bluuebunny/crossref_metadata_2025_split huggingface dataset:
2774. Predictors of Treatment Outcomes in Bloodstream Infections Due to OXA-48-producing Klebsiella pneumoniae
Authors: Huang Po-Han , Chou Sheng-Hua , Chen Wen-Yin , Lin Yi-Tsung 
Published: November 2023

Abstract

Background
Klebsiella pneumoniae causes various infections and the rising prevalence of carbapenem-resistant K. pneumoniae (CRKP) constitutes a major public health threat. Carbapenemase production is the most common mechanism of carbapenem resistance in CRKP, and OXA-48-like-producing strains accounted for about one-fifth of carbapenemase-producing CRKP worldwide. Despite clinical evidence supporting the use of ceftazidime-avibactam (CZA) in treating carbapenem-resistant Enterobacterales (CRE) infections, studies regarding its effectiveness for OXA-48-producing CRKP is limited. OXA-48-producing CRKP may test susceptible to meropenem in vitro, but whether meropenem is effective when phenotypic-genotypic discordance exists is unknown.

Methods
In this retrospective cohort study, we evaluated patients with OXA-48-producing CRKP bacteremia at Taipei Veterans General Hospital from April 2017 through December 2022. Patients were categorized into five groups according to the treatment received: CZA, meropenem, colistin, colistin-meropenem combination, and other treatments. Clinical outcomes were compared according to the antibiotics received, and logistic regression was performed to evaluate risk factors associated with treatment failure.

Results
Forty-five patients were included, with 87% (39/45) having received at least one active antibiotic against the OXA-48-producing CRKP isolated from blood. Fourteen- and 30-day mortality rates were 31% and 38%, respectively. The clinical failure rate was 27% (4/15) for patients treated with CZA, 40% (4/10) with meropenem, 100% (8/8) with colistin, 75% (3/4) with meropenem-colistin-combination, and 38% (3/8) with other treatments (P = 0.010). The clinical failure rate for meropenem-treated patients dropped to 25% (2/8) if only CRKP strains with meropenem minimal inhibitory concentration (MIC) ≤ 4 mg/L were analyzed. In multivariate analysis, clinical failure was associated with Apache II Score (P = 0.022) and colistin use (P = 0.002).
Rates of clinical failure across treatment regimens
Rates of clinical failure at different meropenem MIC values in patients receiving meropenem treatment
MIC, minimum inhibitory concentration
Multivariable analysis of risk factors associated with clinical failure at 30 days
CI, conﬁdence interval

Conclusion
CZA is an important option in the treatment of OXA-48-producing CRKP bacteremia, and meropenem may remain a reasonable alternative if meropenem MIC was ≤ 4 mg/L. Use of colistin is an independent risk factor for treatment failure and should be avoided.

Disclosures
Po-Han Huang, MD, MSc, Pfizer: Honoraria
2781. The Use of Aminoglycosides for Treatment of Urinary Tract Infections in Pediatric Patients, a Carbapenem-Sparing Approach
Authors: Legaspi Jamie , Mongkolrattanothai Kanokporn , Edward Priya , Orbach Regina 
Published: November 2023

Abstract

Background
Urinary tract infections (UTIs) caused by antimicrobial-resistant pathogens have been increasingly reported. Aminoglycosides are known to be effective therapy for UTIs, however their use is not common due to a fear of nephrotoxicity. Overuse of broad-spectrum antimicrobial agents, particularly carbapenems can lead to colonization with carbapenem-resistant pathogens resulting in more difficult-to-treat infections. We aim to evaluate the use of aminoglycosides for UTI therapy in pediatric patients to assess the clinical outcome.

Methods
A retrospective chart review was performed to evaluate all orders of aminoglycosides for the indication of UTI from 2020-2022 at Children’s Hospital Los Angeles. Demographic data, bacterial pathogen, kidney function before and during treatment, and clinical outcomes were collected and analyzed. We also evaluated the resistance patterns of bacterial pathogens, and whether they met our institutional criteria of a multi-drug resistant organism (MDRO). Patients were excluded if they received ≤ 48hrs of treatment with an aminoglycoside or if they did not have a gram-negative pathogen identified on urine culture.

Results
A total of 61 patient encounters included an aminoglycoside order for treatment of UTI during the review period. 45 out of 61 encounters had a positive urinary culture that met our institutional criteria for an MDRO. Among patients receiving aminoglycosides, we observed 4 cases of elevated sCr that met our definition of AKI. The 2 cases with the greatest creatine increase (3-4 x baseline), were also currently receiving empiric vancomycin treatment. No patients had a documented treatment failure requiring change or escalation in therapy, or lack of resolution of fever. Four cases had a recurrence within 30 days after discharge. Three out of the four patients with recurrence had pre-existing anatomical abnormalities of the urinary tract that put them at increased risk for recurrent infection.

Conclusion
Overall, extended interval aminoglycoside therapy was effective and well-tolerated for the treatment of urinary tract infections in our pediatric patient population. For cases of multi-drug resistant urinary pathogens, aminoglycosides represent a reasonable alternative to broader spectrum options such as carbapenems.

Disclosures
All Authors: No reported disclosures
2793. Clinical Outcomes of Combination Therapy with Daptomycin and Ceftaroline for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection
Authors: Chapin Ryan W , McCoy Christopher , Donohoe Kendall , Patel Dimple 
Published: November 2023

Abstract

Background
IDSA MRSA Treatment Guidelines recommend vancomycin or daptomycin as first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). Limited data and few recommendations exist regarding combination treatment for MRSA BSI outside of prosthetic valve endocarditis (PVE). The alternative treatment option of combining daptomycin with ceftaroline for its synergistic mechanism possibly through β-lactam-induced reduction in cell wall cross-linking has been pursued. This regimen is less feasible for home administration and more information on when to de-escalate to monotherapy after blood culture clearance is needed. This study evaluated clinical outcomes for patients with MRSA BSI who received combination therapy with daptomycin and ceftaroline.

Methods
This was a single-center, retrospective study evaluating hospitalized patients mostly with persistent MRSA BSI from 1/2019 to 7/2022 who received a combination of daptomycin and ceftaroline. Patients with a diagnosis of pneumonia, PVE or polymicrobial bacteremia were excluded. The primary endpoint assessed in-hospital mortality for patients on combination therapy. Secondary endpoints included readmission within 90 days, reoccurrence of bacteremia within 30 days, length of stay and adverse drug reactions during treatment.

Results
Of 73 patients screened, 14 patients were included with the primary reason for exclusion being diagnosis of PVE. Notably, half of the patients had a history of IVDU, with the majority of patients (71%) being started on initial therapy with vancomycin. Blood culture clearance occurred within 3 days of starting the combination for 11 of 14 patients. Only 4/14 patients received combination therapy for &gt; 14 days, in which one patient died on a total duration of 26 days.

Conclusion
This study demonstrated a variable duration of combination therapy for MRSA BSI in low-risk patients. The in-hospital mortality rate observed was low. All had microbiological cure. However, further exploration is needed to determine the optimal time for de-escalation after blood culture clearance. Future studies could contribute to creating stewardship efforts to de-escalate patients for MRSA BSI.

Disclosures
All Authors: No reported disclosures
2822. Impact of Restrictive Urinalysis Reflex to Culture Criteria at a Large Community Hospital
Authors: Caveness Christian F , Orvin Alison , Bouchard Jeannette 
Published: November 2023

Abstract

Background
Treatment of asymptomatic bacteriuria (ASB) is a common, but often unnecessary, practice. Some data suggest increased rates of positive urine cultures (UC) lead to ASB treatment. The objective of this study was to determine the impact of restrictive urinalysis reflex to culture (UARC) criteria on rate of UCs ordered and ASB treatment. Previous UARC criteria were any of the following: leukocyte esterase trace or greater, positive nitrites, or white blood cells (WBC) &gt; 10 cells/high powered field (HPF). On March 15, 2023, the criteria were modified to only WBC &gt; 10 cells/HPF.

Methods
This was a pre-post study evaluating UARCs ordered in the emergency department or inpatient units from March 1 to March 31, 2022 (pre-intervention) and March 16 to April 15, 2023 (post-intervention). The primary outcome was the proportion of reflex UCs prevented. Secondary outcomes included the frequency of repeat UARCs and stand-alone UCs ordered after an initial negative UARC, the incidence of patients with gram-negative rod (GNR) bacteremia within 7 days of a negative UARC, and the rate of ASB treatment in a sample of patients with positive UCs after UARC.

Results
In the pre-intervention, 4761 UARCs were ordered compared to 5420 in the post-intervention; 1806 (37.9%) and 1160 (21.4%) reflexed to UCs, leading to a 43.5% reduction in UCs. The rate of repeat UARCs, stand-alone UCs, and rates of GNR bacteremia with a negative UARC were numerically similar between groups. In the sample of pre-intervention patients (n = 100), 70 were women, median age was 74 years old (IQR 61-82), and median Charlson comorbidity index (CCI) was 5 (IQR 2-6). In total, 83 patients with positive UCs were treated, 43 (51.5%) were asymptomatic. In the post-intervention (n=68), 54 (79.4%) were women, median age was 80 (IQR 64-85), and median CCI was 5 (IQR 4-6). Fifty-five (80.9%) patients were treated, 24 (43.6%) were asymptomatic.

Conclusion
The change in UARC criteria led to a 43.5% relative reduction in UCs. A similar number of patients in the post-intervention and the pre-intervention had GNR bacteremia without a reflex UC. ASB treatment rate was lower in the post-intervention; more studies are needed to determine the true effect of restrictive UARC criteria on ASB treatment.

Disclosures
All Authors: No reported disclosures
2827. A mixed-methods analysis of provider-documented and patient-reported urinary tract infection symptoms among Veterans with neurogenic bladder
Authors: Fitzpatrick Margaret A , Wirth Marissa , Solanki Pooja , Suda Katie , Burns Stephen , Weaver Frances , Collins Eileen , Safdar Nasia , Evans Charlesnika T 
Published: November 2023

Abstract

Background
Urinary tract infections (UTI) are common in patients with neurogenic bladder (NB). Non-specific symptoms are frequent in this population, and may lead to inappropriate UTI diagnosis in patients who have asymptomatic bacteriuria. Characterization of patient-reported symptoms can inform interventions to promote appropriate UTI diagnosis.

Methods
Mixed methods study of adults with NB due to spinal cord injury/disorder (SCI/D), multiple sclerosis (MS), or Parkinson’s Disease (PD) and encounters with a UTI diagnosis (via ICD10). Provider-documented symptoms were collected from chart review of 198 encounters at 4 Veterans Affairs medical centers (VAMCs) between 2017-2018. Eleven virtual focus group discussions (FGDs) were conducted between May 2021 and May 2022 with patients from the chart review cohort with a UTI encounter in the prior year. Discussions were recorded, transcribed, and coded. Thematic analysis identified key concepts about symptoms and informed comparisons to provider-documented data from chart review.

Results
Provider-documented (n=198 encounters; SCI/D 51%, MS 20%, PD 28%) and patient-reported (n=23 FGD participants; SCI/D 78%; MS 18.5%) symptoms are in Table 1. Similar to providers, most patients noted urine changes as UTI symptoms (“cloudy” and “smelly” urine). Only 12% of encounters had provider-documented altered mental status, but this was commonly described in FGDs (“brain fog”). Only 25% of encounters had provider-documented dysuria or pelvic pain, but this was also frequently noted in FGDs (“sitting on a stick”). Several patients felt providers ignored their symptoms, particularly when they did not have fever, which may affect provider documentation. Nearly all patients noted diminished quality of life from UTI symptoms, such as difficulty engaging in social activities and psychosocial impacts from worsened mobility and functioning.

Conclusion
Both providers and patients attributed non-specific symptoms like urine changes to UTI, but there was discordance in recognition and reporting of other UTI symptoms. Optimizing care for patients with NB could involve patient and provider education on alternate sources of non-specific symptoms, interventions to improve communication about symptoms, and better assessment of quality of life impacts.

Disclosures
All Authors: No reported disclosures
2889. One vs Three Weekly Doses of Benzathine Penicillin G for Treatment of Early Syphilis in Persons with and without HIV: A Multicenter Randomized Controlled Trial (RCT)
Authors: Hook Edward W , Workowski Kimberly , Dionne Jodie A , McNeil Candice J , Taylor Stephanie N , Teresa Batteiger , Dombrowski Julia C , Mayer Kenneth H , Seña Arlene C , Wiesenfeld Harold C , Perlowski Charlotte , Newman Lori , Zhu Chunming , Mejia-Galvis Jorge E 
Published: November 2023

Abstract

Background
Syphilis rates in the United Stated (U.S.) have increased steadily for over a decade. Despite over 75 years as the drug of choice for syphilis treatment, controversy persists on optimal duration of therapy with benzathine penicillin G (BPG) for persons with early(primary, secondary, and early latent) syphilis, particularly for persons co-infected with HIV. Given the ongoing national shortages of BPG, optimizing duration of therapy is an urgent concern.

Methods
We conducted a multicenter RCT comparing a single intramuscular (IM) injection of BPG, 2.4 million units to BPG administered for three successive weeks for treatment of early syphilis in persons with and without HIV. The primary outcome of the study was a &gt; 4-fold decline in RPR titer measured at 6 months. Intention to treat (ITT) and per protocol analyses were performed and were similar. ITT analyses are presented here.

Results
A total of 249 persons with early syphilis were enrolled at 10 participating sites. Most (97%) participants were were categorized as male sex, black race (62%), and 153 (64%) were living with HIV. The syphilis stage distribution was 19% primary, 47% secondary, and 33% early latent and did not differ significantly by HIV status. Serologic response (&gt; 4-fold decline in RPR titer) at 6 months was 76% (95% Confidence Interval (CI) 0.68-0.82) in the single dose group and did not differ significantly from the three-dose group (70%, 95% CI 0.61-0.77). There were no treatment failures (&gt; 4-fold increase in RPR titer). Among persons with and without HIV there was no significant difference in RPR response at 6 months: 76% in the single-dose group vs. 71% in the 3-dose group (95% CI 0.05-0.17). Most participants experienced mild to moderate local injection site pain and tenderness.

Conclusion
Treatment of persons with early syphilis with more than a single dose of 2.4 million units of BPG offers no therapeutic benefit irrespective of HIV infection status and was associated with increased rates of injection site discomfort.

Disclosures
Edward W. Hook, III, FIDSA, GARPD (Global Antibiotic Resistance Program: Advisor/Consultant|Talis Biomedical: Advisor/Consultant|VISBY Diagnostics: Advisor/Consultant Candice J. McNeil, MD, MPH, BARDA/GSK: Grant/Research Support|Becton Dickinson: Grant/Research Support|Cepheid: Grant/Research Support|Gilead: Grant/Research Support|Hologic: Grant/Research Support|Lupin: study product Julia C. Dombrowski, MD, MPH, Hologic: Grant/Research Support|Mayne Pharmaceuticals: Grant/Research Support
181. COVID-19 Infection is a Key Factor in Mortality for Staphylococcus aureus and Candida sp. Bloodstream Infections: an Evaluation of Outcomes before and during the COVID-19 Pandemic
Authors: Cosimi Reese , Daragjati Florian , Ghosh Subhangi , Perez Moreno Ana Cristina , Miller Collin , Saake Karl , Fakih Mohamad G 
Published: November 2023

Abstract

Background
Staphylococcus aureus and Candida sp. bloodstream infections (BSI) are associated with considerable mortality. The COVID-19 pandemic presented new challenges in the acute care setting which may affect outcomes in high-risk populations.

Methods
Retrospective cross-sectional analysis across a large healthcare system of all admitted patients aged 18 years or older with S. aureus or Candida sp. BSI between pre-pandemic (January 2017-February 2020) and pandemic (March 2020- February 2023). The primary clinical outcome was all-cause mortality. Secondary outcomes include length of stay (LOS) and 30-day readmission. Data was stratified across the pre-pandemic and pandemic period, COVID-19 positive and negative patients, and community and hospital-onset BSI.

Results
A total of 17,730 patients were included in the analysis. Baseline characteristics were similar between pre-pandemic and pandemic groups aside from higher hospital-onset infection rates in the pandemic COVID-19 positive population [Table 1]. No significant differences were found in mortality between COVID-19 negative groups [Table 2]. Concomitant COVID-19 infection was associated with increased mortality in both the S. aureus and Candida sp. BSI patients.

Conclusion
While patients with concomitant COVID-19 infection had a substantially higher mortality compared to those without infection, the mortality in patients with S. aureus and Candida sp. community-onset and hospital-onset BSI did not change during the pandemic compared to pre-pandemic for patients without concomitant COVID-19 infection.

Disclosures
Reese Cosimi, PharmD, Allergen: Advisor/Consultant
187. Risk Factors and Outcomes of Patients with Serratia Bacteremia at an Academic Medical Center
Authors: Doktor Katherine L , King Madeline , Martirosyan Diana , Moore Scott R , Fraimow Henry S 
Published: November 2023

Abstract

Background
The majority of reported Serratia infective endocarditis (SIE) in recent years are healthcare-associated. At our urban institution with a high prevalence of people who inject drugs (PWID), we noted an increasing number of Serratia bacteremias (SB) and SIE over the past decade. Our study describes patient factors associated with SB and SIE.

Methods
We evaluated charts of patients with SB at our institution between 2010 and 2022 to determine risk factors and clinical outcomes.

Results
There were 157 episodes of SB in 153 patients. The majority were male (57%), white (57%) with a mean age 53. The most common source of infection was catheter- line-associated infection (CLABSI) (27%), followed by primary bacteremia (19%). Twenty-six % were PWID with younger mean age (41 years). PWID had lower mortality than non-PWID (23% vs 44%, p=0.023). Sixty-nine (46%) were admitted to the intensive care unit (ICU) with significantly higher mortality associated with ICU admission (48% vs 8%, p=0.015).
Echocardiograms were performed in 59% (93/157) of SB episodes and 14% had SIE (13/93). Most SIE (69%) occurred after 2017 with 89% in PWID (8/9). The most common comorbidity with SIE was injection drug use (IDU) (69%). All non-IDU SIE were CLABSI-related; 75% had hemodialysis catheters. Tricuspid valves were infected in 46%. Sixty-two % of those with SIE had septic emboli. Most SIE (69%) required ICU admission. Overall mortality was 31%.
Only 2% (3/153) of patients with SB developed antibiotic resistance on therapy. Clinical worsening or failure occurred in 20% (32/157). Only 5% (7/157) had microbiologic recurrence within 30 days. 32% of discharged patients re-presented to the hospital within 30 days. Almost all deaths (92%) occurred during initial admission.

Conclusion
Patients with SB were quite ill with a high rate of in-hospital mortality; over half of the patients had antibiotic exposures prior to developing SB or presented within 90 days of a prior hospitalization. The majority of SB were line-associated, including all episodes of non-IDU SIE. IDU was the second most common comorbidity and PWID with SB had a higher rate of SIE, with most IDU-associated SIE diagnosed after 2017. This aligns with other recent studies documenting the increased prevalence of SB, especially in PWID.

Disclosures
Madeline King, PharmD, La Jolla: Advisor/Consultant|Shionogi: Advisor/Consultant
205. The increasing trend of penicillin resistance in Streptococcus suis clinical isolates during the past 5 years in a tertiary hospital in Thailand
Authors: Kiatkangwanchon Natthapol , Wongjarit Kanphai , Nilgate Sumanee , Chatsuwan Tanittha , Suankratay Chusana 
Published: November 2023

Abstract

Background
Streptococcus suis, an emerging zoonotic pathogen, is able to cause a wide spectrum of infections including primary bacteremia, meningitis, endocarditis, and other localized infections. Due to the increasing and widespread use of antibiotics in pig industry in Thailand, will contribute to the emergence of antimicrobial resistance to infection caused by S. suis. We aimed to determine the in vitro susceptibility of S. suis clinical isolates, in accompanying with the treatment outcomes.

Methods
A retrospective study was carried out on all patients with S. suis bacteremia at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from 2017 to 2022. S. suis identification was analyzed by conventional biochemical tests, the API-20 STREP system (bioMérieux, Marcy-l'Étoile, France), or MALDI-TOF MS. In vitro susceptibility test of penicillin, cefotaxime, meropenem, and vancomycin was carried out by E-test according to CLSI recommendation.

Results
There were 32 patients with 17 (53.1%) male and median age of 57 (IQR: 50-65) years. Comorbidities were diabetes (10 patients, 31.3%) and cancer (4, 12.5%). 12 (37.5%) patients had a history of consumption of undercooked pork products. Regarding clinical syndrome, there were 15 (46.9%), 6 (18.8%), 6 (18.8%), and 3 (9.4%) patients with primary bacteremia, infective endocarditis, meningitis, and septic arthritis/spondylodiscitis, respectively. The median length of stay was 13 (IQR: 5-16) days. The most common empirically used antibiotic was ceftriaxone (26 patients, 81.3%), followed by meropenem (3, 9.4%), and ampicillin (2, 6.2%). De-escalation treatment to penicillin G sodium was performed in 11 (34.4%) patients. Of 29 patients with available outcomes, there were 19 (65.5%), 6 (20.7%), and 3 (10.3%) patients with complete recovery, hearing loss, and mortality, respectively.
In vitro susceptibility results are shown in Tables 1 and 2.Table 1.The minimum inhibitory concentration (MIC) distribution for Streptococcus suis blood isolates.Table 2.MIC50, MIC90, MIC ranges, and susceptibility according to 2023 CLSI clinical breakpoints for Streptococcus suis blood isolates.

Conclusion
S. suis bacteremic patients still had favorable outcomes despite the emergence of penicillin resistance. All isolates were susceptible to meropenem and vancomycin, and most were susceptible to cefotaxime. However, only 28.1% was still susceptible to penicillin. Third-generation cephalosporin should be the first agent for empirical treatment in patients with suspected S. suis bacteremia.

Disclosures
All Authors: No reported disclosures