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.

Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus.

BACKGROUND: Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro-inflammatory and remodelling-associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus-induced inflammation and remodelling are less known. OBJECTIVE: We investigated whether BUD and FORM synergize in suppressing RV-induced inflammation and remodelling in the airways. METHODS: In vitro models of RV infection of BEAS-2B and primary normal human bronchial epithelial (NHBE) cells were used. We assessed the effects of individual and combined drugs administered post-infection, at a clinically relevant concentration range (10(-6)-10(-10) m), on the production of CCL5, CXCL10, CXCL8, IL-6 and the remodelling-associated VEGF and bFGF, using ELISA and RT-PCR. RESULTS: BUD effectively suppressed RV-mediated induction of all mediators studied, in a concentration-dependent manner. FORM alone suppressed the production of CXCL8 and bFGF. The combination of BUD and FORM had concentration-dependent, additive or synergistic effects in the suppression of RV-induced CCL5, CXCL8 and CXCL10 in both cell types as well as VEGF in NHBE only. Combination treatment also resulted in an enhanced suppression of RV-induced IL-6, and CCL5 at the mRNA level as compared with BUD or FORM alone. CONCLUSION: BUD and FORM suppress RV-induced chemokines and growth factors in bronchial epithelial cells in a concentration-dependent, synergistic or additive manner. These data further support the combined use of BUD and FORM in asthma and COPD and intensification of this therapy during exacerbations.

Clinical and molecular epidemiology of community-acquired, methicillin-resistant Staphylococcus aureus infections in children in central Greece.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in children have increased considerably in our area. In this study, we prospectively examined the epidemiological, clinical and molecular profile of CA-MRSA infections in children in central Greece. A total of 198 staphylococcal strains were isolated from patients with community-acquired infections over a 28-month period and 88 (44%) were found to be methicillin-resistant. Most patients with CA-MRSA had skin and soft-tissue infections (73%). Hospitalisation and surgery were more commonly required for patients with MRSA strains (p = 0.001 and p < 0.001, respectively). The presence of Panton-Valentine leukocidin (PVL) genes was identified in 28/41 (68%) CA-MRSA strains. All PVL(+) strains were found to carry a staphylococcal chromosomal cassette (SCC) mec element type IV and belonged to a single electrophoretic type similar to the European multi-locus sequence type 80 (ST80). The recent increase in CA-MRSA infections in children in our area is largely associated with the spread of the ST80 clone and their clinical characteristics are similar to those described in other parts of the world where different MRSA clones predominate.

Nationwide surveillance of Streptococcus pneumoniae in Greece: patterns of resistance and serotype epidemiology.

This nationwide study assessed the antimicrobial susceptibility and seroprevalence of Streptococcus pneumoniae in paediatric carriage isolates and in clinical isolates from adult pneumococcal disease in Greece during the years 2004-2006. Among 780 isolates recovered from the nasopharynx of children <6 years old attending day-care centres, non-susceptibility rates to penicillin, cefuroxime, ceftriaxone, erythromycin, tetracycline and trimethoprim/sulfamethoxazole were 34.7%, 25.1%, 1.0%, 33.5%, 26.4% and 44.2%, respectively. Among 89 adult clinical isolates, the respective rates were 48.3%, 46.1%, 5.6%, 48.3%, 32.6% and 40.4%. High-level resistance to penicillin, cefuroxime and ceftriaxone was recorded for 14.4%, 23.3% and 0.1% of paediatric carriage isolates, whereas for clinical adult isolates the respective rates were 25.8%, 38.2% and 2.2%. No resistance to levofloxacin and moxifloxacin was recorded, although 3.5% of paediatric carriage isolates and 23.2% of adult clinical isolates had minimum inhibitory concentrations of ciprofloxacin >2mg/L. Serotypes 19F, 14, 23F and 6B were the most prevalent among carriage and clinical isolates. The 7-valent pneumococcal conjugate vaccine was estimated to provide coverage against 71.7% of paediatric carriage isolates and 51.3% of adult clinical isolates. Resistance rates among clinical isolates from adult sources were higher than those recorded among paediatric carriage S. pneumoniae isolates and displayed an increasingly resistant profile compared with previous reports from our country, warranting continuous vigilance.

Meningococcal group C disease in Greece during 1993-2006: the impact of an unofficial single-dose vaccination scheme adopted by most paediatricians.

The aim of this study was to evaluate the impact of the meningococcal C conjugate vaccine on the epidemiology of meningococcal C disease in Greece. Data from the National Reference Laboratory for Meningococcal Disease and a questionnaire distributed to Greek paediatricians were assessed. Since the introduction of the vaccine in 2001, 72% of Greek paediatricians have administered it as one single dose to patients aged > or =12 months. This vaccination scheme has probably contributed to a dramatic decrease in the number of meningococcal C infections, which reached zero in 2004.

Safety and tolerability of clarithromycin administered to children at higher-than-recommended doses.

A tendency among pediatricians in Greece to use higher-than-recommended doses of clarithromycin was noted over several years, prompting this study of the safety and tolerability of this macrolide in 343 children over a period of 9 months. The study group comprised nonhospitalized patients of 29 pediatricians practicing in Athens. All were prescribed clarithromycin for upper respiratory (n = 257) or lower respiratory tract infection (n = 78). Overall, 77.8% were treated with doses that exceeded the recommended dose of 15 mg/kg/day, and 26% received doses of > or = 30 mg/kg/day (median dose, 20 mg/kg/day). The tolerability of clarithromycin was judged as "very good" in 75% of the children, as "good" in 16%, and as "moderate" in 5%, whereas intolerability was observed in 4% of the cases. Adverse reactions, mainly gastrointestinal in nature, were reported in 17.5% of the cases. With regard to both tolerability and adverse events recorded, there were no statistically significant differences between the group of patients who received the recommended dose and the group who received higher doses. Clarithromycin continues to present a safe and well-tolerated profile for the treatment of common pediatric infections, even when administered at higher-than-recommended doses. Whether it is more efficacious in this setting is a matter for further study.

Human rhinoviruses in otitis media with effusion.

Frequent viral upper respiratory tract infections (URTI) are considered to be risk factors for otitis media with effusion (OME). Atopy has also been associated with both OME and viral infections. The aim of this study was to evaluate the presence of viruses in middle ear effusions (MEE) in children 2-7 yr old with OME, and to determine risk factors for virus detection in the MEE. MEE samples, collected at the time of myringotomy from 37 children with OME were assessed. Physical examination, skin prick tests and a standardized questionnaire on OME and allergy were also performed. Viral RNA was detected by the use of reverse transcription PCR (RT-PCR). Fifteen samples (40.5%) were positive for rhinovirus (RV). One enterovirus and no other respiratory viruses were detected. Two out of five (40%), 3/7 (43%) and 10/25 (40%) were positive for RV in acute, subacute and chronic cases, respectively. Children with frequent episodes of OM, with early onset of OM (<2 yr old), and a positive family history of allergy had a statistically increased risk of RV detection. The two groups were comparable with respect to all other parameters examined. RV is the predominant virus recovered by RT-PCR in the middle ear cavity of children with asymptomatic OME, especially those with a history of longstanding OME or repeated episodes, or children with a family history of allergy. Interactions between allergy and RV infections are likely to predispose to middle ear disease.

Preterm birth due to maternal infection: Causative pathogens and modes of prevention.

Preterm birth represents a major problem for modern obstetrics due to its increasing frequency and the accompanying socioeconomic impact. Although several maternal characteristics related to preterm birth have been identified, the etiology in most cases remains inadequately understood. Various microorganisms have been linked to the pathogenesis of preterm birth. Microbes may reach the amniotic cavity and fetus by ascending from the vagina and cervix, by hematogenous distribution through the placenta, by migration from the abdominal cavity through the fallopian tubes, or through invasive medical procedures. Organisms commonly cultured from the amniotic cavity following preterm delivery include Ureaplasma urealyticum, Mycoplasma hominis, Bacteroides spp., Gardnerella vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and group B hemolytic streptococci. Several trials have examined the effect of antibiotic administration to patients with preterm labor and intact membranes, preterm premature rupture of the membranes, genital mycoplasmal infection, asymptomatic bacteriuria, and bacterial vaginosis. The results of such studies, which were variable and often conflicting, are discussed here.

Serotypes and antimicrobial susceptibilities of 1033 pneumococci isolated from children in Greece during 2001-2004.

Pneumococci (n = 1033) isolated in the major paediatric hospitals of Athens during 2001-2004 from children with invasive infections (n = 186), non-invasive infections (n = 641) and healthy carriers (n = 206) were studied. The most prevalent serotypes were serotypes 14 (44.6%), 19F (43.5%) and 6B (22.8%) in invasive, non-invasive and carriage isolates, respectively. Among invasive isolates, the potential coverage by the seven-valent conjugate vaccine was 75.3%. Resistance rates to penicillin, amoxycillin, cefotaxime, erythromycin, co-trimoxazole, clindamycin, tetracycline and chloramphenicol were 44.6%, 2.7%, 1.2%, 43.6%, 43.5%, 12.4%, 34.7% and 5.9%, respectively. The M-phenotype accounted for 68.0% of the erythromycin-resistant isolates. All isolates were susceptible to ofloxacin.

IgE sensitization, respiratory allergy symptoms, and heritability independently increase the risk of otitis media with effusion.

BACKGROUND AND AIMS: Epidemiological evidence examining the role of atopy and/or allergy in the pathogenesis of otitis media with effusion (OME) is inconclusive. The aim of this study was to assess any increased risk for OME attributable to allergy-related factors, in a well-characterized population using a case-control design and multivariate analysis. SUBJECTS AND METHODS: Eighty-eight 1-7-year-old children with OME, diagnosed by clinical and tympanometric evaluation and 80 matched controls were enrolled. A standardized questionnaire was completed, in order to assess factors related to OME and allergy-related symptoms and diagnoses using strict clinical definitions. Specific IgE was measured by skin-prick tests and/or CAP-FEIA. RESULTS: The patient and control groups were well matched. Factors conferring increased risk for OME in the univariate analysis included IgE sensitization, dyspnea, wheezing, asthma, paroxysmal sneezing, rhinitis, eczema, 'any allergic disease,' family history of otitis media, and family history of allergy. After multivariate analysis IgE sensitization, wheezing, nasal obstruction, family history of otitis, and child-care attendance remained as independent risk factors for development of OME. CONCLUSION: IgE sensitization and respiratory allergy symptoms are independent risk factors for the development of OME, suggesting that both immunological and mechanical pathways may contribute to the development of the disease. Otitis heritability provides additional risk, as well as frequent exposure to viral upper respiratory tract infections in children attending daycare. Treatment and/or prevention of OME using anti-allergic medications should be further examined.

Procalcitonin as a predictor of severe appendicitis in children.

The aim of this study was to assess the diagnostic value of procalcitonin (PCT) in 212 children with appendicitis and compare it with that of the standard diagnostic modalities, C-reactive protein (CRP) level, leukocyte count, and abdominal ultrasound findings, in relation to the surgical and histological findings of the appendix. A PCT value of >0.5 ng/ml was found to be indicative of perforation or gangrene with 73.4% sensitivity and 94.6% specificity, a CRP level of >50 mg/l and a leukocyte count of >10(4)/mm3 were useful diagnostic markers for perforation, while abdominal ultrasonography had a sensitivity of 82.8% and a specificity of 91.2% for detecting appendicitis with imaging findings. PCT measurement seems to be a useful adjunctive tool for diagnosing acute necrotizing appendicitis or perforation, and surgical exploration will probably be required in patients with PCT values >0.5 ng/ml.

Treatment of paediatric visceral leishmaniasis: amphotericin B or pentavalent antimony compounds?

Pentavalent antimony compounds and amphotericin B lipid formulations have been found highly active for the treatment of visceral leishmaniasis. This study focuses on which treatment is preferable in the best interests of the child. Records were reviewed of children in our hospital aged 0-14 years, diagnosed with visceral leishmaniasis, during the last 4 years. Twenty-nine children were identified. Ten were treated with meglumine antimonate (20 mg/kg/day for 21 days) and remained in hospital for 11-28 days (median 19 days), while 19 patients received liposomal amphotericin B at four different dosage schemes and were in hospital for 6-11 days (median 7 days). All of the patients were cured regardless of the treatment regime they followed. No relapses were noted. Liposomal amphotericin B would be preferable to meglumine antimonate if the reduction in hospital stay and hence the convenience of the patient balance the cost of medication. The optimal duration of treatment with liposomal amphotericin B remains to be determined.

Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections.

BACKGROUND: Community-acquired pneumonia (CAP) in young children is most commonly associated with viral infections; however, the role of viruses in CAP of school-age children is still inconclusive. METHODS: Seventy-five school-age children hospitalized with CAP were prospectively evaluated for the presence of viral and bacterial pathogens. Nasopharyngeal washes were examined by polymerase chain reaction for viruses and atypical bacteria. Antibody assays to detect bacterial pathogens in acute-phase and convalescent-phase serum samples were also performed. RESULTS: A viral infection was identified in 65% of cases. Rhinovirus RNA was detected in 45% of patients; infection with another virus occurred in 31%. The most common bacterial pathogen was Mycoplasma pneumoniae, which was diagnosed in 35% of cases. Chlamydia pneumoniae DNA was not detected in any patient; results of serological tests were positive in only 2 patients (3%). Mixed infections were documented in 35% of patients, and the majority were a viral-bacterial combination. CONCLUSIONS: The high prevalence of viral and mixed viral-bacterial infections supports the notion that the presence of a virus, acting either as a direct or an indirect pathogen, may be the rule rather than the exception in the development of CAP in school-age children requiring hospitalization.

Otitis and respiratory distress episodes following a respiratory syncytial virus infection.

OBJECTIVE: To document, over two consecutive respiratory syncytial virus (RSV) seasons, the occurrence of acute otitis media (AOM) and recurrence of respiratory distress in children < 2 years of age hospitalized for respiratory distress. METHODS: Patients were examined during hospitalization and at 6 weeks and 6 months after discharge. RSV testing was performed on all patients, and hospitalized patients were evaluated daily for the occurrence of AOM. RESULTS: In total, 347 children were enrolled; 54.8% were RSV positive, and 45.2% were RSV negative. Children were most frequently diagnosed as having bronchiolitis (71.9%) or asthmatic bronchitis (17.9%); other diagnoses included pneumonia, laryngitis, and rhinitis. During hospitalization, AOM was diagnosed in 16.8% of RSV-positive versus 8.3% of RSV-negative children (P < 0.05). Six weeks after discharge, AOM was reported in 10.4% of RSV-positive as compared with 5.8% of RSV-negative patients. Six months later, AOM was reported in 2.9% of the RSV-positive and 7.6% of the RSV-negative patients. A second episode of acute respiratory distress, which either required (9) or did not require (35) hospitalization, occurred in 18.4% of the total population, with similar proportions of RSV-positive and RSV-negative children (17% versus 18.6%). CONCLUSION: We conclude that RSV appears to be an important contributing factor for the occurrence of AOM in young children hospitalized with respiratory distress. The occurrence of a second episode of acute respiratory distress did not appear to correlate with the previous RSV infection, but longer-term follow-up is required.

An overview of paediatric leishmaniasis.

Leishmaniasis, a parasitic disease transmitted by the bite of some species of sandflies affects various age groups depending on the infecting Leishmania species, geographic location, disease reservoir, and host immunocompetence. Visceral leishmaniasis is the most severe form of the disease affecting children. The extent and presentation of the disease depend on several factors, including the humoral and cell-mediated immune response of the host, the virulence of the infecting species, and the parasite burden. Children are at greater risk than adults in endemic areas. Malnutrition contributes to the development of disease, and incomplete therapy of initial disease is a risk factor for recurrence of leishmaniasis. Children usually present with intermittent fever, paleness, refusal to feed or anorexia, weight loss, and abdominal distension. Splenomegaly, hepatomegaly, lymph node enlargement, thrombocytopaenia, anaemia, leukopaenia and hypergammaglobulinemia are the most common findings in Paediatric leishmaniasis. Molecular methods appear to offer the promise of accurate non-invasive tools for the diagnosis of Leishmaniasis. Till these methods are evaluated, definite diagnosis will rely on the demonstration of the infecting parasite in various tissues. World-wide, with the notable exception of India, pentavalent antimonial compounds remain the most effective and the most affordable therapy for this disease. Lipid formulations of amphotericin B were assessed as short duration treatment and were proved to be effective. However, their cost precludes their wide use in developing countries. Miltefosine, a new oral agent, might prove effective, safe, and affordable. Strategies aimed at control of the micro-population of sandflies, eradication of canine leishmaniasis, and offering personal protection against sandfly bites, together with health education programs in developing countries, can help control the disease. Development of an effective vaccine remains a priority.

Burden of respiratory syncytial viral infections on paediatric hospitals: a two-year prospective epidemiological study.

This study was designed to prospectively investigate the hospitalisation patterns for respiratory syncytial virus (RSV) disease in children up to 2 years of age, both healthy full-term children and high-risk children. The aim was to evaluate children hospitalised for a respiratory tract infection in four regions and seven paediatric hospital departments or clinics in Greece and to estimate the burden of RSV disease on paediatric hospital beds, as well as to determine the target high-risk age group over two consecutive respiratory infection seasons. Among a total of 1,710 children, the overall prevalence of RSV disease was 33.1%, but prevalence differed between seasons (27% vs. 37.7%, P<0.01). The peak prevalence of RSV disease occurred in February, with the onset in November and the end in May. The monthly distribution was similar in all regions. RSV positivity was strongly associated with young age (4.7 vs. 6.6 months, P<0.001); classification within a high-risk group (43% vs. 32.6%, P=0.04); lower respiratory tract infection (93.8% vs. 86%, P=0.001), particularly bronchiolitis (80.9% vs. 63.9%, P=0.001); more severe disease (P<0.001); longer stay in hospital (P<0.001); and poorer outcome (P<0.001). RSV infections accounted for 38% of the total hospitalisation days for all respiratory infections, and 77% of the hospitalisation days for RSV infection were for infants less than 6 months of age.