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BACKGROUND: Influenza A/H7N9 viruses have pandemic potential. METHODS: We conducted an open-label, randomized, controlled trial of AS03-adjuvanted 2017 inactivated influenza A/H7N9 vaccine (H7N9 IIV) in healthy adults. Group 1 received H7N9 IIV and seasonal quadrivalent influenza vaccine (IIV4) simultaneously, followed by H7N9 IIV three weeks later. Group 2 received IIV4 alone and then two doses of H7N9 IIV at three-week intervals. Group 3 received one dose of IIV4. We used hemagglutination inhibition (HAI) and microneutralization (MN) assays to measure geometric mean titers and seroprotection (≥1:40 titer) to vaccine strains and monitored for safety. RESULTS: Among 149 subjects, seroprotection by HAI three weeks after H7N9 IIV dose 2 was 51% (95 %CI 37%-65%) for Group 1 and 40% (95 %CI 25%-56%) for Group 2. Seroprotection by MN at the same timepoint was 84% (95 %CI 72%-93%) for Group 1 and 74% (95 %CI 60%-86%) for Group 2. By 180 days after H7N9 IIV dose 2, seroprotection by HAI or MN was low for Groups 1 and 2. Responses measured by HAI and MN against each IIV4 strain three weeks after IIV4 vaccination were similar in all groups. Solicited local and systemic reactions were similar after a single vaccination, while those receiving simultaneous H7N9 and IIV4 had slightly more reactogenicity. There were no serious adverse events or medically-attended adverse events related to study product receipt. CONCLUSIONS: Adjuvanted H7N9 IIV was modestly immunogenic whether administered simultaneously or sequentially with IIV4, though responses declined by 180 days. IIV4 was immunogenic regardless of schedule. CLINICAL TRIALS REGISTRATION: NCT03318315

Multisystem inflammatory syndrome in children (MIS-C) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; in the United States, reporting of MIS-C after coronavirus disease 2019 (COVID-19) vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5−11 years on 29 October 2021. Covering a period when approximately 7 million children received vaccine, surveillance for MIS-C ≤ 90 days postvaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (

In the present study, population pharmacokinetic (PK) analysis was performed based on meropenem data from a prospective study conducted in 114 critically ill patients with a wide range of renal functions and various disease conditions. The final model was a one-compartment model with linear elimination, with creatinine clearance and continuous renal replacement therapy affecting clearance, and total bodyweight impacting the volume of distribution. Our model is a valuable addition to the existing meropenem population PK models, and it could be particularly useful during implementation of a therapeutic drug monitoring program combined with Bayesian forecasting. Based on the final model developed, comprehensive Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of 16 different dosing regimens. Simulation results showed that 2 g administered every 8 h with 3-h prolonged infusion (PI) and 4 g/day by continuous infusion (CI) appear to be two empirical dosing regimens that are superior to many other regimens when both target attainment and potential toxicity are considered and renal function information is not available. Following a daily CI dose of 6 g or higher, more than 30% of the population with a creatinine clearance of60 mL/min is predicted to have neurotoxicity. With the availability of institution- and/or unit-specific meropenem susceptibility patterns, as well as an individual patient's renal function, our PTA results may represent useful references for physicians to make dosing decisions.

BACKGROUND AND OBJECTIVES Acute hematogenous musculoskeletal infections (MSKI) are medical emergencies with the potential for life-altering complications in afflicted children. Leveraging administrative data to study pediatric MSKI is difficult as many infections are chronic, nonhematogenous, or occur in children with significant comorbidities. The objective of this study was to validate a case-finding algorithm to accurately identify children hospitalized with acute hematogenous MSKI using administrative billing codes. METHODS This was a multicenter validation study using the Pediatric Health Information System (PHIS) database. Hospital admissions for MSKI were identified from 6 PHIS hospitals using discharge diagnosis codes. A random subset of admissions underwent manual chart review at each site using predefined criteria to categorize each admission as either “acute hematogenous MSKI” (AH-MSKI) or “not acute hematogenous MSKI.” Ten unique coding algorithms were developed using billing data. The sensitivity and specificity of each algorithm to identify AH-MSKI were calculated using chart review categorizations as the reference standard. RESULTS Of the 492 admissions randomly selected for manual review, 244 (49.6%) were classified as AH-MSKI and 248 (50.4%) as not acute hematogenous MSKI. Individual algorithm performance varied widely (sensitivity 31% to 91%; specificity 52% to 98%). Four algorithms demonstrated potential for future use with receiver operating characteristic area under the curve greater than 80%. CONCLUSIONS Identifying children with acute hematogenous MSKI based on discharge diagnosis alone is challenging as half have chronic or nonhematogenous infections. We validated several case-finding algorithms using administrative billing codes and detail them here for future use in pediatric MSKI outcomes.

Background Patients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. The management of these infections becomes increasingly complex due to decreased antimicrobial susceptibility and inadequate pharmacokinetic/pharmacodynamic (PK/PD) characterization of the most commonly used antimicrobial agents in this population. Methods One hundred fifty-five pediatric and adult participants receiving cefepime (n=82), meropenem (n=42), or piperacillin-tazobactam (n=31) were enrolled. Opportunistic blood samples were obtained during hospitalization. Population PK (PopPK) analysis was conducted using nonlinear mixed effects modeling in NONMEM, and clinical and demographic characteristics were evaluated as potential covariates. Monte Carlo simulations evaluated the probability of PK/PD target attainment (PTA) for different dosing regimens. Multiple targets, defined as percentage of a 24-h time period that the free drug concentration exceeds the MIC (fT > MIC), were selected based on prior studies of beta-lactam antibiotics. Results Preliminary PopPK modeling results show that lean body weight, creatinine clearance, daily dose, mode of administration (standard vs. extended infusion), and age affect PK parameters, with varying effects by drug. As anticipated, extended or continuous infusions resulted in higher PTA (Table 1). In the cefepime group, the 3-h infusion regimen achieved higher PTAs than the 0.5-h regimen across all age groups (Figure 1, Figure 2). Estimated breakpoints (in which ≥ 90% of patients are expected to achieve a PK/PD target) were 2-4 fold higher in pediatric participants receiving a 3-h infusion vs. 0.5-h infusion, based on age and target fT > MIC (Table 1). In the meropenem group, increased creatinine clearance led to reduced PTA, and in the piperacillin-tazobactam group, total daily dose and interval were the principal drivers of PTA. Table 1:Breakpoints (mg/L, highest minimum inhibitory concentration (MIC) with ≥ 90% PK target attainment) for different infusion durations, based on Monte Carlo simulations.Figure 1:Comparison of PTA between the two durations of infusion for 50 mg/kg (3 to 11 years) or 2 g (12 years and above) cefepime q8h at the target of 65% fT> MIC.Figure 2:Comparison of PTA between two durations of infusion for 50 mg/kg (3 to 11 years) or 2 g (12 years and above) cefepime q8h at the target of 100% fT> MIC. Conclusion To our knowledge, this is the largest PopPK study to date of these antimicrobials in individuals with CF. Clinicians should incorporate local antibiograms with these PopPK models to determine optimal dosing in patients with CF, since standard dosing regimens may fail to achieve specific PK/PD targets. This population may also benefit from beta-lactam therapeutic drug monitoring. Disclosures C. Buddy Creech, MD, MPH, Altimmune: Advisor/Consultant|Astellas: Advisor/Consultant|Merck: Grant/Research Support|Premier: Advisor/Consultant.

The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown.Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-μg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo.On the basis of safety and immunogenicity results in part 1 of the trial, the 25-μg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-μg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-μg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant.Two 25-μg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

In this issue of Cell HostMicrobe, Tsai et al. (2022) provide evidence that Staphylococcus aureus should be numbered among the pathogens for which original antigenic sin governs subsequent immune responses. Their approach may restore the utility of murine models in staphylococcal vaccine development.

BPZE1 is a live, attenuated pertussis vaccine derived from B. pertussis strain Tohama I modified by genetic removal or inactivation of 3 B. pertussis toxins: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin. This Phase 2a study evaluated the safety and immunogenicity of liquid or lyophilized BPZE1 vaccine administered intranasally by needleless tuberculin syringe or mucosal atomization device (VaxINatorFifty healthy male and non-pregnant female participants 18-49 years of age were enrolled. Participants were randomized 3:3:3:1 to a single lyophilized dose of 10Across all groups, 35/50 (70 %) experienced at least one local adverse event (AE) and 31/50 (62 %) experienced at least one systemic AE, with similar AE frequencies observed between the highest 10Lyophilized BPZE1 vaccine was well tolerated and immunogenic at the highest dose (10

Coinfections are more common in patients with cystic fibrosis and bronchiectasis. Infiltrates on imaging studies are seen more commonly in patients with coinfections, but coinfections did not affect treatment outcomes of pulmonary Mycobacterium avium complex.

Data on medium-term outcomes in indivduals with myocarditis after mRNA COVID-19 vaccination are scarce. We aimed to assess clinical outcomes and quality of life at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults.In this follow-up surveillance study, we conducted surveys in US individuals aged 12-29 years with myocarditis after mRNA COVID-19 vaccination, for whom a report had been filed to the Vaccine Adverse Event Reporting System between Jan 12 and Nov 5, 2021. A two-component survey was administered, one component to patients (or parents or guardians) and one component to health-care providers, to assess patient outcomes at least 90 days since myocarditis onset. Data collected were recovery status, cardiac testing, and functional status, and EuroQol health-related quality-of-life measures (dichotomised as no problems or any problems), and a weighted quality-of-life measure, ranging from 0 to 1 (full health). The EuroQol results were compared with published results in US populations (aged 18-24 years) from before and early on in the COVID-19 pandemic.Between Aug 24, 2021, and Jan 12, 2022, we collected data for 519 (62%) of 836 eligible patients who were at least 90 days post-myocarditis onset: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both surveys. Median patient age was 17 years (IQR 15-22); 457 (88%) patients were male and 61 (12%) were female. 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis by their health-care provider, although at the last health-care provider follow-up, 104 (26%) of 393 patients were prescribed daily medication related to myocarditis. Of 249 individuals who completed the quality-of-life portion of the patient survey, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (20%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with depression. Mean weighted quality-of-life measure (0·91 [SD 0·13]) was similar to a pre-pandemic US population value (0·92 [0·13]) and significantly higher than an early pandemic US population value (0·75 [0·28]; p0·0001). Most patients had improvements in cardiac diagnostic marker and testing data at follow-up, including normal or back-to-baseline troponin concentrations (181 [91%] of 200 patients with available data), echocardiograms (262 [94%] of 279 patients), electrocardiograms (240 [77%] of 311 patients), exercise stress testing (94 [90%] of 104 patients), and ambulatory rhythm monitoring (86 [90%] of 96 patients). An abnormality was noted among 81 (54%) of 151 patients with follow-up cardiac MRI; however, evidence of myocarditis suggested by the presence of both late gadolinium enhancement and oedema on cardiac MRI was uncommon (20 [13%] of 151 patients). At follow-up, most patients were cleared for all physical activity (268 [68%] of 393 patients).After at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, most individuals in our cohort were considered recovered by health-care providers, and quality of life measures were comparable to those in pre-pandemic and early pandemic populations of a similar age. These findings might not be generalisable given the small sample size and further follow-up is needed for the subset of patients with atypical test results or not considered recovered.US Centers for Disease Control and Prevention.

Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Waning immunity after two SARS-CoV-2 mRNA vaccinations and the emergence of variants precipitated the need for a third dose of vaccine. We evaluated early safety and immunogenicity after a third mRNA vaccination in adults who received the mRNA-1273 primary series in the Phase 1 trial approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA-1273.351 that encodes Beta variant spike protein, and bivalent vaccine of 25 mcg each of mRNA-1273 and mRNA-1273.351. A third dose of mRNA vaccine appeared safe with acceptable reactogenicity. Vaccination induced rapid increases in binding and neutralizing antibody titers to D614G, Beta, and Delta variants that were similar or greater than peak responses after the second dose. Spike-specific CD4+ and CD8+ T cells increased to similar levels as after the second dose. A third mRNA vaccination was well tolerated and generated robust humoral and T cell responses. ClinicalTrials.gov numbers NCT04283461 (mRNA-1273 Phase 1) and NCT04785144 (mRNA-1273.351 Phase 1)

Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown.Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 μg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported.In part 1 of the trial, 751 children received 50-μg or 100-μg injections of the mRNA-1273 vaccine, and on the basis of safety and immunogenicity results, the 50-μg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 μg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-μg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-μg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant.Two 50-μg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

Waning immunity after two SARS-CoV-2 mRNA vaccinations and the emergence of variants precipitated the need for booster doses. We evaluated safety and serological and cellular immunogenicity through 6 months after a third mRNA vaccination in adults who received the mRNA-1273 primary series in the Phase 1 trial approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA-1273.351 that encodes Beta variant spike protein, and bivalent vaccine of 25 mcg each of mRNA-1273 and mRNA-1273.351. A third dose of mRNA vaccine appeared safe with acceptable reactogenicity. Vaccination induced rapid increases in binding and neutralizing antibody titers to D614G, Beta, Delta and Omicron variants that persisted through 6 months post-boost, particularly after administration of Beta-containing vaccines. Spike-specific CD4 + and CD8 + T cells increased to levels similar to those following the second dose. Boost vaccination induced broad and durable humoral and T cell responses. ClinicalTrials.gov numbers NCT04283461 (mRNA-1273 Phase 1) and NCT04785144 (mRNA-1273.351 Phase 1)

BACKGROUND AND OBJECTIVES Asthma is considered a precaution for use of quadrivalent live attenuated influenza vaccine (LAIV4) in persons aged ≥5 years because of concerns for wheezing events. We evaluated the safety of LAIV4 in children with asthma, comparing the proportion of children with asthma exacerbations after LAIV4 or quadrivalent inactivated influenza vaccine (IIV4). METHODS We enrolled 151 children with asthma, aged 5 to 17 years, during 2 influenza seasons. Participants were randomly assigned 1:1 to receive IIV4 or LAIV4 and monitored for asthma symptoms, exacerbations, changes in peak expiratory flow rate (PEFR), and changes in the asthma control test for 42 days after vaccination. RESULTS We included 142 participants in the per-protocol analysis. Within 42 days postvaccination, 18 of 142 (13%) experienced an asthma exacerbation: 8 of 74 (11%) in the LAIV4 group versus 10 of 68 (15%) in the IIV4 group (LAIV4-IIV4 = −0.0390 [90% confidence interval −0.1453 to 0.0674]), meeting the bounds for noninferiority. When adjusted for asthma severity, LAIV4 remained noninferior to IIV4. There were no significant differences in the frequency of asthma symptoms, change in PEFR, or childhood asthma control test/asthma control test scores in the 14 days postvaccination between LAIV4 and IIV4 recipients. Vaccine reactogenicity was similar between groups, although sore throat (P = .051) and myalgia (P CONCLUSIONS LAIV4 was not associated with increased frequency of asthma exacerbations, an increase in asthma-related symptoms, or a decrease in PEFR compared with IIV4 among children aged 5 to 17 years with asthma.

Background Staphylococcusaureus skin and soft tissue infections (SA-SSTIs) are common in healthcare and community settings, and recurrences occur at variable frequency, even after successful initial treatment. Knowing the exact burden and timing of recurrent disease is critical to planning and evaluating interventions to prevent recurrent SSTIs. Methods In this retrospective study, SSTI cases in patients aged ≥18 years at 3 US medical centers (Columbia, Chicago, Vanderbilt) between 2006 and 2016 were analyzed according to a biennial cohort design. Index SSTIs (with or without key comorbidities), either microbiologically confirmed to be SA-SSTI or not microbiologically tested (NMT-SSTI), were recorded within 1 calendar year and followed up for 12 months for recurrent infections. The number of index cases, proportion of index cases with ≥1 recurrence(s), time to first recurrence, and number of recurrences were collected for both SA-SSTI and NMT-SSTI events. Results In the most recent cohorts, 4755 SSTI cases were reported at Columbia, 2873 at Chicago, and 6433 at Vanderbilt. Of these, 452, 153, and 354 cases were confirmed to be due to S. aureus. Most cases were reported in patients without key comorbidities. Across centers, 16.4%–19.0% (SA-SSTI) and 11.0%–19.2% (NMT-SSTI) of index cases had ≥1 recurrence(s). In patients without key comorbidities, more than 60% of index SSTIs with recurrences had only 1 recurrence, half of which occurred in the first 3 months following primary infection. Conclusions SA-SSTI recurrences are common among healthy adults and occur in at least 1 in 6 individuals during the 1 year following the primary event., The number of Staphylococcus aureus skin and soft tissue infections patients recorded at 3 US medical centers during 2006–2016 was stable and lacked key comorbidities. Most patients with recurrences had 1 recurrence, half of which occurred in the first 3 months following primary infection.

We report our experience caring for an infant with respiratory syncytial virus infection (RSV) and group B Streptococcus (GBS) bacteremia and meningitis. Concurrent GBS meningitis and RSV is rare but highlights the importance of correlating clinical symptoms with viral diagnostic testing during the evaluation of infants at risk for serious bacterial infection.

IMPORTANCE: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear. OBJECTIVE: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. EXPOSURES: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). MAIN OUTCOMES AND MEASURES: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. RESULTS: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). CONCLUSIONS AND RELEVANCE: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC).In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data.Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals.Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted.US Centers for Disease Control and Prevention.

Background Pediatric patients have increasing rates of hospital-associated venous thromboembolism (HA-VTE), and while several risk-prediction models have been developed, few are designed to assess all general pediatric patients, and none has been shown to improve patient outcomes when implemented in routine clinical care. Methods The Children’s Likelihood Of Thrombosis (CLOT) trial is an ongoing pragmatic randomized trial being conducted starting November 2, 2020, in the inpatient units at Monroe Carell Jr. Children’s Hospital at Vanderbilt in Nashville, TN, USA. All admitted patients who are 21 years of age and younger are automatically enrolled in the trial and randomly assigned to receive either the current standard-of-care anticoagulation practice or the study intervention. Patients randomized to the intervention arm are assigned an HA-VTE risk probability that is calculated from a validated VTE risk-prediction model; the model is updated daily with the most recent clinical information. Patients in the intervention arm with elevated risk (predicted probability of HA-VTE ≥ 0.025) have an additional review of their clinical course by a team of dedicated hematologists, who make recommendations including pharmacologic prophylaxis with anticoagulation, if appropriate. The anticipated enrollment is approximately 15,000 patients. The primary outcome is the occurrence of HA-VTE. Secondary outcomes include initiation of anticoagulation, reasons for not initiating anticoagulation among patients for whom it was recommended, and adverse bleeding events. Subgroup analyses will be conducted among patients with elevated HA-VTE risk. Discussion This ongoing pragmatic randomized trial will provide a prospective assessment of a pediatric risk-prediction tool used to identify hospitalized patients at elevated risk of developing HA-VTE. Trial registration ClinicalTrials.gov NCT04574895. Registered on September 28, 2020. Date of first patient enrollment: November 2, 2020.

BACKGROUND: Hospital-associated venous thromboembolism (HA-VTE) is an increasing cause of morbidity in pediatric populations, yet identification of high-risk patients remains challenging. General pediatric models have been derived from case-control studies, but few have been validated. We developed and validated a predictive model for pediatric HA-VTE using a large, retrospective cohort. METHODS: The derivation cohort included 111 352 admissions to Monroe Carell Jr. Children’s Hospital at Vanderbilt. Potential variables were identified a priori, and corresponding data were extracted. Logistic regression was used to estimate the association of potential risk factors with development of HA-VTE. Variable inclusion in the model was based on univariate analysis, availability in routine medical records, and clinician expertise. The model was validated by using a separate cohort with 44 138 admissions. RESULTS: A total of 815 encounters were identified with HA-VTE in the derivation cohort. Variables strongly associated with HA-VTE include history of thrombosis (odds ratio [OR] 8.7; 95% confidence interval [CI] 6.6–11.3; P < .01), presence of a central line (OR 4.9; 95% CI 4.0–5.8; P < .01), and patients with cardiology conditions (OR 4.0; 95% CI 3.3–4.8; P < .01). Eleven variables were included, which yielded excellent discriminatory ability in both the derivation cohort (concordance statistic = 0.908) and the validation cohort (concordance statistic = 0.904). CONCLUSIONS: We created and validated a risk-prediction model that identifies pediatric patients at risk for HA-VTE development. We anticipate early identification of high-risk patients will increase prophylactic interventions and decrease the incidence of pediatric HA-VTE.

Objective In response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children. Study design This multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21 days apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6–35 months of age received 7.5mcg or 15mcg of hemagglutinin (HA)/dose; children 3–17 years of age received 15mcg HA/dose. Safety and reactogenicity were assessed by measuring the occurrence of solicited injection site and systemic reactions in the 7 days after each vaccination; adverse events were assessed for 42 days and serious adverse events for 7 months after the first vaccination. Immunogenicity was evaluated by measuring hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies to H3N2v prior to and 21 days after each vaccination. Cross-reactivity against seasonal H3N2 strains was evaluated. Results The H3N2v vaccine was well tolerated. Transient mild to moderate injection site tenderness, pain and erythema was observed, with the most commonly reported systemic reactogenicity being irritability in children 6–35 months, and headache and fatigue in children 9–17 years old. Children 6–35 months old, whether they received 7.5mcg or 15mcg/dose, had low HAI and Neut antibody responses after two doses compared to older children. Children under 9 years of age required two doses of vaccine to demonstrate a response, while 9–17 year olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 9–17 years of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses. Conclusion The H3N2v vaccine was safe and immunogenic in children and adolescents. Age-related increases in immunogenicity against H3N2v and seasonal H3N2 viruses were observed, suggesting prior priming via infection and/or immunization. Clinical trial registry: The trial is registered with clinicaltrial.gov: NCT02100436 .

Objectives To characterize Staphylococcus aureus isolates recovered from hospitalized children and to determine the concordance between colonizing and invasive isolates. Study design Children with culture-confirmed, community-onset, invasive S aureus infections were enrolled in this prospective case series from a large children's hospital over a 5-year period. Colonization isolates were obtained from the anterior nares, oropharynx, and inguinal folds and were compared with invasive isolates via repetitive-element, sequence-based polymerase chain reaction testing. Isolates with a ≥96% genetic match were characterized as concordant. Results A total of 86 S aureus isolates (44 invasive, 42 colonization) were collected from 44 children with invasive infections. Clinical isolates were genetically diverse, 64% of invasive isolates were methicillin-susceptible S aureus (MSSA), and 59% of cases had a colonizing S aureus isolate at the time of hospitalization. Of those who were colonized, at least 1 of their colonization isolates was indistinguishable from the infecting isolate in 88% of cases. Patients with invasive MSSA were significantly more likely to have a concordant MSSA colonization isolate present compared with patients with invasive methicillin-resistant S aureus (MRSA) (61% vs 38%, P Conclusions Invasive MSSA infection was more common than MRSA infection in this pediatric cohort, and patients with MSSA infection were significantly more likely than those with MRSA infection to have concordant colonizing isolates across multiple anatomic sites. These findings warrant larger scale validation and may have important infection control and epidemiologic implications, as unlike MRSA, transmissibility of MSSA largely is ignored in healthcare settings.

Background Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood. Methods Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types. Results AS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcγ receptor (FcγR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs. Conclusions Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.

Importance Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. Objective To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. Design, Setting, and Participants Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). Exposures Receipt of Ad26.COV2.S vaccine. Main Outcomes and Measures Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. Results Patients’ ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). Conclusions and Relevance The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Background There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. Methods A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results. Results MVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses. Conclusions MVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development. Clinical Trials Registration NCT00914732.

While adult clinical trials of coronavirus disease 2019 (COVID-19) vaccines have moved quickly into phase 3 clinical trials, clinical trials have not started in children in the United States. The direct COVID-19 impact upon children is greater than that observed for a number of other pathogens for which we now have effective pediatric vaccines. Additionally, the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has clearly been underappreciated. Carefully conducted phase 2 clinical trials can adequately address potential COVID-19 vaccine safety concerns. Delaying phase 2 vaccine clinical trials in children will delay our recovery from COVID-19 and unnecessarily prolong its impact upon children’s education, health, and emotional well-being, and equitable access to opportunities for development and social success. Given the potential direct and indirect benefits of pediatric vaccination, implementation of phase 2 clinical trials for COVID-19 vaccines should begin now.

A detailed understanding of the adaptive host response to SARS-CoV-2 infection in humans is urgently needed, as questions abound regarding serologic responses and the development of antibody-mediated immunity against COVID-19. We developed a highly sensitive, high-throughput, and efficient assay using liquid bead array technology. We observed advantages over traditional indirect ELISA for the detection and quantification of binding IgG against the receptor binding domain (RBD) of SARS-CoV-2. Using this sensitive and highly reproducible assay, we sought to determine whether the severity of COVID-19 symptoms is correlated with SARS-CoV-2 binding IgG level. We measured SARS-CoV-2 RBD IgG levels from 67 subjects who had recovered from PCR-confirmed, symptomatic COVID-19. Samples were obtained approximately 6 weeks post-symptom onset. We found that COVID-19 symptom severity, assessed on an 8-point severity scale, strongly correlated with RBD IgG level (p

Background Staphylococcus aureus causes serious health care– and community-associated disease, requiring improved preventive measures such as vaccines. The investigational S. aureus 4-antigen vaccine (SA4Ag), comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant mutant clumping factor A (rmClfA), and recombinant manganese transporter protein C (rP305A or rMntC), was well tolerated, inducing robust functional immune responses to all 4 antigens through 12 months postvaccination. This is a serological extension study through 36 months postvaccination. Methods In 2 previous studies, healthy adults received SA4Ag, SA3Ag (without rMntC), or placebo; serology was also assessed at ~24 and ~36 months postvaccination. Functional immune responses (antibody responses that facilitate killing of S. aureus or neutralize S. aureus virulence mechanisms) were assessed with opsonophagocytic activity killing assays (CP5 or CP8) and a fibrinogen-binding inhibition assay (ClfA). A competitive Luminex immunoassay assessed ClfA and rMntC responses. Adverse events within 48 hours of blood draw were recorded. Results Four hundred forty subjects (18–64 years old, 255; 65–85 years old, 185) were enrolled. At 24 and 36 months postvaccination, subjects receiving SA4Ag had substantially higher geometric mean titers (GMTs) for CP5, CP8, and ClfA vs baseline; geometric mean fold rises (GMFRs) from baseline to month 36 were 2.7–8.1. For rMntC, 36-month GMTs declined from peak levels but remained above baseline for all SA4Ag groups; GMFRs from baseline to month 36 were 1.8 and 1.5 in the younger and older cohorts, respectively. Conclusions Persistent functional immune responses to S. aureus antigens were observed through 36 months in healthy adults. ClinicalTrials.gov NCT01643941 and NCT01364571.

The Infectious Diseases Society of America, HIV Medicine Association, and Pediatric Infectious Diseases Society are concerned by the continued decline in the number of infectious diseases trainees pursuing careers as physician-scientists and the attrition of junior and midcareer physician-scientists. The inability to replace the aging physician-scientist workforce will have a negative, long-lasting impact our biomedical research enterprise and its ability to drive the discovery of new treatments for important infectious diseases. We discuss policy recommendations for securing and optimizing the infectious diseases physician-scientist workforce in the areas of education, training, compensation, and mentorship, as well as ways to improve federal research funding, cross-sector collaboration, and workforce diversity.

BACKGROUND: Systems for standardizing physician payment have been shown to undervalue cognitive clinical encounters. Because health care reform emphasizes value-based approaches, we need an understanding of the way pediatric cognitive specialties are used to contribute to the provision of high-value care. We sought to investigate how clinical and administrative stakeholders perceive the value of pediatric infectious disease (PID) specialists. METHODS: We conducted qualitative interviews with a purposive sample of physicians and administrators from 5 hospitals across the United States in which children are cared for. All interviews were transcribed and systematically analyzed for common themes. RESULTS: We interviewed 97 stakeholders. Analysis revealed the following 3 domains of value: clinical, organizational, and communicative. Clinically, PID specialists were perceived to be highly valuable in treating patients with unusual infections that respond poorly to therapy, in optimizing the use of antimicrobial agents and in serving as outpatient homes for complex patients. Respondents perceived that PID specialists facilitate communication with patients and their families, the health care team and the media. PID specialists were perceived to generate value by participating in systemwide activities, including antimicrobial stewardship and infection prevention. Despite this, much of the valuable work PID specialists perform is difficult to measure causing some administrative stakeholders to question how many PID specialists are necessary to achieve high-quality care. CONCLUSIONS: With our findings, we suggest that pediatric cognitive specialties contribute value in multiple ways to the health care delivery system. Many of these domains are difficult to capture by using current metrics, which may lead administrators to overlook valuable work and to under-allocate resources.

BACKGROUND: Staphylococcus aureus is among the most commonly identified causes of invasive bacterial infection in children; however, reliable results from cultures of sterile-site samples often cannot be obtained, which necessitates prescription of a broad empiric antimicrobial agent(s). Children with invasive S aureus infection rapidly generate high antibody titers to the cytotoxin LukAB; therefore, the aim of this study was to assess the diagnostic utility of an anti-LukAB antibody assay for children with musculoskeletal infection (MSKI). METHODS: We conducted a 2-year prospective study of all eligible children admitted to Vanderbilt Children’s Hospital with an MSKI. Acute and convalescent sera were obtained, and antibodies that target LukAB were measured by an enzyme-linked immunosorbent assay. RESULTS: Forty-two children were enrolled. The median concentrations of LukAB antibodies for children with S aureus infection were 130.3 U/mL in the acute phase and 455 U/mL in the convalescent phase (P < .001). The median concentrations of LukAB antibodies in children with a non–S aureus MSKI were 8.6 U/mL in the acute phase and 9.7 U/mL in the convalescent phase. The assay discriminated between S aureus and non–S aureus infection with areas under the receiver operating characteristic curve of 0.81 (95% confidence interval, 0.67–0.95; P < .001) and 0.95 (95% confidence interval, 0.86–1; P < .001) for samples tested in the acute and follow-up periods, respectively. With no false-negative results, the assay accurately ruled out S aureus in samples obtained during the convalescent phase. CONCLUSION: Culture-independent diagnostics have the potential to improve care by narrowing antimicrobial therapy on the basis of the likelihood of S aureus infection. The results of this proof-of-concept study suggest that a LukAB serologic assay might be useful in the diagnosis of invasive bacterial infections, and larger-scale validation studies are warranted.

The purpose of this study was to determine if a decolonization regimen reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections and if colonization isolates are genetically related to subsequent infectious strains. Trauma patients admitted to the intensive care unit with positive MRSA nasal swabs were randomized to either daily chlorhexidine gluconate (CHG) baths and mupirocin (MUP) ointment to the nares or soap and water baths and placebo ointment for five days. Nasal swabs performed at the end of treatment and invasive MRSA infections during the remaining hospitalization were compared with the original nasal isolate via polymerase chain reaction for genetic relatedness as well as CHG and MUP resistance genes. Six hundred and seventy-eight intensive care unit admissions were screened, and 92 (13.6%) had positive (+) MRSA nasal swabs over a 22-month period ending in 3/2014. After the five day treatment period, there were 13 (59.1%) +MRSA second nasal swabs for CHG + MUP and 9 (90%) for soap and water baths and placebo, P = 0.114. No isolates tested positive for the MUP or CHG resistance genes mupA and qacA/B but 7 of 20 (35%) contained smr. There were seven (31.8%) MRSA infections in the CHG group and six (60%) for soap, P = 0.244. All 13 patients with MRSA infections had the same MRSA isolate present in the original nasal swab. There was no difference in all-cause Gram-negative or positive infections for CHG versus soap, 12 (54.5%) versus 7 (70%), P = 0.467. CHG + MUP are ineffective in eradicating MRSA from the anterior nares but may reduce the incidence of infection. Subsequent invasive MRSA infections are typically caused by the endogenous colonization strain.

To understand the epidemiology of acute hematogenous osteomyelitis and septic arthritis, including clinical and demographic features, microbiology, treatment approaches, treatment-associated complications, and outcomes.Retrospective cohort study of 453 children with acute hematogenous osteomyelitis and/or septic arthritis from 2009 to 2015.Among the 453 patients, 218 (48%) had acute hematogenous osteomyelitis, 132 (29%) had septic arthritis, and 103 (23%) had concurrent acute hematogenous osteomyelitis/septic arthritis. Treatment failure/recurrent infection occurred in 41 patients (9%). Patients with concurrent acute hematogenous osteomyelitis/septic arthritis had longer hospital stays, longer duration of antibiotic therapy, and were more likely to have prolonged bacteremia and require intensive care. Staphylococcus aureus was identified in 228 (51%) patients, of which 114 (50%) were methicillin-resistant S aureus. Compared with septic arthritis, acute hematogenous osteomyelitis and concurrent acute hematogenous osteomyelitis/septic arthritis were associated with higher odds of treatment failure (OR, 8.19; 95% CI, 2.02-33.21 [P = .003]; and OR, 14.43; 95% CI, 3.39-61.37 [P .001], respectively). The need for more than 1 surgical procedure was also associated with higher odds of treatment failure (OR, 2.98; 95% CI, 1.18-7.52; P = .021). Early change to oral antibiotic therapy was not associated with treatment failure (OR, 0.64; 95% CI, 0.24-1.74; P = .386). Most (73%) medically attended treatment complications occurred while on parenteral therapy.Musculoskeletal infections are challenging pediatric infections. S aureus remains the most common pathogen, with methicillin-resistant S aureus accounting for 25% of all cases. Concurrent acute hematogenous osteomyelitis/septic arthritis is associated with more severe disease and worse outcomes. Fewer treatment-related complications occurred while on oral therapy. Early transition to oral therapy was not associated with treatment failure.

BACKGROUND: Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear. METHODS: We conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis. Participants with a skin abscess 5 cm or smaller in diameter were enrolled. After abscess incision and drainage, participants were randomly assigned to receive clindamycin, trimethoprim–sulfamethoxazole (TMP-SMX), or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after the end of treatment. RESULTS: We enrolled 786 participants: 505 (64.2%) were adults and 281 (35.8%) were children. A total of 448 (57.0%) of the participants were male. S. aureus was isolated from 527 participants (67.0%), and MRSA was isolated from 388 (49.4%). Ten days after therapy in the intention-to-treat population, the cure rate among participants in the clindamycin group was similar to that in the TMP-SMX group (221 of 266 participants [83.1%] and 215 of 263 participants [81.7%], respectively; P = 0.73), and the cure rate in each active-treatment group was higher than that in the placebo group (177 of 257 participants [68.9%], P