Infectious Disease

Tuberculous Pleural Effusion

CASE

A 7 year-old girl presents to a hospital in Lilongwe, Malawi with worsening tactile fevers, shortness of breath, and productive cough over the past week. Her mother reports subjective weight loss, but denies night sweats, hemoptysis, or a significant respiratory history.

The patient’s vital signs were significant for a temperature of 100.6 F, pulse of 69, blood pressure of 107/72, tachypnea to 33, and hypoxia to 87% on room air. Her physical exam was notable for diminished breath sounds throughout the right side. An x-ray was performed revealing a large right-sided pleural effusion (Figure 1). A bedside ultrasound was then performed, showing a loculated pleural effusion (Figure 2). The patient underwent a therapeutic and diagnostic thoracentesis, returning straw colored fluid. In addition to standard pleural fluid studies, the patient’s fluid was also sent for Xpert MTB/RIF nucleic acid amplification test given the high prevalence of tuberculosis in the region, eventually returning a confirmatory diagnosis of Mycobacterium tuberculosis

Figure 1. Chest x-ray of a 7 year-old girl presenting with worsening shortness of breath, productive cough, and subjective fevers, found to have a large right-sided pleural effusion.

Figure 1. Chest x-ray of a 7 year-old girl presenting with worsening shortness of breath, productive cough, and subjective fevers, found to have a large right-sided pleural effusion.

Figure 2. Still image of a point-of-care ultrasound performed on a 7 year-old girl with a large right-sided pleural effusion, showing a loculated pleural effusion.

Figure 2. Still image of a point-of-care ultrasound performed on a 7 year-old girl with a large right-sided pleural effusion, showing a loculated pleural effusion.

 FINAL DIAGNOSIS

Tuberculous pleural effusion

 

CLINICAL PRESENTATION

The classic chest x-ray findings of primary pulmonary tuberculosis (TB) are parenchymal consolidation with or without hilar lymphadenopathy. Tuberculous pleural effusion (also known as tuberculous pleurisy) is the second most common form of extrapulmonary TB (after lymphatic involvement) (Figure 3), and is the most common cause of pleural effusions in TB endemic regions.[1] In children, tuberculous pleural effusion most often occur in the setting of primary TB,[2] whereas in adults they occur most frequently due to reactivation disease.[3] Patients typically present with an acute febrile illness with nonproductive cough and pleuritic chest pain, though dyspnea, night sweats, and weight loss can also occur. Most tuberculous pleural effusions are unilateral and, in contrast to our patient, small to moderate in size.[4] On chest x-ray, pleural disease is often appreciated.[5] Loculation of pleural effusions is not uncommon in tuberculous pleural effusion, and is thought to be due to direct pleural infection and the resulting intense intra-pleural inflammation and organization.[6]

Figure 3. Common sites of extrapulmonary TB.

Figure 3. Common sites of extrapulmonary TB.

 

DIAGNOSIS

 Tuberculous pleural effusion should be suspected in patients with pleural effusion and TB risk factors including history of TB infection, TB exposure, or time spent in TB endemic regions. Unfortunately, definitive diagnosis of tuberculous pleural effusion can be challenging. Tuberculin skin test and interferon-gamma release assays do not distinguish between latent tuberculosis infection and active tuberculosis disease, and thus cannot be used for definitive diagnosis. The gold standard of diagnosis remains demonstration of M. tuberculosis in pleural fluid or pleural biopsy specimen.[4] Presumptive diagnosis can reasonably be made in patients with a known history of pulmonary TB and a pleural effusion without any alternative cause.

In the undifferentiated patient, a workup for pulmonary TB should be initiated including sputum smear and culture for acid-fast bacilli (AFB). Next, a diagnostic thoracentesis can be performed. Pleural fluid from tuberculous pleural effusion is typically an exudative, lymphocyte-predominant pleural effusion, and should be sent for smear and culture for AFB, though cultures are positive in less than 30% of HIV-uninfected patients,[4] and only approximately 50% of HIV-infected patients with CD4 counts less than 100 cells/mm3 (a higher sensitivity due to the greater bacterial burden).[7] Pleural fluid should also be sent for analysis, with typical findings shown in Table 1. 

Laboratory test Typical finding
Color Straw colored(14)
Protein concentration >3.0 g/dL(15)
LDH >500 international units/L(15)
pH <7.4
Glucose 60-100 mg/dL(15)
ADA >40 units/L
Cell count 1,000-6,000 cells/mm^3.(16)
Early neutrophil predominance. After the
first few days, lymphocytes predominate.(15)
Table 1. Pleural fluid findings typical for tuberculous pleural effusion.

 A presumptive diagnosis can be made if there is a lymphocytic-to-neutrophil ratio >0.75 and ADA >40 units/L.[8-10] While nucleic acid amplification (NAA) tests for M. tuberculosis that are FDA-approved for use with sputum have not yet been approved for pleural fluid in the United States, some laboratories use NAA testing of pleural fluid as a validated, "off-label" application. If the patient still remains undifferentiated after this testing and there is concern for the medically complex patient or suspected drug resistance, a pleural biopsy can be pursued by thoracoscopy or closed percutaneous needle biopsy with resulting tissue sample sent for AFB smear and culture as well as histopathology for evaluation of granulomas. Additionally, all patients with suspected tuberculous pleural effusions should be tested for HIV infection.

 

TREATMENT

The mainstay of treatment of tuberculous pleural effusion is antituberculosis therapy, the same as active pulmonary tuberculosis. A typical drug regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by isoniazid and rifampin for an additional 18 weeks. Empiric antituberculous therapy is warranted if a presumptive diagnosis is made as described above, and patients typically defervesce within two weeks and pleural fluid is resorbed within six weeks. However, some patients take up to two months to defervesce with fluid resorption taking up to four months. In areas with high rates of antituberculous drug resistance, organism isolation is more critical as it can guide drug selection. Currently, corticosteroids are not recommended as an adjuvant therapy as there is insufficient evidence for benefit.[11] Therapeutic thoracentesis can be considered in patients with larger pleural effusions or significant dyspnea, as it has been shown to more quickly resolve dyspnea, though there is no effect on long-term outcomes.[12,13]

 

DISPOSITION AND CASE CONCLUSION

Empiric antituberculosis therapy was initiated after thoracentesis, with resulting clinical improvement.  The patient was soon thereafter discharged to complete the remainder of her antituberculosis therapy through a directly observed therapy (DOT) program and was doing well at her follow up visit.

 

TEACHING POINTS

  • Tuberculosis is the most common cause of pleural effusions in endemic regions.

  • The gold standard of diagnosis is demonstration of M. tuberculosis in pleural fluid or pleural biopsy specimen.

  • A presumptive diagnosis can be made if pleural fluid shows a lymphocytic-to-neutrophil ratio >0.75 and ADA >40 units/L.

  • Treatment of tuberculous pleural effusions is the same as for pulmonary tuberculosis.


Faculty Reviewer: Dr. Lauren Allister

 


REFERENCES

  1.  Zhai, K, Lu, Y, Shi, HZ. Tuberculous pleural effusion. J Thorac Dis 2016;8:E486-94.

  2. Merino, JM, Carpintero, I, Alvarez, T, Rodrigo, J, Sanchez, J, Coello, JM. Tuberculous pleural effusion in children. Chest 1999;115:26-30.

  3. Torgersen, J, Dorman, SE, Baruch, N, Hooper, N, Cronin, W. Molecular epidemiology of pleural and other extrapulmonary tuberculosis: a Maryland state review. Clin Infect Dis 2006;42:1375-82.

  4. Gopi, A, Madhavan, SM, Sharma, SK, Sahn, SA. Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest 2007;131:880-9.

  5. Seibert, AF, Haynes, J, Jr., Middleton, R, Bass, JB, Jr. Tuberculous pleural effusion. Twenty-year experience. Chest 1991;99:883-6.

  6. Ko, Y, Kim, C, Chang, B, Lee, SY, Park, SY, Mo, EK, et al. Loculated Tuberculous Pleural Effusion: Easily Identifiable and Clinically Useful Predictor of Positive Mycobacterial Culture from Pleural Fluid. Tuberc Respir Dis (Seoul) 2017;80:35-44.

  7. Gil, V, Cordero, PJ, Greses, JV, Soler, JJ. Pleural tuberculosis in HIV-infected patients. Chest 1995;107:1775-6.

  8. Light, RW. Update on tuberculous pleural effusion. Respirology 2010;15:451-8.

  9. Sahn, SA, Huggins, JT, San Jose, ME, Alvarez-Dobano, JM, Valdes, L. Can tuberculous pleural effusions be diagnosed by pleural fluid analysis alone? Int J Tuberc Lung Dis 2013;17:787-93.

  10. Jimenez Castro, D, Diaz Nuevo, G, Perez-Rodriguez, E, Light, RW. Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions. Eur Respir J 2003;21:220-4.

  11. Ryan, H, Yoo, J, Darsini, P. Corticosteroids for tuberculous pleurisy. Cochrane Database Syst Rev 2017;3:CD001876.

  12. Bhuniya, S, Arunabha, DC, Choudhury, S, Saha, I, Roy, TS, Saha, M. Role of therapeutic thoracentesis in tuberculous pleural effusion. Ann Thorac Med 2012;7:215-9.

  13. Lai, YF, Chao, TY, Wang, YH, Lin, AS. Pigtail drainage in the treatment of tuberculous pleural effusions: a randomised study. Thorax 2003;58:149-51.

  14. Levine, H, Metzger, W, Lacera, D, Kay, L. Diagnosis of tuberculous pleurisy by culture of pleural biopsy specimen. Arch Intern Med 1970;126:269-71.

  15. Epstein, DM, Kline, LR, Albelda, SM, Miller, WT. Tuberculous pleural effusions. Chest 1987;91:106-9.

  16. Valdes, L, Alvarez, D, San Jose, E, Penela, P, Valle, JM, Garcia-Pazos, JM, et al. Tuberculous pleurisy: a study of 254 patients. Arch Intern Med 1998;158:2017-21.

Things That Go ‘Mump’ in the Night: What to do with Parotid Swelling

CASE

A healthy graduate student presents to the ER in the middle of the night with facial swelling and voice hoarseness. She states that she has been feeling generally unwell with aches and a sore throat for the past two days. Tonight, she took a throat lozenge shortly before going to bed, but awoke a while later with worsening hoarseness, throat tightness, and facial swelling. She states that the swelling is over her jawline and appears symmetric. She provides her license photo, which shows a dramatic difference in the contour of her mandible.

She is allergic to cats, but denies any recent exposure. She has no other known allergies and multiple prior exposures to this brand of throat lozenge. She denies wheezing, abdominal discomfort, and rash. She is only on birth control. She denies any inhalational drug use. She denies any dental pain or recent dental manipulation.

Her vital signs are within normal limits and she is afebrile. She has no stridor, drooling, or dysphonia, but exam demonstrates marked bilateral parotid/submandibular swelling. The region is not tender nor is it erythematous or warm. Her uvula is midline and without swelling. No lesions are noted in the posterior oropharynx. The tongue is unremarkable. She endorses ongoing throat tightness.

Lab work is obtained. She has a mild leukocytosis to 12.8. EBV and Strep are both negative. Given the extent of swelling and her subjective complaint of throat tightness, you obtain CT imaging (Figure 1).

Picture1.png
Picture2.png
Figure 1: CT neck.

Figure 1: CT neck.

The radiologist calls you to discuss the case. He says that she has enlargement of bilateral parotid glands and submandibular glands. He notes extensive subcutaneous edema in the retromandibular tissues and upper neck. Fortunately he says her airway looks patent. He inquires, “What do you think is going on?”

You start to worry that she may have mumps. You’ve never seen mumps, but you know it exists. Time for a quick review…

The Background

  • Mumps is a viral illness that is generally preventable by vaccine.

  • Peak incidence is late winter and early spring.

  • Mumps still occurs in outbreaks in closed environments such as college dormitories, military barracks, and schools, but is rare <1 yo due maternal antibodies.

  • An outbreak is defined as ≥3 cases linked by place and time.

  • Mumps is much more likely to occur in unvaccinated individuals than in vaccinated individuals, but there are rare reports of vaccinated patients developing mumps.

  • Transmission occurs by direct contact, respiratory droplets and fomites.  Viral shedding precedes onset of symptoms.

  • Prolonged incubation period of 12-25 days.

The Presentation

  • There is often a non-specific prodrome of myalgias, headache, fever, and malaise.

  • Salivary gland swelling usually occurs within the first 2-3 days of symptom onset.

  • The hallmark of mumps is parotid swelling. It can be painful and tender, but not always, and can last up to 10 days.

  • The swelling can be unilateral (25% of cases) or bilateral. The swelling can start on one side and then progress to involve both sides.

  • Other salivary glands such as the sublingual glands and submandibular glands can swell, but this only occurs in 10% of cases.

  • Associated complications:

    • Orchitis (typically develops 5-10 days following parotitis with high fevers and severe testicular pain).

    • Meningitis (more common in males. May develop before, during or after parotitis. In some cases, meningitis occurs in the absence of parotitis. Associated with CSF pleocytosis).

    • Other rare complications: encephalitis, pancreatitis, and arthritis.

The Differential

  • Many other viral infections can cause parotid swelling (EBV, HSV, HIV, CMV, coxsackie, etc.).

  • Bacterial parotitis presents as typically firm, tender swelling associated with high fevers and toxic appearance. S.aureus is most often implicated.

  • Salivary gland stone, salivary tumor, sarcoidosis, Sjögren's syndrome.

The Work-up

  • Patient should be placed on droplet precautions.

  • At the time of presentation, two laboratory specimens should be drawn. A serum mumps IgM level and a buccal or oral swab should be sent for RT-PCR. At our institution, these are send-out labs.

  • The IgM level should be sent in a red-top tube.

  • The IgM level is not always accurate if the sample is obtained within the first 5-days of symptom onset. Therefore, if the IgM level returns as normal and the RT-PCR has not resulted (or was never sent), the CDC recommends a second serum sample be sent 5-10 days after symptom onset.

  • It is recommended that the parotid gland be “milked” and the swab be taken from the site of Stensen’s duct (buccal mucosa).

  • The swab used for strep testing can be used for the buccal swab.

  • Buccal swabs should be obtained as soon as possible after symptom onset. It provides the best means for laboratory confirmation, particularly in patients who have been vaccinated.

  • A CBC typically demonstrates leukopenia and a relative lymphocytosis.

  • Often serum amylase will be elevated.

The Treatment

  • No specific treatment.

  • 20-30% of cases are asymptomatic.

  • Supportive care with NSAIDs/Tylenol.

  • If a patient is admitted, they should be placed on droplet precautions until parotid swelling resolves.

  • Individuals treated on an outpatient basis should remain at home and minimize contact with others for five days following symptom onset.

  • Vaccination:

    • Patients who are incompletely immunized and at risk during a mumps outbreak (i.e. college students on a campus with mumps cases) should receive two doses or the MMR vaccine separated by at least 28-days.

    • As of January 2018, the Advisory Committee on Immunization Practices (AICP) made a change regarding the MMR vaccination. In the setting of a mumps outbreak, they now recommend those individuals at risk and who are >2 years out from their last MMR vaccination receive a third dose of the MMR vaccine. This recommendation comes following a large study involving university students. Approximately 5000 students who had previously received 2-MMR vaccinations received a third MMR vaccination during an outbreak. There was a significant reduction in the attack rate in those individuals receiving a third dose compared to those who had only received two doses (6.7 vs 14.5 cases per 1000). The effect was more pronounced in those students that had >2 years elapse since their last MMR vaccination.

  • Reporting:

    • Reporting varies state by state. Rhode Island DOH mandates reporting within four days of Mumps recognition.

    • Mumps is not mandatorily reported to the CDC, but often the CDC will be aware and involved in large outbreaks.

Case Outcome

Patient reported that she had previously been completely vaccinated. At the time of her evaluation, two local universities had reported mumps cases. Her presentation occurred prior to the AICP recommendation. Serum IgM and buccal samples were collected. Patient was clinically stable and comfortable with discharge. She was advised to stay at home for 5-days. Her IgM levels were undetectable and the buccal PCR returned as negative. She most likely had a viral adenitis.


Faculty Reviewer: Dr. Kristina McAteer


References

  1. Albrecht, M. (2018). Mumps. In E.L.Baron (Ed.), UpToDate. Retrieved February 9, 2018 from https://www.uptodate.com/contents/mumps.

  2. Center for Disease Control and Prevention. (2017). Mumps. Retrieved from https://www.cdc.gov/mumps/index.html.

 

Pediatric Cough: Just Another Virus?

The Case

The patient was a 2-year-old female who had been taking amoxicillin for 8 days for an otitis media. She was brought in by her mother for a recurrence of fever, the development of cough, and increased work of breathing. The mother stated that four days ago, the child started to again spike fevers “over 100” and seemed to be having increased lethargy and decreased appetite. The patient’s vital signs revealed that she was febrile to 102F, tachycardic, and normotensive. On exam, the child was well appearing and in no acute distress. Auscultation to the lungs revealed decreased breath sounds throughout the right hemithorax and mild subcostal retractions. A two-view chest X-ray was obtained for further evaluation.

Figure       SEQ Figure \* ARABIC
   1:       Chest X-ray demonstrating opacification of right hemithorax with foci of gas and air fluid levels

Figure 1: Chest X-ray demonstrating opacification of right hemithorax with foci of gas and air fluid levels

Diagnosis

Figure       SEQ Figure \* ARABIC
   2:       Pulmonary ultrasound demonstrating consolidation of lung tissue and loculated pleural effusion

Figure 2: Pulmonary ultrasound demonstrating consolidation of lung tissue and loculated pleural effusion

The patient’s X-ray showed near complete opacification of the right hemithorax with a small amount of mediastinal shift to the left. Additionally, there were small foci of gas at the right lung base and a larger collection of gas at the right lung apex with an air-fluid level.

In light of these findings, radiology recommended an ultrasound of the right lung to further characterize the disease process. The ultrasound demonstrated a large volume of loculated fluid in the right hemithorax and mobile gas within the pleural space. 

With the findings from both the chest X-ray and the lung ultrasound, the definitive diagnosis of necrotizing pneumonia with empyema and bronchopulmonary fistula was made.

Necrotizing Pneumonia

First identified in adults and later in children, necrotizing pneumonia is a rare, but serious complication of community acquired pneumonia (1). As the name suggests, the disease process involves destruction and necrosis of pulmonary tissue. It is thought that this significant tissue damage is caused by thrombosis of intrapulmonary vessels. This reduced blood flow not only leads to loss of pulmonary tissue, but also results in a reduction in local antibiotic concentration. The decrease in antibiotic penetrance allows for the active infection to flourish (2).

Since first being described in children in 1994, the rates of culture and pathologic proven necrotizing pneumonia are slowly increasing (1). Current reports indicate that necrotizing pneumonia may complicate around 4% of community acquired pneumonias (3) and up to 20% of pneumonias associated with empyema (4). It is thought that this increase is partly due to an increased awareness of the disease process, but also from changes in organisms and in antibiotic prescribing patterns (5). Of the reported cases of necrotizing pneumonia in literature, a majority have been caused by S. pneumoniae or S.aureus (1).  

Clinical Features

The clinical features of necrotizing pneumonia are nearly indistinguishable from those of community acquired pneumonia. Children often present with fever, cough, tachypnea, tachycardia, chest pain, and focal pulmonary findings on physical exam. Of the reported cases, a majority of children had been previously healthy without any significant co-morbid conditions (6). Often, children had been appropriately treated for community acquired pneumonia with outpatient antibiotic therapy, but re-presented with worsening or persistent symptoms (7).

Diagnostic Workup

There should be a high level of suspicion for necrotizing pneumonia for any child who remains unwell despite appropriate antibiotic treatment for community acquired pneumonia. Appropriate treatment most commonly being amoxicillin. Laboratory evaluation often shows an elevation in white blood cell count, elevation in C-reactive protein, hypoalbuminemia, and anemia (1). Additionally, patients who appear to be decompensating may demonstrate signs of septic shock such as a lactic acidosis and end-organ damage. As such, an infectious work-up is recommended including CBC, BMP, Lactic acid, VBG, CRP, and blood cultures.

Chest X-ray is often used as first-line for radiographic evaluation for necrotizing pneumonia and may reveal airspace opacity, gas foci, air-fluid levels, and mediastinal shift from mass effect. However, chest X-ray has poor sensitivity, particularly early in the disease course, as areas of necrosis are fluid filled and often have similar density to that of surrounding lung tissue. It is believed that for this reason, chest x-ray is only diagnostic in 27-41% of children with necrotizing pneumonia (1).

Figure       SEQ Figure \* ARABIC
   3       Representative CT chest demonstrating cavitary lesions within an area of consolidation.   Case  courtesy of Dr Sakher&nbsp; Alkhaderi on  Radiopaedia.org

Figure 3 Representative CT chest demonstrating cavitary lesions within an area of consolidation.

Case courtesy of Dr Sakher  Alkhaderi on Radiopaedia.org

Given the poor performance of chest x-ray in the diagnosis of necrotizing pneumonia, contrast enhanced computed tomography (CT) has become the standard in diagnosing necrotizing pneumonia. With CT imaging of the chest, loss of vascularity, destruction of pulmonary tissue, and cavitary formation can be assessed. All of these findings are hallmark for necrotizing pneumonia (8).

Despite the increased sensitivity of CT, challenges exist in the pediatric population as patients are often unable to tolerate CT or are too sick to travel to radiology. For these reasons, pulmonary ultrasound has been studied in pneumonia and has been found to reliably detect lung consolidation (9). In a study in children with necrotizing pneumonia, doppler ultrasound was used to assess for lung hypoperfusion and was found to correlate well with CT scan results (10). For these reasons, lung ultrasound can be used to detect the consolidation found in community acquired pneumonia as well as the additional features of necrotizing pneumonia such as effusion, hypoechoic cavitary lesions, and decreased regional pulmonary perfusion. Challenges that exists with ultrasound are that it may not be available at all institutions and is highly dependent on operator skill level and comfort with pediatric patients.

Treatment

Once the diagnosis of necrotizing pneumonia has been made, prompt treatment is warranted. Broad spectrum IV antibiotics should be initiated and selection of antibiotic should be based on local antibiogram and organism prevalence data. One suggested antibiotic regimen consists of ceftriaxone or cefotaxime plus clindamycin. At minimum, antibiotic selection should include coverage against gram positive organisms (11). As with all severe infections, antibiotics should be narrowed whenever possible on the basis of culture data.

Surgical intervention is not always warranted as invasive management can cause in an increase in bronchopulmonary fistula formation (12). However, if the initial workup reveals signs of mass effect, such as mediastinal shift, or evidence of loculated empyema, surgical consultation and debridement is required. Very often, video-assisted thoracoscopic surgery (VATS) is necessary for definitive management, but it has been suggested that chest tube drainage alone may suffice in cases of non-loculated parapneumonic effusions (1). Surgical intervention has the added benefit of being able to collect reliable culture data.

Case Conclusion

With the diagnosis of necrotizing pneumonia, the patient was started on vancomycin and ceftriaxone for broad antibiotic coverage. Pediatric surgery was consulted and determined that the patient would benefit from a VATS procedure. The patient was taken to the OR where a VATS was performed and two chest tubes were placed. Cultures were taken during the procedure and grew MRSA. The patient had an overall hospital stay of 8 days, during which the chest tubes were removed, and she was discharged with an extended course of clindamycin and infectious disease follow-up.  

Faculty Reviewer: Dr. Jane Preotle

References

1. Masters LB, Isles AF, Grimwood K. Necrotizing pneumonia: An emerging problem in children? Pneumonia. 2017;9:(11)epub.

2. Chatha N, Fortin D, Bosma KJ. Management of necrotizing pneumonia and pulmonary gangrene: a case series and review of the literature. Can Respir J. 2014;21:239-245.

3. Nicolaou E, Bartlett A. Necrotizing Pneumonia. Pediatric Annals. 2017; 46(2)e65-e68.

4. Ramphul N, Eastham KM, Freeman R, Eltringham G, Kearns AM, Leeming JP, et al. Cavitatory lung disease complicating empyema in children. Pediatr Pulmonol. 2006;41:750–753.

5. Spencer DA, Thomas MF. Necrotising pneumonia in children. Paediatr Respir Rev. 2014;15:240-245

6. Bender JM, Ampofo K, Korgenski K, Daly J, Pavia AT, Mason EO, et al. Pneumococcal necrotizing pneumonia in Utah: does serotype matter? Clin Infect Dis. 2008;46:1346-1352.

7. Fretzayas A, Moustaki M, Alexopoulou E, Nychtari G, Nicolaidou P, Priftis KN. Clinical notations on bacteraemic cavitating pneumococcal pneumonia in nonvaccinated immunocompetent children. J Trop Pediatr. 2009;55:257-261.

8. Hodina M, Hanquinet S, Cotting J, Schnyder P, Gudinchet E. Imaging of cavitary necrosis in complicated childhood pneumonia. Eur Radiol. 2002;12:391-396.

9. Shah VP, Tunik MG, Tsung JW. Prospective evaluation of point-of-care ultrasonography for the diagnosis of pneumonia in children and young adults. JAMA Pediatr. 2013;167:119-125.

10. Lai SH, Wong KS, Liao SL. Value of lung ultrasonography in the diagnosis and outcome prediction of pediatric community-acquired pneumonia with necrotizing change. PLoS One 2015;10(6)epub

11. Islam S, Calkins CM, Goldin AB, et al. The diagnosis and management of empyema in children: a comprehensive review from the APSA outcomes and clinical trial committee. J Pediatr Surg. 2012;47:2101-2110.

12. Hoffer FA, Bloom DA, Colin AA, Fishman SJ. Lung abscess versus necrotizing pneumonia: implications for interventional therapy. Pediatr Radiol. 1999;29:87-91.