Serotype distribution and antimicrobial resistance of pediatric Streptococcus pneumoniae isolated from inpatients and outpatients at Beijing Children's Hospital

Abstract Background Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. Methods S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). Results The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). Conclusions Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae.

Etiology and clinical features of children with bronchiectasis in China: A 10-year multicenter retrospective study.

INTRODUCTION: The current study aims to investigate the etiology spectrum and the clinical characteristics of bronchiectasis in Chinese children. METHODS: The study is designed as a multicenter retrospective study. 193 cases were enrolled in 13 centers in China between 2008 and 2017. The inclusive cases must meet the clinical as well as the HRCT criteria. Only if both two radiologists confirmed the diagnosis, the case could be enrolled. The cases that could not provide clinical and imageology data were excluded. The data were entered into the specialized system and then analyzed. RESULTS: One hundred sixty-nine cases (87%) were found to have the underlying etiology. Post-infective (46%), primary immunodeficiency (14%), and PCD (13%) were the common causes. All cases came from 28 provinces in Mainland China. The median age of symptom onset was 5.8 (2.0, 8.9) years. The median age of diagnosis was 8.4 (4.5, 11.6) years. The main symptoms were cough, sputum expectoration, and fever during the exacerbation. Nineteen percent of patients suffered from limited exercise tolerance. Clubbing was found in 17% of cases. Nearly 30% of patients presented growth limitations. On the HRCT findings, 126 cases had diffused bronchiectasis, and bilateral involvement was found in 94 cases. The lower lobes and right middle lobes were most commonly involved. Approximately 30% of cultures of sputum and bronchoalveolar lavage were positive. CONCLUSION: A majority of cases could be found the underlying etiology. Post-infective, primary immunodeficiency, and PCD were the most common causes. Some clinical figures might indicate a specific etiology.

Camrelizumab-induced anaphylactic shock in an esophageal squamous cell carcinoma patient: A case report and review of literature.

BACKGROUND: Camrelizumab (SHR-1210), an immune checkpoint inhibitor, is clinically used as a therapeutic option for various types of tumors. However, reports of adverse reactions associated with camrelizumab are gradually increasing. Anaphylactic shock due to camrelizumab has not been reported previously, until now. We report here, for the first time, a case of anaphylactic shock associated with camrelizumab in a patient with esophageal squamous cell carcinoma. CASE SUMMARY: An 84-year-old male esophageal cancer patient received radiotherapy and chemotherapy 11 years ago. He was diagnosed with advanced esophageal squamous cell carcinoma with liver metastasis (TxN1M1) and received the first immunotherapy (camrelizumab 200 mg/each time, once every 3 wk) dose in December 2020, with no adverse reactions. Three weeks later, a generalized rash was noted on the chest and upper limbs; palpitations and breathing difficulties with a sense of dying occurred 10 min after the patient had been administered with the second camrelizumab therapy. Electrocardiograph monitoring revealed a 70 beats/min pulse rate, 69/24 mmHg (1 mmHg = 0.133 kPa) blood pressure, 28 breaths/min respiratory rate, and 86% pulse oximetry in room air. The patient was diagnosed with anaphylactic shock and was managed with intravenous fluid, adrenaline, dexamethasone sodium phosphate, calcium glucosate, and noradrenaline. Approximately 2 h after treatment, the patient's anaphylactic shock symptoms had been completely relieved. CONCLUSION: Due to the widespread use of camrelizumab, attention should be paid to anti-programmed cell death 1 antibody therapy-associated hypersensitivity or anaphylactic shock.

Endoscopic retrograde cholangiopancreatography in the treatment of pancreaticopleural fistula in children.

BACKGROUND: Pancreaticopleural fistula (PPF) is a rare disease, especially in children. Conservative treatment and surgery are traditional therapies, but surgery is invasive. The emergence of endoscopic retrograde cholangiopancreatography (ERCP) has provided a new noninvasive treatment for PPF and may become the first choice for children with PPF. AIM: To explore the treatment response to ERCP for PPF in children. METHODS: Seven children with PPF were hospitalized in the Gastroenterology Department of Beijing Children's Hospital from December 2007 to May 2019. Data on these seven patients' clinical characteristics, diagnosis, treatments, and outcomes were analyzed, and their treatment responses following surgery and ERCP were compared. The correlation between the length of hospital stay and conservative treatment was analyzed. Peer-reviewed articles written in English and Chinese published from January 2009 to December 2019 were obtained from various open data sources and reviewed. RESULTS: The seven patients comprised three boys and four girls with a mean age of 6.57 ± 3.26 years. The main symptoms were chest tightness and pain (n = 4), intermittent fever (n = 3), dyspnea (n = 3), and abdominal pain (n = 1), and all patients had bloody pleural effusion. All seven patients were diagnosed with PPF by magnetic resonance cholangiopancreatography, and all were initially treated conservatively for a mean of 34.67 ± 22.03 d with a poor response. Among five patients who underwent ERCP, one required surgery because of intubation failure; thus, the success rate of ERCP was 80%. Two patients were successfully treated with surgery (100%). The postoperative hospital stay of the two patients treated by surgery was 20 and 30 d, respectively (mean of 25 d), and that of the four patients treated by ERCP ranged from 12 to 30 d (mean of 19.25 ± 8.85 d). The recovery time after ERCP was short [time to oral feeding, 4-6 d (mean, 5.33 ± 1.15 d); duration of closed thoracic drainage, 2-22 d (mean, 13.3 d)]. Analysis of previous cases of PPF published worldwide during the past decade showed that the treatment success rate of ERCP is not lower than that of surgery. There was no significant difference in the postoperative hospital stay between surgery (16 ± 10.95 d) and ERCP (18.7 ± 6.88 d, P > 0.05). A positive linear correlation was found between the overall hospital stay and ERCP intervention time (R 2 = 0.9992). CONCLUSION: ERCP is recommended as the first-choice treatment for PPF in children. ERCP should be performed as early as possible if conditions permit.

Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disease in China, and very little large-scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients. METHODS: Pediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016. RESULTS: A total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X-linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P < 0.05). Approximately 64% (92/144) of the pediatric patients suffered from abnormal response to BCG vaccination. The most frequent pathogens were Aspergillus and Mycobacterium tuberculosis. Gene analysis indicated that 132 cases (89%, 132/147) harbored CYBB pathogenic variants, 7 (5%, 7/147) carried CYBA pathogenic variants, 4 (3%, 4/147) had NCF1 pathogenic variants, and 4 (3%, 4/147) had NCF2 pathogenic variants. The overall mortality rate in this study was 43%, particularly the patients were males, with CYBB mutant and did not receive HSCT treatment. CONCLUSIONS: Chronic granulomatous disease is a rare disease affecting Chinese children; however, it is often diagnosed at a later age, and thus, the mortality rate is relatively high. The prevalence and the severity of disease in XL-CGD are higher than AR-CGD.

[Mechanism of macrophage polarization on spinal cord injury].

Spinal cord injury is a serious trauma of the spinal and nervous system, local tissue destruction and microcirculation disturbance can lead to a more serious spinal cord injury and extensive necrosis of neurons. Spinal cord injury often accompany with Inflammation reaction producing a variety of cytokines and bioactive substances, result in macrophage polarization. M1 macrophages polarization are induced by IFN-γ, LPS, TNF-α and so on, it show the damage and proinflammatory effect. M2 macrophages polarization are caused by IL-4, IL-10, IL-13 and show the recovery and anti-inflammatory effect. However, clinical treatment after spinal cord injury is very limited, inhibition of proinflammatory and promotion of anti-inflammatory by regulating the M1 macrophages and M2 macrophages is a new direction for the treatment of spinal cord injury. The article will review different phenotype and function of macrophages after spinal cord injury.

Characteristics and clinical role of bronchoscopy in diagnosis of childhood endobronchial tuberculosis.

BACKGROUND: Endobronchial tuberculosis (EBTB) is the most frequent complication of primary pulmonary tuberculosis (PTB) in children. The aim of the study was to analyze characteristics and clinical role of bronchoscopy in diagnosis of childhood EBTB. METHODS: A retrospective, descriptive study was undertaken in 157 children with EBTB undergone flexible bronchoscopy (FB) between January 2006 and June 2014. RESULTS: The median age of the enrolled patients was 3.4 years, with 73.2% of patients under five years old. The most common subtype was tumorous type (145/157, 92.4%). If only involved bronchus were considered, the common affected sites were right middle lobe bronchus (49/228, 21.5%), left upper lobe bronchus (41/228, 18.0%), right upper lobe bronchus (41/228, 18.0%), right main bronchus (35/228, 15.4%), respectively. Children younger than five years old were at higher risk to have multiple endobronchial lesions (P=0.044), with an odds ratio of 2.313 (95% confidence interval: 1.009-5.299). Before the bronchoscopy, only 16 (10.2%) patients were highly suspected of EBTB, while the others were diagnosed as PTB without EBTB (69.4%), or misdiagnosed as pneumonia or foreign body aspiration (20.4%) on admission. CONCLUSIONS: The patients under five years old are at high risk to progress to EBTB and have multiple endobronchial lesions. The most frequent subtype of EBTB in children is tumorous type. The lesions are seen in the right bronchial system more frequently. FB should be performed to detect the endobronchial lesions in suspected patients as soon as possible.

[Clinical features of four atypical pediatric cases of endemic typhus with pneumonia].

OBJECTIVE: To analyze clinical manifestations, treatment and prognosis of 4 cases with endemic typhus. METHOD: The clinical data of four endemic typhus patients in prognosis were retrospectively analyzed. These four atypical cases of endemic typhus with pneumonia were treated in our department from October 2011 to March 2012. They were all male, with an age range of 15 months to 7 years. The four patients had long history, mild respiratory symptom and no improvement was found after treatment with cephalosporins. There were no evidences of bacterial, viral, or fungal infections and we thought they might have infection with other pathogen. Three were from rural areas. Routine blood tests, Weil-Felix reaction, blood smear (Giemsa staining) , and indirect immunofluorescence assay were performed. RESULT: Blood smear and IFA tests showed evidences for endemic typhus. The clinical presentations were atypical, the patients had no headache, but all had fever, rash, and pneumonia of varying severity. None of the patients had a severe cough, but bronchial casts were observed in one case. Recurrent fever was reported in three cases. Physical examinations showed no eschars, but one patient had a subconjunctival hemorrhage, and one had skin scratches, cervical lymphadenopathy, pleural effusion, pericardial effusion, and cardiac dilatation. Two patients had remarkably increased peripheral blood leukocyte counts; both these patients also had high alanine aminotransferase (ALT) levels and one had a high C-reactive protein (CRP) level. Weil-Felix testing was negative or the OX19 titer was low. The peripheral blood smear (Giemsa stain) showed intracellular pathogens in all four cases. After combined therapy with doxycycline and macrolide antibiotics, all four patients recovered well. CONCLUSION: The endemic typhus children often come from rural areas. The clinical presentations were atypical, they usually have no headache, but have fever (often Periodic fever) , rash, and pneumonia of varying severity in these four cases. Combined therapy with doxycycline and macrolide antibiotics was effective in all four patients.

[Clinical analysis of 20 cases with Streptococcus pneumoniae necrotizing pneumonia in China].

OBJECTIVE: Streptococcus pneumoniae necrotizing pneumonia (SPNP) was reported elsewhere but not in China yet. Inappropriate treatment due to poor recognition of this disease could influence its prognosis. This paper presents the clinical characteristics, diagnosis and treatment of SPNP hoping to elevate pediatrician's recognition level for this disease. METHOD: Clinical manifestations, radiological findings, treatment and prognosis of 20 patients (9 boys, 11 girls) who had been hospitalized with SPNP in Beijing Children's Hospital from 2004-2011 were retrospectively analyzed. RESULT: The patients included in this study aged from 9 months to 6 years [(27.9 ± 15.8) m] and were healthy before admission. They were febrile for 8 to 50 days [(27.7 ± 13.5) d] and hospital day was 24 - 55 days [(36.5 ± 8.3) d]. The general condition of all subjects was relatively poor and they all had fever and cough. One child had moderate fever and nineteen children had high fever. Dyspnea was found in sixteen children. Fine rales were found on auscultation in 18 children, among whom diffuse wheeze appeared in 4 children, and wheezy phlegm was found in two children. Signs of pleural effusion were discovered in all cases by physical examination and chest X-ray. White blood cell (WBC) count was 16.2 - 60.95×10(9)/L and neutrophil was 70.5% - 80.2% in peripheral blood routine test. Erythrocyte sedimentation rate (ESR) was 44 - 109 mm/h [(69.6 ± 16) mm/h]and C-reactive protein (CRP) was 80 - > 160 mg/L. The pleural effusion biochemistry and routine test revealed a WBC count of 6400×10(6)/L-too much to count, polykaryocyte of 51% - 90%, glucose of 0.02 - 1.8 mmol/L, protein of 32 - 51 g/L and LDH of 5475 IU/L-or higher. Pleural effusion culture in all cases and blood culture in 2 cases was positive for Streptococcus pneumoniae. Chest X-ray or CT revealed high density and well-distributed lobar consolidation in one lung or two lungs initially. Single or multiple low density lesions in the area of lobar consolidation were found a week later, accompanied by multiple cystic shadow or cavity at the same time or afterwards. Bulla of lung appeared later. Pleural effusions were found in all patients. Seven cases complicated with hydropneumothorax, two with otitis media, one with heart failure, one with cardiac insufficiency. Seventeen patients were treated with vancomycin or teicoplanin or linezolid two with amoxicillin and clavulanate potassium. Other two patients had been treated with meropenem and cephalosporin antibiotics respectively before admission, and they had been at recovery stage when they were hospitalized. Thoracic close drainage and thoracoscopy were performed respectively in 18 cases and 3 cases, respectively. After a follow up of more than 6 months, chest CT showed that almost all lesions in lungs recovered during 4-6 months. No one received pneumonectomy. CONCLUSION: SPNP has special manifestations. The incidence in infants is higher. Patients' general condition is poor and febrile course is relatively long. All patients manifested fever and cough, with a presence of dyspnea in most of them. WBC, neutrophil and CRP elevated apparently. The characteristic of pleural effusion indicates empyema. In early stage, the chest X-ray and CT showed high-density lobar lesions, followed by low-density lesions and cyst gradually. Bulla of lung and/or hydropneumothorax may appear at the late stage. But if diagnosed and treated promptly, the prognosis of SPNP was relatively good.

[Clinical features and molecular analysis of 2 Chinese children with autosomal recessive chronic granulomatous disease caused by CYBA mutations].

OBJECTIVE: To summarize clinical and molecular features of two children with autosomal recessive chronic granulomatous disease caused by CYBA mutations. METHOD: The clinical records and CYBA mutations were reviewed for analysis of infections and inflammatory complications. RESULT: The first case was a girl diagnosed with "liver and spleen abscess" in our hospital when she was 2.9 years old, with past history of neonatal impetigo and recurrent purulent lymphadenitis and positive family history. The results of DHR123 flow-cytometry showed that positive phagocytes after phorbol ester (PMA) stimulation was 84.63%. CYBA mutation analysis showed that she had heterozygous 35C > T, Q3X and IVS-2A > G. The second case was a boy diagnosed with "sepsis (salmonella D)" when he was 4 years old with a past history of impetigo, sepsis, perianal abscess, skin infection and positive family history. The results of flow cytometry showed that positive phagocytes after PMA stimulation was 96.13%. CYBA mutation analysis showed that he had homozygous 35C > T, Q3X and his parents were all carriers. All of them had BCG related axillary lymphnode calcification. CONCLUSION: A22CGD cases had recurrent purulent infections (skin, lymphnode, liver and spleen, lung, blood), DHR123 flow cytometric analysis helped the diagnosis of CGD, CYBA mutation analysis ascertained the diagnosis of A22CGD.