**9. Treatment**

The most important points in the treatment of chlamydia infection are to make the correct diagnosis and to ensure the patient's compliance with the treatment. Undiagnosed chlamydia infection can progress to PID and result in partial or complete infertility. It is undesirable for this to happen early in life, before childbearing. STIs can often be confused with a urinary tract infection. Therefore, those with a history of recurrent urinary tract infections should be evaluated for STDs. Adolescents are a high-risk group for noncompliance with treatment, especially if they are trying to keep secret from their parents. In this group, single-dose, in-office treatment is increasingly used to ensure compliance and confidentiality. Partner treatment is vital for the prevention of reinfection. The development of PID in an adolescent should be considered as an absolute indication for hospitalization due to noncompliance with prolonged treatment regimens and the possibility of developing infertility. Before starting treatment, samples should be taken from the infection area for laboratory or culture examination, and a pregnancy test should be performed as it may change the treatment and follow-up plan. Antibiotic therapy should be started as soon as possible. Compliance with treatment, cost and potential side effects should be considered in the selection of treatment, and the possibility of coinfection of gonorrhea should be kept in mind. It should be reminded that sexual intercourse should be avoided until treatment is complete and all sexual partners have been tested for infection.

Treatment should be started as soon as genitourinary chlamydial infection is diagnosed or suspected. Chlamydias are sensitive to antibiotics that affect DNA and protein synthesis; these include tetracyclines, macrolides, and quinolones [88]. The CDC recommends azithromycin and doxycycline as first-line drugs for the treatment of chlamydia [55, 60]. Medical treatment with these agents is 95% effective. Alternative medicines include erythromycin, levofloxacin, and ofloxacin [55]. Since the FDA issued a warning in 2013 that azithromycin can cause life-threatening arrhythmias, doxycycline should be preferred in patients with QT-interval anomalies or taking antiarrhythmic drugs. There is no need to retest for a cure after treatment, but a reevaluation is recommended after 3 months due to the high probability of reinfection [60].

In cases where compliance to treatment may decrease due to reasons such as cost, age, and confidentiality, it is recommended to apply single-dose treatment under observation for lower genital infections.

#### *Chlamydia: The Female Reproductive System and Infertility DOI: http://dx.doi.org/10.5772/intechopen.111756*

Due to the severity of potential complications, the presence of a condition affecting the upper genital tract should be carefully and meticulously investigated, especially in adolescents. Improper and inadequately treated PID can result in chronic pelvic pain, infertility, and sepsis. Monitoring of hospital treatment and response to treatment is especially important when PID is suspected, as adolescents may have trouble ignoring symptoms and continuing follow-ups.

In the treatment of PID, even if it is known gonorrhea to be present, treatment against C.trachomatis and anaerobic bacteria should always be included. Oral and parenteral regimens have shown similar efficacy in mild or moderate PID [60]. Patients treated in the hospital should not be discharged until significant clinical improvement is seen and confirmation that the patient will complete medical treatment. The recommended parenteral regimens are a continuation of doxycycline with cefoxitin or cefotetan for 14 days. Alternatively, clindamycin-gentamicin or doxycycline plus ampicillin-sulbactam may be given.

Out-of-hospital treatment for PID; following a single dose intramuscular administration of a second or third-generation cephalosporin, administration of doxycycline for 14 days, with or without metronidazole 500 mg for 14 days. After the emergence of quinolone-resistant cases of *N. gonorrhoeae*, treatments containing quinolone are no longer recommended for the treatment of PID. For sexual partners of the index case, treatment should also be given if the last sexual intercourse was within the last 60 days. Patients undergoing treatment for gonorrhea should also be treated for chlamydial infection.

Regarding treatment during pregnancy, CDC guidelines recommend a single dose, 1 g of azithromycin. Alternatively, amoxicillin 500 mg or erythromycin three times a day for 7 days can be used. Doxycycline, ofloxacin, and levofloxacin are contraindicated in pregnancy. To demonstrate eradication of chlamydia in pregnancy, it is recommended to test 3–4 weeks after the end of treatment, preferably by the NAAT method.

#### **9.1 Treatment failure and novel approaches**

The main causes of treatment failure are noncompliance with treatment, early testing for cure, and reinfection as a result of sexual partners not being adequately informed and adequately treated. In addition, treatment failure can be caused by antibiotic resistance caused by gene mutations in the bacterium or by the bacterium becoming insufficiently cleaned and persistent due to its natural characteristics [89]. In an *in vitro* study of antibiotic resistance, which included Croatia, the country with the highest azithromycin consumption in Europe, resistance was not shown to either azithromycin or doxycycline [90]. However, an experimental study in the UK comparing azithromycin with doxycycline found that treatment failure with azithromycin was higher in nongenital infections [91]. Multidrug-resistant CT serovars may be the reason for the ineffectiveness of azithromycin therapy. Some *in vitro* studies show that point mutations in the ribosomal proteins of the bacterium L genotype are responsible for azithromycin resistance [92]. There is also *in vitro* evidence that previous penicillin exposure may lead to azithromycin resistance in *C. trachomatis* [93].

Based on this evidence, it is clear that new drugs are needed to be developed to successfully combat *C. trachomatis* infection. Some researchers have studied Corallopyronin A, an antimicrobial compound synthesized by *Corallococcus coralloides*, and have shown that it inhibits CT proliferation [94] Shima et al. have also found promising results with this compound and have proposed it as an alternative to CT treatment in the future [94, 95]. A nanoparticle developed by Yang et al. successfully prevented vaginal CT infection by stimulating autophagy in human cells [96].

Recently, Nunez-Otero and his team demonstrated the role of a second-generation 2-pyridone amide molecule (KSK213) in the control of CT infection, in which they reduced its toxicity without damaging the commensal flora. This molecule acts through transcription inhibition in critical genes responsible for the conversion of EB to RB, the key point in the CT infection cycle [97].

In addition to all these, natural anti-chlamydia treatments derived from herbal extracts are also emphasized. Hamarsheh et al. studied the effect of Artemisia Inculta Delile extract and showed that it effectively inhibits infection in Hela cells [98]. As the issue of antibiotic resistance remains critical since 2020, some researchers have studied potential nonantibiotic agents. Lam et al. published their findings on cyclic peptomers that inhibit gram-negative bacteria and recommended 4EpDN cyclic peptomer as a prophylactic treatment against chlamydia [99].

Drug repurposing, which has been researched mostly in cancer treatment, has also been tried in this regard. Itoh et al. have shown that Bortezomib, an anticancer drug, may also be effective in treating CT infection through the induction of apoptosis [100]. More comprehensive studies are needed to be able to apply all these new strategies in the treatment of CT infection and to put the results of research into clinical practice. In order to eradicate this infection worldwide, the development of an effective vaccine in addition to all treatment strategies is critical.

#### **9.2 Posttherapy care**

Due to the high incidence of reinfection, retesting is recommended in the third month after treatment of chlamydia, gonorrhea, and trichomonas. In pregnancy, control testing after amoxicillin and erythromycin treatment should be considered. Due to the positive results from nonviable organisms, it would be better not to use non-culture methods in control tests.

Patients should be reminded to refrain from sexual activity for 7 days after a single dose treatment, and for longer treatments until the end of treatment and all sexual partners have been treated.
