The Thousand Faces of Invasive Group A Streptococcal Infections: Update on Epidemiology, Symptoms, and Therapy.

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children.

Molecular characterization of SARS-CoV-2 Omicron clade and clinical presentation in children.

Since its emergence, SARS-CoV-2 Omicron clade has shown a marked degree of variability and different clinical presentation compared with previous clades. Here we demonstrate that at least four Omicron lineages circulated in children since December 2021, and studied until November 2022: BA.1 (33.6%), BA.2 (40.6%), BA.5 (23.7%) and BQ.1 (2.1%). At least 70% of infections concerned children under 1 year, most of them being infected with BA.2 lineages (n = 201, 75.6%). Looking at SARS-CoV-2 genetic variability, 69 SNPs were found to be significantly associated in pairs, (phi < - 0.3 or > 0.3 and p-value < 0.001). 16 SNPs were involved in 4 distinct clusters (bootstrap > 0.75). One of these clusters (A23040G, A27259C, T23617G, T23620G) was also positively associated with moderate/severe COVID-19 presentation (AOR [95% CI] 2.49 [1.26-4.89] p-value: 0.008) together with comorbidities (AOR [95% CI] 2.67 [1.36-5.24] p-value: 0.004). Overall, these results highlight the extensive SARS-CoV-2 Omicron circulation in children, mostly aged < 1 year, and provide insights on viral diversification even considering low-abundant SNPs, finally suggesting the potential contribution of viral diversification in affecting disease severity.

Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children.

BACKGROUND: Despite its broad spectrum and excellent safety profile, fosfomycin is still rarely used in pediatrics, with very limited experience from clinicians. METHODS: We retrospectively reviewed the medical records of all children admitted to Bambino Gesù Children's Hospital, IRCCS, Rome, Italy, and treated with fosfomycin for any serious infection. Children with immunodeficiency and oncologic diseases were excluded. Of each, we reported and analyzed demographic and clinical data. RESULTS: The clinical charts of 20 patients were reviewed and analyzed. The mean age was 10.2 years. Most children were males (85%). Most patients treated had an osteo-articular infection (65%). In our sample, 7 patients (35%) had an underlying comorbidity. The causative agent was isolated in 14 cases (70%). All patients were treated with a combination of 2-3 antibiotics, including fosfomycin. The average duration of antibiotic treatment was 18 days. After treatment, 8 patients (40%) experienced a mild adverse reaction, possibly correlated with the administration of fosfomycin. All patients were discharged in good clinical condition. CONCLUSIONS: The present study reports on a sample of pediatric patients with complicated infections where administration of fosfomycin led to eradication of the disease with little or no side effects. Role of the underlying condition and concomitant medication in causing the reaction could not be ruled out. These data suggest that fosfomycin is an effective and safe antibiotic in the pediatric population, particularly for deep-seated infections sustained by multi-drug resistant pathogens.

Monocyte-to-lymphocyte, neutrophil-to-lymphocyte and neutrophil-to-monocyte plus lymphocyte ratios in children with active tuberculosis: A multicentre study.

AIM: Higher number of monocytes and neutrophils may correlate with active tuberculosis (TB) in children. However, the few paediatric studies available are limited by the small numbers of children with TB disease or infection included. METHODS: We calculated the monocyte-to-lymphocyte-ratio (MLR), neutrophil-to-lymphocyte-ratio (NLR) and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) in children with active TB, latent TB infection (LTBI), other infectious and non-infectious conditions and healthy children evaluated in two referral centres in Rome. RESULTS: Overall, 649 children were included (41.8% females, mean age of 5.74 years). MLR, NLR and NMLR values were always significantly higher in patients with TB compared with the other groups (p < 0.001). Considering the entire population with the outcome of TB diagnosis, NMLR, with a cut-off of 1.2, had a sensitivity of 63% and a specificity of 76% (AUC: 0.71 [0.64-0.78]); NLR, with a cut-off of 1.5, had a sensitivity of 61% and a specificity of 79% (AUC: 0.72 [0.65-0.79]); MLR, considering a cut-off of 0.2, was less sensitive (56%) but more specific (82%) with a similar AUC (0.72 [0.65-0.79]). CONCLUSION: Our study provides further evidence that MLR, NLR and NMLR can serve as first level diagnostics to support the clinical suspicion of TB in children.

Pediatric COVID-TB: A Clinical Perspective Based on the Analysis of Three Cases.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are currently two major causes of death among infectious diseases. Active tuberculosis and a history of tuberculosis appear to be associated with an increased risk of COVID-19. This coinfection, named COVID-TB, was never described in previously healthy children. We report three cases of pediatric COVID-TB. We describe three girls affected by tuberculosis, who tested positive for SARS-CoV-2. The first patient is a 5-year-old girl who was hospitalized for recurrent TB lymphadenopathy. As she never had any complications related to the concomitant infection with SARS-CoV-2, she received TB treatment. The second case is a 13-year-old patient with a history of pulmonary and splenic tuberculosis. She was admitted to the hospital due to deteriorating respiratory dynamics. She was already undergoing treatment for TB, but in the absence of improvement, she also required treatment for COVID-19. Slowly, the general condition improved until discharge. The last patient, a 10-year-old girl, was hospitalized for supraclavicular swelling. The investigations showed disseminated TB characterized by lung and bone involvement without COVID-19-related complications. She was treated with antitubercular and supportive therapy. Based on the data obtained from the adult population and our small experience, a pediatric patient with COVID-TB infection should be considered potentially at risk of worse clinical outcomes; for this reason, we suggest close observation, careful clinical management, and consideration of targeted anti-SARS-CoV-2 therapies.

The Prevalence of Carbapenemase-Producing Microorganisms and Use of Novel Cephalosporins for the Treatment of Severe Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria in a Pediatric Cardiac Intensive Care Unit.

BACKGROUND: The spread of carbapenem-resistant organisms (CROs) is an increasingly serious threat globally, especially in vulnerable populations, such as intensive care unit (ICU) patients. Currently, the antibiotic options for CROs are very limited, particularly in pediatric settings. We describe a cohort of pediatric patients affected by CRO infections, highlighting the important changes in carbapenemase production in recent years and comparing the treatment with novel cephalosporins (N-CEFs) to Colistin-based regimens (COLI). METHODS: All patients admitted to the cardiac ICU of the Bambino Gesù Children's Hospital in Rome during the 2016-2022 period with an invasive infection caused by a CRO were enrolled. RESULTS: The data were collected from 42 patients. The most frequently detected pathogens were Pseudomonas aeruginosa (64%), Klebsiella pneumoniae (14%) and Enterobacter spp. (14%). Thirty-three percent of the isolated microorganisms were carbapenemase producers, with a majority of VIM (71%), followed by KPC (22%) and OXA-48 (7%). A total of 67% of patients in the N-CEF group and 29% of patients in the comparative group achieved clinical remission (p = 0.04). CONCLUSION: The increase over the years of MBL-producing pathogens in our hospital is challenging in terms of therapeutic options. According to the present study, N-CEFs are a safe and effective option in pediatric patients affected by CRO infections.

Aggregatibacter actinomycetemcomitans infection in a 15-year-old boy with pulmonary empyema: a case report and review of literature.

BACKGROUND: Aggregatibacter actinomycetemcomitans (Aa), previously known as Actinobacillus actinomycetemcomitans, is a slow-growing Gram-negative coccobacillus, member of the HACEK group of bacteria colonizing oral flora. Besides causing infectious diseases in the oral cavity such as dental caries and periodontitis, it is responsible for severe extra-oral infections secondary to hematogenous spread or aspiration, such as endocarditis, soft tissue abscesses and osteomyelitis. The diagnosis depends on prolonged bacterial culture of biological material obtained through biopsy. Aa is susceptible to most antibiotics but complete eradication often requires a long term treatment. CASE PRESENTATION: We report the case of a 15-year-old previously healthy boy diagnosed with both pulmonary empyema and subphrenic chest wall abscess caused by Aa. He was admitted to our Pediatric Emergency department for evaluation of a right mass associated with marked asthenia and dry cough. After radiological findings etiological diagnosis was made by culture of fluid drainage of pleural empyema. He started empirical antibiotic therapy with intravenous piperacillin/tazobactam, whose sensibility was confirmed by the antibiogram, then, for occurrance of hepatopathy it was switched to ciprofloxacin: the patient almost completely recovered after 6-month therapy. CONCLUSIONS: Extra-oral infections caused by Aa are extremely rare, especially in children, and not well described yet. To our knowledge, there is only another similar case described in literature. However, the case described in our manuscript represents the only one presenting with pulmonary empyema without involvement of lung parenchyma in children. We also conducted a brief review of published cases of Aa infection in the pediatric population. This case report reminds us the importance of an accurate inspection of the oral cavity during the examination of pediatric patients.

Abdominal Tuberculosis in Children: A Case Series of Five Patients.

Tuberculosis remains (TB) to be one of the most common causes of child morbidity and mortality. Abdominal TB is not frequently diagnosed and, although its incidence is not definitively established, there are data that seem to indicate that it accounts for approximately 1-3% of all pediatric TB cases and for no more than 10% of those with extrapulmonary manifestations. It seems, however, that abdominal TB is significantly more common than usually thought as signs and symptoms are non-specific and may mimic other diseases. The delayed or wrong diagnosis of pediatric abdominal TB can have dramatic consequences as they can lead to untreated TB with miliary dissemination, unnecessary surgery, or dangerous drug therapies. This report describes five cases of abdominal TB diagnosed among 216 pediatric patients admitted for TB in Italy from 2011 to 2021. Our cases evidence that abdominal TB is a complex and potentially very severe disease that, when not appropriately diagnosed, may be associated with severe complications and prolonged anti-TB therapy. Discussion among specialists is crucial to achieve an early diagnosis and to promptly start the anti-TB treatment. Further studies are needed to clarify the appropriate duration of therapy as well as management of MDR abdominal TB cases.

Performance of QuantiFERON-TB Gold Plus assays in paediatric tuberculosis: a multicentre PTBNET study.

RATIONALE: In 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB). OBJECTIVES: This study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe. METHODS: Multicentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019. MEASUREMENTS AND MAIN RESULTS: 1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4-12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TB in 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB 77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively). CONCLUSIONS: The results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

One Year of Lung Ultrasound in Children with SARS-CoV-2 Admitted to a Tertiary Referral Children's Hospital: A Retrospective Study during 2020-2021.

During the COVID-19 pandemic, the lung ultrasound (LU) turned out to be a pivotal tool to study the lung involvement in the adult population, but the same was not well evaluated in children. We detected the LU patterns through an integrated approach with clinical−laboratory features in children hospitalized for COVID-19 in relation to the temporal trend of the Italian epidemic. We conducted a retrospective study which took place at a pediatric tertiary hospital from 15 March 2020 to 15 March 2021. We compared the characteristics of the initial phase of the first COVID-19 year­in the spring and summer (15 March−30 September 2020)­and those of the second phase­in the autumn and winter (1 October 2020−15 March 2021). Twenty-eight patients were studied both in the first and in the second phase of the first COVID-19 year. The disease severity score (DSS) was significantly greater in the second phase (p = 0.015). In the second phase of the first COVID-19 year, we detected a more significant occurrence of the following LU features than in the first phase: the irregular pleural line (85.71% vs. 60.71%; p = 0.035), the B-lines (89.29% vs. 60%; p = 0.003) and the several but non-coalescent B-lines (89.29% vs. 60%; p = 0.003). The LU score correlated significantly with the DSS, with a moderate relationship (r = 0.51, p < 0.001). The combined clinical, laboratory and ultrasound approaches might be essential in the evaluation of pulmonary involvement in children affected by COVID-19 during different periods of the pandemic.

Clostridioides difficile Infection in Children: A 5-Year Multicenter Retrospective Study.

While there are numerous studies regarding Clostridioides difficile infection (CDI) in adults, literature on the pediatric population is scarce. Therefore, we performed a 5-year retrospective study between January 2014 and December 2018 in two referral centers in Rome, Italy. There were 359 patients tested for CDI who were enrolled: 87 resulted in positive and 272 in negative. CDI children had a higher number of previous-day hospital admissions (p = 0.024), hospitalizations (p = 0.001), and total hospital admissions (p = 0.008). Chronic comorbidities were more frequent in the CDI group (66.7% vs. 33.3%). Previous use of proton pump inhibitors and antibiotics was associated with CDI (p < 0.001). Among the antibiotics, only fluoroquinolones were significantly associated with CDI. Also, CDI children were more frequently exposed to antibiotics during the episode of hospitalization when children were tested. Our study provides an updated clinical and epidemiological analysis of children with CDI compared with a control group of children who tested negative. Further prospective studies could better define risk factors and preventive methods.

Safety of Monoclonal Antibodies in Children Affected by SARS-CoV-2 Infection.

Monoclonal antibody therapies for COVID-19 have been frequently used in adults, whereas there are little data regarding the safety or efficacy of monoclonal antibody treatments in pediatric patients affected by COVID-19. We report our experience in the administration of mAb as a treatment for SARS-CoV-2 infection in children aged from 24 days to 18 years old.

Severe COVID-19 Complicated by Cerebral Venous Thrombosis in a Newborn Successfully Treated with Remdesivir, Glucocorticoids, and Hyperimmune Plasma.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic, affecting all age groups with a wide spectrum of clinical presentation ranging from asymptomatic to severe interstitial pneumonia, hyperinflammation, and death. Children and infants generally show a mild course of the disease, although infants have been observed to have a higher risk of hospitalization and severe outcomes. Here, we report the case of a preterm infant with a severe form of SARS-CoV-2 infection complicated by cerebral venous thrombosis successfully treated with steroids, hyperimmune plasma, and remdesivir.

Virological and immunological features of SARS-COV-2 infected children with distinct symptomatology.

BACKGROUND: Although SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti-SARS-CoV-2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen-specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS patients had lower viral load at diagnosis (p = .004) and faster virus clearance (p = .0002) compared with SY patients. Anti-SARS-CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+ T cells, whereas pro-inflammatory plasma protein profile was found to be associated with symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance.

Clinical characteristics of children infected with SARS-CoV-2 in Italy.

BACKGROUND: Since December 2019 coronavirus disease (COVID-19) emerged in Wuhan and spread rapidly worldwide. Despite the high number of people affected, data on clinical features and prognostic factors in children and adolescents are limited. We propose a retrospective study aimed to evaluate clinical characteristics of children infected with SARS-CoV-2 in Italy. METHODS: A pediatric population admitted with COVID-19 to Bambino Gesù Children's Hospital of Rome (Italy) in the period from the end of February to July 2020 has been studied. Medical history, comorbidities, symptoms and laboratory findings were obtained from patients' electronic medical records. RESULTS: In 66 patients (35 males and 31 females) we found that: i) fever and cough were the dominant symptoms, while vomit and convulsions were rare symptoms; and ii) all ages of childhood were susceptible to COVID-19. Furthermore, we found that, compared to females, males with COVID-19, although not significantly, had higher values of inflammatory markers such as C-reactive protein (CRP) and ESR. Conversely, we found that COVID-19 positive females were older than males and required more days of hospitalization. Both males and females COVID-19 positives had procalcitonin values within the normal range and D-Dimer values slightly higher than the normal range. With regard to this latter marker, the value measured in females, although not significant, was higher than that measured in males. Interestingly, the presence of leukopenia was found in both sexes. CONCLUSIONS: Compared to the adults we found that COVID-19 infection in children is a non-severe inflammatory disease in both males and females. In any case, many detailed studies should be conducted.

HHV6-related mild encephalopathy with reversible splenial lesion (MERS) presenting with urinary and fecal retention in an Italian adolescent.

Mild encephalopathy with a reversible splenial lesion (MERS) is an uncommon clinico-radiological entity characterized by magnetic resonance imaging (MRI) findings of a reversible lesion in the splenium of corpus callosum associated with a significant neurological manifestation of encephalopathy. The majority of reported cases involve the Asiatic population and are closely associated with infection. We report the case of an adolescent with an HHV6-related MERS presenting with hyponatremia and urinary and fecal retention. To our knowledge, urinary retention is not a constant aspect of the disease and has rarely been described, while fecal retention has never been reported before. Despite the self-limiting nature of the disease, it is mandatory to suspect it for a faster diagnosis and it might be useful to know its rare occurrences in order to better understand its etiopathogenetic mechanisms.

Acute cerebellitis in children: an eleven year retrospective multicentric study in Italy.

BACKGROUND: Acute cerebellitis (AC) and acute cerebellar ataxia (ACA) are the principal causes of acute cerebellar dysfunction in childhood. Nevertheless. there is no accepted consensus regarding the best management of children with AC/ACA: the aim of the study is both to assess clinical, neuroimaging and electrophysiologic features of children with AC/ACA and to evaluate the correlation between clinical parameters, therapy and outcome. METHODS: A multicentric retrospective study was conducted on children ≤ 18 years old admitted to 12 Italian paediatric hospitals for AC/ACA from 01/01/2003 to 31/12/2013. A score based on both cerebellar and extracerebellar signs/symptoms was computed for each patient. One point was given for each sign/symptom reported. Severity was divided in three classes: low, moderate, severe. RESULTS: A total of 124 children were included in the study. Of these, 118 children received a final diagnosis of ACA and 6 of AC. The most characteristic finding of AC/ACA was a broad-based gait disturbance. Other common symptoms included balance disturbances, slurred speech, vomiting, headache and fever. Neurological sequelae were reported in 6 cases (5%) There was no correlation among symptoms, cerebrospinal fluid findings, clinical outcome. There was no correlation between clinical manifestations and clinical score on admission and length of hospital stay, sex, age and EEG findings with sequelae (P > 0.05). Children with pathological magnetic resonance imaging (MRI) or computed tomography (CT) had a higher probability of having clinical sequelae. Treatment was decided independently case by case. Patients with a higher clinical score on admission had a higher probability of receiving intravenous steroids. CONCLUSIONS: We confirmed the literature data about the benign course of AC/ACA in most cases but we also highlighted a considerable rate of patients with neurological sequelae (5%). Pathological MRI or CT findings at admission correlate to neurological sequelae. These findings suggest the indication to perform an instrumental evaluation in all patients with AC/ACA at admission to identify those at higher risk of neurological outcome. These patients may benefit from a more aggressive therapeutic strategy and should have a closer follow-up. Randomized controlled trials are needed to confirm these observations. The ultimate goal of these studies could be to develop a standardized protocol on AC/ACA. The MRI/CT data, associated with the clinical manifestations, may allow us to define the class risk of patients for a neurological outcome.

NK cell effector functions in a Chédiak-Higashi patient undergoing cord blood transplantation: Effects of in vitro treatment with IL-2.

NK cell cytotoxicity in Chédiak-Higashi syndrome (CHS) is strongly impaired as lytic granules are not released upon NK-target cell contact, contributing to several defects typical of this severe immunodeficiency. Correction of NK cell defects in CHS should improve the outcome of hematopoietic stem-cell transplantation, proposed as therapy. We investigated NK cell functions in a CHS patient before and after cord-blood transplantation, and the ability of in vitro IL-2 treatment to restore them. Before the transplant, the strong defect in NK cell-mediated natural and antibody-dependent cytotoxicity, as well as in IFN-γ production, could be restored up to normal levels by in vitro IL-2 treatment. This cytokine also caused the appearance of smaller lysosomal granules and their orientation towards the NK-target cell contact area, thus suggesting that IL-2 had a more general capacity to restore NK cell effector functions. Moreover after the transplant, although the successful engraftment, NK cell cytotoxicity resulted still partially impaired at one year, almost normal at ten years and, anyhow, fully recovered by in vitro IL-2 treatment. Taken together, our results indicate that IL-2 had a wide capacity to restore NK cell effector functions, being able to reverse the altered cytotoxic activity, lytic granule pattern, and cytokine production observed in the CHS patient.

Pediatric Tuberculosis in Italian Children: Epidemiological and Clinical Data from the Italian Register of Pediatric Tuberculosis.

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries.

Carbapenem-resistant Enterobacteriaceae Infections in Children: An Italian Retrospective Multicenter Study.

BACKGROUND: The spread of carbapenem-resistant Enterobacteriaceae (CRE) is a health problem of major concern. CRE-related infections have significant morbidity and mortality, but data on CRE infection in pediatric population are limited. The aim of this study was to analyze epidemiologic and clinical characteristics, risk factors, therapeutic options and outcome of CRE infections in children in Italy. METHODS: We performed a retrospective, multicenter, observational study of children with confirmed CRE infection or colonization admitted between January 1, 2011, and March 1, 2014, to 7 Italian pediatric centers. RESULTS: Sixty-nine patients presenting 74 CRE infections and/or colonization were included. The most frequently isolated strain was Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Children with CRE infections had longer length of stay in hospital (P < 0.001), duration of disease (P = 0.001) and antimicrobial treatment (P < 0.001) than colonized children. Oncologic/immunosuppressive conditions are one of the factors significantly associated with a fatal outcome among children with CRE infections. CONCLUSIONS: Our study confirms that CRE infections affect mostly children with oncologic diseases and immunosuppression. Controlled studies in large cohorts are needed to evaluate the best therapeutic options and to assess further risk factors influencing outcomes and the survival of pediatric patients with infections caused by CRE.