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IntroductionThe COVID-19 pandemic is a major global public health crisis. More than 2 years into the pandemic, effective therapeutic options remain limited due to rapid viral evolution. Stemming from the emergence of multiple variants, several monoclonal antibodies are no longer suitable for clinical use. This scoping review aimed to summarize the preclinical and clinical evidence for bebtelovimab in treating newly emerging SARS-CoV-2 variants.MethodsWe systematically searched five electronic databases (PubMed, CENTRAL, Embase, Global Health, and PsycINFO) from date of inception to September 30, 2022, for studies reporting on the effect of bebtelovimab in SARS-CoV-2 infection, using a combination of search terms around ―bebtelovimab‖, ―LY-CoV1404‖, ―LY3853113‖, and ―coronavirus infection‖. All citations were screened independently by two researchers. Data were extracted and thematically analyzed based on study design by adhering to the stipulated scoping review approaches.ResultsThirty-nine studies were included, thirty-four non-clinical studies were narratively synthesized, and five clinical studies were meta-analyzed. The non-clinical studies revealed bebtelovimab not only potently neutralized wide-type SARS-CoV-2 and existing variants of concern such as B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but also retained appreciable activity against Omicron lineages, including BA.2.75, BA.4, BA.4.6, and BA.5. Unlike other monoclonal antibodies, bebtelovimab was able to bind to epitope of the SARS-CoV-2 S protein by exploiting loop mobility or by minimizing side-chain interactions. Pooled analysis from clinical studies depicted that the rates of hospitalization, ICU admission, and death were similar between bebtelovimab and other COVID-19 therapies. Bebtelovimab was associated with a low incidence of treatment-emergent adverse events.ConclusionPreclinical evidence suggests bebtelovimab be a potential treatment for COVID-19 amidst viral evolution. Bebtelovimab has comparable efficacy to other COVID-19 therapies without evident safety concerns.

BackgroundBacterial vaginosis (BV) is a common infection in women of reproductive age group because of vaginal dysbiosis. The impact of BV during pregnancy is still not well defined. The objective of this study is to assess the maternal-fetal outcome in women with BV.Materials and MethodsA prospective cohort study over one-year duration was conducted from December, 2014 until December, 2015, involving 237 women who presented with abnormal vaginal discharge, preterm labour or preterm prelabour rupture of membrane between 22- and 34-weeks period of gestation. Vaginal swabs were sent for culture and sensitivity, BV® Blue testing and PCR for Gardnerella vaginalis (GV).ResultsBV was diagnosed in 24/237 (10.1%) cases. The median gestational age was 31.6 weeks. GV was isolated from 16 out of 24 (66.7%) in the BV positive group. There was a significantly higher preterm birth rate, below 34 weeks (22.7% vs. 6.2%, p = 0.019) in women with BV. There was no statistically significant difference in maternal outcome such as clinical chorioamnionitis or endometritis. However, placental pathology revealed more than half (55.6%) of women with BV had histologic chorioamnionitis. Neonatal morbidity was significantly higher with exposure to BV, with a lower median birth weight, higher rate of neonatal intensive care unit admission (41.7% vs. 19.0%, p = 0.010), increased intubation for respiratory support (29.2% vs. 7.6%, p = 0.004) and respiratory distress syndrome (33.3% vs. 9.0%, p = 0.002).ConclusionMore research is needed to formulate guidelines for prevention, early detection and treatment of BV during pregnancy to reduce intrauterine inflammation and the associated adverse fetal outcomes.

Background:Gardnerella vaginalis (GV) is most frequently associated with bacterial vaginosis and is the second most common etiology causing intrauterine infection after Ureaplasma urealyticum. Intrauterine GV infection adversely affects pregnancy outcomes, resulting in preterm birth, fetal growth restriction, and neonatal pneumonia. The knowledge of how GV exerts its effects is limited. We developed an in vivo animal model to study its effects on fetal development.Materials and Methods: A survival mini-laparotomy was conducted on New Zealand rabbits on gestational day 21 (28 weeks of human pregnancy). In each dam, fetuses in the right uterine horn received intra-amniotic 0.5 × 102 colony-forming units of GV injections each, while their littermate controls in the left horn received sterile saline injections. A second laparotomy was performed seven days later. Assessment of the fetal pups, histopathology of the placenta and histomorphometric examination of the fetal lung tissues was done.Results: Three dams with a combined total of 12 fetuses were exposed to intra-amniotic GV, and 9 fetuses were unexposed. The weights of fetuses, placenta, and fetal lung were significantly lower in the GV group than the saline-inoculated control group [mean gross weight, GV (19.8 ± 3.8 g) vs. control (27.9 ± 1.7 g), p < 0.001; mean placenta weight, GV (5.5 ± 1.0 g) vs. control (6.5 ± 0.7 g), p = 0.027; mean fetal lung weight, GV (0.59 ± 0.11 g) vs. control (0.91 ± 0.08 g), p = 0.002. There was a two-fold increase in the multinucleated syncytiotrophoblasts in the placenta of the GV group than their littermate controls (82.9 ± 14.9 vs. 41.6 ± 13.4, p < 0.001). The mean alveolar septae of GV fetuses was significantly thicker than the control (14.8 ± 2.8 μm vs. 12.4 ± 3.8 μm, p = 0.007). Correspondingly, the proliferative index in the interalveolar septum was 1.8-fold higher in the GV group than controls (24.9 ± 6.6% vs. 14.2 ± 2.9%, p = 0.011). The number of alveoli and alveolar surface area did not vary between groups.Discussion: Low-dose intra-amniotic GV injection induces fetal growth restriction, increased placental multinucleated syncytiotrophoblasts and fetal lung re-modeling characterized by alveolar septal hypertrophy with cellular proliferative changes.Conclusion: This intra-amniotic model could be utilized in future studies to elucidate the acute and chronic effects of GV intrauterine infections.

Bacterial culture and biochemical testing (CBtest) have been the cornerstone of pathogen identification in the diagnostic microbiology laboratory. With the advent of Sanger sequencing and later, next-generation sequencing, 16S rRNA next-generation sequencing (16SNGS) has been proposed to be a plausible platform for this purpose. Nevertheless, usage of the 16SNGS platform has both advantages and limitations. In addition, transition from the traditional methods of CBtest to 16SNGS requires procurement of costly equipment, timely and sustainable maintenance of these platforms, specific facility infrastructure and technical expertise. All these factors pose a challenge for middle-income countries, more so for countries in the lower middle-income range. In this review, we describe the basis for CBtest and 16SNGS, and discuss the limitations, challenges, advantages and future potential of using 16SNGS for bacterial pathogen identification in diagnostic microbiology laboratories of middle-income countries.

Abstract Objective Pregnant women with bacterial vaginosis due to Gardnerella vaginalis (GV) infection presents with a wide-ranging disease symptomatology. We speculate this may be due to interaction that varies between host immune response and the pathogen. We studied the oxidative burst in polymorphonuclear leukocytes (PMNL)s from maternal blood (MB) and cord blood (CB) upon phagocytosis of GV and compared against E. coli and Group B Streptococcus (GBS). Results The PHAGOBURST™ assay detects fluorescence from oxidized dihydrorhodamine during oxidative burst. The average percentage of PMNL showing oxidative burst was almost two-fold greater with GBS (99.5%) and E. coli (98.2%) than GV (56.9%) (p

Introduction: Acute respiratory infection (ARI) contributes to significant mortality and morbidity worldwide and is usually caused by a wide range of respiratory pathogens. This study aims to describe the performance of QIAstat-Dx® Respiratory Panel V2 (RP) and RespiFinder® 2SMART assays for respiratory pathogens detection. Materials and Methods: A total of 110 nasopharyngeal swabs (NPS) were collected from children aged one month to 12 years old who were admitted with ARI in UKMMC during a one-year period. The two qPCR assays were conducted in parallel. Results: Ninety-seven samples (88.2%) were positive by QIAstat-Dx RP and 86 (78.2%) by RespiFinder assay. The overall agreement on both assays was substantial (kappa value: 0.769) with excellent concordance rate of 96.95%. Using both assays, hRV/EV, INF A/H1N1 and RSV were the most common pathogens detected. Influenza A/H1N1 infection was significantly seen higher in older children (age group > 60 months old) (53.3%, p-value < 0.05). Meanwhile, RSV and hRV/EV infection were seen among below one-year-old children. Co-infections by two to four pathogens were detected in 17 (17.5%) samples by QIAstat-Dx RP and 12 (14%) samples by RespiFinder, mainly involving hRV/EV. Bacterial detection was observed only in 5 (4.5%) and 6 (5.4%) samples by QIAstat-Dx RP and RespiFinder, respectively, with Mycoplasma pneumoniae the most common detected. Conclusion: The overall performance of the two qPCR assays was comparable and showed excellent agreement. Both detected various clinically important respiratory pathogens in a single test with simultaneous multiple infection detection. The use of qPCR as a routine diagnostic test can improve diagnosis and management. [ABSTRACT FROM AUTHOR]

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Introduction: OXA-48, a carbapenem-hydrolysing class D ß-lactamase, and its variant, OXA-181, are increasingly reported worldwide. This study aimed to describe the prevalence and distribution of OXA-48 and OXA-181 carbapenem-resistant Enterobacteriaceae (CRE) in a tertiary medical centre in Malaysia. Materials & Methods: A total of 13,098 Enterobacteriaceae isolates from various clinical samples were sent to our laboratory between January 2011 and December 2012. Of these, 90 demonstrated reduced susceptibility to at least one carbapenem and were included in this study. Only 88 isolates were successfully subcultured on blood agar (BA). Another 2 isolates failed to grow and were excluded. Of the 88, 2 isolates had the same identification number (repetitive isolates); therefore, 1 isolate was excluded from further analyses. Only 87 isolates were subjected to molecular detection of the blaOXA-48 and blaOXA-181 genes by polymerase chain reaction. Results: Eighty-seven non-repetitive isolates grew following subculture on BA. Of these, 9 (10.34%) were positive for OXA-48 (7 Klebsiella pneumoniae, 2 Escherichia coli). Each isolate originated from different patients. All patients had a history of treatment with at least one cephalosporin and/or carbapenem prior to the isolation of OXA-48 CRE. OXA-181 was detected in one (1.15%) out of the 87 isolates; Conclusions: The prevalence of OXA-48 and OXA-181 CRE among all Enterobacteriaceae isolates in our institution is 0.069% and 0.008%, respectively. Nevertheless, our findings suggest that OXA-48 and OXA-181 carbapenemases appear to be important and possibly under-recognised causes of carbapenem resistance in Malaysia. [ABSTRACT FROM AUTHOR]

Gardnerella vaginalis (GV) is a facultatively anaerobic gram-variable bacillus and is the major organism involved in bacterial vaginosis. GV-associated bacterial vaginosis has been associated with adverse pregnancy outcomes include preterm parturition and subclinical chorioamnionitis. Inflammatory response induced by GV presents paediatric problems as well. Studies had shown that increased levels of proinflammatory cytokines include TNF-α, IL-1β and IL-6 following fetal inflammatory response syndrome secondary to GV-induced intrauterine infection may result in the development of periventricular leukomalacia and bronchopulmonary dysplasia in the infected fetus. There is increasing evidence that GV-associated BV infection serves as a risk factor for long-term neurological complications, such as cerebral palsy and learning disability. GV is fastidious and could elude conventional detection methods such as bacterial cultures. With current more sophisticated molecular biology detection methods, its role and pathogenic effects have been shown to have a greater impact on intrauterine inflammation and fetal/neonatal infection. This review gives an overview on the characteristics of GV and its virulence properties. Its detrimental role in causing unfavourable GV-related perinatal outcomes, with emphasis on the possible mechanistic pathways is discussed. The discovery of disease mechanisms allows the building of a strong platform where further research on innovative therapies can be based on, for instance, an anti-TLR monoclonal antibody as therapeutic agent to halt inflammation-precipitate adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

Abstract Since diagnostic laboratories handle large COVID-19 samples, researchers have established laboratory-based assays and developed biosensor prototypes. Both share the same purpose; to ascertain the occurrence of air and surface contaminations by the SARS-CoV-2 virus. However, the biosensors further utilize internet-of-things (IoT) technology to monitor COVID-19 virus contamination, specifically in the diagnostic laboratory setting. The IoT-capable biosensors have great potential to monitor for possible virus contamination. Numerous studies have been done on COVID-19 virus air and surface contamination in the hospital setting. Through reviews, there are abundant reports on the viral transmission of SARS-CoV-2 through droplet infections, person-to-person close contact and fecal-oral transmission. However, studies on environmental conditions need to be better reported. Therefore, this review covers the detection of SARS-CoV-2 in airborne and wastewater samples using biosensors with comprehensive studies in methods and techniques of sampling and sensing (2020 until 2023). Furthermore, the review exposes sensing cases in public health settings. Then, the integration of data management together with biosensors is well explained. Last, the review ended with challenges to having a practical COVID-19 biosensor applied for environmental surveillance samples. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa is a notorious gram-negative bacterium that has become a global public health concern owing to the emergence of multi- and pandrug-resistant strains. This study sought to determine the antibiotic susceptibility profile of P. aeruginosa in a tertiary medical center from Malaysia. Materials and Methods: Each isolate's identity was confirmed using the VITEK 2 GN kit, and subjected to antibiotic susceptibility testing using the VITEK 2 AST-N374 card (for testing against piperacillintazobactam, ceftazidime, cefepime, imipenem, meropenem, amikacin, gentamicin and ciprofloxacin) and Etest strips (for testing against doripenem and polymyxin B). Isolates which were not susceptible to >1 carbapenem were tested for carbapenemase production using the modified carbapenem inactivation method (mCIM). Results: Out of 102 isolates studied, 64 (62.7%) were fully susceptible to all the antibiotics tested. Twenty-six (25.5%) were resistant to >1 antibiotic from >2 antibiotic classes, and 21 (20.6%) were resistant to >1 antibiotic from >3 classes. Susceptibility was highest with polymyxin B (100%) and lowest with piperacillin-tazobactam (64.7%). Carbapenem susceptibility was between 78.4% to 81.4%. Out of 22 isolates which were not susceptible to >1 carbapenem, 18 (81.8%) were not susceptible to all three carbapenems. Conclusion: More than half of our P. aeruginosa isolates were fully susceptible to all the anti-pseudomonal antibiotics tested. Multidrug-resistant strains accounted for between 20% to 25% of all our P. aeruginosa isolates. Through mCIM testing, carbapenemase production did not appear to be the dominant resistance mechanism. [ABSTRACT FROM AUTHOR]