Severe acute respiratory syndrome coronavirus 2 infection rate among pediatric patients with respiratory symptoms.

BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) in children has been increasing worldwide since the onset of the pandemic. This study examined the risk factors and characteristics of COVID-19 among pediatric patients compared to other respiratory viral infections. METHODS: This was a prospective cross-sectional study. Patients aged 0-18 years presenting with respiratory symptoms from October 2020 to December 2021 were included. Demographic and clinical data were reviewed. RESULTS: In total, 738 pediatric patients were enrolled. Of these, 48.5% had COVID-19, and 41.3% were infected with another respiratory virus. The COVID-19 incidence increased from 0.5% during the original strain outbreak (October 2020 to March 2021) to 56.5% and 73.4% during the alpha (April to June 2021) and delta (July to December 2021) periods, respectively. Children aged 6-18 years, being female, obesity, exposure to household members with COVID-19, and the delta period were risk factors for COVID-19. Being aged 1-5 years, obesity, shortness of breath, productive cough, and chest pain were associated with COVID-19 pneumonia. Children aged 5-18 years, underlying neurological disease, a history of COVID-19 pneumonia, and the delta period were associated with long COVID. CONCLUSIONS: Pediatric COVID-19 patients presenting with respiratory symptoms who are obese or have been exposed to household members with COVID-19 should be tested for COVID-19. COVID-19 patients who are obese, younger than five years old, or who present with shortness of breath, productive cough, or chest pain should be evaluated for pneumonia. COVID-19 patients with a history of COVID-19 pneumonia or underlying neurological disease should receive follow-up for long COVID.

Hybrid immunity from SARS-CoV-2 infection and mRNA BNT162b2 vaccine among Thai school-aged children.

Objective: To compare the immune response of hybrid immunity - arising from SARS-CoV-2 infection and mRNA BNT162b2 vaccination - to that of 2-doses of vaccine. Methods: In a subanalysis of BNT162b2 vaccine trial in 5 to 11-year-old children, There were 179 children who had hybrid immunity compared with 134 children with solely 2-dose vaccine. The immunological outcome was a surrogate virus neutralization test (sVNT) against the Omicron strain, BA.1, (%inhibition). An sVNT level ≥68 % inhibition was considered as protective immune response. Results: From February to April 2022, 179 children had COVID-19 natural infection resulting in hybrid immunity included: Group1;prior vaccination(n = 17), Group2;after the first dose(n = 61), and Group3;after the second dose(n = 97). The proportion of children with protective immune response was higher in Group 3 and Group 1 - 61.9 % and 58.8 %, compared to 36.1 % and 34.3 % in Group 2 and comparator group (2 doses of vaccine), respectively. The geometric mean % inhibition of sVNT was higher in Group 1 (68.5, 95 %CI 55.5-84.6) and Group 3 (63.5, 95 %CI 55.5-72.6), followed by comparator group (49.6, 95 %CI 44.8-54.9) and Group 2 (42.1, 95 %CI 34.6-51.3), p < 0.001. Conclusions: Immune response that arises from BNT162b2 vaccine after natural infection and infection after 2 doses of BNT162b2 was higher than infection after partially-vaccinated children.

Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients.

Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4-12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV (p = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = -0.553, p = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT (p = 0.03 and p = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.

Clinical manifestations and outcomes of coronavirus disease 2019 among pediatric liver transplant recipients in the delta and omicron variant pandemic: A retrospective study.

To determine the clinical manifestations and outcomes of the coronavirus disease 2019 (COVID-19) in children who underwent liver transplantation (LT). A retrospective study was conducted at a transplant center in Thailand to include LT recipients aged < 18 years who had been infected with COVID-19. Out of a total of 54 children, there were 31 probable cases (57.4%) diagnosed using an antigen test kit and 23 confirmed cases (42.6%) diagnosed using polymerase chain reaction (14 children) or severe acute respiratory syndrome coronavirus 2 antigen (9 children). Approximately half of the children (25, 46.3%) received the BNT162b2 vaccine before the infection, with 3 and 2 doses in 5 and 18 children, respectively. While some had COVID-19 during the delta pandemic, most (46 children, 85.2%) were infected during the omicron pandemic, of which manifestations included fever (67.4%), cough (50%), and rhinorrhea (47.8%), and symptoms lasted approximately 3 days. None had severe diseases. All patients with mild-to-moderate disease were advised to continue the same immunosuppressive therapy as before the infection. Compared to unvaccinated children or children with one dose of the vaccine, fever was less common in those who received ≥ 2 doses (OR: 0.08; 95%CI: 0.01-0.57, adjusted for age and immunosuppressive types). Favipiravir was prescribed in most patients (90.7%). Only a few children had long COVID-19 or abnormal liver function tests lasting > 1 month (4 children, 7.4%, both). Pediatric LT recipients with COVID-19 during the delta and omicron variant pandemic reported mild symptoms despite undergoing immunosuppressive therapy.

PCR-based versus conventional stool tests in children with diarrhea who underwent solid organ transplantation or hematopoietic stem cell transplantation.

Infectious diarrhea is a common problem among post-transplant recipients. Compared to conventional tests, polymerase chain reaction (PCR)-based stool tests have been shown to improve diagnostic yield but the aforementioned data in children remain limited. Our aims were to assess the detection rate of PCR-based tests in post-transplant children and compare with the conventional tests; and to investigate how these stool tests help in managing these children. We enrolled children aged 1 to 19 years who underwent solid organ transplantation or hematopoietic stem cell transplantation that remained on immunosuppressive agents and developed diarrhea ≥ 24 hours between January 2015 and February 2023. Besides stool tests, data on demographics, clinical characteristics and management were collected. We analyzed 68 patients and 92 episodes of diarrhea with PCR-based tests. PCR-based tests provided a detection rate of 41.8% versus 16.5% for the conventional tests. While conventional tests may detect a higher proportion of Clostridiodes difficile infection, PCR-based tests showed greater yields in detecting Salmonella spp. and viruses especially norovirus. PCR-based tests had an impact in management among 22/38 (58%) diarrheal episodes especially with Campylobacter jejuni and C difficile; and among 16 episodes that positive PCR-based tests had a minimal impact, the most common reason was due to the need for continuation of antimicrobial agents for concomitant site-specific infection (69%). Among transplanted children presenting with diarrhea, PCR-based tests provide a higher yield when compared with the conventional tests. The PCR-based stool tests may also further guide clinicians for providing proper antimicrobial agents.

Immunogenicity and reactogenicity of fractional, heterologous primary COVID-19 vaccination schedules with BNT162b2 boosters in 5-11-year-old Thai children: A multicenter, prospective, double-blind, randomized control trial.

OBJECTIVE: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children. METHODS: This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-µg) or half-dose (5-µg) BNT162b2 vaccines as follows: CoronaVac/10-µg-BNT162b2 (Group 1), CoronaVac/5-µg-BNT162b2 (Group 2), 10-µg-BNT162b2/10-µg-BNT162b2 (Group 3), or 10-µg-BNT162b2/5-µg-BNT162b2 (Group 4). A subset of participants from each arm received 10-µg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported. RESULTS: Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter. CONCLUSION: Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines.

Risk factors of cytomegalovirus infection after pediatric liver transplantation and effectiveness of preemptive therapy.

BACKGROUND: Cytomegalovirus (CMV) infection is the most common infection following pediatric liver transplantation (LT). Preemptive therapy (PET) is an approach to initiate antiviral treatment for asymptomatic early CMV viremia detected by surveillance testing. However, data on CMV infection after PET are scarce, and the optimal cut-off remains controversial. This study aimed to evaluate the incidence, risk factors, and consequences of CMV infection in pediatric LT using 2 different viral load (VL) cut-offs. METHODS: We retrospectively reviewed patients aged 0-18 years who underwent LT at Ramathibodi Hospital between March 2001 and August 2020. Demographic data, CMV infection, CMV treatment, and consequences of CMV infection were collected. CMV viremia was monitored by a quantitative nucleic acid amplification test. Clinical outcomes were compared after starting antiviral therapy at a low (>400 but <2000 IU/mL) and a high VL cut-off (≥2000 IU/mL). RESULTS: A total of 126 patients were included. CMV infection was 71% (90/126), with an incidence rate of 5.5 per 1000 patient-day. Higher tacrolimus and prednisolone dosages were associated with CMV infection with an adjusted hazard ratio of 1.2 (95%CI 1.0-1.4, p = .02) and 2.4 (95%CI 1.9-3.4, p < .001), respectively. The consequences of CMV infection did not differ significantly for the low and high CMV VL cut-off groups. CONCLUSION: CMV infection in LT recipients is common and is associated with higher tacrolimus and corticosteroid dosage. Additionally, using the CMV VL cut-off at 2000 IU/mL to initiate antiviral therapy is practical and effective in preventing CMV disease.

Pediatric drug utilization evaluation of cefepime and piperacillin/tazobactam.

BACKGROUND: Drug utilization evaluation (DUE) is a systematic, criteria-based assessment of medicine that aims to optimize the appropriateness of antibiotic prescription. This study aimed to evaluate the performance of the DUE on prescriptions of two commonly used antibiotics in a pediatric population, cefepime and piperacillin/tazobactam, in a tertiary care hospital. METHODS: This quasi-experimental study was conducted at the Department of Pediatrics, Ramathibodi Hospital, between March 2020 and August 2021. All hospitalized children aged 1 month to 20 years who received at least one dose of cefepime or piperacillin/tazobactam were enrolled. Before implementing the DUE, cefepime and piperacillin/tazobactam prescriptions were retrospectively evaluated using the DUE criteria. During the 6 month DUE implementation period, physicians voluntarily chose to use DUE to assess the prescriptions' appropriateness. Demographic data, antibiotic use, and clinical data were recorded. RESULTS: There were 304 prescriptions of cefepime and piperacillin/tazobactam, with 108 empirical prescriptions (72 patients) in the DUE group and 158 prescriptions (138 patients) in the non-DUE group. The appropriateness of empirical prescriptions of cefepime and piperacillin/tazobactam was significantly higher in the DUE group (93.5% vs. 83.5%; P = 0.003). Drug utilization evaluation was significantly associated with appropriate empirical prescriptions (adjusted OR 5.32: 95% CI 1.80-15.73; P = 0.003). Prescriptions in critical care wards and urinary tract infections (UTIs) were associated with not fulfilling the DUE criteria for appropriateness. CONCLUSIONS: Drug utilization evaluation could improve the appropriateness of empirical use of cefepime and piperacillin/tazobactam in pediatric patients. Patients in critical care units and with UTIs appeared to be associated with inappropriate empirical treatment.

Handshake stewardship reduces carbapenem prescription in a pediatric critical care setting.

BACKGROUND: Intensive care unit (ICU) settings typically have a high-volume prescription of carbapenems. Antimicrobial stewardship programs (ASPs) aim to promote appropriate antibiotic use. Handshake stewardship (HS) is adapted from ASPs but focuses on direct feedback to physicians who prescribed antibiotics regarding the appropriateness of antibiotic prescription. This study aimed to evaluate the impact and acceptability of HS on carbapenem consumption in pediatric critical care settings. METHODS: This study was conducted over 18 months spanning pre-and post-implementation of HS. Carbapenem prescriptions were automatically discontinued during the pre-implementation period after 72 h if no indications existed. During the post-implementation, HS was performed by direct feedback to ICU physicians regarding the appropriateness of carbapenem prescriptions within 24 h. The primary outcome was the carbapenem consumption rate, defined as days of therapy (DOT)/1,000 patient-ICU days. Secondary outcomes were the acceptability of HS, length of critical care stay (LOCS), 30-day infection-related mortality rate, and the rate of carbapenem-resistant Enterobacteriaceae (CRE). RESULTS: There were 212 carbapenem prescriptions (163 patients) and 174 carbapenem prescriptions (110 patients) in the pre-and post-implementation periods, respectively. Carbapenem consumption decreased significantly from 667 to 369 DOT/1,000 patient-ICU days, with a median difference of 292 DOT/1,000 patient-ICU days (P < 0.001; 95% confidence interval: 175-408) after HS implementation. The acceptability of the HS was 95.4%. The LOCS, 30-day infection-related mortality, and CRE rate were not significantly different between pre-and post-implementation periods. CONCLUSIONS: Handshake stewardship significantly reduced carbapenem prescription in critically ill pediatric patients without negatively affecting patient outcomes.

Immunogenicity of varicella zoster vaccine in pediatric liver transplantation.

BACKGROUND: Pediatric liver transplant (LT) candidates often miss complete varicella-zoster virus (VZV) vaccination before LT. We aimed to evaluate the immunogenicity of two doses of VZV vaccines in pediatric LT candidates younger than 2 years and persistence of its immunogenicity after LT. METHODS: Patients aged 9-24 months were enrolled before LT. The first dose of VZV vaccine was given at 9 months, and the second dose was given at between 1 to 3 months later, and at least 4 weeks before LT. Varicella-zoster IgG (VZG) was used to detect immunoglobulin G antibodies to VZV and was reported as a test value (TV). A test value ≥ 0.9 was considered as seropositive. TV was measured at enrollment, 1 month after the first and the second dose of VZV vaccine, before LT, and 3 and 6 months after LT. RESULTS: Fourteen children were enrolled in this prospective cohort study. The median age at the first and the second dose of VZV vaccine was 11.5 months (IQR 9-12) and 13 months (IQR 12-33), respectively. The seroconversion rate was 66.7% (8/12) and 70% (7/10) after the first and second VZV vaccine doses, respectively. Seven of nine patients who underwent LT had two doses of VZV vaccine. Six patients were seropositive before LT, which persisted at 3 to 6 months after LT. Of two patients who received only one dose, TV was not detected after LT. CONCLUSIONS: The two doses of VZV vaccine appeared to be more immunogenic than one dose in pediatric LT candidates aged less than 2 years.

Association between adenovirus infection and mortality outcome among pediatric patients after hematopoietic stem cell transplant.

BACKGROUND: Adenovirus can cause severe diseases in post-hematopoietic stem cell transplant (HSCT) patients. Because these patients also have many other factors contributing to mortality, it remains controversial whether adenovirus infection itself contributes to increased mortality in these patients. OBJECTIVE: To determine if adenovirus infection contributes to mortality in pediatric post-HSCT patients. METHODS: This retrospective cohort study was performed in post HSCT patients, aged 0-18 years old, admitted at Ramathibodi Hospital from 2016 to 2020. Adenovirus infection was defined as the detection of adenovirus in blood or urine by polymerase chain reaction. Multivariate cox regression was used to identify factors associated with death. RESULTS: The incidence of overall adenovirus infection (viremia or viruria) in this cohort was 20.8% (26 out of 125 enrolled patients). From the multivariate cox regression analysis, overall adenovirus infection was not significantly associated with death (hazard ratio [HR]: 2.41; 95% confidence interval [CI]: 0.96-6.06; p = .060). However, presence of viremia (HR: 3.90; 95% CI: 1.40-10.86; p = .009), having maximal serum viral load > 10 000 copies/ml (HR: 3.70; 95% CI: 1.20-11.38; p = .023), presence of end-organ diseases (HR: 3.44; 95% CI: 1.18-10.01; p = .023) were associated with mortality. Underlying diseases requiring long-term immunosuppressive drugs before HSCT, invasive fungal disease, invasive bacterial infection, cytomegalovirus infection, and longer engraftment time were also associated with mortality. CONCLUSION: Overall adenovirus infection does not appear to play a significant role in mortality in pediatric post-HSCT patients. However, more invasive forms of adenovirus infection were associated with mortality in these patients.

Invasive Fungal Disease Among Pediatric and Adolescent Patients Undergoing Itraconazole Prophylaxis After Hematopoietic Stem Cell Transplantation.

BACKGROUND: Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Itraconazole has been used for prevention of IFD, but data related to incidence and associated factors of IFD in pediatric and adolescent patients on itraconazole prophylaxis remain scarce. OBJECTIVES: To identify incidence and risk factors associated with IFD among pediatric and adolescent patients receiving itraconazole prophylaxis after HSCT. METHODS: Patients younger than 21 years who received itraconazole prophylaxis after HSCT from January 2007 to December 2016 were retrospectively enrolled. Incidence of IFD within 1 year and associated factors were analyzed. RESULTS: All patients received itraconazole during the pre-engraftment period. Of 170 patients, 29 had IFD, with an incidence of 17.1% at 1 year. IFD at 1 year was significantly associated with increased mortality. Of 29 patients with IFD, only 9 developed IFD while on itraconazole prophylaxis (5.3%), all of whom had invasive pulmonary aspergillosis. No invasive candidiasis occurred during itraconazole prophylaxis. Prolonged neutropenia (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 1.02-1.13), graft-versus-host disease within 100 days after transplantation (HR = 3.17; 95% CI, 1.17-8.57), and using etoposide in preconditioning regimens (HR = 21.60; 95% CI, 2.44-190.95) were significantly associated with IFD at 1 year. No patients had to discontinue itraconazole because of its adverse effects. CONCLUSIONS: Itraconazole proffered good efficacy for prevention of candidiasis during the pre-engraftment period. Most IFD episodes occurred after the engraftment period when itraconazole had been discontinued. During this period, patients with risk factors require appropriate fungal prophylaxis.

A rare case of primary sinonasal tuberculosis presented with phlyctenular keratoconjunctivitis in a pediatric patient: A case report and literature review.

RATIONALE: Tuberculosis is a common cause of phlyctenular keratoconjunctivitis, especially for patients who live in a high endemic area of tuberculosis. We report a rare case of pediatric phlyctenular keratoconjunctivitis associated with primary sinonasal tuberculosis. PATIENT CONCERNS: A 7-year-old boy presented with a 5-month history of redness of the left eye accompanied by mild visual impairment. Physical examination revealed elevated pinkish-white nodules with a circumcorneal hypervascularized lesion on the left conjunctiva. DIAGNOSIS: Computed tomography revealed an enhancing soft tissue mass in the left maxillary sinus with bone destruction. Histopathology of maxillary tissue showed chronic inflammation without granuloma. Special stain, culture and polymerase chain reaction for mycobacterium were initially negative. Left maxillary sinus tuberculosis was diagnosed by positive Mycobacterium tuberculosis polymerase chain reaction from formalin-fixed paraffin-embedded maxillary tissue. INTERVENTIONS: Two month of oral isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 10 months of oral isoniazid and rifampicin without topical eye drops agent were prescribed. OUTCOMES: Two months after initiation of treatment, the phlyctenular lesion had significantly improved. A follow-up computed tomography showed a significant reduction in the size of the maxillary sinus lesion and the extent of adjacent bone destruction. LESSONS: Primary sinonasal tuberculosis is an uncommon cause of phlyctenular keratoconjunctivitis in children. When microbiological and histopathological evidences are absent, polymerase chain reaction analysis has a crucial role in the diagnosis of tuberculosis, especially in patient with uncommon presentation.

High prevalence of multidrug-resistant gram-negative bacterial infection following pediatric liver transplantation.

Bacterial infection has been identified as one of the most significant complications of liver transplantation (LT). Multidrug-resistant (MDR) gram-negative bacteria (GNB) infection remains problematic issue following LT in the adults. However, data in children are scarce. We aimed to examine the prevalence and associated factors of MDR-GNB infection among pediatric LT recipients.We performed a single-center retrospectively study of 118 children who underwent LT between January 2010 and December 2018. Data on the prevalence, clinical characteristics, types, and sites of MDR-GNB infection within 3 months after LT as well as the treatment outcomes were collected. Multidrug resistance was defined as acquired non-susceptibility to at least 1 agent in 3 or more antibiotic classes.In total, 64 (53.7%) patients developed 96 episodes of culture-proven bacterial infection with 93 GNB isolates. Moreover, there were 58 (62.4%) MDR-GNB isolates, with a predominance of Klebsiella pneumoniae (32.7%), Escherichia coli (31%), and Pseudomonas aeruginosa (10.3%). Interestingly, 10 (17.2%) isolates were determined to be carbapenem-resistant Enterobacteriaceae. The median time to MDR-GNB infection was 9 (interquartile range: 5-33) days. The most common type of infection was intra-abdominal infection (47.9%). In the multivariate analysis, the significant variables associated with post-LT MDR-GNB infection include exposure to third-generation cephalosporins (hazard ratio [HR]: 2.16, P = .023), operative time (hazard ratio [HR] 1.20, P = .009), and length of intensive care unit stay (HR 1.03, P = .049). With a focus on carbapenem-resistant Enterobacteriaceae infection, a pediatric end-stage liver disease score >21 was the only significant 6 variable in the multivariate analysis (HR 11.48, P = .024). The overall 3-month mortality rate was 6.8%.This study has highlighted the high prevalence rate of MDR-GNB infection after pediatric LT. Therefore, caution on the emergence of MDR-GNB infection should be paid in at-risk children. Moreover, knowledge regarding the prevalence of MDR-GNB infection and resistant patterns is essential for guideline development to prevent and minimize the risk of MDR-GNB infection in this group of patients.

Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) recipients require hepatitis B (HBV) revaccination. Hepatitis B surface antibody (anti-HBs) seroconversion rates after revaccination range from 64% to 79% in these patients. The seroconversion rate and factors associated with non-seroconversion have not been clearly elucidated in pediatric and young adult recipients after HSCT. OBJECTIVES: To evaluate anti-HBs seroconversion rates in pediatric and young adult patients revaccinated after HSCT, and to identify factors associated with non-seroconversion. METHOD: The current study was prospective and cross-sectional. Post-HSCT recipients aged ≤25 years who had completed a course of three HBV revaccinations were recruited, and their anti-HBs titers were assessed. Non-seroconverted patients were administered a fourth vaccination. Those who subsequently remained seronegative were administered two additional vaccinations. Those who remained seronegative after all six vaccinations were defined as non-responders. RESULTS: A total of 118 patients were enrolled. The HBV-containing vaccines used included DTaP-IPV-HBV-Hib, DTwP-HBV-Hib, and monovalent vaccines. The anti-HBs seroconversion rate after three revaccinations was 82% (95% confidence interval [CI], 73.7-89.2). One patient (0.8%) was classified as non-responder. Factors associated with non-seroconversion after three revaccinations included cytomegalovirus (CMV) reactivation (odds ratio [OR] 10.63, 95% CI 1.16-97.00), anti-HBs seronegativity before HSCT (OR 7.01, 95% CI 1.55-31.78) and three DTwP-HBV-Hib revaccinations (OR 11.71, 95% CI 1.43-96.26). CONCLUSION: In the current study the anti-HBs seroconversion rate after three HBV revaccinations was excellent. CMV reactivation, anti-HBs seronegativity before HSCT, and three DTwP-HBV-Hib revaccinations were associated with non-seroconversion, but the non-responder rate was low.

Bacterial Endocarditis Caused by Actinomyces oris: First Reported Case and Literature Review.

Actinomyces species are gram-positive, facultative anaerobic bacilli. Infection caused by Actinomyces species is usually limited to cervicofacial, thoracic, and abdominopelvic regions. Infective endocarditis due to Actinomyces species is extremely rare with only 30 reported cases since 1939. We report a case of Actinomyces oris endocarditis in a 14-year-old boy who had a 2-week history of dyspnea on exertion without other constitutional signs. Transthoracic echocardiography was suggestive of perforation of the right coronary cusp of aortic valve. No organisms were isolated from blood cultures. The patient underwent surgical valve repair due to deteriorated cardiac function. Valve tissue culture did not initially identify the organism. However, the terminal subculture in a thioglycolate broth grew gram-positive bacilli. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was compatible with Actinomyces oris. After 6 weeks of intravenous ampicillin, the patient remained well with improved cardiac function. We reviewed all reported cases of infective endocarditis caused by Actinomyces species, commenting on clinical characteristics and factors associated with unfavorable outcomes in infective endocarditis due to Actinomyces species. Although infective endocarditis caused by Actinomyces spp is rare, it could be considered in a case of culture-negative endocarditis since the clinical features might be indistinguishable from other bacterial endocarditis. Additionally, MALDI-TOF MS is a useful diagnostic tool for the identification of Actinomyces spp to improve the accuracy of diagnosis.

Outcomes of Empirical Antimicrobial Therapy for Pediatric Community-onset Febrile Urinary Tract Infection in the Era of Increasing Antimicrobial Resistance.

BACKGROUND: Urinary tract infection (UTI) is a common cause of fever in children. Despite the increasing numbers of extended-spectrum beta-lactamase-producing organisms in the community, the empirical therapy of choice is still third-generation cephalosporins. This study was performed to investigate whether inappropriate empirical therapy (IAT) of community-onset UTI results in adverse clinical outcomes. METHODS: We retrospectively studied a cohort of pediatric patients with first-episode community-onset UTI caused by Escherichia coli, Klebsiella pneumoniae and Proteus spp. at Ramathibodi Hospital from 2011 to 2017. The patients were classified into IAT and appropriate empirical therapy (AT) groups. Medical records were reviewed to assess clinical outcomes. RESULTS: One hundred fifty-one eligible patients were enrolled in this study. The most common causative organism was E. coli (88.8% and 96.2% in the AT and IAT groups, respectively). Among the causative organisms, 19.8% were extended-spectrum beta-lactamase-producing organisms. There was no significant difference in clinical failure, microbiologic failure, relapse or time to defervescence between the 2 groups. No patients in either group developed sepsis after receiving empirical therapy. However, the length of hospital stay was significantly longer in the IAT than AT group [4.00 (4.50-6.00) vs. 7.00 (5.00-11.25) days, respectively; P = 0.000]. CONCLUSIONS: No significant difference in treatment outcomes was found between pediatric patients receiving AT and IAT for the treatment of UTI. In the era of increasing antimicrobial resistance, third-generation cephalosporins may still be a good choice as an empirical antimicrobial for children diagnosed with community-onset UTI.

Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children.

OBJECTIVES: The objectives of this study were to investigate the population pharmacokinetics of posaconazole in immunocompromised children, evaluate the influence of patient characteristics on posaconazole exposure and perform simulations to recommend optimal starting doses. METHODS: Posaconazole plasma concentrations from paediatric patients undergoing therapeutic drug monitoring were extracted from a tertiary paediatric hospital database. These were merged with covariates collected from electronic sources and case-note reviews. An allometrically scaled population-pharmacokinetic model was developed to investigate the effect of tablet and suspension relative bioavailability, nonlinear bioavailability of suspension, followed by a step-wise covariate model building exercise to identify other important sources of variability. RESULTS: A total of 338 posaconazole plasma concentrations samples were taken from 117 children aged 5 months to 18 years. A one-compartment model was used, with tablet apparent clearance standardised to a 70-kg individual of 15 L/h. Suspension was found to have decreasing bioavailability with increasing dose; the estimated suspension dose to yield half the tablet bioavailability was 99 mg/m2. Diarrhoea and proton pump inhibitors were also associated with reduced suspension bioavailability. CONCLUSIONS: In the largest population-pharmacokinetic study to date in children, we have found similar covariate effects to those seen in adults, but low bioavailability of suspension in patients with diarrhoea or those taking concurrent proton pump inhibitors, which may in particular limit the use of posaconazole in these patients.

Correction to: Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children.

However, the Original article has been updated with the Open Access under Commercial License.

Analysis of Ganciclovir-Resistant Cytomegalovirus Infection Caused by the UL97 Gene Mutation in Codons 460 and 520 in Pediatric Patients: A Case Series.

BACKGROUND: Drug-resistant cytomegalovirus (CMV) infection has been increasingly recognized. However, there are limited data in pediatric patients. In this study, the prevalence and factors associated with CMV infection with UL97 mutations in pediatric patients treated with ganciclovir but not responding to treatment were evaluated. METHODS: This retrospective study was conducted from January 2013 to December 2017. All patients who were suspected of having ganciclovir-resistant CMV infection and had never had ganciclovir prophylaxis were included. Genotypic assay for UL97 mutations in codons 460 and 520 conferring ganciclovir resistance was performed. Factors associated with the presence of UL97 mutations were analyzed. RESULTS: Of 34 patients included, 10 patients (29.4%) had a genotypically confirmed UL97 mutation. The median age (interquartile range [IQR]) was 3 (0.85-8.68) years. Ganciclovir resistance was tested at a median time (IQR) of 22.5 (14.3-31) days after initiation of ganciclovir. All resistant isolates harbored a UL97 mutation in codon 460. Compared with patients infected with CMV without UL97 mutation, those infected with UL97 mutation strains were younger (median age [IQR], 3.02 [0.85-8.68] vs 10.45 [2.7-16.4] years) and had a higher maximum viral load (median [IQR], 5.06 [4.74-6.05] vs 4.42 [4.03-4.87] copies/mL). Six of 10 (60%) patients were successfully treated with high-dose ganciclovir (7.5 mg/kg twice daily). CONCLUSIONS: UL97 mutation ganciclovir-resistant CMV infection was not uncommon in the pediatric population. Screening for this mutation should be considered in patients experiencing virological worsening while ganciclovir is given, even if patients have not previously received ganciclovir prophylaxis.