Practice Recommendations for Management of Community Acquired Pneumonia in Children
DC Lung, DSY Lam, E Chan, KC Chan, SSS Chiu, PL Ho, VWT Ho, CW Leung, W Luk, AYC Tam, G Wong; On behalf of the CAP Guideline Development Group
Community acquired pneumonia (CAP) is a common condition encountered in both ambulatory and hospital settings in Hong Kong. Two sets of evidence based international guidelines on management of CAP, the Infectious Diseases Society of America and the British Thoracic Society guidelines, are available, but the local epidemiology, the public health infrastructure, vaccination program, social and economic background are all different from Hong Kong. Therefore not all of the recommendations are relevant to Hong Kong practice. The 2015 Hong Kong paediatric CAP guidance drafted by the CAP guideline development group aims at developing a set of local guidance with reference to international recommendations (including American and British guideline), based on the current available local data (including Streptococcus pneumoniae and Macrolide-resistant Mycoplasma pneumoniae) and consensus of the panel. Immunocompotent paediatric patients of age range beyond 3 months are the main focused population of the current set of guidance, in both in-patient and out-patient setting.
Keyword : Community acquired; Mycoplasma pneumoniae; Paediatric; Pneumonia; Streptococcus pneumoniae
Community acquired pneumonia (CAP) is a common condition encountered in both ambulatory and hospital settings in Hong Kong. From 2000-2005, hospital discharge diagnoses revealed that admission rate for clinical pneumonia was 932 per 100,000 population aged 0-5 years in Hong Kong.1 This was similar to the rate of 776 per 100,000 population following chart review of systematically recruited children younger than 5 years.2 CAP has a very wide spectrum of clinical manifestation and severity. An expert panel (CAP guideline development group) has been formed to compile a set of clinical statements and practices to guide and assist clinicians in managing CAP in Hong Kong. The panel consists of paediatricians with special interest in pulmonology and intensive care, paediatric infectious diseases specialists, clinical microbiologists, general paediatrician, emergency physician, private paediatrician and family physician. This practice parameter is jointly developed by Hong Kong College of Paediatricians, Hospital Authority Central Coordinating Committee (COC) in Paediatrics, Family Medicine, and representative from COC (A&E).
Two sets of evidence based international guidelines on management of CAP, the Infectious Diseases Society of America (IDSA)3 and the British Thoracic Society (BTS)4 guidelines, are available, but the local epidemiology, the public health infrastructure, vaccination program, social and economic background are all different from Hong Kong. Therefore not all of the recommendations are relevant to Hong Kong practice. Moreover, specific clinical problems seen in Hong Kong are not addressed in the two sets of international guidelines.
The CAP guideline development group aims at developing a set of local guidance with reference to international recommendations, based on the currently available local data and consensus of the panel. Immunocompetent paediatric patients of age range beyond 3 months are the main focused population of the current set of guidance, in both in-patient and out-patient settings. The management of pneumonia in patients less than 3 months; patients with pre-existing respiratory conditions; hospital acquired pneumonia and pneumonia in immunocompromised patients shall not be included in this set of guidance. The major goal of the panel is to adopt international recommendations relevant for local use. Therefore no further elaboration shall be included for statements or recommendations without any controversy.
The major scope of the current set of guidance includes:
This set of guidance is developed for paediatricians, family physicians working in the private and public sectors, clinicians working in the accident and emergency departments.
The guidance includes the following section:
1. Local Epidemiology
The ever changing epidemiology of CAP is a result of healthcare intervention (such as pneumococcal vaccine), local factors (such as overuse of antibiotics resulting in spread of antimicrobial resistant organisms) and external factors (such as influx of cross-border students and introduction of pathogens which are not endemic in Hong Kong). Combination of factors has resulted in a rapid change in epidemiology of CAP in Hong Kong and there is a need to provide an update and a set of guidance to the local practitioners.
2. Clinical Features of CAP
It is recognised that there is considerable overlap in the clinical features of various respiratory infections syndromes.13 Although it is important for the clinician to make distinction between upper respiratory infection, bronchitis and pneumonia, it is known that often other parts of the respiratory tract, being a continuum, are affected at the same time. The clinical distinction of these syndromes therefore serves as an indication of the part of the respiratory tract most affected, as indicated by the symptoms and signs of the patient. However, the diagnosis of these clinical syndromes will help the clinician to consider the main possible causes of the infection, to assess its severity and to institute treatment.
The diagnosis of various respiratory infection syndromes are therefore mainly clinical, sometimes assisted by an X-ray of the chest or ultrasound imaging. Six main syndromes have been identified:
3. Initial Assessment (Severity Assessment)
Indication for referral and admission to hospital:
4. General Investigations
5. Microbiological Investigations of Community-acquired Pneumonia in Children
Attempting an aetiologic diagnosis of CAP in children is challenging. An accurate and rapid diagnosis of the pathogen can inform clinical decision making, resulting in improved care with targeted narrow-spectrum antimicrobial therapy, fewer unnecessary tests and procedures, and potentially shortened hospitalisation.3,60-63 There is, unfortunately, no single diagnostic test apart from examining a direct lung aspirate that can be considered the gold standard.64 Determining the aetiology of CAP is critically dependent on the thoroughness of the search and the tests used. The more tests that are performed, the more potential causes may be identified. In a review of European paediatric studies, the microbial cause of pneumonia could be identified in 20 to 60% of cases depending on the extent of laboratory testing performed.65 In a UK study, a pathogen was isolated in up to 60% of cases, and considered a definite or probable cause of CAP in 51% of children.66
Despite the limitations of available laboratory tests, establishing a microbiologic diagnosis is important in children with severe or complicated CAP, in those with unusual but treatable causes, and in those infected by novel or emerging pathogens.67 Even when a respiratory pathogen has been identified in upper respiratory tract secretions, its causal role in pneumonia can be difficult to assess as this does not necessarily imply that it is the aetiologic agent of the patient's lower respiratory disease. Likewise, the identification of a potentially causative pathogen does not preclude the possibility of an aetiologic contribution from other pathogens. Respiratory viral infections are frequently complicated by bacterial superinfections and viral-bacterial coinfections are not uncommon.65,68 Viral and bacterial coinfections were identified in 23% of children with pneumonia evaluated at a tertiary-care children's hospital.69
Sputum samples for culture and Gram smear should be obtained in hospitalised children who can expectorate sputum, in those who require intensive care, and in those with complications of CAP. However, infants and young children are often unable to produce sufficient sputum for collection and cultures of these specimens may be contaminated by bacterial flora in upper respiratory secretions which do not correlate with those infecting the lower respiratory tract.
Despite the low overall yield, blood cultures are essential for the investigation of children hospitalised for CAP and in children who fail to demonstrate clinical improvement or have progressive clinical deterioration after initiation of antibiotic therapy. However, blood cultures cannot detect atypical bacterial pathogens such as M. pneumoniae and C. pneumoniae, and all viral pathogens. Repeated blood culture to confirm sterilisation with appropriate antimicrobial therapy is not necessary in children who clearly demonstrate clinical improvement. The overall impact of blood cultures on clinical management may be small because of the low prevalence of accompanying bacteraemia. The cost-effectiveness of obtaining blood cultures in all children hospitalised for CAP is unknown.
A viral aetiology of CAP may be inferred by evaluation of nasopharyngeal secretions with rapid tests (e.g. antigen assay or PCR) for influenza and other common respiratory viruses. Identification of a respiratory virus may obviate the need for antibiotic therapy in the absence of findings suggestive of bacterial coinfection while detection of influenza virus can guide appropriate antiviral treatment.62,70,71 Viral cultures of respiratory secretions are not useful for therapeutic decision making as results will only be available after some time.
For diagnostic evaluation of parapneumonic effusion or empyema, pleural fluid, if obtained, should be sent for Gram smear, culture, pneumococcal antigen detection, and PCR for pneumococcus or other suspected atypical respiratory pathogens. In Hong Kong, an apparent increase in the incidence of pneumococcal pleural empyema caused by serotype 3 is observed. It should be noted that serotype 3 pneumococcal empyema is often culture negative but presence of the pathogen in the pleural pus could be readily detected by pneumococcal specific PCR tests. Urinary antigen detection tests are not recommended for the diagnosis of pneumococcal pneumonia in children as false-positive results are common. Positive results of pneumococcal urinary antigen tests do not reliably distinguish children with pneumococcal pneumonia from those who are merely colonised with pneumococcus in their nasopharynx.72-75 False-positive results may also occur in those who have recently received pneumococcal vaccines. However, urinary antigen detection may be helpful as negative predictor of pneumococcal infection in older children.
6. Chest Radiography
Follow-up Chest Radiography
7. General Management
Advise parents and carers about:
Indications for Intensive Care Admission
Empirical Antibiotics Treatment
Known Pathogen Therapy for S. pneumoniae
Since S. pneumoniae is the most common cause of CAP, the empirical antimicrobial treatment in both outpatient and inpatient setting should be able to cover S. pneumoniae. More than 70% of the local S. pneumoniae isolates are resistant to macrolide, and almost all isolates are resistant to oral cephalosporins (cephalexin, cefaclor, cefuroxime axetil, ceftibuten).89 Utilisation of these agents would result in treatment failures.
According to the Public Health Laboratory Service (PHLS) sentinel data from all public and private laboratories in 2011-2013 (Figure 1),89 almost 90% of the S. pneumoniae isolates had a penicillin MIC ≤2 μg/ml. S. pneumoniae with penicillin MIC =4 μg/ml (intermediate susceptibility to penicillin) is very rare and no isolates had a penicillin MIC is ≥8 μg/ml. The panel therefore recommends amoxicillin equivalent 45 mg/kg/day for mild CAP in children with no prior treatment of beta-lactams, and escalation to 90 mg/kg/day or switch to parenteral P3GC if no clinical improvement after 48 hours. For moderate to severe CAP irrespective of prior treatment, amoxicillin equivalent 90 mg/kg/day right from start. Vancomycin is not indicated for empirical treatment of CAP unless there is concomitant evidence of meningitis, severe adverse reaction towards beta-lactam antibiotics (such as cytopenia, Steven-Johnson syndrome, toxic epidermal necrolysis and type I anaphylatic reaction) or the child presents with septic shock and there is no way to exclude meningitis infection.
Duration of Antibiotic Treatment
9. Specific Problem: Management of Macrolide-resistant M. pneumoniae
Laboratory Diagnosis of MRMP
MRMP was first reported in Japan in 2001.106 Since then, there has been reports in China,107-110 South East Asia,111-113 North America114,115 and various European countries.116-118 In China, the prevalence of MRMP is exceptionally high, constituting over 90% of all isolates of M. pneumoniae.108 The first locally acquired case of MRMP in Hong Kong has been reported in the New Territories West cluster in 2010.119
The true epidemiology of M. pneumoniae and the prevalence of MRMP in Hong Kong remains unclear. There are two local publications providing information on the local situation of MRMP. The first study evaluated different molecular methods to detect genotypic resistance in M. pneumoniae in both adult and paediatric subjects.97 Pyrosequencing identified mutation at the position A2063G in 78.8% of the M. pneumoniae-positive samples, and 39% by Sanger sequencing and melting curve analysis. The difference is mainly due to the ability of pyrosequencing to identify low-frequency MRMP quasispecies. Another local study evaluated the antibiotics treatment efficacy against MRMP in the paediatric age group only.99 Among the paediatric CAP cases with a positive M. pneumoniae PCR, 70% were MRMP. Only A2063G mutation was identified in both studies.
If mycoplasma pneumonia is suspected, nasopharyngeal secretions should be tested for M. pneumoniae by PCR.97,100,120 PCR is superior to serology for the diagnosis of acute M. pneumoniae infection although nucleic acid may remain detectable for prolonged periods after recovery.121 If response to macrolide treatment for presumed mycoplasma pneumonia is lacking, direct rapid genetic testing for MRMP in respiratory specimens positive for M. pneumoniae DNA is indicated to guide alternative antibiotic therapy. Currently, real-time PCR of the domain V of the 23s rRNA gene coupled to melting curve analysis is the most widely used method for identification of MRMP in Hong Kong.97,99,119,122 Genotypic detection of MRMP is available in selected specialised centers, University hospitals and the Government Public Health Laboratory Service in Hong Kong. Since the result of the resistance genotype may not be readily available, empirical initiation of alternative antimicrobial agents may sometimes be required.
Neither IDSA guideline nor BTS guideline have any recommendation on the treatment of MRMP.3,4 The Japanese guideline for management of respiratory infection in children published in 2007 has recommended the switching to tetracycline antibiotics if fever persists for more than 48 hours after macrolide antibiotic initiation.123 In-vitro studies have demonstrated that the tetracyclines and fluoroquinolones have relatively low MIC value against MRMP.109,124-126 Several case series in Japan have suggested the use of minocycline and doxycycline for treatment of MRMP in children.127-129
Both fluoroquinolones and tetracyclines have the potential to cause toxicities in young children.130-133 The doctor should explain the reasons for their use and potential side effects to the parents before prescribing the drug.
10. Discharge Criteria for Children Hospitalised with Community-acquired Pneumonia
Declaration of Interest
The following authors have NO interest to declare:
The following author declares that the following condition concerning him or his immediate family members could cause conflict of interest.
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