Recurrent Bloodstream Infections Research Articles

P-889. Therapeutic Failures of High Inoculum Infections with Cefazolin: Role of A Rapid Test and Prevalence of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus (MSSA) Bloodstream Infections

Abstract Background Cefazolin (CFZ) remains a key therapy for MSSA bloodstream infections (BSIs), yet some studies suggest poorer outcomes when CFZ is used in the presence of cefazolin inoculum effect (CzIE). We developed a rapid colorimetric test with nitrocefin to detect CzIE in MSSA. Here, we report the performance of the rapid test in four recurrent BSIs caused by MSSA exhibiting the CzIE. Furthermore, we assess the local prevalence of CzIE using both standard broth microdilution (BMD) and the rapid test. Methods A chart review collected clinical data from four patients, including demographics, microbiologic features, antibiotic therapies, and clinical outcome. Patients were selected based on positive MSSA BSI after initial clearance, and availability of their index isolate. The nitrocefin-based rapid test was performed according to a published protocol. For the surveillance step, MSSA were collected from initial cultures of adult patients diagnosed with BSIs between July 2023 and April 2024 from 8 hospitals. The CzIE was assessed using BMD at standard (105) and high (107) inocula, with a cutoff CFZ MIC ≥ 16 μg/ml. The rapid test was performed in all isolates. Results All four patients had deep-seated infections, including endocarditis, osteomyelitis, or device-related infections, with two patients undergoing surgical interventions. While receiving CFZ therapy, all patients successfully cleared their MSSA BSI. After initial clearance, these patients received prolonged antibiotic therapy lasting ≥ 6 weeks, with 3 of 4 patients continuing with CFZ, as part of their initial therapy. Despite this, MSSA BSI recurred between 34 and 155 days after initial hospitalization. Notably, all index isolates tested positive for CzIE via the rapid test. During the surveillance period, we collected 196 isolates, with a 40% (79/196) prevalence of the CzIE based on BMD. The rapid nitrocefin test correctly identified 72 of 79 strains exhibiting the CzIE, with 91% sensitivity and 80.3% specificity. Conclusion These findings underscore a high prevalence of MSSA isolates exhibiting CzIE in BSIs. Patients infected with MSSA displaying CzIE may face an increased risk for recurrence when treated with CFZ. Further validation of these observations is warranted to better understand their clinical implications. Disclosures José M Munita, MD, MSD: Grant/Research Support|Pfizer: Grant/Research Support William R. Miller, M.D., Merck: Grant/Research Support|UptoDate: Royalties

P-877. Effectiveness of Oral Step-down Antibiotic Therapy in Uncomplicated Enterococcus faecalis Bloodstream Infection

Abstract Background The transition from intravenous (IV) to oral antibiotic therapy is a common strategy in the management of uncomplicated bloodstream infection (BSI). However, the role of oral step-down therapy in uncomplicated Enterococcus faecalis BSI has not been defined. This retrospective cohort study examines the effectiveness of oral step-down antibiotics compared to standard IV therapy in uncomplicated E. faecalis BSI. Risk factors for treatment failure in uncomplicated Enterococcus faecalis bloodstream infection (BSI) *Early clinical failure criteria include systolic blood pressure <100 mmHg or vasopressor use, heart rate >100 beats/minute, respiratory rate ≥ 22 breaths/minute or mechanical ventilation, altered mental status, white blood cell count >12,000/mm3. Methods Adults with uncomplicated E. faecalis BSI admitted to 10 Prisma Health hospitals in South Carolina from January 2021 to June 2023 were evaluated. Clinically insignificant positive blood cultures, polymicrobial, recurrent, persistent, and complicated BSI were excluded. Deaths within 7 days were excluded to mitigate immortal time bias. Multivariate Cox proportional hazards regression examined the risk of treatment failure (all-cause mortality or recurrence) within 90-day. Wilcoxon rank sum test compared hospital length of stay (HLOS) between the two groups. Results Of 476 screened patients, 131 with uncomplicated E. faecalis BSI were included in the analysis. The median age was 70 years, 84 (64%) were men, and 46 (35%) had a urinary source of infection. Eighty-seven patients (66%) received standard IV therapy and 44 (34%) were transitioned to oral step-down therapy. Median antibiotic treatment durations were 15 and 14 days, respectively. Patients in the oral step-down group received 6 days of IV antibiotics followed by 8 days of oral therapy, most commonly oral aminopenicillins (33/44; 75%). In the multivariate Cox model, oral step-down therapy was not associated with increased risk of treatment failure compared to standard IV therapy (hazard ratio 0.91, 95% confidence intervals 0.31-2.63; Table). HLOS was 7 days in the oral step-down group and 11 days in the standard IV group (p< 0.001). Conclusion Transitioning patients with uncomplicated E. faecalis BSI from IV to oral step-down antibiotic therapy appears to be a promising strategy with shorter HLOS and no significant increase in the risk of treatment failure. These results should be confirmed in larger multicenter studies prior to routine implementation in clinical practice. Disclosures All Authors: No reported disclosures

P-819. Epidemiology of Serratia marcescens Bloodstream Infections in a Hospital System in the Southeast U.S

Abstract Background Serratia marcescens (Sm) is an environmental gram-negative bacilli that can cause a variety of serious human infections. Sm is frequently attributed as a hospital acquired infection. However, there is not extensive documentation as to the common etiologies of Serratia bloodstream infections (BSI), frequency of antibiotic resistance, and risk factors for recurrent infection or mortality. Methods We conducted a retrospective chart review of a cohort of patients (pts) ≥ 18 years old with Serratia marcescens BSI from 5/2016 to 10/2022 at our hospital system. Sm BSI was defined as ≥ 1 blood culture positive for Sm. Multidrug resistance was defined according to Centers for Disease Control (CDC) criteria. Patients were assessed for outcomes of recurrence of bacteremia (positive blood culture with same isolate within 3 months of clearance) and 30-day mortality. Results A total of 243 patients had Sm BSI during the study period. The most frequent etiology was central line-associated BSI (38%) followed by skin and soft tissue infection (12%). The majority (96%) of isolates were not multidrug resistant. Most patients had a repeat blood culture (67%), and of these patients, 15% had recurrence of bacteremia. A total of 44 patients (18%) died within 30 days. Echocardiogram was performed in 60% of our patients, with 7 patients diagnosed as having endocarditis or device endocarditis. Current active or history of injection drug use occurred in 7.5% of patients. Conclusion Our retrospective study demonstrates a low burden of antibiotic resistance in Sm at our hospital system. Similar to prior studies, CLABSI is a frequent cause of Sm BSI, and foreign materials/devices are common in patients with Sm BSI. Our patient population has a lower rate of IVDU compared to other studies of Sm BSI, and endocarditis is not common. Further analysis is needed to evaluate treatment regimens and other risk factors for recurrent BSI and mortality. Disclosures All Authors: No reported disclosures

P-2277. Impacts of Ongoing Quinolone Prophylaxis Following Quinolone-Resistant Bacteremia in Neutropenic Patients

Abstract Background Guidelines that suggest fluoroquinolone (FQ) prophylaxis for intermediate to high-risk hematologic malignancy patients are based primarily on evidence of reduction in bloodstream infections (BSIs) in historic studies, despite no demonstrated reduction in other outcomes such as mortality, septic shock, or ICU admissions. In the era of widespread FQ use for prophylaxis and increasing antimicrobial resistance, ongoing re-evaluation of the benefit is needed. Patients with BSI due to FQ-resistant gram-negative organisms may have particularly reduced benefit from ongoing FQ prophylaxis, however data on this topic is limited. We evaluated characteristics of neutropenic patients with BSI in an attempt to better inform the risk/benefit balance in this population. Figure 1. Numerical breakdown of bacteremia episodes Methods We extracted episodes of gram-negative BSI during a neutropenic episode lasting at least 7 days in adult inpatients with hematologic malignancy and/or stem cell transplant (study period 11/1/2020-11/1/2023). For each BSI episode we collected data on treatment (agent, duration, line removal), FQ susceptibility, underlying disease, neutropenia, and FQ exposure within 90 days. For episodes with an opportunity to resume prophylaxis following treatment of bacteremia (based on persistent neutropenia or recurrent neutropenia with 90 days), we determined rates of recurrent BSI within 90 days, stratified by FQ resistance and decision to resume FQ prophylaxis. Results There were 82 BSI episodes (69 first episodes, 13 recurrent) among 62 patients. FQ resistance was common in first episodes (34/69, 49%) and median prior FQ exposure within 90 days was 16 days. 43 episodes had an opportunity to resume FQ prophylaxis and 19/43 (44%) had FQ resistance. FQ prophylaxis was resumed in 16/19 (84%) with FQ resistance and 21/24 (88%) without, with rates of recurrent bacteremia within 90 days of 44% and 29% respectively. There were no episodes of recurrent bacteremia when FQ prophylaxis was not resumed (0/6).Table 1.Characteristics of bacteremia episodes with an opportunity to resume fluoroquinolone prophylaxis following treatment Conclusion Among bacteremia episodes with eligibility for FQ prophylaxis following treatment, recurrent bacteremia was common, particularly when FQ resistance was present. FQ prophylaxis may have little or no benefit in this setting, however larger studies and controlled data are needed. Disclosures All Authors: No reported disclosures

In vivo selection of carbapenem resistance during persistent Klebsiella pneumoniae sequence type 395 bloodstream infection due to OmpK36 deletion.

Non-carbapenemase-producing carbapenem-resistant Enterobacterales (non-CP CRE) may be associated with a grave outcome. The common underlying mechanism is beta-lactamases and mutations in outer membrane porins. We report a case of a deep-seated infection caused by Klebsiella pneumoniae ST395 not amenable to source control, involving recurrent bloodstream infection, resulting in in vivo selection of carbapenem resistance under therapy. Three consecutive K. pneumoniae blood isolates were studied using short- and long-read sequencing. The genomes were subject to resistome and virulome, phylogenetic, and plasmid analyses. ompK36 porins were analyzed at the nucleotide and amino acid levels. Genomes were compared to 297 public ST395 K. pneumoniae genomes using cgMLST, resistome, and porin analyses and the EuSCAPE project. Relevant ompK36 and micF sequences were extracted and analyzed as above. The three sequential K. pneumoniae blood isolates belonged to the same clone. Subsequent CR isolates revealed a new large deletion of the ompK36 gene also involving the upstream region (deletion of micF). Comparison with public ST395 genomes revealed the study isolates belonged to clade B, representing a separate clone. N-terminal large ompK36 truncations were uncommon in both public data sets. In vivo selection of non-CP CRE K. pneumoniae could have substantial clinical implications. Such selection should be scrutinized through repeated cultures and frequent susceptibility testing during antimicrobial treatment, especially in the context of persistent or recurrent bloodstream infections and when adequate source control cannot be achieved. The occurrence of an unusually large deletion involving the ompK36 locus and upstream micF should be further studied.

Antibiotic duration and route for treatment of adults with uncomplicated streptococcal bloodstream infections: a retrospective study in a large healthcare system.

Data guiding the duration and route of streptococcal bloodstream infection (BSI) treatment are lacking. We conducted a retrospective cohort study of adults hospitalized with uncomplicated streptococcal BSI in a large integrated healthcare system from 2013 to 2020. The exposures of interest were antibiotic duration (5-10 days vs. 11-15 days) and antibiotic route (oral switch vs. entirely intravenous). The primary outcome was a composite 90-day outcome comprised of all-cause mortality, recurrent streptococcal BSI, or readmission. We performed non-inferiority analyses for each exposure. Separate multivariable Cox proportional hazards regression models were constructed for each exposure. The antibiotic duration analysis included 1,407 patients (5-10 days, n = 246; 11-15 days, n = 1,161). We found that 5-10-day courses were non-inferior to 11-15-day courses (P = 0.047). The antibiotic route analysis included 1,461 patients (oral switch, n = 1,112; entirely intravenous, n = 349). Oral step-down therapy did not meet the criteria for non-inferiority (P = 0.06). In the adjusted models, no significant difference was found in the primary outcome rate by antibiotic duration or antibiotic route at discharge. We found that 5-10-day courses were non-inferior to longer courses, and thus may be a safe and effective treatment option in the treatment of uncomplicated streptococcal bacteremia. Randomized controlled trials are needed to confirm the equivalent outcomes with shorter regimens and to definitively determine the optimal antibiotic route on discharge.

Efficacy of short- versus prolonged-courses of antimicrobial therapy for carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A propensity score-matched cohort study

BackgroundAs limited antibiotic options are available for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs), the optimal treatment duration for CRKP BSIs is unclear. Our objective was to investigate whether short courses (6–10 days) are as effective as prolonged courses (≥11 days) of active antibiotic therapy for CRKP BSIs. MethodsA retrospective cohort study comprising adults with monomicrobial CRKP BSI receiving a short or prolonged course of in vitro active therapy at a medical center was conducted between 2010 and 2021. Comparisons of two therapeutic strategies were assessed by the logistic regression model and propensity score analysis. The primary endpoint was 30-day crude mortality. Secondary outcomes included recurrent BSIs, the emergence of multidrug-resistant organisms and candidemia during hospitalization after completing antibiotic therapy for CRKP BSIs. ResultsOf 263 eligible adults, 160 (60.8%) were male, and the median (interquartile range) age was 69.0 (53.0–76.0) years. Common comorbidities included diabetes (143 patients, 54.4%), malignancy (75, 28.5%), cerebrovascular accident (58, 22.1%), and hemodialysis (49, 18.6%). The 30-day mortality rate was 8.4% (22 patients). Of 84 propensity score well-balanced matched pairs, the 30-day mortality was similar in the short-course and prolonged-course group (6.0% and 7.1%, respectively; P = 1.00). However, there were less episodes candidemia in the short-course group (1.2% versus 13.1%; odds ratio, 0.08; 95% confidence interval, 0.01–0.63; P = 0.005). ConclusionShort courses of active therapy for CRKP BSIs demonstrate comparable clinical outcomes to prolonged courses and are associated with a lower risk of subsequent candidemia.

Persistent Gram-negative Bloodstream Infection Increases the Risk of Recurrent Bloodstream Infection With the Same Species.

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection.

Characterization of Prescribing Practices for Uncomplicated Streptococcal and Enterococcal Bacteremias: The NARRATE Study.

Bloodstream infections (BSIs) rank among the top causes of death in North America. Despite the prevalence of these infections, there remain significant practice variations in the prescribing of antibiotics. To investigate current prescribing practices for management of uncomplicated streptococcal and enterococcal BSIs. A retrospective cohort study was conducted using charts for patients admitted to an acute care centre in British Columbia between November 16, 2019, and October 20, 2020. Adult patients (≥ 18 years of age) with a diagnosis of uncomplicated streptococcal or enterococcal BSI were included. Patients were excluded if they had polymicrobial bacteremia or deep-seated infection or had been admitted for no more than 48 hours. The primary outcomes were duration of antibiotic therapy (IV and oral) and time to appropriate oral therapy for treatment of BSI. The secondary outcomes were observed rates of re-initiation of antibiotics and readmission with recurrent BSI. Descriptive statistics were calculated and regression analysis was performed for the primary and secondary outcomes. A total of 96 patients met the inclusion criteria. The median total duration of therapy for uncomplicated streptococcal and enterococcal BSI was about 2 weeks. Streptococcus pneumoniae BSIs were associated with a significantly shorter duration of IV therapy and were more likely to be associated with transition to oral antibiotics. No recurrent BSIs were observed in patients for whom therapy was transitioned to oral antibiotics. Further study is warranted to explore shorter duration of antibiotic therapy and transition to oral therapy as treatment approaches for uncomplicated streptococcal and enterococcal BSI. Other outcomes of interest for future research include determining the optimal time for transition to oral therapy.

Mortality, hospital length of stay, and recurrent bloodstream infections associated with extended-spectrum beta-lactamase-producing Escherichia coli in a low prevalence region: A 20-year population-based large cohort study

ObjectivesThis population-based study aimed to investigate the risk factors and effect of extended-spectrum beta-lactamase (ESBL) production on clinical outcomes in Escherichia coli bloodstream infection (BSI) patients. MethodsThe study population was defined as patients aged ≥15 years with E. coli BSI in Queensland, Australia, from 2000 to 2019. Outcomes were defined as 30-day case fatality, hospital length of stay (LOS), and recurrent E. coli BSI. ResultsA total of 27,796 E. coli BSIs were identified, of which 1112 (4.0%) were ESBL-producers. Patients with ESBL-Ec BSI were more frequently older, male, with comorbidity, recurrent E. coli BSI, and less likely with community-associated community-onset infections as compared to non-ESBL-Ec BSI patients. The standardized mortality rate of ESBL-Ec BSI increased 8-fold from 2000 to 2019 (1 to 8 per million residents) and case fatality was 12.8% (n = 142) at 30 days from positive blood culture. Patients with ESBL-Ec BSI were not at higher risk of 30-day case fatality (adjusted hazard ratio [HR] = 0.98, 95% CI: 0.83-1.17), but had higher risk of recurring episodes (adjusted subdistribution HR = 1.58, 95% CI: 1.29-1.92) and observed 14% longer LOS (adjusted incidence rate ratio = 1.14, 95% CI: 1.10-1.18) than non-ESBL-Ec BSI patients. ConclusionIn this large patient cohort, ESBL-Ec BSI did not increase case fatality risk but observed higher hospital LOS and recurrent E. coli BSI than non-ESBL-Ec BSI. Clinical resources are warranted to account for the higher morbidity risk associated with ESBL production and incidence.

Short-Course Versus Prolonged-Course Antimicrobial Therapy in Adults With Catheter-Related Septic Thrombosis: A Propensity-Weighted Retrospective Study

Abstract Background Optimal duration of antimicrobial therapy (AT) for catheter-related septic deep venous thrombosis (DVT) is unknown. We aimed to compare the outcomes of patients receiving short-course AT (≤21 days) versus prolonged-course AT (>21 days). Methods This was a monocentric retrospective study comparing adults with catheter-related septic DVT from 2015 to 2020 treated with short- or prolonged-course AT. A propensity score–weighted analysis was used to mitigate potential bias. The primary outcome was a composite of all-cause mortality or recurrent bloodstream infection 30 days after AT discontinuation. Results Of 172 patients with catheter-related septic DVT, 104 were treated with prolonged-course AT and 68 with short-course AT. In the propensity score analysis, we found no significant difference in 30-day all-cause mortality or relapse between the 2 groups (inverse probability of treatment weighted hazard ratio [wHR], 2.16 [95% confidence interval {CI}, .68–6.88]; P = .192). No differences in 90-day all-cause mortality and 90-day relapse were observed between the treatment groups (wHR, 1.01 [95% CI, .49–2.05], P = .987 and 1.13 [95% CI, .08–15.62], P = .928, respectively). Conclusions A 21-day AT could be an effective and safe option to treat catheter-related septic DVT. Further randomized studies are needed to establish the optimal duration of AT for patients with catheter-related septic DVT.

Management and outcomes of heart transplant candidates with bloodstream infection on temporary mechanical circulatory support

The outcomes and management of bloodstream infection (BSI) in patients on temporary mechanical circulatory support (TMCS) awaiting heart transplant (HT) are poorly understood. We present outcomes of patients on TMCS with BSI (TMCS-I) relative to matched uninfected patients (TMCS-U) and discuss their management. Between 1/1/2013-4/30/2023, N=136 patients were bridged to transplant with TMCS at Emory Transplant Center. Twenty-one (15.4%) were TMCS-I. Two (9.5%) had infective endocarditis. Median duration of antimicrobial treatment was 24 days (IQR 28.3). All TMCS-I were re-activated for transplant within 48-72 hours of negative blood cultures. None developed recurrent BSI. Post-transplant survival did not differ between TMCS-I and TMCS-U (P=0.38). HT for TMCS-I may be safe as soon as blood cultures clear. Duration of antimicrobial therapy is individualized and depends on the organism, duration of bacteremia, presence of endocarditis, and timing of HT. Additional research is needed to determine optimal duration of treatment.

Temporal dynamics of genetically heterogeneous extended-spectrum cephalosporin-resistant Escherichia coli bloodstream infections.

Extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ec infections. To address the paucity of recent ESC-R-Ec molecular epidemiology data in the United States, we used whole-genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ec at a tertiary care cancer center in Houston, Texas, collected from 2016 to 2020. During the study time frame, there were 1,154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. Using time series analyses, we identified a temporal dynamic of ESC-R-Ec distinct from ESC-susceptible E. coli (ESC-S-Ec), with cases peaking in the last 6 months of the calendar year. WGS of 297 ESC-R-Ec strains revealed that while STc131 strains accounted for ~45% of total BSIs, the proportion of STc131 strains remained stable across the study time frame with infection peaks driven by genetically heterogeneous ESC-R-Ec clonal complexes. bla CTX-M variants accounted for most β-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R-Ec), and amplification of bla CTX-M genes was widely detected in ESC-R-Ec strains, particularly in carbapenem non-susceptible, recurrent BSI strains. Bla CTX-M-55 was significantly enriched within phylogroup A strains, and we identified bla CTX-M-55 plasmid-to-chromosome transmission occurring across non-B2 strains. Our data provide important information regarding the current molecular epidemiology of invasive ESC-R-Ec infections at a large tertiary care cancer center and provide novel insights into the genetic basis of observed temporal variability for these clinically important pathogens. IMPORTANCE Given that E. coli is the leading cause of worldwide ESC-R Enterobacterales infections, we sought to assess the current molecular epidemiology of ESC-R-Ec using a WGS analysis of many BSIs over a 5-year period. We identified fluctuating temporal dynamics of ESC-R-Ec infections, which have also recently been identified in other geographical regions such as Israel. Our WGS data allowed us to visualize the stable nature of STc131 over the study period and demonstrate a limited but genetically diverse group of ESC-R-Ec clonal complexes are detected during infection peaks. Additionally, we provide a widespread assessment of β-lactamase gene copy number in ESC-R-Ec infections and delineate mechanisms by which such amplifications are achieved in a diverse array of ESC-R-Ec strains. These data suggest that serious ESC-R-Ec infections are driven by a diverse array of strains in our cohort and impacted by environmental factors suggesting that community-based monitoring could inform novel preventative measures.

Outcomes associated with empiric cefepime for bloodstream infections caused by ceftriaxone-resistant, cefepime-susceptible Escherichia coli and Klebsiella pneumoniae

BackgroundCefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L. MethodsThis single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours. ResultsFifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2–6) days and 7 (5–10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016). ConclusionMortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Recurrent bloodstream infections after allogeneic hematopoietic cell transplantation

ABSTRACT Background Although colonization is an established risk factor for bloodstream infection (BSI) due to identical strain, prior infection with resistant bacteria should also be considered during the management of febrile neutropenia. This study aimed to analyze the rate and etiology of recurrent BSI in allogeneic hematopoietic cell transplant (allo-HCT) recipients to determine its potential impact on decision-making. Materials and methods The retrospective study included 284 allo-HCT recipients. Recurrent BSI was defined as a new BSI episode occurring in a period of more than 72 hours after antibiotic withdrawal. Results Overall, 104 patients (36.6%) developed at least one BSI, and 23 of them (22.1%) experienced recurrent BSI episodes (n = 30). Median time to recurrent BSI was 41 days (range 5–526 days). Recurrent BSI was associated with second allo-HCT (p < 0.0001), primary (p = 0.021), and secondary graft failure (p = 0.024). Carbapenem-resistant gram-negative bacteria were more common during recurrent BSI episodes (23.7% vs. 6.0%; p = 0.003). In only 17.5% patients experiencing recurrent BSI episode and in only 3.9% of patients with at least one BSI episode phenotypically identical recurring pathogen was isolated. Conclusions In view of low rate of recurrent BSI due to identical pathogen, empirical antimicrobial therapy should not be based on data on previous BSI episodes.

1857. Risk factors for recurrent bacteremia in children undergoing chemotherapy or hematopoietic stem cell transplantation

Abstract Background Sepsis is a complication frequently encountered in children with underlying malignancies, especially due to a majority of patients having indwelling venous catheters. Indications for catheter removal among children with central-line associated blood stream infection (CLABSI) should follow the recommendations for adults, however, difficulties in vascular access often leads to attempting treatment without catheter removal. Therefore, the primary aim of this study was to find risk factors for recurrent sepsis in children undergoing chemotherapy of HSCT and examine whether more aggressive catheter removal after CLABSI in children is necessary. Methods In the Pediatric Bone Marrow Transplant Center of Seoul St. Mary’s Hospital, positive blood cultures were prospectively monitored to control and prevent outbreaks. The date of culture, culture results, symptoms presented, category of blood stream infections (by the CDC/NHSN surveillance definition (2021) of Bloodstream infections), and central-line associated blood stream infection (CLABSI) events were monitored. Results During September 2016 to February 2021, a total 280 cases of laboratory confirmed bloodstream infections (LCBI) or Mucosal Barrier Injury LCBI (MBI-LCBI) were diagnosed in children &amp;lt; 18 years old with underlying malignancies. Of these, 52.9% (n=148) were male, and the mean age was 9.7 (SD±6.1) years old. CLABSI was diagnosed in 51.8% (n=145), and the most common pathogens cultured were S. mitis/oralis (24.0%, n=67), E. coli (15.4%, n=43), and coagulase negative Staphylococci (CNS) (10.4%, n=29). Recurrent sepsis occured in 17.1% (n=48), and 9.6% (n=27) had two indwelling catheters . Multivariable analysis showed that factors associated with recurrent blood stream infections were as follows: duration of indwelling catheter (OR, 1.002; 95% CI, 1.001-1.004; P&amp;lt; 0.001) and no removal of central lines after previous episode (OR, 51.143; 95% CI, 6.6-395.0; P&amp;lt; 0.001). Conclusion Permanent central lines should be removed as soon as possible, and more aggressive approach in permanent catheter removal after LCBSIs in children is necessary to reduce recurrent infections. Disclosures All Authors: No reported disclosures.

1992. Risk of Infective Endocarditis in Streptococcal mitis Bloodstream Infections Among Patients with Neutropenia from Hematologic Malignancies

Abstract Background Streptococcus mitis is a common colonizer of the human oral and gastrointestinal tract. Patients with neutropenia due to hematologic malignancy (HM), particularly those prescribed fluoroquinolone prophylaxis are at increased risk of a S. mitis bloodstream infection (BSI). Risk of infective endocarditis (IE) in this patient population remains unclear. Methods This was a multicenter, retrospective study of neutropenic (ANC &amp;lt; 500 K/uL) patients with HM from November 2016 - February 2022. Patients were included if they had S. mitis isolated in at least 1 blood culture bottle. The primary outcome was number of patients who developed IE based on cardiac imaging. Secondary outcomes included number of patients who underwent IE workup via cardiac imaging and BSI recurrence within 12 weeks. Results Among 171 patients who met the inclusion criteria, 101 (59%) were male and median age was 60 years old (range 19-86). Patient demographics, microbiologic information and outcomes are shown in Table 1. All patients in the cohort had native cardiac valves. Acute leukemia/myelodysplastic syndrome was the most common HM (n=129, 75%), followed by lymphoma (n=27, 16%), multiple myeloma (n=10, 6%) and chronic leukemia (n=5, 3%). Most patients had a transthoracic echocardiogram (TTE) (n=97, 56.7%) within 7 days of BSI. Of these patients, 1 had suspected valvular vegetations on TTE, but transesophageal echocardiogram (TEE) was negative. Two patients had negative TTEs, but there was a high clinical suspicion, so cardiac computed tomography was performed and showed no valvular vegetations. Despite negative cardiac imaging, 1 patient completed 6 weeks of empiric treatment for IE based on radiographic findings in the torso suggesting visceral infarcts. One patient had S. mitis BSI recurrence within 12 weeks of first positive culture. Median duration of antimicrobial therapy for BSI was 15 days (range 8-43). Conclusion IE is uncommon in neutropenic HM patients with native cardiac valves and S. mitis BSI. In this cohort where approximately half had a TTE after bacteremia and median duration of BSI therapy was 15 days, recurrent BSI was rare, suggesting that IE cases were not underdiagnosed in those without cardiac imaging. Cardiac imaging such as TTE to rule out IE may not be necessary for all patients in this population. Disclosures Ramy H. Elshaboury, PharmD, Eli Lilly: Honoraria|Gilead Sciences: Grant/Research Support David W. Kubiak, PharmD, BCPS, BCIDP, FIDSA, Astellas Pharma, Inc.: Advisor/Consultant|AVIR Pharma Inc: Advisor/Consultant|Cidara Therapeutics: Advisor/Consultant Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Scynexis: Grant/Research Support.

152. Molecular Epidemiological Analysis of Relapsed Gram-negative Bloodstream Infection Isolates

Abstract Background Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Many patients experience multiple episodes of GNB-BSI for unclear reasons. This study examines the genetic differences between initial and subsequent isolates of recurrent GNB-BSI. Methods We used a prospective cohort of patients with GNB-BSI at Duke Hospital to identify patients with &amp;gt;1 episode of GNB-BSI due to the same bacterial species. We performed pulsed field gel electrophoresis (PFGE) on paired isolates to determine if the events were Reinfection (paired isolates different) or Relapse (paired isolates genetically identical). We then used whole genome sequencing (WGS) to verify the PFGE findings and explore the genetic similarity between initial and relapsed GNB-BSI isolates. Results Among 1,423 unique patients with GNB-BSI, 60 (4%) experienced recurrent GNB-BSI with the same bacterial species. We performed genotyping (PFGE, followed by WGS) on the paired bacterial isolates from the index and recurrent bloodstream infections for the four most common species in our study population (Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, and Serratia marcescens) (n=48 pairs). We determined that 63% (30/48) of recurrent GNB-BSI episodes were due to relapse and 37% (18/48) were due to reinfection. PFGE correctly identified relapse versus reinfection in 98% (47/48) of cases. The WGS data illustrated the microevolution of relapsed GNB-BSI isolates within patients. When comparing initial to relapsed isolates, we calculated a median of 5 single-nucleotide polymorphisms (SNPs) in relapsed E. coli isolates and 2 SNPs in Klebsiella spp. isolates. Of these SNPs, 37% (E. coli) and 12% (Klebsiella) were non-synonymous changes in coding regions, most commonly genes associated with antimicrobial resistance (AMR), energy metabolism and stress response. Alterations in the AMR profile was common, with 20/30 relapsed isolates demonstrating either loss or acquisition of AMR. Figure 1:Time from initial to recurrent episode of gram-negative bloodstream infection. Relapse (i.e., same bacterial strain noted by green circle) versus reinfection (i.e., different bacterial strain noted by red circle) was determined by pulse field gel electrophoresis followed by WGS. Whole genome sequencing was performed on the initial and recurrent isolate from patients with relapsed GNB-BSI. We identified single nucleotide polymorphisms (SNPs) present in the recurrent isolate, which were not present in the initial isolate. We identified the function of genes containing SNPs in E. coli (n=28 SNPs) and Klebsiella spp. (n=13 SNPs). Synonymous mutations, insertions, deletions, and non-synonymous mutations in hypothetical proteins were excluded. Conclusion Most recurrent GNB-BSI with same species are due to relapse. PFGE has comparable accuracy to WGS to determine reinfection versus relapse. Multiple mutations in genes involved in stress response, AMR and metabolism were identified in relapsed isolates. Disclosures Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds.

Short Course of Antifungal Therapy in Patients With Uncomplicated Candida Bloodstream Infection: Another Case of Less Is More in the Clinical Setting?

The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated Candida bloodstream infections (BSIs). All episodes of uncomplicated Candida BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent Candida BSI and all-cause 1-year mortality) among patients who underwent SC (5-11 days) or PC (12-24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. A total of 114 patients with uncomplicated Candida BSI were included: 35 (30.7%) were classified into the SC group (median [interquartile range {IQR}], 9 [7-11] days) and 79 (69.3%) into the PC group (median [IQR], 14 [14-16] days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%; P = .02) or septic shock at the time of Candida BSI onset (11.4% vs 1.3%; P = .03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 [22.9%] vs 17 [21.5%], respectively; IPTW-adjusted subdistribution hazard ratio [sHR], 0.67; 95% CI, 0.31-1.47; P = .20). The risk for recurrent Candida BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20-5.80; P = .94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35-1.50; P = .38) did not differ between groups. Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia.

Highly versus less bioavailable oral antibiotics in the treatment of gram-negative bloodstream infections: a propensity-matched cohort analysis

ObjectivesIn this study, we evaluated the clinical outcomes associated with the use of highly bioavailable oral antibiotics (fluoroquinolones and trimethoprim-sulfamethoxazole) compared with the less-bioavailable oral antibiotics (β-lactams) in gram-negative bloodstream infections (BSIs). MethodsAmong hospitalized older adult patients in Ontario, Canada, discharged home on oral treatment for gram-negative BSI between 1 January 2017 and 31 December 2019, we used a matched cohort design to compare outcomes among those receiving highly versus less-bioavailable agents; hard-matching 1:1 on sex, BSI pathogen (Escherichia coli vs. non–E. coli), and infection source (urinary vs. non-urinary/unknown source) along with a propensity score, incorporating specific pathogen, patient, and infection characteristics. The primary outcome was the composite of 90-day all-cause mortality, recurrent BSI with the same pathogen (genus and species), and re-admission to any Ontario hospital. ResultsA total of 2012 patients were included in the study (1006 in each bioavailability category). Those who received highly (compared with less) bioavailable antibiotics at discharge had lower rates of the composite outcome (171/1006 [17.0%] vs. 216/1006 [21.5%]), adjusted odds ratio being 0.74 (95% CI, 0.60–0.92). Recurrent BSI at 90 days was the main driver for the composite outcome occurring in 64 (5.4%) and 107 (9.4%) patients of the highly and less-bioavailable groups, respectively (p < 0.001) (adjusted odds ratio, 0.56; 95% CI, 0.40–0.78). DiscussionUse of highly (compared with less) bioavailable antibiotics at discharge was associated with significantly better clinical outcomes among patients with gram-negative BSIs.