Brief Reports AGGREGATIBACTER ACTINOMYCEMCOMITANS PNEUMONIA IN CHILDREN TWO CASE REPORTS AND A REVIEW OF THE LITERATURE
Smadar Shilo, MD,*† Imad Kassis, MD,†‡ Fahed Hakim, MD,†§ and Yael Shachor-Meyouhas, MD†‡ Abstract: Aggregatibacter actinomycemcomitans, previously named Actinobacillus actinomycetemcomitans (Aa), is a facultative Gram-negative slow-growing coccobacillus associated with severe oral and nonoral infections. It is a member of the HACEK group. Pulmonary infection caused by Aa is rare. We describe two cases of Aa pneumonia mimicking malignancy and review published pediatric cases. Key Words: Aggregatibacter actinomycemcomitans pneumonia, children, HACEK Accepted for publication June 25, 2014.
From the *Pediatric Department A; †Bruce-Rappaport Faculty of Medicine Technion, Israel Institute of Technology; ‡Pediatric Infectious Diseases Unit; and §Pediatric Pulmonology Unit, Rambam Health Care Campus Haifa, Israel. The authors have no conflicts of interest to disclose. Address for correspondence: Yael Shachor-Meyouhas, MD, Pediatric Infectious Diseases Unit, Meyer Children’s Hospital, Rambam Health Care Campus, P.O. Box 9602, Haifa 31096, Israel. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000493
A
ggregatibacter actinomycemcomitans previously named Actinobacillus actinomycetemcomitans (Aa) is a facultative Gramnegative slow growing coccobacillus that has been associated with severe oral and nonoral infections.1 It is a member of the HACEK group of bacteria (Haemophilus including paraphrophilus and aphrophilus species, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae), which is considered to be the most common cause of pediatric Gram-negative infective endocarditis.2 These pathogens are frequent colonizers of the oral cavity and are major pathogens in periodontitis.1 Aa can cause periodontal infections, pneumonia, head and neck infections, brain abscesses, soft tissue infections and urethritis.3 The treatment of choice for Aa infections is most commonly ampicillin or penicillin, often in conjunction with an aminoglycoside. The duration of therapy varies and depends on the clinical response of the patient.4 Pulmonary infection caused by Aa is rare and may mimic malignancy, or tuberculosis of the chest. We present two cases of Aa pneumonia mimicking malignancy and a review of previously published pediatric cases.
CASE 1 An 11-year-old boy with a past medical history of insulindependent diabetes mellitus was referred to our hospital for a lung biopsy due to a thoracic mass. He had suffered from intermittent left chest pain for 2 months, and his mother had palpated a mass in the posterior aspect of his left chest. No other symptoms were recorded. Chest radiograph revealed consolidation in the left lung. Computerized tomography (CT) of the lungs revealed a soft tissue mass with periosteal reaction of the left third rib and a second mass in the posterior portion of the rib. The patient was referred to our pediatric oncology team for further investigation. On physical examination, he was comfortable. Blood pressure was 126/82 mmHg; pulse rate 130 beats/minute; temperature 37.3°C; and oxygen saturation was 97% in room air. His weight
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was 33.5 kg. The oropharynx was normal including his dental status. He had a nontender mass in the posterior aspect of his left chest (2 × 2 cm) with otherwise normal physical examination. He had normal complete blood count with high C-reactive protein (170 mg/L). Positron emission tomography-CT revealed a pathologic Fluorodeoxyglucose F-18 uptake in the left chest wall and in the tissues surrounding the left 3rd, 8th, 9th and 10th ribs with a periosteal reaction. Echocardiogram was normal. Lung biopsy revealed a severe inflammatory process and granulation tissue, without the presence of malignant cells but with the presence of sulfur granules, which raised the suspicion for Actinomycosis. Aerobic and anaerobic standard cultures were negative, and blood culture was not taken. Later on, polymerase chain reaction (PCR) (16sRNA) from the biopsy was positive for Aggregatibacter actinomycemcomitans DNA. The patient received intravenous penicillin G for 2 months; therapy was then switched to oral amoxicillin and clindamycin for an additional 10 months. Following this treatment, the patient experienced a full clinical and radiographic recovery.
CASE 2 A 14-year-old boy with past medical history of neurofibromatosis type 1, without specific treatment, was referred to our hospital for evaluation of a dry cough, anorexia, night sweats and a weight loss of 8 kg lasting for 4 months. His mother felt that he was occasionally febrile at home, but his temperature was not measured. No other symptoms were mentioned. On physical examination, he was comfortable with no apparent distress. Blood pressure was 106/62 mmHg; pulse rate 130 beats/minute; temperature 36.8°C; and oxygen saturation was 100% on room air. He was malnourished with a weight of 37.4 kg. The oropharynx was normal including dental status. He had small, soft, nontender, submandibular lymph nodes bilaterally. His chest was asymmetric, and his right ribs were visualized with tender bulging of soft tissue. On auscultation, he had decreased breath sounds and crackles in the left lung with dullness on percussion. Complete blood count demonstrated a white blood cells (WBC) count of 14.1 × 103 cells/μL, with 88% neutrophils; hemoglobin 7.8 g/dL and platelets, 481 × 103 cells/μL. Blood chemistry revealed albumin 2.2 g/dL; total protein, 8.7 g/dL and C-reactive protein, 188 mg/L. Blood cultures and tuberculin skin test were negative. Chest radiograph revealed a large radiodensity in the left lower lung. CT revealed a large space-occupying lesion involving the left chest wall, lung, ribs and diaphragm. In addition, there was pleural effusion and lytic lesions involving ribs 5, 7–12 with pathologic fractures. Owing to his medical history, the suspected diagnosis was malignancy, and the patient underwent a lung biopsy, without obtaining samples for microbiologic evaluation. Pathology revealed fibrosis, with no presence of malignant cells. A second biopsy was necessary to rule out the possibility of an infectious process. In addition, the patient underwent an ultrasound-guided thoracocentesis with drainage of 12 mL clear pleural fluid. PH of the pleural fluid was 7.42, WBC, 2130 cells/μL (56% neutrophils); LDH was 308 U/L, protein 6.3 g/dL and glucose 43 mg/dL. Pathology from the second biopsy revealed many inflammatory cells, leukocytes, histiocytes and a few mesothelial cells with no malignant cells or sulfur granules. Microbiologic cultures from the biopsy were negative, but PCR from the pleural fluid was positive for Aggregatibacter actinomycemcomitans DNA. The patient was initially treated with intravenous ampicillin/ sulbactam for a presumable diagnosis of pulmonary actinomycosis
The Pediatric Infectious Disease Journal • Volume 34, Number 1, January 2015
Chronic inflammation 1Y Survived 6D Died 1Y Survived Ongoing (>3 Mo) Survived 1Y Survived Treatment duration Outcome
DISCUSSION
NF indicates neurofibromatosis; CP, cerebral palsy; DM, diabetes melitus; PE, pleural effusion; Y, year; D, days; W, weeks; Mo, months; UN, unknown; M, male; F, female.
Acute inflammation >3 Mo Survived Acute and chronic inflammation 3W Survived UN
© 2014 Lippincott Williams & Wilkins
Aggregatibacter Pneumonia
with or without anaerobic organisms, due to the extensive involvement of soft tissues pending microbiological results. After 18 days, antibiotic regimen was switched to oral amoxicillin-clavulanic acid and amoxicillin combination in order to achieve higher doses of the penicillin component. In a follow-up visit 3 months later, his cough had resolved and he had gained weight and dramatically improved, and a follow-up chest X-ray showed near complete resolution of infiltrates.
11 M Autism Yes UN Yes 16,000 Yes Pleural effusion Chronic inflammation 6Mo Survived 9 F No Yes 1 Mo No 8400 Yes Empyema 14 F No Yes 1.5 Mo No 18,000 Yes Pleural effusion 13 M No Yes 1Y Yes 12,500 UN 17 F CP Yes 10 D Yes 20,000 UN Empyema
10 M No No 1Y No 8300 Yes Hilar lymphadenopathy UN 14 M NF type 1 No 4 Mo Yes 14,100 Yes Rib destruction, Pleural effusion Acute inflammation 11 M DM No 2 Mo No 15,400 Yes Rib and vertebra destruction Acute inflammation Age (years) Sex Underlying disease Periodontal disease Symptoms duration Fever WBC (μL) Chest wall mass Other clinical manifestation Pathology
Case 35 Case 24 Case 14 Patient # 2 Patient # 1
TABLE 1. Summary of Actinobacillus actinomycetemcomitans Pulmonary Infection Cases in Children
Case 46
Case 57
Case 69
The Pediatric Infectious Disease Journal • Volume 34, Number 1, January 2015
A review of all previous reports of Aa pulmonary infection revealed 9 such cases including 6 in pediatric patients.4–7,9,10 The youngest patient was 9 years old.7 This may be attributed to the predisposing dental status which can be noticed in most of the reports.4,6–8 All pediatric cases reported are summarized in Table 1. Most cases of Aa pneumonia described in the literature were pediatric patients, with an average age of 12.3. The M:F ratio was 5:3, 50% had an underlying disease and 60% had a periodontal disease. Only 50% of the patients were febrile, a fact that can explain why infection was not included in the differential diagnosis. The average WBC count was 14,087/μL. Average duration of symptoms was 142 days before diagnosis. All these factors may contribute to the misconception of the disease being suspected for malignancy rather than infection. In most cases, the diagnosis was made by an appropriate culture from a lung biopsy. Isolation of this pathogen is difficult by standard microbiologic methods and, therefore, it is necessary to take appropriate samples for microbiologic investigation. Our samples might have not been taken properly for anaerobic cultures. The use of modern molecular diagnostic methods may be more rapid and accurate for these difficult-to-isolate pathogens. In both cases, the diagnosis was made using PCR (16S rRNA).11 The typical sulfur granules were present in 1 case. The appearance of sulfur granules is considered typical to Actinomyces israeli and, therefore, actinomycosis was suspected in this case, until the results of the PCR were received. Such infections with Aa may be easily confused with Actinomyces israeli infection. Morris et al9 also reported a case of coinfection with these 2 pathogens. Coinfection with actinomyces in the first case could not be excluded, although bacterial PCR did not detect the organism. Treatment is usually guided by susceptibility tests when applicable. This pathogen is usually susceptible to cephalosporines, mezlocillin, rifampicin, trimethoprim-sulfamethoxazole, aminoglicosides, fluoroquinolones, tetracycline, azithromycin and chloramphenicol. In vitro susceptibility to penicillin and ampicillin is variable, and vancomycin, erythromycin and clindamycin have little activity against the pathogen.1 Our first patient was treated with the addition of clindamycin, when the suspicion of actinomycosis was raised based on the pathology, and later on continued with the dual therapy. The second patient received ampicillin/sulbactam, in order to cover other pathogens such as anaerobes, as he had an acute progression of his pulmonary manifestation, and the suspicion for mixed infection with anaerobes was raised. The optimal duration of therapy is not known, although it is accepted that an extended period of antibiotic therapy is needed. This usually depends on the extent of tissue involvement, clinical response of the patient and resolution of the infective process on follow-up radiography. In the pediatric cases reviewed here, the average duration of treatment was roughly 240 days and duration of 3–12 months is mentioned in the literature.6 REFERENCES 1. Steinberg JP, Burd EM. Other gram-negative and gram–variable bacilli. In: Mandell GL, Bennet JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier Inc.; 2010: 3015–3033.
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The Pediatric Infectious Disease Journal • Volume 34, Number 1, January 2015
2. Ferrieri P, Gewitz MH, Gerber MA, et al; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the American Heart Association Council on Cardiovascular Disease in the Young. Unique features of infective endocarditis in childhood. Circulation. 2002;105:2115–2126. 3. Das M, Badley AD, Cockerill FR, et al. Infective endocarditis caused by HACEK microorganisms. Annu Rev Med. 1997;48:25–33. 4. Kaplan AH, Weber DJ, Oddone EZ, et al. Infection due to Actinobacillus actinomycetemcomitans: 15 cases and review. Rev Infect Dis. 1989;11:46–63. 5. Carlile JR, Beckman EN, Arensman RM. Actinobacillus actinomycetemcomitans pneumonia. Clin Pediatr (Phila). 1984;23:578–580. 6. Chen AC, Liu CC, Yao WJ, et al. Actinobacillus actinomycetemcomitans pneumonia with chest wall and subphrenic abscess. Scand J Infect Dis. 1995;27:289–290. 7. Hagiwara S, Fujimaru T, Ogino A, et al. Lung abscess caused by infection of Actinobacillus actinomycetemcomitans. Pediatr Int. 2009;51:748–751. 8. Nash CB, Hendrickson BA, Alexander KA. Pneumonia with chest wall invasion in a school aged child. J Ped Infect Dis. [published online ahead of print February 16, 2014]. 9. Morris JF, Sewell DL. Necrotizing pneumonia caused by mixed infection with Actinobacillus actinomycetemcomitans and Actinomyces israelii: case report and review. Clin Infect Dis. 1994;18:450–452. 10. Meyer BR, Buttone E, Hirschman SZ, Schneierson SS, Gershengorn K. Infection due to Actinobacillus actinomycetemcomitans. Am J Clin Pathol. 1971;56:204–211. 11. Leys EJ, Griffen AL, Strong SJ, et al. Detection and strain identification of Actinobacillus actinomycetemcomitans by nested PCR. J Clin Microbiol. 1994;32:1288–1294.
PANUVEITIS CAUSED BY BORRELIA BURGDORFERI SENSU LATO INFECTION Jasna Mahne, MD*, Branka Stirn Kranjc, MD, PhD†, Franc Strle, MD, PhD*, Eva Ružić-Sabljić, MD, PhD‡, and Maja Arnež, MD, PhD* Abstract: A 13-year-old boy who presented with a red left eye, painful eye movement, blurred vision, photophobia and increased lacrimation, was diagnosed with 1-sided panuveitis with optic disk edema. Diagnostic workup revealed borrelial antibodies in serum. Diagnosis of Lyme borreliosis was substantiated by demonstration of lymphocytic pleocytosis, intrathecal borrelial antibody synthesis, improvement after treatment with ceftriaxone and exclusion of other causes. Key Words: Panuveitis, Lyme neuroborreliosis, Borrelia burgdorferi sensu lato, pediatric, tick bite Accepted for publication June 25, 2014. From the *Department of Infectious Diseases, University Medical Centre Ljubljana, Japljeva 2, 1525 Ljubljana; †Department of Ophthalmology, University Medical Centre Ljubljana, Grablovičeva 46; and ‡Institute of Microbiology and Immunology, School of Medicine, Zaloška 4, 1000 Ljubljana, Slovenia. Franc Strle’s institution is receiving a grant from the Slovenian Research Agency (No P3-0296). For the remaining authors none were declared. Address for correspondence: Jasna Mahne, MD, Department of Infectious Diseases, University Medical Centre Ljubljana, Japljeva 2, 1525 Ljubljana, Slovenia. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000473
L
yme borreliosis (LB) is a multisystem infectious disease caused by Borrelia burgdorferi sensu lato and transmitted to humans by tick bite. It is endemic in several regions of North America, Asia and Europe, including Slovenia. In European patients, the most common clinical manifestation of the disease is erythema migrans (EM), followed by Lyme neuroborreliosis (LNB).1,2 Data on ocular manifestations of LB are scarce and predominantly restricted to adults. Eyes can be affected primarily as a result of inflammation of eye tissue or secondarily due
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to extraocular manifestations of LB such as paresis of cranial nerves and orbital myositis.3 We report a case of acute, 1-sided panuveitis with optic disc edema in a child in whom diagnostic work-up revealed LNB.
CASE REPORT On April 13, 2011, a 13-year-old boy was referred to the University Medical Centre Ljubljana, Slovenia, with a 7-day history of a red left eye with pain provoked by eye movement, blurred vision, photophobia and increased lacrimation. His previous medical history was unremarkable with the exception of numerous tick bites (the last 1 being several months before the onset of the present illness) and of solitary EM in 2005 that had been treated with azithromycin. The only abnormal finding on physical examination was a red and painful left eye. No skin lesions were uncovered, and neurologic examination disclosed no abnormalities. Ophthalmologic examination revealed impaired vision in the left eye (0.4 Snellen equivalent) while visual acuity in the right eye was normal (1.0 Snellen equivalent). A few tiny keratic precipitates and cells in the aqueous humor and vitreous body, with some floaters, predominantly in the posterior vitreous, were present in the left eye. The pupil was normal, and the lens was clear. The left optic disk was swollen (also seen on optic coherence tomography and ultrasound), pink, without evident hemorrhages, the vessels were slightly congested, the posterior pole, fovea and peripheral chorioretina appeared normal. No clinical abnormalities were seen in the right eye. The initial ocular pressure was ≤16 mm Hg in both eyes and gonioscopy showed normal angle structures with a slightly more pigmented ciliary body bilaterally. Color vision and visual fields were not affected. A diagnosis of panuveitis with left optic disk edema was made and its cause was searched for. Initial laboratory findings revealed a normal C-reactive protein value (3 mg/L) and a slightly elevated leukocyte count (14 × 109/L) with normal differential white cell counts. Basic biochemical blood tests as well as concentration of serum protein, fibrinogen, antinuclear antibodies and C3 were normal or negative, C4 and serum immunoglobulin G were slightly elevated, and human leukocyte antigen-B27 was not expressed. Negative angiotensin-converting enzyme result pointed against sarcoidosis. Testing for serum antibodies to Toxoplasma gondii was unremarkable, however, the diagnostic work-up revealed the presence of borrelial antibodies in serum. The latter result, the presence of unilateral disc edema and the fact that the patient was from a highly endemic region for LB, prompt further testing including lumbar punction and cerebrospinal fluid (CSF) examination in spite of normal findings on neurologic examination. The evaluation revealed lymphocytic pleocytosis and intrathecal borrelial immunoglobulin M as well as immunoglobulin G synthesis (Table 1). B. burgdorferi sensu lato blood and CSF cultures were negative. Therefore a diagnosis of LNB was made and intravenous ceftriaxone 2 g once daily for 14 days was added to therapy with systemic acetazolamide, topical steroids and mydriatics, and triamcinolone sub Tenon. The symptoms started improving within a few days, the signs of the uveitis and optic disk edema regressed in a few weeks, while elevated intraocular pressure (26–36 mm Hg) in the boy’s left eye had to be treated over the next few months. The further course was smooth; there was no relapse of the ophthalmic problems and no clinical signs of LB during 12-month follow-up.
DISCUSSION Panuveitis is an inflammation of the uveal tract involving both the anterior segment (iris and ciliary body) and the posterior segment (chorioretina and optic disc). It can be caused by © 2014 Lippincott Williams & Wilkins
Smadar Shilo, MD,*† Imad Kassis, MD,†‡ Fahed Hakim, MD,†§ and Yael Shachor-Meyouhas, MD†‡ Abstract: Aggregatibacter actinomycemcomitans, previously named Actinobacillus actinomycetemcomitans (Aa), is a facultative Gram-negative slow-growing coccobacillus associated with severe oral and nonoral infections. It is a member of the HACEK group. Pulmonary infection caused by Aa is rare. We describe two cases of Aa pneumonia mimicking malignancy and review published pediatric cases. Key Words: Aggregatibacter actinomycemcomitans pneumonia, children, HACEK Accepted for publication June 25, 2014.
From the *Pediatric Department A; †Bruce-Rappaport Faculty of Medicine Technion, Israel Institute of Technology; ‡Pediatric Infectious Diseases Unit; and §Pediatric Pulmonology Unit, Rambam Health Care Campus Haifa, Israel. The authors have no conflicts of interest to disclose. Address for correspondence: Yael Shachor-Meyouhas, MD, Pediatric Infectious Diseases Unit, Meyer Children’s Hospital, Rambam Health Care Campus, P.O. Box 9602, Haifa 31096, Israel. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000493
A
ggregatibacter actinomycemcomitans previously named Actinobacillus actinomycetemcomitans (Aa) is a facultative Gramnegative slow growing coccobacillus that has been associated with severe oral and nonoral infections.1 It is a member of the HACEK group of bacteria (Haemophilus including paraphrophilus and aphrophilus species, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae), which is considered to be the most common cause of pediatric Gram-negative infective endocarditis.2 These pathogens are frequent colonizers of the oral cavity and are major pathogens in periodontitis.1 Aa can cause periodontal infections, pneumonia, head and neck infections, brain abscesses, soft tissue infections and urethritis.3 The treatment of choice for Aa infections is most commonly ampicillin or penicillin, often in conjunction with an aminoglycoside. The duration of therapy varies and depends on the clinical response of the patient.4 Pulmonary infection caused by Aa is rare and may mimic malignancy, or tuberculosis of the chest. We present two cases of Aa pneumonia mimicking malignancy and a review of previously published pediatric cases.
CASE 1 An 11-year-old boy with a past medical history of insulindependent diabetes mellitus was referred to our hospital for a lung biopsy due to a thoracic mass. He had suffered from intermittent left chest pain for 2 months, and his mother had palpated a mass in the posterior aspect of his left chest. No other symptoms were recorded. Chest radiograph revealed consolidation in the left lung. Computerized tomography (CT) of the lungs revealed a soft tissue mass with periosteal reaction of the left third rib and a second mass in the posterior portion of the rib. The patient was referred to our pediatric oncology team for further investigation. On physical examination, he was comfortable. Blood pressure was 126/82 mmHg; pulse rate 130 beats/minute; temperature 37.3°C; and oxygen saturation was 97% in room air. His weight
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was 33.5 kg. The oropharynx was normal including his dental status. He had a nontender mass in the posterior aspect of his left chest (2 × 2 cm) with otherwise normal physical examination. He had normal complete blood count with high C-reactive protein (170 mg/L). Positron emission tomography-CT revealed a pathologic Fluorodeoxyglucose F-18 uptake in the left chest wall and in the tissues surrounding the left 3rd, 8th, 9th and 10th ribs with a periosteal reaction. Echocardiogram was normal. Lung biopsy revealed a severe inflammatory process and granulation tissue, without the presence of malignant cells but with the presence of sulfur granules, which raised the suspicion for Actinomycosis. Aerobic and anaerobic standard cultures were negative, and blood culture was not taken. Later on, polymerase chain reaction (PCR) (16sRNA) from the biopsy was positive for Aggregatibacter actinomycemcomitans DNA. The patient received intravenous penicillin G for 2 months; therapy was then switched to oral amoxicillin and clindamycin for an additional 10 months. Following this treatment, the patient experienced a full clinical and radiographic recovery.
CASE 2 A 14-year-old boy with past medical history of neurofibromatosis type 1, without specific treatment, was referred to our hospital for evaluation of a dry cough, anorexia, night sweats and a weight loss of 8 kg lasting for 4 months. His mother felt that he was occasionally febrile at home, but his temperature was not measured. No other symptoms were mentioned. On physical examination, he was comfortable with no apparent distress. Blood pressure was 106/62 mmHg; pulse rate 130 beats/minute; temperature 36.8°C; and oxygen saturation was 100% on room air. He was malnourished with a weight of 37.4 kg. The oropharynx was normal including dental status. He had small, soft, nontender, submandibular lymph nodes bilaterally. His chest was asymmetric, and his right ribs were visualized with tender bulging of soft tissue. On auscultation, he had decreased breath sounds and crackles in the left lung with dullness on percussion. Complete blood count demonstrated a white blood cells (WBC) count of 14.1 × 103 cells/μL, with 88% neutrophils; hemoglobin 7.8 g/dL and platelets, 481 × 103 cells/μL. Blood chemistry revealed albumin 2.2 g/dL; total protein, 8.7 g/dL and C-reactive protein, 188 mg/L. Blood cultures and tuberculin skin test were negative. Chest radiograph revealed a large radiodensity in the left lower lung. CT revealed a large space-occupying lesion involving the left chest wall, lung, ribs and diaphragm. In addition, there was pleural effusion and lytic lesions involving ribs 5, 7–12 with pathologic fractures. Owing to his medical history, the suspected diagnosis was malignancy, and the patient underwent a lung biopsy, without obtaining samples for microbiologic evaluation. Pathology revealed fibrosis, with no presence of malignant cells. A second biopsy was necessary to rule out the possibility of an infectious process. In addition, the patient underwent an ultrasound-guided thoracocentesis with drainage of 12 mL clear pleural fluid. PH of the pleural fluid was 7.42, WBC, 2130 cells/μL (56% neutrophils); LDH was 308 U/L, protein 6.3 g/dL and glucose 43 mg/dL. Pathology from the second biopsy revealed many inflammatory cells, leukocytes, histiocytes and a few mesothelial cells with no malignant cells or sulfur granules. Microbiologic cultures from the biopsy were negative, but PCR from the pleural fluid was positive for Aggregatibacter actinomycemcomitans DNA. The patient was initially treated with intravenous ampicillin/ sulbactam for a presumable diagnosis of pulmonary actinomycosis
The Pediatric Infectious Disease Journal • Volume 34, Number 1, January 2015
Chronic inflammation 1Y Survived 6D Died 1Y Survived Ongoing (>3 Mo) Survived 1Y Survived Treatment duration Outcome
DISCUSSION
NF indicates neurofibromatosis; CP, cerebral palsy; DM, diabetes melitus; PE, pleural effusion; Y, year; D, days; W, weeks; Mo, months; UN, unknown; M, male; F, female.
Acute inflammation >3 Mo Survived Acute and chronic inflammation 3W Survived UN
© 2014 Lippincott Williams & Wilkins
Aggregatibacter Pneumonia
with or without anaerobic organisms, due to the extensive involvement of soft tissues pending microbiological results. After 18 days, antibiotic regimen was switched to oral amoxicillin-clavulanic acid and amoxicillin combination in order to achieve higher doses of the penicillin component. In a follow-up visit 3 months later, his cough had resolved and he had gained weight and dramatically improved, and a follow-up chest X-ray showed near complete resolution of infiltrates.
11 M Autism Yes UN Yes 16,000 Yes Pleural effusion Chronic inflammation 6Mo Survived 9 F No Yes 1 Mo No 8400 Yes Empyema 14 F No Yes 1.5 Mo No 18,000 Yes Pleural effusion 13 M No Yes 1Y Yes 12,500 UN 17 F CP Yes 10 D Yes 20,000 UN Empyema
10 M No No 1Y No 8300 Yes Hilar lymphadenopathy UN 14 M NF type 1 No 4 Mo Yes 14,100 Yes Rib destruction, Pleural effusion Acute inflammation 11 M DM No 2 Mo No 15,400 Yes Rib and vertebra destruction Acute inflammation Age (years) Sex Underlying disease Periodontal disease Symptoms duration Fever WBC (μL) Chest wall mass Other clinical manifestation Pathology
Case 35 Case 24 Case 14 Patient # 2 Patient # 1
TABLE 1. Summary of Actinobacillus actinomycetemcomitans Pulmonary Infection Cases in Children
Case 46
Case 57
Case 69
The Pediatric Infectious Disease Journal • Volume 34, Number 1, January 2015
A review of all previous reports of Aa pulmonary infection revealed 9 such cases including 6 in pediatric patients.4–7,9,10 The youngest patient was 9 years old.7 This may be attributed to the predisposing dental status which can be noticed in most of the reports.4,6–8 All pediatric cases reported are summarized in Table 1. Most cases of Aa pneumonia described in the literature were pediatric patients, with an average age of 12.3. The M:F ratio was 5:3, 50% had an underlying disease and 60% had a periodontal disease. Only 50% of the patients were febrile, a fact that can explain why infection was not included in the differential diagnosis. The average WBC count was 14,087/μL. Average duration of symptoms was 142 days before diagnosis. All these factors may contribute to the misconception of the disease being suspected for malignancy rather than infection. In most cases, the diagnosis was made by an appropriate culture from a lung biopsy. Isolation of this pathogen is difficult by standard microbiologic methods and, therefore, it is necessary to take appropriate samples for microbiologic investigation. Our samples might have not been taken properly for anaerobic cultures. The use of modern molecular diagnostic methods may be more rapid and accurate for these difficult-to-isolate pathogens. In both cases, the diagnosis was made using PCR (16S rRNA).11 The typical sulfur granules were present in 1 case. The appearance of sulfur granules is considered typical to Actinomyces israeli and, therefore, actinomycosis was suspected in this case, until the results of the PCR were received. Such infections with Aa may be easily confused with Actinomyces israeli infection. Morris et al9 also reported a case of coinfection with these 2 pathogens. Coinfection with actinomyces in the first case could not be excluded, although bacterial PCR did not detect the organism. Treatment is usually guided by susceptibility tests when applicable. This pathogen is usually susceptible to cephalosporines, mezlocillin, rifampicin, trimethoprim-sulfamethoxazole, aminoglicosides, fluoroquinolones, tetracycline, azithromycin and chloramphenicol. In vitro susceptibility to penicillin and ampicillin is variable, and vancomycin, erythromycin and clindamycin have little activity against the pathogen.1 Our first patient was treated with the addition of clindamycin, when the suspicion of actinomycosis was raised based on the pathology, and later on continued with the dual therapy. The second patient received ampicillin/sulbactam, in order to cover other pathogens such as anaerobes, as he had an acute progression of his pulmonary manifestation, and the suspicion for mixed infection with anaerobes was raised. The optimal duration of therapy is not known, although it is accepted that an extended period of antibiotic therapy is needed. This usually depends on the extent of tissue involvement, clinical response of the patient and resolution of the infective process on follow-up radiography. In the pediatric cases reviewed here, the average duration of treatment was roughly 240 days and duration of 3–12 months is mentioned in the literature.6 REFERENCES 1. Steinberg JP, Burd EM. Other gram-negative and gram–variable bacilli. In: Mandell GL, Bennet JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier Inc.; 2010: 3015–3033.
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The Pediatric Infectious Disease Journal • Volume 34, Number 1, January 2015
2. Ferrieri P, Gewitz MH, Gerber MA, et al; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the American Heart Association Council on Cardiovascular Disease in the Young. Unique features of infective endocarditis in childhood. Circulation. 2002;105:2115–2126. 3. Das M, Badley AD, Cockerill FR, et al. Infective endocarditis caused by HACEK microorganisms. Annu Rev Med. 1997;48:25–33. 4. Kaplan AH, Weber DJ, Oddone EZ, et al. Infection due to Actinobacillus actinomycetemcomitans: 15 cases and review. Rev Infect Dis. 1989;11:46–63. 5. Carlile JR, Beckman EN, Arensman RM. Actinobacillus actinomycetemcomitans pneumonia. Clin Pediatr (Phila). 1984;23:578–580. 6. Chen AC, Liu CC, Yao WJ, et al. Actinobacillus actinomycetemcomitans pneumonia with chest wall and subphrenic abscess. Scand J Infect Dis. 1995;27:289–290. 7. Hagiwara S, Fujimaru T, Ogino A, et al. Lung abscess caused by infection of Actinobacillus actinomycetemcomitans. Pediatr Int. 2009;51:748–751. 8. Nash CB, Hendrickson BA, Alexander KA. Pneumonia with chest wall invasion in a school aged child. J Ped Infect Dis. [published online ahead of print February 16, 2014]. 9. Morris JF, Sewell DL. Necrotizing pneumonia caused by mixed infection with Actinobacillus actinomycetemcomitans and Actinomyces israelii: case report and review. Clin Infect Dis. 1994;18:450–452. 10. Meyer BR, Buttone E, Hirschman SZ, Schneierson SS, Gershengorn K. Infection due to Actinobacillus actinomycetemcomitans. Am J Clin Pathol. 1971;56:204–211. 11. Leys EJ, Griffen AL, Strong SJ, et al. Detection and strain identification of Actinobacillus actinomycetemcomitans by nested PCR. J Clin Microbiol. 1994;32:1288–1294.
PANUVEITIS CAUSED BY BORRELIA BURGDORFERI SENSU LATO INFECTION Jasna Mahne, MD*, Branka Stirn Kranjc, MD, PhD†, Franc Strle, MD, PhD*, Eva Ružić-Sabljić, MD, PhD‡, and Maja Arnež, MD, PhD* Abstract: A 13-year-old boy who presented with a red left eye, painful eye movement, blurred vision, photophobia and increased lacrimation, was diagnosed with 1-sided panuveitis with optic disk edema. Diagnostic workup revealed borrelial antibodies in serum. Diagnosis of Lyme borreliosis was substantiated by demonstration of lymphocytic pleocytosis, intrathecal borrelial antibody synthesis, improvement after treatment with ceftriaxone and exclusion of other causes. Key Words: Panuveitis, Lyme neuroborreliosis, Borrelia burgdorferi sensu lato, pediatric, tick bite Accepted for publication June 25, 2014. From the *Department of Infectious Diseases, University Medical Centre Ljubljana, Japljeva 2, 1525 Ljubljana; †Department of Ophthalmology, University Medical Centre Ljubljana, Grablovičeva 46; and ‡Institute of Microbiology and Immunology, School of Medicine, Zaloška 4, 1000 Ljubljana, Slovenia. Franc Strle’s institution is receiving a grant from the Slovenian Research Agency (No P3-0296). For the remaining authors none were declared. Address for correspondence: Jasna Mahne, MD, Department of Infectious Diseases, University Medical Centre Ljubljana, Japljeva 2, 1525 Ljubljana, Slovenia. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000473
L
yme borreliosis (LB) is a multisystem infectious disease caused by Borrelia burgdorferi sensu lato and transmitted to humans by tick bite. It is endemic in several regions of North America, Asia and Europe, including Slovenia. In European patients, the most common clinical manifestation of the disease is erythema migrans (EM), followed by Lyme neuroborreliosis (LNB).1,2 Data on ocular manifestations of LB are scarce and predominantly restricted to adults. Eyes can be affected primarily as a result of inflammation of eye tissue or secondarily due
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to extraocular manifestations of LB such as paresis of cranial nerves and orbital myositis.3 We report a case of acute, 1-sided panuveitis with optic disc edema in a child in whom diagnostic work-up revealed LNB.
CASE REPORT On April 13, 2011, a 13-year-old boy was referred to the University Medical Centre Ljubljana, Slovenia, with a 7-day history of a red left eye with pain provoked by eye movement, blurred vision, photophobia and increased lacrimation. His previous medical history was unremarkable with the exception of numerous tick bites (the last 1 being several months before the onset of the present illness) and of solitary EM in 2005 that had been treated with azithromycin. The only abnormal finding on physical examination was a red and painful left eye. No skin lesions were uncovered, and neurologic examination disclosed no abnormalities. Ophthalmologic examination revealed impaired vision in the left eye (0.4 Snellen equivalent) while visual acuity in the right eye was normal (1.0 Snellen equivalent). A few tiny keratic precipitates and cells in the aqueous humor and vitreous body, with some floaters, predominantly in the posterior vitreous, were present in the left eye. The pupil was normal, and the lens was clear. The left optic disk was swollen (also seen on optic coherence tomography and ultrasound), pink, without evident hemorrhages, the vessels were slightly congested, the posterior pole, fovea and peripheral chorioretina appeared normal. No clinical abnormalities were seen in the right eye. The initial ocular pressure was ≤16 mm Hg in both eyes and gonioscopy showed normal angle structures with a slightly more pigmented ciliary body bilaterally. Color vision and visual fields were not affected. A diagnosis of panuveitis with left optic disk edema was made and its cause was searched for. Initial laboratory findings revealed a normal C-reactive protein value (3 mg/L) and a slightly elevated leukocyte count (14 × 109/L) with normal differential white cell counts. Basic biochemical blood tests as well as concentration of serum protein, fibrinogen, antinuclear antibodies and C3 were normal or negative, C4 and serum immunoglobulin G were slightly elevated, and human leukocyte antigen-B27 was not expressed. Negative angiotensin-converting enzyme result pointed against sarcoidosis. Testing for serum antibodies to Toxoplasma gondii was unremarkable, however, the diagnostic work-up revealed the presence of borrelial antibodies in serum. The latter result, the presence of unilateral disc edema and the fact that the patient was from a highly endemic region for LB, prompt further testing including lumbar punction and cerebrospinal fluid (CSF) examination in spite of normal findings on neurologic examination. The evaluation revealed lymphocytic pleocytosis and intrathecal borrelial immunoglobulin M as well as immunoglobulin G synthesis (Table 1). B. burgdorferi sensu lato blood and CSF cultures were negative. Therefore a diagnosis of LNB was made and intravenous ceftriaxone 2 g once daily for 14 days was added to therapy with systemic acetazolamide, topical steroids and mydriatics, and triamcinolone sub Tenon. The symptoms started improving within a few days, the signs of the uveitis and optic disk edema regressed in a few weeks, while elevated intraocular pressure (26–36 mm Hg) in the boy’s left eye had to be treated over the next few months. The further course was smooth; there was no relapse of the ophthalmic problems and no clinical signs of LB during 12-month follow-up.
DISCUSSION Panuveitis is an inflammation of the uveal tract involving both the anterior segment (iris and ciliary body) and the posterior segment (chorioretina and optic disc). It can be caused by © 2014 Lippincott Williams & Wilkins
