Diagnostic efficacy of activated partial thromboplastin time waveform and procalcitonin analysis in pediatric meningococcal sepsis.

OBJECTIVE: A biphasic activated partial thromboplastin time waveform predicts sepsis and disseminated intravascular coagulation in adults. This has not been previously investigated in children. Our aim is to ascertain whether there are changes in the activated partial thromboplastin time waveform in children with meningococcal disease and to compare its diagnostic use with procalcitonin. SETTING: Alder Hey Children's National Health Service Foundation Trust, Liverpool, UK. PATIENTS: Thirty-six children admitted to the hospital for the treatment of suspected meningococcal disease had activated partial thromboplastin time waveform and procalcitonin analysis performed at admission. The light transmittance level at 18 secs was used to quantitate the waveform. Severity of disease was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score, Pediatric Risk of Mortality III score, and the Pediatric Logistic Organ Dysfunction score. MEASUREMENTS AND MAIN RESULTS: Twenty-four children had proven meningococcal disease, 12 had a presumed viral illness, and 20 control subjects were recruited. Transmittance level at 18 secs was lower in children with meningococcal disease and those with a viral illness (p < .0001) and control subjects (p < .0005). Sensitivity and specificity was 0.91 and 0.96 for transmittance level at 18 secs and 0.92 and 1 for procalcitonin in identifying meningococcal disease. There was a significant difference in procalcitonin between children with meningococcal disease and those with a viral illness and control subjects (p < .0005). A negative correlation was found between transmittance level at 18 secs and length of hospital stay (p < .0001), C-reactive protein (p < .0001), procalcitonin (p < .0001), Glasgow Meningococcal Septicaemia Prognostic Score (p < .01), Pediatric Risk of Mortality III score (p < .0001), and Pediatric Logistic Organ Dysfunction score score (p < .0001). CONCLUSION: The activated partial thromboplastin time waveform is abnormal in children with meningococcal disease and may be a useful adjunct in the diagnosis and management of sepsis in children.

Glycopeptide insensitive Staphylococcus aureus subdural empyema treated with linezolid and rifampicin.

A 4-year-old boy had surgical debulking of a cerebral astrocytoma followed by chemotherapy. He developed a subdural empyema with a teicoplanin and methicillin resistant Staphylococcus aureus. He was successfully treated with surgical drainage and 6 weeks of antibiotic therapy which included linezolid, rifampicin and metronidazole. Linezolid may be successful in treating other CNS infections caused by antibiotic resistant gram-positive organisms.

A survey of tuberculosis services in the UK.

AIM: To determine the provision of services for children with tuberculosis (TB) living in the UK. METHOD: A postal questionnaire was sent to the most appropriate paediatrician and adult physician in every acute hospital trust in the UK. Information was sought on inpatient and outpatient services for children with TB and for children in contact with TB. RESULTS: Responses were received from 323 individuals in 199 of the 205 trusts approached. The median number of children with TB seen per year at each trust was 1.5 (range 0-30). Inpatients were nearly all admitted to paediatric wards (197 (99%) trusts). In 141 trusts (71%) they were looked after solely by paediatricians or jointly by paediatricians and physicians (47 trusts, 24%). 132 (66%) trusts stated there was a named consultant for children with TB. Negative pressure isolation rooms were reported to be available for children in 42 trusts (21%). As outpatients, children with TB were seen in paediatric clinics in 163 (82%) trusts. Only 10 (5%) trusts had designated family TB clinics. Children in contact with TB were managed by paediatricians in 81 (38%) trusts, by physicians in 67 (34%) trusts and jointly in 51 (26%) trusts. 161 (81%) trusts had access to a TB nurse and directly observed therapy (DOTS) was available in 116 (58%) trusts. CONCLUSIONS: Many paediatricians see few children with TB, but most children with TB are looked after by general paediatricians alone. The survey supports national recommendations to develop family clinics and clinical service networks for children with TB, which may improve the care of these children.

Central venous catheter infection with Bacillus pumilus in an immunocompetent child: a case report.

BACKGROUND: Bacillus organisms are common laboratory contaminants. The majority of Bacillus bacteraemias are transient and not clinically significant. Clinically significant infection due to Bacillus species is rare and mostly due to Bacillus cereus infections in immuno-compromised hosts. CASE PRESENTATION: We report a case of central venous catheter infection with Bacillus pumilus in an immunocompetent child with tufting enteropathy on long-term parenteral nutrition (PN). There were three episodes of central venous catheter infection with Bacillus pumilus in three months. Despite adequate and appropriate use of intravenous antibiotics, the infection failed to clear resulting in the need for removal of the catheter for complete cure. CONCLUSION: Bacillus species can cause clinically significant central venous catheter infection, even in an immunocompetent host. Despite adequate antibiotic treatment, the central venous catheter may need removal for complete cure.

Prospective study of community needlestick injuries.

Fifty three children were referred following community needlestick injuries, August 1995 to September 2003. Twenty five attended for serology six months later. None were positive for HIV, or hepatitis B or C. Routine follow up after community needlestick injury is unnecessary. HIV post-exposure prophylaxis should only be considered in high risk children.

Meningitis without a petechial rash in children in the Hib vaccine era.

AIMS: (1) To determine the causes of meningitis in children immunized with Hib vaccine, presenting without a non-blanching rash; (2) to review the use of dexamethasone in this group. METHOD: Retrospective review of all children with more then 10 white cells/mm(3) in their cerebrospinal fluid (CSF), admitted between January 1998 and August 2002. Children were excluded if they had a non-blanching rash on admission or if their discharge diagnosis was not meningitis. Local guidelines recommended dexamethasone to be given before antibiotics for children with meningitis and no rash. RESULTS: One hundred and eight children were identified. Causes of proven meningitis were: viral 41 (enterovirus 40), bacterial 22. CSF culture or PCR was the only diagnostic test in 31 children. Dexamethasone was given to 16 children. Length of admission was shorter in children with viral compared with bacterial meningitis (4 vs 8 days; P < 0.0001). SUMMARY: Viral meningitis is the commonest cause of meningitis without rash. Enteroviral PCR was the most useful test and needs to be widely available. Confirmation of enteroviral meningitis allowed early discharge. Few children were given dexamethasone, but only 5/108 may have benefited. CONCLUSIONS: The most common cause of meningitis without a rash in British children is enterovirus. The use of dexamethasone in children with meningitis without a rash should be reconsidered or, at least, individualised.

Best paediatric evidence; is it accessible and used on-call?

BACKGROUND: Paediatricians wanting to use evidence based medicine (EBM) strategies, need to be able to track down and critically appraise evidence. This requires access to quality filtered resources (for example, Cochrane Library), bibliographic databases (for example, Medline), and paediatric journals. AIMS: To determine whether paediatricians have access to these resources when on-call and if they use them to answer clinical questions. METHOD: A telephone survey of paediatric and neonatal units was performed during November 2001. The "paediatrician-on-call" was asked whether they could access Medline, Cochrane, and paediatric journals, and if they used these when on-call. RESULTS: Paediatric trainees were available in 87 of the 97 units contacted. All except one had access to Medline; although only 56 (64%) could do this near their ward. Eighty had access to Cochrane. Thirteen (15%) could not gain access to their library out-of-hours. All except one department had local guidelines, with 71% having >15 guidelines. Access to any of the top seven "best evidence" paediatric journals varied from 64% to 100%. Only 26% of trainees had read the evidence based section of Archives of Disease of Childhood, Archimedes. Many trainees claimed to use guidelines when on-call (61; 70%), but few used Medline (14; 16%). CONCLUSIONS: Paediatric trainees mostly have access to facilities to help them to track down and critically appraise evidence. However, few of them have used it to help make clinical decisions when on-call. Many of the doctors contacted said they used local guidelines as their source of information on-call.

Fever in returned travellers: a prospective review of hospital admissions for a 2(1/2) year period.

AIM: To identify causes of fever, treatable diseases, and the most helpful investigations in febrile children, who had travelled to the tropics or subtropics in the preceding year. METHODS: Prospective observational study of all admissions to children's wards in a district general hospital in Birmingham between January 1997 and July 1999. Children with fever >37.5 degrees C and a history of travel to the tropics or subtropics in the preceding 12 months were included. Data were available on 153/162 children; median age was 5 years (range 0.1-15). A total of 133 (85%) children had visited South Asia; only 18/135 had received malarial prophylaxis. Median time to presentation after travel was four weeks. Children were investigated with full blood count, blood film, and stool culture. Other investigations were performed at the discretion of the admitting paediatrician. RESULTS: Diarrhoeal illness (n = 41) and malaria (n = 22) were the most common diagnoses. A treatable cause for the febrile illness was identified in 70 (46%) children. One or more investigations were positive in 60% of children. Stool culture (17% positive) and blood film (14% positive) were the most helpful investigations. Platelet counts greater than 190 x 10(9)/l had a negative predictive value of 97% for malaria in this population. CONCLUSIONS: Children who present with fever and have travelled to the tropics or subtropics in the preceding year, often have a treatable infection. They should have a full blood count, blood film for malarial parasites, stool culture, blood culture, and chest x ray.

Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash.

BACKGROUND: Procalcitonin (PCT), a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. PCT has been proposed as an earlier and better diagnostic marker than C reactive protein (CRP) and white cell count (WCC). This comparison has never been reported in the differentiation of meningococcal disease (MCD) in children presenting with a fever and rash. AIM: To determine if PCT might be a useful marker of MCD in children presenting with fever and rash. METHODS: PCT, CRP, and WCC were measured on admission in 108 children. Patients were classified into two groups: group I, children with a microbiologically confirmed clinical diagnosis of MCD (n = 64); group II, children with a self limiting illness (n = 44). Median ages were 3.57 (0.07-15.9) versus 1.75 (0.19-14.22) years respectively. Severity of disease in patients with MCD was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). RESULTS: PCT and CRP values were significantly higher in group I than in group II (median 38.85 v 0.27 ng/ml and 68.35 v 9.25 mg/l; p < 0.0005), but there was no difference in WCC between groups. Sensitivity, specificity, and positive and negative predictive values were higher for PCT than CRP and WCC. In group I, procalcitonin was significantly higher in those with severe disease (GMSPS >/=8). CONCLUSIONS: PCT is a more sensitive and specific predictor of MCD than CRP and WCC in children presenting with fever and a rash.

Improving promptness of antibiotic treatment in meningococcal disease.

OBJECTIVES: Delays in parenteral antibiotic treatment may contribute to the high mortality in meningococcal disease. This study aimed to record "door to needle" time in children with meningococcal disease before and after the introduction of a specific teaching programme about the disease. METHODS: "Door to needle" time in 33 children with meningococcal disease, admitted June 1995-December 1996, were studied. Regular teaching sessions encouraging prompt treatment were started in January 1997. "Door to needle" time was then studied for 42 children admitted January 1997-December 1998. RESULTS: More of the second cohort attended accident and emergency (A&E) directly (9 of 33 v 24 of 42; p=0.01) rather than being referred by a GP. Similar proportions received pre-admission antibiotics from a GP (8 of 24 v 5 of 18). Mortality was similar in the two groups (2 of 33 v 5 of 42). "Door to needle" time was significantly shorter in the second cohort in those with a typical rash (median 60 minutes v 18 minutes; p=0.0004). Only 1 of 23 (4%) children in the second cohort with a typical, petechial rash waited more than 60 minutes for antibiotics, compared with 6 of 24 in the first cohort (p=0.06). CONCLUSIONS: Significant improvements in "door to needle" time in meningococcal disease can be achieved when awareness is heightened by regular teaching. Those with a typical, petechial rash can be treated within 60 minutes of arrival. Strategies to improve immediate treatment of meningococcal disease should include education of A&E staff, especially as an increasing proportion of cases present directly to A&E.

Clinical studies : an overview.

Disease caused by Neisseria meningitidis is a worldwide problem (1). Epi- demics of meningococcal disease regularly occur in the "meningitis belt" of sub-Saharan Africa and in Asia (2-5) and high or increasing levels of endemic meningococcal disease have been reported recently in the UK (6), New Zealand (7), Cuba (8), Brazil (9), Norway (10), and the Pacific Northwest of the United States (11). Meningococcal disease predominantly affects children and has a high mortality, which has remained unchanged for 30 years, despite advances in antibiotics and intensive care (12). Efforts have therefore been made to understand the pathophysiology of the disease and use this knowledge to improve treatment and develop novel therapies.

Do presenters to paediatric meetings get their work published?

BACKGROUND: Research presented to a scientific meeting is inaccessible to clinicians, unless it is also published in a cited journal. AIMS: To assess the publication rate of studies presented to two UK national paediatric meetings: the Paediatric Research Society (PRS) and the British Paediatric Association (BPA). METHODS: A Medline search in December 1999 for the first authors of all plenary abstracts presented in 1996. If not found, authors contacted by postal questionnaire. RESULTS: Information was obtained on 88/89 presentations. Twenty five of 48 PRS and 31 of 40 BPA studies were published in Medline listed journals. The major reason for non-publication was that they had not been submitted (PRS 15/48, BPA 6/40). Some authors were still hoping to do so (PRS 7, BPA 2). Other reasons were: publication in other forms (theses, book chapters, non-Medline journals) (PRS 5, BPA 2), or still being reviewed (PRS 3, BPA 1). Ten of 11 randomised, controlled trials were published, but only 20 of 37 observational studies were submitted and published. CONCLUSION: Presenters to paediatric meetings need help in submitting and publishing their work.

Increasing microbiological confirmation and changing epidemiology of meningococcal disease on Merseyside, England.

OBJECTIVES: To determine, for the last 5 years in children on Merseyside with clinical meningococcal disease (MCD), the impact on diagnostic yield of newer bacteriologic methods; bacterial antigen detection (AD) and polymerase chain reaction (PCR). METHODS: Prospective data collection at Royal Liverpool Children's Hospital over two epochs: 1 September 1992 to 30 April 1994 (epoch A, n = 126) and 17 November 1997 to 15 September 1998 (epoch B, n = 85). RESULTS: Epoch A was compared with epoch B. Diagnosis was confirmed by detection of meningococci in 78 of 126 (61.9%) versus 64 of 85 (75.3%, P = 0.04), but with a significantly lower rate of positive blood and cerebrospinal fluid culture in the later epoch. The proportion of cases receiving penicillin pretreatment was unchanged at 32%, but the proportion undergoing lumbar puncture decreased significantly. Median ages were higher in epoch B: 1.7 years versus 2.49 years (P = 0.013, Mann-Whitney). There was a significant increase in the proportion of cases due to serogroup C (14/78 (18%) versus 30/64 (46.9%), P = 0.001). CONCLUSIONS: Culture detection of meningococci from children with MCD has reduced, as less lumbar punctures are done. However, improved diagnosis by PCR and AD has increased microbiological confirmation overall. Serogroup C disease and the median age of cases continue to rise.

Admission cortisol and adrenocorticotrophic hormone levels in children with meningococcal disease: evidence of adrenal insufficiency?

OBJECTIVE: To measure admission cortisol and adrenocorticotrophic hormone (ACTH) levels in children with meningococcal disease to try and determine the prevalence of adrenal insufficiency. DESIGN: Prospective observational study. SETTING: Pediatric departments of four hospitals in Merseyside, United Kingdom. PATIENTS: Ninety-six children with meningococcal disease; 29 with hypotension, ten of whom died. MEASUREMENTS AND MAIN RESULTS: Admission cortisol, ACTH, and proinflammatory cytokine levels were measured. Serial cortisol levels also were measured during the first 48 hrs. Significantly lower cortisol levels were found in those who died compared with survivors. Significantly higher ACTH levels also were found in those who died. However, no child had a cortisol level <5 microg/dL (<138 nmol/L) implying definite adrenal insufficiency. Three of 29 children with hypotension had plasma cortisol levels implying possible adrenal insufficiency (<18 microg/dL [<497 nmol/L]), but high ACTH levels were only found in one of those three. Cortisol levels decreased significantly after antibiotic treatment, unless steroid therapy was administered. ACTH levels did not correlate with cortisol or proinflammatory cytokine levels. CONCLUSIONS: Children with meningococcal disease have a wide range of initial plasma cortisol levels, with lower levels found in those who die. Many factors may affect cortisol levels, but adrenal insufficiency is probably uncommon.