Should Empyema with or without Necrotizing Pneumonia in Children Be Managed Differently?

Background: Necrotizing pneumonia (NP) is an increasing lung infection mostly associated with pleural empyema. Objectives: We aimed to compare children with empyema with and without concomitant NP, in terms of risk factors, management and outcome. Methods: We retrospectively included children hospitalized between 2005-2014 with empyema to whom a computed tomography was performed. We recorded patient characteristics, clinical, biological (blood and pleural fluid) and radiological findings, medical and surgical treatments, and clinical, radiological and functional follow-up. Results: 35 children with empyema were included, including 25 with a concomitant NP. Patients with or without NP were undistinguishable, in terms of characteristics, symptoms at admission or detected pathogens. Pleural leucocytes were significantly higher in the empyema group (p = 0.0002) as pleural LDH (p = 0.002), and pleural/blood LDH ratio (p = 0.0005). Medical and surgical managements were similar between both groups. Complications occurred in 1/10 children with empyema alone (pneumatocele) and 5/25 with concomitant NP (bronchopleural fistula (n = 3), lobectomy, pneumothorax). The hospital length of stay and delay for chest X-ray normalization were similar in both groups. Conclusion: Except for minor biological parameters, the presence of concomitant NP in case of empyema does not change the presentation, clinical features, management and outcome, suggesting that the presence of additional NP to empyema should not be managed differently. Therefore, in case of empyema with suspected concomitant NP, chest CT should probably be restricted to abnormal worsening or when mandatory for surgical treatment. How to cite this paper: Anastaze Stelle, K., Mornand, A., Bajwa, N., Vidal, I., Anooshiravani, M., Kanavaki, A., Barazzone Argiroffo, C. and Blanchon, S. (2017) Should Empyema with or without Necrotizing Pneumonia in Children Be Managed Differently? Health, 9, 209-222. https://doi.org/10.4236/health.2017.92014 Received: December 9, 2016 Accepted: January 22, 2017 Published: January 25, 2017 Copyright © 2017 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access K. Anastaze Stelle et al.

NP is characterized by a loss of architecture and pulmonary tissue associated with the formation of thin-walled cavities full of air or liquid without enhancing border [7]. The physiopathology of NP is not yet completely understood, as the reason for its increasing incidence. Some authors argue a selection of more virulent serotypes of Streptococcus pneumoniae [1] [2] [4] [8] [9] [10], or a better identification of NP considering the easier resort to chest computed tomography (CT) [1] [11] [12]. Others theorized that a raising virulence of Staphylococcus aureus, especially when producing Panton-Valentine leukocidin (PVL) known to induce cellular lysis, is responsible for the increasing incidence of NP [13] [14].
There are only few studies focusing on empyema with NP that have been published [2] [5] [16] [17] [18] [19]. Macedo et al. reported, among patients with empyema, prolonged duration of pleural drainage and hospital length of stay in case of concomitant NP [18], while other authors found no difference [17] [19].
In 2012, the American Pediatric Surgical Association (APSA) published a review on the management of empyema and pointed out, that in case of NP, "there are no published data informing the choice of treatment for this specific condition" [16].
These discordant results regarding empyema with NP led us to compare risk factors, management and outcomes of children with pleural empyema with or without concomitant NP.

Patients and Methods
We performed a retrospective study at the University Children's Hospital of Geneva (Switzerland). From the institutional diagnosis registration (CIM10), we selected all children below 16-years old hospitalized between the 1 st January 2005 and the 31 st December 2014 with the diagnosis of pleural effusion and an available chest CT. All medical records were reviewed by two physicians (AS.K and B.S), in order to only include patients with a confirmed diagnosis of empyema, based on Hardie's criteria [20]. Diagnosis of concomitant NP was confirmed by two certified paediatric radiologists (A.M, K.A) who blindly reviewed all CT, according to published criteria of Donelly et al. [21]. CT was mostly performed because of clinical worsening, otherwise because of suspicion of parenchymal necrosis on standard chest X-ray or on surgeon request before procedures.
Among 102 selected children with pleural effusion during the inclusion period to whom a CT was performed, we finally included 35 patients with a confirmed empyema: 25 patients had a concomitant NP (empyema + NP group) and 10 patients had empyema alone (empyema group), as illustrated in the CT images in Figure 1.
We excluded all patients from whom the CT was missing in order to avoid any undiagnosed NP in the empyema group. The design of the study and the flowchart of patient inclusions are summarized in Figure 2.

Results
Patient characteristics and clinical features at admission are summarized in Table 1; there was no difference between the two groups. Past pulmonary medical history was only found in four patients from the empyema + NP group, including bacterial pneumonia (n = 1) and viral bronchitis or bronchiolitis (n = 3). Besides pulmonary diagnoses, one patient from the empyema group presented an hydronephrosis. The median delay time from first symptoms to admission was five days in both groups (from 1 to 5 days in the empyema group and from 0 to 9 days in the empyema + NP group).
Except one patient in the empyema + NP group, all patients underwent blood sample at admission and pleural fluid analysis. The pleural fluid was obtained by thoracocentesis (3 patients in the empyema group and 7 in the empyema + NP group), or during surgical insertion of a chest tube. The results of blood and pleural fluid tests are presented in Table 2. Regarding the blood tests at admission, including white cell count and inflammatory markers such as C reactive protein, we found no difference between the two groups. In the pleural fluid, white blood cells (WBC) and lactate dehydrogenase (LDH) were significantly lower in the empyema + NP group as well as pleura/blood LDH ratio. The pathogens were identified in the pleural fluid for all patients except one in the empyema + NP group (identified in the broncho-alveolar lavage). The involved micro-organisms are described in Table 2 and no difference was found between both groups regarding the proportion or type of pathogens, or the way to identify them.
The medical and surgical management, summarized in Table 3, was not different between the two groups, except the fibrinolytic agents more prescribed in the empyema group (p = 0.047). The initial intravenous antibiotherapy was modified for three patients in the empyema group and seven patients in the  empyema + NP group, according to the anti-microbial susceptibility testing or in order to treat a secondary infection.
The outcomes are detailed in Table 3. We did not observe any difference be-  Among the seven patients with complications, the last available X-ray was still abnormal for two of them from the empyema + NP group: the patient requiring a lobectomy (radiological follow-up at 505 days showed a condensation of the right apex) and the patient requiring a thoracotomy (radiological follow-up at 488 days showed blebs in the right apex). Pulmonary function tests were available in five patients from the empyema group and for three patients from the empyema + NP-group, performed between 1 and 12 months after discharge, and were normal.

Discussion
This paediatric retrospective study aims to evaluate the morbidity effect of con-  [15]. Against all odds, Staphylococcus aureus was never evidenced in the empyema + NP group, and only in one patient from the empyema group. Since the serotype of Streptococcus pneumoniae was not available in most of our patients, we could not evaluate the potential role of specific serotypes, but we did not observe any difference in anti-pneumococcal vaccination (Prevenar 7®) between the two groups. This is surprising, given that VATS was widely put forward in the early 2000's as a treatment of choice for empyema, but was progressively challenged by the chemical debridement, the fibrinolytic agents and a conservative treatment. Paediatric studies showed contradictory conclusion regarding the surgery (including chest tube, VATS and thoracotomy): one study suggested that surgery was not better than thoracocentesis alone [12], and another supported early VATS as a valuable option to avoid prolonged recovery and late thoracotomy compared to conservative treatment [18].  [42]. Other authors showed a high correlation between US and CT for NP diagnosis and recommended routine US in case of severe pneumonia [43]. Given the widely recognized radiation-induced risk of malignancy in children [44], it is of importance to assess and clearly confirm the usefulness of CT. Since we found no relevant difference between the 2 groups, we question the usefulness of confirming, by an irradiating chest CT, a suspected concomitant NP in case of empyema. Therefore, we suggest that CT might be restricted to abnormal worsening of pleural empyema or when mandatory for surgical treatment, until it could be eventually replace by US in the future.
We are aware that this study presents several limitations. We included a limited number of patients due to the mono-centric and retrospective nature of the study. In order to detect a difference of hospital length of stay, 89 patients per group would have been necessary to obtain a power of 80% with an alpha risk of 0.05, but empyema associated to NP is a rare pathology and no one of the few published studies was able to gather data from a suitable number of patients.
Due to the necessity to confirm/infirm NP by a chest CT, considering the poor accuracy of X-ray for detecting NP [17], we clearly selected particularly severe patients especially in our empyema group. This recruitment bias could explain the high proportion of chest tube insertion, fibrinolytic treatment and VATS in this latter group. Furthermore, we did not include a severity scoring of the disease, as the extend of the necrotizing zones, in order to compare patients with extensive necrotizing pneumoniae or with only a small area of necrotizing pneumonia. Finally, we were unable to collect functional follow-up. Indeed, pulmonary function tests after complete recovery would be interesting to study the potential long-term sequela.

Conclusion
As a conclusion, this paediatric survey is the first study comparing as many parameters in empyema associated or not with NP, and showing no difference regarding risk factors, clinical and biological features, pathogens, management and outcome. Empyema with concomitant NP is rarely due to Staphylococcus aureus, leading to recommend the same empiric antibiotic therapy as empyema without NP. Finally, in case of empyema with suspected concomitant NP, chest CT should probably be restricted to abnormal worsening or when mandatory for surgical treatment.