Kooperativer Bibliotheksverbund

In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)

Abstract: Carbapenemase-producing (CP) Escherichia coli (CPEc) are a global public health threat. We describe the epidemiology and outcomes of patients with CPEc isolates obtained in CRACKLE 2, a prospective cohort study of hospitalized patients with positive cultures for CP Enterobacteriaceae. Methods In CRACKLE-2, patients with CPEc were enrolled from 26 hospitals in 6 countries (ClinicalTrials.gov NCT03646227). Clinical data were collected, and bacterial isolates underwent whole genome sequencing (WGS). Here, we included unique patients with CPEc by WGS (n=114). The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Chi squared tests with alpha = 0.05 were used to evaluate differences in culture source and outcomes between metallo-beta-lactamase (MBL) and non-MBL isolates. Results Of 114 CPEc isolates, 57 (50%) represented infection (Table 1). Isolates primarily arose from urine (34%) and blood (21%). Compared to non-MBL isolates, isolates containing MBL were more often from urine (41% vs 29%) and less frequently from blood (6% vs 32%); p=0.02. We observed strong regional variations in CP (Figure 1) and MBL (p & lt; 0.0001). Sequence type (ST) 167 was more common among MBL than non-MBL isolates (31% vs 2%, p & lt; 0.0001); non-MBL isolates were more often ST410 and ST131 (17% and 20%). Extended-spectrum beta-lactamases (ESBL) were present in 52% of isolates; most commonly, CTX-M-15 in both MBL (33%) and non-MBL isolates (34%). Phylogenetic analysis of the isolates and corresponding region, bacterial characteristics, and DOOR outcomes are in Figure 1. Death at 30 days occurred in 18 (16%) of patients, more commonly among non-MBL than MBL CPEc (23% vs 6%; p=0.01). The probability of a better DOOR outcome for a randomly selected MBL was 58% [95% CI: 48.2, 67.4], indicating no significant difference between the groups. Figure 1:Phylogenetic population structures of Carbapenemase-producing Escherichia coli (CPEc) isolates Legend: Infection = categorization as infection or colonization. ST = sequence type. BlaCarb = Carbapenemase gene. BlaESBL = acquired ESBL enzymes. DOOR = desirability of outcome ranking. DOOR rankings: 1 = Alive without events; DOOR 2 = Alive with 1 event; DOOR 3 = Alive with 2 or 3 events; DOOR 4 = dead. Conclusion Emergence of carbapenem resistance with important geographic variations was observed in E coli including among high-risk clones such as ST131. Mortality was higher among non-MBL isolates, which were more frequently from blood, but these findings may be confounded by region. Disclosures Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support David Paterson, MBBS, Accelerate: Honoraria|bioMerieux: Honoraria|Entasis: Advisor/Consultant|Janssen-Cilag: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|PPD: Grant/Research Support|Shionogi: Grant/Research Support|VenatoRx: Advisor/Consultant Karen M. Ordonez, MD, AstraZeneca: Expert Testimony|Biomerieux: Expert Testimony|Farma de Colombia: Expert Testimony|MSD: Expert Testimony|Pfizer: Expert Testimony Souha S. Kanj, Pr, MSD, Pfizer, Gilead, Menarini, Astellas: Advisor/Consultant|MSD, Pfizer, Gilead, Menarini, Astellas: Honoraria Robert Bonomo, MD, Cystic Fibrosis Foundation: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|VA: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt: Grant/Research Support David van Duin, MD, PhD, Achaogen: Advisor/Consultant|Allergan: Advisor/Consultant|Astellas: Advisor/Consultant|MedImmune: Advisor/Consultant|Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|NeuMedicine: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|T2 Biosystems: Advisor/Consultant|Tetraphase: Advisor/Consultant.

Type of Medium: Online Resource

ISSN: 2328-8957

URL: Article

DOI: 10.1093/ofid/ofac492.307

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2757767-3

In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)

Abstract: In the United States, 75% of preterm infants receive ampicillin after birth for evaluation of early onset sepsis. Excess antibiotic exposure in preterm infants is associated with morbidity and mortality. Pharmacokinetic (PK) simulations suggest that very low birthweight ( & lt; 1500g) infants receiving ampicillin may experience excess and prolonged therapeutic exposures to ampicillin after drug discontinuation, called post-discontinuation antibiotic exposures (PDAE). It is unknown if low birthweight ( & gt; 1500g to & lt; 2500g) infants that receive ampicillin experience prolonged PDAE. Methods We conducted a pilot prospective PK clinical trial at a single tertiary care center. We enrolled infants with gestational age (GA) & lt; 36 weeks and birthweight (BW) & gt; 1500g and & lt; 2500g who received ampicillin 200 mg/kg/day per standard of care. All infants received 6 ampicillin 66mg/kg doses administered Q8H within 24 hours following birth. Post-discontinuation PK samples were collected between 8-120 hours after the last dose of ampicillin. We performed descriptive statistics on patient characteristics, and graphically displayed ampicillin plasma concentrations following discontinuation. We defined therapeutic exposures as concentrations above the minimum inhibitory concentration (MIC) for Group B Streptococcus (0.25mcg/mL). Results We analyzed 20 PK samples from 12 infants with median (IQR) GA of 32 weeks (31, 34) and BW of 1838g (1730, 2060). See Table 1 for clinical characteristics. All infants (N=8) with post-discontinuation samples collected within 48 hours of last dose had continued therapeutic ampicillin exposures, only 25% of infants had continued therapeutic exposures between 48 and 72 hours post last dose (N=4), and none had therapeutic ampicillin exposures beyond 72 hours post-dose (Figure 1). Samples (n=5) within 24 hours of last dose had median (IQR) ampicillin concentration of 13.2mcg/mL (9.2, 18.7); those within 25-48 hours (n=3) had median concentration of 0.9 mcg/mL (0.6, 2.2). TABLE 1.Enrolled Patient Characteristics and Plasma Ampicillin ConcentrationsFigure 1.Ampicillin Post-Discontinuation Antibiotic Exposures in Low Birthweight Infants (1500g-2500g)MIC = minimum inhibitory concentration. GBS = Group B Streptococcus. Each individual symbol represents one sample collected. MICs based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (8 for E. coli, 0.25mcg/mL for Group B Streptococcus). Conclusion In this small cohort of premature infants, exposures of ampicillin remained therapeutic for at least 24 hours post drug discontinuation and suggests that shorter duration of empirical ampicillin treatments may be warranted in this population. Disclosures Daniel Benjamin, Jr., MD PhD MPH, Allergan: Advisor/Consultant|Melinta Therapuetics: Advisor/Consultant|Syneos Health: Advisor/Consultant Rachel Greenberg, MD, MB, MHS, Provepharm Inc: Advisor/Consultant|Tellus Therapeutics: Advisor/Consultant.

Type of Medium: Online Resource

ISSN: 2328-8957

URL: Article

DOI: 10.1093/ofid/ofac492.618

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2757767-3

In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)

Abstract: Pediatric chronic osteomyelitis (COM) is an uncommon, poorly defined, debilitating disorder often requiring multiple surgeries and prolonged antibiotic courses. Serious long-term sequelae may occur. As accepted diagnostic criteria do not exist, assessments of disease incidence, medical/surgical approach to management and outcomes are lacking. Methods We created a 14-question web-based survey sent to 390 pediatric infectious disease (PID) physician members of the Emerging Infections Network of the Infectious Diseases Society of America. With no standard definition of COM, respondents were asked to conceptualize this disease as they would during routine clinical practice. Of the 148 (38%) survey respondents so far (Table 1), 126 (85%) reported caring for children with COM. We assessed provider characteristics, diagnostic approach, and site-standard surgical and antibiotic management (including oral and intravenous [IV] antimicrobial choice and duration). We performed descriptive statistics on survey results. Results Of the 126 respondents, most were & gt;5 years post-fellowship training and nearly half reported managing 3-6 cases of COM per year (Table 2). Prolonged duration of symptoms (79%), normal inflammatory markers (45%), and abnormal plain films (44%) were the most common findings used for diagnosis; however, diagnostic criteria varied. The most common risk factor was orthopedic implants (44%). Management choices and duration are in Figure 1. Most treated with IV antibiotics for & lt; 2 weeks (34%), continuing oral antibiotics for at least 3-6 months (55%). In COM with retained orthopedic implant, most physicians (48%) use oral therapy until implant removal. Considerations for transition from IV to oral antibiotics included improved physical examination (60%), inflammatory markers (52%), extent of disease (55%), causative organism (41%) and location of infection (38%). Though 85% reported being comfortable diagnosing and managing COM, practices varied widely. Reported approaches to surgical management (a), duration of IV antibiotics (b), and duration of oral antibiotics (c) in children with COM, and management of COM in patients with implanted hardware (d) Responses from 126 pediatric infectious diseases physician participating in an Emerging Infections Network survey regarding diagnosis and management of chronic osteomyelitis (COM). Figure 1a) missing data for 2 respondents; figure 1b) missing data for 5 respondents; figure 1c) missing data for 2 respondents; figure 1d) missing data for 9 respondents. COM: Chronic osteomyelitis; IV: intravenous; abx: antibiotics. Conclusion Pediatric COM is a complex infection. Formal diagnostic criteria and future prospective studies for medical/surgical management by pathogen/site of infection and presence of foreign material are needed to optimize care and outcomes. Disclosures Daniel Benjamin, Jr., MD PhD MPH, Allergan: Advisor/Consultant|Melinta Therapuetics: Advisor/Consultant|Syneos Health: Advisor/Consultant.

Type of Medium: Online Resource

ISSN: 2328-8957

URL: Article

DOI: 10.1093/ofid/ofac492.1145

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2757767-3

In: Contemporary Clinical Trials, Elsevier BV, Vol. 125 ( 2023-02), p. 107067-

Type of Medium: Online Resource

ISSN: 1551-7144

URL: Article

DOI: 10.1016/j.cct.2022.107067

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2176813-4

In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 149, No. 6 ( 2022-06-01)

Abstract: Throughout the COVID-19 pandemic, masking has been a widely used mitigation practice in kindergarten through 12th grade (K–12) school districts to limit within-school transmission. Prior studies attempting to quantify the impact of masking have assessed total cases within schools; however, the metric that more optimally defines effectiveness of mitigation practices is within-school transmission, or secondary cases. We estimated the impact of various masking practices on secondary transmission in a cohort of K–12 schools. METHODS We performed a multistate, prospective, observational, open cohort study from July 26, 2021 to December 13, 2021. Districts reported mitigation practices and weekly infection data. Districts that were able to perform contact tracing and adjudicate primary and secondary infections were eligible for inclusion. To estimate the impact of masking on secondary transmission, we used a quasi-Poisson regression model. RESULTS A total of 1 112 899 students and 157 069 staff attended 61 K–12 districts across 9 states that met inclusion criteria. The districts reported 40 601 primary and 3085 secondary infections. Six districts had optional masking policies, 9 had partial masking policies, and 46 had universal masking. In unadjusted analysis, districts that optionally masked throughout the study period had 3.6 times the rate of secondary transmission as universally masked districts; and for every 100 community-acquired cases, universally masked districts had 7.3 predicted secondary infections, whereas optionally masked districts had 26.4. CONCLUSIONS Secondary transmission across the cohort was modest ( & lt;10% of total infections) and universal masking was associated with reduced secondary transmission compared with optional masking.

Type of Medium: Online Resource

ISSN: 0031-4005 , 1098-4275

URL: Article

DOI: 10.1542/peds.2022-056687

Language: English

Publisher: American Academy of Pediatrics (AAP)

Publication Date: 2022

detail.hit.zdb_id: 1477004-0

In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 147, No. 5 ( 2021-05-01)

Type of Medium: Online Resource

ISSN: 0031-4005 , 1098-4275

URL: Article

DOI: 10.1542/peds.2021-050212

Language: English

Publisher: American Academy of Pediatrics (AAP)

Publication Date: 2021

detail.hit.zdb_id: 1477004-0

In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 76, No. 3 ( 2023-02-08), p. e1114-e1122

Abstract: La Crosse virus (LACV) is the most common neuroinvasive arboviral infection in children in the United States. However, data regarding predictors of disease severity and neurologic outcome are limited. Additionally, long-term neurologic and neurobehavioral outcomes remain relatively sparse. Methods This was a single-center, retrospective cohort study, followed by recruitment for a cross-sectional analysis of long-term neurobehavioral outcomes, among children aged 0–18 years with proven or probable LACV neuroinvasive disease (LACV-ND) between January 2009 and December 2018. Case ascertainment was assured by International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes cross-referenced with laboratory results detecting LACV. Demographics, diagnostics, radiographs, and outcomes were evaluated. Recruitment of patients with prior diagnosis of LACV-ND occurred from January 2020 to March 2020, with assessment performed by validated pediatric questionnaires. Results One-hundred fifty-two children (83 males; median age, 8 years [interquartile range, 5–11.5 years]) were diagnosed with proven (n = 61 [47%] ) and probable (n = 91 [60%]) LACV-ND. Sixty-five patients (43%) had severe disease. Altered mental status (AMS) (odds ratio [OR] , 6.36 [95% confidence interval {CI}, 2.03–19.95]; P = .0002) and seizures at presentation (OR, 10.31 [95% CI, 3.45–30.86] ; P = .0001) were independent predictors of severe disease. Epileptiform discharges on electroencephalogram (EEG) were independently associated with epilepsy diagnosis at follow-up (OR, 13.45 [95% CI, 1.4–128.77]; P = .024). Fifty-four patients were recruited for long-term neurobehavioral follow-up, with frequent abnormal assessments identified (19%–54%) irrespective of disease severity. Conclusions Severe disease was observed frequently among children with LACV-ND. Seizures and AMS at presentation were independent predictors of severe disease. EEG may help determine long-term epilepsy risk. Long-term neurobehavioral issues are frequent and likely underrecognized among children with LACV-ND.

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciac403

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2023

detail.hit.zdb_id: 2002229-3

In: Pediatrics In Review, American Academy of Pediatrics (AAP), Vol. 41, No. Supplement_1 ( 2020-10-01), p. S85-S88

Type of Medium: Online Resource

ISSN: 0191-9601 , 1526-3347

URL: Article

DOI: 10.1542/pir.2018-0271

Language: English

Publisher: American Academy of Pediatrics (AAP)

Publication Date: 2020

In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 149, No. 5 ( 2022-05-01)

Abstract: We evaluated the safety and efficacy of a test-to-stay program for unvaccinated students and staff who experienced an unmasked, in-school exposure to someone with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serial testing instead of quarantine was offered to asymptomatic contacts. We measured secondary and tertiary transmission rates within participating schools and in-school days preserved for participants. METHODS Participating staff or students from universally masked districts in North Carolina underwent rapid antigen testing at set intervals up to 7 days after known exposure. Collected data included location or setting of exposure, participant symptoms, and school absences up to 14 days after enrollment. Outcomes included tertiary transmission, secondary transmission, and school days saved among test-to-stay participants. A prespecified interim safety analysis occurred after 1 month of enrollment. RESULTS We enrolled 367 participants and completed 14-day follow-up on all participants for this analysis. Nearly all (215 of 238, 90%) exposure encounters involved an unmasked index case and an unmasked close contact, with most (353 of 366, 96%) occurring indoors, during lunch (137 of 357, 39%) or athletics (45 of 357, 13%). Secondary attack rate was 1.7% (95% confidence interval: 0.6%–4.7%) based on 883 SARS-CoV-2 serial rapid antigen tests with results from 357 participants; no tertiary cases were identified, and 1628 (92%) school days were saved through test-to-stay program implementation out of 1764 days potentially missed. CONCLUSION After unmasked in-school exposure to SARS-CoV-2, even in a mostly unvaccinated population, a test-to-stay strategy is a safe alternative to quarantine.

Type of Medium: Online Resource

ISSN: 0031-4005 , 1098-4275

URL: Article

DOI: 10.1542/peds.2021-056045

Language: English

Publisher: American Academy of Pediatrics (AAP)

Publication Date: 2022

detail.hit.zdb_id: 1477004-0

In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 149, No. Supplement_2 ( 2022-02-01)

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related quarantines, which are required after close contact with infected individuals, have substantially disrupted in-person education for kindergarten through 12th grade (K–12) students. In recent recommendations, shortened durations of quarantine are allowed if a negative SARS-CoV-2 test result is obtained at 5 to 7 days postexposure, but access to testing remains limited. We hypothesized that providing access to in-school SARS-CoV-2 testing postexposure would increase testing and reduce missed school days. METHODS This prospective cohort study was conducted in one large public K–12 school district in North Carolina and included 2 periods: preimplementation (March 15, 2021, to April 21, 2021) and postimplementation (April 22, 2021, to June 4, 2021), defined around initiation of an in-school SARS-CoV-2 testing program in which on-site access to testing is provided. Number of quarantined students and staff, testing uptake, test results, and number of missed school days were analyzed and compared between the preimplementation and postimplementation periods. RESULTS Twenty-four schools, including 12 251 in-person learners, participated in the study. During preimplementation, 446 close contacts were quarantined for school-related exposures; 708 close contacts were quarantined postimplementation. Testing uptake after school-related exposures increased from 6% to 40% (95% confidence interval: 23% to 45%) after implementation, and 89% of tests were conducted in-school. After in-school testing implementation, close contacts missed ∼1.5 fewer days of school (95% confidence interval: −2 to −1). CONCLUSIONS Providing access to in-school testing may be a worthwhile mechanism to increase testing uptake after in-school exposures and minimize missed days of in-person learning, thereby mitigating the pandemic’s ongoing impact on children.

Type of Medium: Online Resource

ISSN: 0031-4005 , 1098-4275

URL: Article

DOI: 10.1542/peds.2021-054268J

Language: English

Publisher: American Academy of Pediatrics (AAP)

Publication Date: 2022

detail.hit.zdb_id: 1477004-0