Use of COVID-19 Convalescent Plasma for Treatment of Symptomatic SARS-CoV-2 Infection at a Children's Hospital: A Contribution to a Still Inadequate Body of Evidence.

Data on COVID-19 convalescent plasma (CCP) safety and efficacy in children and young adults are limited. This single-center prospective, open-label trial evaluates CCP safety, neutralizing antibody kinetics, and outcomes in children and young adults with moderate/severe COVID-19 (April 2020-March 2021). A total of 46 subjects received CCP; 43 were included in the safety analysis (SAS); 7.0% < 2 years old, 2.3% 2-<6, 27.9% 6-<12, 39.5% 12-<19, and 23.3% > 19 years old; 28 were included in the antibody kinetic analysis (AbKS); 10.7% < 2 years old, 10.7% 6-<12, 53.8% 12-<19, and 25.0% > 19 years old. No adverse events occurred. The median COVID-19 severity score improved (5.0 pre-CCP to 1.0 by day 7; p < 0.001). A rapid increase in the median percentage of inhibition was observed in AbKS (22.5% (13.0%, 41.5%) pre-infusion to 52% (23.7%, 72%) 24 h post-infusion); a similar increase was observed in nine immune-competent subjects (28% (23%, 35%) to 63% (53%, 72%)). The inhibition percentage increased until day 7 and persisted at 21 and 90 days. CCP is well tolerated in children and young adults, providing rapid and robust increased antibodies. CCP should remain a therapeutic option for this population for whom vaccines are not fully available and given that the safety and efficacy of existing monoclonal antibodies and antiviral agents have not been established.

Ampicillin and Gentamicin Treatment for Early Onset Neonatal Sepsis: When One Size Does Not Fit All.

Based on in vitro susceptibilities and the concern for emergence of resistance and long-term safety, ampicillin plus gentamicin remains the recommended antibiotic regimen for early onset neonatal sepsis. Our objective was to identify potential limitations of this regimen based on clinical and pathogen characteristics while minimizing risks associated with prolonged antibiotic exposure. We identified 43 gram-negative pathogens in 42 patients. Escherichia coli (E coli) occurred in 50% and Streptococcus agalactiae in 23.8% of patient. Ampicillin resistance was common, particularly in E coli (85.7%). Mortality was 23.8%, all due to E coli. We found that E coli is the most frequent pathogen and has a high mortality particularly in neonates < 1500 g; mortality is high with the current dosing strategy when E coli is resistant to ampicillin even when sensitive to gentamicin; resistance to gentamicin remains low but seems to be increasing while resistance to third-generation cephalosporins remains very low.

Invasive Mycobacterium abscessus Outbreak at a Pediatric Dental Clinic.

BACKGROUND: Mycobacterium species, specifically M. abscessus and M. chelonae (MABs), are known to contaminate water systems and are uncommon causes of health care-associated infection, but morbidity can be significant and treatment complex. METHODS: Odontogenic MAB infections occurred in patients following pulpotomy procedures at dental clinic A from 1 January to 6 September 2016. We identified confirmed and probable cases using culture data, imaging, pathology results, and surgical findings. Epidemiologic and clinical data including demographics, symptoms, laboratory findings, treatment regimens, and outcomes were extracted. RESULTS: Of 1082 at-risk patients, 71 case patients (22 confirmed; 49 probable) were identified. Median age was 6 years. Median symptom onset was 85 days postpulpotomy. Pain and/or swelling on admission occurred in 79%. On imaging, 49 of 70 had abnormalities of the mandible or maxilla, 13 of 70 had lymphadenopathy, and 19 of 68 had pulmonary nodules. Seventy were hospitalized (average of 8.5 days). Intravenous antibiotics were administered to 32 cases for a median length of 137 days. Clofazimine was administered to 29 patients as part of their multidrug regimen. Antibiotic treatment was associated with many adverse effects. Treated children showed evidence of jaw healing with resolved/improving pulmonary nodules at 1-year follow-up. CONCLUSIONS: This is the largest outbreak of invasive MAB infections associated with a pediatric dental practice. While infections were indolent, patients suffered medical and surgical consequences of treatment, including permanent tooth loss. Identification of this outbreak led to a change in water standards for pediatric dental procedures in California. Enhanced national dental water quality standards are needed to prevent future outbreaks.

Safety and Antibody Kinetics of COVID-19 Convalescent Plasma for the Treatment of Moderate to Severe Cases of SARS-CoV-2 Infection in Pediatric Patients.

BACKGROUND: Therapies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its life-threatening respiratory infection coronavirus disease 2019 (COVID-19) have been evaluated, including COVID-19 convalescent plasma (CCP). Multiple large reports of CCP treatment in adults exist. Pediatric data on CCP safety and efficacy are limited. METHODS: Single-center prospective, open-label trial looking at safety, antibody kinetics and outcomes of CCP (10 mL/kg, max 1 unit) treatment for COVID-19 in hospitalized pediatric patients with moderate to severe disease or at high-risk for serious illness. RESULTS: Thirteen patients were enrolled. No infusion-related adverse events occurred. No hematologic or metabolic adverse events were noted during hospitalization or at 3-weeks. Ten patients had clinical improvement by day 7 (WHO eight-category ordinal severity scale for COVID-19). Following CCP, anti-SARS-CoV-2 anti-nucleocapsid IgG increased significantly at 24 hours and high levels were sustained at 7- and 21-days. Transient IgM response was noted. Twelve patients (92.3%) were discharged home, 9 (75%) by day 7 post-CCP. One remained on invasive ventilatory support 42 days after CCP and was eventually discharged to an intermediate care facility. The single patient death was retrospectively confirmed to have had brain death before CCP. CONCLUSION: CCP was well tolerated in pediatric patients, resulted in rapid antibody increase, and did not appear to interfere with immune responses measured at 21 days. More pediatric data are necessary to establish the efficacy of CCP, but our data suggest benefit in moderate to severe COVID-19 when used early. Other immunologic or antiviral interventions may be added as supported by emerging data.

Safety and Tolerability of Clofazimine in a Cohort of Children With Odontogenic Mycobacterium abscessus Infection.

Mycobacterium abscessus infections can be challenging to treat. Clofazimine has excellent in vitro activity against M abscessus, but reports of its use, particularly in children, have been limited. In this study, clofazimine was given to 27 children during an outbreak of odontogenic mycobacterial infections and seemed to be well tolerated as part of a multidrug regimen.

Oral Antibiotics for Treating Children With Community-Acquired Pneumonia Complicated by Empyema.

No consensus exists on management of children with community-acquired pneumonia complicated by empyema (CAP-Em). We evaluated outpatient oral (O-Abx) compared with parenteral antibiotics (OPAT) in children with CAP-Em. We also evaluated inflammatory markers to guide length of treatment. We conducted a retrospective cohort study of patients discharged (2006-2016) with CAP-Em. Primary outcome measured was treatment success (no change in antibiotics or readmission to hospital for treatment of CAP-Em). White blood cell (WBC) count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) serial measurements were identified. Success was achieved in 133/144 (92.4%) O-Abx and 7/12 (58%) OPAT patients (P = .0031). WBC and CRP decreased early; and ESR increased initially (admit and switch to O-Abx) and decreased by end of treatment. O-Abx is the modality of choice for treatment of CAP-Em after hospital discharge. WBC and CRP are useful to monitor success of O-Abx switch; and ESR provides guidance for length of treatment.

An Observational Study of Severe Pertussis in 100 Infants ≤120 Days of Age.

BACKGROUND: Pertussis in young infants is a unique, severe, afebrile, cough illness that is frequently fatal. METHODS: All pertussis cases ≤120 days of age admitted to a pediatric intensive care unit in California between October 1, 2013, and April 25, 2015, were evaluated. RESULTS: Of 100 pertussis patients ≤120 days of age admitted to pediatric intensive care unit, there were 5 deaths. The white blood cell counts in the fatal cases were significantly higher than in the nonfatal cases. Thirty-four percent of patients were intubated, 18% received inotropic and/or vasoactive support, 22% received steroid, 4% received extracorporal membrane oxygenation, and 3% underwent exchange blood transfusion. The median age at the time of illness onset in the patients who died was 23 days. CONCLUSIONS: These data, as well as data from previous California studies, suggest updated strategies for the management of severe pertussis. These include perform serial white blood cell counts, treat all presumptive cases with azithromycin, evaluate for pulmonary hypertension, intubate and administer oxygen for apneic episodes and administer inotropic/vasoactive agents for cardiogenic shock. Do not administer steroids or nitric oxide. Criteria for exchange blood transfusion therapy for leukocytosis with lymphocytosis are suggested.

Bordetella pertussis.

Pertussis is a highly infectious vaccine-preventable cough illness that continues to be a significant source of morbidity and mortality around the world. The majority of human illness is caused by Bordetella pertussis, and some is caused by Bordetella parapertussis. Bordetella is a Gram-negative, pleomorphic, aerobic coccobacillus. In the past several years, even countries with high immunization rates in early childhood have experienced rises in pertussis cases. Reasons for the resurgence of reported pertussis may include molecular changes in the organism and increased awareness and diagnostic capabilities, as well as lessened vaccine efficacy and waning immunity. The most morbidity and mortality with pertussis infection is seen in infants too young to benefit from immunization. Severe infection requiring hospitalization, including in an intensive care setting, is mostly seen in those under 3 months of age. As a result, research and public health actions have been aimed at better understanding and reducing the spread of Bordetella pertussis. Studies comparing the cost benefit of cocooning strategies versus immunization of pregnant women have been favorable towards immunizing pregnant women. This strategy is expected to prevent a larger number of pertussis cases, hospitalizations, and deaths in infants <1 year old while also being cost-effective. Studies have demonstrated that the source of infection in infants usually is a family member. Efforts to immunize children and adults, in particular pregnant women, need to remain strong.

Exchange blood transfusion in the management of severe pertussis in young infants.

We analyzed data from 10 young infants who received exchange blood transfusions for management of severe pertussis. Our data are insufficient to address efficacy of the procedure, but our data, as well as previous reports in the literature, indicate that if the procedure is to be successful, it should be done before organ failure has occurred and immediately if shock/hypotension occur.

Characteristics of Severe Bordetella pertussis Infection Among Infants ≤90 Days of Age Admitted to Pediatric Intensive Care Units - Southern California, September 2009-June 2011.

BACKGROUND: Bordetella pertussis infection can cause severe illness and death among young infants. METHODS: We collected demographic and clinical information from the medical records of infants who were ≤90 days of age and hospitalized for pertussis in 5 Southern California pediatric intensive care units (PICUs) from September 1, 2009 to June 30, 2011. Infants who died or were diagnosed with pulmonary hypertension were considered to have more severe pertussis. RESULTS: Thirty-one infants were admitted to a participating PICU. Eight infants had more severe infections, 6 infants had pulmonary hypertension, and 4 infants died. The 8 infants with more severe infections had white blood cell counts that exceeded 30 000, heart rates that exceeded 170, and respiratory rates that exceeded 70 more rapidly after cough onset than the 23 infants with less severe illness. CONCLUSIONS: Identifying higher-risk infants earlier might allow for more rapid implementation of interventions.

Clinical and laboratory features of pertussis in infants at the onset of a California epidemic.

We report clinical characteristics and outcome of infants <3 months of age hospitalized with pertussis compared with viral respiratory infection (respiratory syncytial virus and influenza). Patients with pertussis more often were afebrile, had more visits before admission, and had longer hospital stays. Household coughing contacts were common.

The atherogenic lipoprotein profile associated with obesity and insulin resistance is largely attributable to intra-abdominal fat.

Obesity and insulin resistance are both associated with an atherogenic lipoprotein profile. We examined the effect of insulin sensitivity and central adiposity on lipoproteins in 196 individuals (75 men and 121 women) with an average age of 52.7 years. Subjects were subdivided into three groups based on BMI and their insulin sensitivity index (S(I)): lean insulin sensitive (n = 65), lean insulin resistant (n = 73), and obese insulin resistant (n = 58). This categorization revealed that both obesity and insulin resistance determined the lipoprotein profile. In addition, the insulin-resistant groups had increased central adiposity. Increasing intra-abdominal fat (IAF) area, quantified by computed tomography scan and decreasing S(I), were important determinants of an atherogenic profile, marked by increased triglycerides, LDL cholesterol, and apolipoprotein B and decreased HDL cholesterol and LDL buoyancy (Rf). Density gradient ultracentrifugation (DGUC) revealed that in subjects who had more IAF and were more insulin resistant, the cholesterol content was increased in VLDL, intermediate-density lipoprotein (IDL), and dense LDL fractions whereas it was reduced in HDL fractions. Multiple linear regression analysis of the relation between the cholesterol content of each DGUC fraction as the dependent variable and IAF and S(I) as independent variables revealed that the cholesterol concentration in the fractions corresponding to VLDL, IDL, dense LDL, and HDL was associated with IAF, and that S(I) additionally contributed independently to VLDL, but not to IDL, LDL, or HDL. Thus an atherogenic lipoprotein profile appears to be the result primarily of an increase in IAF, perhaps via insulin resistance.