*3.1.2.3 Treatment of urethritis due to* C. trachomatis

It was shown that nearly all women who have chlamydia cervicitis also have concomitant urethritis [63]. In men, chlamydia disease generally involves the male urethra. *C. trachomatis* is a frequent cause of acute urethritis in young, sexually active individuals and is responsible for more than half of all instances of non-gonococcal urethritis [43, 64, 65]. Most cases of chlamydia urethritis in both men and women go unnoticed. In women, urinary symptoms such as frequent urination and dysuria are common, whereas in male patients additional complaints of urethral discharge and discomfort are prevalent [66]. Ideally, treatment should be given after pathogen detection but quick access to diagnostic data might not always be possible; therefore, presumptive treatment should begin for non-gonococcal urethritis (NGU) for those who have symptoms of urethral discharge from the penis, and patient follow-up cannot be assured or test results are not accessible on the same day. Evaluation and treatment of NGU should also include gonococci. For gonococci, a single intramuscular dose of ceftriaxone (500 mg [or 1 gr for individuals ≥150 kg]) might be considered but the choice of appropriate treatment regimen should be guided according to the local antibiotic resistance patterns [43, 53]. The recommended and alternative treatment options for urethritis due to *C. trachomatis* are the same as other uncomplicated chlamydia infections mentioned above.

#### *3.1.2.4 Treatment of rectal infections due to* C. trachomatis

Acute proctitis and proctocolitis are two distinct manifestations of chlamydia in individuals who have anal exposure to *C. trachomatis* by oral, genital, or digital interaction. Proctitis is the inflammation of the distal part of the rectum and presents with anorectal discomfort, tenesmus, or rectal discharge, whereas proctocolitis is the extension of proctitis to the colonic mucosa above the anus and additional symptoms such as diarrhea or abdominal cramps may be seen [43]. Rectal *C. trachomatis* infection rates in MSM and women are similar and range from 1 to 18%. It was shown that in women, the rectal disease may accompany urogenital infection in up to 83% of cases and can occur regardless of receptive anal sexual behavior [61]. In MSM, the incidence of asymptomatic rectal infection is high and reaches above 80% [62].

Either asymptomatic or not, microbial eradication at the rectal site is crucial for treating urogenital chlamydia. Due to its higher microbiologic cure rates and asymptomatic nature of rectal chlamydia disease, doxycycline is the recommended antibiotic choice for anal infections caused by *C. trachomatis* [54, 59].

A 7-day course of doxycycline 100 mg orally, twice a day is the suggested regimen for proctitis and proctocolitis due to chlamydia. Doxycycline treatment should be extended to 21 days if symptoms indicating lymphogranuloma venereum such as anal bloody discharge, tenesmus, perianal or mucosal ulcers are present. Erythromycin 500 mg, orally, 4 times a day for 14 days is the alternative regimen. Treatment of patients with sexually acquired proctitis should also include treatment for gonococci. For gonococci, a single intramuscular dose of ceftriaxone (500 mg [or 1 gr for individuals ≥150 kg]) should be added. WHO advises a syndromic approach in cases with anorectal discharge and a reported history of receptive anal sex to allow treatment on the day of the visit in regions that have little to no molecular testing or laboratory capacity [53].

#### *3.1.2.5 Treatment of oropharyngeal infections due to* C. trachomatis

*C. trachomatis* can lead to oropharyngeal infection in those having receptive oral intercourse, same as gonorrhea [43]. The prevalence of oropharyngeal chlamydia infection approximately ranges from 1 to 3% in MSM and women [61]. Without

#### *Treatment of Chlamydial Infections DOI: http://dx.doi.org/10.5772/intechopen.109648*

therapy, oropharyngeal chlamydia can spread to other genital locations *via* sexual contact [67, 68]. The optimal antibiotic regimen for oropharyngeal chlamydia has not been thoroughly investigated. It was revealed that doxycycline is more efficient in treating oropharyngeal chlamydia than azithromycin similar to rectal chlamydia infections. The recommended treatment is a 7-day course of oral, twice a daily 100 mg doxycycline [45].

## *3.1.2.6 Treatment of epididymitis due to* C. trachomatis

An uncomfortable, swollen, and inflamed epididymis is symptom of the clinical illness known as epididymitis. Unilateral testicular pain and palpable swelling are common in patients with acute epididymitis. The disease sometimes involves the testicles and is called epididymo-orchitis. Testicular torsion is a complication of epididymitis that requires emergency surgery. Acute epididymitis caused by STIs is a typical complication of young, sexually active men, and the condition frequently coexists with urethritis. Gonococci and *C. trachomatis* testing should be performed on all suspected instances of acute epididymitis. If patients are unable to follow the prescribed antibiotic regimen or if significant pain or fever points to complications such as testicular torsion, abscess, or necrotizing fasciitis, patient evaluation for hospitalization should be considered. All sexually active men who have acute epididymitis should get presumptive therapy Doxycycline 100 mg orally, twice a day for 10 days, is the recommended treatment for acute epididymitis caused by *C. trachomatis*. The therapy should include treatment for gonococci and a single intramuscular dose of ceftriaxone (500 mg [or 1 g for individuals ≥150 kg]) should be added [43]. In patients who report insertive anal sex, enteric organisms might be involved in epididymitis. In such cases, fluoroquinolones are effective against both gram-negative enteric bacteria and chlamydia therefore ofloxacin 300 mg orally, twice a day for 10 days or levofloxacin 500 mg orally, once a day for 10 days (plus ceftriaxone for gonococci) can be offered [43, 69].

### *3.1.2.7 Treatment of PID due to* C. trachomatis

PID is an inflammatory disease affecting female upper genital tract organs including endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. PID is often caused by STIs, with *N. gonorrhoeae* or *C. trachomatis* as the etiological agent in up to half of the cases [43]. Women with PID frequently exhibit mild and vague symptoms such as abnormal vaginal discharge, spotting, and dyspareunia but may also be asymptomatic. Untreated PID might impair reproductive health and lead to complications such as tubal infertility and ectopic pregnancy [53]. Moreover, PID can also extend to abdominal organs and cause Fitzhugh-Curtis syndrome, which requires in-patient treatment and is characterized by peritonitis and inflammation of the liver capsule [32]. Since PID is related to severe morbidity, presumptive therapy should begin for sexually active women at risk for STIs who complain of pelvic or lower abdominal discomfort and there is tenderness on pelvic examination [43].

The women who present with PID should also be evaluated for the need for hospitalization when there is suspicion of surgical emergency, presence of tubo-ovarian abscess, pregnancy status, severe illness [nausea, vomiting, and fever >38.5°C (101°F)], or no clinical benefit from oral antibiotic treatment. Broad-spectrum antibiotics against probable agents should be initiated as soon as possible. Antibiotics should cover *C. trachomatis* and *N. gonorrhoeae* even if endocervical testing is negative as

upper genital tract infection cannot be fully ruled out [43]. The recommended regimen for *C. trachomatis-*related PID is doxycycline 100mg, orally, twice a day for 14 days combined with antibiotics active against gonococci. Facultative anaerobic bacteria and enteric gram-negative rods are among other etiologic agents that should be considered for the treatment of PID [43].

#### *3.1.2.8 Treatment of LGV*

*C. trachomatis* serovars L1, L2, or L3 are the culprits behind LGV and are responsible for a more invasive form of the chlamydial disease called LGV characterized by genital ulcer disease, lymphadenopathy, and proctocolitis. Among them, proctocolitis is a frequent finding in LGV and is especially seen in MSM. Inflammatory bowel disease-like symptoms, such as mucoid or hemorrhagic rectal discharge, anal pain, constipation, fever, or tenesmus, might be clinical indicators of proctocolitis. Until recently, LGV was exclusively a problem in tropical and subtropical regions of the globe with little resources. Since 2003, endemic LGV cases have been observed in MSM across Europe [70, 71]. If untreated, rectal LGV may be invasive and cause chronic colorectal fistulas and strictures. LGV can also cause inguinal or femoral lymphadenopathy with suppurated bubo formation and the condition may lead to genital elephantiasis. Consequently, presumptive treatment should be started if a patient with proctocolitis exhibits symptoms or signs such as bloody discharge, tenesmus, or ulceration at the rectal site; if a patient with a recent history of genital ulcer displays severe inguinal lymphadenopathy with bubo formation; or if the patient has genital ulcer disease and other causes have been ruled out [43, 72].

The most effective antibiotic for the treatment of LGV is doxycycline but unlike uncomplicated chlamydia caused by serovars D-K, treatment of LGV needs a prolonged course of therapy. Doxycycline 100 mg twice a day for 21 days is the standard course of treatment for LGV. Azithromycin 1 g orally once a week for 3 weeks and erythromycin base 500 mg orally four times a day for 21 days are two alternate regimens. Unfortunately, the LGV-specific azithromycin regimen has not been confirmed, and a follow-up test with *C. trachomatis* NAAT is advised about 4 weeks after the end of therapy [43]. Patients who have LGV should be observed until all symptoms and signs have disappeared [43].

#### *3.1.2.9 Treatment of chlamydia and LGV during pregnancy and breastfeeding*

The tetracycline group of antibiotics including doxycycline which is the primary antibiotic option for chlamydia and LGV is contraindicated during pregnancy and breastfeeding due to the possibility of tooth discoloration [43]. In pregnant and breastfeeding women suffering from chlamydia disease, azithromycin, erythromycin, and amoxicillin are the safer antibiotic options [73]. The recommended antibiotic regimen for pregnant and breastfeeding adults and adolescents with cervical, urethral, rectal, and oropharyngeal chlamydia is azithromycin 1 g orally given as a singledose. As a secondary option amoxicillin 500 mg orally, three times a day for 7 days can be used. Beta-lactam antibiotics are associated with the persistence of chlamydia; therefore, caution must be given for re-emergence of viable pathogen after discontinuation of amoxicillin therapy [43]. Erythromycins 500 mg orally, four times a day for 7 days, or erythromycin 500 mg orally, twice a day for 14 days, are two alternative possibilities for pregnant and nursing women with uncomplicated chlamydia. Of note, estolate formulation of erythromycin is contraindicated in pregnancy due to the

#### *Treatment of Chlamydial Infections DOI: http://dx.doi.org/10.5772/intechopen.109648*

risk for drug-related hepatotoxicity, and erythromycin base or erythromycin ethyl succinate should be prescribed instead [53, 74, 75].

For many years, macrolides including azithromycin and erythromycin have been frequently utilized as safe antibiotic options during pregnancy; however, in a recent population-based cohort study it was found that first-trimester usage of macrolides (mainly erythromycin given over several days) was associated with a higher incidence of congenital abnormalities than penicillins [76]. It was also shown that erythromycin medication during 7 weeks of delivery or while breastfeeding has been linked to a higher incidence of IHPS [7]. The impact of azithromycin single-dose regimen on a fetus is unknown but it is considered that the advantages of azithromycin therapy outweigh any potential risks. Finally, although fluoroquinolones can be used in nonpregnant patients, its usage is restricted during pregnancy and breastfeeding due to fetal and neonatal adverse effects [43].

For pregnant women with LGV, the optimum dose and duration of antibiotic therapy are not known. Azithromycin 1 g orally, once a week for 3 weeks, can be used. Erythromycin 500 mg orally, four times a day for 21 days is another option for use in pregnancy and nursing women but gastrointestinal adverse effects are frequent [43, 74].

All pregnant women should get a NAAT retest around 4 weeks following the end of their therapy since the infection can remain and cause serious side effects in both mothers and neonates [45]. Also to detect re-infection, retesting should be repeated in pregnant women 3 months after completing therapy [45].

To prevent maternal complications and infant chlamydial infections, it is advised that pregnant women under 25 years old, pregnant women who have a new sex partner, a sex partner with multiple partners, or a sex partner with an STI, should be checked at the first antenatal control and retested in the third trimester. However, routine antenatal screening of pregnant women at risk for chlamydia disease cannot be utilized in all countries [31, 77].

#### *3.1.2.10 Treatment of chlamydia disease among infants and children*

*C. trachomatis* acquired in the perinatal period can persist for up to 3 years. Any prepubertal youngster with chlamydia disease should be evaluated for the possibility of sexual abuse. In case of a suspect of sexual abuse, local authorities should be notified. The recommended regimens for chlamydia disease among infants and children are as follows:


#### *3.1.2.11 Follow-up recommendations for chlamydia and LGV*

Sexual activity should be avoided by people with *C. trachomatis* (LVG or non-LGV serotypes) and their partners until treatment is complete (7 days after single-dose therapy or after completion of a multiple-dose regimen) and all current partners have recovered [43, 74].

A test of cure to detect therapeutic failure (repeated testing 4 weeks after finishing therapy) is not advocated for non-pregnant patients with uncomplicated chlamydia disease. But if therapeutic adherence is not assured, the patient has persistent symptoms, regimens with low efficacy (such as erythromycin or amoxicillin) have been implemented, or re-infection is suspected, clinician can offer a follow-up visit and retest the patient. Nonviable organisms may persist up to 4 weeks after completion of therapy and may cause false positive test results therefore testing with chlamydial NAATs at less than 4 weeks following the conclusion of medication is not advised [45].

In order to detect re-infection, all patients should be retested for chlamydia in 3 months (or retesting at 3 months is not feasible, within 12-months) after completion of therapy. It is suggested to schedule the follow-up appointment at the time of treatment [43].

If the patient has complaints of chronic or recurring symptoms, non-adherence to the given medication, re-infection, completion of sex partner treatment, and coinfection with other STIs should be questioned and evaluated. Assuming that *C. trachomatis* is found on repeat testing, treating with the same regimen (preferably doxycycline regimen) is advised since drug resistance to doxycycline (or azithromycin) has not yet been proven in *C. trachomatis* as explained previously in the Subsection 2.

#### *3.1.2.12 Management of sex partners of patients who have chlamydia and LGV*

If a patient with chlamydia or LGV had intercourse with a partner within 60 days of the onset of their symptoms or chlamydia diagnosis, the partner should be referred for screening for *C. trachomatis*. A 7-day doxycycline regimen should be presumptively given to asymptomatic partners. In addition, co-infection with other STIs such as gonorrhea, HIV, and syphilis should be investigated in individuals and their sex partners who had a diagnosis of chlamydia or LGV [43]. However, if the clinician is worried that sex partners are unable to access evaluation and treatment services, a strategy termed "expedited partner therapy" (EPT) can be applied as permitted by law. In this strategy, treatment is delivered to the sex partner without examination by either giving an antibiotic/prescription to the index patient (so they can give it to their partners) or by calling in a prescription directly for the partner. Partners who will receive EPT should be informed about the significance of treatment, potential side effects of the medications, and complications of the disease [43].

#### *3.1.3 Treatment of infantile chlamydial pneumonia*

*Chlamydial pneumoniae* is subacute pneumonia that mainly affects newborns between the ages of 1–3 months. *C. trachomatis* testing should be performed in all newborns aged 1–3 months who are suspected of having pneumonia especially if there is a risk for chlamydia infection in the mother such as pregnant women under 25 years old and pregnant women who have a new sex partner, more than one sex partner, a sex partner with multiple partners, or a sex partner with an STI [43].

Erythromycin base or ethyl succinate 50 mg/kg/day orally divided into four doses every day for 14 days is the recommended regimen for infantile chlamydial pneumonia. Azithromycin suspension 20 mg/kg/day orally, once a day for 3 days is the alternative regimen that can be given presumptively when there is a strong suspicion of chlamydia infection and there are limited laboratory resources or infant followup is not possible [43]. It is advised to monitor infants for resolution of pneumonia

#### *Treatment of Chlamydial Infections DOI: http://dx.doi.org/10.5772/intechopen.109648*

symptoms as the efficacy of erythromycin against *C. trachomatis* pneumonia is approximately 80% [43, 78]. Additionally, mothers of babies with infantile chlamydial pneumonia should be assessed, screened, and treated for chlamydia disease [43].
