Bacterial coinfections in hospitalized children with COVID-19 during the SARS-CoV-2 Omicron BA.2 variant pandemic in Taiwan.

Background: Bacterial coinfections have been widely recognized in adults with coronavirus disease 2019 (COVID-19). However, bacterial coinfections in hospitalized children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been sufficiently researched. This study aimed to determine the clinical presentations and risk factors for bacterial coinfections of pediatric inpatients during the SARS-CoV-2 Omicron BA.2 variant pandemic. Methods: This retrospective, observational study included patients younger than 18 years of age who were hospitalized for COVID-19 confirmed by polymerase chain reaction (PCR) or antigen rapid tests during the SARS-CoV-2 Omicron BA.2 variant pandemic. Data and outcomes of these patients with or without bacterial coinfections were compared. Results: During this study period, 161 children with confirmed COVID-19 were hospitalized. Twenty-four had bacterial coinfections. The most frequently reported concurrent diagnosis was bacterial enteritis, followed by lower respiratory tract infections. Children with bacterial coinfections had higher white blood cell (WBC) counts and PCR cycle threshold values. The bacterial coinfection group comprised a relatively greater proportion of patients who required high-flow nasal cannula oxygen and remdesivir. The length of stay in the hospital and that in the intensive care unit were longer for children with COVID-19 with bacterial coinfections. Mortality was not observed in either group. Abdominal pain, diarrhea, and comorbidity with neurologic illnesses were risk factors for bacterial coinfections with COVID-19. Conclusion: This study provides clinicians with reference points for the detection of COVID-19 in children and its possible association with bacterial infections. Children with COVID-19 and neurologic diseases who present with abdominal pain or diarrhea are at risk of bacterial coinfections. Prolonged fever duration and higher PCR test cycle threshold values, WBC levels, and high-sensitivity C-reactive protein (hsCRP) levels may indicate bacterial coinfections in children with COVID-19.

Bacillus Calmette-Guérin (BCG) osteomyelitis among children: Experience in a single tertiary center in central Taiwan.

BACKGROUND: The insidious nature of BCG-osteomyelitis makes it challenging for clinicians to detect it early on. METHODS: This 12-year retrospective analysis was conducted at a single tertiary hospital in central Taiwan. Electronic medical records of pediatric patients treated for BCG-osteomyelitis were reviewed. Demographics, clinical features, and laboratory findings were compared with patients diagnosed with culture-proven pyogenic osteomyelitis. RESULTS: In total, eight patients fulfilled our inclusion criteria. Their median age was 16 months, and no obvious gender prevalence was found. Six of the eight patients had lesions involving the lower extremities. When compared with the pyogenic osteomyelitis group, age of disease onset was found to be significantly younger in the BCG osteomyelitis group (p=0.038). Absence of fever and pain in the BCG osteomyelitis group was found to be statistically significant when compared with the pyogenic group (p=0.002 and p=0.026 respectively). CRP and ESR were found to be significantly higher in the pyogenic osteomyelitis group (p=0.000 and p=0.004 respectively). CONCLUSION: BCG-related osteomyelitis must be considered when evaluating an afebrile child presenting with an unexplainable swelling or limp, and especially when the lesion is located on a lower limb. Laboratory studies may reveal normal WBC and CRP, with a normal to modest elevation of ESR. Imaging studies, including plain radiographs, magnetic resonance imaging (MRI), or computed tomography (CT) should be employed to rule out BCG-related osteomyelitis. Early diagnosis help minimize inappropriate antibiotics use, and may lead to a better outcome.

Detection of respiratory pathogens by application of multiplex PCR panel during early period of COVID-19 pandemic in a tertiary hospital in Central Taiwan.

BACKGROUND: Respiratory tract infections (RTIs) represent a major cause of clinical visits worldwide. Viral epidemiology of RTIs in adults has been less studied compared to children. FilmArray respiratory panel (FA-RP), a multiplex, real time polymerase chain reaction method can simultaneously detect the nucleic acids of multiple pathogens. The purpose of this study is to analyze the epidemiology and clinical presentations of an RTI cohort. METHODS: This retrospective cohort study was conducted at China Medical University Hospital (CMUH) and China Medical University Children's Hospital (CMUCH), from January 2020 to June 2020. The FA-RP results were collected and analyzed according to upper versus lower RTIs. RESULTS: Among 253 respiratory samples tested, 135 (53.4%) were from adults and 118 (46.6%) from children. A total positive rate of 33.9% (86/253) was found, with 21.48% (29/135) in adults and 48.31% (57/118) in children. Human rhinovirus/Enterovirus (HRV/EV) was detected in most of the age groups and was more common in URIs. HRV/EV was found as a frequent co-detection virus. Among children, HRV/EV was the most detected pathogen of URIs, while the most predominant pathogen in LRIs was Mycoplasma pneumoniae. CONCLUSIONS: FA-RP has the potential to improve the detection rate of respiratory pathogens. The positive rate of FA-RP was higher in children compared to adults, which likely corresponds to the higher incidence of viral RTIs in children. Different pathogens may lead to different types of respiratory infections.

Prevention of dextran sulfate sodium-induced mouse colitis by the fungal protein Ling Zhi-8 via promoting the barrier function of intestinal epithelial cells.

The fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in protecting intestinal epithelial cells (IECs) is unknown. In this study, we aim to investigate the functional effect of LZ-8 on IECs. LZ-8 effectively rescued the pro-inflammatory cytokine-induced loss of tight junctions (TJs) by enhancing transepithelial electrical resistance (TEER), reducing permeability, and maintaining the distribution of TJ proteins, in Caco-2 cells. Mechanistically, LZ-8 blocked the upregulation of myosin light chain kinase (MLCK) and NF-kB activation by TLR2-mediated suppression of cytokine signaling (SOCS)-1 expression. Furthermore, LZ-8 pre-treatment reduced the pathological scores of dextran sulfate sodium (DSS)-induced colitis in mice. These results indicated that LZ-8 protected the barrier function of IECs against inflammation. Thus, LZ-8 may potentially be a novel candidate for treating inflammatory bowel disease (IBD).

Association between urine pH and common uropathogens in children with urinary tract infections.

BACKGROUND/PURPOSE: Urinary tract infections (UTIs) are one of the most common pediatric infections. Our objective in this study is to investigate the association between urine pH and uropathogens in pediatric patients. METHODS: The source population comprised 26 066 paired urinalysis (UA) and urine culture (UC) samples obtained from pediatric patients. We classified the paired UA-UC samples into UTI positive (N = 6348) and UTI negative (N = 19 718) according to the colony forming units corresponding to the sampling source. We included UTI positive patients with infection caused by a single species of pathogen (N = 5201) and frequency matched them with UTI negative patients (N = 4729) by age, sex, sampling source, and visit type. RESULTS: This study included 5201 pediatric patients with UTIs and found that urine with Proteus mirabilis or Pseudomonas aeruginosa demonstrated the least acidic pH (mean pH = 6.72 and 6.62, respectively), whereas urine with Escherichia coli or Klebsiella pneumoniae exhibited the most acidic pH (pH = 6.21 and 6.18). After stratifying the UTI samples by their pH range (<6, 6-6.9, 7-7.9, and ≥8). The prevalence of P. mirabilis increased significantly across increasing pH categories. CONCLUSION: This research is the first epidemiological study that linked urine pH to specific uropathogens in a pediatric population. Both urine pH and age are associated with certain causative uropathogens. Urine that grew P. mirabilis or P. aeruginosa had the least acidic pH. Additional studies should validate the role of urine pH in predicting uropathogens and UTI.

Clinical characteristics and outcomes of culture-negative versus culture-positive osteomyelitis in children treated at a tertiary hospital in central Taiwan.

BACKGROUND: The causative pathogen of pediatric osteomyelitis is often unidentified despite culturing attempts. This study evaluated and compared the clinical characteristics, therapeutic approach, and outcomes of osteomyelitis caused by unknown pathogens and identified microorganisms. METHOD: This 17-year retrospective study was conducted at a tertiary hospital in central Taiwan. Medical records of children aged less than 18 years with a diagnosis of osteomyelitis between 2003 and 2019 were reviewed. RESULT: In total, 70 patients (median age = 6.4 years; male = 65.7%) fulfilled the inclusion criteria, of whom 33 (47.1%) were culture negative. Staphylococcus aureus was the main pathogen (67.6% of identified bacteria). The proportion of methicillin-resistant S. aureus (MRSA) was 44% and 54.5% of the MRSA isolates exhibited clindamycin resistance. Compared to children with culture-positive osteomyelitis, those with culture-negative osteomyelitis had a lower rate of concomitant septic arthritis (40.5% vs. 15.2%, p = 0.019) and leukocytosis on presentation (45.9% vs. 21.2%, p = 0.030); they also required fewer surgical interventions (56.8% vs. 24.2%, p = 0.006) and received a shorter course of total antibiotic therapy (49.0 vs. 43.0 days, p = 0.045). In the culture-negative group, the MRSA coverage rate was 18.8% during initial empirical therapy and increased to 59.4% during further adjusted therapy. The overall complication rate was 18.6% and was lower in the culture-negative group (32.4% vs. 3.0%, p = 0.002). CONCLUSION: In areas where community-associated MRSA and clindamycin resistance strains are a concern, empirical glycopeptide-based therapy is suggested in pediatric osteomyelitis, particularly in those with culture-negative infections.

Increased risk of herpes zoster in children with cancer: A nationwide population-based cohort study.

Herpes zoster is rare in healthy children, but immunocompromised persons have an increased risk of herpes zoster and severe diseases. Considering the very limited information on herpes zoster in children with cancer, we performed a nationwide population-based cohort study to estimate the incidence of herpes zoster in children with cancer and to explore the association between the 2 diseases.Data were obtained from the National Health Research Institutes Database in Taiwan. A total of 4432 children with newly diagnosed cancer between 2000 and 2007 were identified as the cancer cohort, and 17,653 children without cancer frequency-matched by sex and age at entry were considered the noncancer cohort. The association between herpes zoster and childhood cancer was determined.Children with cancer had a higher risk of herpes zoster. The incidence rate of herpes zoster was higher in the cancer cohort than in the noncancer cohort (20.7 vs 2.4 per 10,000 person-years; IRR = 8.6; 95% CI = 4.8-15.6). The cumulative incidence was significantly higher in the cancer cohort (P < 0.0001). Leukemia, lymphoma, and solid tumor were all associated with the increased risk, and leukemia had the highest magnitude of strength of association.This nationwide population-based cohort study demonstrated that children with cancer were associated with an increased risk of herpes zoster. In addition to early antiviral treatment, vaccination with heat-treated zoster vaccine or adjuvanted subunit vaccine could be an appropriate policy to decrease the incidence in children with cancer.

Extracorporeal membrane oxygenation use, expenditure, and outcomes in taiwan from 2000 to 2010.

BACKGROUND: No study to date has systematically examined use, expenditure, and outcomes associated with extracorporeal membrane oxygenation (ECMO) use in Taiwan. The aim of this study was to examine ECMO use, expenditure, and outcomes during an 11-year period in Taiwan. METHODS: Claims data were collected from the Taiwan National Health Insurance Research Database for patients who received ≥1 ECMO treatment between January 2000 and December 2010. Measurements included demographics, indications for ECMO use, length of hospital stay, outcome, and expenditure. RESULTS: A total of 3969 patients received ECMO during the study period (median age: 54.6 years). The number of patients receiving ECMO increased from 52 in 2000 to 1045 in 2010. The major indication for ECMO was cardiovascular disease (68.7%), followed by respiratory disease (17.9%). Median length of hospital stay was 13 days in 2000 and 17 days in 2010. Median expenditure (New Taiwan dollars) was $604 317 in 2000 and $673 888 in 2010. Some variables significantly differed by age, sex, hospital setting, calendar year, and indication for ECMO, and were associated with in-hospital and after-discharge mortality. CONCLUSIONS: ECMO use has increased dramatically in Taiwan over the last decade. The high mortality rate of ECMO users suggested that ECMO may be being used in Taiwan for situations in which it provides no added benefit. This situation may be a reflection of the current reimbursement criteria for National Health Insurance in Taiwan. Refinement of the indications for use of ECMO is suggested.

Multidrug-resistant Acinetobacter baumannii infection among neonates in a neonatal intensive care unit at a medical center in central Taiwan.

BACKGROUND: Few studies have focused on multidrug-resistant Acinetobacter baumannii (MDRAB) infection in neonates. The aim of this study was to investigate risk factors for mortality in neonates with MDRAB infection. METHODS: This retrospective case-series study was conducted at the Children's Hospital of China Medical University, Taichung, Taiwan. All patients hospitalized between January 2010 and December 2013 in the neonatal intensive care unit (NICU) with MDRAB infections were reviewed. RESULTS: A total of 67 isolates from 59 neonatal patients were positive for MDRAB. Of the 67 isolates, 38 were from blood (56.72%), 16 from sputum (23.88%), seven from pus (10.45%), three from ascites (4.48%), two from cerebrospinal fluid (2.99%), and one from pleural fluid (1.49%). There were five episodes of MDRAB clusters consisting of 28 cases during the study period. The mortality rate due to MDRAB sepsis was 20.34% (12/59). The statistically significant risk factors for mortality due to MDRAB infection were being infected with MDRAB within 7 days of admission to the NICU, use of umbilical vein catheters, absolute neutrophil count < 1500/mm(3), platelet count < 100,000/mm(3), and a delay in initiating adequate antibiotic treatment. CONCLUSION: MDRAB infection is responsible for a high mortality rate among neonates in the NICU, especially in those who have neutropenia or thrombocytopenia. Infection control and appropriateness of the initial antimicrobial agent with colistin play an important role in reducing mortality.

Pyogenic liver abscess among children in a medical center in Central Taiwan.

BACKGROUND: Pediatric pyogenic liver abscess is uncommon. This study aimed to investigate the clinical characteristics, radiologic features, pathogens, duration of hospitalization, and management of pediatric pyogenic liver abscess. METHODS: Pediatric patients with pyogenic liver abscess admitted to the China Medical University Hospital from 1995 to 2011 were reviewed. Their clinical characteristics, radiological features, laboratory data, clinical management, and outcomes were analyzed. Those with liver abscess due to the complication of oncologic disease were excluded. RESULTS: Fifteen patients were diagnosed with pyogenic liver abscess. Their most common symptoms were fever and abdominal pain. Eight (53.0%) had leukocytosis (>15000/µL) and elevated C-reactive protein (CRP) level (>10 mg/dL). The main imaging presentation was a single abscess in right lobe of the liver (13/15, 86.7%). Blood culture were mainly negative (12/15, 80.0%). Pathogenic microorganisms cultured from pus revealed Klebsiella pneumoniae (6/15, 40.0%) and Streptococcus spp. (6/15, 40.0%) as the two most common pathogens. Percutaneous abscess drainage followed by adequate parenteral antibiotics were effective interventions. Hospitalization of at least 2 weeks was needed in most cases. There were no mortalities. CONCLUSION: Pyogenic liver abscess should be considered in children presenting with fever, abdominal pain, and leukocytosis with a high CRP level. Most cases involve a single lesion on right lobe of the liver. K. pneumoniae and Streptococcus spp. are the two most common pathogens. Drainage with adequate antibiotics has significantly good response.

Immunogenicity and safety of a trivalent inactivated 2010-2011 influenza vaccine in Taiwan infants aged 6-12 months.

This prospective study aimed to investigate the immune responses and safety of an influenza vaccine in vaccine-naïve infants aged 6-12 months, and was conducted from November 2010 to May 2011. Fifty-nine infants aged 6-12 months received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Hemagglutination inhibition titers were measured 4 weeks after the two doses of study vaccine. Based on the assumption that a hemagglutination inhibition titer of 1:40 or greater against the antigen would be protective in adults, two doses of the study vaccine generated a protective immune response of 63.2% against influenza A(H1N1), 82.5% against influenza A(H3N2) and 38.6% against influenza B viruses in infants aged 6-12 months. The geometric mean fold rises against influenza type A and B viruses also met the European Medicines Agency criteria for flu vaccines. The solicited events within 7 days after vaccination were mild in intensity. No deaths or adverse events such as optic neuritis, cranial neuropathy, and brachial neuropathy or Guillain-Barre syndrome were reported. Two doses of inactivated influenza vaccine were well tolerated and induced a protective immune response against influenza in infants aged 6-12 months.