*3.1.4 Reactive arthritis due to* C. trachomatis *infection*

Reactive arthritis is a type of arthritides known as the spondyloarthritides that usually develops following an enteric or venereal infection. Both men and women can develop reactive arthritis after infection due to *C. trachomatis* whether they are symptomatic or not. Moreover, reactive arthritis can occasionally be one of the three symptoms that used to be known as Reiter's syndrome, which also includes urethritis and conjunctivitis [34]. Although randomized studies for long-term anti-chlamydial antibiotic treatment for reactive arthritis showed varied results, the majority of studies showed no benefit. Therefore, antibacterial medication is not recommended in reactive arthritis related to *C. trachomatis* [79, 80].

### **3.2 Treatment of infections due to** *C. pneumoniae*

*C. pneumoniae* is another important human pathogen in the family *Chlamydiaceae* that mainly infects the respiratory tract. The agent causes upper or lower respiratory tract infections including pharyngitis, laryngitis, and community-acquired pneumoniae (CAP). Most *C. pneumoniae*-related respiratory infections are asymptomatic or mild; however, severe complications such as exacerbation of asthma, encephalitis, and myocarditis can occur, which may require hospitalization [81]. *C. pneumoniae* prevalence rates in individuals with CAP range from 1 to 20% of cases [82, 83]. Therefore, empiric treatment of CAP frequently includes the usage of antibiotics effective against *C. pneumoniae* [84].

Among antibacterial medications, beta-lactam antibiotics, aminoglycosides, glycopeptides (such as vancomycin), and sulfonamides are not effective against *C. pneumoniae*, whereas macrolides, doxycycline, and fluoroquinolones are effective options [72, 85]. Acquired and heritable antibacterial resistance have not been revealed in *C. pneumoniae* and laboratory tests for the detection of *C. pneumoniae* are not routinely recommended in CAP management. Decisions for testing can be individualized on a case-by-case basis and the availability of microbiological tests [3, 84]. In the literature, clinical trials that show the efficacy of antibacterial medications on outcomes of pneumonia due to *C. pneumoniae* are limited [86]. However, the performance of antibacterial agents in eradicating nasopharyngeal *C. pneumonia* has been evaluated in several studies. The efficiency of eradicating microorganisms was shown as around 80% in those trials using a 5-day course of azithromycin and between 70% and 100% when using 7 to 10-day courses of clarithromycin, erythromycin, moxifloxacin, or levofloxacin. The authors revealed that the majority of patients improved despite the organism's persistence in the nasopharynx; therefore, the significance of bacterial eradication for treatment success is still controversial [86–90]. Studies have shown that in patients who remained culture positive after treatment, antibiotic failure is the result of the persistent state of the organism and not due to drug resistance [72, 91].

Numerous researchers have questioned the ideal length of antibiotic treatment in CAP. Historically at least 7 days of treatment was recommended for CAP; however, in the last decades there is a tendency toward shorter courses of therapy in both adults and children due to the abundant evidence showing non-inferior efficacy compared

to longer courses [84, 92–95]. In recent years, guidelines have changed their recommendations to the usage of shorter duration of antibiotic regimens for CAP. But not all patients respond to a standard duration of therapy; therefore, it is advised that clinicians should use clinical stability indicators such as the return of normal vital sign patterns, the capacity to eat, and mental function to determine the length of antibiotic therapy. The recommendation is that the treatment is administered for a minimum of 5 days overall and until the patient reaches stability [84, 95, 96].

In adult patients where *C. pneumonia* is the confirmed etiological agent for pneumonia the following therapy regimens can be given as a 5-day course of antibiotic therapy and according to the patients' clinical stability [84, 95]. The necessity of eradication of *C. pneumoniae* from clinical isolates for treatment success is not known but treatment might be extended up to 10 days in selected cases due to the previously mentioned studies about post-treatment bacterial eradication rates.


Intravenous (IV) formulations of levofloxacin and moxifloxacin can be given in the same oral dosages to severe patients who are hospitalized and unable to take oral medication [84, 95]. All patients should be reassessed within 3 days for improvement of symptoms and the possibility of transition to oral medication [95].

For children, the recommendations for assessing the duration of antibiotics for pneumonia are the same as the adult patients [95, 97]. The treatment options for confirmed *C. pneumonia* in pediatric patients are:


Similar to adult patients response to therapy and decision to transition to oral therapy should be assessed within 3 days of treatment [97]. Due to the paucity of clinical trials directly evaluating the efficacy of antibiotics on clinical outcomes in children with *C. pneumoniae* pneumonia, the medications might be lengthened to 10 days according to the physician's decision [97].
