Clinical outcomes and the impact of treatment modalities in children with carbapenem-resistant Enterobacteriaceae bloodstream infections: a retrospective cohort study from a tertiary university hospital.

BACKGROUND: The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections among children represents a significant global concern, leading to elevated mortality rates. The aim of this study was to evaluate the risk factors, outcomes, 30-day mortality rates and contributing factors in children with CRE bloodstream infections (CRE-BSIs). METHODS: Data regarding demographic characteristics, treatment approaches and outcomes of hospitalized children aged 0-18 years diagnosed with CRE-BSIs between January 2018 and December 2022 were extracted from medical records. Mortality within 30 days of diagnosis and the predictive factors were analysed. RESULTS: A total of 114 children, with a median age of 11 months (range: 6-69.5), were included. All cases of CRE-BSIs were either healthcare associated or hospital acquired and presented with at least one underlying comorbidity. A previous history of CRE colonization or infection rate was 48.2% (55/114). Klebsiella pneumoniae 87.7% (100/114) was the most frequently isolated microorganism, with a 30-day mortality rate of 14% (16/114). Multivariate analysis identified paediatric intensive care unit admission, invasive mechanical ventilation, inotropic support and thrombocytopenia due to CRE-BSIs as the most discriminative predictors for 30-day mortality (P < 0.001). Central venous catheter (CVC) removal was associated with a reduced mortality rate (P = 0.012). High-dose prolonged infusion of MEM-based or polymyxin-based antibiotic combinations did not impact survival. Lower MEM MIC values were associated with improved survival. CONCLUSIONS: The mortality rate of CRE-BSI is notably high in childhood. The use of antibiotic combination strategies did not demonstrate a significant impact on 30-day survival; however, the removal of CVCs was found to lower mortality rates.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome secondary to antimicrobial therapy in pediatric bone and joint infections.

Background: Bone and joint infections are common in children, particularly those under 10 years of age. While antimicrobial therapy can often successfully treat these infections, surgical drainage may also be necessary. It is important to note that prolonged courses of treatment have been associated with adverse events and drug reactions. Among these, drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome is particularly severe and potentially life-threatening. We aimed to evaluate the cases of DRESS syndrome that develop during the treatment of bone and joint infections. Methods: A retrospective study was conducted at a tertiary-level university hospital between 2015 and 2022 to determine the incidence and outcomes of definite DRESS Syndrome in children under 18 years of age with bone and joint infections. Results: Of 73 patients with bone and joint infections, 16 (21.9 %) children developed antimicrobial therapy-induced DRESS syndrome. Eight (50 %) of these children were boys; the mean age of the patients was 9.76 ± 5.5 years. DRESS syndrome occurred in 16 children, including 13 children with osteomyelitis, 1 child with osteomyelitis and septic arthritis, and 2 children with septic arthritis and sacroiliitis. The mean duration of intravenous antibiotic therapy was 40.6 ± 16.6 days; the mean hospital stay was 48.7 ± 23.7 days; the mean time for the development of DRESS syndrome after starting antibiotics was 19.6 ± 7.68 days. New onset fever (68.8 %) and rash (43.8 %) were the most common symptoms of DRESS Syndrome. Cefotaxime and vancomycin were drugs responsible for DRESS syndrome in 8 (50 %) of 16. The causative antibiotics were switched to another class of antibiotic, most commonly preferred was ciprofloxacin (n:5; 31.3 %). For children with persistent symptoms, steroids were used in 5 (31.25) patients. Conclusions: Clinicians should be aware of DRESS syndrome in children who develop fever and rash under long-term antibiotics and should check hematological and biochemical parameters to predict the severity of DRESS syndrome. In patients with persistent symptoms, steroids may be used to control the symptoms.

SARS-CoV-2 reinfections in the pediatric cohort-a single-center experience.

BACKGROUND: This study focused on timelines of infection episodes and dominant variants and aims to determine disease severity and outcome of pediatric patients with reinfection. MATERIALS AND METHODS: This study retrospectively evaluated the medical records of the hospitalized patients and/or outpatients aged 0-18 with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction between March 2020 and September 2022 at Ege University Children's Hospital. RESULTS: Ninety-one pediatric patients reinfected with SARS-CoV-2 were included in the study. There was an underlying disease in 26.4% of the patients. The median time between the two infection episodes was 184 (90-662) days. There were 24 patients (26.3%) with the first infection in pre-Delta period; 17 (18.6%) of them were reinfected in Omicron BA.1 period, while 7 (7.6%) in Omicron BA.4/BA.5 period. Forty-five patients (49.4%) were infected initially in the Delta period; 35 patients (38.4%) were reinfected in the Omicron BA.1 period, while 10 patients (10.9%) were reinfected in the Omicron BA.4/BA.5 period. Twenty-two patients (24.1%) had the first infection in the Omicron BA.1 period and then reinfected in the Omicron BA.4/BA.5 period. Patients with reinfection more frequently displayed a symptom (84.6% vs. 94.5%, p = 0.03). The hospitalization rate significantly declined in reinfection (15.3% vs. 7.6%, p = 0.03). Severe disease, treatment needs and steroid use were decreased in reinfections without a significant difference (p > 0.05). Intensive care unit admission was not altered. CONCLUSION: This study revealed that reinfections frequently develop in previously healthy children but do not cause more severe outcomes. The risk of symptomatic reinfections is still high due to the effect of the Omicron variant.

Invasive Fungal Infections in Children With Acute Myeloid Leukemia: A Single-center Experience Over 19 Years.

OBJECTIVE: Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality in children with acute myeloid leukemia (AML). This study aimed to evaluate the incidence, risk factors, etiology, and outcome of IFIs in children with AML and the effect of mold-active antifungal prophylaxis. MATERIALS AND METHODS: We retrospectively reviewed pediatric patients treated for AML between January 2004 and December 2022. Proven, probable, or possible IFIs were defined using standardized definitions of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) classification published at 2008. RESULTS: A total of 298 febrile neutropenia episodes from 78 patients were evaluated. Proven, probable, and possible IFI rates were 3%, 2.6%, and 9.4%, respectively. Profound neutropenia was detected in 18 (58%) and prolonged neutropenia in 20 (64.5%) of the IFI episodes.. Invasive aspergillosis accounted for the majority of IFI episodes; however, non-albicans Candida spp. were the most isolated pathogens in the proven group. Patients with relapsed AML were particularly at risk for the development of IFI ( P =0.02). A significant decrease in IFI episodes was achieved with mold-active antifungal prophylaxis with voriconazole ( P =0.01, odds ratio: 0.288, %95 CI:0.104-0.797). The overall mortality was 35.8%, and the IFI-attributable mortality rate was 25%. In the multivariate analysis, relapsed disease was the most significant risk factor associated with mortality ( P =0.006, odds ratio:4.745; 95% CI: 1.573-14.316). CONCLUSION: Mold-active prophylaxis reduced the rate of IFIs in this cohort however IFI-related mortality was still high as 25% in pediatric AML patients. Relapsed AML was the most significant risk factor associated with mortality.

Evaluation of post-COVID symptoms of the SARS-CoV-2 Delta and Omicron variants in children: a prospective study.

The post-COVID-19 syndrome is a new syndrome defined in patients with a history of probable or confirmed SARS-CoV-2 infection, usually within three months of the onset of COVID-19, with symptoms and effects lasting at least 2 months. This study is aimed at comprehensively comparing symptoms of the post-COVID-19 syndrome in children with Delta and Omicron variants. This prospective study included children with COVID-19 followed in hospitalized or outpatient clinics in a tertiary hospital. We used a special questionnaire to ask about the presence of persistent symptoms more than 12 weeks after the initial diagnosis. Patients with positive SARS-CoV-2 PCR were selected randomly and grouped according to the dominant variants in our country at that time as follows: Omicron group (after December 16, 2021); Delta (B.1.617.2) group (August 15, 2021, and December 15, 2021). This study included 200 children, 71 of whom were in the Delta group and 129 of whom were in the Omicron group. Weakness (8.5% vs. 1.6%; p = 0.017), the impact of physical efforts (5.6% vs. 3.9%; p = 0.020), fatigue (22.5% vs. 8.5%; p = 0.009), anxiety disorder (12.7% vs. 0.8%; p = 0.001), and gastrointestinal changes (12.7% vs. 4.7%, p = 0.050) were statistically significantly higher in patients with the Delta variant compared to patients with the Omicron variant. There were no differences between the groups regarding anorexia, anosmia/ageusia, arthralgia, influenza-like symptoms, sleeping disorders, decreased physical activity daily, headache, need for analgesia, concentration and memory disorder, and weight loss (p > 0.05).  Conclusion: This study showed that weakness, the impact of physical efforts, fatigue, anxiety disorder, and gastrointestinal changes were more frequent in the Delta group compared to the Omicron group. The incidence of post-COVID-19 syndrome is high in children as well as adults and affects several systems; therefore, it should be kept in mind that children should be followed for post-COVID-19 syndrome. What is Known: • Despite the milder severity of acute COVID-19 in children, post-COVID-19 symptoms may occur. The post-COVID-19 condition is complex and novel, especially in the pediatric population. What is New: • Post-COVID-19 symptoms in children differ depending on the viral variant. Post-COVID-19 syndrome has a great impact on the social life of children which may have serious and long-term effects.

A snapshot of pediatric inpatients and outpatients with COVID-19: a point prevalence study from Turkey.

This multi-center point prevalence study evaluated children who were diagnosed as having coronavirus disease 2019 (COVID-19). On February 2nd, 2022, inpatients and outpatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included in the study from 12 cities and 24 centers in Turkey. Of 8605 patients on February 2nd, 2022, in participating centers, 706 (8.2%) had COVID-19. The median age of the 706 patients was 92.50 months, 53.4% were female, and 76.7% were inpatients. The three most common symptoms of the patients with COVID-19 were fever (56.6%), cough (41.3%), and fatigue (27.5%). The three most common underlying chronic diseases (UCDs) were asthma (3.4%), neurologic disorders (3.3%), and obesity (2.6%). The SARS-CoV-2-related pneumoniae rate was 10.7%. The COVID-19 vaccination rate was 12.5% in all patients. Among patients aged over 12 years with access to the vaccine given by the Republic of Turkey Ministry of Health, the vaccination rate was 38.7%. Patients with UCDs presented with dyspnea and pneumoniae more frequently than those without UCDs (p < 0.001 for both). The rates of fever, diarrhea, and pneumoniae were higher in patients without COVID-19 vaccinations (p = 0.001, p = 0.012, and p = 0.027).  Conclusion: To lessen the effects of the disease, all eligible children should receive the COVID-19 vaccine. The illness may specifically endanger children with UCDs. What is Known: • Children with COVID-19 mainly present with fever and cough, as in adults. • COVID-19 may specifically threaten children with underlying chronic diseases. What is New: • Children with obesity have a higher vaccination rate against COVID-19 than children without obesity. • Among unvaccinated children, fever and pneumoniae might be seen at a higher ratio than among vaccinated children.

Misdiagnosis of multisystem inflammatory syndrome in children: A diagnostic challenge.

AIMS: As the COVID-19 pandemic continues, multisystem inflammatory syndrome in children (MIS-C) maintains its importance in the differential diagnosis of common febrile diseases. MIS-C should be promptly diagnosed because corticosteroid and/or intravenous immunoglobulin treatment can prevent severe clinical outcomes. In this study, we aimed to evaluate clinical presentation, diagnostic parameters and management of MIS-C and compare its clinical features to those of common febrile disease. METHODS: This study was conducted at a tertiary-level university hospital between December 2020 and October 2022. One hundred and six children who were initially considered to have MIS-C disease were included in the study. During the follow-up period in the hospital, when the clinical and laboratory findings were re-evaluated, 38 out of 106 children were diagnosed differently. The clinical and laboratory findings of 68 children followed up with the diagnosis of MIS-C and 38 children who were initially misdiagnosed as MIS-C but with different final diagnoses were retrospectively compared. RESULTS: We identified 68 patients with MIS-C and 38 patients misdiagnosed as MIS-C during the study period. Infectious causes (71%), predominantly bacterial origin, were the most frequently confused conditions with MIS-C. Patients with MIS-C were older and had a more severe clinical course with high rates of respiratory distress, shock, and paediatric intensive care unit admission. While rash and conjunctivitis were more common among patients with MIS-C, cough, abdominal pain and diarrhoea were observed more frequently in patients misdiagnosed as MIS-C. Lower absolute lymphocyte counts, platelet counts and higher C-reactive protein and fibrinogen levels, pathological findings on echocardiography were the distinctive laboratory parameters for MIS-C. Multivariate analysis showed that older age, presence of conjunctivitis, high level of serum CRP and lower platelets were the most discriminative predictors for the diagnosis of MIS-C. CONCLUSION: There are still no specific findings to diagnose MIS-C, which therefore can be confused with different clinical conditions. Further data are needed to assist the clinician in the differential diagnosis of MIS-C and the diagnostic criteria should be updated over time.

Electrocardiographic changes in hospitalised children with COVID-19.

OBJECTIVES: Cardiac manifestations of the coronavirus disease 2019 (COVID-19) have mainly been reported in adults. Therefore, we aimed to determine the electrocardiographic abnormalities in hospitalised paediatric patients with COVID-19 and multisystemic inflammatory syndrome in children. METHODS: We retrospectively evaluated hospitalised paediatric patients <18 years of age with a diagnosis of COVID-19 (n = 168) and multisystem inflammatory syndrome in children (n = 48) between March 2021 and December 2021. A daily electrocardiography was performed for the patients who had electrocardiographic abnormalities on admission or developed electrocardiographic abnormality on the follow-up. The characteristics of these patients, underlying predisposing conditions, and clinical course were also examined. RESULTS: Two-hundred sixteen paediatric patients (55% were male) with a mean age of 10.7 ± 4.69 years were evaluated. There was an underlying disease in 84 (38.8%) patients and 51 (23.6%) required paediatric ICU admission. Electrocardiography abnormality was detected in 12 (5.5%) which were as follows: 7 (3.2%) had sinus bradycardia, 3 (1.4%) patients had transient ST elevation and concomitant T negativity, and 2 (0.9%) developed first-degree Atrioventricular (AV) block. The median time from the onset of disease symptoms to detecting electrocardiographic abnormality was 9 days. Electrocardiographic abnormalities returned to normal uneventfully 3 days later. CONCLUSIONS: The prevalence of arrhythmia in paediatric patients with COVID-19 was detected in 5.5% of the patients. While two-thirds of the electrocardiography abnormalities were sinus bradycardia, ST elevation was remarkable (1.4%). Clinicians should be aware of electrocardiographic abnormalities and consider electrocardiographic monitoring in paediatric patients with COVID-19 and multisystemic inflammatory syndrome in children.

Evaluation of candidemia in children at a university hospital: A retrospective cohort.

BACKGROUND: Candidemia is a life-threatening infection in hospitalied children. This study aimed to evaluate candidemia's demographic and clinical characteristics and identify the risk factors and outcomes of Candida albicans (CA) and non-albicans Candida (NAC) spp. METHODS: A retrospective cohort was designed to evaluate paediatric patients with candidemia between January 2008 and December 2020. RESULTS: A total of 342 episodes in 311 patients were evaluated. The median age of the patients was 2.1 years (1 month-17 years and 6 months), and 59.6% were male. The prevalence of NAC (67.5%) candidemia was higher than that of CA (32.5%). The most commonly isolated Candida species was Candida parapsilosis (43.3%), followed by C. albicans (32.5%), Candida glabrata (6.1%) and Candida tropicalis (5.0%). The length of hospital stay prior to the positive culture and the total length of hospital stay were longer in the NAC group (p = .003 and p = .006). The neutrophil count was lower in the NAC group (p = .007). In the multivariate analysis, total parenteral nutrition, antifungal prophylaxis and a history of coagulase-negative staphylococci (CoNS) culture positivity in the past month were risk factors for developing candidemia due to NAC (p values were .003, .003 and .045). C. albicans and C. parapsilosis fluconazole resistance were 9.5% and 46.6%, respectively. The rates of amphotericin B resistance were 1.1% and 7.6% in C. albicans and C. parapsilosis, respectively. Mortality (14-day and 30-day) rates did not differ between the groups. CONCLUSIONS: A history of CoNS culture positivity in the past month, total parenteral nutrition, and antifungal prophylaxis increases the risk of NAC candidemia.

Quantitative Antibody Levels Against SARS-CoV-2 Spike Protein in COVID-19 and Multisystem Inflammatory Syndrome in Children.

The majority of children with coronavirus diseases 2019 (COVID-19) are asymptomatic or develop mild symptoms, and a small number of patients require hospitalization. Multisystem inflammatory syndrome in children (MIS-C) is one of the most severe clinical courses of COVID-19 and is suggested to be a hyperinflammatory condition. This study aimed to compare quantitative antibody levels against SARS-CoV-2 spike protein in children with COVID-19 and MIS-C. Blood samples from 75 patients [n = 36 (48%) with mild/asymptomatic (group 1), n = 22 (29.3%) with moderate-to-severe SARS-CoV-2 infection (group 2) and n = 17 (22.6%) patients with MIS-C (group 3)] were analyzed 3 months after COVID-19. The majority of the children with asymptomatic/mild COVID-19 symptoms (80.6%), moderate/severe disease (90.9%), and MIS-C (82.4%) had detectable IgG antibodies to SARS-CoV-2 spike protein (p = 0.567). The mean antibody value against SARS-CoV-2 spike protein was 321.9 ± 411.6 in group 1, 274 ± 261 in group 2, and 220 ± 299 in group 3, respectively (p > 0.05). Patients diagnosed with COVID-19 (asymptomatic/mild+moderate/severe) and those with MIS-C were also compared; the antibody positivity rates [COVID-19 group: 85.5%, MIS-C group: 82.4%, (p = 0.833)] and mean antibody values [COVID-19 group: 303.9 ± 360.3, MIS-C group: 220 ± 299, (p > 0.05)] were similar in both groups. In conclusion, the majority of children with COVID-19 and MIS-C developed a detectable antibody level against SARS-CoV-2 spike protein 3 months after COVID-19. Quantitative antibody levels were similar in both asymptomatic/mild disease, moderate/severe disease, and MIS-C group. Long-term studies evaluating antibody responses in children with COVID-19 and MIS-C are needed for more accurate vaccine schedules.

Acute Acalculous Cholecystitis due to EBV Infection Presenting as Acute Abdomen.

Epstein-Barr Virus (EBV) is a herpes virus with a high seropositivity rate among the adult population throughout the world. Primary EBV infection is usually asymptomatic among young children. As age increases, it begins to manifest as infectious mononucleosis. Gastrointestinal involvement is often mild and elevations in liver function tests are common in most cases. Here, we report a case of acute acalculous cholecystitis in a 15-year girl during the course of a primary EBV infection which is a very rare presentation in the pediatric population. Our patient recovered without any antibiotic or surgical treatment - parallel to the clinical improvement of the primary disease. Key Words: Epstein-barr virus (EBV) infection, Acute acalculous cholecystitis, Children, Antibiotics.

Nosocomial Non-fermentative gram negative bacteria bloodstream infections in children; Risk factors and clinical outcomes of carbapenem resistance.

INTRODUCTION: Non-fermentative Gram-negative bacterias (NFGNBs) are a major cause of life threatening infections in hospitalized children. In this study, we aimed to evaluate the demographic and clinical characteristics of NFGNBs infections and identify the risk factors and outcomes of bloodstream infections (BSIs) caused by carbapenem-resistant (CR) NFGNBs infections. METHODS: A retrospective cohort was designed to evaluate the patients with a BSI caused by NFGNBs between in January 2014 and December 2017. RESULTS: A total of 131 episodes from 115 patients were evaluated. The mean age of the patients was 4.79±(4.74) year. The most commonly isolated NFGNBs species was Acinetobacter spp. (35.9%), Pseudomonas spp. (34.4%), and Stenotrophomonas maltophilia (13%). The rate of carbapenem-resistance was 38.2% in Acinetobacter spp. and 26.6% in Pseudomonas spp. The comparison of CR group with carbapenem-susceptible (CS) group showed statistical significance for the length of hospital stay prior to onset of infection and total hospital stay (P values were 0.001, 0.008). Based on the univariate analysis, requirement of mechanical ventilation, central venous catheter, nasogastric tube, Foley catheter, severe neutropenia (<100/mm3), prolonged neutropenia (≥14 days), prior intensive care unit admission and prior antimicrobial treatment (carbapenems, colistin, glycopeptide) were more common in carbapenem-resistant NFGNBs infections (P values are 0.001, 0.012, 0.000, 0.005, 0.042, 0.027, 0.007, 0.007). In patients with NFGNBs infections 14-day and 30-day mortality rates were %16.8 and 21.4%. CONCLUSION: CR infections were more common in children with prolonged and severe neutropenia. Prior antimicrobial use and intensive care unit admission were more common in CR infections.

Osteomyelitis Caused by Bacillus Calmette-Guérin Vaccination in a Healthy Toddler.

Bacillus Calmette-Guérin (BCG) osteomyelitis in immunocompetent children is a rare complication of BCG immunization which presents with nonspecific findings and often leads to delayed diagnosis. We report a 1-year and 10-month-old male infant with complaining of knee pain and limping for 5 months. He received surgical debridement due to suspicion of malignancy but BCG osteomyelitis of the distal femur was diagnosed with the culture of the specimens which revealed to have Mycobacterium bovis-BCG strain. He was successfully treated with antituberculous therapy lasting for 1 year.