Subsequent Bacterial Infection Research Articles

Contribution of disease to Australian sea lion (Neophoca cinerea) pup mortality at Seal Bay, Kangaroo Island, 2016–2022

AbstractThe endangered Australian sea lion (Neophoca cinerea) population is declining, and its conservation is threatened by the species' low fecundity and high pup mortality. This study details reasons for pup deaths and quantifies the impacts of disease and comorbidity. Of 284 dead pups reported from five breeding seasons (2016–2022) at the Seal Bay colony, Kangaroo Island, gross necropsy was conducted on 122, with fecal analysis for hookworm (Uncinaria sanguinis) detection, tissue histology, and bacterial culture performed on subsets. Determinable primary causes of mortality were conspecific trauma (± comorbidity, 41.0%), starvation (24.6%), and infectious disease (hookworm‐associated hemorrhagic enteritis [HAHE] ± bacterial infection, 19.7%). Allowing for comorbidity, 37.7% of pups died with an infectious disease, including 44.0% of deaths with trauma and 41.5% with starvation. In higher mortality summer‐autumn breeding seasons, pups were at greater risk of trauma (p = .001) and subsequent bacterial infection (p < .001). Parasiticide treatment significantly reduced HAHE‐associated (p = .005) and overall mortality (p < .001) risk, suggesting hookworm infection increases pup susceptibility to other causes of mortality. Although the exact causal pathways for this treatment‐related overall mortality benefit remain to be confirmed, intervention appears highly impactful and could benefit species conservation efforts.

Investigating dynamics, etiology, pathology, and therapeutic interventions of Caligus clemensi and Vibrio alginolyticus co-infection in farmed marine fish

This study investigated a disease outbreak characterized by caligid copepod infestations and subsequent secondary bacterial infections in European seabass (Dicentrarchus labrax) and flathead grey mullet (Mugil cephalus) cultivated at a private facility in the Deeba Triangle region of Egypt. Moribund fish displayed brown spots on the skin, tongue, and gills, along with lethargy and excess mucus. The fish suffered severe infections, exhibiting external hemorrhages, ulcers, and ascites. The fish had pale, enlarged livers with hemorrhaging. Comprehensive parasitological, bacteriological, molecular, immunity and histopathological analyses were conducted to identify the etiological agents and pathological changes. Caligid copepod infestation was observed in wet mounts from the buccal and branchial cavities of all examined fish, and the caligids were identified as Caligus clemensi through COI gene sequencing and phylogenetic analysis. Vibrio alginolyticus was confirmed as a secondary bacterial infection through biochemical tests, recA gene sequencing, and phylogenetic analyses. Antibiotic susceptibility testing revealed resistance to β-lactams, aminoglycosides, and trimethoprim-sulfamethoxazole in V. alginolyticus isolates. Upregulation of the inflammatory marker IL-1β in gill and skin tissues indicated a robust cell-mediated immune response against the pathogens. Histopathological examination revealed severe tissue damage, hyperplasia, hemorrhage, and congestion in the gills, along with hepatocellular degeneration and steatosis in the liver, providing initial insights into this outbreak. A comprehensive therapeutic regimen was implemented, comprising prolonged hydrogen peroxide immersion baths, followed by the application of the nature-identical plant-based compound Lice-less and probiotic Sanolife Pro-W supplementation. This integrated approach effectively eliminated C. clemensi infestations, controlled secondary bacterial infections, and restored fish health, reducing morbidity and mortality rates to minimal levels.

Infection history imprints prolonged changes to the epigenome, transcriptome and function of Kupffer cells

Liver macrophages fulfill various homeostatic functions and represent an essential line of defense against pathogenic insults. However, it remains unclear whether a history of infectious disease in the liver leads to long-term alterations to the liver macrophage compartment. We utilized a curable model of parasitic infection invoked by the protozoan parasite Trypanosoma brucei brucei to investigate whether infection history can durably reshape hepatic macrophage identity and function. Employing a combination of fate mapping, single-cell CITE-sequencing, single-nuclei multiome analysis, epigenomic analysis, and functional assays, we studied the alterations to the liver macrophage compartment during and after the resolution of infection. We show that T.brucei brucei infection alters the composition of liver-resident macrophages, leading to the infiltration of monocytes that differentiate into various infection-associated macrophage populations with divergent transcriptomic profiles. Whereas infection-associated macrophages disappear post-resolution of infection, monocyte-derived macrophages engraft in the liver, assume a Kupffer cell (KC)-like profile and co-exist with embryonic KCs in the long-term. Remarkably, the prior exposure to infection imprinted an altered transcriptional program on post-resolution KCs that was underpinned by an epigenetic remodeling of KC chromatin landscapes and a shift in KC ontogeny, along with transcriptional and epigenetic alterations in their niche cells. This reprogramming altered KC functions and was associated with increased resilience to a subsequent bacterial infection. Our study demonstrates that a prior exposure to a parasitic infection induces trained immunity in KCs, reshaping their identity and function in the long-term. Although the liver is frequently affected during infections, and despite housing a major population of resident macrophages known as Kupffer cells (KCs), it is currently unclear whether infections can durably alter KCs and their niche cells. Our study provides a comprehensive investigation into the long-term impact of a prior, cured parasitic infection, unveiling long-lasting ontogenic, epigenetic, transcriptomic and functional changes to KCs as well as KC niche cells, which may contribute to KC remodeling. Our data suggest that infection history may continuously reprogram KCs throughout life with potential implications for subsequent disease susceptibility in the liver, influencing preventive and therapeutic approaches.

Role of Nedd4L in Macrophage Pro-Inflammatory Polarization Induced by Influenza A Virus and Lipopolysaccharide Stimulation.

Influenza A virus (IAV) infection often leads to influenza-associated fatalities, frequently compounded by subsequent bacterial infections, particularly Gram-negative bacterial co-infections. Lipopolysaccharide (LPS), a primary virulence factor in Gram-negative bacteria, plays a crucial role in influenza-bacterial co-infections. However, the precise pathogenic mechanisms underlying the synergistic effects of viral-bacterial co-infections remain elusive, posing significant challenges for disease management. In our study, we administered a combination of IAV and LPS to mice and examined associated parameters, including the lung function, lung index, wet/dry ratio, serum inflammatory cytokines, Nedd4L expression in lung tissue, and mRNA levels of inflammatory cytokines. Co-infection with IAV and LPS exacerbated lung tissue inflammation and amplified M1 macrophage expression in lung tissue. Additionally, we stimulated macrophages with IAV and LPS in vitro, assessing the inflammatory cytokine content in the cell supernatant and cytokine mRNA expression within the cells. This combined stimulation intensified the inflammatory response in macrophages and upregulated Nedd4L protein and mRNA expression. Subsequently, we used siRNA to knockdown Nedd4L in macrophages, revealing that suppression of Nedd4L expression alleviated the inflammatory response triggered by concurrent IAV and LPS stimulation. Collectively, these results highlight the pivotal role of Nedd4L in mediating the exacerbated inflammatory responses observed in IAV and LPS co-infections.

The role of macrophage phagocytosis on respiratory pneumovirus infection and host defense

Abstract Lung macrophages play a pivotal role in the defense against viral and bacterial infections. These specialized cells are equipped with multiple mechanisms, such as phagocytosis, to detect the presence of pathogens and clear the infections. Human Metapneumovirus (HMPV) is a leading cause of acute lung infection, affecting particularly young children and the elderly. During and after the HMPV infection, individuals are at an increased risk of secondary bacterial infections due to a decreased immune response capacity, which increases the severity of the disease. However, the cellular contribution of macrophages in the HMPV infection remains understudied. In this work, we investigated the role of macrophage phagocytosis in HMPV infection and the effect of HMPV on macrophage phagocytic activity. For that, we used THP-1- and PBMC-derived macrophages as experimental models. We found that macrophages were susceptible to HMPV infection and that phagocytosis is one of the mechanisms used by the virus to infect the cells. However, macrophages do not replicate the virus efficiently. Furthermore, viral infection decreases the capacity of macrophages to phagocyte bacteria, as demonstrated by the activity of intracellular pH indicator dye. These data highlight the importance of phagocytosis as a mechanism to control respiratory viral infections and the subversion of the host immunity by HMPV that may contribute to subsequent opportunistic bacterial infections.

Common Bacterial Infections during the 3-Month Period after SARS-CoV-2 Infection: A Retrospective Cohort Study.

Correlations between SARS-CoV-2 and bacterial infections have mainly been studied in hospitals, and these studies have shown that such interactions may be lethal for many. In the context of community flora, less is known of the trends and consequences of viral infections relative to subsequent bacterial infections. This study aims to explore the prevalence and characteristics of bacterial infections in the three months following SARS-CoV-2 infections, in a community, real-world setting. In this retrospective cohort study, we compared patients who completed a polymerase chain reaction (PCR) test or an antigen test for SARS-CoV-2 during January 2022, the peak of the Omicron wave, and examined bacterial infections following the test. We searched these cases for diagnoses of the following four bacterial infections for three months following the test: Group A Streptococcus (GAS) pharyngitis, pneumonia, cellulitis, and urinary tract infections (UTI). During January 2022, 267,931 patients tested positive and 261,909 tested negative for SARS-CoV-2. Test-positive compared to test-negative patients were significantly younger (42.5 years old vs. 48.5 years old, p < 0.001), smoked less, and had fewer comorbidities (including ischemic heart disease, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, and chronic renal failure). In the multivariable analysis, test-positive patients had an increased risk for GAS pharyngitis (adjusted odds ratio [aOR] = 1.25, 95% CI 1.14-1.38, p-value < 0.001) and pneumonia (aOR = 1.25, 95% CI 1.15-1.35, p-value < 0.001), a trend towards an increased prevalence of UTI (aOR = 1.05, 95% CI 0.99-1.12, p-value = 0.092), and lower risk for cellulitis (aOR = 0.92, 95% CI 0.86-0.99, p-value < 0.05). A history of SARS-CoV-2 infection in the past three months increased susceptibility to respiratory tract bacterial infections and the prevalence of UTI.

A cooperativity between virus and bacteria during respiratory infections

Respiratory tract infections remain the leading cause of morbidity and mortality worldwide. The burden is further increased by polymicrobial infection or viral and bacterial co-infection, often exacerbating the existing condition. Way back in 1918, high morbidity due to secondary pneumonia caused by bacterial infection was known, and a similar phenomenon was observed during the recent COVID-19 pandemic in which secondary bacterial infection worsens the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) condition. It has been observed that viruses paved the way for subsequent bacterial infection; similarly, bacteria have also been found to aid in viral infection. Viruses elevate bacterial infection by impairing the host’s immune response, disrupting epithelial barrier integrity, expression of surface receptors and adhesion proteins, direct binding of virus to bacteria, altering nutritional immunity, and effecting the bacterial biofilm. Similarly, the bacteria enhance viral infection by altering the host’s immune response, up-regulation of adhesion proteins, and activation of viral proteins. During co-infection, respiratory bacterial and viral pathogens were found to adapt and co-exist in the airways of their survival and to benefit from each other, i.e., there is a cooperative existence between the two. This review comprehensively reviews the mechanisms involved in the synergistic/cooperativity relationship between viruses and bacteria and their interaction in clinically relevant respiratory infections.

Cytomegalovirus durably primes neutrophil oxidative burst.

Cytomegalovirus (CMV) is a ubiquitous herpes virus that infects most humans, thereafter persisting lifelong in tissues of the host. It is a known pathogen in immunosuppressed patients, but its impact on immunocompetent hosts remains less understood. Recent data have shown that CMV leaves a significant and long-lasting imprint in host immunity that may confer some protection against subsequent bacterial infection. Such innate immune activation may come at a cost, however, with potential to cause immunopathology. Neutrophils are central to many models of immunopathology, and while acute CMV infection is known to influence neutrophil biology, the impact of chronic CMV infection on neutrophil function remains unreported. Using our murine model of CMV infection and latency, we show that chronic CMV causes persistent enhancement of neutrophil oxidative burst well after resolution of acute infection. Moreover, this in vivo priming of marrow neutrophils is associated with enhanced formyl peptide receptor expression, and ultimately constitutive c-Jun N-terminal kinase phosphorylation and enhanced CD14 expression in/on circulating neutrophils. Finally, we show that neutrophil priming is dependent on viral load, suggesting that naturally infected human hosts will show variability in CMV-related neutrophil priming. Altogether, these findings represent a previously unrecognized and potentially important impact of chronic CMV infection on neutrophil responsiveness in immunocompetent hosts.

Adherence to vaccination guidelines of patients with complete splenectomy in Norway, 2008–2020

The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.

Identification and antibiotics Sensitivity of Secondary Bacterial Infection in COVID-19 (SARS-CoV-2) Pneumonia patients in Kirkuk/Iraq

Abstract: The unusual virus, now known as Coronavirus 2 (SARS-CoV-2), spread fast throughout China and other regions of the world due to its remarkable ability for human-to-human transmission. Patients with COVID-19 commonly experience significant morbidity and mortality from subsequent bacterial infections. Aim: To determine the incidence of typical bacterial infections in COVID-19 pneumonia, including Klebsiella pneumoniae, Pseudomonas aerogenusa, Escherichia coli, and Staphylococcus aureus. Hundred sputum samples were taken from individuals who had been identified as having the developing Coronavirus and were dwelling in intensive care units in Hospitals (Al Shifa hospital) in Kirkuk city/Iraq. The BDph Phoenix m50 procedure was used to test the antibiotic sensitivity of samples collected on various culture mediums, then transferred to pure cultures and diagnosed. The total of 100 patients, 60% of them had a secondary bacterial infection, whereas 40% of them did not. The most common isolated species was Staphylococcus aureus identification at (40%) followed by K. pneumoniae (33%), Pseud. aeruginosa (22%), and E. coli (5%). The majority of the identified strains were resistant to the study's antibiotics. This study demonstrates that SARS-CoV-2 infected critically sick individuals had a very high frequency of subsequent bacterial infection. The pathogenic bacteria that were identified for this investigation were resistant to the majority of the antibiotics that were utilized.

Bacteriological study and its antibiotics susceptibility pattern of Otitis Media in Iraqi patients

Otitis media is an acute upper respiratory tract infection-related inflammation of the middle ear and tympanic membrane, frequently affecting children. Typically, a subsequent bacterial infection complicates a viral infection, which ultimately causes the condition. The study aims to study the function of bacterial ear infections and its causes, as well as their resistance to medications, which was the focus of this investigation. The first axis of the research was the identification of bacterial isolates using recognized diagnostic tools, and the second axis was determining the antibiotic's resistance and sensitivity. Patients with otitis media were gathered from Al-Hakim General Hospital and Al-Sadr city hospital in Al-Najaf city between November 2020 and April 2021 for 100 clinical samples. More than 80 samples were found to be infected with bacteria. Bacterial strains found in this investigation are ( 30 ) isolates of Pseudomonas aeruginosa, (20) isolates of Klebsiella spp, (20) isolates of Proteus spp, ( 15 ) isolates of Staphylococcus aureus, (8) isolates Escherichia coli and (7) isolates Enterococcus fecalies. As part of this research, the disk diffusion method was used to assess how sensitive the test was. The results showed that Pseudomonas aeruginosa was resistant to most antibiotics, particularly the penicillin family, cephalosporin, and trimethoprim, with the existence of isolates resistant to meropenem. The investigation results varied for the quinolone, aminoglycoside, and macrolide families. Klebsiella spp. were tested for antibiotic sensitivity and found to be resistant to most antibiotics, particularly those in the penicillin family, cephalosporins, and trimethoprim. Some quinolones, aminoglycosides, and macrolides are also resistant. Proteus spp were resistant to most antibiotics, particularly the penicillin family (except for augmentin, which had some sensitive isolates) and cephalosporin (except for cefdinir and cefepime) had some susceptible isolates) and trimethoprim, in addition to the presence of isolates resistant to meropenem. There is a discrepancy in the examination results for the quinolone family. The aminoglycoside family is also highly resistant. S. aureus isolates were resistant to penicillin (except for augmentin, which some isolates were responsive to), trimethoprim, and quinolones, with the presence of isolates resistant to vancomycin. The macrolide class ( azithromycin) also has a significant resistance level. Escherichia coli is susceptible to meropenem, imipenem, and certain cephalosporin generations. Augmentin, cefepime, cephalothin, meropenem, imipenem, and azithromycin were ineffective against Enterococcus fecal. The conclusion is that Pseudomonas spp has a role in ear infections and the germs Klebsiella spp., Proteus spp., Staphylococcus aureus, Escherichia coli, and Enterococcus fecalies. Penicillin and cephalosporin resistance was seen in the majority of the identified isolates. The existence of isolates of Proteus and Pseudomonas species resistant to meropenem. Vancomycin-resistant strains of Staphylococcus aureus isolates are present. Keywords: Otitis media, Resistance antibiotic, S.aureus, P.aerginosa

Metal-coordination synthesis of a natural injectable photoactive hydrogel with antibacterial and blood-aggregating functions for cancer thermotherapy and mild-heating wound repair.

Photothermal therapy (PTT) is a promising approach for treating cancer. However, it suffers from the formation of local lesions and subsequent bacterial infection in the damaged area. To overcome these challenges, the strategy of mild PTT following the high-temperature ablation of tumors is studied to achieve combined tumor suppression, wound healing, and bacterial eradication using a hydrogel. Herein, Bi2S3 nanorods (NRs) are employed as a photothermal agent and coated with hyaluronic acid to obtain BiH NRs with high colloidal stability. These NRs and allantoin are loaded into an injectable Fe3+-coordinated hydrogel composed of sodium alginate (Alg) and Farsi gum (FG), which is extracted from Amygdalus scoparia Spach. The hydrogel can be used for localized cancer therapy by high-temperature PTT, followed by wound repair through the combination of mild hyperthermia and allantoin-mediated induction of cell proliferation. In addition, an outstanding blood clotting effect is observed due to the water-absorbing ability and negative charge of FG and Alg as well as the porous structure of hydrogels. The hydrogels also eradicate infection owing to the local heat generation and intrinsic antimicrobial activity of the NRs. Lastly, in vivo studies reveal an efficient photothermal-based tumor eradication and accelerated wound healing by the hydrogel.

Investigation of susceptibility genes for chickenpox disease across multiple continents

Chickenpox (varicella) is caused by infection with the varicella-zoster virus (VZV), a neurotropic alpha herpes virus with a double-stranded DNA genome. Chickenpox can cause life-threatening complications, including subsequent bacterial infections, central nervous system symptoms, and even death without any risk factors. Few studies have been reported to investigate genetic susceptibility implicated in chickenpox. Herein, our study identified global genetic variants that potentially contributed to chickenpox susceptibility by utilizing the established bioinformatic-based approach. We integrated several databases, such as genome-wide association studies (GWAS) catalog, GTEx portal, HaploReg version 4.1, and Ensembl databases analyses to investigate susceptibility genes associated with chickenpox. Notably, increased expression of HLA-S, HCG4P5, and ABHD16A genes underlie enhanced chickenpox susceptibility in the European, American, and African populations. As compared to the Asian population, Europeans, Americans, and Africans have higher allele frequencies of the extant variants rs9266089, rs10947050, and rs79501286 from the susceptibility genes. Our study suggested that these susceptibility genes and associated genetic variants might play a critical role in chickenpox progression based on host genetics with clinical implications.

Bacterial Biofilms - A Therapeutic Challenge

A bacterial biofilm is a community of bacteria or colony, adhered to a stationary living or non-living surface within a matrix of selfproducedextracellular polymeric material and microbial cells. Bacterial biofilms can result in nosocomial infections and are typicallyharmful in nature. According to the National Institutes of Health (NIH), biofilm formation is the cause of 80% of chronic illnesses and65% of all microbial infections. Bacterial biofilms exhibit resistance to both the host immune system and antibiotics. Infection linked tobiofilms can result in significant productivity losses for the livestock industry. Treating chronic mastitis with commonly available antibioticsis exceedingly challenging when it is caused by biofilm-producing Streptococcus spp. and Staphylococcus aureus. Staphylococci thatproduce biofilm are important contributors to wound infection because they hinder wound healing, which increases the risk of chronicinfection and subsequent bacterial infection. Additionally, biofilm bacteria may act as zoonotic agents. Therefore, we should try withalternate management techniques to combat biofilm microorganisms. In this overview, emphasis has given on status of biofilm associateddiseases in animal, zoonotic importance, probable reason for antibiotic resistance and therapeutic approaches against biofilm infections

Metatranscriptomic Analysis Reveals Disordered Alterations in Oropharyngeal Microbiome during the Infection and Clearance Processes of SARS-CoV-2: A Warning for Secondary Infections

This study was conducted to investigate oropharyngeal microbiota alterations during the progression of coronavirus disease 2019 (COVID-19) by analyzing these alterations during the infection and clearance processes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diagnosis of COVID-19 was confirmed by using positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR). The alterations in abundance, diversity, and potential function of the oropharyngeal microbiome were identified using metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 47 patients with COVID-19 (within a week after diagnosis and within two months after recovery from COVID-19) and 40 healthy individuals. As a result, in the infection process of SARS-CoV-2, compared to the healthy individuals, the relative abundances of Prevotella, Aspergillus, and Epstein-Barr virus were elevated; the alpha diversity was decreased; the beta diversity was disordered; the relative abundance of Gram-negative bacteria was increased; and the relative abundance of Gram-positive bacteria was decreased. After the clearance of SARS-CoV-2, compared to the healthy individuals and patients with COVID-19, the above disordered alterations persisted in the patients who had recovered from COVID-19 and did not return to the normal level observed in the healthy individuals. Additionally, the expressions of several antibiotic resistance genes (especially multi-drug resistance, glycopeptide, and tetracycline) in the patients with COVID-19 were higher than those in the healthy individuals. After SARS-CoV-2 was cleared, the expressions of these genes in the patients who had recovered from COVID-19 were lower than those in the patients with COVID-19, and they were different from those in the healthy individuals. In conclusion, our findings provide evidence that potential secondary infections with oropharyngeal bacteria, fungi, and viruses in patients who have recovered from COVID-19 should not be ignored; this evidence also highlights the clinical significance of the oropharyngeal microbiome in the early prevention of potential secondary infections of COVID-19 and suggests that it is imperative to choose appropriate antibiotics for subsequent bacterial secondary infection in patients with COVID-19.

Pediatric Candida Bloodstream Infections Complicated with Mixed and Subsequent Bacteremia: The Clinical Characteristics and Impacts on Outcomes.

Background: Pediatricians face a therapeutic challenge when patients with Candida bloodstream infections (BSIs) simultaneously have positive bacterial culture. We aim to characterize the clinical characteristics of pediatric Candida BSIs complicated with mixed bacteremia and subsequent bacterial infections, risk factors and impacts on outcomes. Methods: All episodes of pediatric Candida BSIs between 2005 and 2020 from a medical center in Taiwan were reviewed. Mixed Candida/bacterial BSIs were defined as isolation of a bacterial pathogen from blood cultures obtained within 48 h before or after the onset of Candida BSI. The clinical features and impacts of mixed Candida/bacterial BSIs were investigated. Results: During the study period, 320 patients with a total of 365 episodes of Candida BSIs were identified and analyzed. Mixed Candida/bacterial BSIs were 35 episodes (9.6%). No significant difference was found between mixed Candida/bacterial BSIs and monomicrobial Candida BSIs in terms of patient demographics, Candida species distributions, most chronic comorbidities or risk factors. Patients with mixed Candida/bacterial BSIs were associated with a significantly higher risk of subsequent bacteremia (51.4% vs. 21.2%, p &lt; 0.001) and a relatively higher candidemia-attributable mortality rate (37.2% vs. 22.4%, p = 0.061) than those with monomicrobial Candida BSIs. Mixed Candida/bacterial BSIs were not an independent risk factor of treatment failure or final mortality according to multivariate logistic regression analyses. Conclusions: The clinical significance of mixed Candida/bacterial BSIs in children included a longer duration of septic symptoms, significantly higher likelihood to have subsequent bacteremia, and relatively higher risk of candidemia attributable mortality.

Empagliflozin restores neutropenia and neutrophil dysfunction in a young patient with severe congenital neutropenia type 4

Severe congenital neutropenia type 4 (SCN-4) is a rare primary immunodeficiency caused by loss-of-function mutations in the gene G6PC3, encoding the ubiquitously expressed glucose-6-phosphatase-β enzyme, which hydrolyses glucose-6-phosphate to glucose in the endoplasmic reticulum (ER).1 Although it is described as a multisystem autosomal-recessive disorder with a diverse spectrum of nonhematological manifestations, the main life-threatening complication is associated with persistent severe neutropenia, neutrophil dysfunction, and subsequent recurrent bacterial infections in almost all patients.

Exploring the Binding Interaction of Active Compound of Pineapple against Foodborne Bacteria and Novel Coronavirus (SARS-CoV-2) Based on Molecular Docking and Simulation Studies.

Natural resources, particularly plants and microbes, are an excellent source of bioactive molecules. Bromelain, a complex enzyme mixture found in pineapples, has numerous pharmacological applications. In a search for therapeutic molecules, we conducted an in silico study on natural phyto-constituent bromelain, targeting pathogenic bacteria and viral proteases. Docking studies revealed that bromelain strongly bound to food-borne bacterial pathogens and SARS-CoV-2 virus targets, with a high binding energy of −9.37 kcal/mol. The binding interaction was mediated by the involvement of hydrogen bonds, and some hydrophobic interactions stabilized the complex and molecular dynamics. Simulation studies also indicated the stable binding between bromelain and SARS-CoV-2 protease as well as with bacterial targets which are essential for DNA and protein synthesis and are required to maintain the integrity of membranous proteins. From this in silico study, it is also concluded that bromelain could be an effective molecule to control foodborne pathogen toxicity and COVID-19. So, eating pineapple during an infection could help to interfere with the pathogen attaching and help prevent the virus from getting into the host cell. Further, research on the bromelain molecule could be helpful for the management of COVID-19 disease as well as other bacterial-mediated diseases. Thus, the antibacterial and anti-SARS-CoV-2 virus inhibitory potentials of bromelain could be helpful in the management of viral infections and subsequent bacterial infections in COVID-19 patients.

Effect of Pyocyanin on gene expression of norA gene in Staphylococcus aureus and SMR gene in Serratia marcescense

Background: The antibiotics active against Multidrug resistant bacteria have several limitations for their use, which include less clinical experience, During the continuing COVID-19 epidemic, limiting use has been difficult because most hospitalized COVID-19 patients receive antibiotics as a defense against subsequent bacterial infection. , Efflux pumps remove drugs and are linked to biofilm formation, making infections more difficult to treat due to a lack of therapeutic choices and necessitating new antimicrobial tactics. Pyocyanin is a secondary blue redox-active metabolite and a large family member of phenazines, tricyclic compounds. Phenazine has been utilized as a biological pesticide against several harmful microorganisms because of its antibacterial properties. Methods: Total RNA from ( Staphylococcus aureus obtained from respiratory tract diagnosed as MDR and Serratia marcescens obtained from co-infection Covid 19 )were isolated . The gene expression of the norA gene efflux pump of S. aureus, which was normalized to the rpoB HKG, and the smr gene efflux pump of Serratia marcescens, which was normalized to the Adnalyate Kinaze enzyme, was studied using quantitative real-time RT PCR on the extracted RNA.

A case report on wegener’s granulomatosis

Wegener’s Granulomatosis, also known as granulomatosis with polyangiitis, is a rare multisystem autoimmune disease with an unknown etiology that can affect persons of all ages. In most cases, the condition affects the respiratory tract and the kidneys. The initial symptoms include a runny nose (rhinorrhea), nasal crusting, and nasal blockage or congestion. More significant symptoms include nose bleeds, ulcerations of the nasal mucous membranes with subsequent bacterial infection, sinus discomfort, sinus inflammation, and hoarseness. The patient was presented with symptoms like reddish staining of the eyes, hearing loss, and numerous joint discomfort and swelling of the lower limbs. The antineutrophil cytoplasmic antibody, cytoplasmic (C-ANCA), and human leukocyte antigen- B27 (HLA-B27) were both positive, and renal biopsy revealed necrotizing and crescentic glomerulonephritis. The treatment was initiated with corticosteroids and monoclonal antibodies. The patient responded positively to the therapy, and her health appears to be improving.