List of Abbreviations
IgM, G, A - immunoglobulins of groups M, G, A
NASBA — Nucleic Acid Sequence-Based Amplification (method for amplification of RNA molecules in a biological sample)
PID - pelvic inflammatory disease
HIV - human immunodeficiency virus
DNA - deoxyribonucleic acid
STI — sexually transmitted infection
ICD — International Classification of Diseases
PCR — polymerase chain reaction
RNA - ribonucleic acid
RB - reticular body of Chlamydia trachomatis
EB - elementary body of Chlamydia trachomatis
** - drug is included in the VED list
Terms and Definitions
Urogenital chlamydial infection is a sexually transmitted infection caused by Chlamydia trachomatis.
Chlamydia trachomatis is a Gram-negative intracellular bacterium belonging to the order Chlamydiales, family Chlamydiaceae, genus Chlamydia.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Urogenital chlamydial infection is a sexually transmitted infection (STI) caused by Chlamydia trachomatis.
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The causative agent of urogenital chlamydial infection is Chlamydia trachomatis. Chlamydia trachomatis serotypes A, B, Ba, C are the causative agents of trachoma; D, E, F, G, H, I, J, K cause urogenital chlamydiosis, chlamydial conjunctivitis, pharyngitis, and proctitis; L1, L2, L3 cause lymphogranuloma venereum. Chlamydia pneumoniae, Chlamydia psittaci and Chlamydia pecorum have been classified into a separate genus Chlamydophila.
Chlamydia trachomatis are non-motile, coccoid, Gram-negative obligate intracellular microorganisms.
Chlamydia exist in two forms that differ in morphological and biological properties. The highly infectious, spore-like, extracellular form is the elementary body (EB), while the vegetative, reproductive, intracellular form is the reticular body (RB).
The first stage of the infectious process is the adsorption of elementary bodies (EBs) onto the host cell plasmalemma. Chlamydiae enter the cell via endocytosis. Invagination of the plasmalemma region with the adsorbed EBs into the cytoplasm leads to the formation of a phagocytic vacuole. This phase takes 7-10 hours. Following this, over the course of 6-8 hours, the EBs reorganize into the vegetative form—the reticulate body (RB), which is capable of growth and division.
Chlamydial replication leads to the formation of inclusions (Prowazek bodies). Over 18-24 hours of development, they localize within a cytoplasmic vesicle formed from the cell membrane. An inclusion may contain from 100 to 500 chlamydiae. Next, over 3642 hours, the maturation of RBs occurs via transitional (intermediate) bodies and the development of the next generation of EBs. The complete chlamydial reproductive cycle takes 48-72 hours and ends with the destruction of the infected cell. Under adverse conditions, chlamydiae are capable of long-term intracellular parasitism in a dormant state. The dormant state of chlamydiae, protected by the membranes of epithelial and endothelial cells, allows the pathogen to maintain its viability in unfavorable environments. During host cell division, chlamydiae retain the ability to actively replicate in newly formed cells as well. Pathogen replication in epithelial cells leads to a disruption of the epithelial layer integrity, desquamation, and lymphoid infiltration of tissues.
Chlamydiae exhibit a tropism for columnar epithelium and are capable of infecting the mucous membrane of the urethra, cervical canal, fallopian tubes, endometrium, rectum, oropharynx, and eye conjunctiva, as well as epithelial cells of lymphatic and blood vessels, leukocytes, monocytes, and macrophages. In adult women, microorganisms are unable to replicate in unchanged stratified squamous epithelium of the vagina due to high sensitivity to the acidic environment of its contents; therefore, the primary site of infection is typically the mucous membrane of the cervix. In childhood and adolescence, chlamydiae can cause infections of the vulvar and vaginal mucosae, facilitated by the anatomical and physiological characteristics of girls' reproductive systems (immaturity of physiological defense mechanisms, small number of superficial epithelial layers, alkaline reaction of vaginal discharge, and a cervicovaginal secretion acid-base balance close to alkaline).
Women with a history of chlamydial infection have a doubled risk of developing ovarian cancer. Chlamydiae also increase the risk of cervical cancer both with and without human papillomavirus coinfection. Chlamydiae suppress the cell's ability to repair defects and induce premature mitotic exit, promoting cervical metaplasia, which creates target cells for human papillomavirus coinfection and persistence [84, 85].
Infection in adults and adolescents occurs through any form of sexual contact with a person infected with chlamydia; in children, via the intranatal route and through sexual contact; in exceptional cases, young girls may be infected through violations of personal hygiene and childcare rules [36]. Vertical transmission of the infection is also possible [44].
1.3 Epidemiology of the Disease or Condition
Urogenital chlamydial infection is a widespread sexually transmitted infection. According to World Health Organization estimates, 131 million people are infected with Chlamydia trachomatis annually. The prevalence of chlamydial infection in the population varies by age, with the highest incidence rates observed in individuals under 25 years of age [41].
According to federal statistical reporting data in the Russian Federation, the incidence of chlamydial infection in 2021 was 17.9 cases per 100,000 population.
1.4 Features of Coding the Disease or Condition
Sexually transmitted chlamydial infections are represented by code A56 under the category "other sexually transmitted chlamydial diseases". Excluded from this category are: chlamydial lymphogranuloma venereum (A55), congenital chlamydial pneumonia (P23.1); neonatal chlamydial conjunctivitis and dacryocystitis (P39.1); chlamydial pneumonia (J16.0), and other chlamydial diseases (A74).
A56.0 - Chlamydial infections of the lower urinary tract;
A56.1 - Chlamydial infections of pelvic organs and other urogenital organs;
A56.2 - Chlamydial infection of the urogenital tract, unspecified;
A56.3 - Chlamydial infection of the anorectal region;
A56.4 - Chlamydial pharyngitis;
A56.8 - Sexually transmitted chlamydial infections of other localization.
A74.0 - Chlamydial conjunctivitis (H13.1*).
A74.8 - Other chlamydial infections.
A74.9 - Chlamydial infection, unspecified.
1.5 Classification of the disease or condition
There is no universally accepted classification of chlamydial infection. Clinically, the following forms of the disease are distinguished:
1. Chlamydial infections of the lower urinary tract:
a. urethritis;
b. cervicitis;
c. cystitis;
d. vulvovaginitis.
2. Chlamydial infections of pelvic organs and other urogenital organs:
a. paraurethritis;
b. epididymitis;
c. orchitis;
d. prostatitis accompanying urethritis;
d. vestibulitis;
e. salpingo-oophoritis;
f. endometritis.
3. Chlamydial infection of the anorectal region.
4. Chlamydial pharyngitis.
5. Other sexually transmitted chlamydial infections of other localization (pelvioperitonitis, arthritis, pneumonia, perihepatitis).
6. Chlamydial conjunctivitis.
1.6 Clinical presentation of the disease or condition
Monoinfection with Chlamydia trachomatis is oligosymptomatic or asymptomatic in the overwhelming majority of cases.
Chlamydial infections of the lower urogenital tract
Objective symptoms in women with an acute inflammatory process: hyperemia and edema of the mucous membrane of the external urethral meatus, infiltration of the urethral walls, scanty mucopurulent or mucous urethral discharge, edema and hyperemia of the cervical mucosa, mucopurulent discharge from the cervical canal, erosion of the cervical mucosa; in acute vaginitis in girls: edema and hyperemia of the vaginal walls and fornices, mucopurulent discharge in the posterior vaginal fornix.
Objective symptoms in men with an acute inflammatory process: hyperemia and edema of the mucous membrane of the external urethral meatus, infiltration of the urethral walls, scanty mucopurulent or mucous urethral discharge.
Chlamydial infection of the anorectal region
Objective symptoms in an acute inflammatory process: hyperemia of the skin of the anal folds, mucopurulent discharge from the rectum.
Chlamydial pharyngitis
Objective symptoms in an acute inflammatory process: hyperemia and edema of the oropharyngeal mucosa and tonsils.
Chlamydial conjunctivitis
Objective symptoms in an acute inflammatory process: hyperemia and edema of the conjunctiva of the affected eye, scanty mucopurulent discharge in the corners of the affected eye.
Chlamydial infections of the pelvic organs and other urogenital organs Objective symptoms in women:
- vestibulitis: minor mucopurulent vaginal discharge, hyperemia of the external openings of the vestibular gland ducts, tenderness and edema of the ducts upon palpation;
- catarrhal bartholinitis: minor mucopurulent
discharge from the opening of the Bartholin's gland, hyperemia of the gland opening, tenderness and edema upon palpation;
- salpingo-oophoritis: in the acute inflammatory process — enlarged fallopian tubes and ovaries tender upon palpation, shortening of the vaginal fornices, mucopurulent discharge from the cervical canal; in the chronic course of the disease — mild tenderness, induration of the fallopian tubes;
- endometritis: in the acute inflammatory process — tender, enlarged uterus of softer consistency, mucopurulent discharge from the cervical canal; in the chronic course of the disease — dense consistency and restricted mobility of the uterus.
Objective symptoms in men with an acute inflammatory process:
- epididymo-orchitis: mucopurulent urethral discharge, hyperemia and edema of the scrotum, enlargement, induration and tenderness of the testis and epididymis upon palpation;
- prostatitis accompanying urethritis: tender, indurated prostate gland upon palpation.
In individuals of both sexes, chlamydial involvement of the paraurethral glands is possible; objective symptoms in the acute inflammatory process include: mucopurulent urethral discharge, presence of dense, tender millet-sized nodules in the area of the paraurethral gland ducts.
Other sexually transmitted chlamydial infections
Chlamydial pelvioperitonitis has no specific symptoms and is characterized by sharp abdominal pain, nausea, vomiting, weakness, defecation disorders, a characteristic appearance (facies hippocratica), hectic body temperature, hypotension, oliguria, sharp abdominal tenderness on superficial palpation, muscle guarding in the lower abdominal wall, and a positive peritoneal irritation sign.
In some cases, the course of the disease may be complicated by reactive arthritis of chlamydial etiology (the prevalence is 30–40 cases per 100,000 cases of chlamydial infection) [56, 57, 67].
In disseminated chlamydial infection, patients of both sexes may develop pneumonia, perihepatitis, and peritonitis (Fitz-Hugh-Curtis syndrome) [36].
Chlamydial infection in pregnant women
Chlamydial infection can lead to pregnancy termination, miscarriage, development of fetoplacental insufficiency, intrauterine fetal infection, postpartum inflammatory diseases, and neonatal infections.
In the 1st trimester of pregnancy, the most characteristic complications are threatened miscarriage, missed abortion, and spontaneous abortion; in the 2nd and 3rd trimesters, the risk of pregnancy termination, tocolytic therapy for which usually yields an unstable effect. In the placentas of women with genital chlamydia, immune homeostasis is disrupted with the formation of pathogenic immune complexes including IgM, IgG, and IgA, which fix the C3 complement fraction as a marker of pathogenicity. In case of infection of the amniotic membranes, polyhydramnios, specific placental damage (placentitis), placental insufficiency, fetal hypotrophy and hypoxia may develop. Ultrasound examination of pregnant women with intrauterine infection reveals the following signs: polyhydramnios, oligohydramnios, hyperechogenic suspension in amniotic fluid, and placental changes. Ultrasound placentography in women with genital infectious pathology reveals: placental thickening, heterogeneous echogenicity of the placental parenchyma, premature placental "aging", dilation of intervascular spaces, dilation of the subchorianic space, and thickening/doubling of the contour of the basal plate. For pregnant women with chlamydial infection and fetoplacental insufficiency, its primary manifestations are disorders of intraplacental blood flow [47].
Chlamydial infection in newborns
In the presence of chlamydial urogenital infection in pregnant women, chlamydia is transmitted to newborns during delivery in the majority of cases; in 3.2%, intranatal infection occurs. Chlamydial infection in newborns most frequently manifests as conjunctivitis (33.4%), respiratory tract infection (22.2%), urinary tract infection (22.2%), and vulvitis (11.1%); less commonly, chlamydia is isolated from the oropharynx, nasopharynx, and rectum [45]. In addition to manifest forms (conjunctivitis, pneumonia, urogenital system infection), non-specific manifestations may be observed in the form of edema and hemorrhagic syndromes, prolonged hyperbilirubinemia, and delayed weight recovery. In a number of cases, intrauterine infection may manifest as a generalized form, jaundice syndrome, fetal hepatitis, and intrauterine growth restriction [46].
2. Diagnostics, medical indications and contraindications for diagnostic methods
Diagnostic criteria
The diagnosis of chlamydial infection is established based on the detection of Chlamydia trachomatis DNA and/or RNA in biological material using molecular biological laboratory methods.
2.1 Complaints and Anamnesis
Chlamydial infections of the lower urogenital tract
In 70–95% of women, the course of the disease is subjectively asymptomatic. In the acute course of the inflammatory process, the following subjective symptoms may occur: mucopurulent discharge from the urethra and/or genital tract, intermenstrual spotting, pain during sexual intercourse (dyspareunia), discomfort or pain in the lower abdomen, itching, burning, and painful urination (dysuria).
In 50% of men, the course of the disease is subjectively asymptomatic. In the acute course of the inflammatory process, the following subjective symptoms may occur: scanty mucopurulent urethral discharge; itching, burning, and painful urination (dysuria); discomfort, itching, and burning in the urethral area; pain during sexual intercourse (dyspareunia); frequent urination and urgent urinary urges (with proximal spread of the inflammatory process); perineal pain radiating to the rectum.
Subjective symptoms of chlamydial infection in childhood are similar to those in adults. A feature of the clinical course of the disease in girls is more pronounced subjective symptomatology and involvement of the mucous membranes of the vulva and vagina. In the acute course of vaginitis in girls, the following subjective symptoms may occur: itching, burning, pain in the vulvar and vaginal areas, and mucopurulent vaginal discharge.
Chlamydial infection of the anorectal region
In individuals of both sexes, the course of the disease is generally subjectively asymptomatic. In the acute course of the inflammatory process, the following subjective symptoms may occur: with localized rectal involvement – itching, burning in the anorectal region, minor yellowish or reddish rectal discharge; with localization of the process above the anal opening – painful tenesmus, painful defecation, mucopurulent rectal discharge often mixed with blood, and secondary constipation.
Chlamydial pharyngitis
In individuals of both sexes, the course of the disease is generally subjectively asymptomatic. In the acute course of the inflammatory process, the following subjective symptoms may occur: a feeling of dryness in the oropharynx; pain aggravated by swallowing.
Chlamydial conjunctivitis
Subjective symptoms: mild pain in the affected eye, dryness and redness of the conjunctiva, photophobia, and scanty mucopurulent discharge in the corners of the affected eye.
Chlamydial pelvic and other urogenital infections Subjective symptoms in women:
- vestibulitis: minor mucopurulent vaginal discharge, pain and swelling in the vulvar region;
- catarrhal bartholinitis: minor mucopurulent discharge from the duct opening of the Bartholin gland, pain and swelling in the gland region;
- salpingo-oophoritis: in the acute course of the inflammatory process – cramp-like lower abdominal pain, mucopurulent vaginal discharge; in the chronic course, subjective manifestations are less pronounced, and menstrual irregularities are noted;
- endometritis: in the acute course of the inflammatory process – lower abdominal pain, typically dull and aching in nature, mucopurulent vaginal discharge; in the chronic course, subjective manifestations are less pronounced, and scanty post- and intermenstrual spotting are often noted.
Subjective symptoms in men during the acute course of the inflammatory process:
- epididymo-orchitis: mucopurulent urethral discharge, dysuria, dyspareunia, pain in the epididymis and inguinal region, more often unilateral; pain in the perineum radiating to the rectum, lower abdomen, and scrotum; pain may spread to the spermatic cord, inguinal canal, lumbar, and sacral regions;
- prostatitis accompanying urethritis: pain in the perineum and lower abdomen radiating to the rectum, and dysuria.
In individuals of both sexes, chlamydial involvement of the paraurethral glands is possible, with the subjective symptoms being: itching, burning, painful urination (dysuria); mucopurulent urethral discharge; pain during sexual intercourse (dyspareunia); pain in the area of the external urethral meatus.
2.2 Physical Examination
An examination of the skin and visible mucous membranes of the external genitalia is performed; the condition of the mucosa of the external urethral meatus, the presence of free urethral discharge and its character are assessed, and the urethra and regional lymph nodes are palpated.
In sexually active females, an examination of the vestibule of the vagina with palpation of the vestibular gland area, inspection of the mucous membranes of the vaginal walls and fornices, and the visible portion of the cervix using vaginal specula is performed; discharge in the posterior and posterolateral vaginal fornices and cervical canal is evaluated; bimanual vagino-abdominal examination is carried out.
In men, palpation of the scrotal contents and digital rectal examination (as indicated) are performed.
To diagnose extragenital forms of chlamydial infection, an examination of the anorectal region, oropharyngeal mucosa, and conjunctiva is performed.
For objective clinical manifestations of the disease identified during physical examination, see the "Clinical Presentation" section.
2.3 Laboratory Diagnostics
The diagnosis is established based on the detection of Chlamydia trachomatis DNA and/or RNA using molecular diagnostic methods (PCR, real-time PCR) in the biological sample, taking into account the localization of the infection process and sexual history. To diagnose chlamydial infection of the lower urogenital tract, clinical material (scraping) is collected from the urethra in men, from the urethra and cervical canal in women, and from the vagina in girls; if extragenital localization of the pathogen is suspected, from the mucous membrane of the anal orifice, oropharynx, or conjunctiva; in case of pronounced clinical manifestations of urethritis, examination of the first portion of urine (first 10–20 ml) is possible.
It is recommended to verify the diagnosis of chlamydial infection based on the results of laboratory tests using molecular diagnostic methods aimed at detecting specific DNA and/or RNA fragments of Chlamydia trachomatis: molecular biological testing of oropharyngeal smears for chlamydia trachomatis (Chlamydia trachomatis) and/or rectal discharge for chlamydia trachomatis (Chlamydia trachomatis) and/or female genital tract discharge for chlamydia trachomatis (Chlamydia trachomatis) and/or urethral discharge for chlamydia trachomatis (Chlamydia trachomatis) and/or semen for chlamydia (Chlamidia trachomatis) and/or prostate secretion for chlamydia trachomatis (Chlamydia trachomatis) and/or conjunctival discharge for chlamydia trachomatis (Chlamydia trachomatis) and/or urine testing for chlamydia trachomatis (Chlamydia trachomatis) [1-8,15,16].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments:
If pelvic inflammatory disease (PID) is suspected, testing to detect specific DNA and/or RNA fragments of Chlamydia trachomatis from a cervical canal scraping and surgical material is mandatory.
The sensitivity of molecular diagnostic methods is 98–100%, specificity is 100%. Molecular biological testing of urine for chlamydia trachomatis (Chlamydia trachomatis) is used primarily in cases of pronounced clinical manifestations of urethritis.
To obtain reliable laboratory results, a number of requirements must be met, including:
- collection of clinical material from the urethra no earlier than 3 hours after the last urination; in the presence of profuse urethral discharge, 15-20 minutes after urination;
- collection of clinical material from the cervical canal and vagina before menstruation or 2 days after its completion;
- collection of clinical material from the cervical canal and vagina no earlier than 24–48 hours after transvaginal ultrasound and colposcopy;
- exclusion of vaginal douching on the eve of and on the day of the examination;
- avoidance of genital hygiene procedures using intimate hygiene products on the day of the examination;
- avoidance of antimicrobial agents and antiseptics used in gynecology (suppositories, creams, vaginal tablets) for 3–5 days prior to the examination;
- emptying the urinary bladder no later than 2 hours before collecting the first portion of urine;
- collection of clinical material for PCR and real-time PCR testing no earlier than one month after the end of therapy with agents active against Chlamydia trachomatis, and by NASBA method no earlier than 2 weeks after the end of therapy with agents active against Chlamydia trachomatis;
- compliance with the conditions for transporting clinical samples to the laboratory.
It is not recommended to use microbiological (culture) testing to isolate Chlamydia trachomatis in routine clinical practice [9].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
It is not recommended to use direct immunofluorescence, enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Chlamydia trachomatis, or microscopic and morphological methods for diagnosing urogenital and pelvic chlamydial infection, chlamydial conjunctivitis, pharyngitis, and proctitis [9, 10, 16].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
It is not recommended to use biological, chemical, and dietary provocation tests to increase the diagnostic and therapeutic efficacy of chlamydial infection [11,98].
LoR CGoE 3Level of Recommendation C (Level of Evidence - 3)
Comments: Due to the shared routes of transmission of STIs, HIV infection, and hepatitis B and C, patients with chlamydial infection should undergo:
- laboratory tests for syphilis and other STIs;
- determination of IgM and IgG antibodies to human immunodeficiency virus HIV-1/HIV-2 in blood;
- determination of hepatitis B virus surface antigen in blood and total IgM and IgG antibodies to hepatitis C virus in blood;
- for individuals with an unidentified source of infection: a repeat test for syphilis after 3 months, repeat determination of IgM and IgG antibodies to human immunodeficiency virus HIV-1/HIV-2 in blood, determination of hepatitis B virus surface antigen in blood, and determination of total IgM and IgG antibodies to hepatitis C virus in blood after 3–6–9 months.
2.4 Instrumental Diagnostics
It is recommended to refer the patient for a complex pelvic ultrasound examination if it is necessary to rule out pelvic inflammatory disease and complicated courses of chlamydial infection [42-44, 68].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
2.5 Other Procedures
An appointment (examination, consultation) with an obstetrician-gynecologist is recommended when the pelvic organs are involved in the inflammatory process, as well as in the management of pregnant women, breastfeeding women, and patients with chlamydial infection [15].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
An appointment (examination, consultation) with a urologist is recommended to diagnose potential reproductive system complications, in chronic cases, and when prior therapy for epididymo-orchitis or prostatitis accompanying urethritis is ineffective [15,98].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
An appointment (examination, consultation) with an ophthalmologist, otolaryngologist, proctologist, rheumatologist, or (in children) a neonatologist and pediatrician is recommended to determine the scope and nature of additional examinations [67,98].
GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
Indications for therapy
Identification of Chlamydia trachomatis DNA and/or RNA in a biological sample.
Treatment goals [66, 67]:
- eradication of Chlamydia trachomatis;
- clinical recovery;
- prevention of complications;
- prevention of transmission to others.
3.1. Conservative management
It is recommended to prescribe the following orally for the treatment of lower urogenital tract chlamydial infections in adults to achieve eradication of Chlamydia trachomatis:
doxycycline** 100 mg twice daily for 7 days [12-20, 48-51, 53]
LoR AGoE 1Level of Recommendation A (Level of Evidence - 1)
Comments: Doxycycline** is first-line therapy. Doxycycline** in tablet form (active ingredient: doxycycline monohydrate) is preferred due to its better tolerability
or
minocycline 100 mg twice daily for 7 days [70-74]
GCR CLEL 4Grade of Recommendation C (Level of Evidence - 4)
or
ofloxacin** 400 mg twice daily for 7 days [15, 16, 23, 24, 50]
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: Chlamydia trachomatis may develop resistance to macrolides as a result of mutations in 23S rRNA, rplD, and rplV genes; to fluoroquinolones as a result of mutations in gyrA, parC, and ygeD genes; and to tetracyclines as a result of mutations in the rpoB gene. However, to date, there is no evidence of any stable genetic or phenotypic resistance of clinical Chlamydia trachomatis strains to any of the recommended systemic antimicrobial agents of these groups that would affect treatment outcomes. Macrolide and tetracycline resistance in chlamydia has no genetic basis, as the emergence of resistance genes adversely affects the survival capacity of mutant microorganisms. Antimicrobial susceptibility testing of Chlamydia trachomatis for systemic antibacterial drugs when choosing a drug for the treatment of chlamydial infection is impractical [75-81].
It is recommended to prescribe the following orally for the treatment of anorectal chlamydial infections, chlamydial pharyngitis, and chlamydial conjunctivitis in adults to achieve eradication of Chlamydia trachomatis:
doxycycline** 100 mg twice daily for 7 days [12-20, 48-51, 53]
Level of Evidence AGrade of Recommendation 1Level of Recommendation A (Level of Evidence — 1)
or
minocycline [70-74]
GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)
Comment: for adults, 100 mg twice daily for 10 days [70-74]
or
ofloxacin** 400 mg twice daily for 7 days [15, 16, 23, 24, 50] Level of recommendation C (level of evidence quality – 5)
or
It is recommended to prescribe the following orally for the treatment of upper urogenital tract, pelvic, and other organ chlamydial infections in adults to achieve eradication of Chlamydia trachomatis:
doxycycline** 100 mg twice daily for 14 days [12, 15-17, 58, 63, 64,97] Level of recommendation C (level of evidence quality – 5)
or
minocycline 100 mg twice daily for 14 days [82, 83, 99]
LoR CGoE 3Level of Recommendation C (Level of Evidence - 3)
Comment: Contraindicated in children under 8 years of age.
or
ofloxacin** [12, 15-17, 69]
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: The duration of the course of therapy depends on the severity of clinical manifestations of inflammatory processes in the urogenital organs and the results of laboratory and instrumental studies. Depending on the above factors, the duration of therapy may vary from 14 to 21 days [17]. Systemic enzyme therapy, immunomodulating therapy, and therapy with antiseptics and disinfectants are not performed [15].
It is recommended for the treatment of pregnant and lactating women for the eradication of Chlamydia trachomatis to prescribe orally:
azithromycin** 1.0 g once [30, 31, 33]
GCR ALeE 2Grade of Recommendation A (Level of Evidence - 2)
or
amoxicillin** 500 mg 3 times daily for 7 days [20, 30]
LMR CLEL 4Level of recommendation evidence C (level of data validity - 4).
Comments: According to global practice amoxicillin** is prescribed to pregnant women at 500 mg 3 times daily for 7 days [20, 30]
Treatment of pregnant women with chlamydial infection is carried out at any stage of pregnancy using systemic antibacterial drugs, taking into account their effect on the fetus.
When prescribing azithromycin**, breastfeeding should be suspended for the duration of treatment if the expected benefit to the mother outweighs the risk to the newborn. An association has been found between the use of macrolides during pregnancy, especially erythromycin, and adverse outcomes in children [86, 87].
Amoxicillin** is an alternative drug for the treatment of pregnant women with chlamydial infection due to the risk of chlamydial persistence after the use of beta-lactam antibacterial drugs (penicillins), as demonstrated in in vitro animal studies [88, 86, 89].
It is recommended for the treatment of children for the eradication of Chlamydia trachomatis (under 8 years of age and/or weighing less than 45 kg) to prescribe orally:
azithromycin** [37, 38, 65]
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
Comments: Treatment of chlamydial infection in children over 8 years of age and/or weighing more than 45 kg is carried out in accordance with adult treatment regimens, taking into account contraindications.
Data on the efficacy and optimal dose of azithromycin** for the treatment of chlamydial infection in infants and children weighing <45 kg are limited; available data indicate that a short course of therapy (azithromycin** 20 mg per kg of body weight once daily for 3 days), as well as azithromycin** 10 mg per kg of body weight daily for 7 days may be effective [37, 38, 65]
In generalized chlamydial infection and neonatal pneumonia, intravenous erythromycin may be used in an inpatient setting: for children in the first three months of life, 20-40 mg per kg of body weight per day (in severe infections, the dose may be doubled); for children older than 4 months, 30-50 mg per kg of body weight per day divided into 2-4 doses for 14-21 days.
It is recommended to prescribe to newborns with chlamydial conjunctivitis [60-62]:
Erythromycin
LeveL of Recommendation BGrade of Evidence 2LeveL of Recommendation B (Grade of Evidence - 2)
Comments: According to global practice, erythromycin can be prescribed at 50 mg per kg of body weight per day, divided into 4 doses for 14 days [60-62]. Also in global practice azithromycin** is used, prescribed at 20 mg per kg of body weight orally once daily for 3 days; newborns born to mothers with untreated chlamydial infection may be prescribed prophylactic treatment if testing cannot be performed [44].
3.2. Surgical treatment
Not applicable.
3.3. Other treatment
Diet therapy is not used. Analgesia is not used.
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Rehabilitation is not used.
5. Prevention and Dispensary Observation
- early detection of chlamydial infection through screening of sexually active women aged 25 years and younger and men aged 30 years and younger, individuals at risk for STI acquisition (commercial sex workers, sexually active adolescents, etc.), and couples preparing for pregnancy;
- informing the public about the transmission routes of chlamydial infection and its consequences for reproductive health;
- using barrier contraception methods or avoiding all forms of casual sexual contact;
- examination and treatment of sexual partners [41].
6. Organization of Medical Care
Treatment is primarily provided on an outpatient basis in a dermatovenereology healthcare facility, and for pregnant women, in an obstetric and gynecological healthcare facility.
Indications for hospitalization and inpatient treatment include complicated courses of chlamydial infection (moderate and severe pelvic inflammatory disease [PID], moderate and severe epididymitis/epididymo-orchitis, pelvioperitonitis, disseminated chlamydial infection).
Upon diagnosing a patient with chlamydial infection, dermatovenerologists, obstetrician-gynecologists, coloproctologists, urologists, and physicians of other specialties shall fill out form No. 089u/kv "Notification of a patient with a newly established diagnosis of: syphilis, gonococcal infection, chlamydial infections, trichomoniasis, anogenital herpetic viral infection, anogenital (venereal) warts, mycosis, scabies" in the manner established by the letter of the Russian Ministry of Health dated March 2, 2015, No. 13-2/25.
Pregnant women with risk factors for chlamydial infection (age under 25, non-use of condoms during the last sexual intercourse, more than 2 sexual partners in the past 12 months, recent change of sexual partner) should be screened for urogenital chlamydial infection at their first visit to an obstetrician-gynecologist and in the third trimester to prevent postpartum maternal complications and chlamydial infection in the infant [93-96].
Cure assessment for chlamydial infection is performed based on PCR and real-time PCR test results no earlier than one month after the completion of antibiotic therapy, and by NASBA no earlier than 2 weeks after the completion of antibiotic therapy.
Patients with negative test results do not require further follow-up.
In case of treatment failure, it is recommended to rule out reinfection and prescribe a systemic antibacterial drug from another pharmacological group [15].
LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)
7. Additional Information
Treatment outcomes are affected by compliance with the dosage regimen of systemic antibacterial drugs, the use of barrier contraception during therapy and until cure is confirmed, the avoidance of all forms of casual sexual contact, and the treatment of sexual partners.
Criteria for Evaluating the Quality of Medical Care
№ | Quality criteria | Performance evaluation |
|---|---|---|
1 | Confirmation of the diagnosis by molecular biological testing methods | Yes/No |
2 | Doxycycline** or ofloxacin** or minocycline prescribed | Yes/No |
3 | Azithromycin** or amoxicillin** prescribed to pregnant women and women during lactation | Yes/No |
4 | Azithromycin** or erythromycin prescribed to children | Yes/No |
References
Show references
CDC. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae. 2014. MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports. Centers for Disease Control. 2014;63(RR-02):1-19.
Grad A, Vica ML, Matei HV, Grad DR, Coman I, and Tataru DA. Polymerase Chain Reaction as a Diagnostic Tool for Six Sexually Transmitted Infections - Preliminary Results: Clujul Med. 2015;88(1):33-37.
Knox J, Tabrizi SN, Miller P, et al. Evaluation of self-collected samples in contrast to practitioner-collected samples for detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis by polymerase chain reaction among women living in remote areas. Sex Transm Dis. 2002;29(11):647-654.
Chachter J, Chernesky MA, Willis DE, et al. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: Results from a multicenter evaluation of the APTIMA assays for both infections. Sex Transm Dis. 2005;32(12):725-728.
Schachter J, Moncada J, Liska S, Shayevich C, Klausner JD. Nucleic acid amplification tests in the diagnosis of Chlamydial and Gonococcal infections of the oropharynx and rectum in men who have sex with men. Sex Transm Dis. 2008;35(7):637-642.
Mimiaga MJ, Mayer KH, Reisner SL, et al. Asymptomatic gonorrhea and chlamydial infections detected by nucleic acid amplification tests among Boston area men who have sex with men. Sex Transm Dis. 2008;35(5):495-498.
Bachmann LH, Johnson RE, Cheng H, et al. Nucleic acid amplification tests for diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis rectal infections. J Clin Microbiol. 2010;48(5):1827-1832.
Shipitsyna EV, Shalepo KV, Savicheva AM, Domeika M. [Scientific research on optimizing methods of laboratory diagnostics of sexually transmitted infections]. Journal of Obstetrics and Women's Diseases. 2007;(5):32-35. (In Russ.)
Association of Public Health Laboratories (APHL). Laboratory diagnostic testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Expert consultation meeting summary report. Atlanta, GA. Silver Spring, MD, APHL, 2009; uRLhttp://www.aphl.org/aphlprograms/infectious/std/Documents/ID_2009Jan_C TGCLab-Guidelines-Meeting-Report.pdf.
Horner P et al. Enhanced enzyme immunoassay with negative-gray-zone testing compared to a single nucleic acid amplification technique for community based chlamydial screening of men. Journal of Clinical Microbiology. 2005; 43(5):2065-2069.
Renton A, Filatova E, Ison C, Meheus A, Dmitriev G, Akovbian V, et al. A trial of the validity of genital smears and cultures with gonococcal vaccine provocation in diagnosing genital gonorrhoea in women. Int J STD AIDS. 2009; (20):24-29.
Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital Chlamydial infections: a meta-analysis of randomized clinical trials. Sex Transm Dis. 2002;(29):497-502.
Kong FY, Tabrizi SN, Fairley CK, Vodstrcil LA, Huston WM, Chen M, Bradshaw C, Hocking JS. The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis. J Antimicrob Chemother. 2015;70(5):1290-7.
Geisler WM, Koltun WD, Abdelsayed N, et al. Safety and efficacy of WC2031 versus vibramycin for the treatment of uncomplicated urogenital Chlamydia trachomatis infection: a randomized, double-blind, double-dummy, active- controlled, multicenter trial. Clin Infect Dis. 2012;(55):82-8.
CDC. Sexually Transmitted Diseases Guidelines; 2014; URL:http://www.cdc.gov/std/treatment/2014/2014-std-guidelines-peer-reviewers- 08-20-2014.pdf
European guideline for the management of Chlamydia trachomatis infections 2015. URL http://www.iusti.org/regions/europe/pdf72015/Chlamydia2015.pdf .
Adimora AA. Treatment of uncomplicated genital Chlamydia trachomatis infections in adults. Clin Infect Dis. 2002;(35):S183-S186.
Kong FY and Hocking JS. Treatment challenges for urogenital and anorectal Chlamydia trachomatis. BMC Infect Dis. 2015;15:293.
Khosropour CM, Dombrowski JC, Barbee LA, et al. Comparing azithromycin and doxycycline for the treatment of rectal chlamydial infection: A retrospective cohort study. Sex Transm Dis. 2014;41:79-85.
Schwebke JR, Rompalo A, Taylor S, et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens - a randomized clinical trial. Clin Infect Dis. 2011;52:163-170.
Czeizel AE, Rockenbauer M, Olsen J, Sorensen HT. A case-control teratological study of spiramycin, roxithromycin, oleandomycin and josamycin. Acta Obstet Gynecol Scand. 2000;(79):234-7.
Iakubovich AI, Chuprin AE, Rakitin DA. Urogenital chlamydia infection: treatment with wilprafen. Urologiia. 2003;(1):55-8.
Ibsen HH, Moller BR, Halkier-Sorensen L, et al. Treatment of nongonococcal urethritis: comparison of ofloxacin and erythromycin. Sex Transm Dis. 1989;(16): 32-35.
Maiti H, Chowdhury FH, Richmond SJ, et al. Ofloxacin in the treatment of uncomplicated gonorrhea and chlamydial genital infection. Clin Ther.1991;(13): 441-447.
Mikamo H, Sato Y, Hayasaki Y, Hua YX, Tamaya T. Adequate levofloxacin treatment schedules for uterine cervicitis caused by Chlamydia trachomatis. Chemotherapy. 2000;46(2):150-2. .
Khrianin AA and Reshetnikov OV. Is it safe to use josamycin in the obstetrics practice in Russia? Antibiot Khimioter. 2007;(52):32-36.
Primiero FM, Caruso G, Grottanelli F, et al. Josamycin in the treatment of Chlamydia trachomatis cervicitis. J Chemother. 1989;(1):909-910.
Lucisano A, Vitale AM, Cinque B, et al. Josamycin in the treatment of chlamydial genital infections in infertile women. J Chemother. 1989;(1):906-908.
Molochkov VA, Mostakova NN. Vilprafene (josamycin) therapy of chronic chlamydial prostatitis. Urologiia. 2001;(3):34-5.
Rahangdale L, Guerry S, Bauer HM, Packel L, Rhew M, Baxter R, et al. An observational cohort study of Chlamydia trachomatis treatment in pregnancy. Sex Transm Dis. 2006;(33):106-10.
Brocklehurst P, Rooney G. Interventions for treating genital chlamydia trachomatis infection in pregnancy. Cochrane Database of Systematic Reviews. 2007, Issue 4. Art. No.: CD000054.
Soltz-Szots J, Schneider S, Niebauer B, Knobler RM, Lindmaier A. Significance of the dose of josamycin in the treatment of chlamydia infected pregnant patients. Z Hautkr. 1989;(64):129-31.
Galimova ER. [Experience in treating urogenital chlamydial infection in pregnant women with josamycin]. Actual Issues of Obstetrics and Gynecology: Collected Scientific Papers 2001-2002;1(1). (In Russ.)
Darville T. Chlamydia trachomatis infections in neonates and young children. Semin Pediatr Infect Dis. 2005;(16):235-44.
Wang Y, Yang WB, Yuan HY, Zhang QX, Zhu XY. Analysis of the infection status and the drug resistance of mycoplasma and chlamydiae in genitourinary tracts of children with suspected nongonococcal urethritis. Zhonghua Er Ke Za Zhi. 2009;47(1):62-4.
Management of patients with sexually transmitted infections and urogenital infections: Clinical Guidelines. Russian Society of Dermatovenereologists and Cosmetologists. Moscow: Delovoy Ekspress; 2012. 112 p. (In Russ.)
Hammerschlag MR, Gelling M, Roblin PM, Kutlin A, Jule JE. Treatment of neonatal chlamydial conjunctivitis with azithromycin. The Pediatric infectious disease journal. 1998;7(11):1049-1050.
Kohlhoff CA, Hammerschlag MR. Treatment of chlamydial infections: 2014 update (review). Expert Opin. Pharmacother. 2015;16(2):205-212.
Sexually Transmitted Diseases Treatment Guidelines 2015: Chlamydial Infections.
Mikamo H, Yamagishi Y, Takahashi K, et al. Clinical study of levofloxacin 500 mg qd in the treatment of cervicitis and intrauterine infections caused by Chlamydia trachomatis. Jpn J Antibiot. 2011;64(4):217-29.
Global health sector strategy on sexually transmitted infections 2016-2021. https://apps.who.int/iris/bitstream/handle/10665/250268/WHO-RHR-16.09-eng.pdf?sequence=1.
Landers DV, Sweet R.L. Current trends in the diagnosis and treatment of tuboovarian abscess. Am. J. Obstet. Gynecol. 1985;(151):1098-1110.
Moore KR, Smith JS, Cole SR, Dittmer DP, Schoenbach VJ, Baird DD. Chlamydia trachomatis Seroprevalence and Ultrasound-Diagnosed Uterine Fibroids in a Large Population of Young African-American Women. Am J Epidemiol. 2018;187(2):278-286.
Honkila M, Wikstrom E, Renko M, et al. Probability of vertical transmission of Chlamydia trachomatis estimated from national registry data. Sex Transm Infect. 2017;93(6):416-420.
Bekarova AM. [Chlamydial infection in newborns and infants in the first year of life]. Cand. Sci. (Med.) Diss. Moscow; 2003. (In Russ.)
Vinogradova IV. [Epidemiology, diagnostic criteria, and course of chlamydial infection in newborns]. Cand. Sci. (Med.) Diss. St. Petersburg; 2004. (In Russ.)
Budanov PV. [Current problems in the treatment of pregnant women with recurrent chlamydial infection]. Lechashchiy Vrach. 2007;(10):21-5. (In Russ.)
Paez-Canro C, Alzate JP, Gonzalez LM, Rubio-Romero JA, Lethaby A, Gaitan HG. Antibiotics for treating urogenital Chlamydia trachomatis infection in men and non-pregnant women. Cochrane Database Syst Rev. 2019;1(1):CD010871. Published 2019 Jan 25.
Geisler WM, Uniyal A, Lee JY, Lensing SY, Johnson S, Perry RCW, Kadrnka CM and Kerndt PR. Azithromycin versus doxycycline for urogenital chlamydia trachomatis infection. N Engl J Med. 2015;373:2512-2521.
WHO Guidelines for the Treatment of Chlamydia trachomatis. 2016. URL: https://www.ncbi.nlm.nih.gOv/books/NBK379707/pdf7Bookshelf_NBK379707.p df
Nicole HT, Dukers-Muijrers M, Petra F, Wolffs G, De Vries H, Gotz HM, Heijman T, Bruisten S, Eppings L, Hogewoning A, Steenbakkers M, Lucchesi M, Schim van der Loeff MF, Christian J P A Hoebe. Treatment effectiveness of azithromycin and doxycycline in uncomplicated rectal and vaginal Chlamydia trachomatis infections in women: A multicenter observational study (FemCure). Clinical Infectious Diseases. 2019;69(1):1946-1954.
Karl E Miller. diagnosis and treatment of Chlamydia trachomatis infection. Am Fam Physician. 2006;73(8):1411-1416.
Kong FY, Tabrizi SN, Law M, et al. Azithromycin versus doxycycline for the treatment of genital Chlamydia infection: A meta-analysis of randomized controlled trials. Clin Infect Dis. 2014;59:193-205.
Takahashi S, Ichihara K, Hashimoto J, et al. Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with nongonococcal urethritis. J Infect Chemother. 2011;17:392-6.
Lanjouw E, Ossewaarde JM, Stary A, Boag F. European guideline for the management of Chlamydia trachomatis infections. 2010. URL: https://www.aslimnica.lv/sites/default/files/editor/euro_ guideline_chlamydi a_2010.pdf
Carter JD and Hudson AP. The evolving story of Chlamydia-induced reactive arthritis. Curr Opin Rheumatol. 2010;(22):424-430.
Bojovic J, Strelic N and Pavlica L. Reiter"s syndrome - disease of young men - analysis of 312 patients. Med Pregl. 2014;(67):222-230.
CDC 2015. Sexually transmitted infections treatment guidelines. Pelvic Inflammatory Disease. URL. https://www. cdc.gov/std/tg2015/pid.htm.
Belousov YuB, Karpov OI, Belousov DYu. [Clinical and economic rationale for the use of josamycin in the treatment of urogenital chlamydiosis]. Qualitative Clinical Practice. 2006;(1):64-75. (In Russ.)
Tan AK. Ophthalmia Neonatorum. N Engl J Med. 2019;380(2):e2. doi: 0.1056/NEJMicm1808613.
Jin J. Prevention of Gonococcal Eye Infection in Newborns. JAMA. 2019;321(4):414.
Zikic A. et al. Treatment of neonatal chlamydial conjunctivitis: A systematic review and meta-analysis. Journal of the Pediatric Infectious Diseases Society. 2018;7(3):e107-e115.
British Association of Sexual Health and HIV. 2014 Draft UK national guideline for the management of genital infection with Chlamydia trachomatis, http:// www.bashh.org/BASHH/Guidelines/Guidelines/BAS HH/Guidelines/Guidelines.aspx?hkey=072c83ed-0e9b44b2-a989-7c84e4fbd9de (2013, accessed 15 August 2015).
European Branch of the International Union against Sexually Transmitted Infections (IUSTI Europe) and the European Office of the World Health Organisation (WHO-Europe).
Savenkova MS, Afanasyeva AA. [Chlamydiosis in children. Modern aspects of treatment]. Effective Pharmacotherapy. 2012;(53):6-13. (In Russ.)
Workowski KA, Lampe MF, Wong KG et al. Long-term eradication of Chlamydia trachomatis genital infection after antimicrobial therapy evidence against persistent infection. JAMA. 1993;270(17):2071-2075.
Taylor-Robinson D and Keat A. Observations on Chlamydia trachomatis and other microbes in reactive arthritis. Int J STD AIDS. 2015;(26):139-144.
Gradison M. Pelvic Inflammatory Diseases. American Academy of Family Physicians. 2012;(85):791-796.
PID: The role of chlamydial infection (rational therapy methods). Information material prepared by L.A. Marchenko, MD, and L.M. Ilyina, PhD, in 2006 based on official recommendations of the Centers for Disease Control and Prevention (CDC), 2002; articles by V.I. Kulakov, A.S. Ankirskaya, S.M. Beloborodov in Gynecol. (Extra issue: "Modern ERA of Infection Therapy in Gynecology"), 2004; MMWR 2004;(53)42:983; WebMDHealthNews, 2005.
Kovacs GT., Westcott M, len Rusden, Asche V, King H, Haynes SE, Moore EK and Hall BE. A prospective single-blind trial of minocycline and doxycycline in the treatment of genital Chlamydia trachomatis infection in women. The medical journal of Australia. 1989;150(9):483-485.
Romanowski B, Talbot H, Stadnyk M, Kowalchuk P and Bowie WR. Minocycline compared with doxycycline in the treatment of nongonococcal urethritis and mucopurulent cervicitis. Ann Intern Med. 1993;(119):16-22.
Snarskaya ES, Olisova OYu, Shnakhova LM, Kayumova LN. [Experience with minocycline in the treatment of chlamydial infection]. Infectious Diseases. 2018;16(3):93-100. (In Russ.)
Bowie WR, Willetts Val, Binns BA and Brunham RC. Etiology of cervicitis and treatment with minocycline. Can J Infect Dis. 1993;4(2):95-100.
Shao L, You C, Cao J, Jiang Y, Liu Y, Liu Q. High treatment failure rate is better explained by resistance gene detection than by minimum inhibitory concentration in patients with urogenital Chlamydia trachomatis infection. Int J Infect Dis. 2020;(96):121-127.
Shipitsyna EV, Savicheva AM. Antibiotic resistance of Chlamydia trachomatis. Journal of Obstetrics and Women's Diseases. 2002;51(4):77-83. (In Russ.)
Ridgway GL. Treatment of chlamydial genital infection. J. Antimicrob. Chemother. 1997;40:311-314.
Somani J, Bhullar VB, Workowski KA, Farshy CE, Black CM. Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure. J Infect Dis. 2000;181:1421-1427.
Benamri I, Azzouzi M, Sanak K, Moussa A, Radouani F. An overview of genes and mutations associated with Chlamydiae species" resistance to antibiotics. Ann Clin Microbiol Antimicrob. 2021;20(1):59.
Sandoz KM and Rockey DD. Antibiotic resistance in Chlamydiae. Future Microbiol. 2010;(5):1427-1442.
Wang SA, Papp JR, Stamm WE, Peeling RW, Martin DH and Holmes KK. Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis: a meeting report. J Infect Dis. 2005;191:917-923.
O"Neill CE, Seth-Smith HM, Van Der Pol B, et al. Chlamydia trachomatis clinical isolates identified as tetracycline resistant do not exhibit resistance in vitro: whole-genome sequencing reveals a mutation in porB but no evidence for tetracycline resistance genes. Microbiology. 2013;159:748-756.
Surico N, Tavassoli K. Treatment of pelvic inflammatory disease with combined piperacillin and minocycline therapy. Panminerva Med. 1990;32(4):184-9.
Kimura K, Hagiya H, Yamamoto N, Yoshida H, Akeda Y, Nishi I, Tomono K. Pasteurella multocida multiple intrapelvic abscesses in a young woman with uterine cervical cancer. J Infect Chemother. 2019;25(3):197-199.
Trabert B, Waterboer T, Idahl A et al. Antibodies Against Chlamydia trachomatis and Ovarian Cancer Risk in Two Independent Populations. JNCI: Journal of the National Cancer Institute. 2019;111(2):129-136.
Franchini A, Beshoy I, Anwer F. The Role of Chlamydia Trachomatis in the Pathogenesis of Cervical Cancer. Cureus. 2022;14(1): e21331.
Fan H, Li L, Wijlaars L, Gilbert RE. Associations between use of macrolide antibiotics during pregnancy and adverse child outcomes: a systematic review and meta-analysis. PLoS One 2019;14:e0212212.
Fan H, Gilbert R, O"Callaghan F, Li L. Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study. BMJ. 2020;368:m331.
Phillips Campbell R, Kintner J, Whittimore J, Schoborg RV. Chlamydia muridarum enters a viable but non-infectious state in amoxicillin treated BALB/c mice. Microbes Infect 2012;14:1177-85.
Wyrick PB. Chlamydia trachomatis persistence in vitro: an overview. J Infect Dis 2010;201(Suppl 2):S88-95.
Edwards VL, Smith SB, McComb EJ, Tamarelle J, Ma B, Humphrys MS, et al. The cervicovaginal microbiota-host interaction modulates Chlamydia trachomatis infection. MBio 2019;10.
Kroon SJ, Ravel J, Huston WM. Cervicovaginal microbiota, women"s health, and reproductive outcomes. Fertil Steril. 2018;110:327-38.
Tamarelle J, Ma B, Gajer P, Humphrys MS, Terplan M, Mark KS, et al. Nonoptimal vaginal microbiota after Azithromycin treatment for Chlamydia trachomatis infection. J Infect Dis. 2020;221:627-35.
Goulet V, de Barbeyrac B, Raherison S, Prudhomme M, Semaille C, Warszawski J, et al. Prevalence of Chlamydia trachomatis: results from the first national population-based survey in France. Sex Transm Infect. 2010;86:263-270.
Hazra A, Collison MW, Davis AM. CDC Sexually Transmitted Infections Treatment Guidelines, 2021.
LeFevre ML. Screening for chlamydia and gonorrhea: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2014;161:902-10.
Screening for Chlamydia trachomatis and Neisseria gonorrhoeae during pregnancy: a health technology assessment Canadian agency for drugs and technologies in health; 2018 Nov.
Rakhmatoulina MR, et al. [Vestn Dermatol Venerol]. 2012; 6: 35–41. (In Russ.)
Skin and Venereal Diseases: Textbook / ed. by O.Yu. Olisova. — Moscow: Practical Medicine, 2015. — 288 p.: ill. ISBN 978-5-98811-337-9. (In Russ.)
Snarskaya E. S., Minakova M. E. Minoлексин in the etiotropic therapy of urogenital chlamydial infection. //Russian Journal of Skin and Venereal Diseases. – 2014. – Vol. 17. – No. 4. – P. 58-64.
Appendix A1. Working Group Composition
Alexey Alexeevich Kubanov - Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Director of the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, President of the Russian Society of Dermatovenereologists and Cosmetologists.
Serov Vladimir Nikolaevich – Academician of the RAS, Doctor of Medical Sciences, Professor, President of the Russian Society of Obstetricians and Gynecologists.
Margarita Rafikovna Rakhmatulina - Doctor of Medical Sciences, Professor, Deputy Director for Organizational and Analytical Work at the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Chair of the Executive Committee of the Russian Society of Dermatovenereologists and Cosmetologists.
Inna Anatolyevna Apolikhina - Doctor of Medical Sciences, Professor, Head of the Department of Aesthetic Gynecology and Rehabilitation at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.
Mikhail Alexandrovich Gomberg - Doctor of Medical Sciences, Professor, Chief Researcher at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow Healthcare Department, Member of the National Alliance of Dermatovenereologists and Cosmetologists Union.
Elena Alexeevna Gorbunova - Obstetrician-Gynecologist, Researcher at the Department of Aesthetic Gynecology and Rehabilitation, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.
Dolgushina Nataliya Vitalievna – Doctor of Medical Sciences, Professor, Deputy Director for Research, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.
Katunin Georgiy Leonidovich – Candidate of Medical Sciences, Dermatovenereologist, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Member of the Russian Society of Dermatovenereologists and Cosmetologists.
Malova Irina Olegovna — Doctor of Medical Sciences, Professor, Professor at the Department of Dermatovenereology, Irkutsk State Medical University of the Russian Ministry of Health, member of the Russian Society of Dermatovenereologists and Cosmetologists.
Irina A. Nechaeva - Candidate of Medical Sciences, Dermatovenereologist at the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenereologists and Cosmetologists.
Onipchenko Viktoriya Viktorovna - Candidate of Medical Sciences, Chief Physician of the State Budgetary Healthcare Institution of the Novosibirsk Region "Novosibirsk Regional Clinical Dermatovenereological Dispensary", Chief Specialist in Dermatovenereology and Cosmetology of the Novosibirsk Region, member of the Russian Society of Dermatovenereologists and Cosmetologists.
Plakhova Ksenia Ilyinichna - Doctor of Medical Sciences, Scientific Secretary, Acting Head of the STI Department, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.
Potekaev Nikolay Nikolaevich - Doctor of Medical Sciences, Professor, Director of the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow Healthcare Department, Chief freelance specialist in dermatovenereology and cosmetology of the Russian Ministry of Health, President of the National Alliance of Dermatovenerologists and Cosmetologists Union.
Prilepskaya Vera Nikolaevna — Doctor of Medical Sciences, Professor, Deputy Director for Research, Head of the Scientific and Polyclinical Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, member of the Russian Society of Obstetricians and Gynecologists.
Priputnevich Tatyana Valeryevna - Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, member of the Russian Society of Obstetricians and Gynecologists.
Sysoeva Tatyana Aleksandrovna — Candidate of Medical Sciences, Associate Professor at the Department of Dermatovenereology and Cosmetology, Russian Medical Academy of Continuous Professional Education (RMANPO) of the Russian Ministry of Health, member of the Russian Society of Dermatovenereologists and Cosmetologists.
Uvarova Elena Vitalievna - Corresponding Member of the RAS, Doctor of Medical Sciences, Professor, Head of the 2nd Gynecological Department, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, member of the Russian Society of Obstetricians and Gynecologists.
Chikin Vadim Viktorovich - Doctor of Medical Sciences, Senior Researcher at the Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.
Khryanin Aleksey Alekseevich – Doctor of Medical Sciences, Professor of the Department of Dermatovenereology and Cosmetology, Novosibirsk State Medical University of the Russian Ministry of Health, Member of the Russian Society of Dermatovenereologists and Cosmetologists.
Shabanova Natalya Evgenievna – Candidate of Medical Sciences, Associate Professor, Head of the Department of Clinical Pharmacology of Antimicrobial and Immunobiological Drugs, Institute of Microbiology, Antimicrobial Therapy and Epidemiology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.
Conflict of interest: The authors declare no conflict of interest.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
Medical specialists: dermatovenereologists, obstetricians-gynecologists, coloproctologists, urologists, pediatricians, ophthalmologists.
Residents and trainees of continuing professional education programs in the specified specialty.
Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Scale for assessing levels of evidence (LE) for prevention, treatment and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)
LoE | Definition |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 3. Scale for assessing grades of recommendation (GR) for prevention, diagnosis, treatment and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The guideline update mechanism provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
Absent
Appendix B. Physician Action Algorithms
Flowchart 1. Patient Management Algorithm
Appendix C. Patient Information
1. To prevent chlamydial infection, the following measures are necessary:
- use condoms or abstain from all forms of casual sexual contact (oral, vaginal, anal);
- abstinence from all forms of sexual contact with individuals showing symptoms of sexually transmitted infections (unpleasant-colored and odorous genital discharge, rashes, or ulcerations on the external genitalia).
2. It is recommended to screen for chlamydia in all sexually active women under 25 years of age and men up to 30 years of age inclusive, individuals of both sexes at risk of sexually transmitted infections (commercial sex workers, sexually active adolescents, etc.), and married couples preparing for pregnancy.
3. It is recommended to use antiseptics, disinfectants, or systemic antibacterial drugs for emergency prophylaxis of sexually transmitted infections no later than 2 hours after unprotected sexual contact with a potentially infected partner.
4. To prevent reinfection with chlamydia, examination and treatment of sexual partners are required.
5. During treatment and until cure is confirmed, sexual contact should be avoided or barrier contraception methods used.
6. To confirm cure, a follow-up visit to the physician for examination is required one month after completion of treatment.
7. In case of chlamydial infection, screening is recommended for other sexually transmitted infections, HIV infection, and hepatitis B and C.
8. If the source of infection is unidentified, repeat serological testing for syphilis is recommended after 3 months, and for HIV infection, hepatitis B and C, after 3, 6, and 9 months.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Not used.