Clinical Validation of the Xpert MTB/RIF test for Identification of the MTB Complex in AFB Smear-Positive MGIT broth cultures

The identification of the M. tuberculosis complex (MTBC) from smear positive broth cultures can be achieved using several methods including both lab-developed and commercially available molecular assays. In the United States, a commercially available probe-based assay has been used for over a decade by many laboratories for identification of MTBC directly from AFB smear positive broth cultures, including those recovered from the MGIT 960 system. However, recent difficulties in obtaining probe kits for identification resulted in mycobacteriology laboratories looking for alternative platforms to provide for rapid identification of MTBC and detection of rifampicin resistance. The Xpert® MTB/RIF test (Cepheid, Sunnyvale, Ca) has shown high sensitivity for the diagnosis of MTBC from pulmonary specimens but is not often used for identification directly from smear positive, MGIT 960 broth cultures (Becton Dickinson, Sparks, Md). We sought to validate the Xpert MTB/RIF test for use with AFB smear positive MGIT 960 cultures in a clinical hospital setting. Overall, the assay showed a categorical agreement of 100% for identification of MTBC and detection of rifampin resistance. No false positive results or cross-reactivity were noted. Findings indicate that the Xpert MTB/RIF test may be suitable as a rapid replacement for identification of MTBC and detection of rifampicin resistance from AFB smear positive MGIT 960 broth cultures.

Evaluation of Three Culture Media for Isolation of Burkholderia cepacia Complex from Respiratory Samples of Patients with Cystic Fibrosis

Burkholderia cepacia complex (BCC) is a significant pathogen causing respiratory disease in individuals with cystic fibrosis (CF). Diagnosis is typically achieved by isolation of BCC on selective culture media following culture of sputum or other respiratory samples. The aim of this study was to compare the efficacy of three commercially available selective media for the isolation of BCC. The three media comprised Burkholderia cepacia selective agar (BCSA; bioMérieux), BD Cepacia medium (BD: Becton–Dickinson) and MAST Cepacia medium (MAST laboratories). Each medium was challenged with 270 respiratory samples from individuals with CF as well as an international collection of BCC (n = 26) and 14 other isolates of Burkholderia species at a range of inocula. The international collection was also used to artificially “spike” 26 respiratory samples. From a total of 34 respiratory samples containing BCC, 97% were recovered on BD and 94% were detected on MAST and BCSA. All three media were effective for isolation of BCC. BCSA was much more selective than the other two media (p < 0.0001) meaning that fewer isolates required processing to exclude the presence of BCC.

Kết quả điều trị bệnh nhân nhiễm khuẩn huyết thứ phát sau tắc mật

Mục tiêu: Mô tả kết quả điều trị bệnh nhân nhiễm khuẩn huyết thứ phát sau tắc mật. Đối tượng và phương pháp: Gồm 38 bệnh nhân NKH thứ phát sau tắc mật điều trị tại Khoa Điều trị Gan Mật Tụy, Bệnh viện Trung ương Quân đội 108 từ tháng 1/2020 đến tháng 8/2020. Phương pháp nghiên cứu mô tả cắt ngang, tiến cứu. Sử dụng phương pháp cấy máu bằng máy BACTEC 9020 của hãng Becton Dickinson - Mỹ và định danh vi khuẩn bằng hệ thống Vitex II Compact của hãng Bio Merieux - Pháp để để xác định tác nhân gây nhiễm khuẩn huyết. Hoặc sử dụng phương pháp PCR đa mồi với bộ sinh phẩm Sepsis@quick để xác định tác nhân gây nhiễm khuẩn huyết. Kết quả: Nam (63,2%) chiếm tỷ lệ cao hơn nữ (36,8%). Tuổi trung bình của nhóm nghiên cứu là 64,8 ± 12,7 năm. Hai tác nhân gây NKH chiếm tỷ lệ cao hơn cả là Escherichia coli (55,3%) và Klebsiella pneumoniae (31,6%). Số ca nằm điều trị 15 - 21 ngày có tỷ lệ cao nhất chiếm 39,5%, tiếp theo là 8 - 14 ngày chiếm 34,2%. Sử dụng kháng sinh nhóm aminoglycoside (86,8%) và nhóm beta lactam (84,2%) nhiều hơn các nhóm khác. Bệnh nhân được điều trị nội khoa chiếm 60,5%, tiếp đến là ERCP chiếm 36,8%. Số ca khỏi bệnh ra viện chiếm 89,5%, số ca tử vong chiếm 5,3%. Kết luận: Bệnh nhân chủ yếu được điều trị nội khoa. Sử dụng kháng sinh nhóm aminoglycoside và beta lactam là phù hợp làm rút ngắn thời gian nằm viện và nâng cao hiệu quả điều trị, số ca khỏi bệnh ra viện chiếm tỷ lệ cao.

Đặc điểm một số chỉ số lâm sàng, cận lâm sàng ở bệnh nhân nhiễm khuẩn huyết thứ phát sau tắc mật

Mục tiêu: Mô tả đặc điểm lâm sàng, cận lâm sàng và đặc điểm vi khuẩn học ở bệnh nhân nhiễm khuẩn huyết thứ phát sau tắc mật. Đối tượng và phương pháp: Gồm 38 BN nhiễm khuẩn huyết thứ phát sau tắc mật tại Khoa Điều trị Gan Mật Tụy, Bệnh viện Trung ương Quân đội 108 từ tháng 1/2020 đến tháng 8/2020. Phương pháp nghiên cứu mô tả cắt ngang, tiến cứu. Sử dụng phương pháp cấy máu bằng máy BACTEC 9020 của hãng Becton Dickinson - Mỹ và định danh vi khuẩn bằng hệ thống Vitex II Compact của hãng Bio Merieux - Pháp để xác định tác nhân gây nhiễm khuẩn huyết. Hoặc sử dụng phương pháp PCR đa mồi với bộ sinh phẩm Sepsis@quick để xác định tác nhân gây nhiễm khuẩn huyết. Kết quả: Nam (63,2%) chiếm tỷ lệ cao hơn nữ (36,8%). Tuổi trung bình của nhóm nghiên cứu là 64,8 ± 12,7 năm. Bệnh nhân có triệu chứng sốt và vàng da chiếm tỷ lệ 100%, đau bụng chiếm tỷ lệ 89,5%. Số lượng bạch cầu tăng chiếm tỷ lệ 86,8%. Nồng độ bilirubin TP trung bình trong huyết tương là 148,99 ± 114,83µmol/L, nồng độ procalcitonin trung bình trong huyết tương là 22,18 ± 27,16ng/ml. Tác nhân gây nhiễm khuẩn huyết: Escherichia coli (55,3%) và Klebsiella pneumoniae (31,6%). Bệnh nhân được sử dụng kháng sinh nhóm aminoglycoside (86,8%) và nhóm beta lactam (84,2%) chiếm tỷ lệ cao hơn cả. Nguyên nhân tắc mật: Ung thư đường mật (28,9%), sỏi mật (28,9%), ung thư gan (13,2%). Kết luận: Hai tác nhân gây nhiễm khuẩn huyết chiếm tỷ lệ cao nhất là Escherichia coli và Klebsiella pneumoniae. Các nguyên nhân thường dẫn đến tắc mật là ung thư đường mật, sỏi mật và ung thư gan.

398. Multicenter Evaluation of Outcomes of SARS-CoV-2 Positive Patients Treated at Rural vs Urban Hospitals in the United States

Background The SARS-CoV-2 pandemic has revealed socioeconomic and healthcare inequities in the US. With approximately 20% of the population living in rural areas, there are limitations to healthcare access due to economic constraints, geographical distances, and provider shortages. There is limited data evaluating outcomes associated with SARS-CoV-2 positive patients treated at rural vs. urban hospitals. The aim of the study was to evaluate characteristics and outcomes of SARS-CoV-2 positive patients treated at rural vs. urban hospitals in the US. Methods This was a multicenter, retrospective cohort analysis of adult (≥ 18 years) hospitalized patients from 241 US acute care facilities with &gt;1 day inpatient admission with a discharge or death between 3/6/20-5/15/21 (BD Insights Research Database [Becton, Dickinson & Company, Franklin Lakes, NJ]), which includes both small and large hospitals in rural and urban areas. SARS-CoV-2 infection was identified by a positive PCR or antigen during or &lt; 7 days prior to hospital admission. Descriptive statistics were completed. P value of ≤0.05 was considered statistically significant. Results Overall, 42 (17.4%) and 199 (82.6%) of hospitals were classified as rural and urban, respectively. A total of 304,073 patients were admitted to a rural hospital with 12,644 (4.2%) SARS-CoV-2 positive. In comparison, a total of 2,844,100 patients were treated at an urban hospital with 132,678 (4.7%) SARS-CoV-2 positive. Patients admitted to rural hospitals were older compared to those treated at an urban hospital (65.2 ± 17.3 vs. 61.5 ± 18.7, P=0.001) (Table 1). Patients treated at an urban facility had significantly higher rates of ICU admission, severe sepsis, and mechanical ventilation. ICU length of stay was significantly longer for patients admitted to an urban hospital compared to a rural hospital (8.1 ± 9.9 vs. 6.1 ±7.2 days, P=0.001) (Table 2). No difference in mortality was observed. Table 1. Characteristics of SARS-CoV-2 positive patients treated at rural vs. urban hospitals. Table 2. Outcomes of SARS-CoV-2 patients treated at rural vs. urban hospitals. *Patients with available data. Conclusion In this large multicenter evaluation of hospitalized patients positive for SARS-CoV-2, there were significant differences in patient characteristics. There was no observed difference in mortality. These findings are important in evaluating the pandemic’s impact on patients in rural and urban healthcare settings. Disclosures Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kalvin Yu, MD, BD (Employee) Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder) Laura A. Puzniak, PhD, Merck & Co., Inc. (Employee)

786. Facility Reported vs. CLSI MIC Breakpoint Comparison of Carbapenem Non-susceptible (Carb-NS) Pseudomonas aeruginosa (PSA) From 2016-2019: A Multicenter Evaluation

Background CLSI lowered Pseudomonas aeruginosa (PSA) Carbapenem (Carb) interpretive breakpoint minimum inhibitory concentrations (MICs) in 2012. It often takes several years for commercial test manufacturers and microbiology labs to incorporate revised breakpoints. We compare facility-reported rates of Carb-NS PSA to the 2012 CLSI MIC breakpoints, using a large nationwide database for isolates tested in 2016-2020 at United States (US) facilities. Table. Imipenem (IPM)/meropenem (MEM)/doripenem (DOR) interpretation (evaluable isolates) results for PSA. Methods All adults with a positive non-contaminant PSA culture (first isolate per 30-day period from blood, respiratory, urine, skin/wound, intra-abdominal, or other) in ambulatory and inpatient settings from 298 US hospitals from Q1 2016-Q4 2020 were evaluated (BD Insights Research Database, Becton, Dickinson & Company). Facility-reported Carb-non susceptible (NS) was defined as lab information system feed designations of susceptible (S), intermediate (I) or resistant (R) to imipenem (IPM), meropenem (MEM) and/or doripenem (DOR) per commercial panels. Where available, MICs were interpreted using CLSI 2012 Carb breakpoints (µg/ml) of ≤2 (S), 4 (I), ≥8 (R) for IPM/MEM/DOR. For evaluable PSA isolates we compared susceptibility results as reported by the facility to those using CLSI MIC breakpoints. Results Overall, 86.9% (255,844/294,426) of non-duplicate PSA isolates with facility-reported IPM/MEM/DOR susceptibility interpretations also had interpretable MIC results. S rates were 84.9% and 83.3% as reported by facilities and determined by CLSI criteria, respectively (Table). Facilities under-reported Carb-NS by 9.8%, using CLSI criteria as the standard (10.4% and 7.7% of R and I isolates, respectively, were missed by facility reporting). Conclusion Systematic application of CLSI breakpoints in 2016-20 would have had minimal impact on PSA S rates in the US. However, facility reporting failed to identify ~10% of Carb-NS isolates. The clinical implications of this observation are unknown. Facilities should know their local epidemiology, decide if under-reporting might be an issue, and assess if there is any impact on their patients. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder) Kalvin Yu, MD, BD (Employee) Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Janet Weeks, PhD, Becton, Dickinson and Company (Employee) Cornelius J. Clancy, MD, Merck (Grant/Research Support)

221. Evaluation of Rates of Culture Positive Blood Stream Pathogens Prior to and During the SARS-CoV-2 Pandemic: A Multicenter Evaluation

Background Bacterial co-infections or super-infections are well-characterized complications of viral infections, further increasing morbidity and mortality of global viral pandemics. We evaluated trends in the incidence of culture positive gram-negative (GN), gram-positive (GP), and fungal/yeast pathogens from a blood source in hospitalized patients at US hospitals before and during the SARS-CoV-2 pandemic. Table: Incidence and rate of blood pathogens in the pre and post SARS-CoV-2 period. Gray indicates significantly lower rate compared to pre-pandemic time period, black indicates significantly higher rates compared to pre-pandemic. Methods: This was a multi-center, retrospective cohort analysis of all hospitalized patients from 267 US acute care facilities with &gt;1-day inpatient admission between 7/1/19-5/19/21 (BD Insights Research Database [Becton, Dickinson and Company, Franklin Lakes, NJ]). SARS-CoV-2 infection was identified by a positive PCR during or ≤7 days prior to hospitalization. All admissions with a non-contaminant culture positive GN, GP, and fungal/yeast pathogen from a blood source were evaluated prior to and during the SARS-CoV-2 pandemic as rates per 1,000 admissions (p&lt; .05 for significance). Results There were 2,001,793 admissions in the pre-SARS-CoV-2 period (7/2019-2/2020) and 2,875,219 admissions during the SARS-CoV-2 pandemic. Incidence of GN/GP blood stream pathogens was significantly higher prior to the SARS-CoV-2 pandemic than during the pandemic. Higher rates of blood stream pathogens occurred in those who were tested for SARS-CoV-2, but all non-tested patients had significantly lower rates than pre-pandemic. Rates of Candida spp., Enterococcus spp., Serratia marcescens, and Enterobacter cloacae were higher in SARS-CoV-2 positive patients compared to pre-pandemic patients. Compared to the prior pandemic period, the incidence of B. fragilis, Streptococcus, Enterococcus and Candida were higher among those tested for SARS-CoV-2 but were negative. Conclusion In general, rates of positive blood cultures for bacterial pathogens were either lower or similar during the SARS-CoV-2 period compared to the pre-SARS-CoV-2 pandemic period. The patients that were tested for SARS-CoV-2 but were positive who had higher rates of infection than prior may indicate the similarity in viral and bacterial clinical presentation. Further evaluation of higher rates of Enterococcus and Candida in the pandemic period are warranted. Disclosures Laura A. Puzniak, PhD, Merck & Co., Inc. (Employee) Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kalvin Yu, MD, BD (Employee) Pamela Moise, PharmD, Merck (Employee) Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)

176. Antibiotic Resistance Patterns, Seasonality, and Correlation with the Influenza Season in the United States: A Multicenter Evaluation Reveals Surprising Association Between Influenza Season and Gram Negative Pathogens

Background Influenza infection may affect bacterial transmission dynamics and seasonality of antimicrobial resistance (AMR). There is a paucity of data on the association of influenza season and AMR rates. We aimed to describe trends of AMR and their correlation with the influenza season in ambulatory and inpatient settings in the United States (US). Methods We used the BD Insights Research Database (Franklin Lakes, NJ USA) to identify 30 day non-duplicate isolates collected from patients &gt;17 years old with susceptibility profile of Gram-negative (GN) (Enterobacterales (ENT), P. aeruginosa (PSA), A. baumannii spp. (ACB), and S. maltophilia (Sm)) and Gram-positive (GP) pathogens (S. aureus (SA), and S. pneumoniae (Sp)) in up to 257 US healthcare institutions from 2011-19. We defined the outcomes as rates per 100 admissions and % of non-susceptibility (NS), stratified by community and inpatient settings, resistance type (resistance to carbapenem (Carb-NS), quinolone (FQ-NS), macrolide (Macr NS), penicillin (PCN NS), and extended spectrum cephalosporin (ESC NS)) and isolate origin (respiratory and non-respiratory). Influenza data were presented as the % of positive laboratory tests. We used descriptive statistics and generalized estimating equations models to evaluate the monthly trends of AMR outcomes and correlation with the influenza season. Results We identified 16 576 274 confirmed non-duplicate pathogens, of which 154 841 were GN Carb-NS, 1 502 796 GN FQ-NS, 498 012 methicillin resistant SA (MRSA), and 44 131 Macr-NS, PCN-NS, and ESC-NS Sp. Among the Carb-NS pathogens, Influenza rate was correlated with % ACB-NS [β= 0.205, p&lt; .001]. In the FQ-NS group, influenza was associated with overall % ENT-NS [β= 0.041 p&lt; .001] and % PSA-NS [β= 0.039, p = .015]. For the GP pathogens, all Sp. rates were correlated with increased influenza positivity % (See Table). Only MRSA rates of respiratory source were associated with influenza [β= .066, p=.028]. Summary of Multivariate regressions of AMR and % Flu by Source and Setting (controlling for hospital level factors): 2011-2019 Data in each cell is presented as the coefficient and p-value is in parentheses. ^adjusted for region, teaching, urban, bed size, and season. + p&lt;.10 *p &lt;.05 **p &lt;.01 ***p &lt;.001 Conclusion Our study revealed surprising association between influenza epidemics and GN resistance and corroborated the evidence of correlation between respiratory GP and influenza infections. These insights may help inform targeted antimicrobial stewardship initiatives during influenza season. Disclosures Amine Amiche, PhD, Sanofi (Employee, Shareholder) Heidi Kabler, MD, Sanofi Pasteur (Employee) Janet Weeks, PhD, Becton, Dickinson and Company (Employee) Kalvin Yu, MD, BD (Employee) Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)

642. Facility Reported vs. CLSI MIC Breakpoint Comparison of Carbapenem Non-susceptible (Carb-NS) Enterobacteriaceae (ENT) from 2016-2019: A Multicenter Evaluation

Background Carbapenem (Carb) minimum inhibitory concentration (MIC) breakpoints were lowered by CLSI in 2010 and recognized by FDA in 2012. Adoption of revised breakpoints is often slow, which may lead to under-reporting of Carb non-susceptibility (NS) by facilities. We compare facility-reported rates of Carb-NS ENT to the CLSI MIC breakpoints for a large nationwide collection of isolates in the United States (US) from 2016-2019. Methods All adults with a positive non-contaminant ENT culture (first isolate of a species per 30-day period from blood, respiratory, urine, skin/wound, intra-abdominal, or other) in ambulatory/inpatient settings from up to 300 US hospitals from 2016-2019 were evaluated (BD Insights Research Database). Facility-reported Carb-NS was defined as: susceptible (S), intermediate (I) or R to ertapenem (ETP), imipenem (IPM), meropenem (MEM) and/or doripenem (DOR) per commercial panels. Where available, MICs were interpreted using CLSI 2010 MIC breakpoints (µg/ml): ≤ 0.5 (S), 1 (I), ≥ 2 (R) for ETP and ≤1 (S), 2 (I), and ≥ 4 (R) for IPM/MEM/DOR. For evaluable ENT isolates we compared susceptibility results as reported by the facility to CLSI MIC breakpoints. Results Overall, 77.4% (937,926/1,211,845) and 90.6% (2,157,785/2,381,824) non-duplicate ENT isolates with facility-reported susceptibility results also had interpretable MIC results for ETP and IPM/MEM/DOR, respectively (Tables). ETP S rates were 99.3% and 99.1% as reported by facilities and using CLSI criteria, respectively. S rates of other Carbs were 98.9% and 98.4% by facility reporting and CLSI criteria, respectively. Systematic application of CLSI breakpoints under-reported EPT-I and –R isolates by 24.2% and 16.4%, respectively, and identification of IPM/MEM/DOR-I and –R isolates by 31.3% and 22.7%, respectively. Conclusion Systematic application of CLSI breakpoints in 2016-19 would have had minimal impact on ENT S rates in the US. However, facility reporting failed to identify 18.8% of ETP I or R and 26.5% of IPM/MEM/DOR I or R isolates. The clinical implications of this observation are unknown. Facilities should know their local epidemiology, decide if under-reporting might be an issue, and assess if there is any impact on their patients. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder) Kalvin Yu, MD, BD (Employee) Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Janet Weeks, PhD, Becton, Dickinson and Company (Employee) Cornelius J. Clancy, MD, Merck (Grant/Research Support)

171. A Multicenter Analysis of Inpatient Antibiotic Use During the 2015-2019 Influenza Season in the US: Untapped Opportunities for Antimicrobial Stewardship

Background Inappropriate antibiotic (AB) use for viral respiratory illnesses remains widespread in the United States (US) with strong seasonal fluctuations. In contrast to outpatient AB use, the seasonality inpatient AB utilization (IAU) and its correlation with the influenza season are not well understood. We sought to describe trends, seasonality, and the association between IAU use and the 2015-2019 influenza seasons. Methods We used the BD Insights Research Database (Franklin Lakes, NJ USA) to identify IAU that were prescribed in patients &gt;17 years old from up to 236 US acute care facilities from July 2015 to December 2019. We included the following AB categories: extended spectrum cephalosporins (ESCs), macrolides, β-lactam inhibitor combination (BLIC), fluoroquinolones, carbapenems, glycopeptides, lipopeptide, tetracyclines, and others. We defined IAU use as days of therapy (DOT) per 1000 patient days present. We used influenza laboratory data to identify facility-level positivity ratio per 100 tests. We used random effect models to estimate IAU: 1) trends overtime, 2) seasonality, and 3) association with influenza positivity rate. Results For IAU from 2015 to 2019, BLICs, ESCs, and glycopeptides were the most used [average 91, 107, and 96 DOT/1000 days presents, respectively]. Visually, we observed strong seasonality that matches the influenza season for macrolide, ESC, and quinolone use (See Figure). Unadjusted bivariate results showed ascending trends over time for BLICs [β= 3.8, p= .003], ESCs [β= 11.0, p= .005], and macrolides [β=1.5, p= .005]. Unadjusted bivariate results showed descending trends with quinolones [β= -10.9, p&lt; .001] and others [β= -2.060, p&lt; .001]. In the adjusted analysis, increased influenza positivity rate was associated with use of ESCs, glycopeptides, lipopeptides, macrolides, fluoroquinolone, and tetracyclines (see Table). No correlation was observed with BLICs, carbapenems, lipopeptides, and Others. IAU (DOT/1000 days presents) and Flu Rate (% Positive) Trends Over Time Conclusion Our study shows that IAU is on the rise for the ESC and BLIC classes. ESC and macrolide use was strongly correlated with influenza season. Monitoring influenza signals may provide more insights that can inform the interpretation of IAU trends and be incorporated into antimicrobial stewardship programs. Disclosures Amine Amiche, PhD, Sanofi (Employee, Shareholder) Heidi Kabler, MD, Sanofi Pasteur (Employee) Janet Weeks, PhD, Becton, Dickinson and Company (Employee) Kalvin Yu, MD, BD (Employee) Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)