Heterogeneity in defining multiple trauma: a systematic review of randomized controlled trials.

INTRODUCTION: While numerous randomized controlled trials (RCTs) have been conducted in the field of trauma, a substantial portion of them are yielding negative results. One potential contributing factor to this trend could be the lack of agreement regarding the chosen definitions across different trials. The primary objective was to identify the terminology and definitions utilized for the characterization of multiple trauma patients within randomized controlled trials (RCTs). METHODS: A systematic review of the literature was performed in MEDLINE, EMBASE and clinicaltrials.gov between January 1, 2002, and July 31, 2022. RCTs or RTCs protocols were eligible if they included multiple trauma patients. The terms employed to characterize patient populations were identified, and the corresponding definitions for these terms were extracted. The subsequent impact on the population recruited was then documented to expose clinical heterogeneity. RESULTS: Fifty RCTs were included, and 12 different terms identified. Among these terms, the most frequently used were "multiple trauma" (n = 21, 42%), "severe trauma" (n = 8, 16%), "major trauma" (n = 4, 8%), and trauma with hemorrhagic shock" (n = 4, 8%). Only 62% of RCTs (n = 31) provided a definition for the terms used, resulting a total of 21 different definitions. These definitions primarily relied on the injury severity score (ISS) (n = 15, 30%), displaying an important underlying heterogeneity. The choice of the terms had an impact on the study population, affecting both the ISS and in-hospital mortality. Eleven protocols were included, featuring five different terms, with "severe trauma" being the most frequent, occurring six times (55%). CONCLUSION: This systematic review uncovers an important heterogeneity both in the terms and in the definitions employed to recruit trauma patients within RCTs. These findings underscore the imperative of promoting the use of a unique and consistent definition.

Prothrombin complex concentrate (PCC) for treatment of trauma-induced coagulopathy: systematic review and meta-analyses.

BACKGROUND: Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the correction of TIC, but the efficacy, timing, and evidence to support its use in injured patients with hemorrhage are unclear. METHODS: A systematic search of published studies was performed on MEDLINE and EMBASE databases using standardized search equations. Ongoing studies were identified using clinicaltrials.gov. Studies investigating the use of PCC to treat TIC (on its own or in combination with other treatments) in adult major trauma patients were included. Studies involving pediatric patients, studies of only traumatic brain injury (TBI), and studies involving only anticoagulated patients were excluded. Primary outcomes were in-hospital mortality and venous thromboembolism (VTE). Pooled effects of PCC use were reported using random-effects model meta-analyses. Risk of bias was assessed for each study, and we used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. RESULTS: After removing duplicates, 1745 reports were screened and nine observational studies and one randomized controlled trial (RCT) were included, with a total of 1150 patients receiving PCC. Most studies used 4-factor-PCC with a dose of 20-30U/Kg. Among observational studies, co-interventions included whole blood (n = 1), fibrinogen concentrate (n = 2), or fresh frozen plasma (n = 4). Outcomes were inconsistently reported across studies with wide variation in both measurements and time points. The eight observational studies included reported mortality with a pooled odds ratio of 0.97 [95% CI 0.56-1.69], and five reported deep venous thrombosis (DVT) with a pooled OR of 0.83 [95% CI 0.44-1.57]. When pooling the observational studies and the RCT, the OR for mortality and DVT was 0.94 [95% CI 0.60-1.45] and 1.00 [95% CI 0.64-1.55] respectively. CONCLUSIONS: Among published studies of TIC, PCCs did not significantly reduce mortality, nor did they increase the risk of VTE. However, the potential thrombotic risk remains a concern that should be addressed in future studies. Several RCTs are currently ongoing to further explore the efficacy and safety of PCC.

Heterogeneity in the definition of delirium in ICUs and association with the intervention effect in randomized controlled trials: a meta-epidemiological study.

PURPOSE: To evaluate the heterogeneity in the definition of delirium in randomized controlled trials (RCTs) included in meta-analyses of delirium in intensive care units (ICUs) and to explore whether intervention effect depends on the definition used. METHODS: We searched PubMed for meta-analyses including RCTs evaluating prevention or treatment strategies of delirium in ICU. The definition of delirium was collected from RCTs and classified as validated (DSM criteria, CAM-ICU, ICDSC, NEECHAM, DRS-R98) or non-validated (non-validated scales, set of symptoms, physician appreciation or not reported). We conducted a meta-epidemiological analysis to compare intervention effects between trials using or not a validated definition by a two-step method as primary analysis and a multilevel model as secondary analysis. A ratio of odds ratios (ROR) < 1 indicated larger intervention effects in trials using a non-validated definition. RESULTS: Of 149 RCTs (41 meta-analyses), 109 (73.1%) used a validated definition and 40 (26.8%) did not (including 31 [20.8%] not reporting the definition). The primary analysis of 7 meta-analyses (30 RCTs) found no significant difference in intervention effects between trials using a validated definition and the others (ROR = 0.54, 95% CI 0.27-1.08), whereas the secondary multilevel analysis including 12 meta-analyses (67 RCTs) found significantly larger effects for trials using a non-validated versus a validated definition (ROR = 0.36, 95% CI 0.21-0.62). CONCLUSION: The definition of delirium was heterogeneous across RCTs, with one-fifth not reporting how they evaluated delirium. We did not find a significant association with intervention effect in the primary analysis. The secondary analysis including more studies revealed significantly larger intervention effects in trials using a non-validated versus a validated definition.

Thromboelastometry-guided haemostatic resuscitation in severely injured patients: a propensity score-matched study.

BACKGROUND: To accelerate the diagnosis and treatment of trauma-induced coagulopathy (TIC), viscoelastic haemostatic assays (VHA) are increasingly used worldwide, although their value is still debated, with a recent randomised trial showing no improvement in outcome. The objective of this retrospective study was to compare 2 cohorts of injured patients in which TIC was managed with either a VHA-based algorithm or a conventional coagulation test (CCT)-based algorithm. METHODS: Data were retrieved from 2 registries and patients were included in the study if they received at least 1 unit of red blood cell in the first 24 h after admission. A propensity score, including sex, age, blunt vs. penetrating, systolic blood pressure, GCS, ISS and head AIS, admission lactate and PTratio, tranexamic acid administration, was then constructed. Primary outcome was the proportion of subjects who were alive and free of massive transfusion (MT) at 24 h after injury. We also compared the cost for blood products and coagulation factors. RESULTS: From 2012 to 2019, 7250 patients were admitted in the 2 trauma centres, and among these 624 were included in the study (CCT group: 380; VHA group: 244). After propensity score matching, 215 patients remained in each study group without any significant difference in demographics, vital signs, injury severity, or laboratory analysis. At 24 h, more patients were alive and free of MT in the VHA group (162 patients, 75%) as compared to the CCT group (112 patients, 52%; p < 0.01) and fewer patients received MT (32 patients, 15% vs. 91 patients, 42%, p < 0.01). However, no significant difference was observed for mortality at 24 h (odds ratio 0.94, 95% CI 0.59-1.51) or survival at day 28 (odds ratio 0.87, 95% CI 0.58-1.29). Overall cost of blood products and coagulation factors was dramatically reduced in the VHA group as compared to the CCT group (median [interquartile range]: 2357 euros [1108-5020] vs. 4092 euros [2510-5916], p < 0.001). CONCLUSIONS: A VHA-based strategy was associated with an increase of the number of patients alive and free of MT at 24 h together with an important reduction of blood product use and associated costs. However, that did not translate into an improvement in mortality.

Agreement between pulse oximetry and arterial oxygen saturation measurement in critical care patients during COVID-19: a cross-sectional study.

Some publications suggest that pulse oximetry measurement (SpO2) might overestimate arterial oxygen saturation (SaO2) measurement in COVID-19 patients. This study aims to evaluate the agreement between SpO2 and SaO2 among COVID-19 and non-COVID-19 patients. We conducted a multicenter, prospective study including consecutive intensive care patients from October 15, 2020, to March 4, 2021, and compared for each measurement the difference between SpO2 and SaO2, also called the systematic bias. The primary endpoint was the agreement between SpO2 and SaO2 measured with the Lin concordance coefficient and illustrated using the Bland and Altman method. Factors associated with systematic bias were then identified using a generalised estimating equation. The study included 105 patients, 66 COVID-19 positive and 39 COVID-19 negative, allowing for 1539 measurements. The median age was 66 [57; 72] years with median SOFA and SAPSII scores of, respectively, 4 [3; 6] and 37 [31; 47]. The median SpO2 and SaO2 among all measurements was respectively 97 [96-99] and 94 [92-96] with a systematic bias of 0.80 [- 0.6; 2.4]. This difference was, respectively, 0.80 [- 0.7; 2.5] and 0.90 [- 0.3; 2.0] among COVID-19 positive and negative patients. Overall agreement measured with the Lin correlation coefficient was 0.65 [0.63; 0.68] with 0.61 [0.57; 0.64] and 0.53 [0.45; 0.60] among the COVID-19 positive and negative groups, respectively. Factors independently associated with the variation of the SpO2-SaO2 difference were the PaO2/FiO2 ratio and need for mechanical ventilation. In our population, agreement between SpO2 and SaO2 is acceptable. During the COVID-19 pandemic, SaO2 remains an efficient monitoring tool to characterise the level of hypoxemia and follow therapeutic interventions. As is already known about general intensive care unit patients, the greater hypoxemia, the weaker the correlation between SpO2 and SaO2.

Important Issues to Severe Trauma Survivors: A Qualitative Study.

OBJECTIVE: Identify issues that are important to severe trauma survivors up to 3 years after the trauma. BACKGROUND: Severe trauma is the first cause of disability-adjusted life years worldwide, yet most attention has focused on acute care and the impact on long-term health is poorly evaluated. METHOD: We conducted a large-scale qualitative study based on semi-structured phone interviews. Qualitative research methods involve the systematic collection, organization, and interpretation of conversations or textual data with patients to explore the meaning of a phenomenon experienced by individuals themselves. We randomly selected severe trauma survivors (abbreviated injury score ≥3 in at least 1 body region) who were receiving care in 6 urban academic level-I trauma centers in France between March 2015 and March 2018. We conducted double independent thematic analysis. Issues reported by patients were grouped into overarching domains by a panel of 5 experts in trauma care. Point of data saturation was estimated with a mathematical model. RESULTS: We included 340 participants from 3 months to 3 years after the trauma [median age: 41 years (Q1-Q3 24-54), median injury severity score: 17 (Q1-Q3 11-22)]. We identified 97 common issues that we grouped into 5 overarching domains: body and neurological issues (29 issues elicited by 277 participants), biographical disruption (23 issues, 210 participants), psychological and personality issues (21 issues, 147 participants), burden of treatment (14 issues, 145 participants), and altered relationships (10 issues, 87 participants). Time elapsed because the trauma, injury location, or in-hospital trauma severity did not affect the distribution of these domains across participants' answers. CONCLUSIONS: This qualitative study explored trauma survivors' experiences of the long-term effect of their injury and allowed for identifying a set of issues that they consider important, including dimensions that seem overlooked in trauma research. Our findings confirm that trauma is a chronic medical condition that demands new approaches to post-discharge and long-term care.

One-year patient outcomes based on lung morphology in acute respiratory distress syndrome: secondary analysis of LIVE trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) has different phenotypes and distinct short-term outcomes. Patients with non-focal ARDS have a higher short-term mortality than focal ones. The aim of this study was to assess the impact of the morphological phenotypes of ARDS on long-term outcomes. METHODS: This was a secondary analysis of the LIVE study, a prospective, randomised control trial, assessing the usefulness of a personalised ventilator setting according to lung morphology in moderate-to-severe ARDS. ARDS was classified as focal (consolidations only in the infero-posterior part of the lungs) or non-focal. Outcomes were assessed using mortality and functional scores for quality of life at the 1-year follow-up. RESULTS: A total of 124 focal ARDS and 236 non-focal ARDS cases were included. The 1-year mortality was higher for non-focal ARDS than for focal ARDS (37% vs. 24%, p = 0.012). Non-focal ARDS (hazard ratio, 3.44; 95% confidence interval, 1.80-6.59; p < 0.001), age, McCabe score, haematological cancers, SAPS II, and renal replacement therapy were independently associated with 1-year mortality. This difference was driven by mortality during the first 90 days (28 vs. 16%, p = 0.010) but not between 90 days and 1 year (7 vs. 6%, p = 0.591), at which point only the McCabe score was independently associated with mortality. Morphological phenotypes had no impact on patient-reported outcomes. CONCLUSION: Lung morphologies reflect the acute phase of ARDS and its short-term impact but not long-term outcomes, which seem only influenced by comorbidities. TRIAL REGISTRATION: NCT02149589; May 29, 2014.

Characteristics and outcomes of patients undergoing anesthesia while SARS-CoV-2 infected or suspected: a multicenter register of consecutive patients.

BACKGROUND: There are limited data to detail the perioperative anesthetic management and the incidence of postoperative respiratory complications among patients requiring an anesthetic procedure while being SARS-CoV-2 positive or suspected. METHODS: An observational multicenter cohort study was performed including consecutive patients who were SARS-CoV-2 confirmed or suspected and who underwent scheduled and emergency anesthesia between March 17 and May 26, 2020. RESULTS: A total of 187 patients underwent anesthesia with SARS-CoV-2 confirmed or suspected, with ultimately 135 (72.2%) patients positive and 52 (27.8%) negative. The median SOFA score was 2 [0; 5], and the median ARISCAT score was 49 [36; 67]. The major respiratory complications rate was 48.7% (n = 91) with 40.4% (n = 21) and 51.9% (n = 70) in the SARS-CoV-2-negative and -positive groups, respectively (p = 0.21). Among both positive and negative groups, patients with a high ARISCAT risk score (> 44) had a higher risk of presenting major respiratory complications (p < 0.01 and p = 0.1, respectively). DISCUSSION: When comparing SARS-COV-2-positive and -negative patients, no significant difference was found regarding the rate of postoperative complications, while baseline characteristics strongly impact these outcomes. This finding suggests that patients should be scheduled for anesthetic procedures based on their overall risk of postoperative complication, and not just based on their SARS-CoV-2 status.

Withholding and withdrawal of life-sustaining therapy in 8569 trauma patients: A multicentre, analytical registry study.

BACKGROUND: This study aimed to determine the prevalence of withholding or withdrawal of life-sustaining therapy (WLST) decisions in trauma ICU patients, using a large registry. We hypothesised that this prevalence is similar to that of the general population admitted to an ICU. As secondary aims, it sought to describe the trauma patients for whom the decision was made for WLST and the factors associated with this decision. DESIGN: This observational study assessed data from 14 French centres listed in the TraumaBaseTM registry. All trauma patients hospitalised for more than 48 h were pro-spectively included. RESULTS: Data from 8569 trauma patients, obtained from January 2016 to December 2018, were included in this study. A WLST decision was made in 6% of all cases. In the WLST group, 67% of the patients were older men (age: 62 versus 36, P  < 0.001); more often they had a prior medical history and higher median severity scores than the patients in the no WLST decision group; SAPS II 58 (46 to 69) versus 21 (13 to 35) and ISS 26 (22 to 24) versus 12 (5 to 22), P  < 0.001. Neurological status was strongly associated with WLST decisions. The geographic area of the ICUs affected the rate of the WLST decisions. The ICU mortality was 11% (n = 907) of which 47% (n = 422) were preceded by WLST decisions. Fourteen percent of WLST orders were not associated to the death. CONCLUSION: Among 8569 patients, medical history, trauma severity criteria, notably neurological status and geographical areas were associated with WLST. These regional differences deserve to be investigated in future studies.

Human Disease Phenotypes Associated with Loss and Gain of Function Mutations in STAT2: Viral Susceptibility and Type I Interferonopathy.

STAT2 is distinguished from other STAT family members by its exclusive involvement in type I and III interferon (IFN-I/III) signaling pathways, and its unique behavior as both positive and negative regulator of IFN-I signaling. The clinical relevance of these opposing STAT2 functions is exemplified by monogenic diseases of STAT2. Autosomal recessive STAT2 deficiency results in heightened susceptibility to severe and/or recurrent viral disease, whereas homozygous missense substitution of the STAT2-R148 residue is associated with severe type I interferonopathy due to loss of STAT2 negative regulation. Here we review the clinical presentation, pathogenesis, and management of these disorders of STAT2.

Selective Imaging of Microplastic and Organic Particles in Flow by Multimodal Coherent Anti-Stokes Raman Scattering and Two-Photon Excited Autofluorescence Analysis.

Microplastic pollution is an urgent global issue. While spectroscopic techniques have been widely used for the identification of plastics collected from aquatic environments, these techniques are often labor-intensive and time-consuming due to sample collection, preparation, and long measurement times. In this study, a method for the two-dimensional detection and classification of flowing microplastic and organic biotic particles with high spatial and temporal resolutions has been proposed based on the simultaneous detection of coherent anti-Stokes Raman scattering (CARS) and two-photon excited autofluorescence (TPEAF) signals. Poly(methyl methacrylate) (PMMA), polystyrene (PS), and low-density polyethylene (LDPE) particles with sizes ranging from several tens to hundreds of micrometers were selectively detected in flow with an average velocity of 4.17 mm/s by CARS line scanning. With the same flow velocity, flowing PMMA and alga particles were measured using a multimodal system of CARS and TPEAF signals. The average intensities of both PMMA and alga particles in the CARS signals at a frequency of 2940 cm-1 were higher than the background level, while only algae emitted TPEAF signals. This allowed the classification of PMMA and alga particles to be successfully performed in flow by the simultaneous detection of CARS and TPEAF signals. With the proposed method, the monitoring of microplastics in a continuous water flow without collection or extraction is possible, which is game-changing for the current sampling-based microplastic analysis.

The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity.

Nucleotide-binding and oligomerization domain (NOD)-like receptors constitute a first line of defense against invading bacteria. X-linked Inhibitor of Apoptosis (XIAP) is implicated in the control of bacterial infections, and mutations in XIAP are causally linked to immunodeficiency in X-linked lymphoproliferative syndrome type-2 (XLP-2). Here, we demonstrate that the RING domain of XIAP is essential for NOD2 signaling and that XIAP contributes to exacerbation of inflammation-induced hepatitis in experimental mice. We find that XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2. We further show that LUBAC activity is required for efficient NF-κB activation and secretion of proinflammatory cytokines after NOD2 stimulation. Remarkably, XLP-2-derived XIAP variants have impaired ubiquitin ligase activity, fail to ubiquitylate RIPK2, and cannot facilitate NOD2 signaling. We conclude that XIAP and LUBAC constitute essential ubiquitin ligases in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2 signaling contributes to XLP-2 pathogenesis.

Predictive risk factors for postoperative pneumonia after heart transplantation.

BACKGROUND: Pneumonia is a frequent complication in patients undergoing heart transplantation (HTx) that increases morbidity and mortality in this population. Nevertheless, the risk factors for postoperative pneumonia (POP) are still unknown. The aim of this study was to investigate the predictive risk factors for POP in HTx recipients. METHODS: In this retrospective study, all patients undergoing HTx between January 2014 and December 2015 were included. All cases of POP occurring until hospital discharge were investigated. The study aimed to determine risk factors using univariate and multivariate Cox regression models. Data are expressed in Odds Ratio [95% CI]. P < 0.05 was necessary to reject the null hypothesis. RESULTS: A total of 175 patients were included without any patients being lost to follow-up, and 89 instances of POP were diagnosed in 59 (34%) patients. Enterobacteriaceae and Pseudomonas aeruginosa were the most common pathogens. In the multivariate analysis, the risk factors were preoperative mechanical ventilation (OR 1.42 [1.12-1.80], P < 0.01) and perioperative blood transfusion (OR 1.42 [95% CI: 1.20-1.70], P < 0.01). POP significantly impacted mortality at 30 days (OR: 4 [1.3-12.4], P = 0.01) and 1 year (OR: 6.8 [2.5-8.4], P < 0.01) and was associated with a longer duration of mechanical ventilation, time to weaning from venoarterial extracorporeal membrane oxygenation and stay in an intensive care unit. Plasma exchanges and intravenous administration of immunoglobulins did not increase the risk of POP. CONCLUSION: After HTx, preoperative mechanical ventilation and blood transfusion were risk factors for POP and were associated with increased mortality. Enterobacteriaceae and Pseudomonas aeruginosa are the most common pathogens of POP.

A Prematurity Collaborative Birth Equity Consensus Statement for Mothers and Babies.

INTRODUCTION: In 2016, March of Dimes (MOD) launched its Prematurity Collaborative to engage a broad cross section of national experts to address persistent and widening racial disparities in preterm birth by achieving equity and demonstrated improvements in preterm birth. African-American and Native American women continue to have disproportionate rates of preterm birth and maternal death. As part of the Collaborative, MOD created the Health Equity Workgroup whose task was the creation of a scientific consensus statement articulating core values and a call to action to achieve equity in preterm birth utilizing health equity and social determinants of health frameworks. METHODS: Health Equity Workgroup members engaged in-person and virtually to discuss key determinant contributors and resolutions for disparate maternal and birth outcomes. Workgroup members then drafted the Birth Equity Consensus Statement that contained value statements and a call to action. The birth equity consensus statement was presented at professional conferences to seek broader support. This article highlights the background and context towards arriving at the core values and call to action, which are the two major components of the consensus statement and presents the core values and call to action themselves. RESULTS: The result was the creation of a birth equity consensus statement that highlights risks and protections of social determinants based on the prevailing science, and identifies promising solutions for reducing preterm birth and eliminating racial disparities. CONCLUSION: The birth equity consensus statement provides a mandate, guiding the work of March of Dimes and the broader MCH community, for equity-based research, practice, and policy advocacy at local, state, and federal levels. SIGNIFICANCE: This field report adds to the current knowledge base on racial and ethnic disparities in birth and maternal health outcomes. Research has documented the science behind eliminating health disparities. Scientists and practitioners should continue to explore in practice how the social determinants of birth and maternal health, which manifest historically and contemporarily, can be addressed.

Fluorogenic l-alanylaminopeptidase substrates derived from 6-amino-2-hetarylquinolines and 7-amino-3-hetarylcoumarins and their potential applications in diagnostic microbiology.

Six novel fluorogenic enzyme substrates for detecting l-alanylaminopeptidase activity in microorganisms have been prepared and evaluated in Columbia agar media. The substrates are l-alanyl derivatives of 6-amino-2-hetarylquinolines and 7-amino-3-hetarylcoumarins. Both the quinoline and coumarin series of substrates produced fluorescence in the presence of Gram-negative microorganisms. In contrast, fluorescence generation in the presence of the Gram-positive microorganisms and yeasts was limited or absent.

Detection of l-alanylaminopeptidase activity in microorganisms using chromogenic self-immolative enzyme substrates.

Three potential chromogenic enzymatic probes, each possessing a self-immolative spacer unit, were synthesised for the purpose of detecting l-alanylaminopeptidase activity in microorganisms. An Alizarin-based probe was the most effective, allowing several species to generate strongly coloured colonies in the presence of metal ions.

CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth.

Preterm birth (delivery before 37 weeks and 0/7 days of gestation) is a leading cause of infant morbidity and mortality in the United States. In 2013, 11.4% of the nearly 4 million U.S. live births were preterm; however, 36% of the 8,470 infant deaths were attributed to preterm birth (1). Infants born at earlier gestational ages, especially <32 0/7 weeks, have the highest mortality (Figure) and morbidity rates. Morbidity associated with preterm birth includes respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage; longer-term consequences include developmental delay and decreased school performance. Risk factors for preterm delivery include social, behavioral, clinical, and biologic characteristics (Box). Despite advances in medical care, racial and ethnic disparities associated with preterm birth persist. Reducing preterm birth, a national public health priority (2), can be accomplished by implementing and monitoring strategies that target modifiable risk factors and populations at highest risk, and by providing improved quality and access to preconception, prenatal, and interconception care through implementation of strategies with potentially high impact.

Detection of l-alanylaminopeptidase activity in microorganisms using fluorogenic self-immolative enzyme substrates.

A series of fluorogenic enzymatic substrates that incorporate a self-immolative spacer were synthesised for the purpose of identifying l-alanylaminopeptidase activity in microorganisms in agar media. These substrates resulted in the generation of fluorescent microorganism colonies with Gram-negative microorganisms.

2-(Nitroaryl)benzothiazole and benzoxazole derivatives as fluorogenic substrates for the detection of nitroreductase activity in clinically important microorganisms.

A series of carboxy-substituted 2-(nitroaryl)benzothiazole derivatives and carboxy-substituted 2-(nitroaryl)benzoxazole derivatives were prepared and evaluated as potential nitroreductase substrates for the purpose of detecting clinically important microorganisms. Several of the substrates produced highly fluorescent colonies with the majority of a panel of 10 Gram-negative bacteria and also with two of a panel of 8 Gram-positive bacteria.