|Year : 2017 | Volume
| Issue : 3 | Page : 122-129
Epidemiology and antimicrobial resistance of community-acquired pneumonia in children
Maha M. H. K Mansour1, Khalid Mohamed Al Hadidi2, Manal Shafik Hamed3
1 Pediatric Department, Cairo University, Cairo, Egypt; Department of Pediatric, Jeddah Clinic Hospital, Jeddah, KSA
2 Clinical Pathology Department, Ain Shams University, Cairo, Egypt; Department of Clinical Pathology, Jeddah Clinic Hospital, Jeddah, KSA
3 Radiology Department, Ain Shams University, Cairo, Egypt
|Date of Submission||09-Sep-2015|
|Date of Acceptance||07-Oct-2016|
|Date of Web Publication||6-Oct-2017|
Maha M. H. K Mansour
Jeddah Clinic Hospital- AlKandarah, Old Airport Street, P. O. Box: 115, Jeddah - 21411
Source of Support: None, Conflict of Interest: None
Background: Community-acquired pneumonia (CAP) is a common serious infection in childhood. Bacterial resistance is widespread, with large geographical variations related to behaviors in antibiotics prescription. Identification of etiologic organisms of CAP and their resistance pattern must be done to guide the physicians for proper antimicrobial use. Aim: To identify the causative organisms most frequently isolated from children hospitalized for pneumonia and analyze their susceptibility to the antimicrobial agents most often used in pediatric practice. Materials and Methods: Two hundred and ninety-six immunocompetent children hospitalized in Jeddah Clinic Hospital with CAP from January 2010 to September 2011 were enrolled in the study. Their ages ranged between 6 weeks and 15 years. Chest radiograph, complete blood count test (CBC), C-reactive protein, test and sputum culture and sensitivity were done for all patients. Results: One hundred and nine (35.82%) participants were infants <1 year, 43.58% were >1 year ≤5 years, and 20.6% were >5 years. A pathogen was identified in 34.12% of sputum cultures, 56.4% were typical respiratory pathogenic bacteria while 43.56% were normal commensals. Sputum cultures grew Streptococcus pneumonia in 8.77% of respiratory pathogens, coagulase positive Staphylococcus (19.3%), Group B β-hemolytic Streptococcus (8.77%), Escherichia coli (33.3%), Klebsiella spp. (14%), and Pseudomonas (14%). High antimicrobial resistance was recorded for penicillin, amoxicillin-clavulanate, cefaclor, cephalexin, and cefuroxime in Gram-positive organisms. Twenty-one percent of E. coli and 50% of Klebsiella spp. were resistant to spectrin. Conclusions: Higher incidence of CAP due to E. coli was recorded. There is increasing antimicrobial resistance to penicillin and second-generation cephalosporin.
Keywords: Antimicrobial resistance, children, community-acquired pneumonia
|How to cite this article:|
Mansour MM, Al Hadidi KM, Hamed MS. Epidemiology and antimicrobial resistance of community-acquired pneumonia in children. J Health Res Rev 2017;4:122-9
|How to cite this URL:|
Mansour MM, Al Hadidi KM, Hamed MS. Epidemiology and antimicrobial resistance of community-acquired pneumonia in children. J Health Res Rev [serial online] 2017 [cited 2020 Feb 23];4:122-9. Available from: http://www.jhrr.org/text.asp?2017/4/3/122/216067
| Introduction|| |
Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community, as distinguished from hospital-acquired (nosocomial) pneumonia. CAP is a common and potentially serious illness with considerable morbidity.
The wide spectrum of presentation among children can make diagnosing difficult. While CAP can manifest as an acute febrile illness with clinical decompensation in some children, a small percentage of pediatric patients under 5 years of age may simply have fever and abdominal pain without respiratory distress.
The worldwide burden of CAP has decreased over the past decade, largely due to widespread pneumococcal immunization. However, CAP remains a leading cause of pediatric hospitalizations, with increasing rates of complicated disease in the postconjugate vaccine era.
In 2015, CAP accounted for 15% of deaths in children under 5 years globally and 922,000 deaths globally in children of all ages.
The causes of CAP in children as reported in the medical literature must be interpreted with caution largely because many methods for assignment of etiology are inadequate. Pyogenic bacteria present the most difficult challenge because the normal upper respiratory tract flora frequently contains potential pathogens and sputum collection may be difficult in young children. The presence of bacteremia confirms the cause, but blood culture is positive in less than one-tenth of children with bacterial pneumonia.
Despite several attempts, the etiologic diagnosis of pediatric CAP and the estimation of the potential outcome remain unsolved problems in most cases.
Antibacterial, commonly called antibiotics, plays a crucial role in treating severe infections of bacterial origin, including respiratory infections. The widespread use of antibiotics, whether appropriate or inappropriate, has driven the emergence and spread of resistant bacteria. Resistance to frequently used antibiotics among respiratory pathogens has become a common clinical problem.
As the epidemiology of lower respiratory tract infection varies with time and place, periodic reassessment with monitoring of causative organisms and patterns of resistance is required for better therapeutic guidance and definition of control strategies.
The main objectives of this study were to identify the causative organisms most frequently isolated from hospitalized children in Jeddah Clinic Hospital for CAP and analyze their susceptibility to the antimicrobial agents, most often used in pediatric practice, to guide the empirical antibiotic regimen for newly admitted cases.
| Materials and Methods|| |
An epidemiologic prospective study included 296 immunocompetent hospitalized children in Jeddah Clinic Hospital with CAP from January 2010 to September 2011. Their ages ranged between 6 weeks and 15 years. Children were eligible for enrolment if they had preceding fever and had tachypnea, chest retractions, or abnormal auscultatory finding, in addition to radiologic evidence of pneumonia. The study was approved by the Hospital's Ethical Committee.
Indications for hospitalization included severe dehydration, inability to tolerate oral rehydration or medication, moderate-to-severe respiratory distress, altered mental status, oxygen requirement, poor compliance or lack of follow-up after discharge, and unsuccessful outpatient management. Children were excluded if they had proven immunodeficiency or immunosuppression. Signed informed parental consent and the child's assent (if the child was <10 years old) were obtained. Complete blood count, C-reactive protein (levels were considered elevated above 10 mg/L), and sputum culture and sensitivity were done for all patients. Viral and the “atypical” causes of pneumonia, including Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella spp., were not assessed. Sputum sample was taken within 2 days of hospitalization to avoid including possible hospital-acquired infection.
Sputum induction was undertaken on the day of enrolment after 2–3 h fasting. Children were pre-treated with salbutamol (100 μ g in <1 year old, 200 μ g in >1 year old) mixed with 2 cc plain normal saline solution, oxygen-driven nebulization. Thereafter, physiotherapy techniques including chest percussion were applied. Sputum was obtained either by expectoration (in children able to cooperate) or by suctioning through the nasopharynx using a sterile nasogastric tube size 8 or 10.
Specimens were placed in a sterile bottle and transported directly to laboratory for processing. They were assessed for their quality to be accepted by the laboratory. The procedure had to be repeated if the specimen was rejected. Specimens consisting of saliva were examined by macroscopic observation. Gram staining was then performed and specimens containing more than 25 polymorph nuclear neutrophils and fewer than 10 epithelial cells per low-power field were included in the study.
Specimens were placed on blood agar plate (for Staphylococcus and Streptococcus) and MacConkey (for Gram-negative bacteria) and then incubated in 5%–7% CO2 at 35°C. Plates were examined every 24 h. If there is no growth after 48 h, plates were discarded, and if growth occurs, these were followed by identification procedures.
Different combinations of antibiotic discs were used by the laboratory as a policy to cover most of the antibiotics available.
Data were tabulated and subjected to analysis using Microsoft Excel version 5.0 and the Statistical Package for Social Science version 13.0. The following methods were employed:
- Frequency distributions and percentage distributions
- Mean, standard deviation, and range of numerical data
- Comparison of means using the Student's t-test; testing differences between means for statistical significance
- Nonnumerical data were compared using the Chi-square test and Fisher's exact tests
- In general, P < 0.05 is considered significant, <0.01 highly significant, and <0.001 very highly significant.
| Results|| |
Two hundred and ninety-six hospitalized children with CAP were enrolled in the study. A definite seasonal pattern with winter preponderance was seen for hospital admissions due to CAP. November and December showed a peak 3 times higher than August and 12 times higher than July [Figure 1]. One hundred and forty-six (55.4%) were males and 132 (44.6%) were females. One hundred and nine (35.82%) participants were infants, 43.58% were >1 year ≤5 years, and 20.6% were >5 years. The youngest was 1.5 months old and the oldest was 15 years old. Median age was 37.3 months. The most common clinical presentations were cough (100%) and fever (96.9%). Antibiotic administration before admission was reported in 60.81% of cases. The mean length of hospital stay was 3 ± 1.84 days [Table 1].
|Figure 1: Hospitalized patients for community acquired pneumonia in 2010 and 2011|
Click here to view
|Table 1: Characteristics of 296 patients with community-acquired pneumonia|
Click here to view
The most common radiological findings were bronchopneumonia in 49% and right basal pneumonia in 31.4% of cases. Bacterial growth was recovered in 101 (34.12%) children; 57/101 (56.44%) were typical respiratory bacteria in the following order: Escherichia More Details coli in 19 patients (33%), followed by coagulase-positive Staphylococcus (19.3%) and both Klebsiella spp. and Pseudomonas (14%), and Streptococcus pneumoniae was identified in 5 patients (8.77%). Among 101 specimens, 44 (43.56%) of sputum cultures grew respiratory commensals; β-hemolytic Streptococcus Groups C, D, and F not known to cause pneumonia in humans  [Table 2].
|Table 2: Chest radiograph, sputum culture, complete blood count, and C-reactive protein of patients|
Click here to view
Higher percentage (56.63%) of isolates was recorded in the age group ≤1 year [Table 3]. A decreasing proportion of isolates was detected with increasing age [Table 3]; 23% in children >1 year ≤5 years and 4% >5 years.
High rate of antimicrobial resistance to Gram-negative organisms was recorded in 92.3% of those tested to amoxicillin, cefixime (71.43%), cefuroxime (42.3%), amoxicillin-clavulanate (amox-clav) (34.6%), spectrin (29.62%), and cefotaxime (20.68%) [Table 4]. Antimicrobial resistance in Gram-positive organisms showed higher rate with those tested to penicillin (100%), amoxicillin (100%), cefixime (100%), cephalothin (100%), cefotaxime (94.74%), amox-clav (80%), cefaclor (69.23%), ceftriaxone, tetracycline and cephalexin (66.67%), and cefepime (64.7%) [Table 5]. There was a statistically significant correlation between severity of disease, length of hospital stay, antibiotic administration before admission, and the wide range of antimicrobial resistant organisms (P < 0.05).
| Discussion|| |
Nonetheless, CAP remains a common cause of pediatric morbidity and mortality although mortality varies between the industrialized and developing countries. In developing countries, where access to care is limited, and interventions that have improved care in the industrialized world are scarce, more than 150 million CAPs are diagnosed in children annually, and a relevant portion of these patients, particularly the youngest, have severe disease and die. Estimates for 2015 have indicated that approximately 1 million children younger than 5 years of age have died from CAP worldwide, and the majority of these deaths have occurred in the developing world, mainly in South Asia and the Sub-Saharan area.
Despite the remarkable advances in antibiotic therapies, diagnostic tools, and intensive care, CAP is still among the primary causes of mortality worldwide. One hundred and fifty million episodes of pneumonia each year make it a major health problem in developing countries, particularly for children and the elderly.
Our study showed marked seasonal variation with winter preponderance for hospital admissions due to CAP. The peak was recorded in November and December, while the least prevalence was in July. Similar variation was recorded in Oslo, Norway.
This was in concordance with other series showing similar seasonal variation in viral infections such as respiratory syncytial virus, influenza, and parainfluenza 1 + 2., This fact can be explained by coinfection and secondary bacterial infection and same predisposing factors for respiratory tract infections.
Males constituted 55.4% of our cases indicating significant higher rate of pneumonia in males.,,
The median age of cases was 37.3 ± 37.2 months with statistically significant higher incidence of CAP in younger age below 5 years.,,,
In the present study, we focused on sputum culture as the overall yield of blood cultures is probably <20% in hospitalized patients for CAP.
A complete microbiological investigation is recommended in the case of admission to an Intensive Care Unit, failure of antibiotic therapy, radiographic cavities, and these situations were not encountered during the period of our study.,,,
In the present study, a bacterial growth was identified in 101 (34.12%) children. The rate of identification of causative pathogens varied between 30.3% and 81% in different series.,,,,, Most probably, this wide range was due to the different isolation techniques as sputum culture, blood cultures, and polymerase chain reaction and rapid antigen detection tests. On the other hand, the high rate of negative cultures could be attributed to antibiotic use before admission.,
Although the general practice is to obtain specimens before any antibiotic administration, it is very important to avoid delays in initiating antibiotic therapy because these delays are associated with increased mortality.,
Gram-negative organisms were the most common cause (61.4%), followed by Gram-positive organisms (38.6%). E. coli was the most common organism (33%), followed by Staphylococcus aureus(19.3%), Pseudomonas aeruginosa (14%), Klebsiella spp. (14%), S. pneumoniae (8.77%), β-hemolytic Streptococcus-B (8.77%), and β-hemolytic Streptococcus-A (1.75%). In other studies, causative organisms were mainly S. pneumoniae ranging from 73% to 80%.,, Different findings were reported by Chiang et al. as they found typical respiratory bacteria in 10.3% of their cases, of which 64.6% were S. pneumoniae and 21.7% were nontypeable Haemophilus influenzae). In another study conducted in Izmir, Turkey, S. pneumoniae accounted for 20% of their patients.
Another pattern of distribution was found in China as H. influenzae was the most common etiological pathogen, followed by Klebsiella spp., S. pneumoniae, S. aureus, Moraxella More Details catarrhalis, and other Gram-negative organisms. Group A streptococcal infection was found in 1%–7% of cases in other studies.,
In Australia, Ingarfield et al. found that the most common organisms isolated from sputum in both admissions and nonadmissions were H. influenzae in 35.4%, S. pneumoniae in 25.9%, P. aeruginosa in 15.9%, S. aureus in 10.9%, and M. catarrhalis in 6.2%.
Although S. aureus is not a common cause of pediatric pneumonia, it has been increasingly encountered in communities where methicillin-resistant S. aureus (MRSA) is prevalent.
The introduction of the pneumococcal conjugate vaccine (PCV) has been the biggest recent change in pneumonia prevention. These vaccines are immunogenic in children from 2 months of age and have around 97% efficacy against invasive pneumococcal disease.,
Introduction of the PCV-7 conjugate vaccine in the Kingdom of Saudi Arabia in 2010 and followed by PCV-13 in 2011 has almost abolished invasive disease caused by these pneumococcal serotypes in children <2 years and has substantially reduced the number in older children. Same findings were recorded in England and Wales after introduction of the PCV-7 conjugate vaccine in 2006, as well as in the USA.
In addition, H. influenzae was not encountered in our cases as compulsory vaccination of infants was introduced more than 10 years ago.
The different pattern of microbial prevalence is influenced by local vaccination strategy in each country.
Gram-positive organisms isolated in our study showed 100% higher rate resistance to penicillin, amoxicillin, cefixime, and cephalothin, 94.74% to cefotaxime, 80% to amox-clav, 69.23% to cefaclor, 66.67% to ceftriaxone, 64.7% to cefepime, 55.56% to spectrin, and 50% to cefuroxime. In another study conducted in Sri Lanka, high percentage of resistance was recorded to penicillin and third-generation cephalosporins. In the UK, however, penicillin resistance is far less prevalent (4%). Another study by Williams et al. found that there was an improvement at children's hospitals in the use of penicillin to treat pneumonia after the publication of the 2011 Pediatric Infectious Diseases Society/Infectious Diseases Society of America pneumonia guideline. Before the guideline was published, <10% of children's hospitals prescribed penicillin to treat pneumonia versus 27.6% after publication., This is in contrast to much of Mainland Europe where rates are 25%–50% in France and Spain and 58.5% in Singapore. Beta-lactamase-producing H. influenzae was widespread recorded in the study of Muller-Pebody et al. in England, Wales, and Northern Ireland.
Our finding of 27.27% erythromycin resistance was higher than the UK (9.3%), almost same as France (25%), and less than Italy (50%). Resistance to macrolides estimated in our study ranged between 27.27% and 37.5%. US surveillance data for 2000–2004 of respiratory isolates indicate that a stable 30% is macrolide-resistant although an increasing proportion has high-level macrolide resistance. Group A Streptococcus was found to be resistant to macrolide in 40% of cases worldwide. We cannot compare this pattern with our results as we had only one case of Group A Streptococcus and no H. influenzae was isolated.
Although MRSA contributes to 31% of S. aureus bacteremia in the UK, we did not encounter MRSA in our cases.
High rate of antimicrobial resistance to Gram-negative organisms was recorded with those tested to amoxicillin (92.3%), cefixime (71.43%), cefuroxime (42.3%), amox-clav (34.6%), spectrin (29.62%), and cefotaxime (20.68%). Most commonly encountered resistant organisms in the study of Mehrgan et al. were Klebsiella pneumonia and E. coli. P. aeruginosa was found to be highly resistant to penicillin and cephalosporin. The highest resistance grade of Gram-negative bacteria was found to ampicillin and reached 81.6%–94.7%, and the lowest antimicrobial resistance was detected for amikacin, meropenem, and imipenem.
However, amoxicillin was usually recommended as the first-choice treatment for oral antibiotic therapy in all age groups. In ambulatory children older than 5 years, amoxicillin with or without macrolides was recommended in more than 50% of the centers for first-line treatment. For hospitalized patients older than 5 years, macrolides either as a single treatment or in combination with benzylpenicillin or cefotaxime were recommended.,
This high and wider range antimicrobial resistance may have been caused by the excessive use of broad-spectrum antibiotics in our community setting, highlighting the need for evidence-based guidelines to harmonize and improve the diagnostics and treatment of children's lower respiratory tract infections.
Despite this high antimicrobial resistance rate in our study, we had no record for mortality and the average hospital stay was 3 ± 1.84 days. This was comparable to the study of Weiss et al. and less than others.,
| Conclusions|| |
Higher incidence of CAP due to Gram-negative bacteria, particularly E. coli, was recorded. There is increasing antimicrobial resistance to penicillin and second- and third-generation cephalosporins. The selection of an appropriate antibiotic regimen should be based on the prediction of the most likely pathogens and the knowledge of local antimicrobial resistances. Limitation of antibiotic use giving a priority to effective narrow-spectrum antibiotics whenever indicated is recommended to reduce antimicrobial resistance. Our study has provided an insight into the bacteriology of pneumonia diagnosed in our hospital over a 21-month period. The antimicrobial resistance pattern gave us a guide for empiric antibiotic recommendation in newly admitted cases with CAP.
Additional studies including larger number of patients in our community will add on to our epidemiologic and antimicrobial resistance pattern.
Atypical bacteria and viruses as etiological pathogens of CAP which were not included in our study need to be separately evaluated.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Texas Children's Hospital Evidence-Based Outcomes Center. Community-acquired Pneumonia (CAP) Clinical Guideline; February, 2009.
Simon LH, Parikh K, Williams DJ, Neuman MI. Management of community-acquired pneumonia in hospitalized children. Curr Treat Options Pediatr 2015;1:59-75.
Haq IJ, Battersby AC, Eastham K, McKean M. Community acquired pneumonia in children. BMJ 2017;356:j686.
Lee PI, Chiu CH, Chen PY, Lee CY, Lin TY; Taiwan Pediatric Working Group for Guideline on the Management of CAP in Children. Guidelines for the management of community-acquired pneumonia in children. Acta Paediatr Taiwan 2007;48:167-80.
Principi N, Esposito S. Biomarkers in pediatric community-acquired pneumonia. Int J Mol Sci 2017;18. pii: E447.
van de Sande-Bruinsma N, Grundmann H, Verloo D, Tiemersma E, Monen J, Goossens H, et al.
Antimicrobial drug use and resistance in Europe. Emerg Infect Dis 2008;14:1722-30.
Hoa NQ, Larson M, Kim Chuc NT, Eriksson B, Trung NV, Stålsby CL. Antibiotics and paediatric acute respiratory infections in rural Vietnam: Health-care providers' knowledge, practical competence and reported practice. Trop Med Int Health 2009;14:546-55.
Gibson PG, Grootendor DC, Henry RL, Pin I, Rytila PH, Wark P, et al.
Sputum induction in children. Eur Respir J Suppl 2002;37:44s-6s.
Ozyilmaz E, Akan OA, Gulhan M, Ahmed K, Nagatake T. Major bacteria of community-acquired respiratory tract infections in Turkey. Jpn J Infect Dis 2005;58:50-2.
Polverino E, Torres Marti A. Community-acquired pneumonia. Minerva Anestesiol 2011;77:196-211.
Senstad AC, Surén P, Brauteset L, Eriksson JR, Høiby EA, Wathne KO. Community-acquired pneumonia (CAP) in children in Oslo, Norway. Acta Paediatr 2009;98:332-6.
Melegaro A, Edmunds WJ, Pebody R, Miller E, George R. The current burden of pneumococcal disease in England and Wales. J Infect 2006;52:37-48.
Ehlken B, Ihorst G, Lippert B, Rohwedder A, Petersen G, Schumacher M, et al.
Economic impact of community-acquired and nosocomial lower respiratory tract infections in young children in Germany. Eur J Pediatr 2005;164:607-15.
Clark JE, Hammal D, Hampton F, Spencer D, Parker L. Epidemiology of community-acquired pneumonia in children seen in hospital. Epidemiol Infect 2007;135:262-9.
Lee GE, Lorch SA, Sheffler-Collins S, Kronman MP, Shah SS. National hospitalization trends for pediatric pneumonia and associated complications. Pediatrics 2010;126:204-13.
Michelow IC, Olsen K, Lozano J, Rollins NK, Duffy LB, Ziegler T, et al.
Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics 2004;113:701-7.
Weiss AK, Hall M, Lee GE, Kronman MP, Sheffler-Collins S, Shah SS. Adjunct corticosteroids in children hospitalized with community-acquired pneumonia. Pediatrics 2011;127:e255-63.
Harris M, Clark J, Coote N, Fletcher P, Harnden A, McKean M, et al.
British Thoracic Society guidelines for the management of community acquired pneumonia in children: Update 2011. Thorax 2011;66 Suppl 2:ii1-23.
Campbell SG, Marrie TJ, Anstey R, Dickinson G, Ackroyd-Stolarz S. The contribution of blood cultures to the clinical management of adult patients admitted to the hospital with community-acquired pneumonia: A prospective observational study. Chest 2003;123:1142-50.
Corbo J, Friedman B, Bijur P, Gallagher EJ. Limited usefulness of initial blood cultures in community acquired pneumonia. Emerg Med J 2004;21:446-8.
Ingarfield SL, Celenza A, Jacobs IG, Riley TV. The bacteriology of pneumonia diagnosed in Western Australian emergency departments. Epidemiol Infect 2007;135:1376-83.doi:10.1056/NEJMoa1405870.
Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C et al.
Community-acquired pneumonia requiring hospitalization among U.S. children. N
Engl J Med. 2015;372:835-45.
26. Chiang WC, Teoh OH, Chong CY, Goh A, Tang JP, Chay OM. Epidemiology, clinical characteristics and antimicrobial resistance patterns of community-acquired pneumonia in 1702 hospitalized children in Singapore. Respirology 2007;12:254-61.
Huang HH, Zhang YY, Xiu QY, Zhou X, Huang SG, Lu Q, et al.
Community-acquired pneumonia in Shanghai, China: Microbial etiology and implications for empirical therapy in a prospective study of 389 patients. Eur J Clin Microbiol Infect Dis 2006;25:369-74.
Saito A, Kohno S, Matsushima T, Watanabe A, Oizumi K, Yamaguchi K, et al.
Prospective multicenter study of the causative organisms of community-acquired pneumonia in adults in Japan. J Infect Chemother 2006;12:63-9.
Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med 2004;164:637-44.
Waterer GW, Kessler LA, Wunderink RG. Delayed administration of antibiotics and atypical presentation in community-acquired pneumonia. Chest 2006;130:11-5.
Kuroki H, Tateno N, Ikeda H, Saito N. Investigation of pneumonia-causing pathogenic organisms in children and the usefulness of tebipenem pivoxil for their treatment. J Infect Chemother 2010;16:280-7.
Tumgor G, Celik U, Alabaz D, Cetiner S, Yaman A, Yildizdas D, et al.
Aetiological agents, interleukin-6, interleukin-8 and CRP concentrations in children with community- and hospital-acquired pneumonia. Ann Trop Paediatr 2006;26:285-91.
Al-Kaabi N, Solh Z, Pacheco S, Murray L, Gaboury I, Le Saux N. A comparison of group A Streptococcus
versus Streptococcus pneumoniae
pneumonia. Pediatr Infect Dis J 2006;25:1008-12.
Le Saux N, Robinson JL; Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Uncomplicated pneumonia in healthy Canadian children and youth: Practice points for management. Paediatr Child Health 2015;20:441-50.
Ladhani SN, Slack MPE, Andrews NJ, Waight PA, Borrow R, Miller E. Invasive Pneumococcal Disease after Routine Pneumococcal Conjugate Vaccination in Children, England and Wales. Emerging Infectious Diseases. 2013;19:61-68. doi:10.3201/eid1901.120741.
Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al
. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 2015;373:415-27.
Esposito S, Principi N. Pneumococcal vaccines and the prevention of community-acquired pneumonia. Pulm Pharmacol Ther 2015;32:124-9.
Batuwanthudawe R, Karunarathne K, Dassanayake M, de Silva S, Lalitha MK, Thomas K, et al.
Surveillance of invasive pneumococcal disease in Colombo, Sri Lanka. Clin Infect Dis 2009;48 Suppl 2:S136-40.
Williams DJ, Hall M, Gerber JS, Neuman MI, Hersh AL, Brogan TV, et al.
Impact of a National Guideline on Antibiotic Selection for Hospitalized Pneumonia. Pediatrics 2017. pii: e20163231.
Muller-Pebody B, Johnson A, Lillie M, and Duckworth G. Antimicrobial resistance and prescribing in England, Wales and Northern Ireland, 2008. London: Health Protection Agency; 2008.
Farrell DJ, File TM, Jenkins SG. Prevalence and antibacterial susceptibility of mef(A)-positive macrolide-resistant Streptococcus pneumoniae
over 4 years (2000 to 2004) of the PROTEKT US Study. J Clin Microbiol 2007;45:290-3.
Mehrgan H, Rahbar M, Arab-Halvaii Z. High prevalence of extended-spectrum beta-lactamase-producing Klebsiella pneumonia
e in a tertiary care hospital in Tehran, Iran. J Infect Dev Ctries 2010;4:132-8.
Wei-Hong YE, Cui-Yin LI. Pathogen Distribution and Drug-resistance Monitoring in 268 Cases with Gram-negative Bacillary Pneumonia. Chin J Nosocomial; 2008-10.
Hong-Yan W, Bo-Yu T, Li-Jun Y and Nan D. Antibiotic resistance of gram-negative Bacillus isolated from children with bronchopneumonia. Chin J Contemp Pediatr 2011;13:20-22.
Usonis V, Ivaskevicius R, Diez-Domingo J, Esposito S, et al
. Comparison between diagnosis and treatment of community-acquired pneumonia in children in various medical centres across Europe with the United States, United Kingdom and the World Health Organization Guidelines. Pneumonia 2016;8:5.
Ambroggio L, Test M, Metlay JP, Graf TR, Blosky MA, Macaluso M, et al.
Comparative effectiveness of beta-lactam versus macrolide monotherapy in children with pneumonia diagnosed in the outpatient setting. Pediatr Infect Dis J 2015;34:839-42.
Tapiainen T, Aittoniemi J, Immonen J, Jylkkä H, Meinander T, Nuolivirta K, et al.
Finnish guidelines for the treatment of community-acquired pneumonia and pertussis in children. Acta Paediatr 2016;105:39-43.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]