Ranganath, Nischal

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 Human granulocytic anaplasmosis (HGA) is an emerging tick-borne illness endemic to the northeastern and midwestern United States. Risk factors for the severity of infection, predictors for hospitalization, temporal trends, co-infections, and outcomes are poorly studied. Methods We conducted a retrospective review of HGA at Mayo Clinic, Rochester, between 2011-2021. Cases were identified by positive Anaplasma PCR at our reference laboratory. Variables included patients’ characteristics, symptoms, risk factors for tick-borne illness, laboratory parameters, co-infections, treatment, and clinical outcomes. Results We identified 471 cases with a positive Anaplasma PCR, and 146 cases were included in this interim analysis. Table 1 shows a summary of the baseline characteristics. An increasing annual trend in diagnosis of HGA was noted from 2014 to 2016 with lower rates observed during COVID-19 pandemic (2020 to 2022) (Figure 1). Of the 146 patients, 19 (13%) were immunocompromised secondary to hematologic malignancies, solid organ malignancies, and pharmacological immunosuppression. Frequently reported symptoms included fever (79.5%), malaise (68.5%), chills (51.4%), and myalgia (50%). Tick exposure was documented in 79.2 % of cases. Forty-seven (33%) patients were hospitalized; older patients were more likely to be hospitalized (Table 2). The most common complications among the hospitalized patients included respiratory failure (50%), encephalopathy (44.4%) and renal failure (37.5%). One patient required ICU admission. Twenty-five patients (17.5%) and one patient (0.7%) were co-infected with Lyme and Ehrlichiosis, respectively. Higher rates of leukopenia and thrombocytopenia were associated with mono-infection with Anaplasma (p < 0.001). Follow up data was available for 136 patients; all of them had favorable response to doxycycline.Table 1:Summary of baseline characteristics, labs and treatment.Table 2:Predictors of HospitalizationFigure 1:Annual Trends in Anaplasmosis from 2011-2021. Conclusion Our study demonstrated comprehensive clinical characteristics of patients with HGA. Interestingly, tick exposure history was common, yet most patients did not have other tick-borne co-infections. Furthermore, only a minority of patients developed severe diseases and required hospitalization. The recent decline in cases during the early part of the COVID-19 pandemic is worth further investigation. Disclosures All Authors: No reported disclosures

Abstract Background Urinary tract infections (UTIs) caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) have become increasingly challenging to manage due to the limited number of available effective oral agents. Minocycline, a second-generation tetracycline with a broad antimicrobial spectrum and reasonable urinary concentration, has recently gained attention as a potential treatment option for MDR-GNB UTIs. In this study, we aim to review the in vitro minocycline susceptibility against a wide spectrum of urinary GNB isolates performed at our reference lab. Methods We conducted a retrospective review of all minocycline susceptibility testing performed on urinary GNB isolates performed at the Mayo Clinic reference lab between 2013-2022. We stratified our results for different species based on phenotypic resistance profiles as well as known species-specific resistance association. Results During the study timeframe, we identified 28,388 GNB isolates that underwent minocycline susceptibility testing. Among the Escherichia coli (E.Coli) isolates resistant to ceftriaxone, ciprofloxacin, or meropenem, minocycline susceptibility was noted to be 78%, 46%, 76%, respectively (Fig 1). Among the Klebsiella pneumonia (KP) isolate resistant to ceftriaxone, ciprofloxacin, or meropenem, minocycline susceptibilities were 47%, 40%, and 53% respectively (Fig 1). Among the high risk Amp-C group Citrobacter freundii, Enterobacter Cloacae and Klebsiella aerogenes, minocycline susceptibility rate was noted to be 87%, 77%, and 89%, respectively (Fig 2). Finally, among the isolate group of non-fermenters including Achromobacter spp, Acinetobacter spp & Stenotrophomonas spp, susceptibility rates were noted to be 65%, 94%, and 100%, respectively (Fig 3). Conclusion Minocycline showed in vitro activity against many hard to treat GNB urinary isolates, including ceftriaxone and meropenem resistant E.coli & KP isolates. High-risk Amp-C producing GN species & some of the less common GN including Stenotrophomonas, Acinetobacter, and Achromobacter. Disclosures All Authors: No reported disclosures

Abstract Background Achromobacter spp. are important pathogens that are most frequently implicated in opportunistic infections, especially in patients with chronic lung disease, malignancy, and solid organ or hematopoietic stem cell transplantations. They commonly cause pneumonia, bacteremia, and device-associated infections. Intrinsic and acquired resistance mechanisms usually complicate treatment. Further characterization of the changing antibiotic susceptibilities and clinical manifestations of Achromobacter spp. are needed to improve clinical practice. Methods We performed a retrospective review of Achromobacter isolates from 2013 to 2023 in the Mayo Clinic Enterprise with available antimicrobial susceptibility testing (AST) data. Variables included sample source, collection date, and AST by agar dilution with susceptibility defined according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. Samples were categorized into quartiles based on collection date and grouped into source types (respiratory, genitourinary, etc.) and AST. Results A total of 1,506 patients were identified with a total of 1,546 unique Achromobacter spp. isolates from 2013 - 2023. The most common species was A. xylosoxidans, encompassing 40.1% of all isolates (Table 1). Respiratory samples (sputum, bronchoalveolar lavage) were the most common source (57.5%), followed by musculoskeletal and soft tissue (16.4%), genitourinary (12.2%), and oropharyngeal sources (10.3%). AST from 2013 to 2023 showed persistent high levels of resistance to aztreonam and tetracycline, with stable susceptibility to piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and carbapenems (Table 2). Over our 10-year analysis, there was increased resistance to aminoglycosides, fluoroquinolones, ceftazidime, and cefepime.Table 1.Achromobacter Species Identification and Isolate Percentage (%) Stratified by Year Table 1 lists the Achromobacter species identified stratified by the year each sample was collected. Each value represents the number of isolates that were identified as the listed Achromobacter species, with "Achromobacter sp." indicating an isolate without species identification. Percentages of species are listed in parentheses (%). Sample totals are listed in the right column.Table 2.Antibiotic Susceptibility of All Tested Achromobacter Isolates (Percentage of Susceptible Isolates) Table 2 lists antibiotics by class, stratified by year that Achromobacter isolates were tested. Each value is the total number of isolates tested for antimicrobial susceptibility, followed by the percentage of susceptible isolates in parentheses (%). Total isolates tested and overall susceptibility percentage is also listed over the 10-year period. Conclusion Achomobacter continues to be a clinically significant organism with a complex resistance profile. Our dataset shows a significant prevalence of non-respiratory and non-genitourinary samples, in addition to increasing resistance over many antibiotic classes. Our data suggests that piperacillin-tazobactam, imipenem, and minocycline are appropriate empiric regiments for Achromobacter. Disclosures All Authors: No reported disclosures

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.

The prevalence of invasive candidiasis caused by non-Candida albicans has rapidly increased. Candida glabrata (Nakaseomyces glabrata) is an important pathogen associated with substantial mortality. Our study examined the antifungal temporal susceptibility of C. glabrata and cross-resistance/non-wild-type patterns with other azoles and echinocandins. Laboratory data of all adult patients with C. glabrata isolated from clinical specimens at the Mayo Clinic, Rochester, from 2012 to 2022 were collected. Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used. We obtained 1046 C. glabrata isolates from 877 patients. Using CLSI and EUCAST breakpoints, 187 (17.9%) isolates and 256 (24.5%) isolates were fluconazole-resistant, respectively. Focusing on C. glabrata bloodstream infections, fluconazole-resistance ranged from 16 to 22%. Among those 187 fluconazole-resistant isolates, 187 (100%) and 184 (98.4%) isolates were also voriconazole and posaconazole non-wild-type, respectively, with 97 (51.9%) isolates deemed non-wild type for itraconazole. The fluconazole susceptibility pattern has not changed over the past decade. The proportion of fluconazole-resistant C. glabrata is relatively high, which could be due to the complexity of patients and fluconazole exposure. Itraconazole appears to be a compelling step-down therapy for fluconazole-resistant C. glabrata, given the high proportion of wild-type isolates. Further research to examine clinical outcomes is warranted.

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