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Executive summaryWe provide an overview of diagnostic stewardship with key concepts that include the diagnostic pathway and the multiple points where interventions can be implemented, strategies for interventions, the importance of multidisciplinary collaboration, and key microbiologic diagnostic tests that should be considered for diagnostic stewardship. The document focuses on microbiologic laboratory testing for adult and pediatric patients and is intended for a target audience of healthcare workers involved in diagnostic stewardship interventions and all workers affected by any step of the diagnostic pathway (ie, ordering, collecting, processing, reporting, and interpreting results of a diagnostic test). This document was developed by the Society for Healthcare Epidemiology of America Diagnostic Stewardship Taskforce.

BackgroundDiagnostic stewardship is an important partner to antimicrobial stewardship.ContentDiagnostic stewardship focuses on ensuring correct diagnosis of infectious diseases while antimicrobial stewardship aims to optimize antimicrobial treatment. Both aim to improve patient outcomes. Diagnostic stewardship involves interventions that reduce testing in patients with low pretest probability, optimize a test’s likelihood ratio, and seek to warn providers when suboptimal test results might have been reported.ConclusionDiagnostic stewardship interventions have been described primarily in the areas of urinary tract infection, Clostridioides difficile infection, and bloodstream infection diagnosis. However, emerging areas include pneumonia and wound infections in addition to optimization of multiplexed panel-based testing.

This survey investigated diagnostic and antimicrobial stewardship practices related to molecular respiratory panel testing in adults with lower respiratory tract infections at acute care hospitals. Most respondents reported use of rapid respiratory panels, but related stewardship practices were uncommon and the real-world impact of respiratory panels were difficult to quantify.

Background Antimicrobial resistance (AMR) is a pressing global challenge detected by antimicrobial susceptibility testing (AST) performed by clinical laboratories. AST results are interpreted using clinical breakpoints, which are updated to enable accurate detection of new and emerging AMR. Laboratories that do not apply up-to-date breakpoints impede global efforts to address the AMR crisis, but the extent of this practice is poorly understood. Methods A total of 1490 clinical laboratories participating in a College of American Pathologists proficiency testing survey for bacterial cultures were queried to determine use of obsolete breakpoints. Results Between 37.9% and 70.5% of US laboratories reported using obsolete breakpoints for the antimicrobials that were queried. In contrast, only 17.7%–43.7% of international laboratories reported using obsolete breakpoints (P Conclusions These data demonstrate a significant gap in the ability to detect AMR in the US, and to a lesser extent internationally. Improved application of current breakpoints by clinical laboratories will require combined action from regulatory agencies, laboratory accreditation groups, and device manufacturers.

The U.S. Food & Drug Administration (FDA) regulates the marketing of manufacturers’ in vitro diagnostic tests (IVDs), including assays for the detection of SARS-CoV-2. The U.S. government’s Clinical Laboratory Improvement Amendments (CLIA) of 1988 regulates the studies that a clinical diagnostic laboratory needs to perform for an IVD before placing it into use. Until recently, the FDA has authorized the marketing of SARS-CoV-2 IVDs exclusively through the Emergency Use Authorization (EUA) pathway. The regulatory landscape continues to evolve, and IVDs will eventually be required to pass through conventional non-EUA FDA review pathways once the emergency declaration is terminated, in order to continue to be marketed as an IVD in the United States. When FDA regulatory status of an IVD changes or is anticipated to change, the laboratory should review manufacturer information and previously performed internal verification studies to determine what, if any, additional studies are needed before implementing the non-EUA version of the IVD in accordance with CLIA regulations. Herein, the College of American Pathologists’ Microbiology Committee provides guidance for how to approach regulatory considerations when an IVD is converted from EUA to non-EUA status.

We surveyed acute-care hospitals on strategies to reduce inappropriate

While the incidence of COVID-associated pulmonary aspergillosis (CAPA) in COVID-19 patients admitted to the ICU in Europe is widely published (incidence up to 30%) (1), data on CAPA from the United States is lacking or has not been well described (2, 3).….

Background Children who develop malaria after returning to a setting in which the disease is not endemic are at high risk for critical delays in diagnosis and initiation of antimalarial therapy. We assessed the clinical impact of the implementation of malaria rapid diagnostic testing (RDT) on the management of children with malaria at an urban US children’s hospital that serves a large immigrant population. Methods This was a retrospective cohort study of all children diagnosed with laboratory-confirmed malaria at the Children’s Hospital of Philadelphia (CHOP) between 2000 and 2014. RDT using a US Food and Drug Administration–approved immunochromatographic assay was introduced at CHOP on August 1, 2007. We compared clinical management and outcomes of patients with malaria diagnosed before and after RDT introduction. Results We analyzed 82 pediatric malaria cases (32 before and 50 after RDT implementation). The majority of these patients had traveled to West Africa (91.5%) and were infected with Plasmodium falciparum (80.5%). The mean time to a positive result decreased from 10.4 to 0.9 hours (P < .001) after the introduction of RDT for patients with P falciparum. The mean time to antimalarial therapy decreased from 13.1 to 6.9 hours (P =; .023) in hospitalized patients. We found no significant reduction in the mean number of clinical signs of severe malaria between 0 and 48 hours of hospitalization and no difference in the need for exchange transfusion, time to resolution of parasitemia, or length of hospital stay. Conclusions Implementation of RDT for malaria was associated with shorter times to malaria diagnosis and initiation of antimalarial therapy. The results of this study support RDT in the optimal management of patients with malaria who present in settings in which the disease is not endemic.

Fungal infections are a rising threat to our immunocompromised patient population, as well as other nonimmunocompromised patients with various medical conditions. However, little progress has been made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC) was recently created. The FDLC consists of 26 laboratories from the United States and Canada that routinely provide fungal diagnostic services for patient care. A survey of fungal diagnostic capacity among the 26 members of the FDLC was recently completed, identifying the following diagnostic gaps: lack of molecular detection of mucormycosis; lack of an optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, aspergillosis, candidemia, and endemic mycoses; lack of a standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues; lack of robust databases to enhance mold identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; suboptimal diagnostic approaches for mold blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures for cystic fibrosis patients; inadequate capacity for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens; and performance of antifungal susceptibility testing. In this commentary, the FDLC delineates the most pressing unmet diagnostic needs and provides expert opinion on how to fulfill them. Most importantly, the FDLC provides a robust laboratory network to tackle these diagnostic gaps and ultimately to improve and enhance the clinical laboratory's capability to rapidly and accurately diagnose fungal infections.

On behalf of the Microbiology Committee of the College of American Pathologists (CAP), we respond to the recent commentary by Kirby and colleagues on the topic of bringing in new antimicrobial susceptibility testing ([1][1]). The authors state that “there is a lack of clarity regarding

In the clinical microbiology laboratory, the focus when choosing new tests is often on performance, turnaround time, and labor needs. This review examines available rapid, multiplexed tests from a different perspective: that of the patient. It considers whether published evidence supports the notion that use of rapid, on-demand tests (as opposed to batched testing) leads to better patient outcomes and whether broad, syndrome-based, multiplexed panels translate into better patient care than narrower monoplex or duplex assays. Finally, we examine how synergy between the clinical microbiology and antimicrobial stewardship programs is necessary to ensure that rapid tests, if implemented, impact the patients they are designed to support.

Objective In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. Methods ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged

Background Temple University Hospital recently implemented a protocol in which a urinalysis will reflex to culture only in the presence of pyuria. The purpose of this study is to compare appropriate antimicrobial use for patients with positive urine cultures before and after implementation of the urinalysis with reflex to culture protocol. Methods This is a single center, observational chart review. Adult internal medicine patients with a urinalysis and positive urine culture before and after the intervention were included in the pre- and post-intervention groups. Patients in the intensive care unit, undergoing urologic or surgical procedures, with leukopenia, being treated for another infection, who were discharged within 72 hours of the urine culture order, or pregnant were excluded. The primary endpoint was the percentage of patients with appropriate antimicrobial management of the positive urine culture before and after implementation of the protocol. Appropriate management was defined as antimicrobial treatment for a symptomatic urinary tract infection or no antimicrobial treatment for asymptomatic bacteriuria. Duration of therapy was also assessed. A sample size of 334 cultures was needed to detect a 15% difference in initiation of antibiotics between groups. Comparisons of categorical variables were analyzed by Chi-Square/Fisher exact test while continuous variables were analyzed by Wilcoxon test. Results Patient characteristics and outcomes are listed in the tables below. Table 1: Patient Characteristics Table 2: Outcomes Conclusion The urinalysis with reflex to culture intervention appeared to have minimal impact on the management of patients with a positive urine culture, with a possible increase in inappropriate management. Duration of therapy was significantly reduced by approximately one day with the intervention. Additional interventions to improve appropriate management of bacteriuria should be explored. Disclosures Jason C. Gallagher, PharmD, FIDP, FCCP, FIDSA, BCPS, Allergan (Consultant)Astellas (Consultant)Merck (Consultant, Grant/Research Support)Nabriva (Consultant)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant)Spero (Consultant)Tetraphase (Consultant)

Ventilator-associated pneumonia (VAP) is one of the most common infections in the ICU. Prompt diagnosis is vital as mortality increases with delayed antibiotic therapy. However, accurate diagnosis is challenging due to non-specific clinical features in a complicated patient cohort. Microbiological culture data remains a crucial aspect in confirming diagnosis. Literature data comparing the benefit of invasive respiratory sampling to non-invasive is inconclusive. Differences in culturing practices translate in overidentification of organisms of unclear significance. Positive culture data in a low pre-test probability does not differentiate between true infection and colonization resulting in overtreatment. Furthermore, there are also opportunities for modifying the reporting of respiratory tract cultures that can better guide antimicrobial therapy. Under the umbrella of antimicrobial stewardship, diagnostic stewardship can be incorporated to create a systematic approach that would target culturing practices to match the right pre-test probability. Ideal outcome will be targeting cultures to the right patient population and minimizing unnecessary treatment.

We assessed whether implementation of matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry without antimicrobial stewardship support would impact antimicrobial utilization and clinical outcomes in inpatient pneumonia. Implementation significantly reduced time to organism identification and time to optimal therapy but did not have a detectable impact on clinical outcomes.

The current review summarizes advances in rapid diagnostic testing that impacts infection prevention and antimicrobial stewardship programs.A variety of rapid diagnostic technologies to identify organisms in cultured blood are now available. When coupled with antimicrobial stewardship (ASP), these rapid technologies can optimize antimicrobial utilization and patient outcomes. Two rapid molecular panels that detect organisms related to pneumonia are available and may impact infection prevention surveillance definitions. Three molecular tests are available for the detection of meningitis and encephalitis pathogens. Still, the clinical impact of these broad, multiplexed panels need additional clarification. For Clostridioides difficile infections, ultrasensitive toxin A/B assays may provide enhanced sensitivity and specificity compared with enzyme immunoassay and molecular testing respectively. Finally, the adoption of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI TOF MS) for rapid organism identification is growing. Recent US Food and Drug Administration-clearance of a MALDI TOF MS platform for identification of Nocardia, Mycobacteria, and molds may expedite antimicrobial decisions for infections that traditionally required days to weeks for an identification.Tests with broad diagnostic scope and swift turnaround time are rapidly entering the market. Many impact infection prevention and ASP programs. Collaboration with the microbiology laboratory is crucial to ensure that new tests successfully optimize patient care.

The primary purpose of this review is to provide a summary of new and emerging laboratory technologies and testing platforms that impact infection prevention and antimicrobial stewardship programs. This review also summarizes available data describing the clinical impact of implementing these new technologies. While there is ample evidence that rapid organism identification technologies for positive blood cultures can ameliorate antimicrobial utilization, an assay that also provides expedited antimicrobial susceptibility testing results is now available and its clinical impact is under investigation. For C. difficile infection diagnosis, data related to performance and impact of “ultrasensitive” toxin assays is emerging in the literature although their role in C. difficile infection diagnosis remains unclear. For hospital-acquired pneumonia, a variety of rapid, automated, multiplexed, “pneumonia” panels have become commercially available and may impact surveillance definitions for ventilator-associated events. Finally, recent FDA clearance of various biochemical and molecular carbapenemase detection tests will facilitate rapid characterization of carbapenem-resistant organisms. Innovations in infectious diseases diagnostics have been making swift strides, broadening diagnostic scope; increasing accuracy and sensitivity; and reducing turnaround time. Many of these innovations directly impact infection prevention and antimicrobial stewardship operations. Close collaboration between infection control, antimicrobial stewardship, and the microbiology laboratory is necessary to ensure that new tests improve patient outcomes.

Urinary tract infections (UTIs), including catheter-associated UTIs, are among the most common bacterial infections in both inpatient and outpatient settings. Diagnosis of true UTI remains a clinical challenge, and excessive antimicrobial treatment of asymptomatic bacteriuria (ASB) or contaminated urine cultures is common. Challenges with the appropriate diagnosis of UTIs include the lack of specific signs and symptoms, no definitive diagnostic criteria, high incidence of ASB, contamination of samples, and frequent lack of indications for ordering urine cultures. Promising interventions include education and feedback, indication requirements when ordering cultures, and use of reflex culture policies that limit urine cultures. Antimicrobial and diagnostic stewardship interventions can work synergistically to decrease ordering of urine cultures without clear indication and prevent excessive antimicrobial administration in patients without clearly defined UTI.

This survey investigated interventions used by acute-care hospitals to reduce the detection of asymptomatic bacteriuria. Half of the respondents reported using reflex urine cultures but with varied urinalysis criteria and perceived outcomes. Other diagnostic stewardship interventions for urine culture ordering and specimen quality were less common.

The purpose of this review is to investigate the evolution and epidemiology of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and the current and future treatment options for infections caused by KPC-producing isolates. The emergence of resistance in Enterobacteriaceae producing carbapenemases globally has increased the challenges in treating infections caused by these organisms. One of the prominent mechanisms of resistance is the production of KPC enzymes. Infections caused by organisms producing KPCs have limited treatment options and are associated with poor clinical outcomes. The rapid rise of KPC-producing organisms necessitated the use of drugs with pharmacokinetic and toxicity limitations, including polymyxins, tigecycline, fosfomycin, and aminoglycosides. The availability of new beta-lactamase inhibitor combinations that are effective against KPC-producing organisms represent an advance in safety and efficacy. Several agents are currently being studied that have activity against KPC-producing organisms and appear to represent promising additions to our armamentarium. KPC-producing organisms cause infections with high morbidity and mortality. Limited treatment options are available, though new therapies have been developed. Pipeline agents are likely to have a place in therapy for the treatment of infections caused by KPC-producing isolates.

Background Hospitals use antibiograms to guide optimal empiric antibiotic therapy, reduce inappropriate antibiotic usage, and identify areas requiring intervention by antimicrobial stewardship programs. Creating a hospital antibiogram is a time-consuming manual process that is typically performed annually. Objective We aimed to apply visual analytics software to electronic health record (EHR) data to build an automated, electronic antibiogram (“e-antibiogram”) that adheres to national guidelines and contains filters for patient characteristics, thereby providing access to detailed, clinically relevant, and up-to-date antibiotic susceptibility data. Methods We used visual analytics software to develop a secure, EHR-linked, condition- and patient-specific e-antibiogram that supplies susceptibility maps for organisms and antibiotics in a comprehensive report that is updated on a monthly basis. Antimicrobial susceptibility data were grouped into nine clinical scenarios according to the specimen source, hospital unit, and infection type. We implemented the e-antibiogram within the EHR system at Children's Hospital of Philadelphia, a tertiary pediatric hospital and analyzed e-antibiogram access sessions from March 2016 to March 2017. Results The e-antibiogram was implemented in the EHR with over 6,000 inpatient, 4,500 outpatient, and 3,900 emergency department isolates. The e-antibiogram provides access to rolling 12-month pathogen and susceptibility data that is updated on a monthly basis. E-antibiogram access sessions increased from an average of 261 sessions per month during the first 3 months of the study to 345 sessions per month during the final 3 months. Conclusion An e-antibiogram that was built and is updated using EHR data and adheres to national guidelines is a feasible replacement for an annual, static, manually compiled antibiogram. Future research will examine the impact of the e-antibiogram on antibiotic prescribing patterns.

We used an in vitro technique to investigate blood volumes required to detect bacteremia and fungemia with low concentrations of an organism. At 1 to 10 CFU/ml, Escherichia coli , Staphylococcus epidermidis , Staphylococcus aureus , Listeria monocytogenes , Candida albicans , and Candida parapsilosis isolates were detected in volumes as low as 0.5 ml. Detection of Streptococcus agalactiae and detection of bacteremia at

This study compared the performance of the Carba NP assay, published by the Clinical and Laboratory Standards Institute, and the Rosco Rapid Carb Screen kit. Carba NP had superior sensitivity, but both assays required an increased inoculum to detect carbapenemase production in isolates with bla NDM , bla IMP , and bla OXA-48 .

BACKGROUNDWhether contact precautions (CP) are required to control the endemic transmission of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in acute care hospitals is controversial in light of improvements in hand hygiene, MRSA decolonization, environmental cleaning and disinfection, fomite elimination, and chlorhexidine bathing.OBJECTIVETo provide a framework for decision making around use of CP for endemic MRSA and VRE based on a summary of evidence related to use of CP, including impact on patients and patient care processes, and current practices in use of CP for MRSA and VRE in US hospitals.DESIGNA literature review, a survey of Society for Healthcare Epidemiology of America Research Network members on use of CP, and a detailed examination of the experience of a convenience sample of hospitals not using CP for MRSA or VRE.PARTICIPANTSHospital epidemiologists and infection prevention experts.RESULTSNo high quality data support or reject use of CP for endemic MRSA or VRE. Our survey found more than 90% of responding hospitals currently use CP for MRSA and VRE, but approximately 60% are interested in using CP in a different manner. More than 30 US hospitals do not use CP for control of endemic MRSA or VRE.CONCLUSIONSHigher quality research on the benefits and harms of CP in the control of endemic MRSA and VRE is needed. Until more definitive data are available, the use of CP for endemic MRSA or VRE in acute care hospitals should be guided by local needs and resources.Infect Control Hosp Epidemiol 2015;36(10):1163–1172

Objectives: We investigated the performance and the clinical impact of histologic examination of infected tissue in patients with suspected invasive fungal infection (IFI) at a tertiary pediatric center. Methods: Unique episodes of IFI were identified from January 1, 2001, through December 31, 2012. Surgical pathology reports, fungal culture results, and clinical data were abstracted from medical records. Results: Forty-seven patients with IFI were identified. Each patient had one episode of IFI. Risk factors included chemotherapy for an oncologic condition (n = 35), hematopoietic stem cell transplantation (n = 6), solid organ transplantation (n = 4), and primary immunodeficiency (n = 2). Tissue was obtained from deep subcutaneous tissue (n = 21), visceral organs (14 lungs, five livers, and one spleen), or the sinonasal cavity (n = 6). Fungal culture was ordered in 40 of the 47 episodes of IFI. Fungus grew in 27 (68%) of the 40 cultures submitted, and all isolates were concordant with histology. Medical records were available for 36 (77%) of 47 patients. Communication of histology results prompted changes in antifungal therapy 64% of the time. This included initiation of antifungal therapy in 13 patients who were not previously receiving therapy. Fifteen (42%) patients underwent surgical excision within 48 hours of histologic diagnosis. Conclusions: Histology can provide rapid, accurate, and clinically actionable information to clinicians caring for children with IFI.

We compared the performance of algorithmic Clostridium difficile infection (CDI) diagnosis with four molecular tests in children. Stool samples in patients 1-18 years old were tested with an algorithm (C. Diff Quik Chek Complete (QCC) reflexed to illumigene C. difficile); AmpliVue C. difficile (ACD); Lyra Direct C. difficile (Lyra); BD MAX C diff (BDM); and Xpert C. difficile (XCD). The gold standard was positivity by two tests. Sensitivity, specificity, positive predictive value, and negative predictive value were 85%, 99%, 93%, 97% for the algorithm; 21%, 99%, 78%, 87% for QCC's toxin component; 94%, 99%, 94%, 99% for ACD; 88%, 99%, 94%, 98% for Lyra; 94%, 100%, 100%, 99% for BDM, and 94%, 99%, 94% and 99% for XCD. 9.6% of samples were ribotype 027. Algorithms may detect CDI with lower sensitivity compared to molecular methods in children. This may be related to low prevalence of NAP-1/ribotype 027.

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae . We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged fumC-fimH ( E. coli ) or tonB ( Klebsiella pneumoniae ) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections.

Assays that expedite the reporting of organism identification and antibiotic susceptibility status in positive blood cultures can fast track interventions that improve clinical outcomes. We evaluated the Verigene Gram-positive blood culture nucleic acid test (BC-GP) in two pediatric hospitals. Positive BacT/Alert Pediatric FAN blood cultures with Gram-positive organisms were tested using the BC-GP in tandem with routine laboratory procedures. To test organisms underrepresented in the clinical blood culture evaluation, blood culture bottles were spiked with diluted organism suspensions at concentrations of 10 to 100 CFU per milliliter. A total of 249 Gram-positive bacterial isolates were recovered from 242 blood cultures. The BC-GP detected Staphylococcus aureus , methicillin-susceptible S. aureus , and methicillin-resistant S. aureus with sensitivities of 100%, 99%, and 100% and specificities of 100%, 100%, and 99.5%, respectively. The BC-GP detected Staphylococcus epidermidis , methicillin-susceptible S. epidermidis , and methicillin-resistant S. epidermidis with sensitivities of 95%, 80%, and 96%, respectively, and 100% specificity. The BC-GP correctly identified 14/15 cases of Enterococcus faecalis and Enterococcus faecium bacteremia and 9 cases of Streptococcus pneumoniae . It misidentified 5/15 clinical blood cultures with Streptococcus mitis / Streptococcus oralis and 1/3 blood cultures spiked with Streptococcus anginosus group as S. pneumoniae . The BC-GP detected a case of Streptococcus pyogenes bacteremia but failed to detect 2/3 clinical blood cultures with Streptococcus agalactiae . BC-GP's rapid accurate detection of Staphylococcus spp., E. faecium , and E. faecalis and its ability to ascertain mecA , vanA , and vanB status may expedite clinical decisions pertaining to optimal antibiotic use. False-positive S. pneumoniae results may warrant reporting of only “ Streptococcus spp.” when this organism is reported by the BC-GP.

Objective Bacterial colonization of the airway may contribute to the development of bronchopulmonary dysplasia. Whether airway colonization increases risk for later adverse respiratory outcomes is less clear. We described tracheal aspirate culture results obtained from preterm infants receiving mechanical ventilation at 36 weeks postmenstrual age (PMA) and evaluated the association between bacteria type and the risk for prolonged supplemental oxygen use. Study Design We conducted a retrospective, single-center cohort study comparing infants (1) with and without a tracheal aspirate culture that grew a Gram-negative rod (GNR) and (2) with and without a culture that grew a Gram-positive cocci (GPC). Results Among 121 infants, 65 (53.7%) and 51 (42.2%) had a tracheal aspirate culture that grew a potentially pathogenic GNR and GPC prior to 36 weeks PMA, respectively. GNR were associated with increased risk for death or use of supplemental oxygen at discharge (adjusted odds ratio [aOR], 6.2; 95% confidence interval [CI], 1.8–21.1), and use of supplemental oxygen at discharge among survivors (aOR, 5.5; 95% CI, 1.6–19.0). GPC did not affect the risk for any study outcomes. Conclusion GNR but not GPC in the airways of preterm infants receiving mechanical ventilation at 36 weeks PMA is associated with increased risk for prolonged supplemental oxygen use.

BACKGROUND Bloodstream infection is a major cause of morbidity and mortality. Much of our understanding of the epidemiology and resistance patterns of bloodstream infections comes from studies of hospitalized adults. METHODS We evaluated the epidemiology and antimicrobial resistance of bloodstream infections occurring during an 11-year period in a large, tertiary care children's hospital in the US. All positive blood cultures were identified retrospectively from clinical microbiology laboratory records. We excluded repeat positive cultures with the same organism from the same patient within 30 days and polymicrobial infections. RESULTS We identified 8196 unique episodes of monomicrobial bacteremia in 5508 patients. Overall, 46% were community onset, 72% were Gram-positive bacteria, 22% Gram-negative bacteria and 5% Candida spp. Coagulase negative Staphylococcus was the most common isolated organism. ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) accounted for 20% of episodes. No S. aureus isolate was resistant to vancomycin or linezolid, and no increase in vancomycin minimum inhibitory concentration among methicillin-resistant S. aureus was observed during the study period. Clinically significant increases in vancomycin-resistant Enterococcus, ceftazidime-resistant P. aeruginosa or carbapenem-resistant Enterobacteriaceae were not observed during the study period; however, rates of methicillin-resistant S. aureus increased over time (P < 0.01). CONCLUSIONS Gram-positive and ESKAPE organisms are leading causes of bacteremia in hospitalized children. Although antimicrobial resistance patterns were favorable compared with prior reports of hospitalized adults, multicenter studies with continuous surveillance are needed to identify trends in the emergence of antimicrobial resistance in this setting.

The combination of increasing rates of antibiotic resistance and the decreasing pace of new antibiotic development has become an urgent public health crisis (1). Multiple-drug-resistant bacterial organisms (MDROs) have now become common causes of health care-associated infection (HAI), the most prevalent being methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and a variety of multiple-drug-resistant Gram-negative rods (MDR-GNRs; organisms that are resistant to most, if not all, available antibiotic classes through myriad mechanisms, including production of β-lactamases with increasingly broad activity) (2–4).

Physical separation between the mammalian immune system and commensal bacteria is necessary to limit chronic inflammation. However, selective species of commensal bacteria can reside within intestinal-associated lymphoid tissues of healthy mammals. Here, we demonstrate that lymphoid tissue-resident commensal bacteria (LRC) colonized murine dendritic cells and modulate their cytokine production. In germ-free and antibiotic-treated mice, LRCs colonized intestinal-associated lymphoid tissues and induced multiple members of the IL-10 cytokine family, including dendritic cell-derived IL-10 and group 3 innate lymphoid cell (ILC3)-derived IL-22. Notably, IL-10 limited the development of pro-inflammatory Th17 cell responses, and IL-22 production enhanced LRC colonization in the steady state. Furthermore, LRC colonization protected mice from lethal intestinal damage in an IL-10-IL-10R-dependent manner. Collectively, our data reveal a unique host-commensal bacteria dialogue whereby selective subsets of commensal bacteria interact with dendritic cells to facilitate tissue-specific responses that are mutually beneficial for both the host and the microbe.

We evaluated the investigational use only (IUO) version of the rapid Verigene Gram-negative blood culture test (BC-GN), a microarray that detects 9 genus/species targets ( Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli / Shigella spp., Klebsiella oxytoca , Klebsiella pneumoniae , Proteus spp., Pseudomonas aeruginosa , and Serratia marcescens ) and 6 antimicrobial resistance determinants ( bla CTX-M , bla KPC , bla NDM , bla VIM , bla IMP , and bla OXA ) directly from positive blood cultures. BC-GN was performed on positive BacT/Alert Pediatric FAN and Bactec Peds Plus blood cultures with Gram-negative organisms at two tertiary pediatric centers. Vitek MS (bioMérieux, Durham, NC) was used to assign gold standard organism identification. The Check MDR CT-102 microarray (Check Points B.V., Wageningen, Netherlands) was used as an alternative method for detecting resistance determinants. In total, 104 organisms were isolated from 97 clinical blood cultures. BC-GN correctly detected 26/26 cultures with Acinetobacter spp., P. aeruginosa , and S. marcescens , 5/6 with Citrobacter spp., 13/14 with Enterobacter spp., 23/24 with E. coli , 2/3 with K. oxytoca , 16/17 with K. pneumoniae , and 0/1 with Proteus spp. BC-GN appropriately reported negative BC-GN results in 8/13 blood cultures that grew organisms that were not represented on the microarray but failed to detect targets in 3/5 cultures that grew multiple Gram-negative organisms. BC-GN detected 5/5 and 1/1 clinical blood cultures with bla CTX-M and bla VIM . All 6 results were corroborated by Check MDR CT-102 microarray testing. The Verigene BC-GN test has the potential to expedite therapeutic decision making in pediatric patients with Gram-negative bacteremia. Sensitivity was satisfactory but may be suboptimal in mixed Gram-negative blood cultures.

Context.—Timely initiation of directed antimicrobial therapy for Staphylococcus aureus bacteremia is dependent on rapid identification of S aureus to ascertain methicillin-susceptibility status. Objectives.—To investigate the performance of the rapid KeyPath (MicroPhage, Inc, Longmont, Colorado) methicillin-resistant S aureus (MRSA) and methicillin-susceptible S aureus (MSSA) blood culture test (MMBT). Design.—Positive BacT/ALERT Pediatric FAN (fastidious antibiotic neutralization) blood culture bottles (bioMérieux, Inc, Durham, North Carolina) were tested prospectively using MMBT and routine bacterial identification and antibiotic susceptibility testing procedures as the gold standard. The MMBT uses an S aureus–specific bacteriophage cocktail that infects bacterial cells and replicates them, resulting in cellular lysis. Bacteriophage-specific antibodies detect the increase in bacteriophage concentration in an immunoassay device. Phage amplification, in both the presence and absence of cefoxitin, indicates the presence of MRSA. The sensitivity, specificity, positive predictive value, and negative predictive value of MMBT in detecting S aureus, MSSA, and MRSA were calculated. Results.—Of 188 positive blood cultures tested, 199 (63%) had Gram-positive cocci in clusters, 46 (24%) grew S aureus (26 MSSA [57%], 20 MRSA [43%]) with the MMBT detecting 40 of 46 (87%). The sensitivity, specificity, positive predictive value, and negative predictive value among blood cultures with Gram-positive cocci in clusters were 87%, 100%, 100%, and 92% for S aureus; 81%, 100%, 100%, and 95% for MSSA; and 95%, 100%, 100%, and 99% for MRSA. All blood cultures without growth of S aureus tested negative by MMBT. Conclusions.—The MMBT detected MSSA and MRSA directly from positive BacT/ALERT PF bottles with positive predictive values of 100%, suggesting that positive results could be reported immediately, but the sensitivity of this assay limited immediate reporting of negative results.