Shah, Aditya

Abstract Background Antimicrobial resistance (AMR) is a threat to healthcare, and infections with antimicrobial resistant organisms carry significant morbidity and mortality. Owing to high rates of AMR, the Centers for Disease Control and Prevention listed Acinetobacter baumannii as a top priority pathogen for research and development of new antimicrobial agents. Antimicrobial susceptibility testing is challenging for this organism, and susceptibility profiles are variable, leading to need of a potential guidance document with assistance in selecting effective empiric therapeutic regimens. Methods We retrospectively reviewed the microbiology and antimicrobial susceptibility testing (AST) results for Acinetobacter spp. from blood culture isolates submitted to Mayo Clinic Laboratories from December 2012 to 2022. AST was performed using agar dilution and interpretations following Clinical & Laboratory Standards Institute (CLSI) guidelines. Isolates were identified by MALDI mass spectrometry and/or 16S sequencing, as available (Figure 1).Figure 1:Isolate identification Isolate identification description. Isolates were analyzed based on this classification used in out laboratory. Results 804 blood culture isolates were included. A. baumannii/calcoaceticus complex (27%) was most frequently isolated, followed by A. lwoffii (22%), and showed the highest resistance across all antimicrobials (73% susceptible or below) (Figure 2). A. baumannii/calcoaceticus complex showed rising resistance rates over time from 2012 to 2022 for meropenem, minocycline and ampicillin-sulbactam (Figure 3). Cefiderocol non-susceptible rate was 35% for A. baumannii/calcoaceticus complex.Figure 2:Antimicrobial susceptibility profiles for Acinetobacter spp. Description of susceptibility profiles for Acinetobacter spp. isolates, based on the classification used by our laboratory. Antimicrobials are presented at the top and isolates on the left. Number of isolates analyzed are presented in the table with the percentage of the isolates susceptible to each antibiotic class in parenthesis.Figure 3:Acinetobacter baumannii/calcoaceticus complex isolates and resistance, trend Trend of isolates per year and resistance percentage to meropenem, colistin, minocycline and amp-sulb. Number of isolates per year at the base of each bar; percentage of resistance for antimicrobials expressed on lines. Amp-sulb = ampicillin-sulbactam. Conclusion A. baumannii/calcoaceticus complex showed high levels of resistance ( >75%) across multiple antimicrobials and increasing rates of resistance over time from 2012 to 2022. A high number of cefiderocol non-susceptible organisms is also concerning (Figure 2). Disclosures Audrey N. Schuetz, MD, Merck: Advisor/Consultant

Abstract Background Catheter-related bloodstream infection (CRBSI) is an important complication of long-term central venous catheters (CVCs) and is associated with high morbidity and cost. While line removal is optimal, it is not always feasible and is not without complications. Antibiotic lock therapy (ALT) may be an alternative strategy for line salvage, but the efficacy of this approach particularly among immunocompromised hosts is unknown. Methods We retrospectively reviewed adult patients with CRBSI managed with ALT between 2018 and 2022 at our tertiary medical center. We reviewed patient comorbidities, type and indications for CVC use, microbiology of CRBSI, ALT, and use of systemic antibiotics. Outcomes included 30-day mortality, 90-day microbiologic relapse (with same bacteria as index case), 90-day recurrent BSI (with different bacteria from index case), and adverse events. Results 86 patients were reviewed, a majority of whom were immunocompromised (91%) due to hematopoietic stem cell transplantation (85%) and thrombocytopenic (platelet count 36; IQR 17-112). 78% had tunneled CVC for indications including peri-transplant therapy (72%), chemotherapy (15%), and TPN (6%) (Table 1). The median time to CRBSI following CVC insertion was 45 days (IQR 19-86). Infections were frequently monomicrobial (80%) due to Gram-positive organisms (n=75) including coagulase-negative staphylococci and Enterococcus spp. The minority of Gram-negative (n=17) infections were due to E coli and Enterobacter spp. 94% of patients received systemic antibiotics and all patients received ALT for a median of 11 days [IQR 6-15] and 11.5 days [IQR 6-14], respectively (Table 2). The 30-day attributable mortality rate was low at 1%. Rates of 90-day microbiologic relapse (20%) and recurrent BSI (16%) were high, occurring at a median of 42 days (IQR 12-55) and 35 days (IQR 25-50) following completion of ALT, respectively (Table 3). Conclusion Despite high rates of microbiologic relapse and recurrent BSI, ALT may be an effective line salvage strategy extending the use of CVC by up to 30 days with minimal impact on mortality even among immunocompromised patients. Disclosures John C. O'Horo, Sr., MD, MPH, Janssen Pharmaceuticals.: Grant/Research Support|nference: Grant/Research Support

Abstract Background Rhodococcus spp. are a zoonotic, Gram-positive coccobacilli that cause pulmonary and disseminated disease in immunocompromised patients. Rhodococcus infection is associated with high morbidity and mortality and treatment can be challenging due to intrinsic resistance to several antibiotics. There is limited data on antibiotic susceptibility patterns and clinical characteristics of infection in humans. Methods We retrospectively evaluated the microbiology and antibiotic susceptibility testing (AST) of Rhodococcus isolates submitted to our medical reference laboratory between June 2012 and 2022. Identification (ID) was performed by Sanger 16S rRNA gene sequencing or MALDI-TOF mass spectrometry. AST was performed by microbroth dilution. We also reviewed the clinical characteristics, management, and outcomes of patients managed at our local academic medical center. Results Over a 10-year period, 322 isolates of Rhodococcus spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources. R equi/hoagii and R corynebacteriodes were the most frequently isolated species, with 19% of isolates only identified to genus level (Figure 1). 199 isolates were evaluated for AST, with high rates of resistance to cephalosporins and aminoglycosides. Optimal antibiotics based on AST included imipenem, vancomycin, linezolid, clarithromycin, and TMP-SMX. Discordance in susceptibility was noted between ciprofloxacin (62%) and moxifloxacin (94%) (Table 1). Ten clinical cases of Rhodococcus infection were identified. Eight patients were immunocompromised with 6 having pulmonary and 3 with extra-pulmonary disease. Significant variability in choice and duration of therapy was noted, but all patients had positive treatment response with minimal complications (Table 2). Conclusion This study demonstrates high rates of resistance among Rhodococcus isolates with need for accurate ID and AST to guide effective treatment of infection among immunocompromised patients. Disclosures Nancy Wengenack, PhD, Mayo Clinic Laboratories: Employee

Abstract Background 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.

Abstract Objectives Whipple’s disease (WD) results from infection of the bacteria Tropheryma whipplei (TW). This disease is characterized by macrophage infiltration of intestinal mucosa and primarily affects Caucasian males. Genetic studies of host susceptibility are scarce. Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is an innate immune sensor, resides mainly in monocytes/macrophages and contributes to defence against infection and inflammatory regulation. NOD2 mutations are associated with autoinflammatory diseases. We report the association of NOD2 mutations with TW and WD for the first time. Methods A multicentre, retrospective study of three patients with WD was conducted. Patients received extensive multidisciplinary evaluations and were cared for by the authors. NOD2 and its association with infection and inflammation were schematically represented. Results All patients were Caucasian men and presented with years of autoinflammatory phenotypes, including recurrent fever, rash, inflammatory arthritis, gastrointestinal symptoms and elevated inflammatory markers. All patients underwent molecular testing using a gene panel for periodic fever syndromes and were identified to carry NOD2 mutations associated with NOD2-associated autoinflammatory disease. Despite initially negative gastrointestinal evaluations, repeat endoscopy with duodenal tissue biopsy ultimately confirmed WD. After initial ceftriaxone and maintenance with doxycycline and/or HCQ, symptoms were largely controlled, though mild relapses occurred in follow-up. Conclusion Both NOD2 and TW/WD are intensively involved in monocytes/macrophages. WD is regarded as a macrophage disease. NOD2 leucin-rich repeat–associated mutations in monocytes/macrophages cause functional impairment of these cells and consequently may make the host susceptible for TW infection and WD, especially in the setting of immunosuppression.

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010–2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5–647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87–17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18–5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI.

AbstractBackgroundIn the management of Gram‐negative bloodstream infection (GN‐BSI), short antimicrobial courses have been increasingly demonstrated to be non‐inferior to prolonged therapy, with lower risk of Clostridioides difficile infection (CDI) and emergence of multi‐drug resistant (MDR) organisms. However, immunocompromised hosts were excluded from these studies. We investigated outcomes of short (≤10 days), intermediate (11–14 days), and prolonged (≥15 days) antimicrobial durations for GN‐BSI in neutropenic patients.MethodsA retrospective cohort study was conducted on neutropenic patients with monomicrobial GN‐BSI between 2018 and 2022. The primary outcome was a composite of all‐cause mortality and microbiologic relapse within 90 days after therapy completion. The secondary outcome was a composite of 90‐day CDI and development of MDR‐GN bacteria. Cox regression analysis with propensity score (PS) adjustment was used to compare outcomes between the three groups.ResultsA total of 206 patients were classified into short (n = 67), intermediate (n = 81), or prolonged (n = 58) duration. Neutropenia was predominantly secondary to hematopoietic stem cell transplantation (48%) or hematologic malignancy (35%). The primary sources of infection included intra‐abdominal (51%), vascular catheter (27%), and urinary (8%). Most patients received definitive therapy with cefepime or carbapenem. No significant difference in the primary composite endpoint was observed for intermediate versus short (PS‐adjusted hazard ratio [aHR] 0.89; 95% confidence interval [95% CI] 0.39–2.03) or prolonged versus short therapy (PS‐aHR 1.20; 95% CI 0.52–2.74). There was no significant difference in the secondary composite endpoint of CDI or MDR‐GN emergence.ConclusionOur data suggest that short antimicrobial courses had comparable 90‐day outcomes as intermediate and prolonged regimens for GN‐BSI among immunocompromised patients with neutropenia. 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 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.