bluuebunny/crossref_metadata_2025_split huggingface dataset:
2698. Trends of Antibiotic Resistance in E. coli, Klebsiella Spp., Pseudomonas aeruginosa and Enterococcus spp. Urinary Tract Infection in Renal Transplant Recipients from Pakistan over a Decade
Authors: Dodani Sunil Kumar , Nasim Asma 
Published: November 2023

Abstract

Background
Antimicrobial resistance is a major public threat worldwide. In Pakistan many studies reported a rising trend of resistance to antimicrobials in clinical isolates of Klebsiella species (spp.), E-coli, Pseudomonas aeruginosa and Enterococcus spp. Solid organ transplant (SOT) recipients are more prone to infections, particularly with MDR organisms due to immunocompromised status, multiple hospital visits and increase exposure to antibiotics. There is paucity of data on antibiotic susceptibility pattern among renal transplant recipients from Pakistan. This study is conducted to find the trends in antimicrobial resistance pattern among common organisms isolated in urinary tract over a 10-year period in renal transplant recipients. The aim is to guide the physicians regarding decision over empirical antimicrobial choices.

Methods
A retrospective computerized data review of urine cultures from renal transplant recipients in 2010 and 2020 was conducted. The trend and sensitivity patterns of E.coli, Klebsiella spp. Pseudomonas aeruginosa and Enterococcus spp was collected. The resistance pattern of diffferent antibiotics were compared over the 10 years period.

Results
A total of 2,088 out of 6,249 (33%) and 2902 out of 8,115 (36%) urine cultures were positive in 2010 and 2020 respectively. The most common organisms isolated and their trend in the last decade is shown in figure 1. Over the decade, E-coli strains become 100% resistant to ciprofloxacin, ceftriaxone resistance has increased to 85% and imipenem to 10%. In Klebsiella spp. imipenem resistance has increased to 14%. There is no significant change in resistance pattern among Pseudomonas aeruginosa. Regarding Enterococcus spp. there is a rise in vancomycin resistance over the decade from 13% to 17%. (fig. 2)
Trends of organism over decade

Conclusion
Resistance to broad spectrum antimicrobials has been increased with &gt;10% increase in carbapenems resistance over the last 10 years. E-coli have particularly become more resistant over the decade. We are also seeing more vancomycin resistant enterococcus. The alarming increase in resistance may lead to increased morbidity in renal transplant recipients because we left with only injectable options. We need a robust stewardship program for judicious use of antimicrobials to contain increasing resistance.

Disclosures
All Authors: No reported disclosures
158. Diagnostic Yield and Clinical Utility of Broad Range PCR Testing at a Tertiary Children’s Hospital
Authors: Schneider Jack , Prabhudas-Strycker Kirsten , Samaro Matthew , Student Medical , Goings Michael , Mellencamp Kagan A , Khan Haseeba , Boyd LaKeisha 
Published: November 2023

Abstract

Background
Broad range PCR testing (BR-PCR) targets highly conserved DNA sequences of bacteria, fungi, or mycobacteria to detect a broad range of organisms in various clinical samples. Given its potential impact in providing timely diagnoses that cannot always be made through conventional testing (CT), we evaluated the diagnostic yield and clinical impact of BR-PCR at our institution.

Methods
We retrospectively evaluated all clinical specimen types obtained for BR-PCR at Riley Hospital for Children from October 2019 to May 2022. Percent positivity (PP) was determined by specific PCR test type (Bacterial/Fungal/NTM/TB), along with median turn-around times (in days) from sample collection. Medical charts were reviewed, and clinical impact of results was determined.

Results
We identified 956 BR-PCR tests sent from 271 specimens collected from 178 patients. Only 14.5% yielded a positive result with a median days-to-result being the longest for fungal PCR at 8.1 days (7.0, 10.1) and TB PCR being the fastest at 7.8 days (6.8, 9.9). Bacterial BR-PCR yielded an overall PP of 42.6% while Fungal BR-PCR was 10.7%. Positivity rates for NTM and TB were 0% and 0.5%, respectively. Bronchial lavage was the most common specimen type (35.5%) with an overall PP of 19.9%. Of the 271 specimens, 245 returned conclusive results from both BR-PCR and clinical testing (CT) for comparison. A clinically significant organism based on CT was identified in 68 specimens (27.8%), 45 of which were confirmed by BR-PCR. 23 (33.8%) were detected by CT but not BR-PCR. 21 clinically significant organisms not detected by CT were identified by BR-PCR, which led to a change in clinical management in 12 instances: new diagnosis (91.7%); or appropriate initiation (91.7%), escalation (25.0%), or de-escalation (25.0%) of antimicrobial therapy.

Conclusion
BR-PCR overall had low diagnostic yield at our institution but was influenced by specimen type. The clinical utility was predominantly seen in immunocompromised patients in which conventional testing was negative. Further data is needed to determine which specimen types and diagnoses will increase the yield and clinical value of BR-PCR and thus, aid in enhancing diagnostic stewardship.

Disclosures
All Authors: No reported disclosures
2701. Mycobacterial Immune Reconstitution Inflammatory Syndrome Following Hematopoietic Cell Transplantation for GATA2 Deficiency
Authors: Epling Brian P , Cuellar-Rodriguez Jennifer , Arnold Danielle , Avila Daniele , Bauer Thomas , Cole Kristen , Daub Janine , Duncan Lisa , Gea-Banacloche Juan , Ma Stella , Merkel Roxanne , Palmer Cindy , Zerbe Christa , Holland Steven M , Sereti Irini , Hickstein Dennis , Manion Maura 
Published: November 2023

Abstract

Background
Immune reconstitution inflammatory syndrome (IRIS) was first described in patients with HIV and opportunistic infections starting antiretroviral therapy, but may be seen following hematopoietic cell transplantation (HCT) in patients with pre-existing infections. GATA2 deficiency is a genetic disorder with a marked susceptibility to mycobacterial infections, and is treated definitively with HCT. The clinical factors and pathogenesis of IRIS in HCT require further investigation.

Methods
We conducted a retrospective review of 32 patients with GATA2 deficiency and mycobacterial infections who completed &gt; 6 months of follow-up after HCT. Uniform criteria were used to define cases of IRIS (Image 1). IRIS cases were classified as either early (post-HCT day &lt; 60), intermediate (days 61-120), or late (day &gt; 120).
Image 1. Post-Hematopoietic Cell Transplant IRIS Criteria
Criteria were adapted to hematopoietic cell transplantation from the AIDS Clinical Trial Group IRIS criteria.

Results
Clinical characteristics are shown in Image 2. IRIS was identified in 12 (35%) patients (Images 2-3). These patients were more likely to have disseminated infection (P=0.03), an elevated pre-HCT ferritin (P=0.03), and a lower day 30 post-HCT CD4 count (P=0.04).
Median time to IRIS was 100 days (Image 4). Pre-transplant duration of mycobacterial therapy correlated with time to IRIS (Pearson’s r=0.58, P=0.05). Conditioning regimens using total body irradiation with or without cyclophosphamide were associated with longer time to IRIS (hazard ratio=0.04, P=0.02). A rise in CD3 chimerism was seen during early cases of IRIS, but not intermediate to late (P=0.002). IRIS emerged during tapering of systemic immunosuppressive therapy in 33% of cases. IRIS was managed conservatively (50%), by intensification of anti-mycobacterial treatment (8%) or by intensification of immunosuppression (42%).

Conclusion
Development of mycobacterial IRIS after HCT for GATA2 deficiency was associated with disseminated infection, a high pre-transplant ferritin, and low day 30 CD4 count. These findings suggest that antigen burden, a hyperinflammatory state leading into transplantation, and CD4 nadir after HCT have a role in its pathogenesis. Early cases of IRIS may emerge during lymphoid engraftment and CD4 recovery, whereas late cases may emerge with decreases in immunosuppressive therapy and more intensive conditioning regimens. Clinical outcomes were similar to non-IRIS patients.

Disclosures
All Authors: No reported disclosures
2709. Breakthrough fungal infection after isavuconazole primary prophylaxis in patients with hematologic malignancy and hematopoietic stem cell transplant: Systematic Review
Authors: Ishida Keiko , Haraguchi Mizuki , Kimura Muneyoshi , Araoka Hideki , Reynolds John M , Raja Mohammed , Natori Yoichiro 
Published: November 2023

Abstract

Background
Isavuconazole (ISA) is a relatively newer triazole with a broad spectrum of anti-fungal activity and has been used for both treatment and prophylaxis of invasive fungal infections (IFIs) in patients with hematologic malignancy (HM) and hematopoietic stem cell transplant (HSCT) with a more favorable side-effect profile as compared to other agents. Widespread prophylactic use of mold-active agents has resulted in a decline in the incidence of IFIs, but breakthrough (bIFIs) has been reported previously. Thus, we performed a systematic review of HM and HSCT patients receiving ISA as primary prophylaxis to determine incidence and clinical characteristics of bIFI in this vulnerable population.

Methods
We conducted a comprehensive literature search with search term of ISA, prophylaxis and either HM and/or HSCT in several search engines (Embase, Scopus Web of Science, MEDLINE and CENTRAL). The database search strategy was developed by an academic health science librarian. We excluded patients who had ISA as treatment or secondary prophylaxis.

Results
With initial search, 630 unique articles were identified and after reviewing abstracts, we finally conducted a full-text review of 70 articles, of which 27 studies were included (Figure), of which 17 studies included more than or equal to 10 patients on ISA prophylaxis. Overall, ISA was well tolerated during primary prophylaxis. Of note, of the 17 studies, 717 patients received ISA as primary prophylaxis, out of which 58 patients (8.1%) developed bIFI with range of 0%-20% and occurred 13-138 days after initiation (Table). ISA levels were checked in 6 studies with a plasma level between 1.5-6.3 μg/mL. Out of 58 bIFI cases, 33 cases were identified including 6 Mucorales spp., 3 Fusarium spp., 8 Candida spp and 14 Aspergillus spp. Most commonly used regimen for treatment of bIFI was combination of Liposomal amphotericin B with Posaconazole. Overall mortality after bIFI was 0%-66.7%.

Conclusion
Our systematic review shows a high incidence of bIFI in patients with underlying HM or HSCT receiving ISA prophylaxis. Caution should be used in patients receiving long term prophylaxis with ISA. Further studies are needed to assess for risk factors that predispose to bIFI in patients receiving ISA prophylaxis.

Disclosures
John M. Reynolds, MLIS, Pfizer Inc: Stocks/Bonds
2710. Long Term Use of Contezolid in Lung Transplant Recipients Infected with Nocardia Species
Authors: Ju Chunrong 
Published: November 2023

Abstract

Background
Nocardia commonly infects lung transplant recipients (LTR). Current oral options for long-term therapy may result in intolerance or adverse events. Contezolid is a new oxazolidinone antibiotic with potential less toxicity than linezolid that was approved in China. This study describes the use of contezolid in the treatment of nocardiosis among LTR.

Methods
This retrospective study reviewed clinical data of adult LTR who were complicated with nocardiosis between January-2018 and December-2022 at the large transplant center China. Diagnosis of nocardiosis was confirmed by high resolution CT and cultures from representative samples. Nocardia spp. were identified by metagenomic next generation sequencing (mNGS). Drug susceptibility was determined by E-Test for TMP-SMX, Imipenem and Linezolid, and Kirby-Bauer for the others. Patients were followed in hospital and during home therapy for the whole duration of the treatment. Cure was defined by resolution of clinical symptoms, CT scan and culture negative BAL.

Results
During the study period 18 solid organ transplant patients infected with Nocardia spp. were identified. Among these patients 14 had pulmonary nocardiosis and 4 had disseminated diseases. A total of eight species of Nocardia were identified. Nocardia farcinica was the most common (5/8); 8 strains of Nocardia were resistant to ≥1 common antibiotics (Table 1). Linezolid was the only drug which maintained activity against all Nocardia spp. The initial treatment was a combination, usually with TMP-SMX, followed by a continuation regimen reduced to a single antibiotic according to susceptibility. The overall length of combined regimen was 18 days (range 14-25). Linezolid was used in 11 and contezolid in 9 patients, respectively. In 4 patients linezolid was switched to contezolid due to thrombocytopenia (4), anemia (1), and leucopenia (4). The median length of treatment in patients receiving contezolid was 110 days (range 90-210). Overall 16/18 patients were cured, including all patients who received contezolid. Patients’ characteristics, treatment and outcomes are displayed in Table 2.

Conclusion
Our study suggests that contezolid can be used in the long-term treatment of nocardiosis among lung transplant recipients.

Disclosures
All Authors: No reported disclosures
2714. Invasive Fungal Disease in Lung Transplant Recipients: Incidence, Risk Factors, and Outcomes
Authors: Kovac Victor , Goldberg Hilary J , Kim Andy J , Joyce Mary-Ruth M , Mallidi Hari R , Coppolino Antonio , Townsend Keri , Thaniyavarn Tany , Kennedy John C , Lee Stefi F , Durney Valerie , Liakos Alexis , Harris Courtney E , Little Jessica S , Sherman Amy C , Issa Nicolas C , Baden Lindsey R , Sharma Nirmal S , Woolley Ann E 
Published: November 2023

Abstract

Background
Invasive fungal disease (IFD) is common after lung transplant and is associated with increased morbidity and mortality. Antifungal prophylaxis is a common preventative strategy against IFD in lung transplant recipients (LTRs). We assessed the incidence of IFD in the first 3-years post-transplant, diagnosed by EORTC/MSG criteria, risk factors for developing IFD, and outcomes of LTRs stratified by development of IFD at a single center that does not use universal antifungal prophylaxis post-lung transplant.
Table 1
Preoperative and perioperative characteristics and clinical outcomes of lung transplant recipients stratified by invasive fungal disease (IFD) status

Methods
A single-center, retrospective study of lung transplant recipients between January 2017 and December 2019 was performed with 3-year follow-up. Donor and recipient preoperative characteristics, microbiologic and radiographic data, perioperative characteristics, and 1- and 3-year outcomes were adjudicated and analyzed.

Results
In this 3-year study period, 168 patients underwent lung transplant. 26 (15%) developed IFD; 23 (14%) were proven or probable, and 3 (1%) were possible [Table 1]. 21 (81%) had evidence of pulmonary infection and 17 (65%) were mold infections with Aspergillus being the predominant pathogen. 4 (15%) were Candida. 81% (21/26) of patients who developed IFD were recipients of bilateral lung transplants compared to 95% (135/142) of patients who did not develop IFD (p = 0.022). Other donor/recipient characteristics and 12-month outcomes between patients who did vs did not develop IFD were similar. 21% of patients (4/19) who developed IFD had developed antibody-mediated rejection (AMR) by three years post-transplant compared to only 4% of patients without IFD (5/112) (p = 0.025). The incidence of acute cellular rejection, chronic allograft rejection, and overall survival at three years were similar.

Conclusion
Despite the lack of universal antifungal prophylaxis in the first 90 days post-transplant, we observed a low incidence of IFD in LTRs at our center in this 3-year cohort. Other than receipt of a single vs bilateral lung transplant, there were no significant differences in preoperative or perioperative recipient characteristics. Other than an increased proportion of patients who had AMR, patients who developed IFD had similar overall outcomes to those who did not have IFD, including overall survival at 1, 2, and 3 years.

Disclosures
Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Astellas: Grant/Research Support|Boehringer Ingelheim: Advisor/Consultant|Fujifilm: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support
2720. Uninvited Guests in Tiny Tummies: An Assessment of Multidrug Resistant Organism Gut Colonization in Pediatric Transplant Patients
Authors: Parzen-Johnson Simon , Arshad Mehreen , Toia Jacquie , Sajwani Alima , Patel Sameer , Kremer Aspen N , Fishbein Joseph D 
Published: November 2023

Abstract

Background and Objectives
Immunocompromised patients infected with multi-drug resistant (MDR) bacteria are at higher risk of morbidity and mortality. Gut colonization with these strains can increase the risk of invasive infections with the same organism. However, the gut as a reservoir of MDR bacteria is critically understudied in this population. This study therefore aims to determine the prevalence of MDR bacterial gut colonization in pediatric transplant patients and identify associated clinical risk factors.

Methods
A prospective cohort study of pediatric transplant patients was performed at a quaternary medical facility. Patients were enrolled prior to transplant and stool samples were obtained pre-transplant, weekly for one month after transplant, and monthly for the following 5 months. Samples were selectively cultured for ceftriaxone-resistant gram-negative bacilli (CefR-GNB). Immunosuppressant, chemotherapeutic, and antibiotic use was tracked prior to transplant through one year following discharge. Patient demographics, central-line use, admission frequency, and documented infections were also tracked.

Results
Overall, 40 patients have been enrolled with 26 patients having completed the one-year follow-up period. The 26 patients included 11 stem-cell, 5 heart, 7 kidney, and 3 liver transplants. Eleven (42.3%) patients had at least one stool culture with CefR-GNB, and 7 (26.9%) had multiple positive stool cultures. There was no significant association between hospitalizations (P = 0.57), synthetic devices (P = 0.91), median days of gram-negative active antibiotics (P = 0.74), chemotherapeutics (P = 0.64), immunosuppressants (P = 0.43) in the pre-transplant period and risk of colonization with CefR-GNB. One patient developed an invasive infection with a resistant gram-negative organism during the study period.

Conclusion
Pediatric transplant patients have high rates of colonization with resistant gram-negative bacilli in their stool. In our small sample size, there was no association seen between prior medication use, admissions, or synthetic devices in place and risk of colonization with resistant organisms. Multi-center studies need to be conducted to assess these risks further.

Disclosures
All Authors: No reported disclosures
2750. Pseudomonas aeruginosa infections treated with cefiderocol: associations of site of infection and time to first dose with outcomes in PROVE (Retrospective Cefiderocol Chart Review) Study
Authors: Marcella Stephen , Cai Bin , Friedman Bruce , Verardi Stefano , Gozalo Laurence , Slover Christine M 
Published: November 2023

Abstract

Background
Gram-negative (GN) bacterial resistance is a major global health problem. Cefiderocol (CFDC) is active against Pseudomonas aeruginosa (PA). PROVE is an international, retrospective study of CFDC use in Gram-negative infections (GNI). This analysis examines outcomes by infection site and time of first CFDC dose from culture for patients with PA as of March 2023.

Methods
Eligible patients received ≥ 72 hours of CFDC as used in routine clinical practice and had a PA culture attributed to the use of CFDC. Patient characteristics, clinical course severity, and treatment patterns were assessed. Associations of infection site, carbapenem resistance (CR), CFDC susceptibility, and time of first (index) culture sample to first CFDC dose were examined with clinical cure and all-cause mortality (ACM) at 30 days. Clinical cure at the end of treatment was defined as resolution or improvement in infection signs and symptoms without evidence of later relapse.

Results
253 patients were treated with CFDC at 39 sites in the US and Europe for a primary PA infection; 30.8% were polymicrobial with other GN pathogens (Table 1). The median age was 57 years, interquartile range (IQR) 45-65; 70% were male. The most frequent comorbidities were diabetes (34.0%) and chronic pulmonary disease (20.2%). CFDC was given in an ICU setting in 72.3% with 48.6% requiring mechanical ventilation.
The most common sites of infection were respiratory (n=166, 65.6%) of which 22 (15.3%) had secondary bacteremia (Table 1). Most (90.3%) were CR. The median time from a positive culture to start of CFDC was 5 days (IQR 3-8).
Clinical cure was 63.6% and 30-day ACM was 22.5% (Table 1). Clinical cure was comparable in respiratory with and without secondary bacteremia (63.2% and 68.2%, respectively) and was lowest in patients with skin structure infections with bacteremia (40.0%). CFDC started 3-4 days after culture had the greatest cure rate (70.8%); those started later (5-7 days) had the lowest (59.2%). 30-day ACM was also greatest for patients treated later ( &gt; 7 days after index culture) (28.1%) and for salvage after prior treatment failure (26.7%) (Table 2).

Conclusion
CFDC for PA is used in complex patients, most with respiratory disease. The trend of better outcomes with earlier use from culture warrants additional study.

Disclosures
Stephen Marcella, MD, MPH, Shionogi, Inc: contracting work for Shionogi, Inc Bin Cai, MD, PhD, Shionogi Inc.: Shionogi employee Bruce Friedman, MD, Shionogi: Honoraria Stefano Verardi, MD, Shionogi B.V.: Employee Laurence Gozalo, PhD, Shionogi, Inc: Analyst Christine M. Slover, PharmD, Shionogi,INC: Employee