermenting)

Risk factors:

  • New or multiple sexual partners
  • Unprotected sex
  • Substance abuse
  • Low educational level
  • Low socioeconomic status
  • MSM
  • History of STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections
  • Gonorrhea is an independent factor for the transmission of HIV.

Pathophysiology

Transmission

  • Sexual contact with the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis, vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor, mouth, or anus of an infected individual
  • Perinatal (during vaginal delivery)

Virulence factors

  • Antigenic variation:
    • Allows expression of distinct surface antigens
    • Impedes recognition by the host’s immune system
  • Pili (fimbriae): 
    • Long, hair-like appendages on the bacterial surface
    • Able to lengthen and retract
    • Initiate attachment to host cells
    • Furnish resistance to phagocytosis
    • Provide antigenic variation among different strains 
  • Opacity-associated protein: 
    • Outer membrane protein
    • Aids in attachment to host cell receptors
  • Lipooligosaccharide (LOS) envelope protein:
    • Endotoxin
    • An oligosaccharide with a lipid A component 
    • Aids in evading the host’s defenses:
      • Can mimic a host’s glycosphingolipids
      • Able to provide antigenic variation
    • Responsible for toxicity by causing:
      • Fever
      • Ciliary loss
      • Mucosal cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death
  • Por protein: 
    • The most abundant surface protein
    • Provides aqueous channels
    • Renders some strains resistant to complement activation and deposition
    • Interferes with phagosome-lysosome fusion and may prevent intracellular killing by neutrophils
  • IgA protease: 
    • Cleaves and inactivates IgA-1 immunoglobulin 
    • Reduces the host’s immune defense

Pathogenesis

  • Bacterium adheres to the mucosal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium → competes with microbiota → colonizes and invades the epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium via transcytosis with the help of pili and opacity-associated proteins
  • LOS is released → activates toll-like receptor (TLR) and nucleotide-binding oligomerization domain-containing protein (NOD) signaling in:
    • Epithelial cells
    • Macrophages
    • Dendritic cells 
  • Production of cytokines and chemokines → influx of neutrophils → phagocytosis of harmful bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview → neutrophil-rich purulent exudate
  • Since N. gonorrhoeae has defense mechanisms Defense mechanisms Defense mechanisms are normal subconscious means of resolving inner conflicts between an individual's subjective moral sense and their thoughts, feelings, or actions. Defense mechanisms serve to protect the self from unpleasant feelings (anxiety, shame, and/or guilt) and are divided into pathologic, immature, mature, neurotic, and other types. Defense Mechanisms to resist being killed, the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview-laden neutrophils act as agents of transmission to another host.
Gonorrhea neisseria gonorrhoeae pathogenesis

Pathogenesis of N. gonorrhoeae:
DC: dendritic cell
LOS: lipooligosaccharide
TLR: toll-like receptor
NOD: nucleotide-binding oligomerization domain-containing protein
NLR: NOD-like receptor

Image by Lecturio.

Antimicrobial resistance

  • Penicillin and tetracycline resistance occurs from the acquisition of R factor (plasmid) coding for:
    • B-lactamase (penicillinase) → disrupts penicillin’s internal structure
    • TetM protein → prevents tetracycline from binding to its target 30S ribosomal subunit site
  • Quinolone resistance occurs from alterations in DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure gyrase and topoisomerase IV.
  • Macrolide (e.g., azithromycin) resistance can result from either:
    • Alterations in the ribosomal binding target
    • Under- and overexpression of influx and efflux systems
  • 3rd-generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with "cef-" or "ceph-." Cephalosporins (e.g, ceftriaxone): 
    • Remain highly effective as a single dose, but resistant strains have been isolated in Japan and in Europe
    • Resistant strains may have mutations in:
      • PenA gene → encodes a penicillin-binding protein
      • Multiple transferable resistance regulator (mtrR) gene → ↑ drug efflux
      • PenB gene → ↓ drug influx through por proteins

Clinical Presentation

Urogenital infection in men

  • Incubation period: 2–7 days
  • Most will be symptomatic.
  • Acute urethritis (most common presentation): 
    • Urethral discharge: 
      • Mucopurulent
      • Copious
    • Dysuria
    • Regional lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  • Complications:
    • Epididymitis: 
      • Unilateral testicular swelling
      • Tenderness
    • Prostatitis: 
      • Enlarged prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands gland
      • Pain and tenderness to palpation
    • Balanitis ( inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the glans penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis): 
      • Pain and pruritus
      • Ulceration
      • Swollen foreskin 
      • Phimosis
    • Periurethral abscess: 
      • Pain
      • Tenderness
      • Fluctuant mass
    • Cowper (bulbourethral) gland inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation or abscess: 
      • Fever
      • Pain and tenderness to palpation of the perineum
    • Seminal vesiculitis: 
      • Dysuria
      • Fever
      • Perineal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
      • Ejaculation of purulent material
Urethritis due to gonorrhea

Purulent penile discharge due to urogenital gonorrhea infection

Image: “4065” by CDC. License: Public Domain

Urogenital infection in women

  • Incubation period: < 10 days
  • Up to 70% of women are asymptomatic.
  • Cervicitis: 
    • Vaginal pruritus
    • Mucopurulent vaginal discharge
    • Physical examination: 
      • May be normal
      • Mucopurulent cervical discharge
      • Friable cervical mucosa
  • Urethritis:
    • Dysuria
    • Urinary urgency and frequency
  • Complications:
    • Infection of Bartholin’s or Skene’s glands:
      • Swollen glands
      • Pus may be expressed from the orifices. 
    • Pelvic inflammatory disease (PID): 
      • Occurs in 10%–20% of women with cervical gonorrhea
      • Pelvic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
      • Lower abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and tenderness
      • Abnormal vaginal bleeding
      • Dyspareunia
      • Fever 
      • Cervical motion tenderness
      • Adnexal tenderness
    • Perihepatitis (Fitz-Hugh-Curtis syndrome): 
      • Occurs in 4% of infected women; associated with PID
      • Inflammation of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver capsule

Extragenital infections

  • Ocular gonorrhea ( conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis):
    • Usually caused by autoinoculation from a primary site of infection in adults
    • Manifestations range in severity from asymptomatic to sight threatening.
    • Signs and symptoms:
      • Eyelid edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
      • Hyperemic conjunctiva
      • Chemosis 
      • Purulent discharge
      • Photophobia
      • Pain
    • Severe complications:
      • Corneal ulceration
      • Perforation
      • Blindness
  • Pharyngeal gonorrhea ( pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis): 
    • Due to orogenital sexual exposure
    • Often coexists with genital infection
    • Usually mild or asymptomatic
    • Signs and symptoms:
      • Sore throat
      • Pharyngeal exudates
      • Cervical lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
    •  Most cases resolve spontaneously.
  • Anorectal gonorrhea (proctitis):
    • In women: 
      • Most often occurs concurrently with cervicitis
      • Usually asymptomatic
    • In men:
      • More often associated with MSM
      • More likely to exhibit symptoms
    • Possible symptoms: 
      • Rectal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and fullness
      • Pruritus
      • Tenesmus
      • Purulent discharge
      • Rectal bleeding
Eye infection due to gonorrhea

Hyperemia, chemosis, and purulent discharge due to gonococcal conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis:
The patient developed partial blindness as a result of the infection.

Image: “Eye infection due to gonorrhea” by CDC/Arthur E. Kaye. License: Public Domain

Disseminated gonococcal infection

  • Bacteremia:
    • Fever
    • Chills
  • Purulent arthritis:
    • Abrupt onset
    • Mono- or oligoarthritis
    • Pain and swelling
    • Distal joints (e.g., knees, wrists, ankles)
  • Arthritis-dermatitis syndrome:
    • Occurs 2–3 weeks after genitourinary infection
    • Polyarthralgia:
      • Small or large joints
      • Asymmetric
      • Migratory
    • Tenosynovitis: often involves distal joints (e.g., fingers, toes, wrists, ankles)
    • Dermatitis: 
      • Painless
      • Pustular
      • Hemorrhagic papules or macules may occur.
  • Rare manifestations:
    • Endocarditis (common before antibiotics were available)
    • Myopericarditis
    • Meningitis
    • Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis
Gonococcal lesion on skin

Close-up view of a gonococcal lesion on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin of a patient’s arm Arm The arm, or "upper arm" in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm:
A gray pustule associated with disseminated gonococcal infection

Image: “2038” by CDC/Emory University, Dr. Thomas F. Sellers. License: Public Domain

Clinical presentation in children

Newborn Newborn A neonate, or newborn, is defined as a child less than 28 days old. A thorough physical examination should be performed within the first 24 hours of life to identify abnormalities and improve outcomes by offering timely treatment. Physical Examination of the Newborn infections:

  • Caused by exposure to infected cervical secretions at birth
  • Ophthalmia neonatorum: 
    • Purulent conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
    • Corneal ulcerations
    • Panophthalmitis
    • Blindness
  • Other mucosal sites of infection (usually asymptomatic): 
    • Vaginitis
    • Anorectal infection
    • Pharyngeal infection
  • Disseminated gonococcal infection:
    • Fever
    • Lethargy
    • Poor feeding
    • Vomiting
    • Arthritis (refusal to move the affected limb) 
    • Scalp abscesses
Gonococcal ophthalmia neonatorum

A newborn presenting with gonococcal ophthalmia neonatorum, caused by a maternally transmitted gonococcal infection.

Image: “Gonococcal ophthalmia neonatorum” by CDC/J. Pledger. License: Public Domain

After the neonatal period:

  • Suspect sexual abuse Sexual Abuse Sexual abuse and assault are major public health problems that affect many people from all walks of life, including people of all ages and genders, but it is more prevalent in women and girls, with reports of up to 1 in 3 experiencing sexual assault at some time in their life. Sexual Abuse if gonorrhea (or any other STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections) is diagnosed.
  • Vulvovaginitis Vulvovaginitis The term vulvovaginitis is used to describe an acute inflammation of the vulva and vagina. Vulvovaginitis can be caused by several infectious and non-infectious etiologies, and results from disruption of the normal vaginal environment. Common signs and symptoms include pain, pruritis, erythema, edema, vaginal discharge and dyspareunia. Vulvovaginitis is the most common manifestation.
  • Anorectal and pharyngeal infections are also common, but are usually asymptomatic.

Diagnosis

Laboratory evaluation

  • Nucleic acid amplification test:
    • The test of choice
    • > 95% sensitive and specific 
    • Amplifies N. gonorrhoeae DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure or RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure sequences
    • Specimens:
      • Endocervical or vaginal swab (women only)
      • Urethral swab (men only)
      • Oropharynx swab
      • Rectal swab
      • 1st-catch urine samples can also be analyzed for concurrent Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis (C. trachomatis).
    • Does not provide antibiotic susceptibility information
  • Gram staining: 
    • Sensitivity varies among sites:
      • > 90% in urethral exudates from men
      • 50% for endocervical exudates 
      • < 10% for joint fluid
      • Gram stain is not helpful for oropharynx or rectal samples because nonpathogenic Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria often colonize the sites. 
    • Findings: gram-negative intracellular diplococci
  • Cultures: 
    • Provides antibiotic susceptibility data
    • Helpful if suspicious of treatment failure
    • Sensitivity:
      • 72%–95% in symptomatic patients
      • 50%–85% in asymptomatic patients
  • Patients should also be evaluated for other STIs: 
    • C. trachomatis 
    • Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis
    • HIV
    • HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 & 2
    • Hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and C

Disseminated gonococcal infection evaluation

In addition to the laboratory evaluations above, the following testing may be performed in patients suspected of having disseminated gonococcal infection:

  • Blood cultures:
    • Positive culture is diagnostic.
    • More often positive in arthritis-dermatitis syndrome than with purulent arthritis
  • Synovial fluid:
    • WBC is usually > 50,000 cells/μL.
    • ↓ Glucose
    • Cultures: 
      • Positive in only 50% of cases
      • Less likely to be positive in arthritis-dermatitis syndrome
    • Nuclear acid amplification test can be used and is more sensitive.

Management

Uncomplicated gonococcal infection management

Antibiotic management:

  • Single IM dose of ceftriaxone
  • Dual treatment with ceftriaxone and azithromycin is no longer recommended due to increased resistance.
  • Doxycycline should be added if C. trachomatis coinfection has not been excluded.

Additional measures:

  • Pharyngeal infections: 
    • More difficult to cure 
    • Retest to confirm treatment was effective.
  • Ocular gonorrhea:
    • Ophthalmology evaluation 
    • Topical fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
    • Saline irrigation
  • Epididymitis and proctitis: Ceftriaxone is followed by a course of doxycycline.

Disseminated gonococcal infection management

  • IV ceftriaxone
  • Perform joint drainage in patients with septic arthritis Septic arthritis Septic arthritis is an infection of the joint due to direct inoculation, contiguous extension, or hematogenous spread of infectious organisms into the joint space. This process causes an acute, inflammatory, monoarticular arthritis. Septic Arthritis.

Management for sexual partners

  • All individuals who had sexual contact within the past 60 days with the patient should be notified for evaluation and treatment.
  • Expedited partner therapy (EPT): 
    • A prescription for cefixime is provided for sexual partners without a formal evaluation.
    • Limited to heterosexual contacts
    • Depends on individual country and state regulations
    • Not recommended for MSM due to the high risk of:
      • Coexisting infections (especially HIV)
      • Treatment failure (especially for pharyngeal infection)

Prevention and risk reduction

  • Latex condoms are one of the most effective preventative measures.
  • STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections testing every year if: 
    • Multiple sex partners 
    • History of STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections
  • Educate regarding the transmission of gonorrhea to other mucosal surfaces.

Complications

  • Infertility
  • Chronic pelvic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Fetal loss
  • Ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy
  • Urethral strictures
  • Increased risk of HIV transmission

Differential Diagnosis

  • Nongonococcal pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease: an ascending mono- or polymicrobial infection caused by C. trachomatis (most common), Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or "walking" pneumonia. Mycoplasma genitalium (M. genitalium), anaerobic organisms, enteric gram-negative rods, streptococci, genital mycoplasmas, and Gardnerella vaginalis. Patients may have cervical discharge, vaginal bleeding, lower abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Nuclear acid amplification tests and cultures of the endocervix aid in diagnosis, but management is usually with empiric antibiotics.
  • Nongonococcal cervicitis: other acute, infectious causes include Trichomonas vaginalis (T. vaginalis), C. trachomatis, or M. genitalium. Chronic cervicitis usually has a noninfectious cause, most often either mechanical or chemical irritation (e.g., tampon, diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm, or latex). Patients may have vaginal discharge, bleeding, and an erythematous, friable cervix. The etiology can be diagnosed by nuclear acid amplification tests: Gram stains and cultures are not as sensitive. Management involves antibiotics for the causative organism.
  • Nongonococcal urethritis in men: Gonococcal urethritis (GU) is usually more severe than nongonococcal urethritis, including those caused by C. trachomatis and M. genitalium. However, most cases of urethritis in the United States are caused by neither gonorrhea nor chlamydia. Diagnosis of GU is by gram staining and nuclear acid amplification tests. Other possible pathogens, which can be differentiated by specific laboratory testing, include Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria meningitidis, T. vaginalis, HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 & 2, and syphilis.
  • Epididymitis: Acute epididymitis Epididymitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis is usually infectious. The most common organisms responsible for acute epididymitis Epididymitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis in men < 35 years of age are N. gonorrhoeae and C. trachomatis. Coliform (e.g., Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli) and Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas species are more frequent in older men. Viral and mycotic causes of epididymitis Epididymitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis are rare. Nuclear acid amplification tests and cultures should be performed for diagnosis. Management depends on the etiology but can include antibiotics, scrotal elevation, ice packs, and analgesics.
  • Urinary tract infection: an infection (usually due to bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview) of the urinary system. Patients may develop urinary frequency, urgency, and/or suprapubic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Urinary tract infections Urinary tract infections Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections usually do not have vaginal discharge, but may have fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and flank pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain if the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys are affected. Nuclear acid amplification tests, microscopic examination, and urine specimen cultures help to diagnose the disease. Management includes appropriate antibiotic coverage for the causative organism.
  • Conjunctivitis: Acute conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis usually has a viral etiology, but bacterial causes include Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus, Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae, Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus, and C. trachomatis. Patients may experience eye irritation, hyperemia, and discharge. The diagnosis of conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis is clinical. Management is usually empirical with topical and/or systemic antibiotics.

References

  1. Riedel, S., Hobden, J.A. (2019). In Riedel, S, Morse, S.A., Mietzner, T., Miller, S. (Eds.), Jawetz, Melnick, & Adelberg’s Medical Microbiology (28th ed, pp. 295-301).
  2. Ram, S., Rice, P.A. (2018). In Jameson, J.L., et al. (Ed.), Harrison’s Principles of Internal Medicine (20th ed. Vol 1, pp. 1122-1129). 
  3. Morris, S.R. (2020). Gonorrhea. MSD Manual Professional Edition. Retrieved January 27, 2021, from https://www.msdmanuals.com/professional/infectious-diseases/sexually-transmitted-diseases-stds/gonorrhea
  4. Cyr, S. S. (2020). Update to CDC’s treatment guidelines for gonococcal infection, 2020. MMWR. Morbidity and Mortality Weekly Report, 69. Retrieved on January 29, 2021, from https://doi.org/10.15585/mmwr.mm6950a6
  5. Infectious diseases | 2021 National Notifiable Conditions. (n.d.). Retrieved January 29, 2021, from https://wwwn.cdc.gov/nndss/conditions/notifiable/2021/infectious-diseases/
  6. Lovett, A., & Duncan, J. A. (2019). Human immune responses and the natural history of Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae infection. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.03187
  7. Lockwood, C.J., Magriples U. (2020). Prenatal care Prenatal care Prenatal care is a systematic and periodic assessment of pregnant women during gestation to assure the best health outcome for the mother and her fetus. Prenatal care prevents and identifies maternal and fetal problems that adversely affect the pregnancy outcome. Prenatal Care: Initial assessment. UpToDate. Retrieved January 30, 2021, from https://www.uptodate.com/contents/prenatal-care-initial-assessment
  8. Price, G.A., and Bash, M.C. (2019). Epidemiology and pathogenesis of Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae infection. In Bloom, A. (Ed.), UpToDate. Retrieved February 23, 2021, from https://www.uptodate.com/contents/epidemiology-and-pathogenesis-of-neisseria-gonorrhoeae-infection
  9. Ghanem, K.G. (2020). Clinical manifestations and diagnosis of Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae infection in adults and adolescents. In Bloom, A. (Ed.), UpToDate. Retrieved February 23, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-neisseria-gonorrhoeae-infection-in-adults-and-adolescents
  10. Klausner, J.D. (2021). Disseminated gonococcal infection. In Bloom, A. (Ed.), UpToDate. Retrieved February 23, 2021, from https://www.uptodate.com/contents/disseminated-gonococcal-infection
  11. Seña, A.C., Cohen, M.S. (2021). Treatment of uncomplicated Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae infections. UpToDate. Retrieved January 30, 2021, from https://www.uptodate.com/contents/treatment-of-uncomplicated-neisseria-gonorrhoeae-infections
  12. Wong, B. (2018). Gonorrhea. In Chadrasekar, P.H. (Ed.), Medscape. Retrieved February 23, 2021, from https://emedicine.medscape.com/article/218059-overview

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