Genetic variations of interleukin-8, CXCR1 and CXCR2 genes and risk of acute pyelonephritis in children.

Acute pyelonephritis (APN) is the most severe form of urinary tract infection, the etiopathogenesis of which is still not well understood. Previous studies demonstrated that chemotaxis of neutrophils into the tissue and across the infected epithelial layer is a key step in rapid bacterial clearance. Variations within genes encoding the major chemokine interleukin-8 and its receptors CXCR1 and CXCR2 are therefore attractive candidates for participation in genetic predisposition to APN. The aim of our study was to evaluate the association of single nucleotide polymorphisms (SNPs) -251 T/A, +781 C/T, +1633 C/T and +2767 A/T in the IL-8 gene, +2608 G/C in the CXCR1 gene and +1208 C/T in the CXCR2 gene with susceptibility to APN in the Slovak population. PCR-SSP and PCR-RFLP were used to genotype SNPs in 147 children with APN (62 with recurrent and 85 with episodic form) and 215 healthy individuals. Statistical analysis revealed significantly increased frequency of CXCR1 +2608 C allele (P = 0.0238, OR = 2.452, 95% CI = 1.147-5.243) and GC genotype (P = 0.0201, OR = 2.627, 95% CI = 1.188-5.810) and lower frequency of CXCR2 +1208 T allele (P = 0.0408, OR = 0.645, 95% CI = 0.429-0.972) and TT+TC genotypes (P = 0.0497, OR = 0.5273, 95% CI = 0.288-0.964) in patients with recurrent APN compared with healthy controls. Furthermore, the A allele of IL-8 -251 T/A SNP was also significantly overrepresented in patients with recurrent APN when compared with those with only single episode of APN (P = 0.0439, OR = 1.627, 95% CI = 1.019-2.599). Our results indicate that the minor CXCR1 +2608 C allele is associated with significantly increased susceptibility to APN in childhood, while the CXCR2 +1208 T allele confers protection from recurrent APN. Moreover, allele A of the IL-8 -251 T/A may also increase the risk of developing recurrent attacks after the first-time APN.

Nosocomial meningitis caused by Staphylococcus other than S. aureus in children: multicentre study.

Analysing 101 cases of nosocomial meningitis due to staphylococci other than S. aureus within last 15 years, coagulase negative staphylococci represented the commonest pathogen. Major risk factor for staphylococcal meningitis was prior neurosurgery, mainly ventriculoperitoneal shunt insertion. Ten of 101 cases were caused by glycopeptide intermediate resistant strains in patients pretreated with multiple combination of antibiotics including vancomycin and shunt exchanges: 76% of strains were also oxacillin resistant.

Neuroinfections complicating foreign body implants after perinatal trauma or meningitis in 60 children.

Meningitis after artificial implants in 60 children, mainly after foreign body infections (FBI) was caused more frequently by coagulase negative staphylococci and Ps. aeruginosa than other organisms and was significantly associated with perinatal trauma, hydrocephalus, haemorrhage or VLBW and had more neurologic sequels despite mortality was similar to other nosocomial meningitis.

Breakthrough fungaemia in neonates and infants caused by Candida albicans and Candida parapsilosis susceptible to fluconazole in vitro.

Breakthrough fungaemias due to Candida albicans and Candida parapsilosis appearing during fluconazole therapy in neonates and infants were assessed for risk factors and outcome. Forty fungaemias occurred during therapy with fluconazole within a 12 year national survey and were compared with 161 cases of non-breakthrough paediatric fungaemias. The agar disc diffusion test method was used for antifungal susceptibility testing and the Vitek system for species identification. Univariate and multivariate analysis for risk factors for breakthrough fungaemia were carried out. All the fungaemias were a result of strains susceptible to fluconazole at 0.25-4 mg/L in vitro [C. albicans (85%) and C. parapsilosis (15%)]. The mean number of positive blood cultures per episode was 2.2. Sixteen children had 'early' breakthrough fungaemias (within 4-5 days) and 24 fungaemias appeared on day 6 and later. Mean fluconazole MICs in the 'early' group were 1.2, and 2.8 mg/L in the 'late' group (P < 0.03, t-test). However, no difference was observed in the average dose of fluconazole used in the two groups. Neonatal age, total parenteral nutrition, very low birth weight, before surgery, central or umbilical venous catheterization and artificial ventilation were all significantly related to breakthrough fungaemia in univariate analysis but only central or umbilical venous catheterization were significant in multivariate analysis. The outcome of breakthrough fungaemia was better overall and attributable mortalities in non-breakthrough fungaemia was significantly higher in comparison with breakthrough fungaemia.

Prospective study of antibacterial susceptibility, risk factors and outcome of 157 episodes of Acinetobacter baumannii bacteremia in 1999 in Slovakia.

This study prospectively investigated all 157 cases of Acinetobacter baumannii bacteremia occurring in major university hospitals or tertiary care institutions in Slovakia during 1999 in order to determine the antimicrobial susceptibility, risk factors and outcome. Resistance to meropenem was 7.4, gentamicin 35.6, amikacin 26.5, cefepime 20.4 and ciprofloxacin 32.7%, but was only 17.3% to cefoperazone/sulbactam or ampicillin/sulbactam. Antimicrobial susceptibility of A. baumanii was lowest among isolates from cancer patients (ceftazidime 58%, piperacillin/tazobactam 52% and azthreonam 48%; p < or = 0.01-0.001). In univariate analysis, several risk factors, such as wound infection (p < or = 0.01) and ventilatory support (p < or = 0.0001), were significantly related to A. baumannii bacteremia in surgical patients. Neutropenia (p < or = 0.0001), antineoplastic chemotherapy (p < or = 0.0001) and prior antibiotic therapy (p < or = 0.0006) were significant risk factors for A. baumannii bacteremia in cancer patients. In addition, ventilatory support and surgery (p < or = 0.0001) and prior antibiotic therapy (p < or = 0.01) were significantly related to A. baumannii bacteremia in children. Colonization at other body sites (p < or = 0.05), diabetes mellitus (p < or = 0.04) and decubital ulcers/burns (p < or = 0.002) as underlying disease were significantly related to death due to A. baumannii bacteremia. In a multiple logistic regression model, decubital ulcers/burns as underlying disease (p < or = 0.0006; relative risk 5.08) and nosocomial pneumonia (p < or = 0.045; relative risk 5.08) were independent predictors of mortality. Mortality was similar between cancer and surgical patients but significantly lower in children vs. adults (p < or = 0.009).

Ciprofloxacin in treatment of nosocomial meningitis in neonates and in infants: report of 12 cases and review.

Twelve cases of neonatal and infant nosocomial meningitis treated with intravenous ciprofloxacin in doses of 10 to 60 mg/kg/day are described. Four neonates were 21 to 28 days old and eight infants were 2 to 6 months old. Six presented with Gram-negative meningitis: Escherichia coli (2), Salmonella enteritidis (1), Acinetobacter calcoaceticus (1), two with two organisms, and (H. influenzae plus Staphylococcus epidermidis, Acinetobacter spp. plus S. epidermidis), and six were attributable to Gram-positive cocci (four S. aureus and two Enterococcus faecalis). Ten cases were cured. In two cases, reversible hydrocephalus appeared that responded to intraventricular punctures. In seven children, no neurologic sequellae appeared after a 2- to 4-year follow-up. One neonate had relapse of meningitis 3 months later and was ultimately cured, but developed a sequellae of psychomotoric retardation. Follow-up varied from 27 months to 10 years. Current published case reports from Medline on quinolone use in meningitis in neonates and infants are reviewed.

Nosocomial meningitis in children after ventriculoperitoneal shunt insertion.

This study reviews 33 cases of ventriculoperitoneal shunt (VPS) meningitis among 415 children after 540 shunt insertions within 8 y, in 9 paediatric intensive care units from 5 centres in Slovakia. The incidence of VPS meningitis was 6.3% per insertion. The most common organisms isolated from cerebrospinal fluid (CSF) and shunt were coagulase-negative staphylococci (52.8%), followed by Staphylococcus aureus (13.1%) and Pseudomonas aeruginosa (7.5%). Seven of 15 assessed risk factors were significantly associated with VPS meningitis, compared with non-VPS meningitis: prior meningitis with hydrocephalus (15.1 vs 1.5%, p < 0.015), perinatal pathology (51.1 vs 1.5%, p < 0.001), very low birthweight (66.6 vs 16.2%, p < 0.001), polymicrobial nosocomial meningitis (30.3 vs 5.9%, p < 0.002), S. aureus (21.2 vs 7.3%, p < 0.05), coagulase-negative staphylococci (84.8 vs 30.9%, p < 0.001) and P. aeruginosa and Acinetobacter calcoaceticus (30.3 vs 4.5%, p < 0.001) in aetiology.

Candida fungemia in neonates treated with fluconazole: report of forty cases, including eight with meningitis.

PURPOSE OF THE STUDY: To assess efficacy and safety of fluconazole in neonates with Candida fungemia. STUDY DESIGN: Multicenter prospective protocol of all fungemias appearing between January 1, 1993, and December 31, 1997, in four major university hospitals. RESULTS: Forty neonates, 28 of them with very low birth weight (<1500 g; 30.5 median gestation week), with documented Candida albicans fungemia were treated with intravenous fluconazole in a daily dosage of 6 mg/kg once daily for 6 to 48 days. Thirty-four received fluconazole as monotherapy and 6 received it in combination with amphotericin B. Thirty-two (80%) were cured; 4 of them relapsed despite at least 14 days of therapy, but they were ultimately cured without sequelae. Eight other neonates died, 4 because of fungal infection and 4 because of prematurity or hemorrhage or lung failure, with fungemia (20% overall and 10% attributable mortality). Two neonates had elevated liver enzymes during fluconazole therapy and 2 others had elevated serum creatinine during fluconazole monotherapy. In none of them did these abnormalities necessitate discontinuation of antifungal therapy. In 8 neonates fungal meningitis developed as a complication of fungemia. All but 3 fungemias were C. albicans; 3 were Candida parapsilosis. CONCLUSIONS: Fluconazole was safe and effective antifungal therapy even in complicated or Candida fungemia in neonates and in infants with very low birth weight.

Prospective study of nosocomial fungal meningitis in children--report of 10 cases.

Within an 8-year period, 10 cases of fungal nosocomial meningitis in children 0-13 y old were prospectively identified, 3 caused by yeasts other than Candida spp. (Rhodotorula rubra, Aureobasidium mansoni, Clavispora lusitaniae) and 7 by Candida albicans. Seven patients survived. whereas 3 neonates with fungal meningitis (all due to C. albicans) died. Risk factors for fungal nosocomial meningitis included cancer (2 children), previous neurosurgery (2 children), cranial trauma (1 case) and prematurity with low birthweight (5 cases). All patients except 1 had received broad-spectrum antibiotics before onset of meningitis. In addition to yeasts, bacteria were isolated from CSF of 4 children. One child had additional fungaemia. Univariate analysis was used to compare 10 cases of fungal to 91 cases of bacterial nosocomial meningitis. Except for concurrent bacteraemia, (60 vs 25.3%, P < 0.03), which was more frequently observed among fungal meningitis, there were no significant differences in risk factors, sequelae or outcome (mortality) between patients with fungal vs bacterial meningitis. A review of fungal meningitis reported within the last 20 y is included.

[Claforan in the treatment of serious infections in children]. / Claforan v liecbe závazných infekcií u detí.

To 63 critically sick patients on account of serious infection Claforan was administered. Forty-six patients were hospitalized at the intensive care and resuscitation unit and 17 patients suffered from oncological conditions. Claforan treatment was successful in 69.56% of the patients treated at the intensive care and resuscitation unit and in 30.44% in the group of oncological patients.