Pathogens in Pediatric Septic Arthritis: A Multi-Center Study in Turkiye (PEDSART Study).

OBJECTIVES: Septic arthritis (SA) is a serious bacterial infection that must be treated efficiently and timely. The large number of culture-negative cases makes local epidemiological data important. Accordingly, this study aimed to evaluate the etiology, clinical characteristics, and therapeutic approach of SA in children in Turkiye, emphasizing the role of real-time polymerase chain reaction (PCR) techniques in the diagnosis. METHODS: In this multi-center, prospective study, children hospitalized due to SA between February 2018 and July 2020 in 23 hospitals in 14 cities in Turkiye were included. Clinical, demographic, laboratory, and radiological findings were assessed, and real-time PCR was performed using synovial fluid samples. RESULTS: Seventy-five children aged between 3 and 204 months diagnosed with acute SA were enrolled. Joint pain was the main complaint at admission, and the most commonly involved joints were the knees in 58 patients (77.4%). The combination of synovial fluid culture and real-time PCR detected causative bacteria in 33 patients (44%). In 14 (18.7%) patients, the etiological agent was demonstrated using only PCR. The most commonly isolated etiologic agent was Staphylococcus aureus, which was detected in 22 (29.3%) patients, while Streptococcus pyogenes was found in 4 (5.3%) patients and Kingella kingae in 3 (4%) patients. Streptococcus pyogenes and Kingella kingae were detected using only PCR. Most patients (81.3%) received combination therapy with multiple agents, and the most commonly used combination was glycopeptides plus third-generation cephalosporin. CONCLUSIONS: Staphylococcus aureus is the main pathogen in pediatric SA, and with the use of advanced diagnostic approaches, such as real-time PCR, the chance of diagnosis increases, especially in cases due to Kingella kingae and Streptococcus pyogenes.

COVID-19 in hospitalized infants aged under 3 months: multi-center experiences across Turkey.

To investigate coronavirus disease 2019 (COVID-19) in infants aged 0 to 3 months because there is currently a significant gap in the literature on the subject. A cross-sectional study was conducted with the involvement of 19 medical centers across Turkey and 570 infants. The majority of the patients were male (58.2%), and the three most common symptoms were fever (78.2%), cough (44.6%), and feeding intolerance (39.9%). The results showed that a small percentage of infants had positive blood (0.9%) or urine cultures (10.2%). Most infants presented with fever (78.2%). Children without underlying conditions (UCs) had mostly a complicated respiratory course and a normal chest radiography. Significant more positive urine culture rates were observed in infants with fever. A higher incidence of respiratory support requirements and abnormal chest findings were seen in infants with chronic conditions. These infants also had a longer hospital stay than those without chronic conditions.  Conclusions: Our study discloses the clinical observations and accompanying bacterial infections found in infants aged under 3 months with COVID-19. These findings can shed light on COVID-19 in infancy for physicians because there is limited clinical evidence available. What is Known: • COVID-19 in infants and older children has been seen more mildly than in adults. • The most common symptoms of COVID-19 in infants are fever and cough, as in older children and adults. COVID-19 should be one of the differential diagnoses in infants with fever. What is New: • Although most infants under three months had fever, the clinical course was uneventful and respiratory complications were rarely observed in healthy children. • Infants with underlying conditions had more frequent respiratory support and abnormal chest radiography and stayed longer in the hospital.

Evaluation of 601 children with multisystem inflammatory syndrome (Turk MISC study).

PURPOSE: Due to its link with the 2019 coronavirus, the multisystem inflammatory syndrome in children (MISC) has garnered considerable international interest. The aim of this study, in which MISC patients were evaluated multicenter, and the data of the third period of the Turk-MISC study group, to compare the clinical and laboratory characteristics and outcomes of MISC patients who did and did not require admission to an intensive care unit (ICU). METHODS: This retrospective multicenter observational study was carried out between June 11, 2021, and January 01, 2022. The demographics, complaints, laboratory results, system involvements, and outcomes of the patients were documented. RESULTS: A total of 601 patients were enrolled; 157 patients (26.1%) required hospitalization in the intensive care unit (ICU). Median age was 8 years (interquartile range (IQR) 4.5-11.3 years. The proportion of Kawasaki disease-like features in the ICU group was significantly higher than in the non-ICU group (56.1% vs. 43.2% p = 0.006). The ICU group had considerably lower counts of both lymphocytes and platelets (lymphocyte count 900 vs. 1280 cells × µL, platelet count 153 vs. 212 cells × 103/ µL, all for p< 0.001). C-reactive protein, procalcitonin, and ferritin levels were significantly higher in the ICU group (CRP 164 vs. 129 mg/L, procalcitonin 9.2 vs. 2.2 µg/L, ferritin 644 vs. 334 µg/L, all for p< 0.001). Being between ages 5-12 and older than 12 increased the likelihood of hospitalization in the ICU by four [95% confidence intervals (CI)1.971-8.627] and six times (95% CI 2.575-14.654), respectively, compared to being between the ages 0-5. A one-unit increase in log D-dimer (µg/L) and log troponin (ng/L) was also demonstrated to increase the need for intensive care by 1.8 (95% CI 1.079-3.233) and 1.4 times (95% CI 1.133-1.789), respectively.     Conclusion: By comparing this study to our other studies, we found that the median age of MISC patients has been rising. Patients requiring an ICU stay had considerably higher levels of procalcitonin, CRP, and ferritin but significantly lower levels of lymphocyte and thrombocyte. In particular, high levels of procalcitonin in the serum might serve as a valuable laboratory marker for anticipating the need for intensive care. WHAT IS KNOWN: • Lymphopenia and thrombocytopenia were an independent predictor factors in patients with MISC who needed to stay in intensive care unit. • The possibility of the need to stay in the intensive care unit in patients with MISC who had Kawasaki disease-like findings was controversial compared with those who did not. WHAT IS NEW: • A one-unit increase log D dimer and log troponin was demonstrated to require for intensive care unit by 1.8 and 1.4 times, respectively. • Serum procalcitonin levels had the best performance to predict stay in the intensive care unit stay.

Community-acquired S. aureus infection in childhood: a multi-center study.

BACKGROUND: The prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA) has been increasing worldwide. We aimed to investigate the prevalence of MRSA in community-acquired S. aureus infections, the risk factors for CA-MRSA infection and the clinical features of CA-MRSA. METHODS: A multi-center study with prospective and retrospective sections was conducted. Patients ≥ 3 months old and ≤18 years of age who were diagnosed with community-acquired S. aureus infections were included in this study and the patients` information were reviewed from the medical and microbiological database of the hospital. A standard question form about living conditions and exposure risk factors was administered to the parents of patients. The CA-MRSA infections were compared with the methicillin-susceptible S. aureus (CAMSSA) infections in terms of the queried risk factors and clinical variables. RESULTS: We identified 334 pediatric patients with S. aureus infection, 58 (17.4%) had an infection with CAMRSA. The refugee rate was higher in the CA-MRSA group. There was no significant difference regarding the exposure risk. The treatment modalities and outcomes were similar. CONCLUSIONS: The study was not able to show reliable clinical variables or epidemiological risk factors except for being a refugee for CA-MRSA infections. Empirical antibiotic treatment should therefore be determined according to the local CA-MRSA prevalence in patients presenting with a possible staphylococcus infection.

Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria.

Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/ß-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/ß immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/ß. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/ß-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/ß-dependent antiviral immunity.

Comparison of clinical features of COVID-19 infection in children with asthma and their healthy peers.

AIM: We aimed to assess the impact of COVID-19 on asthma exacerbations and to compare the severity of symptoms of SARS-CoV-2 infection of asthmatic children with those of healthy children. METHODS: The clinical course of COVID-19 was compared among 89 children with asthma and 84 healthy children with age- and gender-matched. Demographic factors, severity of asthma, duration of asthma, presence of atopy, type of treatment, and compliance to treatment in asthmatic children on clinical course of infection and to determine the risk factors for severe course for asthma exacerbation during COVID-19 were evaluated retrospectively. Demographic characteristics, clinical symptoms, duration of complaints, and hospitalization rates were statistically compared between the two groups. RESULTS: Both groups had similar rates of symptomatic disease, hospitalization, and duration of fever. Among children with asthma mean age was 10.3 years, 59.6% were male, and 84.3% had mild asthma. Dyspnea was more prevalent in asthmatic children (p:0.012), but other clinical findings were not different from those of healthy controls. 12.4% (n:11) of asthmatic children had asthma exacerbation, 2.2% (n:2) of them were hospitalized; one (1.1%) of which was due to asthma exacerbation. CONCLUSION: The course of COVID-19 in patients with mild to moderate asthma, who were followed up regularly and who were compliant with their treatment, was similar to their healthy peers. Since there was no severe asthma case in our study, the results could not have been generalized to all asthmatic patients. Further comprehensive and multicenter studies are required in pediatric population.

COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group.

Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × µL, p = 0.028; platelet count 166 vs. 216 cells × 103/µL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559). CONCLUSION: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD. WHAT IS KNOWN: • In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. • Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C. WHAT IS NEW: • Half of the patients had clinical features that overlapped with Kawasaki disease. • In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. • Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. • Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.

Multisystem inflammatory syndrome in children associated with COVID-19 in 101 cases from Turkey (Turk-MISC study).

AIM: Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. METHODS: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. RESULTS: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 µg/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. CONCLUSION: The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management.

Lifesaving Treatment of Aortic Valve Staphylococcus aureus Endocarditis: Daptomycin and Early Surgical Therapy.

Infective endocarditis (IE) is an uncommon infection in children. The recommended treatment for native valve endocarditis secondary to methicillin-susceptible Staphylococcus aureus infection is antistaphylococcal penicillins such as nafcillin or oxacillin. If the initial therapy fails in IE, it can lead to catastrophic results. Nowadays, daptomycin is the best alternative antimicrobial agent to treat children with severe infections, when standard antimicrobial therapy does not yield a result. Herein, in this article, we described a case of a 16-year-old boy who had aortic valve S. aureus endocarditis with septic embolization and stroke. The patient was successfully treated only with daptomycin as well as surgical therapy in the early phase of the infection.

Subdural empyema, brain abscess, and superior sagittal sinus venous thrombosis secondary to Streptococcus anginosus.

Streptococcus anginosus can be frequently isolated from brain abscesses, but is a rare cause of the liver, lung, and deep tissue abscesses. In this report, we present a patient with subdural empyema, brain abscess, and superior sagittal cerebral venous thrombosis as complications of rhinosinusitis whose purulent empyema sample yielded S. anginosus. A 13-year-old female patient was referred to our pediatric intensive care unit with altered mental status, aphasia, and behavioral change. On a brain computed tomography scan, subdural empyema extending from the left frontal sinus to the frontal interhemispheric area and left hemispheric dura was detected. Intravenous ceftriaxone, vancomycin, and metronidazole treatments were started. Subdural empyema was surgically drained. Postoperative brain magnetic resonance venography imaging showed superior sagittal sinus thrombosis. Cultures obtained from purulent empyema sample revealed S. anginosus. On the third day of hospitalization, a brain computed tomography scan showed brain edema, especially in the left hemisphere and significantly increased subdural empyema that had been previously drained. She was reoperated and decompressive craniectomy was performed. On the fifth day, partial epileptic seizures occurred. Brain magnetic resonance imaging showed a brain abscess on the interhemispheric area. The magnetic resonance imaging findings of abscess formation improved on 30th day and she was discharged on the 45th day after the completion of antibiotic therapy.

Multicenter prospective surveillance study of viral agents causing meningoencephalitis.

The frequency of bacterial factors causing central nervous system infections has decreased as a result of the development of our national immunization program. In this study, it is aimed to obtain the data of our local surveillance by defining the viral etiology in cases diagnosed with meningoencephalitis for 1 year. Previously healhty 186 children, who applied with findings suggesting viral meningoencephalitis to 8 different tertiary health centers between August 2018 and August 2019, in Istanbul, were included. The cerebrospinal fluid (CSF) sample was evaluated by polymerase chain reaction. The M:F ratio was 1.24 in the patient group, whose age ranged from 1 to 216 months (mean 40.2 ± 48.7). Viral factor was detected in 26.8%. Enterovirus was the most common agent (24%) and followed by Adenovirus (22%) and HHV type 6 (22%). In the rest of the samples revealed HHV type 7 (10%), EBV (6%), CMV (6%), HSV type 1 (6%), Parvovirus (4%) and VZV (2%). The most common symptoms were fever (79%) and convulsions (45.7%). Antibiotherapy and antiviral therapy was started 48.6% and 4% respectively. Mortality and sequela rate resulted 0.53% and 3.7%, respectively. This highlights the importance of monitoring trends in encephalitis in Turkey with aview to improving pathogen diagnosis for encephalitis and rapidly identifying novel emerging encephalitis-causing pathogens that demand public health action especially in national immunisation programme.

A Rare Presentation of Neurobrucellosis in a 6-Year-Old Pediatric Patient with Sagittal Sinus Thrombosis.

Brucellosis is one of the most common zoonosis worldwide. It is still endemic in many regions of the world. A 6-year-old female was admitted to the emergency department (ED) due to a sudden change in consciousness, urinary incontinence, vomiting, and difficulty in walking. Neurological examination demonstrated abducens nerve paralysis, mild-to-moderate motor deficit in hemiparesis in the left arm. Brain magnetic resonance imaging showed a hemorrhagic focus at the right frontal lobe and thrombosis in the superior sagittal sinus of the brain. The diagnosis of neurobrucellosis was confirmed by identifying Brucella spp. in the blood culture on the day 6 of pediatric intensive care unit admission; thus, trimethoprim-sulfamethoxazole and rifampicin, and ceftriaxone were promptly initiated. Despite neuroprotective management and acetazolamide, the patient's neurological problems and high intracranial pressure (ICP) persisted. An external ventricular drainage tube and a Codman ICP monitor were placed to be on the consent vigilance of the patient's neurological condition. The patient's ICP continued to increase despite the current treatment regimen; therefore, a decompressive bitemporal craniectomy was performed. The ICP level of the patient returned to its normal range immediately after the craniectomy. The patient did not have any notable neurologic sequelae at the first-year follow-up. Neurobrucellosis is a rare complication of systemic brucellosis and may present as meningitis, encephalitis, myelitis, radiculitis, and/or neuritis. Herein, we describe a six-year-old girl with brucellosis complicated with cerebral vein thrombosis. This case illustrates the need for close monitoring of patients with unexplained neurological signs or symptoms for brucellosis in endemic areas.

A Snapshot of Pediatric Patients with COVID-19 in a Pandemic Hospital.

AIM: Reports describing coronavirus disease 2019 (Covid-19) in children are fewer than adult studies due to milder clinical picture. We aimed to share our experience at a single center with an emphasis on collective decision making. MATERIALS AND METHODS: A suspected case was defined as the presence of symptoms suggestive of COVID-19 and/or positive contact history. SARS-CoV-2 PCR positive patients were defined as confirmed COVID-19. Between March 12, 2020, and May 15, 2020, all children presenting with fever, cough, or respiratory difficulty were investigated for COVID-19. A total of 719 children were examined at outpatient clinics, and 495 were tested with polymerase chain reaction (PCR) for suspicion of COVID-19. A team was organized for monitoring and treating patients either as outpatients or hospitalization. Patients were evaluated in terms of age, gender, travel history, epidemiological history, clinical symptoms and signs, laboratory and radiological findings, treatment, and outcome. RESULTS: Sixty patients were hospitalized for suspicion of COVID-19. Forty-three patients were diagnosed as probable or confirmed COVID-19. 21 of 43 patients (48.8%) were PCR confirmed. The remaining 22 were diagnosed by epidemiologic history, clinical assessment, and computerized thorax tomography (CT) findings. The median age was 126 and 78.5 months in PCR positives and PCR negatives, respectively and the youngest patient was a 28 days old baby. Nineteen of the patients had an upper respiratory infection (44.1%). Although five patients had no clinical signs, chest X-ray, or CT revealed pneumonia. CONCLUSIONS: As previously reported, the clinical manifestations of COVID-19 in children are mostly mild. Even very young kids can become infected following exposure to sick family members. International and local guidelines are valuable for decision making since it is a new disease. A combination of chest disease, infectious diseases, and emergency care physicians approach will aid the appropriate management of cases.

A 13-Year-Old Boy Who Has Kawasaki Disease Shock Syndrome Presents with Parotitis.

We report a 13-year-old boy who (initially) had symptoms of toxic shock-like syndrome and mumps. Then, the patient was hospitalized in the pediatric intensive care unit (PICU) because of his ongoing hemodynamic instability (low blood pressure of 70/30 mm Hg and capillary refill time of > 4 seconds). During his stay in the PICU, the patient was treated with fluid resuscitation and vasoactive infusion and at the same time was diagnosed with Kawasaki disease shock syndrome (KDSS), when giant right coronary artery aneurysms were detected on echocardiographic examination. This case illustrates the risk of KDSS in patient who carries both parotitis and toxic shock-like syndrome. The clinicians should be cautious about detecting any types of coronary artery aneurysms in such patients. This is the first case of KDSS associated with parotitis reported in the literature.