Ranganath, Nischal

AbstractBackgroundCurrent guidelines recommend immunomodulators, tocilizumab or baricitinib, for the management of severe coronavirus disease‐2019 (COVID‐19) in patients with increasing oxygen requirements. Given their immunosuppressive effects, there is a concern for higher rates of infection among transplant recipients.MethodsA retrospective cohort study of transplant patients with severe COVID‐19 between April 2020 and January 2022 was performed at the Mayo Clinic. The primary outcome was incidence of secondary infections after COVID‐19 diagnosis. Secondary outcomes were 90‐day mortality, ventilatory days, and thromboembolic events.ResultsA total of 191 hospitalized transplant patients were studied, including 77 (40.3%) patients who received an immunomodulator. Overall, 89% were solid organ transplant recipients, with kidney as the most common transplanted organ (50.3%). The majority (89.0%) required oxygen supplementation on admission, and 39.8% of these patients required mechanical ventilation during the hospital course. There was no significant difference in the incidence of secondary infections between those who received or did not receive an immunomodulator (p = .984). Likewise, there was no difference in 90‐day mortality between patients who received or did not receive an immunomodulator (p = .134). However, higher mortality was observed among patients that developed a secondary infection (p < .001).ConclusionThe use of immunomodulators in transplant patients with severe COVID‐19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all‐cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID‐19. image

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.

Abstract Background 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.

Abstract Background 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.

Abstract Background 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.

Abstract Background 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.

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.

Abstract In a cohort of 483 high-risk patients treated with nirmatrelvir/ritonavir for COVID-19, 2 patients (0.4%) required hospitalization by day 30. Four patients (0.8%) experienced rebound of symptoms, which were generally mild, at a median of 9 days after treatment, and all resolved without additional COVID-19–directed therapy.

AbstractBackgroundCryptococcus spp. infection involving the central nervous system (CNS) is associated with poor outcomes. Current guidelines recommend repeating a cerebrospinal fluid (CSF) fungal culture after 2 weeks of treatment to evaluate for clearance. However, this practice has not clearly been associated with outcomes.ObjectivesWe sought to assess the relationship between CSF fungal clearance at 2 weeks and 12‐month mortality in patients with CNS cryptococcosis.MethodsThis is a retrospective cohort study from 2011 to 2020 of patients with CNS cryptococcosis. Factors associated with 12‐month mortality were assessed with Fisher’s exact test for categorical variables and Mann–Whitney test for continuous variables.ResultsAmong 51 patients with CNS cryptococcosis, 42 (82.4%) were initially CSF culture positive. Among 27 patients with follow‐up CSF culture at 2 weeks, 6 (22.2%) had a positive result. Factors associated with a positive CSF culture at 2 weeks were an initial CSF cryptococcal antigen titre ≥1:2560, fungaemia, and an elevated intracranial pressure requiring therapeutic lumbar punctures. The 12‐month mortality rate was 33.3%, and this was significantly associated with baseline fungaemia, extra‐CNS cryptococcal involvement and requirement of intensive care unit level of care. Lack of CSF culture clearance by 2 weeks was not associated with 12‐month mortality.ConclusionsCNS cryptococcosis has a high mortality rate. A markedly elevated CSF cryptococcal antigen, and opening CSF pressure was associated with lack of CSF culture clearance at 2 weeks of treatment. Severe disseminated disease and cryptococcemia were associated with 12‐month mortality.