Clinical and Radiological Features of Pneumocystis jirovecii Pneumonia in Children: A Case Series.

BACKGROUND: Pneumocytis jirovecii pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to present the radiological and clinical pathway of PJP in a pediatric population. DESCRIPTION OF CASES: All PJP cases in non-HIV/AIDS patients diagnosed at Istituto Giannina Gaslini Pediatric Hospital in Genoa (Italy) from January 2012 until October 2022 were retrospectively evaluated. Nine cases were identified (median age: 8.3 years), and of these, 6/9 underwent prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX; five once-a-week schedules and one three times-a-week schedule), while 3/9 did not receive this. PJP was diagnosed by real-time PCR for P. jirovecii-DNA in respiratory specimens in 7/9 cases and two consecutive positive detections of ß-d-glucan (BDG) in the serum in 2/9 cases. Most patients (6/8) had a CT scan with features suggestive of PJP, while one patient did not undergo a scan. All patients were treated with TMP/SMX after a median time from symptoms onset of 3 days. In 7/9 cases, empirical TMP/SMX treatment was initiated after clinical suspicion and radiological evidence and later confirmed by microbiological data. Clinical improvement with the resolution of respiratory failure and 30-day survival included 100% of the study population. DISCUSSION: Due to the difficulty in obtaining biopsy specimens, PJP diagnosis is usually considered probable in most cases. Moreover, the severity of the clinical presentation often leads physicians to start TMP/SMX treatment empirically. BDG proved to be a useful tool for diagnosis, and CT showed good accuracy in identifying typical patterns. In our center, single-day/week prophylaxis was ineffective in high-risk patients; the three-day/week schedule would, therefore, seem preferable and, in any case, should be started promptly in all patients who have an indication of pneumonia.

Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Clinical and Microbiological Characteristics of Deep Neck Abscesses in Pediatrics: Analysis of a Case Series from a 3rd Level Pediatric Hospital.

As there is currently no consensus on managing deep neck infections in pediatric populations, we report a case series from a large pediatric hospital. Clinical data of patients discharged from Istituto Gaslini-Children's Hospital from January 2014 to June 2020 with peritonsillar, parapharyngeal, or retropharyngeal abscess diagnoses were collected. A total of 59 patients were identified. Patients underwent surgical drainage in 47% of cases. Streptococcus mitis/oralis was the most isolated pathogen. Surgically treated patients did have larger abscesses compared to others, but there were no differences in the duration of hospitalization. Children who received NSAIDs at home had significant delays in diagnosis (median 4 vs. 1.5 days, p = 0.008). In our experience, clinical presentation of DNIs is often evocative, but evaluation should include imaging with CT/MRI. Surgery is effective in larger abscesses, allowing for etiological diagnosis with consequent antibiotic adjusting. From an anamnestic point of view, home medications such as NSAIDs could delay diagnosis.

Sirolimus Restores Erythropoiesis and Controls Immune Dysregulation in a Child With Cartilage-Hair Hypoplasia: A Case Report.

Cartilage-hair hypoplasia (CHH) is a syndromic immunodeficiency characterized by metaphyseal dysplasia, cancer predisposition, and varying degrees of anemia. It may present as severe combined immunodeficiency in infancy, or slowly progress until fully manifesting in late adolescence/adulthood. No targeted treatment is currently available, and patients are usually managed with supportive measures, or are offered a bone marrow transplant if the clinical phenotype is severe and a suitable donor is available. We report the case of a young girl presenting with transfusion-dependent erythropoietic failure and immunological features resembling autoimmune lymphoproliferative syndrome who responded well to empirical sirolimus. She later developed a marked growth delay, which was ultimately attributed to metaphyseal dysplasia. A diagnosis of CHH was reached through whole-genome sequencing (WGS), after a less sensitive genetic diagnostic strategy failed. The patient eventually underwent a haploidentical bone marrow transplant due to progressive combined immunodeficiency manifested as cryptococcal meningoencephalitis. This case illustrates the potential role of sirolimus in correcting anemia and partially controlling the immune aberrations associated with CHH, and serves as a reminder of the invaluable role of WGS in diagnosing patients with complex and atypical presentations.

Pharmacokinetics and pharmacodynamics of antibiotics in cystic fibrosis: a narrative review.

Cystic fibrosis affects several organs, predisposing patients to severe bacterial respiratory infections, including those caused by methicillin-resistant Staphylococcus aureus. Cystic fibrosis is also associated with a wide spectrum of pathological changes that can significantly affect the absorption, distribution, metabolism, and/or elimination of several drugs, including antibacterial agents. Therefore, awareness of the pharmacokinetic derangements in patients with cystic fibrosis is mandatory for the optimisation of antibiotic therapy. This review discusses the basic principles of pharmacokinetics and the pathophysiology of the pharmacokinetics changes associated with cystic fibrosis; it also provides an update of available data for the most widely used antibiotics. Evidence accumulated in the last few years has clearly shown that a significant number of cystic fibrosis patients treated with conventional dosing schemes have sub-therapeutic antibiotic concentrations, increasing their risk of therapeutic failure and/or the emergence of resistant pathogens. Some proposals to optimise antibiotic therapies in this clinical setting based on therapeutic drug monitoring are also discussed.

Procalcitonin and Early Postoperative Infection After Pediatric Cardiopulmonary Bypass Surgery.

OBJECTIVES: Systemic inflammation and bacterial infections are critical occurrences after pediatric cardiac surgery. Elevated white blood cell count and C-reactive protein cannot discriminate between these two conditions in the early postoperative period. The aim of this study was to understand whether procalcitonin (PCT) values within 48 hours of surgery could be a useful marker of postoperative infection. DESIGN: Retrospective observational study. SETTING: The study was performed in a teaching hospital. PARTICIPANTS: All patients ≤six years of age. INTERVENTIONS: Cardiac surgery on cardiopulmonary bypass from January 1, 2017 to January 1, 2020. MEASUREMENT AND MAIN RESULTS: PCT, white blood cell count, and C-reactive protein values were measured at intensive care unit admission and at 24 and 48 hours after surgery. All positive cultures in the first seven days after surgery were recorded. Out of 177 consecutive patients, 22 (12%) developed infections. PCT at 48 hours after surgery was the only laboratory predictor of infections in the first seven days after surgery (p = 0.02). Receiver operating curve analyses on PCT values at 48 hours identified an optimal cut-off value of 1.85 ng/mL in the overall population. Area under the curve was 0.63, sensitivity 63%, and specificity 69%. CONCLUSIONS: In light of this preliminary result, the clinical relevance and predictive accuracy of PCT are promising in patients with increasing values of PCT but need to be confirmed in a larger sample.

Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality.

Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.

8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation.

Paediatric patients with cancer and those undergoing allogeneic haematopoietic cell transplantation have an increased susceptibility to invasive fungal diseases. In addition to differences in underlying conditions and comorbidities relative to adults, invasive fungal diseases in infants, children, and adolescents are unique in terms of their epidemiology, the validity of current diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of phase 3 clinical trials to provide data to guide evidence-based interventions. To re-examine the state of knowledge and to further improve invasive fungal disease diagnosis, prevention, and management, the 8th European Conference on Infections in Leukaemia (ECIL-8) reconvened a Paediatric Group to review the literature and to formulate updated recommendations according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) grading system, which are summarised in this Review.

8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation.

Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.

Resistance to Antibiotics of Uropathogen Bacteria Isolated From Urine and Blood in Pediatric Cancer Patients: A Single Center, 12-year Study.

Resistant pathogens have become a major healthcare problem in children with cancer, causing different kinds of infections such as the bloodstream ones, most common, and most frequently described and the urinary tract ones, of which less data are available. We analyzed and compared the proportions, and the trends of resistance in pathogens isolated from blood and urines in children with cancer followed in IRCCS Istituto Giannina Gaslini, Genova, Italy, from January 2007 to December 2018. Overall, 345 strains detected in urines and 282 in bloodstream infections were analyzed. Enterobacteriales were the most frequently isolated pathogens. During the study period in urines, there was a significant increase of resistance to ceftazidime, ciprofloxacin, piperacillin/tazobactam, and trimethoprim-sulfamethoxazole, but pathogens from blood were significantly more frequently resistant to amikacin, piperacillin/tazobactam, and combination therapy piperacillin/tazobactam+amikacin, even if with a decreasing trend during the study period. These data confirm the importance of surveillance of isolated microorganism and antibiotic resistance in cancer children.

Intravenous isavuconazole can be administered 5 days-a-week. A possibility suggested by a real-life observation.

In this report it is shown that intravenous formulation of isavuconazole could be administered 5/7 days a week in patients who can not swallow capsules, once the steady state has been stably reached and maintained, thanks to its very long half-life. In this case TDM should be highly recommended.

Failures of once-a-week trimethoprim-sulfamethoxazole prophylaxis in children undergoing allogeneic hematopoietic stem cell transplant.

Once-a-week cotrimoxazole is an effective prophylaxis for pneumocystosis during antineoplastic chemotherapy or autologous stem cell transplant. Following allogeneic stem cell transplant, this schedule is at risk of pneumocystosis or neurotoxoplasmosis, as demonstrated by these case reports. Therefore, a 3-times-a-week schedule must be adopted in these patients.

Diagnosis of invasive fungal disease in children: a narrative review.

Introduction: Invasive fungal diseases (IFD) represent important causes of morbidity and mortality in pediatrics. Early diagnosis and treatment of IFD is associated with better outcome and this entails the need to use fast and highly sensitive and specific methods that can support clinicians in the management of IFD.Areas covered: A narrative review was performed on conventional diagnostic methods such as culture, microscopy and histopathology are still gold standard but are burdened by a lack of sensitivity and specificity; on the other hand, imaging and noninvasive antigen-based such as beta-D-glucan, galactomannan and molecular biomarkers are the most convenient nonculture methods for diagnosis and monitoring effects of therapy. Aim of the present review is to summarize what is available in these fields at end of the second decade of the third millennium and look for future perspectives.Expert opinion: Promising and useful diagnostic methods have been applied in infectious disease diagnosis in clinical practice or in designing platforms. Unfortunately, most of them are not standardized or validated in pediatric population. However, clinicians should be aware of all innovative diagnostic tools to use in combination with conventional diagnostic methods for a better management of pathology and patient.