Open Forum Infectious Diseases

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EISSN: 23288957
Total articles ≅ 21,355

Latest articles in this journal

Niamh Simmons, , Joanna Buss, Thomas Bailey,
Published: 1 February 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad050

Abstract:
Background: Tuberculosis meningitis (TBM) has high mortality and morbidity. Diagnostic delays can impact TBM outcomes. We aimed to estimate the number of potentially missed opportunities (MO) to diagnose TBM, and determine its impact on 90-day mortality. Methods: Retrospective cohort of adult patients with a central nervous system (CNS) TB ICD-9/10 diagnosis code (013*, A17*) identified in the Healthcare Cost and Utilization Project, State Inpatient and State Emergency Department (ED) Databases from eight states. MO was defined as composite of ICD-9/10 diagnosis/procedure codes that included CNS signs/symptoms, systemic illness, or non-CNS TB diagnosis during a hospital/ED visit 180 days prior to the index TBM admission. Demographics, comorbidities, admission characteristics, mortality, and admission costs were compared between those with and without a MO, and 90-day in-hospital mortality, using univariate and multivariable (MV) analyses. Results: Of 893 patients with TBM median age at diagnosis was 50 years (IQR 37, 64), 61.3% were male, and 35.2% had Medicaid as primary payer. Overall, 407 (45.6%) had a prior hospital or ED visit with a MO code. In-hospital 90-day mortality was not different between those with and without a MO, regardless of the MO coded during an ED visit (13.7% vs 15.2%, p=0.73) or a hospitalization (28.2% vs 30.9%, p=0.74). Independent risk of 90-day in-hospital mortality was associated with older age, hyponatremia (RR 1.62, 95%CI 1.1–2.4, p=0.01), septicemia (1.6, 1.03–2.45, p=0.03), and mechanical ventilation (3.4, 2.25–5.3, p<0.001) during the index admission. Conclusion: Almost half the patients coded for TBM had a hospital or ED visit in the previous 6 months meeting the MO definition. We found no association between having a MO for TBM and 90-day in-hospital mortality.
, Fatimah S Dawood, Eduardo Azziz-Baumgartner, Yeny Tinoco, Giselle Soto, Oswaldo Gonzalez, Santiago Cabrera, Richard Florian, Edwin Llajaruna, Danielle Rentz Hunt, et al.
Published: 1 February 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad033

Abstract:
Background: Few studies have examined influenza vaccine effectiveness (VE) among women during pregnancy in middle-income countries. We used data from a prospective cohort of women who were pregnant in Peru to estimate effectiveness of the 2018 Southern Hemisphere influenza vaccine. Methods: Women at 1 of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing. Time-varying Cox proportional hazard regression models were used to estimate the risk of RT-PCR-confirmed influenza infection after adjusting for inverse probability treatment weight. Results: We followed 1,896 women for a median of 127 days (IQR; 86-174). Participants had a median age of 29 years (IQR: 24–34). Among the 1,896 women, 49% were vaccinated with the 2018 influenza vaccine and 1,039 (55%) developed influenza-like illness of which, 76 (7%) had RT-PCR-confirmed influenza. Incidence rates of RT-PCR-confirmed influenza were 36.6 and 15.3 per 100,000 person-days among women who were unvaccinated and vaccinated, respectively. Adjusted influenza VE was 22% (95% CI: -64.1%, 62.9%). Conclusion: Participants vaccinated against influenza had more than 50% lower incidence of RT-PCR-confirmed influenza illness. While the VE estimated through propensity weight-adjusted time-varying Cox regression did not reach statistical significance, our findings provide additional evidence about the value of maternal influenza vaccination in middle-income countries.
, , Noah D Peyser, Feng Lin, Sara J Knight, Audrey Djibo, Rasha Khatib, Heather Kitzman, Emily O’Brien, Natasha Williams, et al.
Published: 1 February 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad047

Abstract:
Background: Few prospective studies of Long COVID risk factors have been conducted. The purpose of this study was to determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute SARS-CoV-2 infection are associated with Long COVID. Methods: The COVID-19 Citizen Science (CCS) study is an online cohort study that began enrolling March 26, 2020, with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection. Adult participants who reported a positive SARS-CoV-2 test result prior to April 4, 2022, were surveyed for Long COVID symptoms. The primary outcome was at least 1 prevalent Long COVID symptom greater than 1 month after acute infection. Exposures of interest included age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, variant wave, number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, and exercise. Results: Of 13,305 participants who reported a SARS-CoV-2 positive test, 1480 (11.1%) responded. Respondents’ mean age was 53 and 1017 (69%) were female. 476 (32.2%) reported Long COVID symptoms at a median 360 days after infection. In multivariable models, number of acute symptoms (OR 1.30 per symptom, 95%CI 1.20-1.40), lower socioeconomic status/financial insecurity (OR 1.62, 95%CI 1.02-2.63), pre-infection depression (OR 1.08, 95%CI 1.01-1.16), and earlier variants (OR 0.37 for Omicron compared to ancestral strain, 95%CI 0.15-0.90) were associated with Long COVID symptoms. Conclusions: Variant wave, severity of acute infection, lower socioeconomic status and pre-existing depression are associated with Long COVID symptoms.
, M Pini, T Mulas, A A Materazzi, E E Ippolito, J Wagemans, M Kutateladze, C Fontana, , A A Tavanti, et al.
Published: 1 February 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad051

Abstract:
Prosthetic joint infection (PJI) caused by Pseudomonas aeruginosa represents a severe complication in orthopaedic surgery. We report the case of a patient with chronic PJI from P. aeruginosa successfully treated with personalised phage therapy (PT) in combination with meropenem. A 62-year-old woman was affected by a chronic right hip prosthesis infection since 2016 caused by P. aeruginosa. The patient was treated with phage Pa53 (I day 10 ml q8h, then 5 ml q8h via joint drainage for two weeks) in association with meropenem (2gr q12h iv) after a surgical procedure. A two-year clinical follow-up was performed. An in vitro bactericidal assay of the phage alone and in combination with meropenem against a 24h-old biofilm of bacterial isolate was also carried out. No severe adverse events were observed during PT. Two years after suspension there were no clinical signs of infection relapse, and a marked leukocyte scan showed no pathological uptake areas. In vitro studies showed that the minimum biofilm eradicating concentration of meropenem was 8 µg/ml. No biofilm eradication was observed at 24h incubation with phages alone (108 PFU/ml). However, the addition of meropenem at sub-eradicating concentration (1µg/ml) to phages at lower titer (103 PFU/ml) resulted in a synergistic eradication after 24h incubation. Personalized PT, in combination with meropenem, was found to be safe and effective in eradicating P. aeruginosa infection. These data encourage the development of personalized clinical studies aimed at evaluating the efficacy of PT as an adjunct to antibiotic therapy for chronic persistent infections.
Published: 31 January 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad046

Abstract:
As the frequency of metallo-β-lactamase (MBL)–producing Enterobacterales is increasing worldwide, effective antimicrobials to treat the infections caused by these organisms are urgently needed. The activity of aztreonam-avibactam and comparators were evaluated against 27,834 Enterobacterales isolates collected from 74 US medical centers in 2019–2021. Isolates were susceptibility tested by broth microdilution. An aztreonam-avibactam pharmacokinetic/pharmacodynamic breakpoint of ≤8 mg/L was applied for comparison. Antimicrobial susceptibility and the frequency of key resistance phenotypes were assessed then stratified by year and infection type. Carbapenem-resistant Enterobacterales (CRE) were screened for carbapenemase (CPE) genes by whole genome sequencing (WGS). Aztreonam-avibactam inhibited >99.9% of Enterobacterales at ≤8 mg/L. Only 3 isolates (0.01%) had an aztreonam-avibactam MIC >8 mg/L. CRE rates were 0.8%, 0.9%, and 1.1% in 2019, 2020, and 2021, respectively; 99.6% (260/261) of CRE isolates were inhibited at an aztreonam-avibactam MIC of ≤8 mg/L. CRE susceptibility to meropenem-vaborbactam decreased from 91.7% in 2019 to 83.1% in 2020 and 76.5% in 2021 (82.1% overall). CRE, multidrug-resistant, and extensively drug-resistant phenotypes were markedly higher among isolates from pneumonia compared to other infections. The most common carbapenemase among CRE was KPC (65.5% of CRE), followed by NDM (11.1%), OXA-48–like (4.6%), SME (2.3%), and IMP (1.5%). Among non-CPE–producing CRE isolates (n=44; 16.9% of CRE), 97.7% were inhibited at ≤8 mg/L of aztreonam-avibactam and 85.4% were meropenem-vaborbactam susceptible. The frequencies of MBL and OXA-48 type producers increased markedly. Aztreonam-avibactam demonstrated potent and consistent activity against Enterobacterales across infection types and over time.
Morgan Simpson, Terry Bilverstone, Jhansi Leslie, Alexandra Donlan, Md Jashim Uddin, William A Petri, Natasha Marin, Sarah Kuehne,
Published: 31 January 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad040

Abstract:
Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. While the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection. To determine the contribution of the separate components of CDT during infection, we developed strains of C. difficile expressing either CDTa or CDTb individually. We then infected both mice and hamsters with these novel mutant strains and monitored them for development of severe illness. While expression of CDTb without CDTa did not induce significant disease in a mouse model of C. difficile infection, we found that complementation of a CDT-deficient C. difficile strain with CDTb alone restored virulence in a hamster model of C. difficile infection. Overall, this study demonstrates that the binding component of C. difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection.
Maiweilidan Yimingjiang, Abudusalamu Aini, Talaiti Tuergan, Wei Zhang
Published: 31 January 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad031

Abstract:
Alveolar echinococcosis (AE) is a worldwide zoonosis caused by Echinococcus Multilocularis. AE is a severe chronic parasitic disease that exhibits a tumor-like growth, with the potential for invasion and distant metastasis; however, the molecular mechanism underlying this condition remains unclear. Transcriptome analyses were performed to detect differentially expressed genes (DEGs) in samples from patients with AE with invasion and distant metastasis. The results were further verified by immunohistochemistry. A total of 1796 DEGs were identified, including 1742 upregulated and 54 downregulated DEGs. A subsequent functional analysis showed that the significant DEGs were involved in the angiogenesis process. Immunohistochemical analysis confirmed the reliability of the transcriptomic data. These results suggest that angiogenesis is a possible mechanism underlying the tumor-like biological behavior observed during E. multilocularis infection. Genes related to this process may play important roles in AE invasion and distant metastasis.
, Laura J Rojas, Steven H Marshall, Andrea M Hujer, Anna Cmolik, Emma Marshall, Helen W Boucher, Alejandro J Vila, Maxime Soldevila, Seydina M Diene, et al.
Published: 31 January 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad014

Abstract:
Elizabethkingia anophelis is an emerging Gram-negative non-lactose fermenter in the healthcare setting where it causes life-threatening infections in immunocompromised patients. We aimed to characterize the molecular mechanisms of antimicrobial resistance and evaluate the utility of contemporary antibiotics with the intent to offer targeted therapy against an uncommonly encountered pathogen. Whole genome sequencing (WGS) was conducted to accurately identify isolate species and elucidate the determinants of β-lactam resistance. Antimicrobial susceptibility testing (AST) was performed using broth microdilution (BMD) and disk diffusion assays. To assess the functional contribution of the major metallo-β-lactamase (MBL) encoding genes to the resistance profile, blaBlaB was cloned into pBC SK (-) phagemid vector and transformed into Escherichia coli DH10B. WGS identified the organism as E. anophelis. MBL genes blaBlaB-1 and blaGOB-26 were identified, in addition to blaCME-2 which encodes for an extended-spectrum β-lactamase (ESBL). Plasmids were not detected. The isolate was non-susceptible to all commonly available β-lactams, carbapenems, newer β-lactam β-lactamase inhibitor (BL-BLI) combinations, and to the combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Susceptibility to the novel siderophore cephalosporin cefiderocol (FDC) was determined. A BlaB-1 transformant E. coli DH10B isolate was obtained and demonstrated increased MICs to cephalosporins, carbapenems, and CAZ-AVI, but not ATM. Using WGS, we accurately identified and characterized an extensively drug resistant E. anophelis in an immunocompromised patient. Rapid evaluation of the genetic background can guide accurate susceptibility testing to better inform antimicrobial therapy selection.
, John H Kimbrough, Sean DeVries, ,
Published: 27 January 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad038

Abstract:
The temporal and longitudinal trends of β-lactamases and their associated susceptibility patterns were analyzed for Escherichia coli and Klebsiella pneumoniae isolates consecutively collected in 56 U.S. hospitals during 2016-2020. Isolates (n = 19,453) were susceptibility tested by reference broth microdilution methods. Isolates that displayed MIC values ≥2 mg/L for at least two of the following compounds—ceftazidime, ceftriaxone, aztreonam, or cefepime—or resistance to the carbapenems were submitted to whole genome sequencing for identification of β-lactamases. Longitudinal and temporal trends were determined by slope coefficient. New CTX-M and OXA-1 variants were characterized. ESBLs were detected among 88.0% of the isolates that displayed elevated cephalosporin/aztreonam MICs without carbapenem resistance. blaCTX-M-15 was detected among 55.5% of the ESBL producers. ESBL rates were stable over time, but significant increases were noted among bloodstream infection and K. pneumoniae isolates, mainly driven by an increase in blaCTX-M. Carbapenem resistance and carbapenemase genes were noted among 166 and 145 isolates, respectively, including 137 blaKPC, 6 blaSME, 3 blaOXA-48-like, and 3 blaNDM. Ceftazidime-avibactam and carbapenems were very active (>99% susceptibility) against ESBL producers without carbapenem resistance. Ceftazidime-avibactam inhibited 97.0% of the carbapenem-resistant isolates. This agent and meropenem-vaborbactam inhibited 96.4% and 85.0% of the 2020 isolates, respectively. Overall, ESBL-producing isolates were stable, but an increase was noted for K. pneumoniae isolates driven by CTX-M production. CRE rates decreased in the study period. The prevalence of metallo-β-lactamases and OXA-48-like remains low. Continuous surveillance of β-lactamase-producing isolates is prudent.
Paul Amstutz, Nathan C Bahr, Karen Snyder,
Published: 27 January 2023
Open Forum Infectious Diseases; https://doi.org/10.1093/ofid/ofad043

Abstract:
Pneumocystis jiroveciipneumonia (PCP) is a serious, emerging complication of coronavirus disease 2019 (COVID-19). We describe six new cases of PCP/COVID-19 co-infection and performed a systematic review of published cases. Among our cases (n=6) and those in the literature (n=69) with available data, median age was 59 [IQR: 44-77, n=38] years, 72% (47/65) were male, and the mortality rate was 30.9% (21/68). Long-term corticosteroid use was noted in 45.1% (23/51), advanced human immunodeficiency virus (HIV) infection (defined as a CD4 count less than 200 cells per microliter (cells/mm3)) in 17.6% (9/51), and antineoplastic chemotherapy in 13.7% (7/51); consistent with known PCP risk factors. Notably, 56.7% (38/47) had verifiable risk factors for PCP (high-dose corticosteroids, immunosuppressive therapy, and HIV infection) prior to COVID-19 infection. A median absolute lymphocyte count of 0.61 x 103 cells/mm3[0.28-0.92, n=23] and a CD4 count 66 cells/mm3 [33-291.5, n=20] were also discovered among the study population. These findings suggest a need for greater attention to PCP risk factors among COVID-19 patients and consideration of PCP prophylaxis in these high-risk populations.
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