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Metagenomic Next-Generation Sequencing (mNGS) holds promise in diagnosing fever of unknown origin (FUO) by detecting diverse pathogens. We systematically reviewed the literature to evaluate mNGS's accuracy, clinical efficacy, and limitations in FUO diagnosis. Nine studies revealed mNGS's positivity rate ranging from 66.7% to 93.5% for bacterial bloodstream infections and systemic infections. Meta-analysis of three studies involving 857 patients, including 354 with FUO, showed a sensitivity of 0.91 (95% CI: 0.87-0.93) and specificity of 0.64 (95% CI: 0.58-0.70). Despite lower specificity, mNGS demonstrated a higher Diagnostic Odds Ratio (DOR) of 17.0 (95% CI: 4.5-63.4) compared to conventional microbiological tests (CMTs) at 4.7 (95% CI: 2.9-7.6). While mNGS offers high sensitivity but low specificity in identifying causative pathogens for FUO, its superior DOR suggests potential for more accurate diagnoses and targeted interventions. Further research is warranted to optimize its clinical application in FUO management.
Subject(s)
Fever of Unknown Origin , High-Throughput Nucleotide Sequencing , Metagenomics , Sensitivity and Specificity , Humans , Fever of Unknown Origin/diagnosis , Fever of Unknown Origin/microbiology , High-Throughput Nucleotide Sequencing/methods , Metagenomics/methods , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/classification , Bacterial Infections/diagnosis , Bacterial Infections/microbiologyABSTRACT
Objective: Antimicrobials are frequently used for palliation during end-of-life care, but adverse effects, such as antimicrobial resistance, are a concern. Shared decision-making is beneficial in end-of-life care conversations to help align antimicrobial-prescribing with patient preferences. However, there is limited data regarding optimal incorporation of antimicrobial-prescribing discussions into shared decision-making conversations. We explored healthcare provider, patient, and support caregiver (eg, family member/friend) perceptions of barriers and facilitators to discussing antimicrobial-prescribing during the end-of-life period. Design: Qualitative study. Participants: Healthcare providers; palliative care/hospice care patients/caregivers. Methods: We conducted semi-structured interviews on shared attitudes/beliefs about antimicrobial-prescribing during end-of-life patient care at one acute-care and one long-term-care facility. Interviews were analyzed for thematic content. Results: Fifteen providers and 13 patients/caregivers completed interviews. Providers recognized the potential benefit of leveraging shared decision-making to guide antimicrobial-prescribing decisions. Barriers included limited face-to-face time with the patient and uncertainty of end-of-life prognosis. Patients/caregivers cited trust, comprehension, and feeling heard as important characteristics which act as facilitators in fostering effective shared decision-making around antimicrobial use. Communication in which providers ensure patients are involved in shared decision-making discussions could be increased to ensure patients and their providers develop a mutually agreeable care plan. Conclusions: Shared decision-making is a practice that can guide antimicrobial-prescribing decisions during end-of-life care, thus potentially minimizing antimicrobial-related adverse effects. Our findings highlight opportunities for increased shared decision-making around antimicrobial use during end-of-life care. Interventions designed to address the identified barriers to shared decision-making have the potential to improve antimicrobial-prescribing practices at end-of-life.
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Background: Penicillin's long-standing role as the reference standard in syphilis treatment has led to global reliance. However, this dependence presents challenges, prompting the need for alternative strategies. We performed a systematic literature review and meta-analysis to evaluate the efficacy of these alternative treatments against nonneurological syphilis. Methods: We searched MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science from database inception to 28 August 2023, and we included studies that compared penicillin or amoxicillin monotherapy to other treatments for the management of nonneurological syphilis. Our primary outcome was serological cure rates. Random-effect models were used to obtain pooled mean differences, and heterogeneity was assessed using the I2 test. Results: Of 6478 screened studies, 27 met the inclusion criteria, summing 6710 patients. The studies were considerably homogeneous, and stratified analyses considering each alternative treatment separately revealed that penicillin monotherapy did not outperform ceftriaxone (pooled odds ratio, 1.66 [95% confidence interval, .97-2.84]; I2 = 0%), azithromycin (0.92; [.73-1.18]; I2 = 0%), or doxycycline (0.82 [.61-1.10]; I2 = 1%) monotherapies with respect to serological conversion. Conclusions: Alternative treatment strategies have serological cure rates equivalent to penicillin, potentially reducing global dependence on this antibiotic.
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Objective: We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) in the pediatric population. Design: Systematic literature review/meta-analysis. Methods: We searched PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to August 14, 2023, for studies evaluating the COVID-19 vaccine effectiveness against post-COVID conditions among vaccinated individuals < 21 years old who received at least 1 dose of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present 4 or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% CI) for post-COVID conditions between vaccinated and unvaccinated individuals. Results: Eight studies with 23,995 individuals evaluated the effect of vaccination on post-COVID conditions, of which 5 observational studies were included in the meta-analysis. The prevalence of children who did not receive COVID-19 vaccines ranged from 65% to 97%. The pooled prevalence of post-COVID conditions was 21.3% among those unvaccinated and 20.3% among those vaccinated at least once. The pooled DOR for post-COVID conditions among individuals vaccinated with at least 1 dose and those vaccinated with 2 doses were 1.07 (95% CI, 0.77-1.49) and 0.82 (95% CI, 0.63-1.08), respectively. Conclusions: A significant proportion of children and adolescents were unvaccinated, and the prevalence of post-COVID conditions was higher than reported in adults. While vaccination did not appear protective, conclusions were limited by the lack of randomized trials and selection bias inherent in observational studies.
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ABSTRACT: We conducted a systematic literature review and meta-analysis to assess the efficacy of alternative treatments for neurosyphilis. We searched MEDLINE, CINAHL, Embase, Cochrane, Scopus, and Web of Science from database inception to September, 2023, for studies in neurosyphilis that compared penicillin monotherapy to other treatments. We focused on the impact of these therapies on treatment response, but also assessed data regarding reinfection and adverse drug events. Random-effect models were used to obtain pooled mean differences. Of 3,415 screened studies, six met the inclusion criteria for the systematic literature review. Three studies provided quantitative data that allowed for inclusion in the meta-analysis. Our analysis revealed that the efficacy of intravenous ceftriaxone 2 g daily for 10 days (51 patients) did not appear statistically different compared to intravenous penicillin G 18-24 million units daily for 10 days (185 patients) for neurosyphilis (pooled OR, 2.85; 95% CI, 0.41-19.56; I2 = 49%). No statistical difference between ceftriaxone and penicillin was identified in people living with HIV (pooled OR, 4.51; 95% CI, 0.50-40.49; I2 = 34%). We concluded that alternative therapy with IV ceftriaxone appears similar to penicillin, potentially expanding treatment options for neurosyphilis. Other treatment options including doxycycline warrant further study.
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With the rapid advancement of artificial intelligence (AI), the field of infectious diseases (ID) faces both innovation and disruption. AI and its subfields including machine learning, deep learning, and large language models can support ID clinicians' decision making and streamline their workflow. AI models may help ensure earlier detection of disease, more personalized empiric treatment recommendations, and allocation of human resources to support higher-yield antimicrobial stewardship and infection prevention strategies. AI is unlikely to replace the role of ID experts, but could instead augment it. However, its limitations will need to be carefully addressed and mitigated to ensure safe and effective implementation. ID experts can be engaged in AI implementation by participating in training and education, identifying use cases for AI to help improve patient care, designing, validating and evaluating algorithms, and continuing to advocate for their vital role in patient care.
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BACKGROUND: Central line-associated bloodstream infections (CLABSIs) increased nationally during the COVID-19 pandemic. We described CLABSIs at our institution during 2019 to 2022. METHODS: This retrospective observational study examined CLABSIs among adult inpatients at an 866-bed teaching hospital in the Midwest. CLABSI incidence was trended over time and compared to monthly COVID-19 admissions. Manual chart review was performed to obtain patient demographics, catheter-associated variables, pathogens, and clinical outcomes. RESULTS: We identified 178 CLABSIs. The CLABSI incidence (cases per 1,000 line days) tripled in October 2020 as COVID-19 admissions increased. CLABSIs in 2020 were more frequently caused by coagulase-negative staphylococci and more frequently occurred in the intensive care units 7+ days after central line insertion. The CLABSI incidence normalized in early 2021 and did not increase during subsequent COVID-19 surges. Throughout 2019 to 2022, about half of the nontunneled central venous catheters involved in CLABSI were placed emergently. One-quarter of CLABSIs involved multiple central lines. Chlorhexidine skin treatment adherence was limited by patient refusal. CONCLUSIONS: The increase in CLABSIs in late 2020 during a surge in COVID-19 admissions was likely related to central line maintenance but has resolved. Characterizing CLABSI cases can provide insight into adherence to guideline-recommended prevention practices and identify areas for improvement at individual institutions.
Subject(s)
Bacteremia , COVID-19 , Catheter-Related Infections , Catheterization, Central Venous , Central Venous Catheters , Sepsis , Adult , Humans , Catheterization, Central Venous/adverse effects , Catheter-Related Infections/prevention & control , Iowa/epidemiology , Pandemics , Central Venous Catheters/adverse effects , Retrospective Studies , Hospitals, Teaching , Sepsis/epidemiology , COVID-19/epidemiology , COVID-19/complications , Bacteremia/prevention & controlABSTRACT
Of the 2,668 patients admitted with coronavirus disease 2019 (COVID-19), 4% underwent prolonged isolation for >20 days. Reasons for extended isolation were inconsistent with Centers for Disease Control and Prevention (CDC) guidelines in 25% of these patients and were questionable in 54% due to an ongoing critically ill condition at day 20 without CDC-defined immunocompromised status.
Subject(s)
COVID-19 , Humans , Inpatients , Iowa , SARS-CoV-2 , Tertiary Care Centers , Retrospective StudiesABSTRACT
Approximately 45% of patients receive medical services with minimal or no benefit (low-value care). In addition to the increasing costs to the health system, performing invasive procedures without an indication poses a potentially preventable risk to patient safety. This study aimed to determine whether a managed quality improvement programme could prevent cholecystectomy and surgery for endometriosis treatment with minimal or no benefit to patients.This before-and-after study was conducted at a private hospital in São Paulo, Brazil, which has a main medical remuneration model of fee for service. All patients who underwent cholecystectomy or surgery for endometriosis between 1 August 2020 and 31 May 2021 were evaluated.The intervention consisted of allowing the performance of procedures that met previously defined criteria or for which the indications were validated by a board of experts.A total of 430 patients were included in this analysis. The programme prevented the unnecessary performance of 13% of cholecystectomies (p=0.0001) and 22.2% (p=0.0006) of surgeries for the treatment of endometriosis. This resulted in an estimated annual cost reduction to the health system of US$466 094.93.In a hospital with a private practice and fee-for-service medical remuneration, the definition of clear criteria for indicating surgery and the analysis of cases that did not meet these criteria by a board of reputable experts at the institution resulted in a statistically significant reduction in low-value cholecystectomies and endometriosis surgeries.
Subject(s)
Endometriosis , Female , Humans , Endometriosis/surgery , Brazil , HospitalsABSTRACT
Objective: We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) among fully vaccinated individuals. Design: Systematic literature review/meta-analysis. Methods: We searched PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to June 2, 2023, for studies evaluating the COVID-19 vaccine effectiveness (VE) against post-COVID conditions among fully vaccinated individuals who received two doses of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present four or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% confidence interval) for post-COVID conditions between fully vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% x (1-DOR). Results: Thirty-two studies with 775,931 individuals evaluated the effect of vaccination on post-COVID conditions, of which, twenty-four studies were included in the meta-analysis. The pooled DOR for post-COVID conditions among fully vaccinated individuals was 0.680 (95% CI: 0.523-0.885) with an estimated VE of 32.0% (11.5%-47.7%). Vaccine effectiveness was 36.9% (23.1%-48.2%) among those who received two doses of COVID-19 vaccine before COVID-19 infection and 68.7% (64.7%-72.2%) among those who received three doses before COVID-19 infection. The stratified analysis demonstrated no protection against post-COVID conditions among those who received COVID-19 vaccination after COVID-19 infection. Conclusions: Receiving a complete COVID-19 vaccination prior to contracting the virus resulted in a significant reduction in post-COVID conditions throughout the study period, including during the Omicron era. Vaccine effectiveness demonstrated an increase when supplementary doses were administered.
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BACKGROUND: Since its beginning, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a challenge for clinical and molecular diagnostics, because it has been caused by a novel viral agent. Whole-genome sequencing assisted in the characterization and classification of SARS-CoV-2, and it is an essential tool to genomic surveillance aiming to identify potentials hot spots that could impact on vaccine immune response and on virus diagnosis. We describe two cases of failure at the N2 target of the RT-PCR test Xpert® Xpress SARS-CoV-2. METHODS: Total nucleic acid from the Nasopharyngeal (NP) and oropharyngeal (OP) swab samples and cell supernatant isolates were obtained. RNA samples were submitted to random amplification. Raw sequencing data were subjected to sequence quality controls, removal of human contaminants by aligning against the HG19 reference genome, taxonomic identification of other pathogens and genome recovery through assembly and manual curation. RT-PCR test Xpert® Xpress SARS-CoV-2 was used for molecular diagnosis of SARS-CoV-2 infection, samples were tested in duplicates. RESULTS: We identified 27 samples positive for SARS-CoV-2 with a nucleocapsid (N) gene drop out on Cepheid Xpert® Xpress SARS-CoV-2 assay. Sequencing of 2 of 27 samples revealed a single common mutation in the N gene C29197T, potentially involved in the failed detection of N target. CONCLUSIONS: This study highlights the importance of genomic data to update molecular tests and vaccines.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Nucleocapsid/genetics , Mutation , COVID-19 TestingABSTRACT
Background: Blood culture contamination may lead to misdiagnosis, overutilization of antibiotics, and prolonged length of stay. Blood specimen diversion devices can reduce contamination rates during blood culture collection procedures. We performed a systematic literature review and meta-analysis evaluating the influence of blood specimen diversion devices in blood culture contamination rates. Methods: We searched Medline, Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science, from database inception to 1 March 2023, for studies evaluating the impact of a diversion device on blood culture contamination. Blood culture contamination was a positive blood culture with microorganisms not representative of true bacteremia, but rather introduced during collection or processing the blood sample. Random-effects models were used to obtain pooled mean differences, and heterogeneity was assessed using the I2 test. Results: Of 1768 screened studies, 12 met inclusion criteria for this systematic literature review. Of them, 9 studies were included in the meta-analysis. Studies were substantially heterogeneous, but stratified analyses considering only high-quality studies revealed that venipuncture using a diversion device was associated with a significant reduction in blood culture contamination in comparison to the standard procedure of collection (pooled odds ratio [OR], 0.26 [95% confidence interval {CI}, .13-.54]; I2 = 19%). Furthermore, the stratified analysis showed that the adoption of a diversion device did not reduce the detection of true infection (pooled OR, 0.85 [95% CI, .65-1.11]; I2 = 0%). Conclusions: Blood culture diversion devices was associated with decreased contamination rates and could improve quality of care, reduce costs, and avoid unnecessary antibiotic use.
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Objective: To evaluate the impact of a multicenter, try automated dashboard on ASP activities and its acceptance among ASP leaders. Design: Frontline stewards were asked to participate in semi-structured interviews before and after implementation of a web-based ASP information dashboard providing risk-adjusted benchmarking, longitudinal trends, and analysis of antimicrobial usage patterns at each facility. Setting: The study was performed at Iowa City VA Health Care System. Participants: ASP team members from nine medical centers in the VA Midwest Health Care Network (VISN 23). Methods: Semi-structured interviews were conducted pre- and post-implementation, with interview guides informed by clinical experiences and the Consolidated Framework for Implementation Research (CFIR). Participants evaluated the dashboard's ease of use, applicability to ongoing ASP activities, perceived validity and reliability, and relative advantage over other ASP monitoring systems. Results: Compared to established stewardship data collection and reporting methods, participants found the dashboard more intuitive and accessible, allowing them to reduce dependence on other systems and staff to obtain and share data. Standardized and risk-adjusted rankings were largely accepted as a valuable benchmarking method; however, participants felt their facility's characteristics significantly influenced the rankings' validity. Participants recognized staffing, training, and uncertainty with using the dashboard as an intervention tool as barriers to consistent and comprehensive dashboard implementation. Conclusions: Participants generally accepted the dashboard's risk-adjusted metrics and appreciated its usability. While creating automated tools to rigorously benchmark antimicrobial use across hospitals can be helpful, the displayed metrics require further validation, and the longitudinal utility of the dashboard warrants additional study.
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Objective: To compare the long-term vaccine effectiveness between those receiving viral vector [Oxford-AstraZeneca (ChAdOx1)] or inactivated viral (CoronaVac) primary series (2 doses) and those who received an mRNA booster (Pfizer/BioNTech) (the third dose) among healthcare workers (HCWs). Methods: We conducted a retrospective cohort study among HCWs (aged ≥18 years) in Brazil from January 2021 to July 2022. To assess the variation in the effectiveness of booster dose over time, we estimated the effectiveness rate by taking the log risk ratio as a function of time. Results: Of 14,532 HCWs, coronavirus disease 2019 (COVID-19) was confirmed in 56.3% of HCWs receiving 2 doses of CoronaVac vaccine versus 23.2% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001), and 37.1% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 22.7% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). The highest vaccine effectiveness with mRNA booster was observed 30 days after vaccination: 91% for the CoronaVac vaccine group and 97% for the ChAdOx1 vaccine group. Vacine effectiveness declined to 55% and 67%, respectively, at 180 days. Of 430 samples screened for mutations, 49.5% were SARS-CoV-2 delta variants and 34.2% were SARS-CoV-2 omicron variants. Conclusions: Heterologous COVID-19 vaccines were effective for up to 180 days in preventing COVID-19 in the SARS-CoV-2 delta and omicron variant eras, which suggests the need for a second booster.
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OBJECTIVE: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP). METHODS: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up. RESULTS: Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID. CONCLUSIONS: Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.
Subject(s)
COVID-19 , Humans , Female , Male , COVID-19/epidemiology , SARS-CoV-2 , Post-Acute COVID-19 Syndrome , Brazil/epidemiology , COVID-19 Vaccines , Case-Control Studies , Risk FactorsABSTRACT
OBJECTIVE: We aimed to estimate antibiotic use during the last 6 months of life for hospitalized patients under hospice or palliative care and identify potential targets (i.e. time points) for antibiotic stewardship during the end-of-life period. METHODS: We conducted a retrospective cohort study of nationwide Veterans Affairs (VA) patients who died between January 1, 2014 and December 31, 2019 and who had been hospitalized within 6 months prior to death. Data from the VA's integrated electronic medical record were collected, including demographics, comorbid conditions, and duration of inpatient antibiotics administered, along with outpatient antibiotics dispensed. A propensity score-matched cohort analysis was conducted to compare antibiotic use between hospitalized patients placed into palliative care or hospice matched to hospitalized patients not receiving palliative care or hospice. RESULTS: There were 9808 and 40 796 propensity score-matched patient pairs in the hospice and palliative care groups, respectively. Within 14 days of placement or consultation, 41% (4040/9808) of hospice patients and 48% (19 735/40 796) of palliative care patients received at least one antibiotic, while 25% (2420/9808) matched nonhospice and 27% (10 991/40 796) matched nonpalliative care patients received antibiotics. Entry into hospice was independently associated with a 12% absolute increase in antibiotic prescribing, and entry into palliative care was associated with a 17% absolute increase during the 14 days post-entry vs. pre-entry period. DISCUSSION: We observed that patients receiving end-of-life care had high levels of antibiotic exposure across this VA population, particularly during admissions when they received hospice or palliative care consultation.