Performance evaluation of InfectID-BSI: A rapid quantitative PCR assay for detecting sepsis-associated organisms directly from whole blood.

BACKGROUND: Bloodstream infections (BSIs) (presence of pathogenic organism in blood) that progress to sepsis (life-threatening organ dysfunction caused by the body's dysregulated response to an infection) is a major healthcare issue globally with close to 50 million cases annually and 11 million sepsis-related deaths, representing about 20% of all global deaths. A rapid diagnostic assay with accurate pathogen identification has the potential to improve antibiotic stewardship and clinical outcomes. METHODS: The InfectID-Bloodstream Infection (InfectID-BSI) test is a real-time quantitative PCR assay, which detects 26 of the most prevalent BSI-causing pathogens (bacteria and yeast) directly from blood (without need for pre-culture). InfectID-BSI identifies pathogens using highly discriminatory single nucleotide polymorphisms located in conserved regions of bacterial and fungal genomes. This report details the findings of a patient study which compared InfectID-BSI with conventional blood culture at two public hospitals in Queensland, Australia, using 375 whole blood samples (from multiple anatomical sites, eg. left arm, right arm, etc.) from 203 patients that have been clinically assessed to have signs and symptoms of suspected BSI, sepsis and septic shock. FINDINGS: InfectID-BSI was a more sensitive method for microorganism detection compared with blood culture (BacT/ALERT, bioMerieux) for positivity rate (102 vs 54 detections), detection of fastidious organisms (Streptococcus pneumoniae and Aerococcus viridans) (25 vs 0), detection of low bioburden infections (measured as genome copies/0.35 mL of blood), time to result (<3 h including DNA extraction for InfectID-BSI vs 16 h-48 h for blood culture), and volume of blood required for testing (0.5 mL vs 40-60 mL). InfectID-BSI is an excellent 'rule out' test for BSI, with a negative predictive value of 99.7%. InfectID-BSI's ability to detect 'difficult to culture' microorganisms re-defines the four most prevalent BSI-associated pathogens as E. coli (28.4%), S. pneumoniae (17.6%), S. aureus (13.7%), and S. epidermidis (13.7%). INTERPRETATION: InfectID-BSI has the potential to alter the clinical treatment pathway for patients with BSIs that are at risk of progressing to sepsis.

Genomic analysis of an outbreak of toxin gene bearing Corynebacterium diphtheriae in Northern Queensland, Australia reveals high level of genetic similarity.

Toxigenic diphtheria is rare in Australia with generally fewer than 10 cases reported annually; however, since 2020, there has been an increase in toxin gene-bearing isolates of Corynebacterium diphtheriae cases in North Queensland, with an approximately 300% escalation in cases in 2022. Genomic analysis on both toxin gene-bearing and non-toxin gene-bearing C. diphtheriae isolated from this region between 2017 and 2022 demonstrated that the surge in cases was largely due to one sequence type (ST), ST381, all of which carried the toxin gene. ST381 isolates collected between 2020 and 2022 were highly genetically related to each other, and less closely related to ST381 isolates collected prior to 2020. The most common ST in non-toxin gene-bearing isolates from North Queensland was ST39, an ST that has also been increasing in numbers since 2018. Phylogenetic analysis demonstrated that ST381 isolates were not closely related to any of the non-toxin gene-bearing isolates collected from this region, suggesting that the increase in toxigenic C. diphtheriae is likely due to the expansion of a toxin gene-bearing clone that has moved into the region rather than an already endemic non-toxigenic strain acquiring the toxin gene.

Molecular characterisation of Neisseria gonorrhoeae associated with disseminated gonococcal infections in Queensland, Australia: a retrospective surveillance study.

OBJECTIVES: Gonorrhoea caused by Neisseria gonorrhoeae is the second most notified sexually transmitted infection (STI) in Australia and the case numbers for this STI have been increasing globally. Progressive gonococcal infection may lead to disseminated gonococcal infection (DGI), which causes significant morbidity among patients. This study aims to examine the genetic diversity of N. gonorrhoeae isolates collected in Queensland from January 2010 to August 2015 and to determine factors associated with DGI in Queensland. DESIGN: Retrospective surveillance study for epidemiological purposes. SETTING: All gonorrhoeae isolates referred by private and public pathology laboratories to the state of Queensland, Australia Neisseria reference laboratory. METHODS: Between January 2010 and August 2015, 3953 N. gonorrhoeae isolates from both metropolitan and regional Queensland infections were typed with NG-MAST (N. gonorrhoeae multiantigen sequence typing) to assess the genetic diversity between strains. Whole-genome sequencing (WGS) was used to investigate strain-related factors associated with DGI. RESULTS: ST6876 was the most common NG-MAST type, detected in 7.6% of the isolates. DGI was significantly more likely in females <30 years (OR 13.02, p<0.0001) and in older males >30 years (OR 6.04, p<0.0001), with most cases originating from North Queensland (OR 8.5, p<0.0001). Strains harbouring PIA class of porB type were associated with DGI (OR 33.23, p<0.0001). CONCLUSION: Genotyping techniques, such as NG-MAST and WGS, are proving instrumental in providing an insight into the population structure of N. gonorrhoeae, and genetic mechanisms of pathogenesis, such as for DGI.

Implementing a Hospital-Based Safe Sleep Program for Newborns and Infants.

BACKGROUND: An unsafe sleep environment remains the leading contributor to unexpected infant death. PURPOSE: To determine the effectiveness of a quality improvement initiative developed to create a hospital-based safe sleep environment for all newborns and infants. METHODS: A multidisciplinary team from the well-baby nursery (WBN) and neonatal intensive care unit (NICU) of a 149-bed academic, quaternary care, regional referral center developed and implemented safe sleep environments within the hospital for all prior to discharge. To monitor compliance, the following were tracked monthly: documentation of parent education, caregiver surveys, and hospital crib check audits. On the inpatient general pediatric units, only hospital crib check audits were tracked. Investigators used Plan-Do-Study-Act (PDSA) cycles to evaluate the impact of the initiative from October 2015 through February 2018. RESULTS: Safe sleep education was documented for all randomly checked records (n = 440). A survey (n = 348) revealed that almost all caregivers (95.4%) reported receiving information on safe infant sleep. Initial compliance with all criteria in WBN (n = 281), NICU (n = 285), and general pediatric inpatient units (n = 121) was 0%, 0%, and 8.3%, respectively. At 29 months, WBN and NICU compliance with all criteria was 90% and 100%, respectively. At 7 months, general pediatric inpatient units' compliance with all criteria was 20%. IMPLICATIONS FOR PRACTICE: WBN, NICU and general pediatric inpatient unit collaboration with content experts led to unit-specific strategies that improved safe sleep practices. IMPLICATIONS FOR RESEARCH: Future studies on the impact of such an initiative at other hospitals are needed.

A dental student view on learning gained through Inter-Professional Engagement with people experiencing homelessness.

Community engagement is an important element of the undergraduate programme at the Faculty of Medicine and Dentistry, University of Plymouth, United Kingdom. This report presents a project that a group of second year dental students undertook with people experiencing homelessness, and provides an in-depth reflective account of its impact on the students' learning. The project formed part of the students' inter-professional engagement module and delivered an intervention to enable residents at a temporary accommodation centre to access dental treatment. As a result of the project, 14 residents received dental treatment. The groups' confidence in engaging with people experiencing homelessness and their understanding of the complex needs of this group also significantly improved. Community engagement modules can be an important learning tool for students' future practice and can help promote access to dental care for vulnerable populations.

A Comparison of Pain Management Protocols Following Total Knee Arthroplasty: Femoral Nerve Block versus Periarticular Injection of Liposomal Bupivacaine with an Adductor Canal Block.

BACKGROUND: Total knee arthroplasty (TKA) results in significant postoperative pain and a demanding postoperative path for recovery. This study was conducted to determine whether a femoral nerve block (FNB) or a periarticular injection of liposomal bupivacaine with an adductor canal block (LB+ACB) is superior for pain management. MATERIALS AND METHODS: A total of 557 consecutive primary TKA cases performed at a single hospital between 2010-2014 were retrospectively reviewed. After enrollment criteria were met, 390 cases remained (FNB=181, LB+ACB=209). Inpatient and post-discharge variables related to pain, narcotic use, healthcare resource utilization, and cost were compared. RESULTS: There were no significant differences in demographics between the two groups. There was also no significant difference in inpatient postoperative pain between the two groups. The FNB group consumed fewer narcotics overall compared to the LB+ACB group (p<0.001). However, the LB+ACB group experienced fewer opioid-related adverse events (p<0.001). The LB+ACB group had a shorter length of stay (p<.001), fewer readmissions (p=0.017) and reoperations (p=0.025), and lower costs (p<0.001). DISCUSSION: LB+ACB proved to be an equally effective postoperative TKA pain management tool compared to FNB while displaying superiority in other increasingly important areas such as length of stay and cost. The larger amount of narcotic consumption is a concern, however, and there may be a small population of patients for whom LB+ACB is not the best option.

Prognosis of teeth in the line of jaw fractures.

BACKGROUND/AIM: The decision as to whether teeth in the line of jaw fractures should be extracted or retained remains a controversial issue. The aim of this study was to assess the prognosis of teeth directly in the line of, and adjacent to, jaw fracture sites. MATERIALS AND METHODS: The study consisted of 50 patients with facial fractures in the dentate region, the diagnosis of which was made on the basis of clinical and radiographic examinations. A total of 124 teeth were present in 69 fracture sites (50 patients), of which 89 teeth were evaluated both, clinically (tooth mobility, pocket depth, pulp sensibility) and with periapical radiographs (degree of fracture displacement, marginal bone loss, root resorption). RESULTS: The results revealed that 61.9% of teeth in directly in the line of fractures showed no response to electric pulp testing compared with 48.9% teeth adjacent to fractures. The maximum frequency of non-responsive teeth was observed in Type I fractures followed by Type II fractures. Response to pulp tests was highly significant at postoperative 3- and 6-month periods (Wilcoxon's test). There was continuous reduction in the measurement for mean pocket depth at both test and control sites of teeth. The measurement of marginal bone levels of teeth in the line of fractures revealed a significant reduction (P < 0.01) from preoperative to postoperative 7-day period only. In teeth adjacent to fracture sites, the mean marginal bone levels of control site and test sites were not significant at any time interval. There was no difference in postoperative complications pertaining to whether the tooth at the fracture site was extracted or retained. CONCLUSIONS: Teeth in line of jaw fractures should not be removed on a prophylactic basis and should be followed up clinically and radiographically to determine any treatment needs.

Odontogenic infections: Microbiology and management.

OBJECTIVE: The aim of this retrospective study was to evaluate the involvement of fascial spaces, their bacteriology, sensitivity to antibiotics and management of odontogenic infection in 100 patients of age less than 60 years. RESULS: The mandibular 3(rd) molar was found to be the most commonly offending tooth, followed by the mandibular 2(nd) molar. The submandibular space was the most frequently involved fascial space both in single fascial space infections and multiple fascial space infections. Mixed growth (aerobic and anaerobic) was seen in culture smears of 60 patients, only aerobic bacterial growth was seen in 25 patients and anaerobic bacterial growth was seen in culture smears of 15 patients. Streptococcus viridans was the most frequently isolated bacteria among the aerobes, whereas Bacteroides and Prevotella were the most common bacterial species among anaerobes. Empirical antibiotic therapy in the form of Co amoxiclav and Metronidazole was given. Incision and drainage followed by extraction of the offending tooth/teeth was carried out. CONCLUSION: It was concluded that odontogenic infections were mixed aerobic-anaerobic infections. Anaerobic as well as aerobic cultures were necessary to isolate all pathogens. Successful management of these infections depends on changing the environment through decompression, removal of the etiologic factor and by choosing the proper antibiotic.

MicroRNAs activate natural killer cells through Toll-like receptor signaling.

MicroRNAs (miRNAs) bind to complementary sequences of target mRNAs, resulting in translational repression or target degradation and thus gene silencing. miRNAs are abundant in circulating blood, yet it is not known whether, as a class of regulatory molecules, they interact with human natural killer (NK) cells. Here we found that the treatment of human NK cells with several mature miRNAs in the presence of a low concentration of interleukin-12 induced CD69 expression, interferon-γ production, and degranulation marker CD107a expression. In vivo, infusion of several miRNAs alone in murine peripheral blood also resulted in comparable NK-cell activation, but not T-cell activation. Furthermore, miRNA administration significantly protected mice from tumor development in an NK cell-dependent manner. Mechanistically, we found that miRNA stimulation led to downstream activation of nuclear factor κB (NF-κB), an effect that was blunted by a block in Toll-like receptor 1(TLR1) signaling and attenuated in lymphoma patients. Knockdown of TLR1 resulted in less activation by miRNAs. Collectively, we show that miRNAs have a capacity to selectively activate innate immune effector cells that is, at least in part, via the TLR1-NF-κB signaling pathway. This may be important in the normal host defense against infection and/or malignant transformation.

Radiographic study of the positional changes and eruption of impacted third molars in young adults of an Asian Indian population.

PURPOSE: The aim of the study was to assess changes in the angular position and eruption status of third molars in students of an Asian Indian population during a 4-year follow-up period. PATIENTS AND METHODS: The series consisted of 43 students (11 males, 32 females). Standardized panoramic radiographs were taken at baseline (mean age, 19.1 +/- 0.7 years) and at the end of study (mean age 23.1 +/- 0.7 years). Angulation and degree of impaction of third molars were determined by their sagittal relationship to the adjacent second molar and eruption to the occlusal plane. Root formation was also assessed. RESULTS: During the 4-year follow-up period, 11 of 72 of the mandibular teeth (15%) and 17 of 74 of the maxillary teeth (23%) changed their sagittal inclination. Thirty-one of 118 impacted teeth (26%; level B + C) achieved level A eruption more so in the mandible, ie, 15 of 52 (29%), than in the maxilla, ie, 16 of 66 (24%). In the mandible, 9 of 24 impacted vertical teeth (37.5%), 3 of 6 distoangular teeth (50%), and 3 of 22 mesioangular impacted teeth (13.6%) erupted to the occlusal plane. In the maxilla, 9 of 36 impacted vertical teeth (25%) and 7 of 27 distoangular teeth (26%) erupted to the occlusal plane during the follow-up. The number of teeth with complete root formation increased in mandible from 61% to 93% and in maxilla from 62% to 94.5%. CONCLUSIONS: Unpredictable changes in the position and angulation of teeth continued to occur even after the age of 19 years, more so in vertical and distoangular teeth than in mesioangular teeth.

Radiographic evaluation of the status of third molars in the Asian-Indian students.

PURPOSE: The purpose of this study is to assess the prevalence and agenesis of third molars, their impaction status, and the time and sequence of their eruption in the students of Asian-Indian population. PATIENTS AND METHODS: One hundred students with ages ranging from 17.5 to 20.0 years were randomly selected. This age group was selected because this is the age at which third molars normally begin to erupt. Students who had undergone any tooth extraction or orthodontic treatment previously were not included in the study. RESULTS: The incidence of congenital missing third molars was 11.5%, with a higher incidence in females. Of the third molars present, 31% were in mesioangular position, 42% were in the vertical position, 27% were in the distoangular position, and none were in the horizontal position. Of the 354 teeth examined, 24% of teeth were found to be erupted and 76% were in various stages of eruption. The level of eruption of third molars was 27% at A; 39%, B; and 34%, C. CONCLUSIONS: The present study showed that at the baseline (mean age, 19.3 years), 24% of third molars were erupted, 76% were in various stages of eruption, and 11.5% were congenitally missing in the Asian-Indian student population.

Aspergillosis: a rare case of secondary delayed mandibular involvement.

Invasive aspergillosis in healthy hosts is a very rare occurrence, but it may become pathogenic under certain circumstances. In the head and neck region, aspergillosis usually involves the maxillary sinus. This case report describes secondary Aspergillus infection of the mandible in a 35-year-old female patient in whom the maxillary sinus was primarily involved 5 years previously.