Martina Di Giuseppe

RESEARCH, TEACHING, or OTHER INTERESTS

Pediatrics, Perinatology and Child Health, Infectious Diseases

Scopus Publications

Therapeutic Drug Monitoring-Guided Linezolid Therapy for the Treatment of Multiple Staphylococcal Brain Abscesses in a 3-Month-Old Infant
Anna Cascone, Maia De Luca, Raffaele Simeoli, Bianca Maria Goffredo, Laura Cursi, Costanza Tripiciano, Lorenza Romani, Stefania Mercadante, Martina Di Giuseppe, Francesca Ippolita Calo Carducci,et al.
MDPI AG
Brain abscesses are invasive infections of the central nervous system with a high level of treatment complexity especially in pediatric patients. Here, we describe a 3-month-old infant with multiple brain abscesses caused by methicillin-susceptible Staphylococcus aureus (MSSA). The patient was initially treated with empirical antibiotics (ceftriaxone, metronidazole, vancomycin). Upon MSSA identification, therapy was optimized by switching vancomycin to linezolid to improve tissue penetration. Therapeutic drug monitoring (TDM) was performed to check linezolid levels in the plasma and pus of the abscess, confirming drug penetration into brain tissue. A two-stage surgical drainage approach, consisting of repeated pus aspiration through an intracystic catheter, was then performed to achieve a significant reduction in abscess size. After nine weeks of antibiotic therapy, the patient was discharged in good clinical condition. This case highlights the role of linezolid for the treatment of complicated CNS infections and the importance of a multidisciplinary approach, combining TDM-based antibiotic therapy with timely and eventually repeated surgery, in order to effectively treat brain abscesses.


Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children
Marco Roversi, Antonio Musolino, Martina Di Giuseppe, Costanza Tripiciano, Laura Cursi, Laura Lancella, and Andrzej Krzysztofiak
Ovid Technologies (Wolters Kluwer Health)
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.


The Thousand Faces of Invasive Group A Streptococcal Infections: Update on Epidemiology, Symptoms, and Therapy
Stefania Mercadante, Andrea Ficari, Lorenza Romani, Maia De Luca, Costanza Tripiciano, Sara Chiurchiù, Francesca Ippolita Calo Carducci, Laura Cursi, Martina Di Giuseppe, Andrzej Krzysztofiak,et al.
MDPI AG
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.


Safety of Nirmatrelvir-Ritonavir Administration in Children With Immunodeficiency and/or Comorbidities With SARS-CoV-2 Infection A Retrospective Clinical Report
Stefania Bernardi, Marco Roversi, Antonio Torelli, Antonio Musolino, Emanuele Nicastri, Paolo Palma, Paolo Rossi, Leonardo Vallesi, Tiziana Corsetti, Laura Lancella,et al.
Ovid Technologies (Wolters Kluwer Health)
Introduction: Despite the generally mild course of COVID-19 in children, immunocompromised patients may experience complications or severe infection. This study reports the clinical outcomes of pediatric patients treated with nirmatrelvir and ritonavir (N/R) for SARS-CoV-2 infection. Methods: We retrospectively reported the data of children with any immunodeficiency with COVID-19 who received N/R treatment between March 2022 and June 2023 at the Bambino Gesù Children’s Hospital. Patients were treated with N/R for 5 days. We compared liver and kidney function before and after treatment with N/R and looked for a relationship between the duration of COVID-19 infection and the time from positivity to administration of N/R administration. Results: A total of 85 pediatric immunocompromised patients with COVID-19 were included in the study, with a mean age of 10.7 years (SD 4.8), mostly males (60%). We found a significant difference in the viral load before and after N/R administration. Four patients (4.7%) experienced adverse events related to N/R therapy. One of these had to discontinue N/R administration. Three patients (3.5%) experienced negative effects of drug interactions during N/R therapy, namely an increase of sirolimus and ciclosporin serum levels. A significant positive correlation was found between the time from SARS-CoV-2 positivity to N/R administration and the duration of SARS-CoV-2 swab positivity (R = 0.78, P < 0.001), suggesting that the earlier N/R is administered, the shorter the duration of COVID-19 in the study sample. Conclusion: Our experience shows that N/R is reasonably safe in the pediatric population and could favor viral clearance, thus reducing the duration of infection.


Monocyte-to-lymphocyte, neutrophil-to-lymphocyte and neutrophil-to-monocyte plus lymphocyte ratios in children with active tuberculosis: A multicentre study
Laura Cursi, Laura Lancella, Francesco Mariani, Laura Martino, Bianca Leccese, Martina Di Giuseppe, Francesco Venuti, Russo Cristina, Leonarda Gentile, Michela Sali,et al.
Wiley
AbstractAimHigher 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.MethodsWe 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.ResultsOverall, 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]).ConclusionOur study provides further evidence that MLR, NLR and NMLR can serve as first level diagnostics to support the clinical suspicion of TB in children.


Adeno-associated virus 2 infection in children with non-A–E hepatitis
Antonia Ho, Richard Orton, Rachel Tayler, Patawee Asamaphan, Vanessa Herder, Chris Davis, Lily Tong, Katherine Smollett, Maria Manali, Jay Allan,et al.
Springer Science and Business Media LLC



Pediatric COVID-TB: A Clinical Perspective Based on the Analysis of Three Cases
Fabrizio Leone, Martina Di Giuseppe, Maia De Luca, Laura Cursi, Francesca Ippolita Calo Carducci, Andrzej Krzysztofiak, Sara Chiurchiù, Lorenza Romani, Cristina Russo, Laura Lancella,et al.
MDPI AG
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
Costanza Tripiciano, Lorenza Romani, Stefania Mercadante, Laura Cursi, Martina Di Giuseppe, Francesca Ippolita Calo Carducci, Tiziana Fragasso, Luca Di Chiara, Cristiana Garisto, Annamaria Sisto,et al.
MDPI AG
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.


Clinical report and predictors of sequelae of 319 cases of pediatric bacterial osteomyelitis
Andrzej Krzysztofiak, Marco Roversi, Antonio Musolino, Marco Cirillo, Renato Maria Toniolo, Osvaldo Mazza, Livia Gargiullo, Laura Lancella, Paolo Rossi, Alberto Villani,et al.
Springer Science and Business Media LLC
AbstractPediatric osteomyelitis is an insidious disease that can lead to permanent sequelae, the management of which still relies on lengthy intravenous antibiotic therapy. The purpose of this study is to report and describe the clinical course and outcome of pediatric bacterial osteomyelitis in our experience. We reported the clinical, diagnostic, and treatment characteristics of all cases of osteomyelitis in children younger than 18 years of age who were hospitalized between January 2010 and December 2021 at the Bambino Gesù Children’s Hospital in Rome, Italy, we compared patients with and without complications at follow-up, to identify any predictive factor for sequelae. The study sample included 319 cases of pediatric bacterial osteomyelitis. The median age was 7.77 years. Males (60.8%) were more affected than females. The most affected bones were the femur, tibia, and spine. Etiology was identified in 40.1% of cases, with S.aureus as the most common causative agent. Sequelae were reported in 43 cases (13.5%). The main predictors of sequelae were sepsis on admission and hypergammaglobulinemia. Our results show that a severe presentation with sepsis and hypergammaglobulinemia on admission may be associated with a higher frequency of late sequelae. Early recognition and aggressive treatment of this subgroup of patients may lead to a reduction in complications.


Safety of Monoclonal Antibodies in Children Affected by SARS-CoV-2 Infection
Lorenza Romani, Francesca Ippolita Calò Carducci, Sara Chiurchiù, Laura Cursi, Maia De Luca, Martina Di Giuseppe, Andrzej Krzysztofiak, Laura Lancella, Paolo Palma, Leonardo Vallesi,et al.
MDPI AG
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.


Post-discharge telephonic follow-up of pediatric patients affected by SARS-CoV2 infection in a single Italianpediatric COVID center: a safe and feasible way to monitor children after hospitalization
Vitangelo Clemente, Costanza Tripiciano, Patrizio Moras, Daniele Deriu, Martina Di Giuseppe, Anna Lucia Piscitelli, Michela Cammerata, Maria Antonietta De Ioris, Francesca Ippolita Calò Carducci, Stefania Bernardi,et al.
Springer Science and Business Media LLC
Abstract Background SARS-CoV-2 infection in children is often non severe and in the majority of cases does not require long term hospitalization, nevertheless it is burdened with social issues and managing difficulties. To our knowledge there is no literature on telephonic follow up in pediatric patients with positive PCR for SARS-CoV-2 on rhino-pharyngeal swab after discharge. The aim of the study is to describe our experience in a telephonic follow up which can allow early and safe discharge from hospital while keeping the patients under close clinical monitoring. Materials and methods Sixty-five children were admitted for SARS-CoV-2 infection at Bambino Gesù Pediatric Hospital COVID Center from 16th March to 3rd July. We monitored through a telephonic follow-up, using a specific survey, the patients discharged still presenting a positive PCR for SARS-CoV-2. We checked if any symptoms occurred at home until recovery, defined as two consecutive negative PCR for SARS-CoV-2 on rhino-pharyngeal swabs. Results During the follow up 7 patients had mild and self-limited symptoms related to SARS-CoV-2 infection, while 2 patients were re-hospitalized. One patient had Multisystem Inflammatory Syndrome in Children (MIS-C), the other patient had an increase in troponin and D-dimers. We also monitored the average time of viral shedding, resulting in a median duration of 28 days. Conclusion Our experience describes the daily telephonic follow up as safe in pediatric patients discharged with positive PCR. As a matter of fact it could avoid long term hospitalization and allow to promptly re-hospitalize children with major complications such as MIS-C.


Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies
Nicola Cotugno, Alessandra Ruggiero, Francesco Bonfante, Maria Raffaella Petrara, Sonia Zicari, Giuseppe Rubens Pascucci, Paola Zangari, Maria Antonietta De Ioris, Veronica Santilli, E.C. Manno,et al.
Elsevier BV
As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.


Vipera aspis bite neurotoxicity: two pediatric cases in Central Italy
M. Marano, M. Di Giuseppe, S. Pro, M. Pisani, M. Montibeller, G. Bottari, J. Nunziata, and C. Cecchetti
Informa UK Limited
Dear editor,There are four venomous species of viper distributed in different geographic regions of Italy, Vipera aspis, Vipera berus, Vipera ammodytes and Vipera ursinii. Neurological signs follow...