The Impact of the FilmArray-Based Detection of Microbial Pathogens from Positive Blood Culture Vials on the Time to Optimal Antimicrobial Regimen in Intensive Care Units of the Helios University Clinic Wuppertal, Germany

The role of empirical therapy and time to first effective treatment, including the antimicrobial stewardship program, are decisive in patients presenting with bloodstream infections (BSI). The FilmArray® Blood Culture Identification Panel (FA BCID 1.0) detects 24 bacterial and fungal pathogens as well as 3 resistance genes from positive blood cultures in approximately 70 min. In this paper, we evaluate the impact of the additional FA BCID analysis on the time to an optimal antimicrobial therapy and on the length of stay in the ICU, ICU mortality, and PCT level reduction. This retro-/prospective trial was conducted in BSI patients in the ICU at a German tertiary care hospital. A total of 179 individual patients with 200 episodes of BSI were included in the prospective intervention group, and 150 patients with 170 episodes of BSI in the retrospective control group. In the intervention group, BSI data were analyzed including the MALDI-TOF MS (matrix assisted laser desorption ionization time-of-flight mass spectrometry) and FA BCID results from January 2019 to August 2020; the data from the control group, including the MALDI-TOF results, were collected retrospectively from the year 2018. The effective and appropriate antimicrobial regimen occurred in a median of 17 hours earlier in the intervention versus control group (p = 0.071). Furthermore, changes in the antimicrobial regimens of the intervention group that did not immediately lead to an optimal therapy occurred significantly earlier by a median of 24 hours (p = 0.029). Surrogate markers, indicating an earlier recovery of the patients from the intervention group, such as length of stay at the ICU, duration of mechanical ventilation, or an earlier reduction in PCT level, were not significantly affected. However, mortality did not differ between the patient groups. A postulated reduction of the antimicrobial therapy, in those cases in which coagulase-negative Staphylococcus species were identified, did occur in the control group, but not in the intervention group (p = 0.041). The implementation of FA BCID into the laboratory workflow can improve patient care by optimizing antimicrobial regimen earlier in BSI patients as it provides rapid and accurate results for key pathogens associated with BSI, as well as important antimicrobial resistance markers, e.g., mecA or vanA.

Creation of a Combination Antibiogram for Pseudomonas aeruginosa in a Pediatric Intensive Care Unit

OBJECTIVE This study describes the creation of a combination antibiogram directed toward Pseudomonas aeruginosa to determine the most appropriate empiric antimicrobial regimen(s). METHODS P aeruginosa isolates were collected from all sites between January 2013 and December 2017 for patients admitted to the PICU. Patients with cystic fibrosis and isolates from the same site and susceptibility pattern obtained within 30 days were excluded. β-Lactam susceptibilities were determined and compared with the addition of an aminoglycoside or fluroquinolone and summarized in a combination antibiogram. RESULTS One hundred ninety-nine P aeruginosa isolates were included for analysis. The addition of a second agent to piperacillin-tazobactam was shown to have the most significant improvement among the β-lactams, with 70% susceptibility as monotherapy and increases to above 90% with the addition of an aminoglycoside or fluroquinolone. The addition of an aminoglycoside or fluroquinolone to cefepime and meropenem increased coverage to above 95%. The addition of a second agent was likely to increase susceptibility of a monotherapy backbone; however, as the susceptibility of the first-line agent decreased, the susceptibility of the second agent needed to be higher to achieve a 95% coverage threshold. CONCLUSIONS Our results support use of a second agent to significantly improve the likelihood of appropriate empiric coverage of P aeruginosa. Use of a combination antibiogram may be more beneficial than a simple antibiogram for units with increasing resistance rates, or for coverage of specific resistant organisms.

86. Access to Antimicrobial Susceptibility Testing for Novel Gram-Negative Antibiotics

Background Antimicrobial susceptibility testing (AST) is critical in identifying the optimal antimicrobial regimen for individual patients with serious gram-negative infections. Limitations to AST for newly developed antibiotics include the lack of commercially available AST methods, challenges of implementation due to regulations, and delays in obtaining results. The purpose of this study was to evaluate the access to AST for cefiderocol (FDC), imipenem-relebactam (IPR), meropenem-vaborbactam (MEV), and eravacycline (ERV) in hospitals across the U.S. Methods An electronic survey was distributed to the American College of Clinical Pharmacist Infectious Diseases Practice and Research Network in May 2021. Hospital baseline demographics and current practices were collected. Results Based on 50 responses, specimens were sent to in-house microbiology labs (37, 74%), core microbiology labs (8, 16%), and 3rd party reference microbiology labs (5, 10%). AST for FDC was performed by 13 (35%) in-house labs, 4 (50%) core labs, and 1 (20%) reference lab. AST for IPR was performed by 11 (30%) in-house labs, 2 (25%) core labs, and 1 (20%) reference lab. AST for MEV was performed by 25 (68%) in-house labs, 3 (37.5%) core labs, and 1 (20%) reference lab. AST for ERV was performed by 1 (20%) in-house lab, 1 (20%) core lab, and 0 reference labs. 15 (30%) respondents were not able to get AST for any of the novel agents at their respective microbiology labs. Turn-around-times (TATs) for FDC, IPR, MEV, and ERV were ≥72 hours for 33 (66%), 35 (70%), 21 (42%), and 35 (70%) hospitals, respectively. When compared with 3rd party reference labs, in-house labs with the ability to perform AST for these novel agents had significantly shorter TATs (p< 0.05). The average number of requests for AST for these novel agents was 20 times a year with an average of 113 minutes spent per patient on the coordination of AST. Conclusion Access to AST for these novel agents varied across hospitals in the U.S. Nearly 1/3 of the respondents were not able to obtain AST for these agents at all. Long TATs exist and a great deal of time is spent per patient for coordinating AST for these novel agents. There is a crucial need for a multidisciplinary, collaborative approach to resolve the challenges in obtaining AST for newly developed antibiotics to provide patient care. Disclosures All Authors: No reported disclosures

1157. Determining the Clinical Utility of 16S rRNA in the Management of Pediatric Infections

Background Conventional culture remains the gold standard to facilitate a targeted antimicrobial regimen in the treatment of bacterial infections. However, certain pediatric infections are caused by fastidious organisms and treatment with antibiotics prior to specimen collection may hamper growth of pathogens in routine culture. The use of 16S rRNA in culture negative infections has improved identification of bacterial pathogens in select scenarios. However, the specific impact of 16S rRNA on clinical decision making, especially in pediatric infections, is not well-defined. This study aims to elucidate the utility of 16S rRNA on clinical management of pediatric infections. Methods A retrospective analysis was done on different clinical specimens which had 16S rRNA performed from August 2016 – March 2020 in our institution. Detailed chart review was performed to determine how the 16S rRNA result impacted clinical decision making. Clinical utility was defined as change in patient’s overall antimicrobial regimen, pathogen confirmation, and treatment duration. Results Seventy-four samples from 71 pediatric patients were included in the analysis: 32 (43%) were fluid specimens and 42 (57%) were tissue specimens. Significant clinical utility was identified in 30 (40.5%) of 74 clinical samples (p < 0.0001). Of all specimens, pulmonary samples yielded the most clinical utility (n=9, 30%) followed equally by joint fluid (n=6, 20%) and bone (n=6, 20%). There was no significant difference in clinical utility between fluid and tissue specimens (p= 0.346). In 64 patients whose antimicrobial spectrum coverage was analyzed, patients with broad spectrum coverage was decreased from 48 to 21 and narrow spectrum coverage increased from 16 to 43 using 16S rRNA result, though not significant (p= 0.4111). Of all patients included in the analysis, the median number of antibiotics used before 16S rRNA result, 2, was significantly decreased to 1 (p < 0.0001). Conclusion 16S rRNA has a significant impact in terms of decreasing number of antibiotics used in treatment of pediatric infections. Pulmonary specimens have the highest clinical utility among all samples. Additional cost benefit analysis needs to be completed to further determine clinical benefit. Disclosures All Authors: No reported disclosures

Comparative Study of Parenteral Penicillin G vs. Amoxicillin-Clavulanate for the Treatment of Dentoalveolar Abscess in Hospitalized Children

Objectives: To compare the clinical efficacy and the safety profiles of parenteral penicillin G vs. amoxicillin-clavulanate for the treatment of dentoalveolar abscess (DA) in hospitalized pediatric patients.Methods: A retrospective cohort study that was conducted at the Schneider Children's Medical Center in Israel.Results: Seventy-one patients that were included, 25 received parenteral penicillin G and 46 amoxicillin-clavulanate. There were no significant differences in the baseline clinical features except for higher rate of females in the amoxicillin-clavulanate group. Patients that were treated with penicillin G had shorter duration of fever, swelling and total length-of-stay (4.16 vs. 5 days in the penicillin G vs. amoxicillin-clavulanate groups, respectively, p = 0.007) and lower need for surgical intervention. Side effect were minor in both groups. In multivariate analysis, antimicrobial regimen was the only significant factor related with the total length-of-stay (p < 0.001).Conclusions: In pediatric patients hospitalized for DA, parenteral penicillin G was associated with better outcome compared with amoxicillin-clavulanate.

Clinical Characteristics of Carbapenem-Resistant Klebsiella Pneumoniaee Infections In A Tertiary Hospital In China

Background：The infections due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) have become an important problem. The aim of the study is to evaluate the clinical characteristics of CR-KP.Methods: A retrospective cohort study has been made on all patients presenting with CR-KP infections. 615 patients with CR-KP humor infections diagnosed were identified. 135 patients who did not meet the requirements were excluded. Clinical characteristics, antimicrobial regimens, and outcomes of patients have been analyzed.Results: The CR-KP infections overall mortality was 37.3%, and bloodstream infections mortality was 66.2%. Survival analysis revealed that there were statistically significant differences between bloodstream infection and pulmonary and drainage fluid infection. Logistics regression analysis showed that hemopathy, age (>60 years), solid tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality. Multivariate linear regression was performed in APACHE II score, SOFA score, lymphocyte absolute value (LYM) and survival time. Survival time was negatively correlated with APACHE II score and SOFA score, while positively correlated with LYM. Finally, we investigated different antimicrobial regimens for CR-KP infections. Chi-square test showed that antimicrobial regimen combined carbapenems, tigecycline with polymyxin B was superior the one combined carbapenems with polymyxin B. Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens.Conclusions: Our study confirmed there is a high mortality rate in CR-KP infections, especially in the bloodstream infections. The outcome is greatly influenced by the patients’ clinical conditions. Antimicrobial regimen combined carbapenems, tigecycline with polymyxin B might be a better choice.

Risk Factors of 30-Day All-Cause Mortality in Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection

An optimal antimicrobial regimen for the treatment of patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is currently unavailable. This study aimed to identify the appropriate antibiotics and the risk factors of all-cause mortality for CRKP BSI patients. This retrospective cohort study included the hospitalized patients with CRKP BSI. Primary outcome was 30-day all-cause mortality. Cox regression analysis was used to evaluate the risk factors of 30-day mortality. A total of 89 patients were included with a 30-day mortality of 52.1%. A total of 52 (58.4%) patients were treated with appropriate antimicrobial regimens and 58 (65.2%) isolates carried blaKPC-2 genes. Microbiologic eradication within 7 days (adjusted hazard ratio [HR] = 0.09, p < 0.001), platelet count (per 1 × 104/mm3, adjusted HR = 0.95, p = 0.002), and Pitt bacteremia scores (adjusted HR = 1.40, p < 0.001) were independently associated with 30-day all-cause mortality. No effective antimicrobial regimens were identified. In conclusion, risk factors of 30-day mortality in patients with CRKP BSI included microbiologic eradication > 7 days, lower platelet count, and a higher Pitt bacteremia score. These findings render a new insight into the clinical landscape of CRKP BSI.

Association between radical cystectomy prophylactic antimicrobial regimen and postoperative infection

Introduction: Infections are common after radical cystectomy. The objective of this study was to determine the association between antimicrobial prophylactic regimen and infection after radical cystectomy. Methods: A retrospective cohort study was performed on patients who underwent radical cystectomy at one tertiary Canadian center between January 2016 and April 2020. Patients received antimicrobial prophylaxis based on surgeon preference (cefazolin/metronidazole or ampicillin/ciprofloxacin/metronidazole or other). A univariable and multivariable logistic regression model was created to determine the association between antimicrobial regimen and postoperative infection within 30 days. The association between patient demographic factors, as well as preoperative and intraoperative variables and infection was also determined. Infection characteristics, including type, timing, and antimicrobial susceptibilities were reported. Results: One hundred and sixty-five patients were included. Mean age was 69.8 years, 121 (73.3%) were male, and 72 (43.6%) received orthotopic neobladder diversion. Ninety-six patients (58%) received cefazolin/metronidazole prophylaxis, 50 (30%) received ampicillin/ciprofloxacin/metronidazole, and 19 (11.5%) received another regimen. Fifty-four patients (32.7%) developed a postoperative infection (surgical site infection or urinary tract infection). Surgical site infection occurred in 35 patients (21.2%) and urinary tract infection occurred in 34 (21.0%). There was no association between antimicrobial regimen and incidence of postoperative infection (surgical site infection or urinary tract infection, relative risk [RR] 0.99, 95% confidence interval [CI] 0.50–1.99). Conclusions: The overall incidence of infection was 32.7% following radical cystectomy. The preoperative prophylactic antibiotic regimen used was not associated with incidence of postoperative infection.

Clinical and epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae infections in a tertiary hospital in China

Background：The infections due to carbapenem-resistant Klebsiella pneumonia (CR-KP) have become an important problem. The aim of the study is to evaluate the clinical and epidemiological characteristics of CR-KP. Results: The CR-KP infections overall mortality was 37.3%, and bloodstream infections mortality was 66.2%. Survival analysis revealed that there were statistically significant differences between bloodstream infection and pulmonary and drainage fluid infection. Hemopathy, age (>60 years), tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality. Multivariate linear regression showed that survival time was negatively correlated with APACHE II score and SOFA score, while positively correlated with LYM. Chi-square test showed that antimicrobial regimen combined carbapenems, tigecycline with polymyxin B was superior the one combined carbapenems with polymyxin B. But there was not statistically significant difference between carbapenems plus tigecycline and carbapenems plus polymyxin B. Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens. Conclusions: Our study confirmed there is a high mortality rate in CR-KP infections, especially in the bloodstream infections. The outcome is greatly influenced by the patients’ clinical conditions. Antimicrobial regimen combined carbapenems, tigecycline with polymyxin B might be a better choice.