Intravenous fosfomycin indications and treatment outcomes in pediatric usage: analysis from a single center in Turkey.

Current data on fosfomycin usage in children are limited. We present data on the clinical use of intravenous (IV) fosfomycin in children. Hospitalized patients who received ≥3 days of IV fosfomycin between April 2021 and March 2023 were analyzed retrospectively. Forty-three episodes of infection in 39 patients were evaluated. The mean age of the patients was 5.35 (10 days to 17.5 years) years, and 54% were male. Infections were hospital-acquired in 79% of the episodes. Indications for fosfomycin were urinary tract infection (35%), bacteremia (32.6%), catheter-related bloodstream infection (16.3%), soft tissue infection (4.7%), sepsis (4.7%), surgical site infection (2.3%), burn infection (2.3%), and pneumonia (2.3%). Klebsiella pneumoniae was identified in 46.5% of the episodes, and a pan-drug or extensive drug resistance was detected in 75% of them. Carbapenem was used before fosfomycin at significantly higher rates in K. pneumoniae episodes (P = .006). Most (88.5%) patients received fosfomycin as a combination therapy. Culture negativity was achieved in 80% of episodes within a median treatment period of 3 (2-22) days, which was significantly shorter in K. pneumoniae episodes (P < .001). Treatment-related side effects were seen in 9.3% of the episodes. Side effects were significant after 3 weeks of treatment (P = .013). The unresponsivity rate to fosfomycin was 23.3%. Nine (21%) of the patients who were followed up in the intensive care units mainly died because of sepsis (56%). IV fosfomycin is an effective agent in treating severe pediatric infections caused by resistant microorganisms. Fosfomycin can be used in various indications and is generally safe for children.

Assessment of blood viral load in asymptomatic and symptomatic cases of congenital cytomegalovirus infection.

This study aimed to retrospectively evaluate the baseline and follow-up viral loads and viral clearance times in cases followed for asymptomatic and symptomatic congenital cytomegalovirus (cCMV) infection between August 2010 and August 2022. Among 93 cases, they had asymptomatic (n: 55) and symptomatic (n: 38). The median baseline blood viral load detected in the symptomatic cCMV (ScCMV) infection (13 054 IU/mL) was significantly higher than that of asymptomatic cCMV (AcCMV) infection (4636 IU/mL) (p < 0.013). There was no difference in median viral clearance times (75 and 90 days, respectively) in baseline viremic cases in the ScCMV and AcCMV infection groups. There were no differences in median baseline blood viral load (6930 IU/mL and 14 268 IU/mL, respectively) and median viral clearance times (75 and 85 days, respectively) between the 6-week and 6-month antiviral treatment group. No correlation was found between baseline blood viral load, clinical severity, and the number of systems involved. However, in initial viremic cases, the viral load threshold for a symptomatic case was 8856 IU/mL, with 85.7% sensitivity and 54.5% specificity.

Catheter-related Infections in Pediatric Patients Due to a Rare Pathogen: Herbaspirillum huttiense.

BACKGROUND: Herbaspirillum species are nonfermenting, aerobic, helical or curved, Gram-negative bacteria belonging to the class Betaproteobacteria, order Burkholderiales. To date, only a few studies have reported on the epidemiology, clinical symptoms, antibiotic susceptibility profiles, treatment and outcomes of Herbaspirillum huttiense -related infections in pediatric patients. METHODS: The aim of this study was to present 3 years of H.huntiense data, antibiotic susceptibility profiles, systemic antibiotics and antibiotic lock therapy (ALT) options and clinical outcomes. RESULTS: Fourteen episodes of infection in 12 patients were included in this retrospective study. The patients had a male/female ratio of 1:1 and a median age of 160.5 months (range, 3-198 months). Catheter-related bloodstream infection (CRBSI) was detected in 11 patients. Only 1 patient developed catheter-related infective endocarditis. The patient's catheter was removed, and she was successfully treated with systemic antibiotics for 4 weeks. Systemic antibiotics were used in all infections related to H. huttiense . In septic, critically ill patients, the catheter was removed, and systemic antibiotics were started. Port catheters were removed in 5 patients. ALT was performed in clinically stable patients. ALT using amikacin was administered to 6 patients through the port catheter. Two patients had a 2nd attack. After the 2nd ALT treatment, 1 patient cured, and the catheter of the other patient was removed due to persistent microbial growth in cultures. Antimicrobial susceptibility testing of the reported isolates showed susceptibility to meropenem (90%), ceftazidime (87%) and piperacillin/tazobactam (65%), with 92% resistance to colistin. CONCLUSION: H. huttiense is an emerging pathogen in CRBSI. Piperacillin/tazobactam, ceftazidime and meropenem appear to be good therapeutic options for the treatment of H. huttiense infections. ALT and systemic antibiotics can be used in H. huttiense -CRBSI to sterilize and preserve the central venous catheter.

Is SARS-CoV-2 Now More Like the Seasonal Coronaviruses Following Its Evolution?

BACKGROUND: SARS-CoV-2 has evolved significantly since the beginning of the COVID-19 pandemic. COVID-19 mortality has decreased due to increased population immunity and possibly the reduced intrinsic severity of the new variants. SARS-CoV-2 is now considered an endemic virus, but the extent to which its clinical findings resemble those of seasonal coronaviruses (sCoV) is not fully understood. METHODS: Pediatric patients under 18 years of age who were sent for SARS-CoV-2 polymerase chain reaction real-time reverse transcription polymerase chain reaction between January 1, 2022 and January 14, 2023 and whose results were positive were included in this study. To include only symptomatic COVID-19 patients in the study, asymptomatic patients who were positive in their screening tests were excluded. For the sCoV patients' group, patients who had a respiratory viral polymerase chain reaction assay between January 10, 2022 and January 11, 2023 and were positive for any type of sCoV were included in the study. The 2 groups were compared for clinical and laboratory characteristics. RESULTS: The study included 213 patients with COVID-19 and 194 patients with sCoV infection. Fever was a more common symptom in patients with COVID-19. sCoV was associated with lower respiratory involvement while increasing age was protective. The likelihood of hospitalization was decreased by increasing age but increased by the presence of comorbid conditions and lower respiratory tract involvement. The type of virus had no effect on the likelihood of hospitalization. CONCLUSIONS: In conclusion, sCoV infections carry a higher risk for lower respiratory involvement than COVID-19, and COVID-19 has a milder course than sCoV infections in children.

Relationship between biologic modifying agents and development of latent tuberculosis in pediatrics.

INTRODUCTION: Biologic modifying agents are associated with an increased risk for infection with mycobacteria. The aim of this study is to document patients who received different biologic modifying therapies in our pediatric rheumatology department and the possibility of development of tuberculosis (TB). METHODOLOGY: This retrospective study was conducted in Ankara City Hospital. Pediatric patients who were treated with biologic modifying agents between 2010-2020 were documented. Development of TB and the risk factors were assessed in this patient group. RESULTS: There were 72 patients who were treated with different biologic modifying agents. Tuberculin skin test (TST) was positive in 7 (9.7%) patients during follow up. Three patients whose TST was positive had received canakinumab, 2 received etanercept, 1 received adalimumab and 1 received anakinra. Median duration of therapy was 43.5 (16.5-168) months for these patients and the duration was longer than patients who did not develop latent tuberculosis (p = 0.04). Patients who developed latent TB under treatment were significantly older than the patients who did not (p = 0.01). CONCLUSIONS: According to our findings, 9.7% of pediatric patients who received biologic modifying agent therapy developed latent TB. Patients who developed latent TB were older, and the duration of treatment was longer than patients who did not develop latent TB. Although not statistically significant, canakinumab, which is known as an agent less likely to cause TST conversion, was in fact the most common agent that caused TST conversion.

Monitoring of adenoviremia in pediatric patients undergoing hematopoietic stem cell transplantation: Is it alone sufficient to predict adenoviral disease?

BACKGROUND: We aimed to evaluate our pediatric HSCT recipients routinely monitored for adenoviremia and to determine the adequacy of this monitoring in predicting adenoviral disease (AD). METHODS: A retrospective cohort of patients who underwent allogeneic HSCT between January 2021 and August 2022, and routinely monitored for adenoviremia by real-time PCR was included in our survey. Demographic and clinical data of the patients were recorded. Incidence rates, risk factors, and mortality rates related to adenoviremia, and AD were analyzed. RESULTS: Among 104 HSCTs performed in 94 patients adenovirus (AdV) was revealed in 27 (26%) episodes and adenoviremia in 18 (17.3%) HSCT episodes. AD without adenoviremia developed in nine episodes (8.6%). Disseminated disease was significantly more frequently detected in episodes with adenoviremia (p = .008). GVHD was independent risk factor for AdV detection (OR: 8.6, 95% CI: 2.03-33.7, p = .001). Viremia developed within a shorter time interval after HSCT in isolated episodes of adenoviremia compared to those with concomitant AD (p = .006). Initial and peak viral loads were significantly higher in adenoviremia with AD (p < .001). Mortality was higher in the AdV-detected episodes (p < .001) than in the AdV-undetected episodes. AdV-related mortality was found to be 22.2%. Adenoviremia increased the risk of mortality (OR: 1.2, 95% CI: 0.22-1.33, p = .01). CONCLUSIONS: Adenoviremia monitoring is an important process in the detection of AD. Since some patients may develop AD without accompanying by adenoviremia, monitoring for AdV in blood samples should be supported with other monitoring methods in order to evaluate the probable involvement of different organs or systems.

Evaluation of vascular and perfusional changes in the retina and choroid of children with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is hyperinflammation following coronavirus disease 2019 (COVID-19), which affects many organs. The retina and choroid are affected by COVID-19 through microangiopathy and thrombosis but the literature on MISC-C is limited. METHODS: Thirty children (60 eyes) with MIS-C (the study group, or SG) and 32 age-and gender-matched healthy children (64 eyes) (the control group, or CG) were included in the prospective case-control study. Complete ophthalmological examinations, measurements of the vessel densities of the retinal layers, and flow area of the outer retina and choriocapillaris in both groups were conducted with optical coherence tomography angiography (OCT-A). RESULTS: The mean age of the SG was 11.9 ± 3.9 and that of the CG was 12.5 ± 4.6 years (p = 0.197). In this study we found that the vessel density of the deep layer of the inner retina was decreased significantly and was reduced in the outer retina of flow area in the SG in comparison with the CG (p < 0.05, for all). However, there was no significant difference between the groups regarding other measurements. CONCLUSIONS: In MIS-C patients, vessel densities in the deep layer of the inner retina and in the flow area of the outer retina decreased significantly. This OCTA-A finding suggests that MIS-C is related to endothelial thrombotic condition problems in small branches of the retinal artery. The results of this study support the idea that there is a need for screening of MIS-C patients for the presence of these microangiopathic and perfusional complications.

Admission and follow-up cardiac magnetic resonance imaging findings in BNT162b2 Vaccine-Related myocarditis in adolescents.

BACKGROUND: There is limited data on the pattern and severity of myocardial injury in patients with COVID-19 vaccination associated myocarditis. OBJECTIVE: We aimed to define the myocardial damage occurring after BNT162b2 vaccination, raise awareness about adverse reactions developing after vaccination, and determine the patterns and scope of Cardiac magnetic resonance imaging (MRI) findings. PATIENTS/METHODS: A total of 9 patients diagnosed with vaccine-associated myopericarditis were followed up. RESULTS: The mean age of the patient at diagnosis was 15.3 ± 1.0 (range: 14-17) years, and all patients were male. Seven patients presented with myocarditis symptoms after their second vaccine dose, one patient presented with pericarditis symptoms after his first dose, and the other patient presented with myocarditis symptoms after his booster dose. The median time at presenting to the hospital was 3 (range: 2-22) days. Seven (77.7%) patients had abnormal electrocardiography (ECG) findings, and the most prevalent finding was diffuse ST-segment elevation. Initial cardiac MRI results were abnormal in all patients, where 8 (88.8%) patients had late gadolinium enhancement, and 5 (55.5%) had myocardial edoema. Three patients showed local left ventricular wall-motion abnormalities. In their follow-up MRIs 3-6 months later, myocardial edoema was present in 2 (28.5%) patients, while late gadolinium enhancement was present in all patients (7/7, 100%, 2 patients did not have control MRI time). Hypokinetic segments were still present in one of the 3 patients. No negative cardiac events were observed in the short-term follow-up of any patient. CONCLUSION: Further follow-up evaluation and larger multicenter studies are needed to determine the clinical significance of persistent cardiac MRI abnormalities.

Do parents vaccinated against COVID-19 protect their children from hospitalization due to COVID-19?

OBJECTIVE: This study aimed to determine whether parental vaccination against coronavirus disease 2019 (COVID-19) prevents hospitalization of COVID-19-infected children. METHODS: This study was based on data obtained from the records of pediatric patients that were followed up for virologically proven COVID-19 infection between August and October 2021, during which time the delta variant was dominant in Turkey and the children were isolating at home. RESULTS: There were 151 patients in the inpatient group and 218 in the outpatient group; the mean age was 172.5 and 145.5 months in the groups, respectively. The rates of obesity (22.5% and 6.4%, respectively, p < 0.001) and neurological-neurodevelopmental disorders (8.6% and 1.4%, respectively, p < 0.001) were significantly higher in the inpatient group than in the outpatient group. Of the outpatients' parents, 67.4% (n = 147) were fully vaccinated vs. 38.4% (n = 58) in the inpatient group. In all, 39.7% (n = 60) of the inpatients' parents were unvaccinated vs. 18.3% (n = 40) in the outpatient group. There was a significant correlation between the vaccination status and the patient groups (p < 0.001); it was determined that the COVID-19 infection would be mild in children if both parents were fully vaccinated. When both parents were fully vaccinated against COVID-19, the hospitalization rate decreased and the outpatient follow-up rate increased. CONCLUSION: Having both parents fully vaccinated against COVID-19 can indirectly protect their subsequently infected children from hospitalization and the long-term effects of infection. Nonetheless, more comprehensive research on delta and non-delta variants is needed.

Psychiatric symptoms in children with COVID-19, mothers` psychological resilience and related factors: pandemic hospital inpatient experiences.

BACKGROUND: Information on psychological problems and affecting factors in children hospitalized with the suspicion or diagnosis of COVID-19 is limited. We aimed to screen the psychiatric symptoms of children hospitalized with COVID-19 in Ankara City Children`s Hospital and evaluate the caregivers` depression, anxiety, stress, and resilience levels during hospitalization. METHODS: Among the children and adolescents hospitalized in Ankara City Children`s Hospital between 1 May 2020 and 31 May 2020 due to the diagnosis of COVID-19, those who agreed to participate in the study were included. The Strengths and Difficulties Questionnaire (SDQ), the Depression Anxiety Stress Scale-21 (DASS- 21) scale, and the Brief Resilience Scale (BRS) were used to determine the symptoms. RESULTS: The mean age of study group (n = 49) was 8.7 ± 5.0 years, 59.2% (n = 29) were girls. The mean children`s SDQ-externalizing problems scores were higher in the COVID-19 positive mothers group than the COVID-19 negative mothers` group. The SDQ-total score was positively and strongly correlated with the DASS total score, DASS-depression score, and DASS-anxiety score. BRS scale scores were negatively correlated with the SDQtotal, externalizing, and DASS-21scale scores. CONCLUSIONS: COVID-19 positivity in mothers could be associated with externalizing problems in children. The high resilience of caregivers of inpatients seems to be related to less psychopathology in children. During hospitalization, caregivers` psychological evaluation and psychosocial support may be important for preventive child mental health.

Potential and promising marker for serious bacterial infections in children: Delta neutrophil index.

AIM: This study aimed to evaluate the usefulness and accuracy of the delta neutrophil index (DNI), an index expressing the number of immature granulocytes as a proportion of the total, as an inflammatory marker in predicting serious bacterial infections (SBIs). METHODS: Paediatric patients admitted to our hospital with fever were divided into four groups: SBI, non-SBI, COVID-19 and control group. White blood cell count, absolute neutrophil count, C-reactive protein and the DNI were recorded, and their accuracy in predicting SBI was evaluated. RESULTS: Mean DNI was 4.96 ± 8.38 in the SBI group (150 patients), 0.67 ± 1.68 in the non-SBI group (397 patients), 0.29 ± 0.99 in the COVID-19 group (112 patients) and 0.14 ± 0.21 in the control group (102 patients). The DNI was significantly higher in the SBI group compared with the non-SBI (P < 0.001); the non-SBI group also had higher levels than the COVID-19 group (P = 0.005). One percent increase in the DNI increased the SBI rate 1.36 times (odds ratio 1.36 (95% confidence interval 1.23-1.49), P < 0.001). Based on the determined cut-off value (>2.5%), the DNI (odds ratio 6.27 (95% confidence interval 3.85-10.21), P < 0.001) significantly predicted SBIs with 90.4% specificity and 47.7% sensitivity. CONCLUSIONS: SBIs in childrenare associated with an increase in DNI levels. Compared to other biomarkers, the DNI had higher specificity in predicting SBIs. The DNI may also be usefulin differentiating bacterial and non-bacterial infections in individualclinical syndromes. Currently, there is no evidence that serum DNI aids indifferentiating COVID-19 and upper respiratory tract infection.

Challenges of the treatment of pediatric hepatosplenic bartonellosis: case report and literature review.

The hepatosplenic (HS) form of cat scratch disease (CSD) is rarely seen; however, management of the treatment is challenging for clinicians. Monotherapy or combination regimens may be preferred based on severity of cases. Along with that, there are uncertainties as to the combination and duration of antibiotics effective against the microorganisms. In this report, a 12-year-old girl diagnosed with HS-CSD and unresponsive to primary treatment with macrolide group antibiotic was presented. The patient had liver findings compatible with CSD, confirmed radiologically and pathologically, and Bartonella henselae indirect immunofluorescence assay IgG was positive at 1/2048 titre. A combination therapy for six months with doxycycline and rifampicin was initiated, and the patient was successfully treated. The preference for monotherapy or combination regimen in HS-CSD is predominantly determined by the clinician according to the severity of the patient's clinical findings. The effectivity of antimicrobial regimen in HS-CSD requires further investigation.

Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C).

Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS:  Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN: • Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19.  • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW: • In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.