Invasive candidiasis in pediatric intensive care in Greece: a nationwide study.

PURPOSE: To record the practices for prevention and management of invasive candidiasis in the PICU and investigate the epidemiology of candidiasis and its outcome nationwide. METHODS: A multicenter national study among PICUs throughout Greece. A questionnaire referring to local practices of prevention and management of candidemia was filled in, and a retrospective study of episodes that occurred during 5 years was conducted in all seven Greek PICUs. RESULTS: Clinical practices regarding surveillance cultures, catheter replacement protocols and antibiotic use were similar, although the case mix differed. In all PICUs prophylactic antifungal treatment was administered in transplant and neutropenic oncology patients. Discrepancy existed between PICUs concerning the first-line antifungal agents and treatment duration of candidemia. Twenty-two candidemias were nationally recorded between 2005 and 2009 with a median incidence of 6.4 cases/1,000 admissions. Median age was 8.2 (0.3-16.6) years. Candida albicans was isolated in 45.4 % of episodes followed by Candida parapsilosis (22.7 %). Common findings were presence of central venous and urinary catheters as well as mechanical ventilation and administration of antibiotics with anti-anaerobic activity in almost all patients with candidemia. Total parenteral nutrition was administered to five (22.7 %) patients. Most of the patients had a chronic underlying disease; five were oncology patients, and two-thirds of those with candidemia were colonized with Candida spp. Lipid amphotericin B formulations were the predominant therapeutic choice (54.5 %). Thirty-day mortality was 18.2 %. CONCLUSION: This first national study adds information to the epidemiology of candidemia in critically ill children. In these special patients, candidemia has a relatively low incidence and tends toward non-albicans Candida preponderance.

Invasive meningococcal disease in children in Greece: comparison of serogroup A disease with disease caused by other serogroups.

Although invasive meningococcal disease caused by serogroup A is not prevalent in developed countries, a considerable number of cases were recently recorded in Greece. In this study, serogroup A meningococcal disease was compared prospectively with meningococcal disease caused by other serogroups, using similar settings of testing and management during a 5-year period between 1999 and 2003. The Neisseria meningitidis serogroup was determined in 262 cases. Serogroup B predominated, accounting for 158 (60%) of the cases. Serogroup A was second most frequent (19%), followed by serogroups W135 (11%), C (8%), and Y (2%). No cases due to serogroup C were recorded during the last year of the study. Patients with serogroup A disease were older and had a milder course compared to patients infected with serogroups B or C. Toxic appearance, purpura, thrombocytopenia, abnormal coagulation tests, and the need for admission to the intensive care unit, fluid resuscitation, inotropic drugs, and mechanical ventilation were less common. Although morbidity and mortality were lower in these patients, the differences were not significant. Serogroup B is predominant in our area, and the introduction of an effective vaccine against it is a priority. Serogroup A has emerged as the second most common serogroup, but the illness associated with it is milder.

Paraquat poisoning in a family.

A familial occurrence of acute paraquat (PQ) poisoning is reported. The mother administered a PQ solution to their 3 children aged 8 y, 6 y and 15 mo and then ingested an unknown amount of the herbicide herself. In the absence of history or diagnostic signs, the poisoning was initially misdiagnosed as gastroenteritis. Thirty h after the ingestions, serum PQ concentrations of the children were 60, <6 and 25 ng/ml respectively. Hemoperfusion was performed on all patients, and 2 of the children also received plasmapheresis and erythropheresis. The 3 children recovered fully but the mother died. According to these patients' data, the extracorporeal techniques had little effect on PQ removal, and the decreases in serum PQ were related to its urinary excretion.

Non-Q wave acute myocardial infarction in acute meningococcemia in a 10-year-old girl.

INTRODUCTION: Children with acute meningococcemia may have impaired myocardial function resulting in low cardiac output despite normal intravascular volume. Severe meningococcal infection has been associated with acute interstitial myocarditis, endocarditis, and pericarditis, but not with myocardial infarction. CASE: We present the case of a 10-year-old girl with positive family history for premature myocardial infarction who sustained an acute myocardial infarction temporally related to meningococcemia. DISCUSSION: This is the first pediatric case of non-Q wave acute myocardial infarction associated with purpura fulminans in meningococcemia. Similarly, the association of high troponin I levels and meningococcemia has not been described previously. Although, the patient's genetic predisposition for myocardial infarction might have been a potential contributing factor, there was no angiographic evidence of coronary artery disease in this patient. Thereby, other factors related to shock, endotoxin, microthrombi of meningococcemia, and their treatment might have been also contributing. We propose possible mechanisms for this rare but serious complication of meningococcemia and review the literature.

Correlation between serum IL-6 and CRP levels and severity of head injury in children.

OBJECTIVE: To examine interleukin-6 (IL-6) and C-reactive protein (CRP) release in children with head injury (HI) and investigate if there is a correlation between the levels of these two proteins and the severity of HI. DESIGN: Prospective clinical investigation. SETTING: Eight-bed paediatric intensive care unit in a university hospital. PATIENTS: Forty-five children were followed up for 4 days after HI and their serum IL-6 and CRP levels were measured. MEASUREMENTS AND RESULTS: Peak serum IL-6 levels occurred 4 h postinjury, decreasing over time. CRP was normal 4 h after injury, then increased reaching peak levels in 48 h. Children with admission Glasgow Coma Scale (GCS) scores of 8 or less had higher IL-6 levels compared to children with GCS scores higher than 8, 4 and 12 h post-injury (p<0.01 and p<0.05, respectively). IL-6 was higher in children with admission PRISM scores of 10 or more than in those with PRISM scores lower than 10 at 4 and 12 h (p<0.05). CRP levels were higher in patients with GCS scores of 8 or less compared to patients with GCS scores higher than 8 at 24, 48 and 72 h (p<0.05, p<0.02 and p<0.02, respectively) . Patients with PRISM scores of 10 or more had higher CRP levels compared to those with PRISM scores lower than 10 at 24, 48 and 72 h (p<0.05). Peak CRP levels correlated well with peak IL-6 levels (r = 0.49, p<0.001). No correlation between IL-6 or CRP levels and mortality or clinical outcome was found. CONCLUSIONS: Serum IL-6 and CRP levels are elevated in children with HI and there is a relation between the severity of HI and the levels of these proteins. There was no correlation between IL-6, CRP and outcomes of the patients.

Lamotrigine childhood overdose.

A 2-year-old male developed generalized tonic-clonic seizure activity, tremor of limbs, muscle weakness, ataxia, and hypertonia after he swallowed 16 50-mg tablets of lamotrigine. His vital signs were normal, as were electroencephalography and laboratory investigation tests. The urine toxicologic screen revealed no other drugs. Treatment included midazolam and gastric lavage followed by activated charcoal and fluid loads. Symptoms resolved within 24 hours, and the child was discharged without any further complications. Serial blood samples revealed plasma lamotrigine levels at the high adult therapeutic range (3.8 mg/L) but a slow elimination rate. This is the first report of seizure activity reported in a patient receiving an overdose of lamotrigine. However, no evident concentration-effect-side-effect relationship has been established in children. Interestingly in this child, lamotrigine overdose presented exclusively with treatment-emergent neurologic abnormalities, sparing all other systems.

Assessment of the effect of candidate anti-inflammatory treatments on the interaction between meningococci and inflammatory cells in vitro in a whole blood model.

A wide range of immunomodulating agents are now available which may be of benefit in reducing inflammatory cell activation in meningococcal sepsis. In order to facilitate selection of candidate anti-inflammatory agents for clinical trials, we have used an in vitro whole blood model to evaluate the effects on meningococcal induced neutrophil and monocyte activation, of dexamethasone, prostacyclin, pentoxifylline and a human IgM anti-lipid A monoclonal antibody (HA-1A). Known concentrations of heat and penicillin killed meningococci were added to whole blood and the time course of cellular activation was determined. Using elastase alpha 1-antitrypsin (elastase-alpha 1-AT) and TNF alpha production as markers of neutrophil and monocyte activation respectively, plasma levels of elastase-alpha 1-AT and TNF alpha were found to increase in a dose-dependent manner. Elastase-alpha 1-AT was detected early, with most release occurring between 15-30 min whereas TNF alpha was detected later, between 120-180 min. Dexamethasone, prostacyclin and pentoxifylline caused a dose-dependent inhibition of TNF alpha release but had no effect on elastase release. HA-1A had no effect on either TNF alpha or elastase release. This model may be useful in determining the sequence of inflammatory cell activation and in selecting candidate anti-inflammatory agents for evaluation in clinical trials.

Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene?

Inherited defects in specific components of the immune system have provided many clues to the immunological mechanisms underlying resistance to microbial infection. We report a familial immune defect predisposing to disseminated atypical mycobacterial infection in childhood. 6 children with disseminated atypical mycobacterial infection and no recognised form of immunodeficency were identified. Four, including two brothers, come from a village in Malta, and two are brothers of Greek Cypriot origin. They presented with fever, weight loss, lymphadenopathy, and hepatosplenomegaly. They had anaemia and an acute phase response. A range of different mycobacteria (Mycobacterium fortuitum, M chelonei, and four strains of M avium intracellulare complex) were isolated. Treatment with multiple antibiotics failed to eradicate the infection, although treatment with gamma interferon was associated with improvement. Three have died and the surviving children have chronic infection. Tumour necrosis factor-alpha production in response to endotoxin and gamma-interferon was found to be defective in affected patients and their parents. T-cell proliferative responses to mycobacterial and recall antigens were reduced in parents of affected children and gamma-interferon production was diminished in the affected patients and their parents. Clinical and immunological features suggest that these patients are phenotypically similar to Lsh/Ity/Bcg susceptible mice. Understanding of this defect may provide insights into the mechanisms responsible for susceptibility to mycobacteria.