Pneumonia caused by Chlamydia pneumoniae in children

INTRODUCTION — Pneumonia caused by Chlamydia pneumoniae in children will be discussed here. Infections caused by other species of Chlamydia and community-acquired pneumonia in children are discussed separately:

●(See "Chlamydia trachomatis infections in the newborn".)

●(See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections".)

●(See "Treatment of Chlamydia trachomatis infection".)

●(See "Psittacosis".)

●(See "Pneumonia in children: Epidemiology, pathogenesis, and etiology".)

●(See "Community-acquired pneumonia in children: Clinical features and diagnosis".)

MICROBIOLOGY — C. pneumoniae is an obligate intracellular pathogen that belongs to the Chlamydiaceae family and Chlamydia genus [1]. Although there was a proposal to divide the Chlamydia genus into two genera, Chlamydia and Chlamydophila [2], an international committee on the taxonomy of Chlamydiae agreed that the Chlamydiaceae family contains a single genus, Chlamydia [3].

Chlamydia spp are unusual in several ways. Their genome is smaller than that of any other prokaryote except Mycoplasma. Their cell wall contains very small amounts of peptidoglycan [4]. Their growth cycle is complex and biphasic, consisting of two distinct forms [5-7]:

●Elementary bodies – Elementary bodies are the infectious form. They can survive in the extracellular environment.

●Reticulate bodies – Reticulate bodies are the form in which C. pneumoniae replicates within a membrane-bound inclusion.

EPIDEMIOLOGY — C. pneumoniae is a common respiratory pathogen [7,8]. C. pneumoniae pneumonia occurs worldwide [9]. Outbreaks in closed populations (eg, schools, military recruits, nursing homes) have been described [10-13].

In case series of children with community-acquired pneumonia, the proportion of cases associated with C. pneumoniae varies from study to study, ranging from 0.3 to 44 percent, depending upon the diagnostic method and population studied [7,14-20]. When culture or polymerase chain reaction (PCR)-based assays were used, the proportion ranged from 0.3 to 7.8 percent [7,17,19,20]. Epidemiologic studies that used serology for diagnosis of C. pneumoniae must be interpreted with caution. Serology has poor correlation with culture and PCR [7,9,21-23]. (See 'Diagnosis' below.)

The initial infection typically occurs between 5 and 15 years of age but may occur earlier in tropical and resource-limited countries [21,24,25]. In the United States, approximately 30 percent of adolescents younger than 20 years are seropositive for C. pneumoniae [24], although patients with culture-documented C. pneumoniae infection, particularly children younger than five years, may not develop antibodies [9,26-31].

C. pneumoniae is thought to be transmitted from person to person via respiratory tract secretions [25]. It is shed from the respiratory tract during acute illness and for as long as one year after [26]. Whether symptoms increase the risk of transmission is unclear [8]. The mean incubation period is 21 days [25].

Coinfection with other pathogens, including Streptococcus pneumoniae, Mycoplasma pneumoniae, and viruses, is common [14,21,32].

PATHOGENESIS — At the onset of C. pneumoniae infection, elementary bodies (EBs), the infectious form of C. pneumoniae, attach to respiratory mucosal epithelial cells and enter the cells via a phagosome. Once inside the cell, EBs reorganize to reticulate bodies (RBs), which then replicate, forming intracytoplasmic inclusions. RBs are unstable and revert to EBs, which are released through cell lysis or exocytosis and go on to infect other cells [5,7]. When C. pneumoniae is involved in coinfections, it may disrupt normal clearance mechanisms, allowing the other pathogen to invade [7].

The host immune response is induced by chlamydial antigens, which are released onto the host cell surface during replication [5]. Because immunity is short-lived, reinfection or persistent infection is possible [5,7].

CLINICAL FEATURES — Clinical features of C. pneumoniae pneumonia are similar to those of other types of community-acquired pneumonia (CAP) and include fever, cough, tachypnea, and shortness of breath [33,34].

No clinical, laboratory, or radiographic findings reliably differentiate C. pneumoniae pneumonia from other causes of CAP [21,28]. (See "Community-acquired pneumonia in children: Clinical features and diagnosis".)

C. pneumoniae infection is frequently asymptomatic or only mildly symptomatic (table 1) [35]. However, severe and life-threatening infections can occur [36,37]. Coinfection with other pathogens may affect the clinical presentation [38].

In small case series, common features of C. pneumoniae pneumonia include gradual onset of symptoms, associated pharyngitis, and often hoarseness (table 2) [21,39,40]. Sinusitis frequently accompanies C. pneumoniae pneumonia or develops as a complication. Pneumonia caused by Mycoplasma spp and respiratory viruses can present in a similar fashion.

The white blood cell count is usually normal or mildly elevated [33]. Chest radiograph findings generally are nonspecific and include patchy subsegmental infiltration, bilateral infiltrates, and pleural effusion [21,33,36].

Although there are rare reports of extrapulmonary manifestations (eg, meningoencephalitis [41-43], Guillain-Barré syndrome [44], and myocarditis [45-49]), a causal role for C. pneumoniae has not been definitively established.

DIAGNOSIS

●Indications for laboratory evaluation – We individualize decisions about laboratory testing for C. pneumoniae based upon severity of illness, test availability, and whether the results would affect management (eg, to provide specific therapy in critically ill children). General indications for microbiologic testing in children with community-acquired pneumonia (CAP) are discussed separately (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Indications for microbiologic testing'.)

We usually perform laboratory evaluation for C. pneumoniae only in hospitalized children who are critically ill and require mechanical ventilation; the sample is obtained from a tracheal aspirate or bronchoalveolar lavage. Our institution does not have an in-house multiplex respiratory panel that includes C. pneumoniae.

Testing is rarely necessary in the outpatient setting, where empiric therapy with activity against C. pneumoniae typically is initiated in children ≥5 years with CAP and clinical features suggestive of atypical pneumonia (table 2). (See "Community-acquired pneumonia in children: Outpatient treatment" and "Community-acquired pneumonia in children: Outpatient treatment", section on 'Factors influencing choice of regimen'.)

●Microbiologic confirmation – When confirmation of C. pneumoniae is necessary, polymerase chain reaction (PCR)-based assays are preferred if available [23,50]. Cell culture is an alternative, but results will not be available to guide initial treatment. Serology is not helpful in the diagnosis of acute C. pneumoniae infection. (See 'Antimicrobial therapy' below.)

•PCR-based assays – PCR-based assays have high sensitivity and specificity and provide rapid results [9,23]. However, positive results for C. pneumoniae should be correlated with clinical findings because PCR-based assays do not differentiate between acute symptomatic infection and asymptomatic infection or persistent C. pneumoniae following resolution of symptoms [21,26,51]. Identification of C. pneumoniae does not exclude coinfection.

PCR-based assays can be performed on a variety of respiratory specimens (eg, nasopharyngeal swab or aspirate, oropharyngeal swab, bronchial lavage fluid). However, the sensitivity and specificity of most PCR-based assays, including multiplex assays, when used on different clinical samples and in the clinical setting are unknown. Pending additional information, results of PCR-based assays should be used in conjunction with clinical and epidemiologic information to make treatment decisions.

Availability of PCR-based assays for C. pneumoniae vary from laboratory to laboratory. Clinicians should check with their laboratory for details about appropriate specimen types, specimen collection, and transport [23].

Commercially available multiplex panels for respiratory infection that include C. pneumoniae are used by some institutions and general practitioners in the evaluation of patients with respiratory tract infections [52-56]. If the panel is sent to an outside laboratory, turnaround time is usually one to three days; if it is performed on site, turnaround time is usually three to four hours.

•Cell culture – Although cell culture permits genotyping and antimicrobial susceptibility testing, it is rarely used for routine clinical testing because it requires specialized techniques with variable sensitivity and specificity depending on the expertise of the laboratory and can take weeks to obtain results [7,9,23]. It is not widely available and is costly.

•Serology – Serology is not helpful in the diagnosis of acute C. pneumoniae infection. It is not standardized, has poor correlation with culture and PCR, and requires collection of both acute and convalescent sera for diagnosis [7,9,21-23,57].

ANTIMICROBIAL THERAPY

Empiric therapy for community-acquired pneumonia — Treatment for community-acquired pneumonia (CAP) in children usually is initiated empirically, based upon the age of the child and the clinical presentation. Among children who are treated as outpatients, microbiologic testing generally is not obtained. Empiric therapy may or may not include coverage for atypical pathogens, including C. pneumoniae. If C. pneumoniae is suspected (eg, outbreak setting, clinical features suggestive of atypical pathogens (table 2)), empiric therapy should include activity against C. pneumoniae (eg, a macrolide antibiotic with or without additional coverage for typical bacterial pathogens). Empiric therapy for CAP in children is discussed separately. (See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Empiric therapy' and "Pneumonia in children: Inpatient treatment", section on 'Empiric therapy' and "Community-acquired pneumonia in children: Outpatient treatment".)

Therapy for C. pneumoniae

●Outpatient setting

•Preferred regimen – For children with microbiologically confirmed C. pneumoniae pneumonia in the outpatient setting, we suggest treatment with azithromycin 10 mg/kg per day orally (maximum daily dose 500 mg) on day 1 followed by 5 mg/kg per day orally (maximum daily dose 250 mg) on days 2 through 5.

•Alternative regimen – Doxycycline 2 to 4 mg/kg per day orally divided into two doses (maximum daily dose 200 mg) for seven days is an alternative for children of all ages [58-60].

We prefer azithromycin because its treatment course is shorter and it is associated with fewer adverse effects than other oral agents with activity against C. pneumoniae (eg, other macrolides, doxycycline, levofloxacin, moxifloxacin) [61-64]. Fluoroquinolones generally are reserved for children in whom there is no safe and effective alternative or an oral fluoroquinolone is the only alternative to parenteral therapy [65]. (See "Fluoroquinolones", section on 'Children'.)

●Hospitalized children

•Preferred regimen – For children who require hospitalization for severe microbiologically confirmed C. pneumoniae pneumonia (table 1), we suggest initial treatment with azithromycin 10 mg/kg intravenously (IV) once per day on day 1 and day 2, followed by transition to oral therapy (if possible) with azithromycin 5 mg/kg orally once per day to complete a five-day course [58].

•Alternative regimens – Alternative initial IV regimens include [58]:

-Erythromycin 20 mg/kg per day IV divided in four doses, or

-Levofloxacin – Age 6 months to 5 years: 16 to 20 mg/kg per day IV divided in two doses; age 5 to 16 years: 8 to 10 mg/kg per day IV once per day (maximum daily dose 750 mg)

When the child is ready to transition to oral therapy, one of the following regimens can be used to complete a 7- to 10-day course of therapy:

-Clarithromycin 15 mg/kg per day orally divided in two doses

-Erythromycin 50 mg/kg per day orally divided in four doses

-Doxycycline 2 to 4 mg/kg per day orally divided in two doses (maximum daily dose 200 mg)

-Levofloxacin 500 mg orally once daily (for skeletally mature adolescents)

-Moxifloxacin 400 mg orally once daily (for skeletally mature adolescents)

Clinical trials directly evaluating the efficacy of antibiotics on clinical outcomes in children with C. pneumoniae pneumonia are lacking. However, in randomized trials and observational studies of children with radiographically confirmed CAP, azithromycin and clarithromycin appear to have clinical efficacy similar to that of erythromycin [14,63,66,67].

Although it is not known whether microbiologic eradication is necessary for clinical cure, in subgroup analysis of patients with culture-confirmed C. pneumoniae from several clinical trials, the efficacy of microbiologic eradication was approximately 80 percent with a 5-day course of azithromycin [63,68] and 70 to 100 percent with a 10-day course of clarithromycin, erythromycin, or moxifloxacin or a 7- to 10-day course of levofloxacin [28,69,70]. Failures are thought to be due to lack of eradication of the pathogen in its persistent state and not due to drug resistance [71].

RESPONSE TO THERAPY — Children with community-acquired pneumonia who receive appropriate antimicrobial therapy generally are clinically improved within 48 to 72 hours of treatment. Management of those who do not improve as expected is discussed separately. (See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Treatment failure' and "Pneumonia in children: Inpatient treatment", section on 'Treatment failure'.)

PROGNOSIS — C. pneumoniae pneumonia is usually mild and most patients recover without complications [8]. In some children, C. pneumoniae may be associated with prolonged cough (mean duration 25 to 30 days) [8,72-75]. Although C. pneumoniae has been associated with asthma [76-79] and reactive arthritis [80-82], a causal relationship has not been established.

PREVENTION — C. pneumoniae is thought to be transmitted from person to person via respiratory tract secretions or fomites. Frequent hand washing and respiratory hygiene/cough etiquette are suggested to prevent transmission [12,25,83].

For patients hospitalized with C. pneumoniae pneumonia or community-acquired pneumonia of unknown etiology, standard precautions are recommended [25,84]. (See "Infection prevention: Precautions for preventing transmission of infection".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pediatric pneumonia".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Pneumonia in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Chlamydia pneumoniae is an obligate intracellular pathogen that causes a minority of cases of community-acquired pneumonia (CAP) in children. Outbreaks have been reported in closed populations. Coinfection with other pathogens is common. The initial infection usually occurs between 5 and 15 years of age but may occur earlier. (See 'Epidemiology' above.)

●Clinical features of C. pneumoniae are similar to those of other types of CAP and include fever, cough, tachypnea, and shortness of breath. Common features include gradual onset of symptoms, associated pharyngitis, and often hoarseness (table 2). However, no clinical, laboratory, or radiographic findings reliably differentiate C. pneumoniae pneumonia from other causes of CAP. (See 'Clinical features' above.)

●We individualize decisions about laboratory testing for C. pneumoniae based upon severity of illness, test availability, and whether the results would affect management (eg, to provide specific therapy in critically ill children). Testing is rarely necessary in the outpatient setting. When confirmation of C. pneumoniae is necessary, polymerase chain reaction-based assays are preferred if available. (See 'Diagnosis' above.)

●For children with microbiologically confirmed C. pneumoniae pneumonia and clinical findings compatible with CAP, we suggest treatment with azithromycin rather than other macrolides, tetracyclines, or fluoroquinolones (Grade 2C). Azithromycin has a shorter treatment course and is associated with fewer adverse effects than other available agents. We use 10 mg/kg per day orally (maximum daily dose 500 mg) on day 1 followed by 5 mg/kg per day orally (maximum daily dose 250 mg) on days 2 through 5. Doxycycline is an alternative for children of all ages. (See 'Therapy for C. pneumoniae' above.)

●Children with CAP who receive appropriate antimicrobial therapy generally are clinically improved within 48 to 72 hours of treatment. Most patients recover without complications. (See 'Response to therapy' above and 'Prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Dori Zaleznik, MD, who contributed to an earlier version of this topic review.