bluuebunny/crossref_metadata_2025 huggingface dataset:
2723. High Mortality and Resistance in Patients with Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections (MBI-LCBI)
Authors: Salazar Grace Johanna , Reyes Flavio , Salgado Johana , Galarza Margarita , Peralta Amy
Published: November 2023

Background

Since its definition, MBI-LCBI is a pathology increasingly studied and frequent, however, with the growing threat of multidrug resistance (MDR), it is very important to have pharmacological resources for the treatment and local epidemiology. The economic constraints that many institutions suffer in lower middle-income countries may result in worse outcomes in MBI-LCBI and carbapenem-resistant Enterobacteriaceae (CRE) patients. In Ecuador, only ceftazidime/avibactam is available for the CRE treatment, and it is not considered in the Ecuadorian National formulary (EFN), that means it is not available in public health institutions.

Methods

A retrospective study was conducted in two cancer reference hospitals in Ecuador, from January 2019 to December 2021. All patients with MBI-LCBI according to CDC criteria were included. Demographic, diagnostic, and microbiological isolation data were collected. Strains identification and susceptibility were performed on Vitek 2 system and Kirby Bauer, following CLSI 2022 recommendations and cut-off points. The CRE resistance mechanism was confirmed by PCR. Thirty-day episode mortality was assessed, and compared between susceptible and MDR cases. Data are shown with means, and Chi-Square test was used to evaluate differences between mortality. SPSS version 25 was used.

Results

148 episodes of MBI-LCBI in cancer patients were detected. Figure 1 shows etiology and susceptibity of strains. Sixty one (41.3%) MBI-LCBI causing microorganisms were MDR; 25 (68.8%) were BLEE/AmpC isolates and 19 (31.1%) were CRE. The mortality rate of MBI-LCBI patients was 48.6% (72). There was no difference between deaths from BLEE/AMPc versus susceptible bacteremia (22,2% vs. 27,6% p=0,44), however, mortality from CRE strains was higher compared to susceptible strains (20,8% vs. 2,6% p=0.001) figure 2. The risk of dying with MBI-LCBI with CRE strains was OR: 4.5 (95% CI;1.3-15; p=0.01).

Conclusion

There is a high percentage of resistance and mortality in MBI-LCBI, more notorious when the cause is CRE. This alerts us to the need of further research in this pathology and its appropriate treatment. Ecuadorian health authorities should consider review the EFN to include new active drugs for treatment CRE infections.

Disclosures

All Authors: No reported disclosures
2726. A Retrospective Single Center Study to Assess the Risk Factors for Infection with Multi-Drug-Resistant Organisms in Liver Transplant Recipients
Authors: Swaminathan Neeraja , McCort Margaret E , Frager Shalom , Kinkhabwala Milan , Bartash Rachel , Vasa Aastha
Published: November 2023

Background

Infections with multidrug resistant organisms (MDROs) are common in liver transplant recipients. We aimed to understand the prevalence and risk factors for MDRO infections during the peri-transplant period.

Methods

We conducted a retrospective chart review of adults ( >18 years) who underwent deceased donor liver transplant (LT) from Jan 2018-Dec 2020. Demographics and clinical information, including antibiotic use, microbiological data, and adequacy of perioperative antibiotics based on CLSI breakpoints, were reviewed. Peri-transplant period was defined as 12 months pre- and 3 months post-transplant. MDRO was defined as resistance to one or more classes of antibiotics. Statistical analysis was performed with IBM SPSS 29.0, using Chi2 or Fischer’s exact tests as appropriate for categorical variables and independent t-test for continuous variables.

Results

Baseline demographics for the 121 LT recipients are summarized in Table 1. In the 3 months post-transplant, 47 patients (38.8%) were noted to have positive cultures, of which 22 were MDRO. MDRO distribution for pre- and post-transplant infections is shown in Figure 1. Univariate analyses of predictors for post-transplant MDRO infection are shown in Table 2. Mean length of stay for patients with post-transplant MDRO infection was 65.3 days versus 28.6 days in those without MDRO infection (p< 0.001). Among 36 patients with positive cultures < 1month post-transplant, 55% (n=20) received perioperative antibiotics covering the identified organism. Eleven of 23 patients (47.8%) who received ampicillin-sulbactam (AS) and 3 of 8 patients (37.5%) who received piperacillin-tazobactam (PT) perioperatively developed infections not covered by their respective regimens < 1-month post-transplant. In the first month post-transplant, 17 patients had organisms cultured which were resistant to AS, of which all but one was also resistant to PT.Table 1Baseline Demographics

Conclusion

Admission to the intensive care unit, antibiotic use prior to transplant, and longer transplant hospitalizations were associated with MDRO infections. Tailoring of surgical prophylaxis may be indicated for high-risk patients as PT did not offer superior coverage over AS.

Disclosures

All Authors: No reported disclosures
2729. Clinical characteristics, treatment and outcomes of infections among adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies patients: A single-center 10-year review from tertiary care hospital in Thailand
Authors: Wongpaiboonwatana Sorakai , Feungpunya Thanarak , Diewsurin Jaruwan , Treebupachatsakul Pornpit
Published: November 2023

Background

Adult-onset immunodeficiency (AOI) with anti-interferon (IFN)-γ autoantibodies is an acquired immunodeficiency syndrome increasingly recognized in East and Southeast Asia. Antibody against IFN- γ or its receptor is the main pathophysiology leading to opportunistic infections especially mycobacterial, dimorphic fungal or Salmonella infection. However, clinical information of infectious complications in this patient population remains scarce.

Methods

A retrospective study was conducted in Buddhachinaraj hospital, Phitsanuloke, Thailand. We collected data on demographic, infectious complications, treatment and outcomes in patients with AOI with anti-IFN-γ autoantibodies who presented to our center between March 2013 and February 2023. All patients were diagnosed by elevation of anti-IFN- γ antibody level in serum more than 1.0.

Results

A total of 35 patients. 54.3% were men with a median age of 58 years (IQR 14-63). Lymphadenopathy was the most common initial presentation (57%), followed by prolonged fever (40%), cough (11%) and skin lesions (11%). Lymph node involvement was found in 80% while 31% and 11% had intra-abdominal abscess and osteomyelitis.

Organisms were identified in 21 patients (60%). Mycobacterial infections were found in 19 patients (90%) which the main etiologic agent was Mycobacterium abscessus (43%). Six patients (28%) had evidence of mycobacterial infection but were unable to specified. Histoplasma capsulatum was found in 2 patients (9%). Another 14 patients (40%) were presumptive treated as non-tuberculous mycobacterium (NTM) infection without retrieving specific organism.

All patients were treated with antimicrobial agents according to identified causative organism. Fourteen patients with presumptive NTM infection were empirically treated with combination antibiotics. Median time of treatment was 24 months (IQR 12-35). Seven patients (20%) experienced relapse after antimicrobial discontinuation requiring retreatment. Three patients (6%) had died at median duration of 4 months from diagnosis.

Conclusion

AOI with (IFN)-γ autoantibodies should be considered in patient whom suspected mycobacterium or fungal infection among non-HIV patients. Diagnosis and treatment are challenge and recurrent infection is common.

Disclosures

All Authors: No reported disclosures
2730. Clinically significant cytomegalovirus infection in patients with lymphoma and no prior cellular therapy
Authors: Zubovskaia Anna , Khawaja Fareed , Chemaly Roy F , Primeaux Brian , Waleed Mohammad
Published: November 2023

Background

Reactivation of cytomegalovirus (CMV) is commonly reported in lymphoma patients who undergo cellular therapy, with often poor outcomes. The risk for CMV reactivation in patients with lymphoma prior to cellular therapy is not well understood. As new alternative immunosuppressive therapies emerge for lymphoma, understanding baseline risk for CMV reactivation is paramount to improve clinical and oncologic outcomes. Our goal was to identify risk factors, and describe outcomes associated with clinically significant CMV infection (CS-CMVi) in lymphoma patients with no prior cellular therapy.

Methods

We performed a retrospective cohort study for all lymphoma patients who underwent testing for CMV by PCR from blood between 1/2017 and 12/2020. Patients with prior history of transplantation or chimeric antigen receptor therapy were excluded. Patients with and without CS-CMVi were identified for risk factor analysis by univariate analysis.

Results

A total of 217 lymphoma patients were included in our analysis; CS-CMVi was identified in 41 (19%) patients. When compared to patients without CS-CMVi (control group), lymphoma patients with CS-CMVi were more likely to have history of HIV (5% vs 0%; p= 0.0350), primary central nervous system lymphoma (7% vs 1%; p= 0.0220) and relapsed disease (54% vs 25%; p= 0.0005) (Table 1). CS-CMVi was also more common if testing was done at time of relapse diagnosis (32% vs 10%; p= 0.0007), during work up for infection (98% vs 68%; p < 0.0001) and more often (3 vs 1; p < 0.0001) (table 1). Mortality and remission rates within 1 year of testing were worse in patients with CS-CMVi (table 2 and figure 1).

Conclusion

CS-CMVi in lymphoma patients is associated with poor outcomes including oncologic outcomes. Further analysis to better define patients with lymphoma at high-risk for CS-CMVi should be studied for future preventative strategies.

Disclosures

Fareed Khawaja, MBBS, MEDSCAPE: Honoraria|Viracor: Grant/Research Support Roy F. Chemaly, MD/MPH, Eurofins-VViracor: Grant/Research Support|Karius: Advisor/Consultant
2732. Peri-Operative Antibiotic Management for Lung Transplant Recipients with Cystic Fibrosis
Authors: Gordon Melissa , Nichols Courtney , Marschalk Nicholas , Sarwar Sajed
Published: November 2023

Background

Lung transplant (LTx) recipients universally receive peri- and post-transplant antibiotics. Approaches to antibiotics for candidates with cystic fibrosis (CF) are institution specific. Little has been published about these practices. Routine LTx perioperative prophylaxis at our institution is 96 hours of vancomycin and cefepime with antibiotics then adjusted for positive intraoperative donor and recipient cultures. In recipients with CF, perioperative prophylaxis is determined pre-LTx to cover colonizing organisms isolated in culture from the 2 years before LTx, adjusted for intraoperative cultures, and administered for 14-21 days post-LTx. Our study aims to add to the current literature by describing our center’s experience with antibiotic management and outcomes in lung transplant recipients with CF to help guide best practices for prophylaxis strategies for this patient population.

Methods

We performed a retrospective chart review of patients with CF who underwent LTx from 3/1/2015-11/18/21 at our center and were colonized pre-LTx with MRSA, Pseudomonas aeruginosa, or Burkholderia cepacia complex. Peri- and post-operative antibiotic regimens, donor and recipient culture results, changes in antibiotic therapy post-LTx, and duration of antibiotic therapy were documented. Outcomes included rehospitalization, isolation in culture of the prophylaxis-targeted organisms post-LTx, and mortality, within 6 months of LTx.

Results

Nineteen incidents of LTx were included in this study. Pre-LTx colonizing organisms and antibiotics administered are outlined in table 1. Prophylaxis-targeted organisms were infrequently isolated in culture after LTx (table 2), with 7/19 (36.8%) developing post-transplant infection with prior colonizing organisms. Four (21.1%) recipients developed post-LTx Clostridioides difficile infection. One (5.3%) recipient died within 6 months post-LTx.

Conclusion

LTx recipients with CF who received targeted perioperative prophylaxis for pre-LTx colonizing organisms infrequently developed post-LTx culture positivity with the same bacteria including none during the antimicrobial prophylaxis period. Future prospective studies are needed to determine optimal antibiotic duration of peri-LTx antibiotics in this patient population.

Disclosures

All Authors: No reported disclosures
2739. Evaluation of a Perioperative Fungal Prophylaxis Protocol Change in Orthotopic Liver Transplant
Authors: Shulkosky Megan , Xhemali Xhilda , Eckardt Jamie , Ward Jessica , Schlick Heather , Brizendine Kyle D , Palm Nicole
Published: November 2023

Background

Orthotopic liver transplant (OLT) carries a high rate of fungal infections, including invasive fungal infections (IFI). A targeted antifungal prophylaxis protocol can identify OLT patients who warrant antifungal prophylaxis and optimize agent selection. In January 2021, a targeted antifungal prophylaxis post-liver transplant protocol was implemented at Cleveland Clinic. Since its introduction, rates of fungal infections and adherence to the protocol have not been assessed. The goal of this project is to describe the impact of a protocol change in OLT recipients.

Methods

This was a retrospective observational cohort study of patients ≥ 18 years old with an OLT +/- sequential kidney transplant at Cleveland Clinic. Review of perioperative fungal prophylaxis from June 1, 2019 – May 31, 2020 was performed and used as the baseline. The post-intervention period was June 1, 2021 – May 31, 2022. The primary objective was to determine adherence to the new OLT fungal prophylaxis protocol on post-operative day (POD) 0. Secondary objectives included the 90-day incidence of proven or probable IFI post-OLT before and after implementation.

Study Population

Results

A total of 134 patients pre-protocol and 166 patients post-protocol were included. Prior to protocol implementation, 73% patients were prescribed clotrimazole, 13% fluconazole, 13% micafungin, and 1% nystatin. After protocol implementation, 63% were prescribed clotrimazole, 16% fluconazole, and 21% micafungin. In the post-protocol group, there was an adherence rate of 66% on POD0 which increased to 84% over the duration of prophylaxis. Prior to initiation of the antifungal protocol, 6.7% of patients developed an IFI while 3.6% of patients developed an IFI post-protocol (p=0.22). Median time to IFI was 8 days (IQR 2-19) pre-protocol and 15 days (IQR 6-17) post-protocol. Mortality and ICU length of stay were comparable between groups.

Primary and Secondary Results

OLT: orthotopic liver transplant; POD: post-operative day; ICU: intensive care unit; IFI: invasive fungal infection

Characteristics of Patients with Invasive Fungal Infections

IFI: invasive fungal infection; TPN: total parenteral nutrition; IAI: intra-abdominal infection; n/a: not applicable; pRBC: packed red blood cells; OR: operating room; RRT: renal replacement therapy; ICU: intensive care unit; Dose dep.: dose dependent; GI: gastrointestinal

Conclusion

The implementation of a targeted antifungal prophylaxis post-liver transplant protocol can be a powerful strategy for promoting consistency in antifungal prophylaxis within a population at high risk for IFIs. Our study showed an 84% adherence rate to the implemented protocol, with numerically lower rates of IFIs post-protocol compared to pre-protocol.

Disclosures

All Authors: No reported disclosures
2741. Hit Me with Your Best Shot: Improving Pre-Lung Transplant Vaccination Rates with Infectious Disease Evaluation
Authors: Contreras Gustavo , Holubar Marisa , Shen Sa , Dhillon Gundeep , Tulu Zeynep , Nelson Joanna K
Published: November 2023

Background

Vaccine preventable diseases and reactivation of latent infections occur commonly post-solid organ transplant and can result in severe infections. Vaccination and screening for latent infections in the pre-transplant period are important tools to mitigate this risk. Previous studies have shown that, despite guidelines, vaccine uptake in the pre-transplant population is suboptimal.

Methods

We performed a quality improvement project in which all patients >=18 years old being evaluated for lung transplant (LT) were referred for Infectious diseases (ID) evaluation with the endorsement of our LT Quality Council starting in 11/2021. ID evaluation included screening for and treating latent infections, vaccination history and drug allergy review, adjusting peri-operative antibiotics, and patient education. To assess the impact of our intervention, we conducted a retrospective chart review and extracted demographics, transplant status, and recommended and completed vaccinations. We compared vaccination adherence of consecutive patients who underwent ID evaluation (11/2021 – 8/2022) to a historical cohort of patients who were not evaluated by ID but underwent LT (1/2019 – 12/2020). We defined adherence for each vaccine (Table 1) and compared the odds of vaccination between groups using odds ratios. This project was deemed non-human subject research.

Results

We included 59 patients in the pre- and 61 patients in the post-ID group(Table 2). By the end of the observation period, in those patients evaluated by ID, 30(49%) patients had undergone LT, 10 (16%) were active on waiting list,18 (30%) were not yet listed, and 4 (12.5%) were declined for LT. Among those who underwent pre-transplant ID evaluation, 53 (85.5%) patients were seen via telemedicine. Adherence was significantly higher across all vaccines among the patients evaluated by ID; the biggest change was seen in HBV, Tdap, and Zoster (Figure 1).

Conclusion

ID evaluation of patients being evaluated for LT significantly improved vaccination rates. Pre-transplant ID evaluation provides the added value of a focused discussion of infection risk and can help to avoid morbidity and mortality post-transplant.

Disclosures

All Authors: No reported disclosures
2747. Aztreonam-Avibactam Susceptibility Testing Program for Metallo-β-Lactamase-Producing Enterobacterales collected through the Antimicrobial Resistance Laboratory Network, March 2019 to April 2023
Authors: Bhatnagar Amelia , Bumpus-White Porscha , Sabour Sarah , Bodnar Janine , Burks Albert , Chen Arlene , Craft Bradley , Jacobsen Christine , Karlsson Maria , Marmerow Michael , Lonsway David , Neff Lindsay , Maruca Tyler , Nazarian Elizabeth , Perry Zachary , Rossi Alessandro , Vagnone Paula S , Tran Michael , Valley Ann M , Brown Allison C
Published: November 2023

Background

Metallo-β-lactamase-producing Enterobacterales (MBL-E) are a major public health concern as they cause infections with few effective treatment options. Aztreonam-avibactam (AZA) is a β-lactam/β-lactamase inhibitor combination agent in the drug development pipeline that is active against MBL-E. Though clinical studies are ongoing, the effective components can be administered by combining two FDA-approved drugs: aztreonam and ceftazidime-avibactam. In 2019, CDC initiated a program in the Antimicrobial Resistance Laboratory Network (AR Lab Network), the Expanded Antimicrobial Susceptibility Testing Program for Hard-to-Treat Infections, to provide antimicrobial susceptibility testing (AST) of MBL-E for AZA. We provide a summary of the program’s results.

Methods

Seven AR Lab Network laboratories validated the use of a digital dispenser to create custom broth microdilution panels for AZA AST. Testing requests must be for clinical decision-making purposes. Isolates must be an Enterobacterales and have laboratory results positive for an MBL gene (i.e., blaNDM, blaVIM, or blaIMP), or be not susceptible to all β-lactams tested. AZA testing results for confirmed MBL-E were reported back to submitters within 3 working days from receipt of the isolate and shared with CDC.

Results

From March 2019 through April 2023, AZA AST was performed for 250 isolates: 103 Escherichia coli, 86 Klebsiella pneumoniae, 46 Enterobacter cloacae complex, 8 K. oxytoca, 2 Providencia rettgeri, 1 K. aerogenes, 1 Morganella morganii, 1 Proteus mirabilis, 1 E. hormaechei, and 1 Citrobacter amalonaticus. Carbapenemase genes detected were: 206 blaNDM, 24 blaNDM/blaOXA-48-like, 14 blaKPC/blaNDM, 2 blaIMP, 2 blaKPC/blaIMP, and 2 blaNDM/blaIMP. All isolates were resistant to ceftazidime-avibactam; 227/250 (90.8%) were not susceptible to aztreonam (≥8 µg/mL). For isolates not susceptible to aztreonam, the addition of avibactam resulted in a median 128-fold MIC reduction of aztreonam. The MIC range of AZA was ≤0.03/4 - >64/4 µg/mL. Overall, the MIC50 and MIC90 of AZA were 0.5/4 µg/mL and 8/4 µg/mL, respectively; the MIC50 and MIC90 for E. coli were higher than other species, 4/4 µg/mL and 16/4 µg/mL.

Conclusion

Our data suggest that AZA has potent in vitro activity against MBL-E collected in the United States.

Disclosures

All Authors: No reported disclosures
164. Performance of ePlex® Blood Culture Identification Panels in Clinical Isolates and Characterization of Antimicrobial Stewardship Opportunities
Authors: Thomas Jenni , Clark Justin A , Arora Vaneet , Burgess David , Burgess Donna R , Mynatt Ryan , VanHoose Jeremy , Wallace Katie L , Cotner Sarah
Published: November 2023

Background

Rapid diagnostic testing allows pathogen identification within hours of a positive blood culture. GenMark’s ePlex® Blood Culture Identification (BCID) Panels detect bacteria, fungi, and antibiotic resistance genes. This study assessed concordance of ePlex® organism identification with standard microbiologic identification methods and concordance of ePlex® genotypic resistance mechanism detection and standard susceptibility testing. Secondary outcomes included panel specific performance and characterization of antimicrobial stewardship opportunities.

Methods

This retrospective, single center study included patients with a positive blood culture from May 2020 – January 2021. Polymicrobial cultures were excluded. Identification concordance was evaluated between ePlex® and MALDI-TOF, BD Phoenix™, and biochemical tests. Resistance mechanism/phenotypic susceptibility concordance was evaluated between ePlex® and BD PhoenixTM/ETEST®. MecA was assessed via oxacillin resistance, vanA via vancomycin resistance, CTX-M via ceftriaxone resistance, and KPC via carbapenem resistance. Opportunities for antimicrobial stewardship were also quantified.

Results

The overall identification concordance rate in 1276 positive blood cultures was 98.2%, with rates of 98.5%, 98.1%, and 93.3% for Gram-positive, Gram-negative, and fungal isolates, respectively. In 381 staphylococcal isolates, concordance rates were 98.3% and 100% for the presence and absence of mecA. Both the presence and absence of vanA were 100% concordant in 63 enterococcal isolates. CTX-M and KPC were evaluated in 189 Enterobacterales. Concordance rates were 96.8% for the presence of CTX-M and 60% for the presence of KPC, demonstrating that 40% of carbapenem resistance was due to non-enzymatic mechanisms. Ceftriaxone and carbapenem susceptibility correlated with the absence of CTX-M and KPC, respectively, in 100% of cultures. A majority of ePlex results (69.5%) represented opportunities for potential antimicrobial stewardship intervention.

Conclusion

High concordance rates between ePlex® and standard identification and susceptibility testing methods enable rapid antimicrobial optimization. Numerous opportunities for antimicrobial stewardship were identified based on ePlex® results.

Disclosures

All Authors: No reported disclosures
2765. Dalbavancin for challenging left ventricular assist device driveline infections
Authors: Doligalski Christina , Lachiewicz Anne , Friedland Anne , Snider Cynthia , Bowen Amanda , Marx Ashley H , Byku Mirnela , Bartelt Luther A
Published: November 2023

Background

Driveline tract and exit site infections (DLI) in patients on left ventricular assist device (LVAD) support occur frequently and are associated with significant morbidity, mortality and recurrence. Dalbavancin is a gram+ active lipoglycopeptide antibiotic with a prolonged half-life. Given a variety of scenarios including prior antibiotic failure, interacting concurrent therapies and socioeconomic factors, dalbavancin may be of interest for use in LVADs with challenging gram+ DLIs.

Case Series Details

Methods

A chart review was conducted for all LVADs at a single center who received at least one dose of dalbavancin prior to 1/1/2023 to assess safety and to describe utilization. Demographic data, microbiologic and antibiotic histories, and dalbavancin therapies along with further suppressive antibiotics were recorded.

Results

Six patients on LVAD support received dalbavancin for different gram+ infections (Figure 1). Five of the six had confirmed DLI. Three patients received two doses of dalbavancin 1500mg 1-2 weeks apart, followed by suppressive doxycycline with no infection recurrence to date. Three patients received dalbavancin initial doses 1-2 weeks apart followed by planned suppressive dalbavancin at 3-4 week intervals. One of these patients developed anaphylaxis with dose #5 and was subsequently changed to suppressive sulfamethoxazole/trimethoprim. Another received 10 of 14 planned doses over a 14 month period, with controlled infection while adherent to infusion. The final patient remains on suppressive dalbavancin ( >1100 days). Apart from the anaphylactic reaction, no other adverse events were documented related to dalbavancin therapy.

Conclusion

In our limited case series, adherence with dalbavancin was a successful therapeutic option for patients with LVAD-related gram+ infections after failure of other therapies or socioeconomic limitations. Anaphylaxis was observed in one patient during infusion #5, suggesting the need for ongoing monitoring despite prior tolerability. One patient remains on prolonged suppressive intermittent dalbavancin, suggesting extended use may be viable in highly select patient scenarios. Further data is needed on prolonged durations and optimal dosing strategies in complex device-related infections.

Disclosures

Anne Lachiewicz, MD, MPH, Cidara: Grant/Research Support|Contrafect: Grant/Research Support|Novartis: Grant/Research Support|Pfizer: Grant/Research Support|Shiongi: Grant/Research Support Mirnela Byku, MD, Abbott: Advisor/Consultant
2768. In Vitro Antibiotic Susceptibility Pattern of Non-diphtheriae Corynebacterium Isolates 2012-2023, reference lab experience
Authors: Saleh Omar M Abu , Zein Said El , Rivera (O'Connor) Christina G , Stevens Ryan W W , Schuetz Audrey N , Fida Madiha
Published: November 2023

Background

Non-diphtheriae Corynebacterium spp. are important human pathogens responsible for a broad spectrum of clinical syndromes. Data on species-specific susceptibility patterns is limited. In this study we aim to study these susceptibility patterns over time and summarize the species-specific resistance profile that could be used by clinicians to guide therapeutic decisions.

Methods

We conducted a retrospective review of all the Non-diphtheriae Corynebacterium isolates that were submitted for antimicrobial susceptibility testing (AST) between January-2012 and February of 2023 to our reference lab.

Results

A total of 1925 Corynebacterium isolates were submitted for susceptibility testing over the study period. The most commonly identified species was C. striatum (35.6%) followed by C. amycolatum (24.4%). Figure-1 outlines the species distribution. Temporal analysis showed decreasing susceptibility rates over the study period from 47.5% to 20.6% for penicillin & from 50% to 7.6% for clindamycin.

Linezolid and vancomycin were universally active against all species (Table-1). Daptomycin non-susceptibility was reported in 25% of C. jeikeium isolates (MIC=2). High level resistance to daptomycin with MIC >256 were noted in seven C. striatum and single C. amycolatum isolate. Doxycycline has the highest susceptibility rates among the tested oral agents after linezolid for the non-striatum species.

Significant variation in species-specific susceptibility pattern was noted and summarized in Table 1. C. striatum was associated with concerning resistance rates to beta-lactams, tetracyclines, trimethoprim-sulfamethoxazole & fluoroquinolones with limited reliable oral treatment options beside linezolid. C. kroppenstedtii (associated with granulomatous mastitis) showed high susceptibility rate to tetracyclines and trimethoprim-sulfamethoxazole despite prevalent penicillin resistance.

Conclusion

Non-diphtheriae Corynebacterium spp are commonly isolated from clinical specimens and are associated with various clinical syndromes. Significant variation in resistance profile exists between different species. Prevalent resistance among the most common species such as C. Striatum is associated with therapeutic challenges.

Disclosures

Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Audrey N. Schuetz, MD, Merck: Advisor/Consultant
2770. Investigating the Impact of Non-CTX-M Producing ESBL-E Bloodstream Infections on Patient Outcomes
Authors: Hareza Dariusz A , Simner Patricia J , Fiawoo Suiyini , Lee Jae Hyoung , Bergman Yehudit , Jacobs Emily B , Cosgrove Sara E , Tamma Pranita
Published: November 2023

Background

Studies investigating optimal treatment and patient outcomes for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) generally do not distinguish between ESBL genes in bloodstream infections (BSI). To address a key knowledge gap, we compare the clinical outcomes of patients with non-CTX-M and CTX-M-producing ESBL-E BSIs.

Methods

We collected 500 ceftriaxone-resistant Enterobacterales bloodstream isolates from patients in the Johns Hopkins Health System between 2018-2021. Broth microdilution confirmed antimicrobial susceptibilities, and whole genome sequencing identified ESBL genes. We used 1:3 propensity score matching (PSM) to compare the odds of 30-day mortality between patients infected with non-CTX-M and CTX-M ESBL-Es. Propensity scores were derived using seven variables: age, sex, severe immune compromise, Pitt bacteremia score ≥4, Charlson comorbidity index ≥5, adequate source control, and carbapenem use.

Results

ESBL genes were confirmed in 396 isolates, including 370 (93%) blaCTX-M genes and 26 (7%) non-blaCTX-M ESBL genes: blaSHV (13), blaOXY (8), blaVEB (5). Common species harboring blaCTX-M were: Escherichia coli (265), Klebsiella pneumoniae (88), K. oxytoca (5), and Enterobacter cloacae (5); and non-blaCTX-M were: K. pneumoniae (8), K. oxytoca (8), and Proteus mirabilis (5). After PSM, baseline patient characteristics were similar, and the aOR of 30-day mortality was 0.94 (95% CI 0.89-0.99) comparing patients with non-blaCTX-M and blaCTX-M isolates. In an exploratory analysis limited to patients with non-blaCTX-M isolates: 2 of 15 patients (13%) receiving meropenem and 6 of 11 (55%) not receiving meropenem died within 30 days (aOR=0.61; 95% CI 0.42-0.90).

Conclusion

Mortality was slightly lower in patients with BSIs due to non-CTX-M-producing ESBL-Es compared to CTX-M-producing ESBL-Es. Similar to what has been observed with CTX-M-producing ESBL-Es, meropenem is protective against mortality in patients infected with non-CTX-M producing ESBL-Es, underscoring the importance of diagnostics to detect a comprehensive array of ESBL genes among diverse Enterobacterales.

Disclosures

Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant
2794. Assessing the impact of inappropriate antibiotic therapy on mortality among intensive care unit patients
Authors: Pereira Rogério , Silva Sinval Lins , Couto Braulio
Published: November 2023

Background

This study evaluates the potential association between inappropriate antibiotic therapy and adverse clinical outcomes in infected patients admitted to ICUs.

Methods

We analyzed data from infected patients admitted to a medical-surgical Intensive Care Unit (ICU) in Belo Horizonte, a city with a population of three million in Brazil. The data was collected between January 2020 and June 2021, and included patients with healthcare-associated and community-acquired infections. In order to determine the appropriateness of antibiotic therapy, cultures and susceptibility reports were utilized. Empiric antimicrobial therapy was classified as inappropriate if the isolated strain was resistant to all empirically administered antimicrobials, while it was considered adequate if the isolated strain was susceptible to at least one of the antimicrobials used empirically.

Results

A total of 470 patients who received antimicrobials in the ICU were included in the analysis, all of whom had a positive culture. Among them, 65 patients experienced a FAILURE of the antimicrobial regimen, resulting in an overall failure rate of 14%. The monthly rate of inappropriate antibiotic therapy showed significant heterogeneity during the study period, ranging from 100% success in March 2021 to a failure rate of 33% in June 2021 (Fig 1). The failure rate of antimicrobial regimen was found to be significantly higher in cases where the infection was caused by multidrug-resistant (MR) strains compared to multisensitive (MS) strains, as shown in Table 1. Failure of the antimicrobial regimen was a significant risk factor for patient death, regardless of whether the infection was caused by MS or MR strains (Tables 1 and Fig 2). Patients who died tended to receive more antimicrobials compared to those who were discharged, with an average of three antimicrobials prescribed for patients who progressed to death, while discharged patients received an average of two drugs.

Conclusion

Inappropriate antibiotic therapy in ICU patients is associated with increased mortality risk, regardless of the type of infection. Timely and appropriate antimicrobial therapy is crucial in the management of ICU infections to improve clinical outcomes.

Disclosures

All Authors: No reported disclosures
2796. A Decade of Rhodococcus spp. Infections: Microbiology, Antimicrobial Susceptibility, and Clinical Experience
Authors: Ranganath Nischal , Mendoza Maria Alejandra , Stevens Ryan W W , Wengenack Nancy , Shah Aditya
Published: November 2023

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
2806. The Mechanism of β-Lactam Antibiotic Action: Structural Analysis of Mycobacterium abscessus l,d-Transpeptidases, d,d-Carboxypeptidase and penicillin-binding-proteins binding by imipenem, ceftaroline, and amoxicillin
Authors: Shin Eunjeong , Nantongo Mary , Dousa Khalid M , Bethel Christopher R , Taracila Magdalena A , Kreiswirth Barry N , Holland Steven M , Bonomo Robert A
Published: November 2023

Background

M. abscessus (Mab) is among the most clinically challenging pathogens. There are significant gaps remaining in mechanism of β-lactams action in Mab. β-Lactams preferentially inactivate one or multiple different L,D-Transpeptidases (LDTs) and penicillin-binding proteins (PBPs). Founded on our LDT binding data and in vitro synergistic efficacy of imipenem (IPM), ceftaroline (CFT), and amoxicillin (AMX) in Mab, this study aimed to identify binding affinities, conformational changes and the thermal stability of five LDTs and PBPs via β-lactam binding for further structure-activity relationship.

Methods

Binding affinity was measured by kinetic studies, MS analysis, or Bocillin-FL inhibition assay. We investigated changes in the secondary structure of five LDTs (LDT1-5), d,d-carboxypeptidase, PBPB, and PBP-lipo in response to bind of IPM, CFT, and AMX using circular dichroism (CD) spectroscopy in the far-UV region. To assess the thermal stability of these LDTs, we employed a Differential Scanning Fluorimetry (DSF) assay.

Results

CD analysis revealed a significant negative shift of LDT1, LDT2, and PBPB upon binding with either single or combination of imipenem (IPM) and ceftriaxone (CFT), particularly in the 210-220 nm range. Using DSF, IPM and CFT binding to LDTs, DDC and PBPB were found to alter the thermal stability of these protein enzymes. IPM induced a decrease in the melting temperature (Tm) in the range of 2.6-6.8 ˚C for LDTs and PBPB, while caused an increase in Tm for DDC. CFT caused decrease in Tm in the range of 1.4-3 ˚C for LDTs but increase in Tm for DDC and PBPB. In contrast, amoxicillin (AMX) only targeted DDC, PBPB, and PBP-lipo and caused changes in Tm. The magnitude of the change in Tm varied between combinations and single β-lactams. Although there was no evidence of a correlation between changes in protein stability upon ligand binding and ligand binding affinity, IPM with high binding affinity (lower value of Ki,app) resulted in larger decreases in Tm compared to CFT.

Conclusion

β-Lactam binding in single and combination leads to distinct structural changes of LDTs and PBPs, likely reflecting synergistic interactions between the two β-lactams. Further crystallography will be required to gain a better understanding of the induced structural changes.

Disclosures

Robert A. bonomo, MD, Entasis, Merck, VenatoRx, Wockhardt: Grant/Research Support
2808. Evaluation of a Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide empiric therapy in pneumonia cases
Authors: Skoglund Erik , Banuelos Leslie , Farihi Destiny
Published: November 2023

Background

Empiric antibiotic selection must balance the need for prompt active coverage against the risk of antibiotic resistance pressure imposed by using broad agents. The guidance available from conventional antibiograms is limited in this setting as they provide no information about the relative frequency of pathogens for a given infectious syndrome. Weighted-Incidence Syndromic Combination Antibiograms (WISCAs) overcome this limitation. To better promote appropriate empiric antibiotic use at our institution, we sought to develop a WISCA depicting empiric activity of various regimens against previous cases of bacterial pneumonia.

Methods

Patients admitted between 2018-2022 were screened for respiratory cultures with positive bacterial growth and a discharge diagnosis code consistent with bacterial pneumonia. Patients were excluded if they lacked radiologic evidence or clinical symptoms. The first episode of pneumonia per admission was considered. Interpretations were determined using CLSI breakpoints, and assumptions were used to extrapolate the activity of agents for which no breakpoints or MICs were available. A case was considered susceptible to a given regimen if all cultures in that case were covered by at least one agent in the regimen. The expected performance of WISCA-directed empiric therapy was compared to the activity of actual empiric therapy received by a retrospective cohort of pneumonia patients.

Results

The WISCA was built using 674 respiratory cultures from 441 unique patient cases. The most common empiric agents received in the retrospective cohort were vancomycin (158, 77%), piperacillin-tazobactam (133, 65%), ceftriaxone (77, 38%), and meropenem (57, 28%). Among this cohort, 126 (61%) of patients received active empiric coverage against all case pathogens. According to the WISCA, the combination of piperacillin-tazobactam + levofloxacin provides active empiric coverage for 63% of cases, which is not significantly different than that achieved in the retrospective cohort while avoiding use of carbapenems or vancomycin.

Conclusion

Our findings suggest that WISCAs provide additional guidance for empiric antibiotic prescribing compared to conventional antibiograms alone.

Disclosures

All Authors: No reported disclosures
2813. Impact of a Recent Change in Tobramycin Breakpoints (CLSI) on the Proportion of Pseudomonas aeruginosa Clinical Isolates that are Multidrug-Resistant: CANWARD, 2016 to 2021
Authors: Walkty Andrew , Adam Heather , Baxter Melanie , Lagace-Wiens Philippe , Karlowsky James , Zhanel George
Published: November 2023

Background

Pseudomonas aeruginosa (PA) is an important nosocomial pathogen. In 2023, tobramycin (TM) susceptibility breakpoints for PA were lowered (from ≤4 to ≤1 µg/mL) by the Clinical and Laboratory Standards Institute (CLSI). The purpose of this study was to evaluate whether this change will result in an increase in the proportion of PA clinical isolates that are considered multidrug-resistant (MDR).

Methods

PA clinical isolates were obtained from patients evaluated at hospitals across Canada (January 2016 to December 2021) as part of an ongoing national surveillance study (CANWARD). Susceptibility testing was carried out using custom broth microdilution panels. MICs were interpreted using current (2023) CLSI breakpoints, with the exception of TM (interpreted using the 2022 and 2023 breakpoints). MDR PA were defined as isolates testing not susceptible at least three of the following: ceftazidime, ciprofloxacin, meropenem, piperacillin-tazobactam, and TM (assessed with both the 2022 and 2023 CLSI breakpoints).

Results

1649 PA isolates were included in this study. The proportion of isolates testing susceptible to TM using the 2022 (S ≤4 µg/mL) and 2023 (S ≤1 µg/mL) CLSI breakpoints were 93.6% and 84.8%, respectively. Overall, 21.6% (356/1649) and 22.7% (374/1649) of PA isolates were MDR, using the 2022 and 2023 CLSI breakpoints. Below, the in vitro activities of common antipseudomonal antimicrobials versus PA isolates from this study (all and MDR subset) are presented.

Conclusion

In this dataset, the proportion of MDR PA isolates was minimally altered by a recent change to the CLSI TM susceptibility breakpoints. A reduction in the proportion of PA isolates that were susceptible to TM using the new breakpoints was most pronounced for the MDR subset.

Disclosures

George Zhanel, PhD, Avir: Grant/Research Support|Iterum: Grant/Research Support|Merck: Grant/Research Support|Orimed: Grant/Research Support|Paladin Labs: Grant/Research Support|Pfizer: Grant/Research Support|Verity: Grant/Research Support|Zambon: Grant/Research Support
2814. The Impact of Novel Antibiotics on Curbing Antimicrobial Resistance and Infection Spread a Dynamic Modeling Study
Authors: Ambavane Apoorva , Litkiewicz Michal , Sardesai Aditya , Teloian Diana , Obi Engels N , Yang Joe
Published: November 2023

Background

Antimicrobial resistance (AMR) is a growing global concern. Novel antibiotics (ABXs) target resistant pathogens causing gram-negative (GN) bacterial infections. This study assesses the broader impact of novel ABX use on the US healthcare system, including preventing the onward spread of infections and reducing the level of high-threat AMR.

Methods

A stochastic dynamic transmission model was developed to simulate the interaction between infection transmissibility, bacterial resistance development, and multiple lines of ABX. Included infection types were intra-abdominal infections, urinary tract infections and hospital-acquired /ventilator-associated pneumonia. Included AMR types were carbapenem-resistant and ESBL-producing enterobacterales (CRE and ESBLE), and multi-drug resistant pseudomonas aeruginosa (MDRP). The model has compartments for non-infected, colonized, or infected patients, with a sensitive or resistant strain in a US hospital. Infected patients receive antibiotics resulting in infection clearance or use of an alternate ABX class. Sensitive pathogens gain resistance due to drug pressure or conversely could lose resistance. Ordinary differential equations were used to estimate compartment membership. The primary data source was the Premier healthcare database (172 hospitals, 2016-2020). The model examined the potential reduction in AMR levels and avoided hospital infections, by comparing two scenarios: targeted use of novel ABX for specific AMR types and the status quo with limited novel ABX use.

Results

When even novel ABXs are reserved as the 2nd or 3rd line of treatment, compared to the status quo, it could result in a ∼1.5% reduction in hospital infections and a change in CRE, ESBLE, and MDRP by −2.5%, −3.6%, and −2.1%, respectively, on an annual basis. The cumulative impact of novel ABXs over 5-10 years was much larger but subject to higher prediction uncertainty. The primary driver of results are infection clearance rates, risk of resistance gain on various ABX, and uptake of novel ABX.

Conclusion

Targeted use of novel ABXs for resistant pathogens could lead to improved, earlier infection clearance with most types of infections and pathogens, thereby reducing infection transmission and rise of high-threat AMR in the long-term.

Disclosures

Apoorva Ambavane, PhD, Merck & Co., Inc: Grant/Research Support Michal Litkiewicz, MSc, Merck & Co., Inc: Grant/Research Support Aditya Sardesai, MSc, CSL Seqirus: Advisor/Consultant|Merck & Co. Inc: Grant/Research Support|Merck & Co. Inc: Grant/Research Support Diana Teloian, MA, Merck & Co., Inc: Grant/Research Support Engels N. Obi, PhD, Merck & Co Inc: Employee Joe Yang, PhD, Merck & Co., Inc: Employee|Merck & Co., Inc: Stocks/Bonds