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  • 1
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    Online Resource
    Leptotrichia Bacteremia: 10-Year Retrospective Clinical Analysis and Antimicrobial Susceptibility Profiles
    American Society for Microbiology ; 2023
    In:  Journal of Clinical Microbiology Vol. 61, No. 2 ( 2023-02-22)
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 61, No. 2 ( 2023-02-22)
    Abstract: Leptotrichia species are anaerobic, Gram-negative bacilli increasingly recognized as pathogens capable of causing invasive infections such as bloodstream infection (BSI), particularly among immunocompromised patients. However, there is a paucity of data regarding epidemiology, antimicrobial susceptibility, optimal treatment, and clinical outcomes among patients with Leptotrichia bacteremia. Patient risk factors, treatment approaches, and outcomes of a retrospective cohort of adult patients with Leptotrichia BSI at a tertiary medical center (Mayo Clinic Rochester [MCR]) were evaluated. Concurrently, species, temporal trends, and antimicrobial susceptibility testing (AST) results of Leptotrichia isolates submitted to a reference laboratory (Mayo Clinic Laboratories) over the past 10 years were examined. We identified 224 blood culture isolates of Leptotrichia species, with 26 isolates from patients treated at MCR. The most frequent species included L. trevisanii (49%), L. buccalis (24%), and L. wadei (16%). Leptotrichia species demonstrated 〉 90% susceptibility to penicillin, metronidazole, ertapenem, and piperacillin-tazobactam. However, 96% (74/77) of isolates were resistant to moxifloxacin. For patients treated at MCR, the mean patient age was 55 years (standard deviation [SD], 17), with 9 females (35%), and all were neutropenic at the time of BSI. The primary sources of infection were gastrointestinal (58%), intravascular catheter (35%), and odontogenic (15%). Patients were treated with metronidazole (42%), piperacillin-tazobactam (27%), or carbapenems (19%). The mean duration of treatment was 11 days (SD, 4.5), with a 60-day all-cause mortality of 19% and no microbiologic relapse. Leptotrichia species are rare but important causes of BSI in neutropenic patients. Due to evolving antimicrobial susceptibility profiles, a review of AST results is necessary when selecting optimal antimicrobial therapy.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/jcm.01733-22
    RVK:
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 1498353-9
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  • 2
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    1801. LVAD antimicrobial prophylaxis and infections, a 12-year experience
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: The incidence of end-stage heart failure necessitating advanced cardiac therapy continues to increase in the United states. Implantable left ventricular assist devices (LVADs) represent an important modality that is utilized both as a bridge to heart transplant or as destination therapy. LVAD-associated infections, ranging from driveline exit site or pocket infections to endovascular infections, are a major complication with high mortality. Antibiotic prophylaxis at time of LVAD implantation is therefore an important strategy to mitigate infections. However, a clear surgical infection prophylaxis regimen and associated outcomes have not been reported. Methods We performed a single center, retrospective cohort study evaluating the impact of antimicrobial prophylaxis on risk of infection in patients who underwent LVAD implantation between February 2007 and June 2019 at Mayo Clinic. LVAD-specific and related infections were defined according to the International Society of Heart Lung Transplantation criteria. Single drug prophylaxis (SDP) included cefazolin only, vancomycin only, or cefazolin and vancomycin; multidrug (MDP) regimen includes either of the SDP regimens plus another antibiotic. We compared incidence of infection within 90-day and within one-year of implantation, as well as risk of C. difficile infections between the SDP and MDP cohorts. Results We reviewed 403 patients who received LVAD implantation (Table 1), 402 of had information on surgical prophylaxis. 307 (76%) patients received SDP and 95 patients (24%) received MDP. 14 patients developed an infection within 1 year of implantation (Table 2). There was no difference in the incidence of infections between SDP and MDP arms both at 90 days and 1-year post-implantation (p=0.11). The median time of infection since LVAD implantation was similar between SDP and MDP (p=0.37) arms. Incidence of C. difficile infection was not different between groups (p=0.10) (Table 3). Conclusion There was no significant difference in incidence or time to first infection, within 90-day and 1-year of implantation, between single- and multidrug antibiotic surgical prophylaxis regimens administered at the time of LVAD implantation. Future prospective trials are needed to develop a clear LVAD antibiotic prophylaxis protocol. Disclosures John C. O'Horo, Sr., MD, MPH, Bates college: Advisor/Consultant|MITRE corporation: Grant/Research Support|nferenec, Inc: Grant/Research Support.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.1431
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 3
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    Comparing Complication Rates of Midline Catheter vs Peripherally Inserted Central Catheter. A Systematic Review and Meta-analysis
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases Vol. 10, No. 2 ( 2023-02-03)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 2 ( 2023-02-03)
    Abstract: Peripherally inserted central catheters (PICCs) and midlines are commonly used devices for reliable vascular access. Infection and thrombosis are the main adverse effects of these catheters. We aimed to evaluate the relative risk of complications from midlines and PICCs. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. The primary outcomes were catheter-related bloodstream infection (CRBSI) and thrombosis. Secondary outcomes evaluated included mortality, failure to complete therapy, catheter occlusion, phlebitis, and catheter fracture. The certainty of evidence was assessed using the GRADE approach. Results Of 8368 citations identified, 20 studies met the eligibility criteria, including 1 RCT and 19 observational studies. Midline use was associated with fewer patients with CRBSI compared with PICCs (odds ratio [OR], 0.24; 95% CI, 0.15–0.38). This association was not observed when we evaluated risk per catheter. No significant association was found between catheters when evaluating risk of localized thrombosis and pulmonary embolism. A subgroup analysis based on location of thrombosis showed higher rates of superficial venous thrombosis in patients using midlines (OR, 2.30; 95% CI, 1.48–3.57). We did not identify any significant difference between midlines and PICCs for the secondary outcomes. Conclusions Our findings suggest that patients who use midlines might experience fewer CRBSIs than those who use PICCs. However, the use of midline catheters was associated with greater risk of superficial vein thrombosis. These findings can help guide future cost-benefit analyses and direct comparative RCTs to further characterize the efficacy and risks of PICCs vs midline catheters.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofad024
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 4
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    755. Predictors of Mortality in Invasive Mold Infections Among Patients with Hematologic Malignancies and Hematopoietic Stem Cell Transplant Recipients
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Invasive Mold Infections (IMI) cause significant morbidity and mortality, particularly in patients with hematologic malignancies (HM) and hematopoietic stem cell transplant (HSCT) recipients. Although the risk has significantly decreased with the use of triazole agents as primary prophylaxis, breakthrough infections still occur. Risk factors for IMI have been well-described. Limited data exist on factors predicting mortality. Methods We identified cases using the Cancer registry and Microbiology data at Mayo Clinic Minnesota from 11/19/2011–8/6/2021 and Mayo Clinic Arizona and Florida from 09/13/2017–11/19/2021. We conducted a retrospective review to identify cases of proven/probable IMI per EORTC/MSG criteria. Patients who received at least 7 days of anti-mold prophylaxis were considered having breakthrough infection (Br-IMI). Survival function was estimated using the Kaplan-Meier method. We evaluated predictors of mortality using Cox regression analysis. Results 401 cases of IMI were included (80.2% aspergillosis, 10.2% fusariosis, 8.4% mucormycosis, 1.2% scedosporiosis). 189 patients had proven/probable and 212 had possible disease. 12-week mortality for the entire cohort was 33%. There were 87 cases of Br-IMI (21.6%) on mold-active prophylaxis (posaconazole n=54, voriconazole n=26, isavuconazole n=5, itraconazole n=1, liposomal amphotericin B n=1). A comparison between patients not receiving prophylaxis and those with Br-IMI is shown in Table 1. Higher proportion of patients with Br-IMI had prolonged neutropenia/lymphopenia and graft-versus-host disease involving the gastrointestinal tract or lungs. Positive Aspergillus galactomannan (index ≥ 1.0) was seen more in patients who were not on mold-active prophylaxis. Mortality was 31.5% in patients not receiving prophylaxis and 41.3% with Br-IMI (Figure 1). In multivariate analysis, age, prolonged neutropenia, active HM, Br-IMI and HSCT were associated with increased mortality (Table 2). Conclusion In this cohort, the rate of Br-IMI was significant despite the use of primary prophylaxis (mainly posaconazole). Mortality was higher in patients with Br-IMI compared to those not receiving mold-active prophylaxis. Therefore, clinicians should remain alert to the possibility of Br-IMI. Disclosures Paschalis Vergidis, MD, AbbVie: DSMB|Cidara: Grant/Research Support|Scynexis: Grant/Research Support.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.040
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 5
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    Left Ventricular Assist Device: Review of Antimicrobial Prophylaxis Strategies and Incidence of Infections at a Tertiary Care Center 12-Year Experience
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases Vol. 10, No. 9 ( 2023-09-01)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 9 ( 2023-09-01)
    Abstract: Left ventricular assist devices (LVAD) have an associated infection rate of 13%–80% postimplant. An optimal strategy for surgical infection prophylaxis (SIP) at the time of implantation has not been well defined. We aimed to evaluate the different LVAD implantation antibiotic prophylaxis regimens as well as the incidence of LVAD infection at our institution. Methods We performed a single-center, retrospective study of patients who underwent LVAD implantation between February 2007 and June 2019. The primary outcome was the incidence of LVAD infection (LVADI), within 3 months and 1 year of placement, between patients who received expanded or narrow-spectrum regimens for SIP. We assessed outcomes using Kaplan-Meier, time-to-first event. We used a noninferiority analysis, which was established if the narrow-spectrum event rate was no more than 5% greater than the expanded-spectrum event rate. Results We included 399 patients, 305 (76.4%) patients received narrow-spectrum SIP, whereas the remaining 94 (23.6%) patients received the expanded-spectrum regimen. Statistical noninferiority of the narrow spectrum to the multiple drug regimen was demonstrated at both time points, and statistical superiority of the narrow-spectrum group across 12-month follow up was further evident (P = .037). Conclusions We report evidence supporting noninferiority, or even superiority, of the narrow-spectrum over expanded-spectrum antimicrobial prophylaxis strategy with respect to LVADI. These findings support data-driven antimicrobial prophylaxis strategies.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofad465
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 6
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    Impairment of the type I interferon response by HIV-1: Potential targets for HIV eradication
    Elsevier BV ; 2017
    In:  Cytokine & Growth Factor Reviews Vol. 37 ( 2017-10), p. 1-16
    Details
    In: Cytokine & Growth Factor Reviews, Elsevier BV, Vol. 37 ( 2017-10), p. 1-16
    Type of Medium: Online Resource
    ISSN: 1359-6101
    URL: Article
    DOI: 10.1016/j.cytogfr.2017.04.004
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2025966-9
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  • 7
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    The Oncolytic Virus MG1 Targets and Eliminates Cells Latently Infected With HIV-1: Implications for an HIV Cure
    Oxford University Press (OUP) ; 2018
    In:  The Journal of Infectious Diseases Vol. 217, No. 5 ( 2018-02-14), p. 721-730
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 217, No. 5 ( 2018-02-14), p. 721-730
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jix639
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1473843-0
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  • 8
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    HIV-Infected Macrophages Are Infected and Killed by the Interferon-Sensitive Rhabdovirus MG1
    American Society for Microbiology ; 2021
    In:  Journal of Virology Vol. 95, No. 9 ( 2021-04-12)
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 95, No. 9 ( 2021-04-12)
    Abstract: The use of unique cell surface markers to target and eradicate HIV-infected cells has been a longstanding objective of HIV-1 cure research. This approach, however, overlooks the possibility that intracellular changes present within HIV-infected cells may serve as valuable therapeutic targets. For example, the identification of dysregulated antiviral signaling in cancer has led to the characterization of oncolytic viruses capable of preferentially killing cancer cells. Since impairment of cellular antiviral machinery has been proposed as a mechanism by which HIV-1 evades immune clearance, we hypothesized that HIV-infected macrophages (an important viral reservoir in vivo ) would be preferentially killed by the interferon-sensitive oncolytic Maraba virus MG1. We first showed that HIV-infected monocyte-derived macrophages (MDM) were more susceptible to MG1 infection and killing than HIV-uninfected cells. As MG1 is highly sensitive to type I interferons (IFN-I), we then investigated whether we could identify IFN-I signaling differences between HIV-infected and uninfected MDM and found evidence of impaired IFN-α responsiveness within HIV-infected cells. Finally, to assess whether MG1 could target a relevant, primary cell reservoir of HIV-1, we investigated its effects in alveolar macrophages (AM) obtained from effectively treated individuals living with HIV-1. As observed with in vitro -infected MDM, we found that HIV-infected AM were preferentially eliminated by MG1. In summary, the oncolytic rhabdovirus MG1 appears to preferentially target and kill HIV-infected cells via impairment of antiviral signaling pathways and may therefore provide a novel approach to an HIV-1 cure. IMPORTANCE Human immunodeficiency virus type 1 (HIV-1) remains a treatable, but incurable, viral infection. The establishment of viral reservoirs containing latently infected cells remains the main obstacle in the search for a cure. Cure research has also focused on only one cellular target of HIV-1 (the CD4 + T cell) while largely overlooking others (such as macrophages) that contribute to HIV-1 persistence. In this study, we address these challenges by describing a potential strategy for the eradication of HIV-infected macrophages. Specifically, we show that an engineered rhabdovirus — initially developed as a cancer therapy — is capable of preferential infection and killing of HIV-infected macrophages, possibly via the same altered antiviral signaling seen in cancer cells. As this rhabdovirus is currently being explored in phase I/II clinical trials, there is potential for this approach to be readily adapted for use within the HIV-1 cure field.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01953-20
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
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  • 9
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    Karius With a Q: Role for Microbial Cell-Free DNA Next-Generation Sequencing in Diagnosis of Acute Q Fever
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases Vol. 10, No. 1 ( 2023-01-04)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 1 ( 2023-01-04)
    Abstract: The diagnosis of Q fever can be challenging and a high index of suspicion is necessary. Within this case series, we highlight the utility of the microbial cell-free DNA next-generation sequencing or Karius Test in the timely diagnosis and management of acute Q fever.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac666
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 10
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    2118. Patient Characteristics and Clinical Outcomes of Leptotrichia spp. Bacteremia
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Leptotrichia spp. are anaerobic, gram-negative bacilli that are part of the normal oral and intestinal microbiota. Although traditionally considered non-pathogenic, these bacteria can result in invasive infections including bacteremia in immunosuppressed patients, particularly those with neutropenia. There are limited published data to inform best management strategies in those with Leptotrichia bacteremia. Methods All cases of Leptotrichia spp. bacteremia between January 2012 and 2022 at our tertiary academic medical center were retrospectively reviewed to determine patient risk factors, clinical outcomes, and antimicrobial susceptibilities. Descriptive statistical methods were used. Antimicrobial susceptibilities were performed by agar dilution. Results 26 cases of Leptotrichia spp. bacteremia were identified (Figure 1). The mean patient age was 55 years (SD 17), with 9 female patients (35%). All 26 patients were immunocompromised, predominantly due to hematologic malignancy (69%) or hematopoietic stem cell transplant (23%) (HSCT). 25 of 26 patients were actively neutropenic, with a median duration of neutropenia of 21 days (13-26) (Table 1). The most frequent sources of Leptotrichia bacteremia were gastrointestinal translocation (60%), followed by catheter-related infection (35%). 10 patients had polymicrobial bacteremia (38.5%). The primary antibiotics utilized to treat Leptotrichia bacteremia included metronidazole (42%), piperacillin-tazobactam (27%), and carbapenems (19%). Overall, the mean duration of treatment was 11 days, with a 60-day all-cause mortality of 19% (Table 1) with no cases of microbiologic relapse. In the 22 clinical isolates evaluated for susceptibility, Leptotrichia spp. were largely susceptible to metronidazole, penicillin, ertapenem, and piperacillin-tazobactam, but uniformly resistant to moxifloxacin (Table 2). Figure 1:Leptotrichia spp. identified as cause of bacteremia in 26 patientsTable 1:Baseline characteristics of patients with Leptotrichia bacteremia (n=26) between January 2012 to January 2022Table 2:Antimicrobial susceptibility profile of the Leptotrichia spp. (n=22) Conclusion Leptotrichia spp. may be a rare cause of bacteremia in neutropenic hosts, particularly those with underlying hematologic malignancies and HSCT. The pathogen has a favorable susceptibility profile to penicillins and carbapenems, but has high degree of resistance to fluoroquinolones. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.1739
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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