Body surface area compared to body weight dosing of valganciclovir is associated with increased toxicity in pediatric solid organ transplantation recipients.

Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, P <.001), lymphopenia (51% vs 15.0%, P <.001), and acute kidney injury causing treatment modification (8.0% vs 1.8%, P <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.

Vasoactive inotropic score as a predictor of mortality in neonatal septic shock.

BACKGROUND: Although many improvements in neonatal care have been achieved, mortality rates for sepsis and septic shock in newborns are still high. The vasoactive inotropic score (VIS) was designed and studied to predict mortality in different settings. There are currently no data on the predictive ability of the VIS for mortality in newborn patients with septic shock. METHODS: Patients with late-onset neonatal sepsis who required inotropes because of fluid-refractory septic shock during the study period were included in the study. Four distinct VIS values were calculated for each septic shock episode after inotropic treatment had begun, that is, at the initiation of inotropic treatment and at 24 and 48 h after inotropic treatment had begun, and the highest VIS (VISmax) at any time after initiation of inotropic agents. RESULTS: The 98 episodes studied were divided into two groups according to the outcomes of their sepsis episodes as survivors (n = 39) or nonsurvivors (n = 59). The areas under the curve of the VIS values for the prediction of mortality were the VISmax (0.819, p < 0.001), followed by the VIS48 (0.802, p < 0.001), VIS24 (0.762, p = 0.001) and VIS0 (0.699, p = 0.015). Patients with a VISmax of greater than 20 had significantly higher odds of mortality (p < 0.001, ß = 14.7, 95% confidence interval [4.7-45.9]). CONCLUSION: We found that the VISmax was an easy-to-use and helpful tool for predicting a poor outcome in neonatal sepsis. Physicians should be aware that the prognosis is poor for any newborn with a VIS of 20 or greater at any point after the onset of sepsis.

Neonatal sepsis is still one of the most important causes of mortality and morbidity in the neonatal period, and it is also a significant public health problem. Researchers have been looking for reliable biomarkers and scoring systems to detect neonatal sepsis and predict outcomes. The vasoactive inotropic score has been validated and found to be useful for predicting mortality in septic shock in adults and children and newborns who underwent cardiac surgeries. However, there are no neonatal sepsis data. In this retrospective study, we showed that a maximal vasoactive inotropic score of 20 or greater is an easy, noninvasive and useful tool to determine the poor outcome.

Clinical Outcomes of Oral Antibiotic Switch in Children with Staphylococcus aureus Bacteremia.

Staphylococcus aureus is one of the leading causes of bacteremia in children. In this study, we aimed to evaluate our center's experience on the etiology, management, and outcomes of pediatric Staphylococcus aureus bacteremia (SAB) with particular focus on transitioning to oral antibiotic therapy. This retrospective cohort study included children aged ≤ 19 years diagnosed with SAB over a 5-year period. The main outcome was poor clinical outcome related to SAB defined as (1) recurrence of SAB within 30 days after discontinuation of SAB treatment and (2) any-cause mortality within 30 days after detection of SAB. Over a 5-year period, 88 SAB episodes of 76 unique patients were included. The most common source of SAB attributed to central line (n = 34), followed by osteoarticular (n = 24), infections. All patients received at least one day of intravenous (IV) antibiotics and treatment was switched to an oral agent in 45.5% of SAB episodes. Sources of SAB in the oral switch group were osteoarticular (n = 21), skin and soft tissue (n = 7), central line (n = 3), thrombophlebitis (n = 2), head and neck infection (n = 1), and unknown (n = 6). 30-day mortality and SAB recurrence within 30 days after initial treatment completion occurred in 3 and 5 SAB episodes, respectively. None of the patients in oral switch group had poor clinical outcomes. Our study results indicate that 30-day any-cause mortality and SAB-related mortality is low in children. Similar to growing adult literature, oral switch in SAB treatment was not associated with poor SAB outcomes in selected patients.

Skin and Soft Tissue Actinomycosis in Children and Adolescents.

BACKGROUND: Pediatric actinomycosis studies are limited to case reports or small case series. In this retrospective cohort study, we aimed to describe characteristics of skin and soft tissue actinomycosis in adolescents and children. METHODS: We conducted the study from January 2019 to December 2022, including patients ≤21 years of age with at least 1-year follow-up data. All clinical cultures obtained under sterile conditions with Actinomyces growth were included. RESULTS: One hundred four patients met inclusion criteria; median age 19 (interquartile range: 17-20) years, 68.3% female, 46.2% Black and 47.1% Hispanic. The median antibiotic treatment duration was 10 (7-10) days, and majority of patients received treatment with non-first-line Actinomyces antibiotics. Infectious disease consultation was requested for only 7 patients during their initial skin and soft tissue actinomycosis treatment. One-third of the patients with skin and soft tissue actinomycosis had documented recurrence within a median of 10 (interquartile range: 6-16) months of the initial episode. Monobacterial culture growth (85.7% vs. 63.8%, P = 0.02), patients with body mass index >25 (75% vs. 52.6%, P = 0.04) and patients with prior abscess in the same area (18.8% vs. 51.4%, P = 0.001) were significantly higher in patients with recurrent actinomycosis compared to the nonrecurrent group. In a univariate logistic regression model, they were found to be significantly associated with recurrence; monobacterial growth [odds ratio (OR): 3.4; 95% confidence interval (CI): 1.2-9.9], body mass index >25 (OR: 2.7; 95% CI, 1.1-7.0) and prior abscess (OR: 4.6; 95% CI: 1.9-11.2). CONCLUSIONS: Our study results highlight the importance of considering Actinomyces species in skin and soft tissue infections, especially in recurrent ones, and risk factors for recurrence. Suboptimal antibiotic utilization, very low numbers of consultations with infectious diseases and high recurrence rate suggest that providers should be informed and updated regarding this rare but hard-to-treat infection.

Pediatric Clinical Outcomes of Nasal Methicillin-resistant Staphylococcus aureus Polymerase Chain Reaction Utilization.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a clinical challenge in selecting empiric antimicrobials for pediatric infections. We implemented nasal MRSA polymerase chain reaction (nMRSA PCR) screening as a diagnostic tool and evaluated its impact on empiric antibiotic use and clinical outcomes. METHODS: A retrospective single-center study of patients hospitalized with infections who were empirically prescribed anti-MRSA antibiotics was conducted prior to and following the initiation of nMRSA PCR screening. Electronic medical records, pharmacy data and bacterial cultures results were reviewed. Predictive values of nMRSA PCR testing were calculated and the duration of anti-MRSA empiric therapy and clinical outcomes preimplementation and postimplementation were compared. RESULTS: During the preimplementation period, there were 382 distinct episodes (294 unique patients) that met the inclusion criteria and during post-nMRSA PCR implementation, 394 episodes (360 unique patients) were identified. The median time to discontinuation of anti-MRSA antibiotics and proportion of patients prescribed anti-MRSA antibiotics at discharge were significantly lower in postimplementation compared with preimplementation period; 48 versus 56 hours, P < 0.001 and 20.1% versus 40.3%, P < 0.001, respectively. The negative and positive predictive values of nMRSA PCR compared to clinical culture results were 95.6% and 51.2%, respectively. Predefined adverse outcomes were documented in 11 patients who had early anti-MRSA discontinuation with negative nMRSA PCR results but only 3 were restarted on anti-MRSA treatment and none grew MRSA in clinical cultures. CONCLUSIONS: Shortened anti-MRSA antibiotic duration, high negative predictive value and low adverse events provide promising evidence that nMRSA PCR is an effective, rapid antimicrobial stewardship tool for hospitalized children.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results: Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions: CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

Differences in the Clinical Manifestations and Host Immune Responses to SARS-CoV-2 Variants in Children Compared to Adults.

The COVID-19 pandemic challenged the medical field to rapidly identify and implement new approaches to the diagnosis, treatment and prevention of SARS-CoV-2 infections. The scientific community also needed to rapidly initiate basic, translational, clinical and epidemiological studies to understand the pathophysiology of this new family of viruses, which continues to evolve with the emergence of new genetic variants. One of the earliest clinical observations that provided a framework for the research was the finding that, in contrast to most other respiratory viruses, children developed less severe acute and post-acute disease compared to adults. Although the clinical manifestations of SARS-CoV-2 infection changed with each new wave of the pandemic, which was dominated by evolving viral variants, the differences in severity between children and adults persisted. Comparative immunologic studies have shown that children mount a more vigorous local innate response characterized by the activation of interferon pathways and recruitment of innate cells to the mucosa, which may mitigate against the hyperinflammatory adaptive response and systemic cytokine release that likely contributed to more severe outcomes including acute respiratory distress syndrome in adults. In this review, the clinical manifestations and immunologic responses in children during the different waves of COVID-19 are discussed.

Surgical and Medical Management of Purulent Bacterial Pericarditis With Pericardial Mass in a Young Child.

Purulent bacterial pericarditis is rare and associated with significant short- and long-term morbidity. We report a case of purulent bacterial pericarditis caused by Group A Streptococcus in an immunocompetent young child presenting with a pericardial mass. She was successfully treated with a combined medical and early surgical approach. (Level of Difficulty: Intermediate.).

Early-Onset Neonatal Sepsis in Turkey: A Single-Center 7-Year Experience in Etiology and Antibiotic Susceptibility.

BACKGROUND: The pathogen distribution and antibiotic susceptibility of the pathogens in early-onset sepsis (EOS) differ between countries. The epidemiological data from a limited number of studies about EOS in Turkey are insufficient. In this study, we aimed to evaluate the culture-proven EOS cases, causative microorganisms, antibiotic susceptibility patterns, and risk factors for mortality in EOS. METHODS: This is a retrospective, single-center study over a 7-year period, from 2013 to 2020, at Zeynep Kamil Maternity and Children's Hospital, Istanbul, Turkey. RESULTS: During the study period, 8229 newborns were admitted to our neonatal intensive care unit. Culture-proven EOS was detected in 101 patients (0.12%). Out of these, 56 (55.4%) were Gram-positive, and 45 (44.5%) were Gram-negative sepsis. The most common isolated organism was E. coli (28.7%, n = 29), followed by GBS (16.8%, n = 17) and S. aureus (15.8%, n = 16). An ampicillin and gentamicin combination had antimicrobial coverage in 92.6% of cases. Seventeen patients (16.8%) died because of EOS. Severe neutropenia was found to be an independent risk factor for mortality in EOS (p = 0.001, OR = 14.4, CI 95%: 2.8-74). CONCLUSIONS: Although the majority of causative agents were Gram-positive (55.4%), the most common isolated organism was E. coli. An empirical antibiotic regimen of ampicillin and gentamicin continues to have an adequate coverage for EOS in our population.

Lipid accumulation product is a predictor of nonalcoholic fatty liver disease in childhood obesity.

BACKGROUND: Lipid accumulation product (LAP) is associated with the presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults. PURPOSE: Here we evaluated the ability of LAP to predict NAFLD in obese children. METHODS: Eighty obese children (38 girls; age 6-18 years) were included. Anthropometric measurements and biochemical values were obtained from the patients' medical records. LAP was calculated as [waist circumference (WC) (cm) - 58]×triglycerides (mmol/L) in girls; [WC (cm) - 65]×triglycerides (mmol/ L) in boys. The minLAP and adjLAP were described (3% and 50% of WC values, respectively) and the total/high-density lipoprotein cholesterol index (TC/HDL-C) was calculated. NAFLD was observed on ultrasound, and patients were divided into 3 groups by steatosis grade (normal, grade 0; mild, grade 1; moderate-severe, grade 2-3). The area under the curve (AUC) and appropriate index cutoff points were calculated by receiver operator characteristic analysis. RESULTS: LAP was positively correlated with puberty stage (rho=0.409; P<0.001), fasting insulin (rho= 0.507; P<0.001), homeostasis model assessment of insulin resistance (rho=0.470; P<0.001), uric acid (rho=0.522; P<0.001), and TC/HDL-C (rho=0.494; P<0.001) and negatively correlated with HDL-C (rho=-3.833; P<0.001). LAP values could be used to diagnose hepatosteatosis (AUC=0.698; P=0.002). The LAP, adjLAP, and minLAP cutoff values were 42.7 (P=0.002), 40.05 (P=0.003), and 53.47 (P= 0.08), respectively. For LAP, the differences between the normal and mild groups (P=0.035) and the normal and moderate-severe groups were statistically significant (P=0.037), whereas the difference between the mild and moderate-severe groups was not (P>0.005). There was a statistically significant difference between the normal and mild groups for adjLAP (P=0.043) but not between the other groups (P>0.005). There was no significant intergroup difference in minLAP (P>0.005). CONCLUSION: LAP is a powerful and easy tool to predict NAFLD in childhood. If LAP is ≥42.7, NAFLD should be suspected. This is the first study to assess LAP diagnostic accuracy for childhood obesity.

Personality traits in cancer patients.

BACKGROUND: This study was planned to investigate the personality traits of cancer patients in different treatment settings, and to correlate the demographics with the personality features. MATERIALS AND METHODS: A total of 237 patients referred either to Marmara University School of Medicine (MUSM) Oncology Outpatient Unit or to the private office of the faculty between March 10th and April 22nd, 2010 were enrolled in the study. The Big Five Mini Test was used to evaluate the 40 personality traits of the patients. RESULTS: The study group consisted of 98 males (41.35%) and 139 females (58.65%) with a mean age of 51. Out of the 237, 73.9% had an educational level beyond the junior high school, and 47.3% of all patients reported a positive family history for cancer. A significant difference in terms of reconcilability, extraversion, and responsibility was observed between patients admitting to the university outpatient clinic and the private office (p<0.05). Reconcilability and extraversion were found to differ between genders significantly (p<0.05). The description of the patients by him/herself or by relatives displayed a significant difference in terms of openness (p<0.05). Parameters such as educational level, family history of cancer, age and marital status showed no relevance to their characters. No discordance was observed between the self-analysis of the patient and the patient's relatives. CONCLUSIONS: Patients with cancer are typically highly reconcilable and responsible, moderately stable, open and extraverted.