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BACKGROUND/OBJECTIVE: Throughout the pandemic, febrile seizures have resulted from infection secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The objective of this study is to determine if there is an increased association between COVID-19 and febrile seizures as compared with other causes of febrile seizures. METHODS: This was a retrospective case control study. Data were collected from the National Institute of Health (NIH) supported National COVID Cohort Collaborative (N3C). Patients from 6 to 60 months who were tested for COVID-19 were included; cases were defined as COVID-19-positive patients whereas controls were defined as COVID-19-negative patients. Febrile seizures diagnosed within 48 hours of the COVID-19 test were considered to be associated with the test result. Patients were subjected to a stratified gender and date matching design followed by a logistic regression controlling for age and race. RESULTS: During the study period, 27,692 patients were included. Of those, 6923 patients were COVID-19-positive, among which 189 had febrile seizures (2.7%). After logistic regression, the likelihood of having febrile seizures concurrently with COVID-19 as compared with other causes was 0.96 ( P = 0.949; confidence interval, 0.81, 1.14). CONCLUSIONS: There were 2.7% of the patients with COVID-19 that were diagnosed with a febrile seizure. However, when subjected to a matched case control design with logistic regression controlling for confounding variables, there does not appear to be an increased risk of febrile seizures secondary to COVID-19 as compared with other causes.
Subject(s)
COVID-19 , Seizures, Febrile , Humans , Seizures, Febrile/epidemiology , Seizures, Febrile/etiology , Seizures, Febrile/diagnosis , COVID-19/complications , COVID-19/epidemiology , Case-Control Studies , Retrospective Studies , SARS-CoV-2ABSTRACT
Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.
Subject(s)
Communicable Diseases , Mpox (monkeypox) , Orthopoxvirus , Sexual and Gender Minorities , Animals , Child , Female , Homosexuality, Male , Humans , Male , Mpox (monkeypox)/diagnosis , Mpox (monkeypox)/epidemiology , Monkeypox virus/genetics , Orthopoxvirus/genetics , Travel , United States/epidemiologyABSTRACT
Objectives: We evaluated the performance and time to result for pathogen identification (ID) and antimicrobial susceptibility testing (AST) of the Accelerate Pheno™ system (AXDX) compared with standard of care (SOC) methods. We also assessed the hypothetical improvement in antibiotic utilization if AXDX had been implemented. Methods: Clinical samples from patients with monomicrobial Gram-negative bacteraemia were tested and compared between AXDX and the SOC methods of the VERIGENE® and Bruker MALDI Biotyper® systems for ID and the VITEK® 2 system for AST. Additionally, charts were reviewed to calculate theoretical times to antibiotic de-escalation, escalation and active and optimal therapy. Results: ID mean time was 21 h for MALDI-TOF MS, 4.4 h for VERIGENE® and 3.7 h for AXDX. AST mean time was 35 h for VITEK® 2 and 9.0 h for AXDX. For ID, positive percentage agreement was 95.9% and negative percentage agreement was 99.9%. For AST, essential agreement was 94.5% and categorical agreement was 93.5%. If AXDX results had been available to inform patient care, 25% of patients could have been put on active therapy sooner, while 78% of patients who had therapy optimized during hospitalization could have had therapy optimized sooner. Additionally, AXDX could have reduced time to de-escalation (16 versus 31 h) and escalation (19 versus 31 h) compared with SOC. Conclusions: By providing fast and reliable ID and AST results, AXDX has the potential to improve antimicrobial utilization and enhance antimicrobial stewardship.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/microbiology , Microbial Sensitivity Tests/methods , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship , Blood Culture/methods , Blood Culture/standards , Child , Child, Preschool , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/standards , Female , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Humans , In Situ Hybridization, Fluorescence/methods , In Situ Hybridization, Fluorescence/standards , Infant , Male , Microbial Sensitivity Tests/standards , Middle Aged , Phenotype , Prospective Studies , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/standards , Young AdultSubject(s)
Azithromycin , Child Mortality , Child , Humans , Azithromycin/therapeutic use , Africa/epidemiologySubject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , Renal Dialysis/adverse effects , SARS-CoV-2/immunology , Seroconversion , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/transmission , COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19 Serological Testing/statistics & numerical data , Child , Female , Hospitals, Pediatric/statistics & numerical data , Humans , Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data , Longitudinal Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viral Load/immunologyABSTRACT
BACKGROUND: Nearly half of all pediatric musculoskeletal infections (MSKIs) are culture negative. Plasma microbial cell-free DNA (mcfDNA) sequencing is noninvasive and not prone to the barriers of culture. We evaluated the performance of plasma mcfDNA sequencing in identifying a pathogen, and examined the duration of pathogen detection in children with MSKIs. METHODS: We conducted a prospective study of children, aged 6 months to 18 years, hospitalized from July 2019 to May 2022 with MSKIs, in whom we obtained serial plasma mcfDNA sequencing samples and compared the results with cultures. RESULTS: A pathogen was recovered by culture in 23 of 34 (68%) participants, and by initial mcfDNA sequencing in 25 of 31 (81%) participants. Multiple pathogens were detected in the majority (56%) of positive initial samples. Complete concordance with culture (all organisms accounted for by both methods) was 32%, partial concordance (at least one of the same organism(s) identified by both methods) was 36%, and discordance was 32%. mcfDNA sequencing was more likely to show concordance (complete or partial) if obtained prior to a surgical procedure (82%), compared with after (20%), (RR 4.12 [95% CI 1.25, 22.93], pâ =â .02). There was no difference in concordance based on timing of antibiotics (presample antibiotics 60% vs no antibiotics 75%, RR 0.8 [95% CI 0.40, 1.46], pâ =â .65]). mcfDNA sequencing was positive in 67% of culture-negative infections and detected a pathogen for a longer interval than blood culture (median 2 days [IQR 1, 6 days] vs 1 day [1, 1 day], pâ <â .01). CONCLUSIONS: Plasma mcfDNA sequencing may be useful in culture-negative pediatric MSKIs if the sample is obtained prior to surgery. However, results must be interpreted in the appropriate clinical context as multiple pathogens are frequently detected supporting the need for diagnostic stewardship.
Subject(s)
Blood Culture , High-Throughput Nucleotide Sequencing , Child , Humans , Prospective Studies , Sequence Analysis, DNA , Anti-Bacterial Agents/therapeutic useABSTRACT
Data are limited on the clinical impact of nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) testing (nMRSA-PCR) for orbital cellulitis. This two-center, retrospective study demonstrated a negative predictive value of 98.0% and an overall lower use of anti-MRSA antibiotics, without a concomitant increase in hospital readmission.
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Background: Cryptococcal meningitis is an uncommon but serious infection with high mortality and morbidity. Classically described in immunocompromised patients, including those with solid organ transplants or HIV/AIDS, cryptococcosis has also been reported in young and otherwise healthy patients, albeit rarely. Methods: We retrospectively searched for all cases of cryptococcal meningitis in young (≤50 years) and previously healthy patients with no known immunocompromising conditions from January 2015 to January 2022 at Indiana University Health (IU Health). Additionally, a PubMed literature review was performed with the keywords "cryptococcal meningitis" and "immunocompetent" from January 1988 to January 2022. Clinical courses, including outcomes and treatment regimens, were evaluated. Results: We identified 4 local cases of cryptococcal meningitis in otherwise healthy patients age ≤50 years. Three cases were due to Cryptococcus neoformans, with 1 experiencing a postinfectious inflammatory response syndrome (PIIRS). The PubMed search identified 51 additional cases, with 32 (63%) being caused by Cryptococcus neoformans and 8 (17%) by Cryptococcus gattii. Of the 51 cases, only 2 resulted in death directly due to cryptococcosis. Fifteen (29%) had PIIRS, with steroid treatment documented in 11 of 15. Antifungal induction regimens and duration were varied but predominately consisted of amphotericin and flucytosine, with a mean induction duration of 5.0 weeks. Conclusions: Cryptococcal meningitis in young, previously healthy patients is likely under-recognized. PIIRS (akin to immune reconstitution inflammatory syndrome observed in HIV/AIDS) with prolonged recovery should be of concern. Determining risk factors for cryptococcosis in these patients remains elusive.
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Background Demographic and clinical risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children presenting with respiratory viral symptoms are not well defined. An understanding of risk factors for SARS-CoV-2 infection can help prioritize testing. Methodology We evaluated potential demographic and clinical factors in children who had respiratory viral symptoms and were tested by polymerase chain reaction (PCR) for SARS-CoV-2 and other respiratory viral infections. Results Among the 263 symptomatic children tested for routine seasonal respiratory viruses by PCR, 18 (6.8%) tested positive for SARS-CoV-2. Overall, 22.2% of SARS-CoV-2-infected children and 37.1% of SARS-CoV-2-uninfected children had infection with one or more non-SARS-CoV-2 pathogens (p = 0.31). Higher proportions of children with compared to without SARS-CoV-2 infection were male (77.8 vs. 51.8%, p = 0.05), Hispanic (44.4% vs. 9.8%, p < 0.001), or had the symptoms of fatigue (22.2% vs. 2.5%, p = 0.003) or anosmia/ageusia (11.1% vs. 0%, p = 0.004). History of hypoxic-ischemic encephalopathy (HIE) and obesity were more common in children with versus without SARS-CoV-2 infection (11.1% vs. 1.2%, p = 0.04, and 11.1% vs. 0%, p = 0.004, respectively). In a multivariate analysis, Hispanic ethnicity, symptoms of fatigue or anosmia/ageusia, and presence of obesity (as noted on physical examination) or HIE were independently associated with SARS-CoV-2 infection. Numbers in each category were small, and these preliminary associations require confirmation in future studies. Conclusions In this area of the United States, infection with other viruses did not rule out infection with SARS-CoV-2. Additionally, children with respiratory viral symptoms who were of Hispanic ethnicity, had symptoms of weakness/fatigue, or had obesity or HIE were at an increased risk for SARS-CoV-2 infection. Future studies should assess if these factors are associated with risk in populations in other areas of the United States.
ABSTRACT
Ehrlichiosis is an infection of white blood cells that affects various mammals, including mice, cattle, dogs, and humans. It was first reported in dogs in 1935, and the first human case was documented in the United States in 1986. Ehrlichia are obligate, intracellular bacteria that are transmitted by ticks to humans. They grow as a cluster (morula) in neutrophils (Anaplasma phagocytophilum and E. ewingii) and in monocytes (E. chaffeensis). The infection may cause prolonged fever and general aches, and is characterized by leukopenia, cytopenia, and elevated liver transaminases. In the first week of infection, ehrlichiae can be detected by finding intracellular aggregates on the blood/body fluid smears and various other laboratory findings. Immunofluorescent antibodies (IFA) titers and PCR are generally needed for confirmation and a definitive diagnosis. Early diagnosis is necessary as antibiotic treatment with doxycycline is very effective.
Subject(s)
Anaplasmosis , Ehrlichiosis , Anaplasma phagocytophilum/growth & development , Anaplasma phagocytophilum/isolation & purification , Anaplasmosis/diagnosis , Anaplasmosis/microbiology , Anti-Bacterial Agents/therapeutic use , Doxycycline/therapeutic use , Ehrlichia/growth & development , Ehrlichia/isolation & purification , Ehrlichiosis/diagnosis , Ehrlichiosis/drug therapy , Ehrlichiosis/epidemiology , Ehrlichiosis/microbiology , Humans , Leukocytes/microbiology , Male , Middle AgedABSTRACT
OBJECTIVES: To compare the performance and time-to-result (TTR) for antimicrobial susceptibility testing (AST) of positive blood cultures (PBC) using the Accelerate Pheno™ system (AXDX) and both a direct VITEK® 2 card inoculation workflow (DV2) and traditional FDA-approved VITEK® 2 workflow using subcultured isolates (V2). METHODS: Patient samples with monomicrobial Gram-negative rod bacteremia were tested on AXDX and DV2 in tandem and compared to V2 AST results. Categorical agreement (CA) errors were adjudicated using broth microdilution. Instrumentation times and AST TTR were compared. RESULTS: AXDX and DV2 had a CA of 93.4% and 97.4%, respectively, compared to V2. Postadjudication, AXDX, DV2, and V2 had CA of 94.7%, 95.7%, and 96.5%, respectively. Instrument run times were 6.6â¯h, 9.4â¯h, and 9.2â¯h, and AST TTR were 8.9â¯h, 12.9â¯h and 35.5â¯h, respectively. CONCLUSIONS: AXDX and DV2 ASTs are fast and reliable, which may have significant antimicrobial stewardship implications.