Antibiotic prophylaxis in neutropenic children with acute leukemia: Do the presently available data really support this practice?

Antibiotics are frequently administered for prophylaxis of fever in neutropenic children with cancer. This strategy is mainly derived from adults' data, and various pediatric studies evidenced the effectiveness of antibiotics (eg, fluoroquinolones) in the prevention of febrile neutropenia. However, only two pediatric randomized, double-blind, placebo-controlled trials have been performed, with a total of 262 leukemic children enrolled, and no other one was ever powered for analyzing effectiveness over other infectious complications. In an era of increasing antibiotic resistance, the widespread use of antibiotic prophylaxis in neutropenic leukemic children needs to be strongly supported.

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

Plasma 1,3-ß-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.

Magicplex(TM) Sepsis Real-Time test to improve bloodstream infection diagnostics in children.

UNLABELLED: Sepsis is the major cause of morbidity and mortality in children, especially in immunocompromised patients, and a rapid identification of causative pathogen is strongly related with a better outcome. This prospective study analyzes the role of a multiplex real-time polymerase chain reaction in sepsis' etiological diagnosis. Magicplex(TM) Sepsis Real-Time tests were performed in tertiary Regina Margherita Children's Hospital (Turin, Italy), and the medical records of children who underwent a Magicplex test were prospectively evaluated. Results of the Magicplex test were compared with those of blood culture collected at a close time point. One hundred fifty Magicplex tests were collected from 89 patients (54 males and 35 females, age interquartile range: 2.6-12.1 years). Etiological definition was achieved in 60 bloodstream infection cases (40 %). In 32 episodes, Magicplex test alone gave a positive result, and blood culture alone permitted the etiological diagnosis in 5 septic episodes. Magicplex test allowed a 143 % increase in the diagnostic value of blood cultures. CONCLUSION: These results suggest that molecular biology can be useful for rapid pathogen's identification also in children. WHAT IS KNOWN: • Sepsis represents a major cause of morbidity and mortality in children. • Sepsis outcome is strongly related to rapid microbiological identification and prompt initiation of an appropriate chemotherapy. What is New: • This manuscript is the first that describes the use of Magicplex (TM) Sepsis Real-Time test in children. • The results suggest that molecular biology can be useful for rapid pathogen's identification also in children.

The second generation of HIV-1 vertically exposed infants: a case series from the Italian Register for paediatric HIV infection.

BACKGROUND: In the Highly Active Antiretroviral Therapy (HAART) era, the prognosis of children perinatally infected with HIV-1 has significantly improved, so the number of perinatally-infected females entering child-bearing age and experiencing motherhood is increasing. METHODS: A description of the medical history and pregnancy outcomes of women with perinatal acquired HIV-1 infection enrolled in the Italian Register for HIV infection in Children. RESULTS: Twenty-three women had 29 pregnancies. They had started an antiretroviral therapy at a median of 7.7 years (interquartile range, IQR 2.3 - 11.4), and had experienced a median of 4 therapeutic regimens (IQR 2-6). Twenty women (87%) had taken zidovudine (AZT) before pregnancy, in 14 cases as a starting monotherapy. In 21 pregnancies a protease inhibitor-based regimen was used. At delivery, the median of CD4+ T lymphocytes was 450/µL (IQR 275-522), and no viral load was detectable in 15 cases (reported in 21 pregnancies). Twenty-eight children were delivered through caesarean section (median gestational age: 38 weeks, IQR 36-38, median birth weight: 2550 grams, IQR 2270 - 3000). Intravenous AZT was administered during delivery in 26 cases. All children received oral AZT (median: 42 days, IQR 31 - 42), with no adverse events reported. No child acquired HIV-1 infection. CONCLUSIONS: Despite a long history of maternal infection, multiple antiretroviral regimens and, perhaps, the development of drug-resistant viruses, the risk of mother-to-child transmission does not seem to have increased among the second-generation of HIV-1 exposed infants.

Interleukin 28B rs12979860 single-nucleotide polymorphism predicts spontaneous clearance of hepatitis C virus in children.

OBJECTIVE: Recent genome-wide association studies performed in adults correlated single-nucleotide polymorphisms (SNPs rs12979860 and rs8099917) located on chromosome 19, upstream of the interleukin 28B gene, with spontaneous clearance of hepatitis C virus and with response to treatment with paginated interferon and ribavirin. The aim of the present collaborative study was to evaluate the rs12979860 SNP in a large cohort of Italian children with perinatal acquisition of hepatitis C. METHODS: Children were prospectively enrolled in 2 Italian centers. The interleukin 28B rs12979860 SNP was studied according to the diagnosis of chronic infection or spontaneous clearance. RESULTS: One hundred thirty children (86.7%) with chronic infection and 23 (13.3%) with spontaneous clearance of the virus were enrolled. Overall, the interleukin 28B C/C and C/T-T/T genotypes were found in 57 (37.3%) and 96 (62.7%) children, respectively. The proportion of C/C genotype was higher among children who cleared infection (14/23; 60.9%) compared with children with chronic infection (43/130; 33.1%; P = 0.01; odds ratio 3.15; 90% confidence intervals 1.34-7.53). CONCLUSIONS: The present study showed that, as already demonstrated in adults, children with the rs12979860 C/C SNP of the interleukin 28B gene have a higher probability of spontaneous clearance of hepatitis C virus.

Natural history of vertically acquired HCV infection and associated autoimmune phenomena.

UNLABELLED: The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9-15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria. CONCLUSIONS: Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.

The Importance of RSV Epidemiological Surveillance: A Multicenter Observational Study of RSV Infection during the COVID-19 Pandemic.

The restrictive measures adopted worldwide against SARS-CoV-2 produced a drastic reduction in respiratory pathogens, including RSV, but a dramatic rebound was thereafter reported. In this multicenter retrospective observational study in 15 Pediatric Emergency Departments, all children <3 years old with RSV infection admitted between 1 September and 31 December 2021 were included and compared to those admitted in the same period of 2020 and 2019. The primary aim was to evaluate RSV epidemiology during and after the COVID-19 pandemic peak. The secondary aims were to evaluate the clinical features of children with RSV infection. Overall, 1015 children were enrolled: 100 in 2019, 3 in 2020 and 912 in 2021. In 2019, the peak was recorded in December, and in 2021, it was recorded in November. Comparing 2019 to 2021, in 2021 the median age was significantly higher and the age group 2-3 years was more affected. Admissions were significantly higher in 2021 than in 2020 and 2019, and the per-year hospitalization rate was lower in 2021 (84% vs. 93% in 2019), while the duration of admissions was similar. No difference was found in severity between 2019-2020-2021. In conclusion, after the COVID-19 pandemic, an increase in RSV cases in 2021 exceeding the median seasonal peak was detected, with the involvement of older children, while no difference was found in severity.

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 ±â€ŠSD linezolid treatment duration was 26.13 ±â€Š17 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.

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.

Gastrointestinal involvement in paediatric COVID-19 - from pathogenesis to clinical management: A comprehensive review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the first pandemic of the 21st century. As found in adults, signs and symptoms related to the disease mainly involve the respiratory tract in the paediatric population. However, a considerable number of children present with gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. The purpose of this review is an accurate description, from pathogenesis to clinical presentation, diagnosis and treatment, of COVID-19 effects on the gastrointestinal system at a paediatric age. SARS-CoV-2 can be identified in stool specimens of affected children by real-time polymerase chain reaction techniques. Positivity can last for several weeks after the end of the symptomatic phase. Gastrointestinal signs and symptoms are generally self-limited, can correlate with blood tests and imaging alterations, and may require supportive treatment such as hydration. However, they can precede severe disease manifestations such as the COVID-19-related multisystem inflammatory syndrome. Children belonging to risk categories such as those affected by celiac disease, inflammatory bowel disease, and hepatic disease seem to not have a more severe course than the others, even if they are undergoing immunosuppressant treatment. Medical follow-ups of patients with chronic diseases need to be revised during the pandemic period in order to postpone unnecessary tests, mainly endoscopic ones.

Long-term clinical and serological follow-up of paediatric patients infected by SARS-CoV-2.

Studies concerning Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in paediatrics are limited to children mainly selected from hospitals, where patients with complications and co-morbidities are managed. We aimed to describe the course of the Coronavirus Disease 2019 (COVID-19) in a population of children enrolled by place of residence, from diagnosis to recovery, with a long-term clinical and serological follow-up. We identified patients aged <14 years old living in the Turin Health District 3 who had SARS-CoV-2 detected in at least one nasopharyngeal swab from 1st March to 1st June 2020. Epidemiological and clinical features of SARS-CoV-2 infection were collected by way of a telephone inquiry. Enrolled patients were tested for SARS-CoV-2 serology in order to provide evidence of seroconversion and persistence of specific antibodies some time after the infection. A total of 46 patients with SARS-CoV-2 infection/COVID-19 were identified. The main pattern of viral transmission was intra-family. Eleven children were totally asymptomatic. If symptoms appeared, the disease had a mild course. A single case of COVID-19-related respiratory insufficiency was registered. Among children who underwent serological evaluation, 84% had seroconversion. No significant differences in antibody development were found according to the age and the burden of the disease. Children tested farther from the primary infection had lower antibody index titre values than the others. In conclusion, COVID-19 has a good prognosis in paediatric age. Children are able to develop a valid immune response, although their index titres seem to decrease a long time after the disease.

Clinical features of hospitalised children with 2009 H1N1 influenza virus infection.

Clinical features and outcome of 2009 H1N1 influenza virus in the paediatric setting is ill-defined. The epidemiologic and clinical features of children with confirmed H1N1 influenza virus infection admitted to an Italian tertiary paediatric hospital from August through December 2009 were evaluated. A total of 63 children (mean age 4.3 years) were studied; of these, 29 (46%) had chronic underlying diseases. The most frequent symptoms and signs at admission were fever (97%), cough (60%) and respiratory disturbances (24%). Forty patients (63.5%) had H1N1-related complications: 32 (51%) pulmonary diseases, three (5%) neurological disorders, such as acute encephalitis or acute disseminated encephalomyelitis, and two (3%) haematological alterations. Three patients were admitted to the Intensive Care Unit. Most children (81%) were treated with oseltamivir: one developed rash during treatment; no other adverse events were noticed. All children survived without sequelae. In conclusions, 2009 H1N1 influenza virus infection in children is associated with a wide spectrum of clinical manifestations. Neurological disorders are not exceptional complications. Oseltamivir therapy seems safe also in infants.

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.

Extended-Spectrum Beta Lactamase-producing Enterobacteriaceae among the pediatric population: who is at risk and why? Results from a single-centre prospective study.

A prospective 18-month case-control study was performed in a tertiary Paediatric Centre in Turin (Italy) to analyse the disease burden and identify risk factors for acquisition of Extended Spectrum Beta Lactamase-producing Enterobacteriaceae (ESBL-pE). Children with ESBL-pE isolation were enrolled as cases, with controls matched according to age, type of pathogen isolated and sample of isolation. Out of 83 children (37 males, mean age 4.7 ± 5.46 years), 45 were identified as infected (54.2%) and 38 as colonised (45.8%) by ESBL-pE. Twenty-nine (64.4%) infectious disease episodes were categorised as community-acquired, 16 (35.6%) as healthcare-associated. Escherichia coli was the most frequently isolated pathogen (52, 62.7%) and the urinary tract the most frequent site involved (26, 57.9%). No deaths occurred, even in bloodstream infection cases. Hospitalisation and exposure to broad-spectrum penicillins and III/IV generation cephalosporins in the 90-day period before bacteria isolation were found to be independent risk factors at multivariate analysis. Immunodepression, prolonged central venous catheter (CVC) and urine catheter stay, and receiving a total parenteral nutrition (TPN) in the previous 30 days were otherwise recognized as potential risk factors at univariated analysis. ESBL-producing Enterobacteriaceae infections are a growing threat even in children. Careful recognition of patients at risk should promote targeted interventions in order to reduce the ESBL burden.

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.

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 Children's 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. Cohen's 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.

Medical care related laboratory-confirmed bloodstream infections in paediatrics.

The aim of this survey was to describe the incidence, epidemiology, microbiology, risk factors and outcome of medical care related laboratory-confirmed bloodstream infections (LCBIs) observed during a twelve-month prospective study in a Paediatric Teaching Hospital in Turin, Italy. Inclusion criteria were clinical signs of sepsis and positivity of one or more of the following tests: blood culture, polymerase chain reaction for bacterial and fungal DNA on blood, and culture on intravascular device tips. In all, 140 episodes of sepsis were documented in 131 children: 37 (26.4%) were healthcare outpatient-associated, 91 (65.0%) healthcare-associated and 12 (8.6%) community-acquired. The overall incidence of healthcare-associated LCBIs was 13.6/1,000 hospitalized patients and incidence density 1.4/1,000 inpatient days. The overall mortality was 3.9%. Forty-seven (36.7%) episodes involved newborns and 107 (83.6%) episodes were observed in children with an indwelling central venous catheter. Coagulase-negative staphylococci (26.8%), Staphylococcus aureus (15.2%), Escherichia coli (8.7%) and Candida spp. (7.2%) were responsible for the majority of cases. 9.5% of S. aureus isolates were methicillin-resistant and 6.5% of Gram negatives were extended-spectrum beta-lactamase-producing. Incidence and epidemiology of medical care related LCBIs were similar to the existing literature data. LCBIs caused by antibiotic-resistant microorganisms were fewer and mortality rate was lower. Most of the LCBIs recorded involved newborns and oncological children.

An atypical deep neck infection in a two-year-old child.

Non-tuberculous mycobacteria are one of the major causes of lymphadenitis in children and seldom of deep neck infections. We reported the case of an immunocompetent two-year-old girl with adenitis and retropharyngeal abscess caused by an atypical mycobacterium. She had a positive tuberculin skin test, whereas the Quantiferon TB Gold test was negative. The child underwent a complete nodal excision. The search for acid fast bacilli was positive and Mycobacterium scrofulaceum was isolated from the surgically removed material. The retropharyngeal abscess was treated only with antimicrobial therapy, which resulted in an appreciable size reduction of the abscess. After two months antimicrobial treatment was interrupted, and complete resolution was achieved after twelve months. No relapse of disease or possible long-term complications were observed. The surgical wound healed completely, with normal overlying skin and a good aesthetic result. The clinical management of atypical mycobacteria lymphadenitis and retropharyngeal abscess in children is discussed.