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.

Subclinical VZV reactivation in immunocompetent children hospitalized in the ICU associated with prolonged fever duration.

A prospective observational study was conducted to examine whether asymptomatic VZV reactivation occurs in immunocompetent children hospitalized in an ICU and its impact on clinical outcome. A secondary aim was to test the hypothesis that vaccinated children have a lower risk of reactivation than naturally infected children. Forty immunocompetent paediatric ICU patients and healthy controls were enrolled. Patients were prospectively followed for 28 days. Clinical data were collected and varicella exposure was recorded. Admission serum levels of TNF-a, cortisol and VZV-IgG were measured. Blood and saliva samples were collected for VZV-DNA detection via real-time PCR. As a comparison, the detection of HSV-DNA was also examined. Healthy children matched for age and varicella exposure type (infection or vaccination) were also included. VZV reactivation was observed in 17% (7/39) of children. Children with VZV reactivation had extended duration of fever (OR = 1.17; 95% CI, 1.02-1.34). None of the varicella-vaccinated children or healthy controls had detectable VZV-DNA in any blood or saliva samples examined. HSV-DNA was detected in saliva from 33% of ICU children and 2.6% of healthy controls. Among children with viral reactivation, typing revealed wild-type VZV and HSV-1. In conclusion, VZV reactivation occurs in immunocompetent children under severe stress and is associated with prolonged duration of fever.

Liposomal amphotericin B in critically ill paediatric patients.

WHAT IS KNOWN AND OBJECTIVE: Literature provides much evidence regarding liposomal amphotericin B treatment for fungal infections in neonates and infants. Relevant data regarding critically ill paediatric patients of older age are scarce. We aimed to present our experience regarding liposomal amphotericin B use in critically ill paediatric patients from a tertiary-care paediatric hospital in Athens, Greece. METHODS: We prospectively identified all paediatric patients who received treatment with liposomal amphotericin B in the intensive care unit of a tertiary-care paediatric hospital during a 3-year period (2005-2008). Data were retrieved from the evaluation of the available medical records. RESULTS AND DISCUSSION: Twenty-three (nine females, mean age: 26·4 months, range: 5-39 months) critically ill paediatric patients were included; 12 had malignancy. In 16 of the 23 included children, liposomal amphotericin B was administered for the treatment of confirmed fungal infections (all but one were invasive), whereas in seven patients, it was used as pre-emptive treatment. One patient received voriconazole concomitantly. Eleven of the 16 children with documented infections were cured; five improved. Six of the seven children who received pre-emptive treatment also showed clinical improvement. Nine deaths were noted, all attributed to underlying diseases. Two cases of hepatotoxicity and one case of nephrotoxicity (all leading to drug-discontinuation) occurred. Seven and five cases of mild reversible hypokalaemia and hyponatraemia, respectively, were also noted. WHAT IS NEW AND CONCLUSION: According to the findings of our small case series, liposomal amphotericin B may provide a useful treatment option for fungal infections of vulnerable critically ill paediatric patients with considerable comorbidity.

Ciprofloxacin in critically ill children.

Data regarding the use of fluoroquinolones in critically ill children are scarce. We present our experience regarding the use of ciprofloxacin in this specific patient population. We prospectively identified all paediatric patients who received ciprofloxacin treatment in the intensive care unit of the tertiary care P. & A. Kyriakou Children's Hospital during a three year period (2005 to 2008). Eighteen paediatric patients (mean age 23 months, 12 females) who received intravenous ciprofloxacin were identified. Various underlying diseases, including malignancy and immunodeficiency, were observed. None of the evaluated patients had cystic fibrosis. Fourteen patients had bacteraemia (mainly caused from Gram-negative pathogens), one had Stenotrophomonas maltophilia pneumonia, while no pathogen was identified in three patients. The latter patients received ciprofloxacin due to the severity of their clinical manifestations. All patients with microbiologically documented infections recovered. Three deaths attributed to the underlying diseases were noted. Within a 10-day follow-up, two cases of diarrhoea, one case of vomiting and one case of reversible supraventricular tachycardia were noted. No case of QT prolongation was noted. The short-term follow-up hampered any assessment of joint and cartilage toxicity, potentially associated with ciprofloxacin treatment. Our study suggests that ciprofloxacin may be a useful option for critically ill children without cystic fibrosis. Even though firm conclusions regarding the safety profile of ciprofloxacin in critically ill children could not be drawn, our study provides useful information regarding short-term adverse events associated with ciprofloxacin.

Thrombotic thrombocytopenic purpura: prospective neurologic, neuroimaging and neurophysiologic evaluation.

BACKGROUND AND OBJECTIVES: Neurologic symptoms are present in 60% of patients with thrombotic thrombocytopenic purpura (TTP) on initial examination and ultimately develop in about 90% of cases during the course of the disease. Despite central nervous system involvement being frequent, abnormalities in the brain of patients with TTP are infrequent on neuroimaging (CT/MRI) and neurophysiologic (EEG) evaluation, often reversible and mainly limited to symptomatic stages of the disease. The aim of our study was to establish the value of a complete neurologic screening as part of the work up of TTP. DESIGN AND METHODS: We prospectively evaluated 16 TTP patients, performing serial neurologic, neuroimaging and EEG examinations, independently of the presence of an objective central nervous system involvement. RESULTS: Our study shows that a complete neurologic evaluation is of modest help in improving the diagnosis of TTP, but may be useful for the neurologic management. INTERPRETATION AND CONCLUSIONS: Accurate neuroimaging and, especially, EEG evaluation and monitoring allowed us to identify patients who could benefit from anticonvulsive therapy, avoiding the unnecessary administration of the latter. The prognostic utility of complete neurologic screening in TTP remains to be conclusively demonstrated in larger prospective neurologic studies.

Epileptic patients refractory to drug therapy.

We compared two groups of patients with idiopathic epilepsy, 41 patients whose seizure frequency was not controlled by adequate therapy and 39 patients in good seizure control, in respect of hematology, kidney and liver function tests, serum IgG, IgA and IgM concentrations and drug concentrations. The only difference that emerged were in the serum immunoglobulins, which were raised in the drug refractory group, significantly (p less than 0.01) so in the case of IgG. Failure of seizure control did not depend on inadequacy of drug dose or of blood concentration. Although the serum Ig changes do not warrant the assumption of an immunological origin for drug resistance, they do suggest a useful research line.

Periodic activity in electroencephalography.

We report ana analysis of 12 cases in which periodic activity was observed in more than one EEG recording in patients with subacute sclerosing panencephalitis (4 cases), encephalitis of unknown etiology (1 case) and vascular disease (7 cases). In the patients with infective disease periodic high voltage potentials were elicited from all over the brain and the background rhythm was markedly impaired. In the patients with vascular disease the bursts were localized, reversible and sometimes recurrent. The impression gained is that a periodic EEG pattern denotes a pathological modification of behavior of the cerebral cortex rather than any particular disease.

Effects of carotid compression, as assessed by near infrared spectroscopy, upon cerebral blood volume and hemoglobin oxygen saturation.

Near infrared spectroscopy, a recently developed optoelectronic technique, has been studied as a possible method of monitoring the adequacy of cerebral perfusion in 22 patients who were candidates for carotid endarterectomy. Using this technique, changes in haemoglobin volume, haemoglobin oxygen saturation and redox level of cytochrome-c-oxidase were recorded from the frontoparietal region during routine carotid compression tests performed under continuous electroencephalographic (EEG) monitoring. A highly significant association was found between EEG slowing, indicating impaired cerebral function, and a fall in haemoglobin volume and oxygen saturation, indicating a reduced blood and oxygen supply to the brain (Fisher exact test, P less than 10(-5]. In a few tests haemoglobin volume and oxygen saturation were reduced without changes in the EEG recording. This study raises new issues concerning the compensatory mechanisms taking place during carotid occlusion and suggests that near infrared spectroscopy might be useful in monitoring the blood and oxygen supply to the brain during carotid endarterectomy.

Anticonvulsant therapy and its possible consequences on peripheral nervous system: a neurographic study.

We studied 80 epileptic patients receiving antiepileptic drugs in mono- or polytherapy. For every patient, peroneal and median nerve motor conduction velocities and median nerve sensory conduction velocity were calculated. The average conduction velocity values were remarkably slower than those of a group of 55 normal subjects. We found at least one abnormal conduction velocity value in patients treated with carbamazepine (CBZ), phenobarbital, and phenytoin. There was no specific prevalence of one of these drugs. We found a noticeable relationship between conduction velocity slowing and daily dosage for CBZ only. There was no relationship between conduction velocity slowing and drug blood levels or duration of treatment.

Influence of glucoregulation with continuous subcutaneous insulin infusion on nerve conduction velocity and beat to beat variation in diabetics.

Limited and contrasting data are available on the relationship between metabolic control and diabetic neuropathy. In eight type I diabetics peripheral and autonomic neuropathy were studied, first in conditions of poor metabolic control and then after one and three months during which an improved control of glycemic levels had been obtained by continuous subcutaneous insulin infusion. Autonomic neuropathy was investigated by evaluating beat to beat variation during deep breathing; peripheral neuropathy by measuring maximum motor conduction velocity of peroneal and median nerves and sensory conduction velocity of median nerve. Our data showed significant improvement of motor conduction velocity in both nerves studied, whilst sensory conduction velocity did not show any significant variation. The changes observed in beat to beat variation in five subjects with initially abnormal scores might reflect an improvement in autonomic nervous function, even if long-term studies are needed.

[Calcium-phosphorus changes in chronic anticonvulsant therapy: effects of the administration of 25-hydroxyvitamin D3 on secondary hyperparathyroidism]. / Alterazioni calcio-fosforiche nella terapia cronica con anticonvulsivi: effetti della somministrazione di 25-OHD3 sull'iperparatiroidismo secondario.

The present study represents a contribution to the knowledge of secondary hyperparathyroidism (SHP) in patients treated with anticonvulsant drugs (AC). In these subjects alterations of the calcium: phosphorus metabolism as rickets and osteomalacia are frequent; however literature data on SHP are scarce. Our research carried out on 29 adult patients under treatment with one or more AC for periods ranging from 9 months to 12 years confirmed that 25-OHD levels in the serum are low, especially in patients treated for longer times. The iPTH levels in the serum are increased with respect to normal controls, while blood calcium and phosphate levels are normal as are urine calcium and phosphate. The 25-OHD levels in serum present the same seasonal variations as the normal controls. The administration of 25-OHD3 (20 micrograms/day for 3 months) to 12 of these patients who had the lowest 25-OHD spring levels rendered the 25-OHD levels attain normal values. Cyclic AMP was normalized; serum and urine calcium and phosphorus and urinary hydroxyproline were not modified significantly. On the basis of the present data it is recommended that chronic AC treatment should be accompanied by long term administration of 25-OHD3 for prophylaxis and/or for treatment of SHP.

Kearns-Sayre syndrome. A case of the complete syndrome with encephalic leukodystrophy and calcification of basal ganglia.

A case of a complete Kearns-Sayre syndrome, of early onset, associated with cerebral and cerebellar leukodystrophy and basal ganglia calcification is reported. The clinical, neurophysiological and morphological findings suggest multisystem involvement.

Congenital fiber type disproportion with fatal outcome: a case report.

A child with congenital fiber type disproportion without structural changes in muscle fibres is reported. Although this pattern suggests a favorable prognosis, the clinical worsening followed by death at the age of 17 months shows that there is as yet no predictor for a benign course for this myopathy.

A longitudinal electroencephalographic study in acute leukaemia.

A longitudinal electroencephalographic study of 100 patients suffering from acute leukaemia is reported. An high incidence of EEG abnormalities indicates the central nervous system involvement with no clinical manifestations. The patients have been divided in two groups: A) with normal EEG and B) with pathological (cerebro-meningeal localisation) but many causes (metabolic, toxic or microcirculatory disturbances) can produce the abnormalities. Moreover therapy may cause CNS disturbances with EEG evidence. The most damaging seems to be the simultaneous association of radiation therapy and methotrexate.

[Kleine-Levin syndrome]. / Sindrome di Kleine-Levin.

A case of a 15 years old boy with a Kleine-Levin syndrome is presented. Neurological examination and X-ray studies, including pneumoencephalography, were normal. Laboratory findings were also normal except for a flattened response to glucose load. The EEG was mildly abnormal, showing bifrontal discharges at 3 c/s, a finding already presented in other cases of Kleine-Levin syndrome. The differential diagnoses among the group of periodic hypersomnias is discussed.

[Epileptic psychoses]. / Psicosi epilettica.

A psychotic episode is described in a 21 year old male suffering since the age of 14 of generalized convulsions and tipical absences, scarecely controlled by antiepileptic drugs. The psychotic episode took place after a "Petit Mal Status", and was characterized by behaviour disorders, psycomotor excitement and delusions. During the episode the EEG became normal and epileptic seizures were not observed. Treatment with neuroleptics was followed by reduction of psychic disturbances.