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Clinical characteristics of 323 children with parapneumonic pleural effusion and pleural empyema due to community acquired pneumonia
J Infect Chemother 22 (2016) 292e297
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Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Original article
Clinical characteristics of 323 children with parapneumonic pleural effusion and pleural empyema due to community acquired pneumonia Katarzyna Krenke a, *, Emilia Urbankowska a, Tomasz Urbankowski b, Joanna Lange a, Marek Kulus a a b
Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Poland Department of Internal Medicine, Pneumonology and Allergology, Medical University of Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history: Received 14 October 2015 Received in revised form 25 December 2015 Accepted 16 January 2016 Available online 23 February 2016
Background: An increasing incidence of parapneumonic effusion and pleural empyema (PPE/PE) in children has been found in several studies published in the last decades. The aim of the study was to evaluate the incidence, etiology, clinical features, treatment strategies and outcomes of PPE/PE in children treated in a referral pulmonary center in central Poland. Material and methods: We performed a retrospective analysis of clinical, radiological and laboratory data of all children aged between 1 month and 18 years with PPE/PE due to community acquired pneumonia (CAP) between January 2002 and December 2013. Results: One thousand nine hundred and thirty three children with CAP were hospitalized between 2002 and 2013. Parapneumonic effusion or PE was diagnosed in 323 children (16.7%). The proportion of children with CAP related PPE/PE increased from 5.4% in 2002 to 18.8% in 2013. Streptococcus pneumoniae was the most common causative microorganism, responsible for 66.7% cases of known etiology. All children were treated with antibiotics and in 22.6%, and 74.3% of the patients therapeutic thoracentesis, pleural drainage with or without intrapleural fibrinolysis was performed, respectively. Approximately 3% of patients required surgical intervention. Conclusions: A significant increase in the incidence of PPE/PE in children with CAP treated in our institution in the last twelve years was found. S. pneumoniae was the most common causative microorganism. Antibiotic therapy with chest drain insertion ± intrapleural fibrinolysis is an effective treatment of PPE/PE and surgical intervention is seldom necessary. With proper management, the overall prognosis in children with CAP related PPE/PE is good. © 2016, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Pneumonia Streptococcus pneumoniae Pleural effusion Pleural drainage Children
1. Introduction Parapneumonic effusion and pleural empyema (PPE/PE) are the most common complications of community acquired pneumonia (CAP) in children. Although the percentage of children with CAP complicated by PPE/PE is relatively low (approximately 1%) [1,2], the high frequency of pneumonia in children worldwide makes its local complications an important problem. Moreover, an increasing
* Corresponding author. Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Zwirki i Wigury 63A, 02-091 Warsaw, Poland. Tel./fax: þ48 22 572 01 09. E-mail address: [email protected] (K. Krenke).
incidence of PPE/PE has been reported since the 1990s. Currently, the incidence of PPE/PE ranges between 3.5 per 100.000 and 12.5 per 100.000 children, depending on the geographical region [3,4]. Streptococcus pneumoniae is invariably the leading etiologic factor of PPE/PE, even in countries where pneumococcal conjugate vaccine (PCV) is widely used. Streptococcus pyogenes and Staphylococcus aureus are usually reported as the second and the third most common cause of PPE/PE in children, with an increasing incidence of staphylococcal PPE/PE observed in some parts of the world [5]. The most effective management of PPE/PE is challenging. Proper systemic antibiotic therapy based on local microbiological and epidemiological data and early local intervention are the major determinants of successful treatment. Since only few randomized controlled trials on management of PPE/PE in children have been
http://dx.doi.org/10.1016/j.jiac.2016.01.016 1341-321X/© 2016, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
K. Krenke et al. / J Infect Chemother 22 (2016) 292e297
published, the therapeutic approach is at least partially, based on local guidelines and individual center experience. In this context, case series reported by specialized centers are an important factor in improving the knowledge on optimal management. Therefore, we undertook a study evaluating the incidence, etiology, clinical features, treatment strategies and outcomes of PPE/PE in children treated in a referral pulmonary center in central Poland. 2. Material and methods This retrospective study was carried out at the Department of Pediatric Pneumonology and Allergy of the Medical University of Warsaw e a referral center for pulmonary and pleural infections in children. Data on all children (aged between 1 month and 18 years) with CAP complicated by PPE/PE treated in our institution between January 2002 and December 2013 were reviewed. The major inclusion criterion required to select patients for the study group was CAP complicated by pleural effusion that required local intervention, i.e. at least a diagnostic thoracentesis. Exclusion criteria were as follows: primary and secondary immunodeficiency, PPE/PE in the course of hospital acquired pneumonia, pleural effusion related to pulmonary or extrapulmonary diseases other than CAP. 2.1. Definitions Parapneumonic effusion was defined as pleural effusion that met laboratory criteria for PPE (according to the British Thoracic Society statement) [6] diagnosed in children with clinical signs and symptoms of CAP. Pleural empyema was defined as pleural effusion that was described as pus (on gross appearance) during thoracentesis. 2.2. Data collection Prespecified data on all children with PPE/PE were collected. These included: demographic data, history of allergy, chronic illnesses, immunization against S. pneumoniae, the results of blood and pleural fluid culture, serum IgM antibodies to M. pneumoniae, Ch. pneumoniae, adenovirus, influenza virus and RS virus, clinical features (fever, tachypnea, cough, chest pain, abdominal pain), blood test results (complete blood count, C-reactive protein (CRP), total protein and albumin concentration), the results of pleural fluid analysis, treatment strategies (antibiotic treatment, local treatment), duration of treatment and data on treatment outcomes. The sources of data were: an electronic database of patients with pneumonia which has been running in our institution since 2003 and medical records of patients with PPE/PE. Data were presented as median and range or interquartile range (IQR). The results of the study were summarized by standard descriptive statistics. Statistical analysis was performed using Statistica 10.0 (Statsoft, Tulsa, USA) software. Non-parametric ManneWhitney U test was used to compare quantitative variables between different groups. We considered p < 0.05 as statistically significant. Pearson Chi-squared test was used to analyze the differences between PPE and PE groups in terms of different sign and symptoms as well as applied methods of local treatment. The protocol of the study was accepted by Institutional Review Board of the Medical University of Warsaw. 3. Results One thousand nine hundred and thirty three children with CAP were hospitalized in our institution between 2002 and 2013. Parapneumonic pleural effusion or pleural empyema was diagnosed in 323 children (16.7%). There were 283 (87.6%) patients with PPE and
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40 (12.4%) patients with PE (14.6% and 2.1% of all children with CAP, respectively). The percentage of children with PPE/PE differed significantly in subsequent years, data are presented in Fig. 1. There was a perfectly even gender distribution in patients with PPE/PE, with 161 girls and 162 boys, median age 5 years, (IQR 4e8, range 1e17). Medical history revealed following comorbidities and chronic or recurrent conditions: recurrent respiratory tract infections 27 cases (8.4%), asthma 25 (8%), other allergic diseases 20 (6.2%), adenoid hypertrophy 9 (2.8%), history of non-complicated CAP 8 (2.5%), recurrent urinary tract infections 7 (2.2%), congenital heart disease 3 (0.9%), diabetes mellitus 1 (0.3%), arterial hypertension 1 (0.3%). There were no children with primary or secondary immunodeficiency in the study group. Thirty three children (10.2%) were vaccinated against S. pneumoniae. Data on vaccine type were available in 23 cases (PCV7 - 15, PCV10 - 3, 23-valent pneumococcal polysaccharide vaccine e 5). Fever, tachypnea and cough were the most common presenting symptoms. Abdominal pain was significantly more common in children with PE as compared to PPE. The median duration of fever before hospital admission was 9 days (range 7e12 days). Data on clinical presentation of PPE/PE in the study group are summarized in Table 1. The results of basic laboratory tests on admission are presented in Table 2. There were significantly elevated acute phase reactants, with the median CRP value 13.7 mg/dl (upper limit of normal 1 mg/ dl) (IQR 5.8e23.3). The median WBC count was 14.6 109/L (IQR 10.2e19.3) with neutrophil predominance. The results of pleural fluid analysis in children with PPE and PE differed significantly in terms of pH, specific gravity, lactate dehydrogenase and glucose level. Table 3 shows comparative data on biochemical properties and cellular composition of pleural fluid in patients with PPE and PE. Data on blood and pleural fluid cultures were available in 192 (59.4%) and 254 children (78.6%), respectively. Blood cultures were positive in 21 children (10.9%), while pleural fluid cultures in 34 cases (13.4%). In 9 children with positive pleural fluid culture for S. pneumoniae data on pneumococcal serotypes were available. The results were as follows: serotypes 1, 3, 6A and 23F were found in single patients, while serotype 6B and serotype 19A were identified in 2 and 3 patients, respectively. The results of blood and pleural fluid cultures are presented in Table 4. Data on serum IgM antibodies to atypical pathogens and respiratory viruses were available in 113 (35%) of children. High IgM levels suggesting M. pneumoniae, Ch. pneumoniae, adenoviral, influenza or RSV infection were found in 35 (30%), 10 (9%), 10 (9%), 8 (7%) and 7 (6%) patients, respectively. In 3 children bacteriological and serological results proved concurrent infections with typical bacteria, atypical bacteria and/or viruses (S. pneumoniae þ M. pneumoniae, S. pneumoniae þ C. pneumoniae and S. aureus þ M. pneumoniae þ RSV). The majority of children, i.e. 197 (61%), were treated with antibiotics before admission to our hospital (in regional hospital or at home). Amoxicilin, ampicillin, amoxicillin/clavulanic acid, cefuroxime and macrolides were the most common preadmission treatment. Initial antibiotic therapy applied in our institution largely depended on the previous treatment and its efficacy. In general, first line antibiotic therapy included ampicillin or amoxicillin/clavulanic acid with or without macrolides. When second line therapy was necessary (due to prolonged signs and symptoms and/or the results of microbiological studies), the most common choice was: cefotaxime, ceftriaxone with clindamycin, vancomycin and carbapenems. In children who were severely ill and those who were unsuccessfully treated with antibiotics before hospital admission ceftriaxone, cefotaxime,
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Fig. 1. The percentage of children with pleural complications of CAP (compared to all CAP patients) treated in consecutive subsequent years between 2002 and 2013. The numbers in bars show the number of patients with PPE/PE treated in each year. PPE e parapneumonic pleural effusion, PE e pleural empyema.
Table 1 Signs and symptoms in children with pleural empyema and parapneumonic pleural effusion (data on admission). Clinical signs and symptoms
Pleural empyema n ¼ 40 (%)
Parapneumonic pleural effusion n ¼ 283 (%)
Fever Tachypnea Cough Abdominal pain Chest pain
38 36 27 18 14
270 (95,4) 229 (80.9) 195 (68.9) 80 (28.3) 79 (29.9)
(95.0) (90.0) (67.5) (45.0) (35.0)
NS NS NS p ¼ 0.03 NS
Table 2 The results of basic laboratory tests in children with PPE/PE, data presented as median and IQR; normal range presented in square brackets. CRP- C-reactive protein, WBC e white blood cell count, NS e not significant. Laboratory test [range of normal values]
Pleural empyema Result, median (IQR)
Parapneumonic pleural effusion Result, median (IQR)
CRP (mg/dl) [<1.0] WBC (109/L) [4.5e13] Hemoglobin (g/dl) [10.9e14.2] Neutrophils (%) [age dependent] Platelets (109/L) [150e400] Total serum protein (g/L) [60.0e80.0] Serum albumin (g/L) [35.0e52.0]
15.56 15.34 10.7 73.9 426 59 27.5
13.2 14.35 11 70 387 62 29
(10.2e23.9) (10.6e22.2) (10.2e12) (63e83.7) (310e605) (52e63) (24e32)
(5.58e22.9) (9.9e19.2) (10.2e11.8) (60e80) (310e486) (56e68) (25e33)
NS NS NS NS NS NS NS
Table 3 Pleural fluid laboratory tests results in patients with parapneumonic pleural effusion and pleural empyema. Data presented as median and IQR (in brackets); * true number of cells could not have been established in the majority of patients with empyema due to cell damage and necrosis; NS e not significant, NA not applicable.
pH Specific gravity Total protein, g/L Lactate dehydrogenase, IU/L Glucose (mg/dL) Total cell count, cells/mL* Neutrophils (%)
Pleural empyema (n ¼ 40)
Parapneumonic pleural effusion (n ¼ 274)
7 (7e7.4) 1.02 (1.015e1.02) 40 (35e47) 7418 (2298e20,191) 27 (10e52) NA 80 (66e89)
7.5 1.02 44 3319 63.5 2750 72
clindamycin (alone or with beta-lactam antibiotics) were administered as first line treatment. The median duration of antibiotic treatment in children treated with pleural drainage was 21 days (range 15e33 days), while in children treated with
(7.25e8) (1.015e1.02) (38e49) (1081e8280) (26e78) (470e6800) (48e86)
p ¼ 0.0000 NS NS p ¼ 0.004 p ¼ 0.001 NA NS
single or repeated therapeutic thoracentesis was 18 days (range 14e24 days). At the same time the median duration of antibiotic treatment of children with non-complicated CAP was 9 days (range 6e14 days).
K. Krenke et al. / J Infect Chemother 22 (2016) 292e297 Table 4 Bacteria detected by blood and pleural fluid culture in children with parapneumonic effusion/pleural empyema. Blood culture Streptococcus pneumoniae Coagulase e negative staphylococci Oral streptococci Pleural fluid culture Streptococcus pneumoniae Streptococcus pyogenes Staphylococcus aureus Klebsiella pneumoniae Coagulase e negative staphylococci Enterobacter hafniae Oral streptococci
Number (%) 14 (66.7) 6 (28.6) 1 (4.8) 23 (67.7) 2 (5.8) 1 (2.9) 1 (2.9) 5 (14.7) 1 (2.9) 1 (4.8)
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especially serotype 1, 3 and 19A [4,7e9]. Data from the United States, where PCV was introduced in 2000, showed that despite the reduction of hospitalization rate due to CAP (33% reduction of hospitalizations due to CAP and 61% reduction of hospitalizations due to CAP caused by S. pneumoniae in children younger than 2 years), a 2-fold increase of empyema rate was noted. Data from some centers indicate an even higher (up to 5-fold) increase in the incidence of PPE/PE in children after implementation of PCV [10]. Similar, or even higher increase was found in our institution. The percentage of children with CAP who developed pleural complications increased from 5.4% and 2.3% in 2002 and 2003, respectively to 21.2% in 2012 and 18.8% in 2013. However, this finding cannot be explained by the use of PCV, since in Poland PCV is not
Table 5 Procedures applied as the local treatment of parapneumonic effusion and pleural empyema in the study group. NS - no significant difference; *Local treatment refers to the most invasive therapeutic procedure applied in individual patient (e.g. when therapeutic thoracentesis and chest tube were applied only chest tube drainage was listed in the table). Local treatment*
Pleural empyema n ¼ 40 (%)
Parapneumonic pleural effusion n ¼ 248 (%)
Therapeutic thoracentesis Chest tube drainage Chest tube drainage with intrapleural fibrinolitics (urokinase) VATS
0 3 30 7
65 37 144 2
(0.0) (7.5) (75.0) (17.5)
Local treatment modalities applied in children with PPE/PE are shown in Table 5. By definition, all children underwent a diagnostic thoracentesis. Therapeutic thoracentesis was the only local treatment necessary in almost one fourth of patients. In the remaining children, more invasive procedures had to be used (Table 5), including chest tube drainage or chest tube drainage with intrapleural fibrynolytic administration (urokinase; the procedure was applied since 2004). Surgical procedures (VATS) were reserved for children who did not respond to the above described treatment (persisting fever in association with a persistent pleural fluid formation, despite chest tube drainage with intrapleural fibrinolysis and antibiotics). Only less than 3% of patients required surgical intervention. The median duration of pleural drainage was 6 days (IQR 5e9 days) and the median total amount of pleural fluid drained was 525 ml (IQR 290e1000 ml). The median length of hospital stay was 19.5 (IQR 15e25.5) days. In 32 cases PPE/PE was a consequence of necrotizing pneumonia. The most common complications were bronchopleural fistula (n ¼ 29; 9%), pneumothorax (n ¼ 25; 7.7%) and lung abscess (n ¼ 6; 1.8%). Directly after the end of treatment, changes in the chest radiogram were observed in all children (reduced lung volume, pleural thickenings). Normalization of the radiological appearance was observed 6e12 months after discharge. No recurrences of CAP and/or recurrent pleural infections were found during 12 months of follow-up. The mortality rate was 0%. 4. Discussion Our study showed a significant increase in the incidence of PPE/ PE in children with CAP treated in our institution in the last twelve years. We found, that S. pneumoniae was invariably the most common causative microorganism responsible for pleural infections associated with CAP. An increasing incidence of PPE/PE in children has also been reported by other authors [3,4,6,7]. The reason for this phenomenon is not clear. One hypothesis suggests that this is a consequence of pneumococcal conjugate vaccine (PCV) introduction and the emergence of pneumococcal serotypes not covered in the PCV7,
(23.0) (13.1) (50.9) (0.7)
p ¼ 0.0002 NS p ¼ 0.04 p < 0.0001
refunded for the whole population of children and only 10.2% of children in our study group were vaccinated against S. pneumoniae. Our results are in agreement with some other studies. In some welldeveloped countries, an increasing incidence of PPE/PE has already been noted in 1990s, that is before the implementation of PCV [11]. Rising percentage of children with PPE/PE was later reported in countries where PCV had not been widely introduced [12]. These findings suggest that other factors may play a significant role in the observed trends in childhood PPE/PE. For example, changes in etiology of PPE/PE have been reported. Despite the fact that S. pneumoniae remains the most common causative agent of PPE/ PE, other bacteria like S. aureus are increasingly recognized as the etiologic factors [3,5]. The most common presenting symptoms in our study group were fever, tachypnea and cough. This is consistent with data from other studies [12]. We did not find significant differences between children with PPE and PE in terms of the above mentioned symptoms. Interestingly, abdominal pain was more frequently observed in children with pleural empyema. The relationship between pleural empyema and abdominal pain was earlier reported by Lahti et al. CAP [13]. In our retrospective study, the etiology of PPE/PE could have been determined in only a minority of patients. Blood cultures were positive in 10.9% of children. Similar data on the percentage of positive blood cultures were published by Lahti et al. (11%), while higher percentages (26%) were reported by other authors [13,14]. The diagnostic yield of pleural fluid cultures in our study was not significantly different than that found for blood cultures. The etiologic factor responsible for pleural infection was identified in 13.4% of pleural fluid samples. In other studies significant differences in the percentage of positive pleural fluid results were demonstrated, with the proportion of culture positive specimens ranging from 19% to 36% [13,14]. Our study showed that S. pneumoniae remains the most common bacteria responsible for PPE/PE in children. This pathogen was identified as an etiologic factor in two thirds of children with PPE/PE of known etiology. Similar numbers indicating that S. pneumoniae is a leading cause of PPE/PE were reported in other studies, including those performed in countries where PCV had been widely applied [3]. On the other
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hand, some changes in the etiology of PPE/PE in children were also noticed. These refer to a significant increase in the incidence of PPE/ PE caused by S. aureus [3,5]. This was not the case in our study in which S. aureus was a marginal pathogen identified in only one pleural fluid sample. Similar findings were published by Sakran et al. and Grisaru-Soen et al. [12,14]. All other bacterial species that were cultured in our patients were responsible for 31% of positive blood and pleural fluid cultures. S. pyogenes and Klebsiella pneumoniae were identified in 2 and 1 pleural fluid samples, respectively. The true pathogenic role of coagulase e negative staphylococci and viridans streptococci cultured in our study is unknown. Although, the presence of these bacteria in blood and/or pleural fluid cultures has also been reported in other studies on etiology of PPE/PE in children, their causative role is regarded as negligible by some authors. The likelihood of pathogenicity of the above mentioned bacteria increases, if the organism is detected in multiple blood cultures obtained by independent venipunctures [15]. As in our study, all these bacteria were identified in single pleural or blood fluid cultures, it is not clear whether they should be considered the cause of pleural complications. While the role of microbiological testing (blood and pleural fluid cultures) in children with PPE/PE is well established, the usefulness of acute phase reactants and other blood tests, as well as biochemical pleural fluid analysis in management of children with PPE/PE is not so evident [6]. The authors of the British Thoracic Society (BTS) guidelines for the management of pleural infection in children suggest that full blood count, CRP, electrolytes and serum albumin level should be performed as the initial laboratory investigations. However, as PPE/PE due to CAP is rarely caused by viral infection and the serum level of acute phase reactants cannot reliably distinguish between viral and bacterial infection, it seems that the white blood cell count and CRP level may have only very limited impact on the choice of treatment [6]. This also refers to the differentiation between PPE and PE. Although our children with PPE/PE had significantly elevated WBC count with neutrophil predominance and elevated CRP levels, we were not able to demonstrate significant differences between the results in children with PPE as compared to PE. According to a widely accepted opinion, the role of biochemical pleural fluid analysis in children is not as important as in adult patients. This is because the spectrum of causal diagnoses in adults with pleural effusion is much wider than in children, and pleural fluid analysis plays a crucial role in the diagnostic approach [16]. Conversely, the majority of pleural effusions in children are related to pulmonary infections and the choice of treatment is only rarely based on the results of pleural fluid analysis [17e19]. Therefore the BTS and the Pediatric Infectious Diseases Society and Infectious Diseases Society of America (PIDS/IDSA) guidelines suggest that biochemical testing of pleural fluid in children with PPE associated with pneumonia is not required [6,16]. We found that the results of biochemical tests of pleural fluid in children with PPE/PE are similar to those seen in adults [20] with a significant difference between PPE and PE in terms on pH, LDH and glucose level. Both antibiotic therapy and local intervention have an important role in the treatment of PPE/PE. Since the positive results of microbiological studies can be expected in only a minority of patients, the choice of antibiotics is based on local epidemiological and microbiological data, as well as current national and international guidelines. The antibiotics that were most commonly prescribed in our study group included ampicillin, amoxicillin/ clavulanic acid, cefotaxime or ceftriaxone (alone or with clindamycin) and macrolides (with beta-lactam antibiotics). These choices are in accordance with the current PIDS/IDSA guidelines, as well as the experience of other centers [6,13,15,16]. It has been suggested that the first line antibiotic therapy in severely ill
children should include vancomycin or clindamycin. This is because the increasing frequency of PPE/PE caused by communityassociated methicillin-resistant S. aureus (CA-MRSA) [5]. The results of our microbiological studies do not indicate that S. aureus plays an important role in PPE/PE in Polish children, however careful monitoring of changing microbiological trends should be conducted. While the guidelines on the antibiotic management of PPE/PE are rather unequivocal, more controversies refer to the choice of local intervention. The therapeutic options include: single or repeated therapeutic thoracentesis, chest tube drainage (with or without intrapleural fibrynolysis) and VATS [6,16,21,22]. The choice between these methods is mainly based on disease severity and anatomical factors, i.e. pleural fluid volume, its location and the presence of loculations and adhesions. However, personal and center experience are also very important factors affecting the management strategy [22,23]. In our institution, the usual therapeutic regimen includes: antibiotics ± therapeutic thoracentesis in case of small pleural effusion (less than ¼ of pleural cavity), antibiotics þ chest tube drainage when there is moderate or large pleural effusion, chest tube drainage with intrapleural fibrynolysis in case of loculated pleural effusion and VATS, when the above mentioned treatment is ineffective. Most of the current guidelines suggest that pleural drainage ± intrapleural fibrynolysis is a reasonable first treatment option and VATS should be considered as a second line therapy [16]. 5. Conclusions A significant increase in the incidence of PPE/PE in children with CAP treated in our institution in the last twelve years was found. S. pneumoniae was the predominant pathogen responsible for pleural complications. Antibiotic therapy with chest drain insertion ± intrapleural fibrinolysis is an effective treatment of PPE/ PE and surgical intervention is seldom necessary. With proper management, the overall prognosis in children with CAP related PPE/PE is good. Conflict of interest The authors declare no conflict of interest. References [1] Harris M, Clark J, Coote N, Flether 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:ii1e23. [2] Paraskakis E, Vergadi E, Chatzimichael A, Bouros D. Current evidence for the management of paediatric parapneumonic effusions. Curr Med Res Opin 2012;28:1179e92. [3] Grijalva CG, Nuorti JP, Zhu Y, Griffin MR. Increasing incidence of empyema complicating childhood community-acquired pneumonia in the United States. Clin Infect Dis 2010;50:805e13. [4] Byington CL, Hulten KG, Ampofo K, Sheng X, Pavia AT, Blaschke AJ, et al. Molecular epidemiology of pediatric pneumococcal empyema from 2001 to 2007 in Utah. J Clin Microbiol 2010;48:520e5. [5] Schultz KD, Fan LL, Pinsky J, Ochoa L, Smith EO, Kaplan SL, et al. The changing face of pleural empyemas in children: epidemiology and management. Pediatrics 2004;113:1735e40. [6] Balfour-Lynn IM, Abrahamson E, Cohen G, Hartley J, King S, Parikh D, et al. BTS guidelines for the management of pleural infection in children. Thorax 2005;60:i1e21. V, Pahissa A. The increasing incidence of empyema. Curr Opin [7] Burgos J, Falco Pulm Med 2013;19:350e6. lez MA, Molinos A, [8] Obando I, Camacho-Lovillo MS, Porras A, Gandía-Gonza Vazquez-Barba I, et al. Sustained high prevalence of pneumococcal serotype 1 in paediatric parapneumonic empyema in southern Spain from 2005 to 2009. Clin Microbiol Infect 2012;18:763e8. [9] Weil-Olivier C, van der Linden M, de Schutter I, Dagan R, Mantovani L. Prevention of pneumococcal diseases in the post-seven valent vaccine era: a European perspective. BMC Infect Dis 2012;12:207.
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Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Original article
Clinical characteristics of 323 children with parapneumonic pleural effusion and pleural empyema due to community acquired pneumonia Katarzyna Krenke a, *, Emilia Urbankowska a, Tomasz Urbankowski b, Joanna Lange a, Marek Kulus a a b
Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Poland Department of Internal Medicine, Pneumonology and Allergology, Medical University of Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history: Received 14 October 2015 Received in revised form 25 December 2015 Accepted 16 January 2016 Available online 23 February 2016
Background: An increasing incidence of parapneumonic effusion and pleural empyema (PPE/PE) in children has been found in several studies published in the last decades. The aim of the study was to evaluate the incidence, etiology, clinical features, treatment strategies and outcomes of PPE/PE in children treated in a referral pulmonary center in central Poland. Material and methods: We performed a retrospective analysis of clinical, radiological and laboratory data of all children aged between 1 month and 18 years with PPE/PE due to community acquired pneumonia (CAP) between January 2002 and December 2013. Results: One thousand nine hundred and thirty three children with CAP were hospitalized between 2002 and 2013. Parapneumonic effusion or PE was diagnosed in 323 children (16.7%). The proportion of children with CAP related PPE/PE increased from 5.4% in 2002 to 18.8% in 2013. Streptococcus pneumoniae was the most common causative microorganism, responsible for 66.7% cases of known etiology. All children were treated with antibiotics and in 22.6%, and 74.3% of the patients therapeutic thoracentesis, pleural drainage with or without intrapleural fibrinolysis was performed, respectively. Approximately 3% of patients required surgical intervention. Conclusions: A significant increase in the incidence of PPE/PE in children with CAP treated in our institution in the last twelve years was found. S. pneumoniae was the most common causative microorganism. Antibiotic therapy with chest drain insertion ± intrapleural fibrinolysis is an effective treatment of PPE/PE and surgical intervention is seldom necessary. With proper management, the overall prognosis in children with CAP related PPE/PE is good. © 2016, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Pneumonia Streptococcus pneumoniae Pleural effusion Pleural drainage Children
1. Introduction Parapneumonic effusion and pleural empyema (PPE/PE) are the most common complications of community acquired pneumonia (CAP) in children. Although the percentage of children with CAP complicated by PPE/PE is relatively low (approximately 1%) [1,2], the high frequency of pneumonia in children worldwide makes its local complications an important problem. Moreover, an increasing
* Corresponding author. Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Zwirki i Wigury 63A, 02-091 Warsaw, Poland. Tel./fax: þ48 22 572 01 09. E-mail address: [email protected] (K. Krenke).
incidence of PPE/PE has been reported since the 1990s. Currently, the incidence of PPE/PE ranges between 3.5 per 100.000 and 12.5 per 100.000 children, depending on the geographical region [3,4]. Streptococcus pneumoniae is invariably the leading etiologic factor of PPE/PE, even in countries where pneumococcal conjugate vaccine (PCV) is widely used. Streptococcus pyogenes and Staphylococcus aureus are usually reported as the second and the third most common cause of PPE/PE in children, with an increasing incidence of staphylococcal PPE/PE observed in some parts of the world [5]. The most effective management of PPE/PE is challenging. Proper systemic antibiotic therapy based on local microbiological and epidemiological data and early local intervention are the major determinants of successful treatment. Since only few randomized controlled trials on management of PPE/PE in children have been
http://dx.doi.org/10.1016/j.jiac.2016.01.016 1341-321X/© 2016, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
K. Krenke et al. / J Infect Chemother 22 (2016) 292e297
published, the therapeutic approach is at least partially, based on local guidelines and individual center experience. In this context, case series reported by specialized centers are an important factor in improving the knowledge on optimal management. Therefore, we undertook a study evaluating the incidence, etiology, clinical features, treatment strategies and outcomes of PPE/PE in children treated in a referral pulmonary center in central Poland. 2. Material and methods This retrospective study was carried out at the Department of Pediatric Pneumonology and Allergy of the Medical University of Warsaw e a referral center for pulmonary and pleural infections in children. Data on all children (aged between 1 month and 18 years) with CAP complicated by PPE/PE treated in our institution between January 2002 and December 2013 were reviewed. The major inclusion criterion required to select patients for the study group was CAP complicated by pleural effusion that required local intervention, i.e. at least a diagnostic thoracentesis. Exclusion criteria were as follows: primary and secondary immunodeficiency, PPE/PE in the course of hospital acquired pneumonia, pleural effusion related to pulmonary or extrapulmonary diseases other than CAP. 2.1. Definitions Parapneumonic effusion was defined as pleural effusion that met laboratory criteria for PPE (according to the British Thoracic Society statement) [6] diagnosed in children with clinical signs and symptoms of CAP. Pleural empyema was defined as pleural effusion that was described as pus (on gross appearance) during thoracentesis. 2.2. Data collection Prespecified data on all children with PPE/PE were collected. These included: demographic data, history of allergy, chronic illnesses, immunization against S. pneumoniae, the results of blood and pleural fluid culture, serum IgM antibodies to M. pneumoniae, Ch. pneumoniae, adenovirus, influenza virus and RS virus, clinical features (fever, tachypnea, cough, chest pain, abdominal pain), blood test results (complete blood count, C-reactive protein (CRP), total protein and albumin concentration), the results of pleural fluid analysis, treatment strategies (antibiotic treatment, local treatment), duration of treatment and data on treatment outcomes. The sources of data were: an electronic database of patients with pneumonia which has been running in our institution since 2003 and medical records of patients with PPE/PE. Data were presented as median and range or interquartile range (IQR). The results of the study were summarized by standard descriptive statistics. Statistical analysis was performed using Statistica 10.0 (Statsoft, Tulsa, USA) software. Non-parametric ManneWhitney U test was used to compare quantitative variables between different groups. We considered p < 0.05 as statistically significant. Pearson Chi-squared test was used to analyze the differences between PPE and PE groups in terms of different sign and symptoms as well as applied methods of local treatment. The protocol of the study was accepted by Institutional Review Board of the Medical University of Warsaw. 3. Results One thousand nine hundred and thirty three children with CAP were hospitalized in our institution between 2002 and 2013. Parapneumonic pleural effusion or pleural empyema was diagnosed in 323 children (16.7%). There were 283 (87.6%) patients with PPE and
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40 (12.4%) patients with PE (14.6% and 2.1% of all children with CAP, respectively). The percentage of children with PPE/PE differed significantly in subsequent years, data are presented in Fig. 1. There was a perfectly even gender distribution in patients with PPE/PE, with 161 girls and 162 boys, median age 5 years, (IQR 4e8, range 1e17). Medical history revealed following comorbidities and chronic or recurrent conditions: recurrent respiratory tract infections 27 cases (8.4%), asthma 25 (8%), other allergic diseases 20 (6.2%), adenoid hypertrophy 9 (2.8%), history of non-complicated CAP 8 (2.5%), recurrent urinary tract infections 7 (2.2%), congenital heart disease 3 (0.9%), diabetes mellitus 1 (0.3%), arterial hypertension 1 (0.3%). There were no children with primary or secondary immunodeficiency in the study group. Thirty three children (10.2%) were vaccinated against S. pneumoniae. Data on vaccine type were available in 23 cases (PCV7 - 15, PCV10 - 3, 23-valent pneumococcal polysaccharide vaccine e 5). Fever, tachypnea and cough were the most common presenting symptoms. Abdominal pain was significantly more common in children with PE as compared to PPE. The median duration of fever before hospital admission was 9 days (range 7e12 days). Data on clinical presentation of PPE/PE in the study group are summarized in Table 1. The results of basic laboratory tests on admission are presented in Table 2. There were significantly elevated acute phase reactants, with the median CRP value 13.7 mg/dl (upper limit of normal 1 mg/ dl) (IQR 5.8e23.3). The median WBC count was 14.6 109/L (IQR 10.2e19.3) with neutrophil predominance. The results of pleural fluid analysis in children with PPE and PE differed significantly in terms of pH, specific gravity, lactate dehydrogenase and glucose level. Table 3 shows comparative data on biochemical properties and cellular composition of pleural fluid in patients with PPE and PE. Data on blood and pleural fluid cultures were available in 192 (59.4%) and 254 children (78.6%), respectively. Blood cultures were positive in 21 children (10.9%), while pleural fluid cultures in 34 cases (13.4%). In 9 children with positive pleural fluid culture for S. pneumoniae data on pneumococcal serotypes were available. The results were as follows: serotypes 1, 3, 6A and 23F were found in single patients, while serotype 6B and serotype 19A were identified in 2 and 3 patients, respectively. The results of blood and pleural fluid cultures are presented in Table 4. Data on serum IgM antibodies to atypical pathogens and respiratory viruses were available in 113 (35%) of children. High IgM levels suggesting M. pneumoniae, Ch. pneumoniae, adenoviral, influenza or RSV infection were found in 35 (30%), 10 (9%), 10 (9%), 8 (7%) and 7 (6%) patients, respectively. In 3 children bacteriological and serological results proved concurrent infections with typical bacteria, atypical bacteria and/or viruses (S. pneumoniae þ M. pneumoniae, S. pneumoniae þ C. pneumoniae and S. aureus þ M. pneumoniae þ RSV). The majority of children, i.e. 197 (61%), were treated with antibiotics before admission to our hospital (in regional hospital or at home). Amoxicilin, ampicillin, amoxicillin/clavulanic acid, cefuroxime and macrolides were the most common preadmission treatment. Initial antibiotic therapy applied in our institution largely depended on the previous treatment and its efficacy. In general, first line antibiotic therapy included ampicillin or amoxicillin/clavulanic acid with or without macrolides. When second line therapy was necessary (due to prolonged signs and symptoms and/or the results of microbiological studies), the most common choice was: cefotaxime, ceftriaxone with clindamycin, vancomycin and carbapenems. In children who were severely ill and those who were unsuccessfully treated with antibiotics before hospital admission ceftriaxone, cefotaxime,
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Fig. 1. The percentage of children with pleural complications of CAP (compared to all CAP patients) treated in consecutive subsequent years between 2002 and 2013. The numbers in bars show the number of patients with PPE/PE treated in each year. PPE e parapneumonic pleural effusion, PE e pleural empyema.
Table 1 Signs and symptoms in children with pleural empyema and parapneumonic pleural effusion (data on admission). Clinical signs and symptoms
Pleural empyema n ¼ 40 (%)
Parapneumonic pleural effusion n ¼ 283 (%)
Fever Tachypnea Cough Abdominal pain Chest pain
38 36 27 18 14
270 (95,4) 229 (80.9) 195 (68.9) 80 (28.3) 79 (29.9)
(95.0) (90.0) (67.5) (45.0) (35.0)
NS NS NS p ¼ 0.03 NS
Table 2 The results of basic laboratory tests in children with PPE/PE, data presented as median and IQR; normal range presented in square brackets. CRP- C-reactive protein, WBC e white blood cell count, NS e not significant. Laboratory test [range of normal values]
Pleural empyema Result, median (IQR)
Parapneumonic pleural effusion Result, median (IQR)
CRP (mg/dl) [<1.0] WBC (109/L) [4.5e13] Hemoglobin (g/dl) [10.9e14.2] Neutrophils (%) [age dependent] Platelets (109/L) [150e400] Total serum protein (g/L) [60.0e80.0] Serum albumin (g/L) [35.0e52.0]
15.56 15.34 10.7 73.9 426 59 27.5
13.2 14.35 11 70 387 62 29
(10.2e23.9) (10.6e22.2) (10.2e12) (63e83.7) (310e605) (52e63) (24e32)
(5.58e22.9) (9.9e19.2) (10.2e11.8) (60e80) (310e486) (56e68) (25e33)
NS NS NS NS NS NS NS
Table 3 Pleural fluid laboratory tests results in patients with parapneumonic pleural effusion and pleural empyema. Data presented as median and IQR (in brackets); * true number of cells could not have been established in the majority of patients with empyema due to cell damage and necrosis; NS e not significant, NA not applicable.
pH Specific gravity Total protein, g/L Lactate dehydrogenase, IU/L Glucose (mg/dL) Total cell count, cells/mL* Neutrophils (%)
Pleural empyema (n ¼ 40)
Parapneumonic pleural effusion (n ¼ 274)
7 (7e7.4) 1.02 (1.015e1.02) 40 (35e47) 7418 (2298e20,191) 27 (10e52) NA 80 (66e89)
7.5 1.02 44 3319 63.5 2750 72
clindamycin (alone or with beta-lactam antibiotics) were administered as first line treatment. The median duration of antibiotic treatment in children treated with pleural drainage was 21 days (range 15e33 days), while in children treated with
(7.25e8) (1.015e1.02) (38e49) (1081e8280) (26e78) (470e6800) (48e86)
p ¼ 0.0000 NS NS p ¼ 0.004 p ¼ 0.001 NA NS
single or repeated therapeutic thoracentesis was 18 days (range 14e24 days). At the same time the median duration of antibiotic treatment of children with non-complicated CAP was 9 days (range 6e14 days).
K. Krenke et al. / J Infect Chemother 22 (2016) 292e297 Table 4 Bacteria detected by blood and pleural fluid culture in children with parapneumonic effusion/pleural empyema. Blood culture Streptococcus pneumoniae Coagulase e negative staphylococci Oral streptococci Pleural fluid culture Streptococcus pneumoniae Streptococcus pyogenes Staphylococcus aureus Klebsiella pneumoniae Coagulase e negative staphylococci Enterobacter hafniae Oral streptococci
Number (%) 14 (66.7) 6 (28.6) 1 (4.8) 23 (67.7) 2 (5.8) 1 (2.9) 1 (2.9) 5 (14.7) 1 (2.9) 1 (4.8)
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especially serotype 1, 3 and 19A [4,7e9]. Data from the United States, where PCV was introduced in 2000, showed that despite the reduction of hospitalization rate due to CAP (33% reduction of hospitalizations due to CAP and 61% reduction of hospitalizations due to CAP caused by S. pneumoniae in children younger than 2 years), a 2-fold increase of empyema rate was noted. Data from some centers indicate an even higher (up to 5-fold) increase in the incidence of PPE/PE in children after implementation of PCV [10]. Similar, or even higher increase was found in our institution. The percentage of children with CAP who developed pleural complications increased from 5.4% and 2.3% in 2002 and 2003, respectively to 21.2% in 2012 and 18.8% in 2013. However, this finding cannot be explained by the use of PCV, since in Poland PCV is not
Table 5 Procedures applied as the local treatment of parapneumonic effusion and pleural empyema in the study group. NS - no significant difference; *Local treatment refers to the most invasive therapeutic procedure applied in individual patient (e.g. when therapeutic thoracentesis and chest tube were applied only chest tube drainage was listed in the table). Local treatment*
Pleural empyema n ¼ 40 (%)
Parapneumonic pleural effusion n ¼ 248 (%)
Therapeutic thoracentesis Chest tube drainage Chest tube drainage with intrapleural fibrinolitics (urokinase) VATS
0 3 30 7
65 37 144 2
(0.0) (7.5) (75.0) (17.5)
Local treatment modalities applied in children with PPE/PE are shown in Table 5. By definition, all children underwent a diagnostic thoracentesis. Therapeutic thoracentesis was the only local treatment necessary in almost one fourth of patients. In the remaining children, more invasive procedures had to be used (Table 5), including chest tube drainage or chest tube drainage with intrapleural fibrynolytic administration (urokinase; the procedure was applied since 2004). Surgical procedures (VATS) were reserved for children who did not respond to the above described treatment (persisting fever in association with a persistent pleural fluid formation, despite chest tube drainage with intrapleural fibrinolysis and antibiotics). Only less than 3% of patients required surgical intervention. The median duration of pleural drainage was 6 days (IQR 5e9 days) and the median total amount of pleural fluid drained was 525 ml (IQR 290e1000 ml). The median length of hospital stay was 19.5 (IQR 15e25.5) days. In 32 cases PPE/PE was a consequence of necrotizing pneumonia. The most common complications were bronchopleural fistula (n ¼ 29; 9%), pneumothorax (n ¼ 25; 7.7%) and lung abscess (n ¼ 6; 1.8%). Directly after the end of treatment, changes in the chest radiogram were observed in all children (reduced lung volume, pleural thickenings). Normalization of the radiological appearance was observed 6e12 months after discharge. No recurrences of CAP and/or recurrent pleural infections were found during 12 months of follow-up. The mortality rate was 0%. 4. Discussion Our study showed a significant increase in the incidence of PPE/ PE in children with CAP treated in our institution in the last twelve years. We found, that S. pneumoniae was invariably the most common causative microorganism responsible for pleural infections associated with CAP. An increasing incidence of PPE/PE in children has also been reported by other authors [3,4,6,7]. The reason for this phenomenon is not clear. One hypothesis suggests that this is a consequence of pneumococcal conjugate vaccine (PCV) introduction and the emergence of pneumococcal serotypes not covered in the PCV7,
(23.0) (13.1) (50.9) (0.7)
p ¼ 0.0002 NS p ¼ 0.04 p < 0.0001
refunded for the whole population of children and only 10.2% of children in our study group were vaccinated against S. pneumoniae. Our results are in agreement with some other studies. In some welldeveloped countries, an increasing incidence of PPE/PE has already been noted in 1990s, that is before the implementation of PCV [11]. Rising percentage of children with PPE/PE was later reported in countries where PCV had not been widely introduced [12]. These findings suggest that other factors may play a significant role in the observed trends in childhood PPE/PE. For example, changes in etiology of PPE/PE have been reported. Despite the fact that S. pneumoniae remains the most common causative agent of PPE/ PE, other bacteria like S. aureus are increasingly recognized as the etiologic factors [3,5]. The most common presenting symptoms in our study group were fever, tachypnea and cough. This is consistent with data from other studies [12]. We did not find significant differences between children with PPE and PE in terms of the above mentioned symptoms. Interestingly, abdominal pain was more frequently observed in children with pleural empyema. The relationship between pleural empyema and abdominal pain was earlier reported by Lahti et al. CAP [13]. In our retrospective study, the etiology of PPE/PE could have been determined in only a minority of patients. Blood cultures were positive in 10.9% of children. Similar data on the percentage of positive blood cultures were published by Lahti et al. (11%), while higher percentages (26%) were reported by other authors [13,14]. The diagnostic yield of pleural fluid cultures in our study was not significantly different than that found for blood cultures. The etiologic factor responsible for pleural infection was identified in 13.4% of pleural fluid samples. In other studies significant differences in the percentage of positive pleural fluid results were demonstrated, with the proportion of culture positive specimens ranging from 19% to 36% [13,14]. Our study showed that S. pneumoniae remains the most common bacteria responsible for PPE/PE in children. This pathogen was identified as an etiologic factor in two thirds of children with PPE/PE of known etiology. Similar numbers indicating that S. pneumoniae is a leading cause of PPE/PE were reported in other studies, including those performed in countries where PCV had been widely applied [3]. On the other
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hand, some changes in the etiology of PPE/PE in children were also noticed. These refer to a significant increase in the incidence of PPE/ PE caused by S. aureus [3,5]. This was not the case in our study in which S. aureus was a marginal pathogen identified in only one pleural fluid sample. Similar findings were published by Sakran et al. and Grisaru-Soen et al. [12,14]. All other bacterial species that were cultured in our patients were responsible for 31% of positive blood and pleural fluid cultures. S. pyogenes and Klebsiella pneumoniae were identified in 2 and 1 pleural fluid samples, respectively. The true pathogenic role of coagulase e negative staphylococci and viridans streptococci cultured in our study is unknown. Although, the presence of these bacteria in blood and/or pleural fluid cultures has also been reported in other studies on etiology of PPE/PE in children, their causative role is regarded as negligible by some authors. The likelihood of pathogenicity of the above mentioned bacteria increases, if the organism is detected in multiple blood cultures obtained by independent venipunctures [15]. As in our study, all these bacteria were identified in single pleural or blood fluid cultures, it is not clear whether they should be considered the cause of pleural complications. While the role of microbiological testing (blood and pleural fluid cultures) in children with PPE/PE is well established, the usefulness of acute phase reactants and other blood tests, as well as biochemical pleural fluid analysis in management of children with PPE/PE is not so evident [6]. The authors of the British Thoracic Society (BTS) guidelines for the management of pleural infection in children suggest that full blood count, CRP, electrolytes and serum albumin level should be performed as the initial laboratory investigations. However, as PPE/PE due to CAP is rarely caused by viral infection and the serum level of acute phase reactants cannot reliably distinguish between viral and bacterial infection, it seems that the white blood cell count and CRP level may have only very limited impact on the choice of treatment [6]. This also refers to the differentiation between PPE and PE. Although our children with PPE/PE had significantly elevated WBC count with neutrophil predominance and elevated CRP levels, we were not able to demonstrate significant differences between the results in children with PPE as compared to PE. According to a widely accepted opinion, the role of biochemical pleural fluid analysis in children is not as important as in adult patients. This is because the spectrum of causal diagnoses in adults with pleural effusion is much wider than in children, and pleural fluid analysis plays a crucial role in the diagnostic approach [16]. Conversely, the majority of pleural effusions in children are related to pulmonary infections and the choice of treatment is only rarely based on the results of pleural fluid analysis [17e19]. Therefore the BTS and the Pediatric Infectious Diseases Society and Infectious Diseases Society of America (PIDS/IDSA) guidelines suggest that biochemical testing of pleural fluid in children with PPE associated with pneumonia is not required [6,16]. We found that the results of biochemical tests of pleural fluid in children with PPE/PE are similar to those seen in adults [20] with a significant difference between PPE and PE in terms on pH, LDH and glucose level. Both antibiotic therapy and local intervention have an important role in the treatment of PPE/PE. Since the positive results of microbiological studies can be expected in only a minority of patients, the choice of antibiotics is based on local epidemiological and microbiological data, as well as current national and international guidelines. The antibiotics that were most commonly prescribed in our study group included ampicillin, amoxicillin/ clavulanic acid, cefotaxime or ceftriaxone (alone or with clindamycin) and macrolides (with beta-lactam antibiotics). These choices are in accordance with the current PIDS/IDSA guidelines, as well as the experience of other centers [6,13,15,16]. It has been suggested that the first line antibiotic therapy in severely ill
children should include vancomycin or clindamycin. This is because the increasing frequency of PPE/PE caused by communityassociated methicillin-resistant S. aureus (CA-MRSA) [5]. The results of our microbiological studies do not indicate that S. aureus plays an important role in PPE/PE in Polish children, however careful monitoring of changing microbiological trends should be conducted. While the guidelines on the antibiotic management of PPE/PE are rather unequivocal, more controversies refer to the choice of local intervention. The therapeutic options include: single or repeated therapeutic thoracentesis, chest tube drainage (with or without intrapleural fibrynolysis) and VATS [6,16,21,22]. The choice between these methods is mainly based on disease severity and anatomical factors, i.e. pleural fluid volume, its location and the presence of loculations and adhesions. However, personal and center experience are also very important factors affecting the management strategy [22,23]. In our institution, the usual therapeutic regimen includes: antibiotics ± therapeutic thoracentesis in case of small pleural effusion (less than ¼ of pleural cavity), antibiotics þ chest tube drainage when there is moderate or large pleural effusion, chest tube drainage with intrapleural fibrynolysis in case of loculated pleural effusion and VATS, when the above mentioned treatment is ineffective. Most of the current guidelines suggest that pleural drainage ± intrapleural fibrynolysis is a reasonable first treatment option and VATS should be considered as a second line therapy [16]. 5. Conclusions A significant increase in the incidence of PPE/PE in children with CAP treated in our institution in the last twelve years was found. S. pneumoniae was the predominant pathogen responsible for pleural complications. Antibiotic therapy with chest drain insertion ± intrapleural fibrinolysis is an effective treatment of PPE/ PE and surgical intervention is seldom necessary. With proper management, the overall prognosis in children with CAP related PPE/PE is good. Conflict of interest The authors declare no conflict of interest. References [1] Harris M, Clark J, Coote N, Flether 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:ii1e23. [2] Paraskakis E, Vergadi E, Chatzimichael A, Bouros D. Current evidence for the management of paediatric parapneumonic effusions. Curr Med Res Opin 2012;28:1179e92. [3] Grijalva CG, Nuorti JP, Zhu Y, Griffin MR. Increasing incidence of empyema complicating childhood community-acquired pneumonia in the United States. Clin Infect Dis 2010;50:805e13. [4] Byington CL, Hulten KG, Ampofo K, Sheng X, Pavia AT, Blaschke AJ, et al. Molecular epidemiology of pediatric pneumococcal empyema from 2001 to 2007 in Utah. J Clin Microbiol 2010;48:520e5. [5] Schultz KD, Fan LL, Pinsky J, Ochoa L, Smith EO, Kaplan SL, et al. The changing face of pleural empyemas in children: epidemiology and management. Pediatrics 2004;113:1735e40. [6] Balfour-Lynn IM, Abrahamson E, Cohen G, Hartley J, King S, Parikh D, et al. BTS guidelines for the management of pleural infection in children. Thorax 2005;60:i1e21. V, Pahissa A. The increasing incidence of empyema. Curr Opin [7] Burgos J, Falco Pulm Med 2013;19:350e6. lez MA, Molinos A, [8] Obando I, Camacho-Lovillo MS, Porras A, Gandía-Gonza Vazquez-Barba I, et al. Sustained high prevalence of pneumococcal serotype 1 in paediatric parapneumonic empyema in southern Spain from 2005 to 2009. Clin Microbiol Infect 2012;18:763e8. [9] Weil-Olivier C, van der Linden M, de Schutter I, Dagan R, Mantovani L. Prevention of pneumococcal diseases in the post-seven valent vaccine era: a European perspective. BMC Infect Dis 2012;12:207.
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