Diagnostic accuracy of TB-LAMP for pulmonary tuberculosis: a systematic review and meta-analysis.

BACKGROUND:The need for a rapid, molecular test to diagnose tuberculosis (TB) has prompted exploration of TB-LAMP (Eiken; Tokyo, Japan) for use in resource-limited settings. We conducted a systematic review to assess the accuracy of TB-LAMP as a diagnostic test for pulmonary TB. METHODS:We analyzed individual-level data for eligible patients from all studies of TB-LAMP conducted between Jan 2012 and October 2015 to compare the diagnostic accuracy of TB-LAMP with that of smear microscopy and Xpert MTB/RIF® using 3 reference standards of varying stringency. Pooled sensitivity and specificity and pooled differences in sensitivity and specificity were estimated using random effects meta-analysis. Study quality was evaluated using QUADAS-2. RESULTS:Four thousand seven hundred sixty individuals across 13 studies met eligibility criteria. Methodological quality was judged to be low for all studies. TB-LAMP had higher sensitivity than sputum smear microscopy (pooled sensitivity difference + 13·2, 95% CI 4·5-21·9%) and similar sensitivity to Xpert MTB/RIF (pooled sensitivity difference - 2·5, 95% CI -8·0 to + 2·9) using the most stringent reference standard available. Specificity of TB-LAMP was similar to that of sputum smear microscopy (pooled specificity difference - 1·8, 95% CI -3·8 to + 0·2) and Xpert MTB/RIF (pooled specificity difference 0·5, 95% CI -0·9 to + 1·8). CONCLUSIONS:From the perspective of diagnostic accuracy, TB-LAMP may be considered as an alternative test for sputum smear microscopy. Additional factors such as cost, feasibility, and acceptability in settings that continue to rely on sputum smear microscopy should be considered when deciding to adopt this technology. Xpert MTB/RIF should continue to be preferred in settings where resource and infrastructure requirements are adequate and where HIV co-infection or drug-resistance is of concern

Influence of Antibiotic Exposure Intensity on the Risk of Clostridioides Difficile Infection

Antibiotics are a strong risk factor for Clostridioides difficile infection (CDI), and CDI incidence is often measured as an important outcome metric for antimicrobial stewardship interventions aiming to reduce antibiotic use. However, risk of CDI from antibiotics varies by agent and dependent on the intensity (i.e., spectrum and duration) of antibiotic therapy. Thus, the impact of stewardship interventions on CDI incidence is variable, and understanding this risk requires a more granular measure of intensity of therapy than traditionally used measures like days of therapy (DOT)

209. What’s So Complicated About Complicated Staphylococcus aureus Bacteremia: Does Day 5 Matter?

Abstract Background Prolonged Staphylococcus aureus bacteremia (SAB) poses challenges in clinical practice, particularly when a source is not readily identified. While SAB greater than 3 days has been identified as a risk factor for complications, little is known about risk for specific complications with each successive day of bacteremia. We sought to determine the risk for specific complications with the duration of bacteremia. Methods We retrospectively reviewed all cases of SAB between 1 January 2017 and 31 December 2017 at a 500-bed academic hospital. Adult patients (≥18 years) with at least one blood culture positive for S. aureus were identified. Patients were excluded if withdrawal of care or death occurred within 48 hours of blood culture results or if the infection was associated with a ventricular assist device. Medical records were reviewed for the duration of bacteremia, complications, treatment decisions and clinical outcomes. This study was approved by the Institutional Review Board. Results One hundred forty-two discrete episodes of SAB were identified with a median age of 54 years (IQR 40–63). Most cases were community-acquired (83.8%) and 33.8% were MRSA. Active injection drug use was present in 22.5% (33.3% MRSA, 17% MSSA). The median duration of bacteremia was 2.6 days (IQR 1.8–4.6) and 3.9 days (IQR 2.2–7.5) for MSSA and MRSA, respectively. The median time to first source control procedure was twice as long with bacteremia over 5 days than with a shorter duration of bacteremia (2.6 vs. 1.3 days). Complication rates increased with bacteremia duration and bacteremia longer than 5 days was associated with significantly higher rates of endocarditis (46.2%, P &lt; 0.001), epidural abscesses (35.9%, P = 0.001), intracranial infections (12.8%, P = 0.02), and presence of at least one endovascular nidus (76.9%, P &lt; 0.001) compared with bacteremia less than 5 days (28.4%), but 30 day mortality rates were similar (7.7% and 9.8%, respectively). Conclusion Complication rates increase significantly with SAB greater than 5 days duration. Early source control and investigation to identify metastatic and especially endovascular foci of infection are paramount in patients with prolonged bacteremia even if complications are not discovered on initial evaluation. Disclosures All authors: No reported disclosures. </jats:sec

81. Reducing Unnecessary Blood Cultures Through Diagnostic Stewardship

Abstract Background At our institution, we learned the frequency of blood cultures was sometimes being changed from “Once” to “Daily” without a defined number of days. We hypothesized this led to unnecessary blood cultures being performed. Methods Over a 3 month period from 12/6/2019-3/6/2020, we retrospectively evaluated the charts of patients who had a blood culture frequency changed to “Daily”. We evaluated if there was an initial positive blood culture within 48 hours of the “Daily” order being placed and the number of positive, negative, or “contaminant” sets of cultures drawn with the order. Contaminant blood cultures were defined as a contaminant species, present only once in the repeat cultures, and not present in initial positive cultures. Results 95 unique orders were placed with 406 sets of cultures drawn from 89 adults. ~20% of the time (17 orders) the order was placed without an initial positive blood culture. This led to 62 sets of cultures being drawn, only 1 of which came back positive. 78/95 orders had an initial positive blood culture. The most common initial organisms were Staphylococcus aureus (SA) (38), Candida sp (10), Enterobacterales sp (10), and coagulase negative staphylococci (7). 43/78 (55%) orders with an initial positive set had positive repeat cultures. SA (26) and Candida sp (8) were most common to have positive repeats. Central line associated bloodstream infections (CLABSI) were found in 5 of the orders and contaminant species were found in 4 of the orders. 54% of the patients who had a “Daily” order placed did not have positive repeat cultures. The majority of the cultures were drawn from Surgical (40 orders) and Medical (35 orders) services. Assuming that SA and Candida sp require 48 hours of negative blood cultures to document clearance and other species require 24 hours, it was estimated that 51% of the cultures drawn using the "Daily" frequency were unnecessary. Cost savings over a year of removing the "Daily" frequency would be ~&amp;14,000. Data from "Daily" blood culture orders drawn at Oregon Health &amp; Science University from 12/6/2019-3/6/2020 Conclusion Unnecessary blood cultures are drawn when the frequency of blood cultures is changed to "Daily". Repeat blood cultures had the greatest utility in bloodstream infections due to SA or Candida sp, and with CLABSI where the line is still in place. These results led to a stewardship intervention to change blood culture ordering at our institution. Disclosures All Authors: No reported disclosures </jats:sec

84. A Survey Based Assessment of Provider Practice Around Obtaining Repeat Blood Cultures

Abstract Background Apart from Staphylococcus aureus and Candida species, there is little guidance on whether to obtain repeat blood cultures after an initial positive set. We have noted heterogeneity in practice amongst our Infectious Disease (ID) group at Oregon Health and Science University (OHSU) and suspect there is heterogeneity amongst adult hospitalist providers as well. Methods We created a survey using clinical vignettes encompassing commonly encountered scenarios among hospitalized patients on medical wards to assess provider practices in obtaining repeat blood cultures. The survey was sent to adult ID providers and adult hospitalist providers at OHSU. These vignettes represented 9 of the most common bacteria seen in positive blood cultures and asked the question of whether providers would obtain repeat blood cultures after an initial positive set. The organisms included beta hemolytic streptococcus, Enterococcus faecalis, Streptococcus gallolyticus, coagulase-negative staphylococci, alpha hemolytic strep, E coli, Proteus mirabilis, Pseudomonas aeruginosa, and Bacteroides fragilis. We then asked questions around repeat blood culture practices for Staphylococcus aureus and Candida species, understanding that while repeat blood cultures for these organisms is recommended, the manner in which individual providers implement this may vary. Results The survey response rate was ~45%. Results were heterogenous with only 3 questions having inter- and intra- group agreement. Those 3 questions represented a case of E faecalis bacteremia without known source, a case of asymptomatic Staphylococcus epidermidis blood culture positivity, and a case of E. coli bacteremia from a pyelonephritis. All other vignettes had inter- and intra- group differences signifying clinical uncertainty around the practice of obtaining repeat blood cultures. There was similar heterogeneity among the responses asking how providers obtain repeat blood cultures around S. aureus and Candida bloodstream infections. Clinical vignette survey answers Answers from 10 clinical vignettes on obtaining repeat blood cultures after an initial positive set for stable patients on medical wards. Staphylococcus aureus Candida sp Conclusion There is significant heterogeneity amongst adult ID and hospitalist providers on what organisms and situations should prompt repeat blood cultures. There are differences around how repeat blood cultures should be obtained, including for Staphylococcus aureus and Candida sp. Disclosures All Authors: No reported disclosures </jats:sec

75. Utility of Fungal Blood Cultures in Portland, Oregon

Abstract Background Fungal blood cultures (fungal isolators) should be used, if at all, primarily for identification of mold infections. At our institution we noted patients having fungal blood cultures drawn in many other situations, including when the primary team was concerned for candida bloodstream infection. We sought to describe the utility of this practice and of fungal blood cultures in general. Methods We retrospectively reviewed the results of fungal blood cultures for 2 years, from 3/1/2019-3/1/2021. We evaluated the number of episodes, culture results, whether there was a had prior bloodstream infection, and risk factors for fungal infection including renal replacement (RRT), ECMO, and immunosuppression (IS). Immunosuppression was defined as chronic systemic steroid use, recent receipt of high dose steroids within 2 weeks, history of organ transplantation, history of stem cell transplantation, hematologic malignancies, or receipt of a biologic agent. Results 187 fungal blood cultures were drawn in 143 patients - 80 cultures in 70 patients from 3/2019-3/2020 and 107 cultures in 73 patients from 3/2020-3/2021. Only 3 patients had positive fungal blood cultures:1 (Candida krusei) from 3/2019-3/2020 and 2 (Candida albicans and Cyrptococcus neoformans) from 3/2020-3/2021; in all 3 cases the organism also grew from standard blood culture isolators. From 3/2019-3/2020, 1/80 cultures were drawn from an individual on ECMO while 15/80 were drawn from individuals on RRT, and 32/80 were in a IS individuals. From 3/2020-3/2021, 45/107 cultures were drawn from an individual on ECMO, 24/107 were drawn in an individual on RRT, and 73/107 were drawn in a IS individuals. The majority of individuals in whom a fungal blood culture was drawn during 3/2020-3/2021 were individuals with COVID-19. Upon chart review most of the cultures were drawn due to concern for candidemia. Results of fungal blood cultures drawn from 3/2019-3/2021 at OHSU Conclusion Fungal blood cultures have an extremely low yield at our institution, with a 1.6% positivity rate over a 2 year period, and all of those cultures were detected by standard blood culture isolators. Most of these cultures were drawn in situations where this test has no utility. Furthermore, the test has limited utility to detect dimorphic and mold bloodstream infections. Restriction of this test may limit inappropriate use. Disclosures All Authors: No reported disclosures </jats:sec

257. <i>Staphylococcus aureus</i> Bacteremia: Does Intravenous Drug Use Impact Quality of Care and Clinical Outcomes?

Abstract Background Individuals with intravenous drug use (IDU) have higher risk for Staphylococcus aureus bacteremia (SAB) and increased management complexity. The goal of this study was to compare differences in SAB characteristics, adherence to standard of care metrics, and clinical outcomes in those with and without IDU. Methods A retrospective chart review was conducted on cases of SAB between January 1, 2016 and December 31, 2017 at a 500-bed teaching hospital. Inclusion criteria was age &amp;gt; 18 years and ≥ one blood culture positive for S. aureus. Patients were excluded if they transferred hospitals, had care withdrawn or died within 48 hours of diagnosis or had a ventricular assist device infection. Records were reviewed for substance use, SAB characteristics, standards of care, and outcomes. Data were analyzed using SPSS software. The study was approved by the Institutional Review Board. Results In 248 patients with SAB, 28.2% had documented IDU. Median age was 37 (IDU) and 57 (non-IDU). In the IDU group, 75.7% had the formal diagnosis of opioid use disorder and 78.9% of stimulant use disorder. IDU was associated with hepatitis C and houselessness while non-IDU was associated with diabetes, hemodialysis, and cancer. Those with IDU had higher rates of MRSA, endocarditis, and spinal infections, but did not have higher rates of polymicrobial infections or venous thrombosis. There was no difference in appropriate repeat blood cultures, antibiotic management, and ID consultation. Length of stay and against medical advice (AMA) discharges were higher in those with IDU. There was no difference in 90-day recurrence or readmission, but 90-day mortality was higher in the non-IDU group. Conclusion There was no difference in adherence to SAB quality of care metrics between groups with and without IDU. Despite the IDU group being younger with fewer comorbidities, 90-day readmissions were not different between groups. This bears further analysis but may represent the influence of therapy completion, AMA discharges, and unmeasured social determinants of health. Disclosures All Authors: No reported disclosures </jats:sec

Clinical Practice Variation Among Adult Infectious Disease Physicians in the Management of Staphylococcus aureus Bacteremia

Infectious disease management of Staphylococcus aureus bacteremia (SAB) was surveyed through the Emerging Infections Network. While there were areas of consensus, we found substantial practice variation in diagnostic evaluation and management of adult patients with SAB. These findings highlight opportunities for further research and guidance to define best practices