Rationale: Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. Objectives: To estimate the effect of ECMO on 90-day mortality versus IMV only. Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 80 or PaCO2 ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. Measurements and Main Results: A total of 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0–9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, −2%; 95% confidence interval, −10 to 5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic. Conclusions: In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.
Quinolone resistance is a major global clinical problem. It primarily emerges in microbiota under selective pressure. Studies evaluating the incidence and risk factors for carrying quinolone-resistant bacteria in hospitalized patients treated with fluoroquinolones (FQs) are lacking. We prospectively included hospitalized patients treated with FQs. Nasal, throat and rectal swabs were performed before FQ treatment, at the end of FQ treatment and 30 days later. A 'reference group' of patients not receiving FQs was also included to determine the rates of quinolone resistance acquisition not linked to FQ treatment. Prevalence and incidence of quinolone-resistant strains of nasal coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, pharyngeal α-haemolytic streptococci and faecal Escherichia coli, and risk factors for emergence of quinolone resistance in FQ-treated patients were assessed. Four-hundred and fifty-one FQ-treated patients were included, as well as 119 subjects in the 'reference group'. Emergence of quinolone resistance occurred in 110/213 (51.6%), 50/336 (14.9%), 53/290 (18.3%) and 46/336 (13.7%) of FQ-treated patients for CoNS, S. aureus, α-haemolytic streptococci and E. coli, respectively, significantly more than for reference patients for CoNS (23/65; P < 0.05), S. aureus (5/91; P < 0.02) and E. coli (4/84; P < 0.05), but not for α-haemolytic streptococci (15/70; P = 0.55). Emergence of resistance was not associated with the type of FQ received, the duration of therapy or the duration of hospital stay, but was associated with host factors such as immunosuppression and altered performance status. FQs received during hospitalization account for high rates of emergence of resistance to FQs in clinically relevant bacteria from human microbiota, reflecting the important ecological impact of FQs. Host factors outweighed treatment or hospitalization characteristics as risk factors for carrying quinolone-resistant strains.
(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities; (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers’ approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases; (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012–2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived; (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines.
Pediatricians need to be aware that adolescents with high level of immunosuppression including rituximab may develop severe forms of COVID-19.These cases may be complicated by organizing pneumonia and long term sequelae.
Pending the authorization of new anti-CMV drugs with fewer adverse effects, exploring the possibilities offered by CMV immunoglobulins (CMVIG) seems necessary. In France, access to CMVIG requires official authorization by the national Health authority and is restricted to second line rescue therapy for CMV infection/disease. The aim of this multicenter retrospective study is to describe the indications and clinical situations that justified its use in France.A multicenter retrospective study included 22 lung transplant patients over a 3-year period. Data on clinical indication, tolerance and efficacy were collected.The main indication for CMVIG initiation, which was documented in 17 of them (82%) was complex clinical situations resulting from side effects to antiviral drug. CMVIG indication was documented as treatment for 15 patients (68%) and as a secondary prophylaxis for 7 patients (32%). Only one side effect (pruritus during infusion with no anaphylactic symptoms) attributable to CMVIG was reported. After CMVIG initiation, no recurrence of infection or disease was observed during a median follow-up of 174 (12-682) days after treatment initiation for respectively 68% and 66% of the patients.This study describes an unusual indication of CMVIG use as a last resort treatment in complex situations, based on clinical needs. CMVIG could be useful to change the course of CMV infection with minimal adverse effects or comorbidity.
Abstract Background. Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. Methods. This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. Results. Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 second percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors found associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and regarding pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas maltophilia bronchial colonization. Conclusion. Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.
Background: Infections caused by drug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa, are emerging in pediatric hospitals. New ß-lactam/ ß-lactamase inhibitor combinations exhibit activity against these pathogens; however, there is limited data regarding their use in pediatric populations. Objectives: The study aimed to describe the characteristics of ceftazidime-avibactam (CAZ/AVI) and ceftolozane-tazobactam (C/T) prescriptions in children and assess their appropriateness. Methods: We retrospectively analyzed all CAZ/AVI or C/T prescriptions in children hospitalized in a French tertiary hospital between 2017 and 2022. All clinical, biological, and pharmacological data were collected prospectively as part of the antibiotic monitoring program set up by our antimicrobial stewardship (AMS) team. Results: In total, 50 CAZ/AVI and 25 C/T prescriptions were recorded, which concerned 21 and 20 patients, respectively. All patients had an underlying chronic condition. Most prescriptions originated from Pediatric Intensive Care Units and the Department of Pediatric Pulmonology and were mainly initiated for respiratory tract infections (n = 41/50, 82% of the CAZ/AVI prescriptions and n = 14/25, 56% of the C/T prescriptions). P. aeruginosa was the primary pathogen in documented infections for both CAZ/AVI and C/T prescriptions (n = 26/48, 54% and n = 16/19, 84%, respectively). Almost all prescriptions of CAZ/AVI and C/T were considered appropriate (n = 47/50, 94% for CAZ/AVI and n = 23/25, 92% for C/T, respectively) by the AMS team. Both CAZ/AVI and C/T treatments were well tolerated and resulted in clinical success in 33 (66%) and 19 (76%) cases, respectively. Conclusion: Our study suggests that CAZ/AVI and C/T are reasonable treatment options for children infected with Gram-negative pathogens resistant to carbapenems.
