The investigation and successful management of a monoclonal Acinetobacter baumannii outbreak in a... more The investigation and successful management of a monoclonal Acinetobacter baumannii outbreak in a neonatal intensive care unit are described. Upon the first clustered carbapenem-resistant A. baumannii (CRAB) infections, a bundle of actions were taken, including enhanced infection control, active surveillance (weekly stool samples), case-control study, staff education, daily audits and discontinuation of new admissions. Between September and December 2011, eight neonates developed 10 CRAB infections (five blood, four respiratory and one eye). A total of 216 active surveillance cultures were obtained from 96 neonates (43 % had ≥2 samples). During weeks 12, 16 and 17, active surveillance detected 3, 1 and 2 new CRAB acquisitions, respectively. Prevalence of infections/colonizations decreased, and no event occurred after 20th week. A colonized neonate developed CRAB sepsis and died. All CRAB isolates harboured bla OXA-58 and the intrinsic chromosomal bla OXA-51 carbapenemase genes. Active surveillance and enhanced infection control measures effectively contained spread of CRAB clone in the neonatal intensive care unit.
Background We describe demographic features, treatments and clinical outcomes in the Internationa... more Background We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and ...
Background There are experimental data demonstrating synergistic in-vitro activity of colistin an... more Background There are experimental data demonstrating synergistic in-vitro activity of colistin and daptomycin against extremely drug-resistant (XDR) strains of Acinetobacter baumannii.Aim of this study is the description of a case-series of patients with confirmed XDR A. baumannii bloodstream infection (BSI) receiving an antimicrobial regimen including colistin and daptomycin. Methods Prospective study of patients with BSI caused by XDR A. baumannii from May 2021 to February 2022 in a tertiary level hospital. Demographic, clinical and laboratory data were recorded and evaluated from all patients. BacT Alert system (BiomerieuxR) was used for blood cultures and bacterial identification and susceptibility testing was performed using VITEK® 2. Colistin susceptibility testing (dilution method) were interpreted in accordance to Clinical and Laboratory Standards Institute (CLSI) criteria. Results A total of 16 episodes of XDR A. baumannii were recorded in 16 patients (14 males). Median age...
Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant p... more Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020–March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the C3, C5, CFB, CFD, CFH, CFHR1, CFI, CD46, CD55, MASP1, MASP2, MBL2, COLEC11, FCN1, and FCN3 genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of t...
Respiratory syncytial virus (RSV) is the most common viral pathogen causing respiratory disease i... more Respiratory syncytial virus (RSV) is the most common viral pathogen causing respiratory disease in the pediatric population. An unexpected sudden upsurge of RSV infections among children was observed in September 2021 in Greece. Forty-one rhinopharyngeal samples from children under the age of 2 years with confirmed RSV bronchiolitis were tested to identify the genotype(s) of the RSV strain(s). The children were hospitalized during September-November 2021 in three tertiary hospitals in northern Greece. A one-step RT-PCR which amplifies a fragment of the second hypervariable region of the G protein gene was applied. PCR products were sequenced, and phylogenetic analysis was performed. Most (80.5%) RSV cases were typed as RSV-A, with RSV-B accounting for 19.5% of cases. RSV-A and RSV-B sequences clustered within the ON1 and BA genotypes, respectively. Since the same genotypes were detected in cases observed during 2016-2018 in northern Greece, it was suggested that the early upsurge of infections was not related to the emergence of novel strain(s), but it was the result of the absence of immunity among children and their mothers due to the restriction measures taken during the COVID-19 pandemic in the previous RSV season. Awareness is needed to diagnose even the out-of-season RSV infections, while molecular epidemiology plays a key role in monitoring the efficacy of currently available therapeutics and for those under development. This article is protected by copyright. All rights reserved.
Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We... more Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005–2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhi...
Whether active therapy with β‐lactam/β‐lactamase inhibitors (BLBLI) is as affective as carbapenem... more Whether active therapy with β‐lactam/β‐lactamase inhibitors (BLBLI) is as affective as carbapenems for extended‐spectrum β‐lactamase‐producing Enterobacterales (ESBL‐E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear.
Background In hospitalized critically ill children both antimicrobial consumption and prevalence ... more Background In hospitalized critically ill children both antimicrobial consumption and prevalence of multidrug resistant bacteria is higher than other pediatric inpatients, increasing the need for development and implementation of Antibiotic Stewardship Programs (ASPs). In this study, we aimed to identify studies implementing ASPs in Pediatric Intensive Care Units (PICUs) and analyze their strategy, structure, implementation and outcome metrics. Methods PUBMED was searched for studies reporting interventions for judicious use of antimicrobials in a PICU setting and published after 2006. Only studies that reported at least one outcome on antimicrobial use were included. Studies that applied ASPs throughout the hospital were included only if they reported separate results for PICUs. A checklist tool was created to assess the strategy of intervention, the structure of ASP team, the implementation and outcomes in all eligible studies. Results From 854 records found, 21 full text articles...
As most children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prese... more As most children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present with mild symptoms or they are asymptomatic, the optimal strategy for molecular testing it is not well defined. The aim of the study was to determine the extent and aetiology of molecular testing for SARS-CoV-2 in Greek paediatric departments during the first phase of the pandemic and identify possible differences in incidence, depending on the age group and geographical area. We conducted a nationwide study of molecular testing for SARS-CoV-2 of children in paediatric departments between March and June 2020. A total of 65 paediatric departments participated in the study, representing 4901 children who were tested for SARS-CoV-2 and 90 (1.8%) were positive. Most paediatric cases were associated with topical outbreaks. Adolescents 11–16 years had the highest positivity rate (3.6%) followed by children 6–10 years (1.9%). However, since the testing rate significantly differed between age...
Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromi... more Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromised hosts. We collected data of pediatric mucormycosis cases from all 7 Greek Hematology-Oncology Departments for the years 2008-2017. Six cases of invasive mucormycosis diagnosed during treatment for malignancies were included in the study. In 4 children (66%) mucormycosis occurred within the first 20 days after diagnosis of the underlying disease. Two cases were classified as proven mucormycosis and 4 as probable. The most frequently recorded species was Rhizopus arrhizus (2 patients), followed by Mucor spp (1), and Lichtheimia spp (1). All patients received liposomal amphotericin B. Combined antifungal treatment was used in 5 cases. Surgical excision was performed in 4 cases (66%). Two patients died at 6 and 12 months after the diagnosis, respectively, 1 (17%) because of mucormycosis. Our data suggest that mucormycosis may occur early after the initiation of intensive chemotherapy in children with malignancies.
Background The ISARIC prospective multinational observational study is the largest cohort of hosp... more Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs...
BackgroundBoth pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of... more BackgroundBoth pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation.Methods349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets.ResultsRSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly asso...
Objective: To audit clinical practice and implement an intervention to promote appropriate use of... more Objective: To audit clinical practice and implement an intervention to promote appropriate use of perioperative antimicrobial prophylaxis (PAP). Design: Prospective multicenter before-and-after study. Setting: This study was conducted in 7 surgical departments of 3 major Greek hospitals. Methods: Active PAP surveillance in adults undergoing elective surgical procedures was performed before and after implementation of a multimodal intervention. The surveillance monitored use of appropriate antimicrobial agent according to international and local guidelines, appropriate timing and duration of PAP, overall compliance with all 3 parameters and the occurrence of surgical site infections (SSIs). The intervention included education, audit, and feedback. Results: Overall, 1,447 patients were included: 768 before and 679 after intervention. Overall compliance increased from 28.2% to 43.9% (P = .001). Use of antimicrobial agents compliant to international guidelines increased from 89.6% to 96...
The investigation and successful management of a monoclonal Acinetobacter baumannii outbreak in a... more The investigation and successful management of a monoclonal Acinetobacter baumannii outbreak in a neonatal intensive care unit are described. Upon the first clustered carbapenem-resistant A. baumannii (CRAB) infections, a bundle of actions were taken, including enhanced infection control, active surveillance (weekly stool samples), case-control study, staff education, daily audits and discontinuation of new admissions. Between September and December 2011, eight neonates developed 10 CRAB infections (five blood, four respiratory and one eye). A total of 216 active surveillance cultures were obtained from 96 neonates (43 % had ≥2 samples). During weeks 12, 16 and 17, active surveillance detected 3, 1 and 2 new CRAB acquisitions, respectively. Prevalence of infections/colonizations decreased, and no event occurred after 20th week. A colonized neonate developed CRAB sepsis and died. All CRAB isolates harboured bla OXA-58 and the intrinsic chromosomal bla OXA-51 carbapenemase genes. Active surveillance and enhanced infection control measures effectively contained spread of CRAB clone in the neonatal intensive care unit.
Background We describe demographic features, treatments and clinical outcomes in the Internationa... more Background We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and ...
Background There are experimental data demonstrating synergistic in-vitro activity of colistin an... more Background There are experimental data demonstrating synergistic in-vitro activity of colistin and daptomycin against extremely drug-resistant (XDR) strains of Acinetobacter baumannii.Aim of this study is the description of a case-series of patients with confirmed XDR A. baumannii bloodstream infection (BSI) receiving an antimicrobial regimen including colistin and daptomycin. Methods Prospective study of patients with BSI caused by XDR A. baumannii from May 2021 to February 2022 in a tertiary level hospital. Demographic, clinical and laboratory data were recorded and evaluated from all patients. BacT Alert system (BiomerieuxR) was used for blood cultures and bacterial identification and susceptibility testing was performed using VITEK® 2. Colistin susceptibility testing (dilution method) were interpreted in accordance to Clinical and Laboratory Standards Institute (CLSI) criteria. Results A total of 16 episodes of XDR A. baumannii were recorded in 16 patients (14 males). Median age...
Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant p... more Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020–March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the C3, C5, CFB, CFD, CFH, CFHR1, CFI, CD46, CD55, MASP1, MASP2, MBL2, COLEC11, FCN1, and FCN3 genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of t...
Respiratory syncytial virus (RSV) is the most common viral pathogen causing respiratory disease i... more Respiratory syncytial virus (RSV) is the most common viral pathogen causing respiratory disease in the pediatric population. An unexpected sudden upsurge of RSV infections among children was observed in September 2021 in Greece. Forty-one rhinopharyngeal samples from children under the age of 2 years with confirmed RSV bronchiolitis were tested to identify the genotype(s) of the RSV strain(s). The children were hospitalized during September-November 2021 in three tertiary hospitals in northern Greece. A one-step RT-PCR which amplifies a fragment of the second hypervariable region of the G protein gene was applied. PCR products were sequenced, and phylogenetic analysis was performed. Most (80.5%) RSV cases were typed as RSV-A, with RSV-B accounting for 19.5% of cases. RSV-A and RSV-B sequences clustered within the ON1 and BA genotypes, respectively. Since the same genotypes were detected in cases observed during 2016-2018 in northern Greece, it was suggested that the early upsurge of infections was not related to the emergence of novel strain(s), but it was the result of the absence of immunity among children and their mothers due to the restriction measures taken during the COVID-19 pandemic in the previous RSV season. Awareness is needed to diagnose even the out-of-season RSV infections, while molecular epidemiology plays a key role in monitoring the efficacy of currently available therapeutics and for those under development. This article is protected by copyright. All rights reserved.
Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We... more Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005–2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhi...
Whether active therapy with β‐lactam/β‐lactamase inhibitors (BLBLI) is as affective as carbapenem... more Whether active therapy with β‐lactam/β‐lactamase inhibitors (BLBLI) is as affective as carbapenems for extended‐spectrum β‐lactamase‐producing Enterobacterales (ESBL‐E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear.
Background In hospitalized critically ill children both antimicrobial consumption and prevalence ... more Background In hospitalized critically ill children both antimicrobial consumption and prevalence of multidrug resistant bacteria is higher than other pediatric inpatients, increasing the need for development and implementation of Antibiotic Stewardship Programs (ASPs). In this study, we aimed to identify studies implementing ASPs in Pediatric Intensive Care Units (PICUs) and analyze their strategy, structure, implementation and outcome metrics. Methods PUBMED was searched for studies reporting interventions for judicious use of antimicrobials in a PICU setting and published after 2006. Only studies that reported at least one outcome on antimicrobial use were included. Studies that applied ASPs throughout the hospital were included only if they reported separate results for PICUs. A checklist tool was created to assess the strategy of intervention, the structure of ASP team, the implementation and outcomes in all eligible studies. Results From 854 records found, 21 full text articles...
As most children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prese... more As most children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present with mild symptoms or they are asymptomatic, the optimal strategy for molecular testing it is not well defined. The aim of the study was to determine the extent and aetiology of molecular testing for SARS-CoV-2 in Greek paediatric departments during the first phase of the pandemic and identify possible differences in incidence, depending on the age group and geographical area. We conducted a nationwide study of molecular testing for SARS-CoV-2 of children in paediatric departments between March and June 2020. A total of 65 paediatric departments participated in the study, representing 4901 children who were tested for SARS-CoV-2 and 90 (1.8%) were positive. Most paediatric cases were associated with topical outbreaks. Adolescents 11–16 years had the highest positivity rate (3.6%) followed by children 6–10 years (1.9%). However, since the testing rate significantly differed between age...
Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromi... more Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromised hosts. We collected data of pediatric mucormycosis cases from all 7 Greek Hematology-Oncology Departments for the years 2008-2017. Six cases of invasive mucormycosis diagnosed during treatment for malignancies were included in the study. In 4 children (66%) mucormycosis occurred within the first 20 days after diagnosis of the underlying disease. Two cases were classified as proven mucormycosis and 4 as probable. The most frequently recorded species was Rhizopus arrhizus (2 patients), followed by Mucor spp (1), and Lichtheimia spp (1). All patients received liposomal amphotericin B. Combined antifungal treatment was used in 5 cases. Surgical excision was performed in 4 cases (66%). Two patients died at 6 and 12 months after the diagnosis, respectively, 1 (17%) because of mucormycosis. Our data suggest that mucormycosis may occur early after the initiation of intensive chemotherapy in children with malignancies.
Background The ISARIC prospective multinational observational study is the largest cohort of hosp... more Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs...
BackgroundBoth pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of... more BackgroundBoth pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation.Methods349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets.ResultsRSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly asso...
Objective: To audit clinical practice and implement an intervention to promote appropriate use of... more Objective: To audit clinical practice and implement an intervention to promote appropriate use of perioperative antimicrobial prophylaxis (PAP). Design: Prospective multicenter before-and-after study. Setting: This study was conducted in 7 surgical departments of 3 major Greek hospitals. Methods: Active PAP surveillance in adults undergoing elective surgical procedures was performed before and after implementation of a multimodal intervention. The surveillance monitored use of appropriate antimicrobial agent according to international and local guidelines, appropriate timing and duration of PAP, overall compliance with all 3 parameters and the occurrence of surgical site infections (SSIs). The intervention included education, audit, and feedback. Results: Overall, 1,447 patients were included: 768 before and 679 after intervention. Overall compliance increased from 28.2% to 43.9% (P = .001). Use of antimicrobial agents compliant to international guidelines increased from 89.6% to 96...
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