Systemic amyloidosis complicating multidrug-resistant tuberculosis in childhood

Multidrug-resistant tuberculosis is increasingly common and is associated with long diagnostic delay and high morbidity. We present a 7-year-old child who developed steroid-resistant nephrotic syndrome while receiving treatment for tuberculosis. Renal biopsy results showed systemic amyloidosis; culture of peritoneal tissue confirmed disseminated multidrug-resistant tuberculosis.     

T-cell-based diagnosis of neonatal multidrug-resistant latent tuberculosis infection

Young children exposed to tuberculosis have a high risk of progression to severe tuberculosis disease, but diagnosis of recent infection is hindered by the poor sensitivity of the tuberculin skin test. Whether new blood tests can detect latent infection in this vulnerable group is unknown because there is no gold standard. We monitored a tuberculin skin test-negative infant whose mother had infectious multidrug-resistant tuberculosis with enzyme-linked immunospot, a blood test that enumerates Mycobacterium tuberculosis-specific T cells. The enzyme-linked immunospot test became persistently positive by 6 months, and 18 months later the child developed active tuberculosis despite appropriate chemoprophylaxis. At this point, the magnitude of the enzyme-linked immunospot response increased >10-fold. Our findings demonstrate that this blood test detected latent infection with dormant, yet viable, bacilli and illustrate how enzyme-linked immunospot could improve diagnosis of childhood tuberculosis infection.     

Two pediatric cases of multidrug-resistant tuberculosis treated with linezolid and moxifloxacin

We report here 2 pediatric cases of multidrug-resistant (MDR) tuberculosis (TB) that were observed in Italy. Both families came from an Eastern European country, which is notably an area with a high prevalence of MDR TB. An increase of new cases of MDR TB in developed countries is expected over the next years because of migratory flow, and specific measures and strategies need to be taken to prevent the propagation and dissemination of MDR TB. An efficacious treatment including linezolid and moxifloxacin was administered for 13 months in 1 case. No adverse reactions were detected during close child monitoring. Linezolid and newer fluoroquinolones such as moxifloxacin have been reported to be effective for MDR-TB treatment in adults. On the contrary, there is limited available evidence regarding the effectiveness and safety of these drugs in infants and children with MDR TB. The use of second-line drugs not approved for use in children may be necessary to treat a life-threatening disease such as MDR TB, but it requires careful monitoring to quickly recognize the occurrence of dose- and duration-dependent adverse drug reactions.     

Management of multidrug-resistant tuberculosis in children: a survival guide for paediatricians

WHO estimated that of 9.4 million cases of tuberculosis (TB) worldwide in 2008, 440,000 (3.6%) had multidrug-resistant (MDR)-TB. Childhood TB is estimated at 10-15% of the total burden, but little is known about the burden of MDR-TB in children. Children in close contact with MDR-TB cases are likely to become infected with the same resistant strains and are vulnerable to develop disease. Although MDR-TB is a microbiological diagnosis, children should be treated empirically according to the drug susceptibility result of the likely source case, as often cultures cannot be obtained from the child. MDR-TB treatment in children is guided by the same principles, using the same second-line drugs as in adults, with careful monitoring for adverse effects. Co-infection with HIV poses particular challenges and requires early initiation of antiretroviral therapy. Preventive therapy for high-risk MDR-TB contacts is necessary, but no consensus guidance exists on how best to manage these cases. Pragmatic and effective Infection control measures are essential to limit the spread of MDR-TB.     

Failure of chemoprophylaxis with standard antituberculosis agents in child contacts of multidrug-resistant tuberculosis cases

BACKGROUND: There is little published information on optimal chemoprophylaxis for children with multidrug-resistant tuberculosis (MDR-TB) contacts. Current guidelines of World Health Organization suggest that isoniazid (INH), the standard first-line chemoprophylaxis, be used for those exposed to MDR-TB. METHODS: This is a retrospective review of medical records of 5 children residing in the Western Cape Province, South Africa, who developed MDR-TB while receiving conventional chemoprophylaxis with either INH or a combination of INH, rifampin, and pyrazinamide. RESULTS: Adult MDR-TB source cases were identified for all children and resistance patterns of patient and source case isolates matched in all cases. The median age of the patients was 0.4 years. One patient participated in a trial of INH chemoprophylaxis for HIV-infected children. Four HIV-uninfected infants presented with TB-related symptoms several months after being given chemoprophylaxis because of a known source case. Stigmata of TB were cough >3 weeks in 4, weight loss or a history of failing to thrive in 3, fever in 2 infants, and reported night sweats in 1. Chest radiographs at diagnosis revealed lymphadenopathy, lobar opacification, and airway narrowing. All patients were treated for varying time periods at a TB referral institution in the Western Cape. CONCLUSIONS: Standard, first-line anti-TB agents were inadequate to prevent MDR-TB in children exposed to MDR-TB contacts. Second-line chemoprophylaxis, reflecting the susceptibility profile of the source case's isolate, with at least 2 drugs with activity against the drug-resistant isolate for 6-12 months should be considered.     

Evaluation of young children in household contact with adult multidrug-resistant pulmonary tuberculosis cases.

BACKGROUND: The prevention and management of multidrug-resistant (MDR) tuberculosis has received much attention, but little attention has been given to children with MDR tuberculosis or children in contact with adults with MDR tuberculosis. The aim of this study was to determine the prevalence of tuberculous infection and disease in childhood contacts of adults with MDR pulmonary tuberculosis. METHOD: All children <5 years of age in household contact with 75 recently diagnosed adults with MDR pulmonary tuberculosis were evaluated. Evaluation included clinical examination, tuberculin skin test, chest radiography and culture for Mycobacterium tuberculosis from gastric aspirates. RESULTS: One hundred twenty-eight children, median age 27 months, were evaluated. Fifty children had recent contact with other adult tuberculosis cases. Sixty-six children previously had chemoprophylaxis or treatment of whom 36 defaulted treatment or received insufficient chemoprophylaxis. One child had HIV infection. Forty-seven children were classified as noninfected, 66 were considered infected only (Mantoux test, > or = 15 mm) and 15 had disease. Three children, who had not previously received antituberculosis drugs, had positive cultures for M. tuberculosis; all were multidrug-resistant. CONCLUSION: This study documents the transmission of multidrug-resistant M. tuberculosis to childhood contacts, the development of disease in these contacts and the importance of knowing the index case's M. tuberculosis susceptibility pattern in choosing a proper treatment regimen for the childhood contact.     

Transmission of mycobacterium tuberculosis to and from children and adolescents

Although adult-type pulmonary tuberculosis frequently arises from a long-dormant infection with Mycobacterium tuberculosis, children usually develop tuberculosis as a direct complication of the initial infection. Adults with pulmonary tuberculosis frequently are infectious, but children with typical primary tuberculosis—enlarged hilar or mediastinal lymph nodes with or without bronchial obstruction and subsequent atelectasis—rarely, if ever, transmit the organism to others. This article reviews the pathophysiology of pediatric tuberculosis and the published evidence concerning transmission of M tuberculosis to and from children and adolescents. Children with congenital tuberculosis or older children with the characteristics of adult-type tuberculosis should be considered potentially infectious. However, there is no evidence that children with primary-type tuberculosis infect other individuals. Recommendations are made concerning the handling of children with suspected tuberculosis and their family members in pediatric healthcare settings. Copyright © 2001 by W.B. Saunders Company     

Transmission of tuberculosis to contacts of sputum positive adults in Malawi

Over a period of one year from June 1993 to May 1994, 282 children under 6 years old who were household contacts of sputum positive adults with tuberculosis were evaluated in a screening clinic. Of these, 180 (63.8%) had evidence of tuberculosis, a much higher transmission rate than reported elsewhere. HIV seropositivity was 77.4% in the adult index cases and 18% in the contact children. No increased infectivity to household contacts was detected in HIV seropositive index adults compared with those who were seronegative. Child tuberculosis contact tracing is essential in these families, where transmission of disease is higher than reported elsewhere, and attention to the health needs of the children may be diminished by the high morbidity and mortality among adult family members.     

Transmission of tuberculosis from a seven-year-old child in a Sydney school

OBJECTIVES: To determine whether a 7-year-old child with extrapulmonary and pulmonary tuberculosis (TB) and direct smear positive sputum for acid-fast bacilli was infectious to home and school contacts, and to ascertain potential adult sources of infection for these contacts. METHODS: Contact tracing by Mantoux testing was conducted on 220 children at a primary school and after-school care facility, and 59 selected adults considered potential sources of infection. RESULTS: The participation rate for the children was 98% and 92% for the adults. Mantoux positivity (induration >/= 10 mm, or >/= 15 mm with previous BCG) among children was 13% at the school (anticipated rate 2-3%), 26% among school staff, and 7% among children at the after-school care centre where the index case attended. One exposed adult hospital staff member converted from Mantoux negative to positive. No other cases of TB disease were detected among children or adults tested. CONCLUSION: Although spread of TB from children to others is rare, the findings of this investigation indicate that transmission of TB from a young child to other children and an adult may have occurred, and that sputum testing and contact tracing for sputum smear positive children should be considered.     

Transmission of tuberculosis to contacts of sputum positive adults in Malawi.

Over a period of one year from June 1993 to May 1994, 282 children under 6 years old who were household contacts of sputum positive adults with tuberculosis were evaluated in a screening clinic. Of these, 180 (63.8%) had evidence of tuberculosis, a much higher transmission rate than reported elsewhere. HIV seropositivity was 77.4% in the adult index cases and 18% in the contact children. No increased infectivity to household contacts was detected in HIV seropositive index adults compared with those who were seronegative. Child tuberculosis contact tracing is essential in these families, where transmission of disease is higher than reported elsewhere, and attention to the health needs of the children may be diminished by the high morbidity and mortality among adult family members.     

多重耐药菌的发展趋势

多重耐药菌感染呈现增长趋势,已成为全球性棘手问题,抗菌药物选择方案很少.传统糖肽类药物抗菌活性已呈现下降趋势.虽然新的抗菌药物包括利奈唑胺、达托霉素和替加环素对某些革兰阳性菌感染有较强的抗菌活性,但对于多重耐药革兰阴性菌,包括耐碳青霉烯类铜绿假单胞菌、鲍曼不动杆菌和肠杆菌的治疗,有效药物仅限于多黏菌素和替加环素.多重耐药菌的分布呈动态变化,近年来,多数医疗机构特别是重症监护病房监测的菌株中,以革兰阴性细菌为主,部分地区多重耐药/泛耐药铜绿假单胞菌、鲍曼不动杆菌等呈现迅速增多趋势.应重视和执行多重耐药菌感染的监测、预防、隔离和抗菌药物选择等综合防控策略,以减少多重耐药菌的扩散.     

多重耐药菌的定植与感染

多断耐药菌在重症监护病房的检出率日益增高,确定其为定植还是感染对临床合理使用抗生素、减少耐药菌产生、降低院内感染率十分重要.但如何区分定植与感染是困惑临床医师的一大难题,除了将细菌培养结果与临床症状、体征相结合外,尚应更多地采用一些客观指标来指导临床.本文将对多重耐药菌的定植与感染的定义、关系、判断等作一阐述.     

鲍曼不动杆菌耐药性及防治策略

随着抗生素的广泛应用,多重耐药的鲍曼不动杆菌(MDR-AB)感染发生率迅速上升,对碳青霉烯类抗生素耐药的不动杆菌菌株超过48%,甚至出现对常用抗菌药物全耐药现象.细菌耐药主要是由于产生抗菌药物的灭活酶、外膜蛋白缺失和膜通透性下降以及靶位或外排泵功能改变.对MDR-AB的治疗可选择药物很少,根据药物敏感试验,可选择含舒巴坦制剂、多黏菌素、替加环素、碳氢酶烯类等药物,重症病例建议联合用药.最好的解决耐药性现状的办法是防止耐药菌的传播.良好的手卫生、标准的预防措施、适当的隔离措施、耐药性监测、抗生素管理等是有效的预防方法 .     

多重耐药鲍曼不动杆菌的耐药机制及治疗进展

近年来随着广谱抗生素的大量使用,多重耐药细菌、甚至是泛耐药及全耐药细菌不断产生.鲍曼不动杆菌是一种常见的条件致病菌,目前多重耐药鲍曼不动杆菌(multidrug-resistant acinetobacter baumannii,MDRAB)的院内感染已成为最为棘手的问题之一.MDRAB的耐药机制主要在于产生抗菌药物灭活酶、靶位或细胞功能改变、外膜屏障及药物主动外排泵作用.治疗MDRAB感染的药物包括舒巴坦制剂、碳青霉烯类、多黏菌素类、四环素类及其他药物.但是由于缺乏大规模的临床研究,目前对于MDRAB的治疗尚无统一的规范,儿科的临床经验更少.     

Ventriculitis and choroid plexitis caused by multidrug-resistant Nocardia pseudobrasiliensis

We describe a case of ventriculitis and choroid plexitis caused by a multidrug-resistant Nocardia pseudobrasiliensis in an immunocompetent child. Difficulties establishing an etiologic diagnosis, inconsistencies of antibiotic susceptibility testing, and the side effects of various antimicrobials presented challenges to her treatment and eventual favorable outcome.