Carmelina Calitri

Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression

The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.

Use of linezolid in infants and children: a retrospective multicentre study of the Italian Society for Paediatric Infectious Diseases

OBJECTIVES Because of the spread of drug-resistant Gram-positive bacteria, the use of linezolid for treating severe infections is increasing. However, clinical experience in the paediatric population is still limited. We undertook a multicentre study to analyse the use of linezolid in children. METHODS Hospitalized children treated with linezolid for a suspected or proven Gram-positive or mycobacterial infection were analysed retrospectively. Side effects were investigated, focusing on younger children and long-term treatments. RESULTS Seventy-five patients (mean age 6.8 years, range 7 days to 17 years) were studied. Mean ± SD linezolid treatment duration was 26.13 ± 17 days. Clinical cure was achieved in 74.7% of patients. The most frequent adverse events were diarrhoea and vomiting. Two patients had severe anaemia, two neutropenia and one thrombocytopenia. Two cases of grade 3 liver function test elevation and one case of pancreatitis were reported. The overall frequency of adverse events was similar between patients treated for >28 days and those receiving shorter treatments (30.8% versus 28.6%, P = 0.84). Children aged <2 years received linezolid for a shorter duration than older children (21.2 days versus 28.4 days, P = 0.05), whereas the frequency of adverse events was similar in the two age groups. CONCLUSIONS In our paediatric population, linezolid appeared safe and effective for the treatment of selected Gram-positive and mycobacterial infections. The adverse reactions encountered were reversible and appeared comparable to those reported in paediatric clinical trials. Nevertheless, the potential for haematological toxicity of linezolid in children means that careful monitoring is required during treatment.

Effectiveness and safety of the A-H1N1 vaccine in children: A hospital-based case - Control study

Objective To verify whether vaccination against the A-H1N1 virus in the paediatric population was effective in preventing the occurrence of influenza-like illness (ILI) or was associated with adverse events of special interest. Design, setting and patients A case–control analysis was performed as part of surveillance of children hospitalised through the emergency departments of eight paediatric hospitals/wards for ILI, neurological disorders, non-infectious muco-cutaneous diseases and vasculitis, thrombocytopaenia and gastroduodenal lesions. Results Among 736 children enrolled from November 2009 to August 2010, only 25 had been vaccinated with the pandemic vaccine. Out of 268 children admitted for a diagnosis compatible with the adverse events of special interest, six had received the A-H1N1 vaccine, although none of the adverse events occurred within the predefined risk windows. Only 35 children out of 244 admitted with a diagnosis of ILI underwent laboratory testing: 11 were positive and 24 negative for the A-H1N1 virus. None of the A-H1N1 positive children had received the pandemic vaccine. The OR of ILI associated with any influenza vaccination was 0.9 (95% CI 0.1 to 5.5). Conclusions The study provides additional information on the benefit–risk profile of the pandemic vaccine. No sign of risk associated with the influenza A-H1N1 vaccine used in Italy was found, although several limitations were observed: in Italy, pandemic vaccination coverage was low, the epidemic was almost over by mid December 2009 and the A-H1N1 laboratory test was performed only during the epidemic phase (in <10% of children). This study supports the importance of the existing network of hospitals for the evaluation of signals relevant to new vaccines and drugs.

Daptomycin for Children in Clinical Practice Experience.

Data on daptomycin use in the pediatric setting are scanty. We conducted a multicenter, retrospective study on 46 children treated with intravenous daptomycin at a mean dosage of 7.0 mg/kg/d, for a median of 14 days. Three children had adverse events possibly related to daptomycin. The drug was overall well tolerated, even with prolonged treatment.

Etiological diagnosis of bloodstream infections through a multiplex real-time polymerase chain reaction test in pediatric patients: a case series from a tertiary Italian hospital

Abstract Background: The outcome of bloodstream infections (BSIs) is strongly related to microbiological diagnosis. Several factors may reduce blood culture (BC) diagnostic yield in pediatric BSIs, making the application of molecular methods quite promising. Methods: Multiplex real-time polymerase chain reaction (PCR) tests (the LightCycler Septifast Test MGRADE by Roche Diagnostics - LC-SF) performed in the tertiary centre of Regina Margherita Childrens Hospital (Turin, Italy) over a 3-year period were retrospectively evaluated. Results of the LC-SF test were compared with those of BC (Automated Bact/Alert 3D, Biomerieux) collected at a close time point. Results: 545 LC-SF tests were collected from 289 patients (183 males, median age 6.8 years, interquartile range (IQR) = 2.7–13.1); 163 had congenital or acquired immunodeficiency. In 515 cases (94.5%) the LC-SF test was performed with ongoing empirical antimicrobial therapy. Etiological definition was achieved in 111 BSI cases (20.4%). Both LC-SF and BC identified the responsible pathogen in 39 episodes. The LC-SF test alone gave a positive result in 29 septic episodes; BC alone permitted the etiological diagnosis in 43 episodes, but isolates were not included in the LC-SF master list in 10 cases. A 26% increase in bacterial identification chances due to the LC-SF test was documented. Cohens kappa test indicated a moderate strength of agreement (0.49) between LC-SF tests and BCs closely collected. Conclusions: BC remains the gold standard for the etiological diagnosis of BSIs, but PCR methods proved to be a valuable adjunctive diagnostic tool in pediatric BSIs, especially in children receiving empirical chemotherapy.

Carbapenemase-Producing Enterobacteriaceae (CPE) in the Pediatric Setting: Results from an 18-Month Survey

18-Month Survey Author(s): Sara Colombo, MD; Carlo Scolfaro, MD; Carmelina Calitri, MD; Marco Denina, MD; Francesca Carraro, MD; Gianfranco De Intinis, MD; Pier-Angelo Tovo, MD Source: Infection Control and Hospital Epidemiology, Vol. 35, No. 5 (May 2014), pp. 599-601 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/675843 . Accessed: 24/06/2014 23:13

Performance of 1,3-β-D-glucan for diagnosing invasive fungal diseases in children

Plasma 1,3‐β‐D‐glucan (BDG) is indicated as a tool for early diagnosis of invasive fungal diseases (IFD). However, data on its diagnostic value are scarce in children. Therefore, definition of BDG test performance in paediatrics is needed. BDG was evaluated in children admitted to “Istituto Giannina Gaslini,” Genoa, Italy, who developed clinical conditions at risk for IFD. Results were analysed for sensitivity, specificity, predictive values, likelihood ratios, accuracy, informedness and probability of missing one case by a negative test. A total of 1577 BDG determinations were performed on 255 patients (49% males, median age 5.4 years). Overall 46 IFD were diagnosed, 72% proven/probable. The test performance was evaluated for 80 pg/mL, 120 pg/mL, 200 pg/mL, 350 pg/mL, 400 pg/mL cut offs. Sensitivity was always <0.80 and specificity > 0.90 only for cut offs ≥200 pg/mL. Negative predictive value was ≥0.90 for all the cut offs evaluated, while positive predictive value resulted barely 0.50 (8% IFD prevalence). Accuracy was never >0.90, and informedness was at best 0.50. The risk of missing one IFD by a negative result was < 10%. Analyses in haemato‐oncological or newborn patients did not show major differences. Detection of serum BDG does not appear a valuable adjunctive diagnostic tool for IFD in paediatrics.

Primary sternal osteomyelitis in paediatric age: a case report with review of the literature

Osteomyelitis of the sternum is a rare clinical entity, mostly described in adults following cardiothoracic surgery, sternotomy, blunt chest traumas, intravenous line insertion and mediastinitis. When no predisposing factors can be demonstrated and no focus of infection other than sternal localization can be found, a diagnosis of primary sternal osteomyelitis (PSO) can be made. To date, slightly more than 20 cases of PSO have been documented in children: sternum ossification points are in their maximal activity phase in earlier paediatric age, representing a privileged area for bacterial growth after haematogenous bacterial spread. 1‐3 A healthy 15-month-old male came to our attention for midsternal swelling. He had a 20-day history of nocturnal awakening and weeping, with a febrile episode treated with paracethamol one week before hospital admission. Thenceforward he looked nervous and presented respiratory difficulties. No local traumas were reported. Upon examination, the child was afebrile, easily irritable and without apparent respiratory disturbances. An ill-defined midsternal swelling of 3 cm in diameter was palpable: it was tender, warm, painful, with reddening of the upper skin. White cell count was elevated (16.31610 3 /ml) with neutrophilia (53.7%, 8.76610 3 /ml); erythrocyte sedimentation rate and C-reactive protein were increased (120 mm/hour and 66.4 mg/l, respectively). No sternum alteration at X-rays was evident. Ultrasounds revealed a hypoecogen colliquating mass, with underlying cartilage and periosteum alterations. The magnetic resonance imaging (MRI) showed capsular exudate and synovial hyperplasia, with manubrium sterni joint’s arthritis and osteomyelitis of the underlying bone. As osteonecrosis and skeletal abnormalities were also sorted out, a diagnosis of PSO was made. Blood cultures performed at admission were sterile, even though the child had not been treated with antimicrobials. An increased antistaphylolysin titer (.8 U/ml, normal value ,2 U/ml) was documented, suggesting a possible staphylococcal infection. The child was given empiric antibiotic therapy with IV teicoplanin (10 mg/kg/day following a loading dose of 20 mg/kg/ day) and ceftriaxone (80 mg/kg/day), which lead to a prompt decrease in white cells, neutrophil count, inflammation indices and clinical improvement. Given the clinical and laboratory findings, fine needle aspiration of the mass was deemed unnecessary. After 10 days of antimicrobial therapy, due to the onset of a febrile maculopapular rash, teicoplanin and ceftriaxone were replaced by IV meropenem (60 mg/kg/day) and oral rifampicin (20 mg/kg/day). The child was discharged after 31 days in good general conditions, with a sensible reduction of the midsternal swelling. Oral rifampicin and trimethoprim/sulfamethoxazole (TMP/SMX, 10 mg/kg/day of TMP) were administered as outpatient for a total antibiotic course of 6 weeks. No relapses were found at follow-up: in particular, the MRI test of the sternum performed 3 months later showed complete bone resolution. In spite of its rarity, PSO should be considered in the differential diagnosis of sternal swelling in paediatric patients. Unfortunately, clinical symptoms are not specific, and history of trauma is absent in the majority of cases. Sickle cell disease is the sole predisposing condition clearly identified in paediatric age, 4 as these

Surveillance Study of Healthcare-Associated Infections in a Pediatric Neurosurgery Unit in Italy

Background: This prospective surveillance study was designed to estimate the incidence of healthcare-associated infections (HAIs) and to analyze the risk factors for their development in a pediatric neurosurgical unit. Methods: The study was performed in an Italian teaching hospital from October 2008 through March 2010. All children (0–18 years) undergoing neurosurgery were included and monitored daily for the development of HAIs. Results: The study included 260 patients, with a mean age of 4.3 ± 4.7 years. Thirty-six HAIs were detected in 25 patients; catheter-related infections were the most frequent. Etiological identification was available in 22 cases; Gram-negative bacteria were the most commonly isolated pathogens. The incidence density was 11.0/1,000 patient days, and the incidence rate was 13.8/100 patients. The crude mortality was 0%. The risk of developing HAIs was related to the length of hospital stay, while the higher the age of the patients, the lower the risk of developing HAIs. Conclusion: To our knowledge, this survey is the first study to evaluate the overall incidence of HAIs and to explore the risk factors implicated in their development in neurosurgical pediatric patients. The most effective strategies to prevent these infections are reduction of the length of the hospital stay and improvement in device management.