A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients.

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.

Impact of Organism Reporting from Endotracheal Aspirate Cultures on Antimicrobial Prescribing Practices in Mechanically Ventilated Pediatric Patients.

Endotracheal aspirate cultures (EACs) help diagnose lower respiratory tract infections in mechanically ventilated patients but are limited by contamination with normal microbiota and variation in laboratory reporting. Increased use of EACs is associated with increased antimicrobial prescribing, but the impact of microbiology reporting on prescribing practices is unclear. This study was a retrospective analysis of EACs from mechanically ventilated patients at Children's Hospital Colorado (CHCO) admitted between 1 January 2019 and 31 December 2019. Chart review was performed to collect all culture and Gram stain components, as well as antibiotic use directed to organisms in culture. Reporting concordance was determined for each organism using American Society for Microbiology guidelines. Days of therapy were calculated for overreported and guideline-concordant organisms. A multivariable model was used to assess the relationship between organism reporting and total days of therapy. Overall, 448 patients with 827 EACs were included in this study. Among patients with tracheostomy, 25 (8%) organisms reported from EACs were overreported and contributed 48 days of excess therapy, while 227 (29%) organisms from the EACs of endotracheally intubated patients were overreported, contributing 472 excess days of therapy. After adjustment, organism overreporting was associated with a >2-fold-higher rate of antimicrobial therapy than guideline-concordant reporting (incident rate ratio [IRR], 2.83; 95% confidence interval [CI], 1.23, 6.53; P < 0.05). Overreported organisms from respiratory cultures contribute to excess antimicrobial therapy exposure in mechanically ventilated patients. Microbiology laboratories have an opportunity to mitigate antimicrobial overuse through standardized reporting practices.

The Pediatric Endotracheal Aspirate Culture Survey (PETACS): Examining Practice Variation across Pediatric Microbiology Laboratories in the United States.

In the absence of evidence-based laboratory guidelines, the workup and interpretation of tracheal aspirate (TA) cultures remains controversial and confusing within the fields of clinical microbiology, infectious diseases, and critical care. Between 22 January and 24 February 2020, we conducted a national, web-based survey of microbiology laboratory personnel in free-standing pediatric hospitals and adult hospitals containing pediatric facilities regarding the laboratory practices used for TA specimens. We hypothesized there would be substantial center-level variability in laboratory processing of TA cultures. The response rate for the survey was 48% (73/153). There was a high level of variability in the criteria used for all processes, including specimen receipt, Gram staining, and culture reporting. Most respondents (77%) reported they do not reject TA specimens based on Gram stain criteria, and 44% of labs do not require that a minimum number of Gram stain fields be reviewed prior to reporting results. Overall, nonacademic hospital laboratories and pediatric-only laboratories are more likely to identify, report, and perform susceptibility testing on organisms from TA cultures, regardless of organism quantity or predominance. There is a substantial amount of process variability among pediatric microbiology laboratories that affects TA culture reporting, and which guides treatment decisions. This variation within and among labs makes clinical outcome studies related to TA cultures difficult to interpret. This study serves as a pragmatic step in informing the development of robust clinical guidelines. Clinical outcome and implementation studies are necessary to determine the effectiveness of guidelines for TA cultures.

Navigating the network: a narrative overview of AMR surveillance and data flow in the United States.

The antimicrobial resistance (AMR) surveillance landscape in the United States consists of a data flow that starts in the clinical setting and is maintained by a network of national and state public health laboratories. These organizations are well established, with robust methodologies to test and confirm antimicrobial susceptibility. Still, the bridge that guides the flow of data is often one directional and caught in a constant state of rush hour that can only be refined with improvements to infrastructure and automation in the data flow. Moreover, there is an absence of information in the literature explaining the processes clinical laboratories use to coalesce and share susceptibility test data for AMR surveillance, further complicated by variability in testing procedures. This knowledge gap limits our understanding of what is needed to improve and streamline data sharing from clinical to public health laboratories. Successful models of AMR surveillance display attributes like 2-way communication between clinical and public health laboratories, centralized databases, standardized data, and the use of electronic health records or data systems, highlighting areas of opportunity and improvement. This article explores the roles and processes of the organizations involved in AMR surveillance in the United States and identifies current knowledge gaps and opportunities to improve communication between them through standardization, communication, and modernization of data flow.

Breaking Boundaries in Pneumonia Diagnostics: Transitioning from Tradition to Molecular Frontiers with Multiplex PCR.

The advent of rapid molecular microbiology testing has revolutionized infectious disease diagnostics and is now impacting pneumonia diagnosis and management. Molecular platforms offer highly multiplexed assays for diverse viral and bacterial detection, alongside antimicrobial resistance markers, providing the potential to significantly shape patient care. Despite the superiority in sensitivity and speed, debates continue regarding the clinical role of multiplex molecular testing, notably in comparison to standard methods and distinguishing colonization from infection. Recent guidelines endorse molecular pneumonia panels for enhanced sensitivity and rapidity, but implementation requires addressing methodological differences and ensuring clinical relevance. Diagnostic stewardship should be leveraged to optimize pneumonia testing, emphasizing pre- and post-analytical strategies. Collaboration between clinical microbiologists and bedside providers is essential in developing implementation strategies to maximize the clinical utility of multiplex molecular diagnostics in pneumonia. This narrative review explores these multifaceted issues, examining the current evidence on the clinical performance of multiplex molecular assays in pneumonia, and reflects on lessons learned from previous microbiological advances. Additionally, given the complexity of pneumonia and the sensitivity of molecular diagnostics, diagnostic stewardship is discussed within the context of current literature, including implementation strategies that consider pre-analytical and post-analytical modifications to optimize the clinical utility of advanced technologies like multiplex PCR.

Time to positivity of blood cultures in a level IV NICU varies based on organism category and population subgroups: is a 36-hour rule out safe?

BACKGROUND: Time to positivity (TTP) of blood cultures and organism characteristics may be different in a Level IV NICU population. METHODS: Retrospective study of 309 Level IV NICU positive blood cultures between January 2012 to December 2018 describing TTP and organism characteristics. RESULTS: Median TTP [IQR] was 21.1 [14.3, 25.2] hours, with 91.2% positive at 36 h, and 96.1% positive at 48 h. Gram negative definite pathogens had the shortest TTP (13.0 [11.4, 15.4] hours) compared to gram positive definite pathogens (16.3 [13.0, 22.4] hours). TTP for treated gram positive commensal organisms (22.3 [20.1, 30.4] hours) and those considered contaminants (23.6 [21.4, 26.0] hours), was significantly longer than both gram positive and negative definite pathogens. CONCLUSION: When antimicrobials are initiated due to concern for bacteremia and blood cultures have not identified a causative pathogen at 36 h, antimicrobials may be safely discontinued in the majority of Level IV NICU patients.

Change of Plans: Overview of Bacterial Taxonomy, Recent Changes of Medical Importance, and Potential Areas of Impact.

The process of bacterial nomenclature change has evolved in complexity over time and continues to be an iterative process that is not without challenges. The importance and feasibility of such changes vary among basic researchers, clinical microbiologists, and clinicians. In recent years, clinically relevant changes have been made across Gram-positive and Gram-negative organism groups, as well as the mycobacteria. Updated clinical laboratory accreditation requirements state that clinical laboratories must update their reporting practices in the case of clinically relevant nomenclature changes. These updates may significantly affect various sectors of health care, including antimicrobial stewardship, laboratory protocols, and infection prevention procedures and policies. While regularly updating bacterial nomenclature aims to improve the accuracy and consistency of our microbial language, the potential impact of such changes must be considered.

#AMRrounds: a systematic educational approach for navigating bench to bedside antimicrobial resistance.

Antimicrobial resistance (AMR) continues to serve as a major global health crisis. Clinicians practising in this modern era are faced with ongoing challenges in the therapeutic management of patients suffering from antimicrobial-resistant infections. A strong educational understanding and synergistic application of clinical microbiology, infectious disease and pharmacological concepts can assist the adventuring clinician in the navigation of such cases. Important items include mobilizing laboratory testing for pathogen identification and susceptibility data, harnessing an understanding of intrinsic pathogen resistance, acknowledging epidemiological resistance trends, recognizing acquired AMR mechanisms, and consolidating these considerations when constructing an ideal pharmacological plan. In this article, we outline a novel framework by which to systematically approach clinical AMR, encourage AMR-related education and optimize therapeutic decision-making in AMR-related illnesses.

Diagnostic Stewardship as a Team Sport: Interdisciplinary Perspectives on Improved Implementation of Interventions and Effect Measurement.

Diagnostic stewardship aims to deliver the right test to the right patient at the right time and is optimally combined with antimicrobial stewardship to allow for the right interpretation to translate into the right antimicrobial at the right time. Laboratorians, physicians, pharmacists, and other healthcare providers have an opportunity to improve the effectiveness of diagnostics through collaborative activities around pre-analytical and post-analytical periods of diagnostic testing. Additionally, special considerations should be given to measuring the effectiveness of diagnostics over time. Herein, we perform a narrative review of the literature on these potential optimization opportunities and the temporal factors that can yield changes in diagnostic effectiveness. Our objective is to inform on these considerations to ensure enhanced value through improved implementation and measurement of effectiveness for local stakeholder metrics and/or clinical outcomes research.

Cefadroxil Comparable to Cephalexin: Minimum Inhibitory Concentrations among Methicillin-Susceptible Staphylococcus aureus Isolates from Pediatric Musculoskeletal Infections.

Cephalexin and cefadroxil are oral first-generation cephalosporins used to treat methicillin-susceptible Staphylococcus aureus (MSSA) infections. Despite its shorter half-life, cephalexin is more frequently prescribed, although cefadroxil is an appealing alternative, given its slower clearance and possibility for less frequent dosing. We report comparative MIC distributions for cefadroxil and cephalexin, as well as for oxacillin, cephalothin, ceftaroline, and cefazolin, for 48 unique clinical MSSA isolates from pediatric patients with musculoskeletal infections. Both cefadroxil and cephalexin had MIC50 values of 2 µg/mL and MIC90 values of 4 µg/mL. MIC50s for oxacillin, cephalothin, and ceftaroline were ≤0.25 µg/mL, and cefazolin's MIC50 was 0.5 µg/mL. While cefadroxil and cephalexin MICs are higher than those for other active agents, the distributions of MICs for cefadroxil and cephalexin are statistically equivalent, suggesting similar in vitro MSSA activities. Cefadroxil should be further considered an alternative agent to cephalexin, although additional work is needed to identify the optimal dose and frequency of these antibiotics for the treatment of serious MSSA infections. IMPORTANCE Cephalexin and cefadroxil are oral antibiotics that are used to treat serious infections due to the bacteria MSSA. While cephalexin is used more commonly, cefadroxil is excreted from the body more slowly; this generally allows patients to take cefadroxil less frequently than cephalexin. In this study, we compared the abilities of cefadroxil, cephalexin, and several other representative intravenous antibiotics to inhibit the growth of MSSA in the laboratory. Bacterial samples were obtained from children with bone, joint, and/or muscle infections caused by MSSA. We found that cefadroxil and cephalexin inhibited the growth of MSSA at similar concentrations, suggesting similar antibacterial potencies. The selected intravenous antistaphylococcal antibiotics generally inhibited bacterial growth with lower antibiotic concentrations. Based on these results, cefadroxil should be further considered an alternative oral antibiotic to cephalexin, although future research is needed to identify the optimal dose and frequency of these antibiotics for serious infections.

Association of Endotracheal Aspirate Culture Variability and Antibiotic Use in Mechanically Ventilated Pediatric Patients.

Importance: Endotracheal aspirate cultures are commonly collected from patients with mechanical ventilation to evaluate for ventilator-associated pneumonia or tracheitis. However, the respiratory tract is not sterile, making differentiating between colonization from bacterial infection challenging, and results may be unreliable owing to variable specimen quality and sample processing across laboratories. Despite these limitations, clinicians routinely interpret bacterial growth in endotracheal aspirate cultures as evidence of infection, sometimes regardless of organism significance, prompting antibiotic treatment. Objective: To assess the variability in endotracheal aspirate culture rates and the association between culture rates and antibiotic prescribing among patients with mechanical ventilation across children's hospitals in the US. Design, Setting, and Participants: Cross-sectional retrospective analysis of data obtained from the Children's Hospital Association Pediatric Health Information System database between January 1, 2016, through December 31, 2019. Participants were all patients hospitalized with mechanical ventilation aged less than 18 years. Exposures: A charge for an endotracheal aspirate culture on a ventilated day. Main Outcomes and Measures: Endotracheal aspirate culture rate and antibiotic days of therapy per ventilated days. For mechanical ventilation, clinical transaction classification codes for mechanical ventilation other unspecified ventilator assistance were used. To identify respiratory cultures, the laboratory test code for aerobic culture was used and relevant keywords (ie, respiratory tract, sputum) were used to identify sources in the hospital charge description master. Results: A total of 152 132 patients were identified among 31 hospitals. Among these patients, 79 691 endotracheal aspirate cultures were collected on a ventilator-day (patients aged less than 1 year, 44%; 1-4 years, 27%, 5-11 years. 16%, and 12-18 years, 13%; 3% were Asian; 17% Hispanic; 21% non-Hispanic Black; 45% Non-Hispanic White patients; 14% were other; 56% of patients were male, 44% were female). The overall median rate of culture use was 46 per 1000 ventilator-days (IQR, 32-73 cultures per 1000 ventilator-days). The endotracheal aspirate culture rate was positively correlated with the hospital's antibiotic days of therapy rate (R = 0.46; P = .009). In a multivariable model adjusting for patient-level and hospital-level characteristics and among patients with mechanical ventilation, each additional endotracheal aspirate culture was associated with 2.87 (95% CI, 2.74-3.01) higher odds of receiving additional days of therapy compared with patients who did not receive and endotracheal aspirate culture. Conclusions and Relevance: In this study, notable variability was found in endotracheal aspirate culture rates across US pediatric hospitals and pediatric intensive care units, and endotracheal aspirate culture use was associated with increased antibiotic use. These findings suggest an opportunity for diagnostic and antibiotic stewardship to standardize testing and treatment of suspected ventilator-associated infections in pediatric patients with mechanical ventilation pediatric patients.

Time to Blood Culture Positivity by Pathogen and Primary Service.

OBJECTIVES: Initiation and continuation of empirical antimicrobial agents for a 48-72-hour observation period is routine practice in the diagnosis and treatment of infants and children with concern for bacteremia. We examined blood cultures at a freestanding pediatric hospital over a 6-year period to determine the time to positivity. METHODS: Data were extracted for all patients who were hospitalized and had blood cultures drawn between January 2013 and December 2018. Time to positivity was calculated on the basis of date and time culture was collected compared with date and time growth was first reported. RESULTS: Over a 6-year period, 89 663 blood cultures were obtained, of which 6184 had positive results. After exclusions, a total of 2121 positive blood culture results remained, including 1454 (69%) pathogens and 667 contaminants (31%). For all positive blood culture results, the number and percentage positive at 24, 36, and 48 hours were 1441 of 2121 (68%), 1845 of 2121 (87%) and 1970 of 2121 (93%), respectively. One hundred twenty-five (66 pathogens, 59 contaminants) of the 89 663 cultures (0.14%) yielded positive results between 36 and 48 hours, indicating that 719 patients would need to be treated for 48 hours rather than 36 hours to prevent 1 case of antibiotic termination before positive result. Median times to positive result by pathogen and service line are presented. CONCLUSIONS: This study reveals that ≤36 hours may be a sufficient period of observation for infants and children started on empirical antimicrobial agents for concern for bacteremia. These findings highlight opportunities for antimicrobial stewardship to limit antimicrobial .

Reliability of mecA in Predicting Phenotypic Susceptibilities of Coagulase-Negative Staphylococci and Staphylococcus aureus.

The mecA gene is commonly used to identify resistance in Staphylococcus aureus, but historically is not used for coagulase-negative staphylococci (CoNS). Analysis of 412 staphylococcal blood cultures (2014-2018) revealed that the absence of mecA had high concordance (100%) with oxacillin susceptibility for S. aureus and CoNS alike.

Rapid identification of nonblood sterile site broth cultures using the FilmArray blood culture identification panel.

The FilmArray Blood Culture Identification Panel was validated for nonblood sterile site specimens with clinical impact of rapid identification compared to conventional diagnostics. The panel accurately identified target organisms from 98% of positive broth cultures a median 1.1 day faster than conventional techniques (P < 0.0001) with potential clinical impact in 22% of cases.