Multiple Bacterial Infections Research Articles

Bacteriophage-cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice.

Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed-healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed-healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage-cocktail) was encapsulated in a porous hydrogel dressing made with three-dimensional printing. The phage-cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full-thickness skin wound in diabetic mice. The phage-cocktail dressing released 1.7%-5.7% of the phages embedded in 24 h, and reduced between 37%-79% of the surface bacteria compared with the blank dressing (p <.05). The phage-cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full-thickness wound treated with a phage-cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage-cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage-cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re-epithelialization (p <.05). The slow-released phage has demonstrated positive effects in repairing diabetic skin wounds.

CNS Aspergillosis and Cryptococcosis with Cytomegalovirus Pneumonia in a Patient with Chronic Lymphocytic Leukemia Treated with Acalabrutinib.

Bruton's tyrosine kinase inhibitors (BTKis) are the preferred treatment for chronic lymphocytic leukemia (CLL). Despite their therapeutic benefits, these targeted agents have been associated with an increased risk of invasive infections. We describe a 68-year-old male who developed multiple bacterial, fungal and viral infections while on treatment with acalabrutinib. To our knowledge, this is the first reported case of concomitant CNS infections with Cryptococcus neoformans and Aspergillus fumigatus, along with cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) pneumonia while on acalabrutinib. This case adds to the scarce literature of fungal and bacterial infections associated with acalabrutinib, raising the suspicion that infection risk is a medication class effect for BTKis.

Detecting Multiple Mixed Bacteria Using Dual-Mode Hyperspectral Imaging and Deep Neural Networks

Identifying and analyzing mixed pathogenic bacteria is important for clinical diagnosis and antibiotic therapy of multiple bacterial infection. In this paper, a dual-mode hyperspectral microscopic detection technology with hybrid deep neural networks (DNNs) was proposed for simultaneous quantitative analysis of four kinds of pathogenic bacteria in mixed samples. To acquire both transmission and fluorescence spectra regarding the mixed pathogens, we developed a dual-mode hyperspectral detection system with fine spectral resolution and wide wavelength range, which can also generate spatial images that can be used to calculate the total amount of mixed bacteria. The dual-mode spectra were regarded as mixed proportion characteristics and the input of the neural network for predicting the proportion of each bacterium present in the mixture. To better analyze the dual-mode spectral data, we customized a mixed bacteria measurement network (MB-Net) with hybrid DNNs architectures based on spectral feature fusion. Using the fusion strategy, two DNNs frameworks applied for transmission/fluorescence spectral feature processing were stacked to form the MB-Net that processes these features simultaneously, and the achieved average coefficient of determination (R2) and RMSE of validation set are 0.96 and 0.03, respectively. To the best of our knowledge, it is the first time of simultaneously detecting four types of mixed pathogenic bacteria using spectral detection technology, showing excellent potential in clinical practice.

P25 Nowhere to hide: broad-spectrum antimicrobial guideline adherence in outpatients

Abstract Background The NHS Acute Trusts Standard1 contract requires a 10% reduction in broad-spectrum antibiotics by 10% by March 2024 from a 2017 baseline. Co-amoxiclav is a broad-spectrum antibacterial that comprises 30% of broad-spectrum consumption at University Hospitals Birmingham. It is widely used across all specialities and is a perfect candidate to review to influence downward trend in consumption. Outpatient prescriptions do not receive the same level of scrutiny from pharmacy or antimicrobial stewardship team as inpatient prescriptions. If deviations from guidelines are identified, then this could be a potential area to address to reduce consumption. Methods Sixty outpatient co-amoxiclav prescriptions were reviewed to assess appropriateness of prescribing during December 2022. Parameters assessed included the indication and duration of co-amoxiclav therapy and adherence to Trust antimicrobial guidelines. The speciality prescribing outpatient co-amoxiclav was also documented to identify whether prescribing trends could be identified. Results Of 60 reviewed outpatient prescriptions written in December 2022, 54 were issued by acute medicine with other specialities including cardiothoracic, renal medicine, elderly care, ENT, urology and cardiology. All prescriptions had a documented indication and duration, however only three were adherent to Trust antimicrobial guidelines. The graph below represents the different indications co-amoxiclav was prescribed for to outpatients across all three hospital sites. Co-amoxiclav was most frequently prescribed for respiratory tract infections, followed by skin and then urinary tract infections. Conclusions This audit has highlighted that outpatient co-amoxiclav is commonly prescribed inappropriately and does not comply with Trust antimicrobial guidelines. The speciality most frequently prescribing outpatient co-amoxiclav inappropriately was acute and emergency medicine. The lack of clarity regarding the infection indication is a potentially important factor in this setting, resulting in broad-spectrum antimicrobial use to cover multiple potential bacterial infections. A limitation of this audit is it was carried out over a short and busy winter period.

Low Mortality from COVID-19 Infection in Patients with B-Cell Lymphoma after Bispecific CD20xCD3 Therapy

Introduction: Patients with hematological malignancies are at an increased risk of morbidity and mortality after COVID-19 infection.Especially patients treated with chimeric antigen receptor T-cell (CAR-T) therapy for B-cell malignancies have shown poor outcomes after COVID-19, resulting in reported COVID-19 attributable mortality rates between 41%-50%.Outcomes after COVID-19 infection in patients treated with CD20xCD3 bispecific antibodies have not been reported. We investigated the impact and clinical course of COVID-19 in 130 Danish patients with B-NHL who have received bispecific antibodies. Methods: Using clinical data from electronic health charts, the national Danish database of microbiology (MiBA), and the national drug- and vaccination registry (SharedMedicineCard), we collected data on date of positive COVID-19 test, quantitative PCR-determined COVID-19 variant, symptoms, reactivations, resolution of disease (either clinical, confirmed by negative PCR test or death), vaccination status and treatment. Disease duration was defined as the time from diagnosis of COVID-19 to clinical resolution. Results: A total of 130 patients who received bispecific CD20xCD3 antibodies (glofitamab or epcoritamab) as part of clinical trials in Denmark were assessed. Of the 130 patients, 109 were alive after March 8, 2020. We identified 43 patients infected with COVID-19, 34 of whom were during CD20xCD3 specific treatment or after end-of-treatment (Table 1). A total of 26 patients (79%) were in complete remission at the time of COVID-19 diagnosis, 5 patients (15%) had progressive disease, 2 patients (6%) had stable disease and 1 patient had no data on lymphoma status at COVID-19 diagnosis. With regards to COVID-19 symptom burden, 4 patients (12%) were asymptomatic during infection. The most common symptoms included fever (n=15), cough (n=12), and dyspnea (n=6). There were 16 patients (48%) admitted to the hospital for the treatment of COVID-19. Of these, 2 patients required oxygen support. Twelve patients (35%) received no specific treatment for COVID-19, while the most commonly prescribed treatments were sotrovimab in 13 patients (42%) and remdesivir in 9 patients (29%). At six months after COVID-19 infection, 3 patients had died, two before recovering from COVID-19. The two cases, where COVID-19 presumably was a cause of death, had a combination of multiple bacterial infections and progression of malignant disease. The 6-month cumulative incidence of death related to COVID-19 was 6.4% (95% CI 0% to 14.9%, Figure 1), while the cumulative incidence of death overall was 9.6% (95%CI 0% to 19.9 %). Of the 25 patients who were alive and had data available at 6 months follow-up after COVID-19 infection, 20 were in complete remission, while the rest (n=5) had refractory/relapsed lymphoma. Of the patients with COVID-19 during CD20xCD3 specific treatment or after end-of-treatment, 13 out of 34 had at least one reactivation. The mean number of COVID-19 reactivations was 1.2 (95%CI 0.44 to 2.03), ranging from 0 up to 9. An additional patient had a reactivation 20 days after first infection and 4 days after first treatment with bispecific antibodies. Only 9% (1 out of 11) of the patients who tested positive for SARS-CoV-2 before bispecific antibody treatment had a reactivation compared to 38% of those testing positive after or during bispecific antibody treatment. In an adjusted multivariable regression for age and sex only hospitalization during the first COVID-19 infection was significantly associated to reactivations (OR: 18.9, 95%CI 2.84-238, p=0.007). Conclusions: To our knowledge, this study presents the first data on COVID-19 incidence and severity in patients with relapsed/refractory lymphoma who have received CD3xCD20 bispecific antibodies. The COVID-19 attributable mortality after bispecific CD20xCD3 antibody therapy, when compared to CAR-T cell therapy, was much lower and comparable to the mortality reported in other cohorts of less heavily treated hematological malignancies infected with omicron variants. However, these patients present with considerable number of COVID-19 reactivations. In conclusion, it seems relatively safe to prescribe bispecific CD20xCD3 antibodies for lymphoma for patients who have been vaccinated for COVID-19 with the currently circulating virus variants.

A Mendelian Randomization-Based Causal Investigation on Bacterial Infection-Related Genes and Neurodegenerative Diseases.

Neurodegenerative diseases remain the most prevalent and unsolved health problems in human society, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The pathogenesis, pathology, and potential clinical treatments of neurodegenerative diseases still require in-depth research. In the wake of the association between pandemics and a growing number of neurodegeneration patients, there has been growing speculation that infections are linked to AD and PD. The Aβ peptide is an important causal-related biomarker of AD and is reported to share structural and functional similarities with certain antimicrobial peptides, suggesting that it has a role in eliciting an immune response against microbes. But how neurodegeneration is related to bacterial chronic infection has not been thoroughly investigated. Using the data from genome-wide association studies (GWAS), we performed Mendelian Randomization (MR) and map 7 genes in multiple bacterial infection pathways as exposure, which show a significant association with the outcome of AD or PD. As co-verification, we perform Gene Set Enrichment Analysis (GSEA) on selected genetic variants incorporating their perturb-seq gene list (combining single-cell RNA-seq and CRISPR-based perturbations). We observed clustering of the differentially expressed genes (DEGs) in the upstream and downstream of AD and PD-related KEGG pathways, hence confirming their causal association with AD and PD and providing new perspectives on the true cause of neurodegeneration.

Inactivation of two oyster pathogens by photocatalysis and monitoring of changes in the microbiota of seawater: A case study on Ostreid herpes virus 1 μVar and Vibrio harveyi.

The pollution of seawater by both biotic (bacteria, viruses) and abiotic contaminants (biocides, pharmaceutical residues) frequently leads to economic losses in aquaculture activities mostly mortality events caused by microbial infection. Advanced Oxidation Processes (AOPs) such as heterogeneous photocatalysis allow the removal of all organic contaminants present in water and therefore could reduce production losses in land-based farms. Oysters in land-based farms such as hatcheries and nurseries suffer from a large number of mortality events, resulting in significant losses. If photocatalysis has been widely studied for the decontamination, its application for disinfection is still overlooked, especially on seawater for viruses. We therefore studied seawater disinfection using the photocatalysis (UV365/TiO2) method in the context of Pacific oyster mortality syndrome (POMS). POMS has been defined as a polymicrobial disease involving an initial viral infection with Ostreid Herpes Virus 1, accompanied by multiple bacterial infections. We investigated the impact of treatment on Vibrio harveyi, a unique opportunistic pathogenic bacterium, and on a complex microbial community reflecting a natural POMS event. Viral inactivation was monitored using experimental infections to determine whether viral particles were still infectious after. Changes in the total bacterial community in seawater were studied by comparing UV365/TiO2 treatment with UV365-irradiated seawater and untreated seawater. In the case of OsHV-1, a 2-h photocatalytic treatment prevents POMS disease and oyster mortality. The same treatment also inactivates 80% of viable Vibrio harveyi culture (c.a. 1.5 log). Since OsHV-1 and Vibrio harveyi are effectively inactivated without long-term destabilization of the total bacterial microbiota in the seawater, photocatalysis appears to be a relevant alternative for disinfecting seawater in land-based oyster beds.

Urchin-Shaped Au-Ag@Pt Sensor Integrated Lateral Flow Immunoassay for Multimodal Detection and Specific Discrimination of Clinical Multiple Bacterial Infections.

A new lateral flow immunoassay strip (LFIA) combining sensitive detection and identification of multiple bacteria remains a huge challenge. In this study, we first developed multifunctional urchin-shaped Au-Ag@Pt nanoparticles (UAA@P NPs) with a unique combination of colorimetric-SERS-photothermal-catalytic (CM/SERS/PT/CL) properties and integrated them with LFIA for multiplexed detection and specific discrimination of pathogenic bacteria in blood samples. Unlike the conventional LFIA that relied on antibody (Ab), this novel LFIA introduced 4-mercaptophenylboronic acid (4-MPBA) as an ideal Ab replacer that was functionalized on UAA@P NPs (UAA@P/M NPs) with outstanding binding and enrichment capacities toward bacteria. Taking Staphylococcus aureus (S. aureus) as model bacteria, the limit of detection (LOD) was 3 CFU/mL for SERS-LFIA, 27 CFU/mL for PT-LFIA, and 18 CFU/mL for CL-LFIA, three of which were over 330-fold, 37-fold, and 55-fold more sensitive than ordinary visual CM-LFIA, respectively. Besides, this SERS-LFIA is capable of identifying three types of bacterial spiked blood samples (E. coli, S. aureus, and P. aeruginosa) effectively according to specific bacterial Raman "fingerprints" by partial least-squares-discriminant analysis (PLS-DA). More importantly, this LFIA was successfully applied to blood samples with satisfactory recoveries from 90.3% to 108.8% and capable of identifying the infected patients (N = 4) from healthy subjects (N = 2) with great accuracy. Overall, the multimodal LFIA incorporates bacteria discrimination and quantitative detection, offering an avenue for early warning and diagnosis of bacterial infection.

Fabrication and Evaluation of Amoxicillin and Potassium Clavulanate Medicated Chocolate

The purpose of this investigation was to develop a formulation of amoxicillin and potassium clavulanate in chocolate form. Amoxicillin is an antibiotic belonging to the beta-lactam family. By binding to penicillin-binding proteins, beta-lactams stimulate autolytic enzymes in the bacterial cell wall, which in turn inhibits transpeptidation (the cross-linking stage in cell wall production). The streptomyces-derived, semi-synthetic beta-lactamase inhibitor potassium clavulanate. Multiple bacterial infections may be treated well with the antibiotic combination of amoxicillin and potassium clavulanate acid. It prevents germs from multiplying. Chocolate refers to a family of sweets made by combining cocoa (cacao), cocoa butter, and sugar in various proportions to form a solid. For improved patient compliance, the medicated chocolate formulation is often utilized for pediatric administration. The traditional chocolate formulation, which includes cocoa powder, moisture content, and blooming tests, is inferior to the one that incorporates carob powder, which lowers gastrointestinal troubles. The whole medication from the F4 formulation is released within 60 minutes, leading to a wide range of GIT disorders such heartburn and acid reflux. The formulation is stable throughout chocolate formulation manufacturing, with no drug excipient interactions and no drug degradation detected. The dimensions of the finished product are 28.5mm in length, 18mm in width, and 14mm in height. Batch F4 is the finest of all batches.

Biomimetic peptide dynamic hydrogel inspired by humanized defensin nanonets as the wound-healing gel coating

Clinical treatment of chronic wounds, particularly those prone to relapse, has been hampered by the regeneration, infection complications, and malignant transformation of disordered tissue adhesions. At the surface of intestinal endothelial, human defensins self-assemble into higher-order nanonets that defend host cells, fight inflammation and promote wound healing. Inspired by this antimicrobial nanostructured network, we herein attempted to construct an antimicrobial nanonet with hemostatic function integrated as wound dressing. Aiding by molecular docking and dynamics analysis, we designed a hemostatic nanogel called ACFP, which was constructed by spontaneously assembling two RADA16-based hydrogelators with one θ-defensin-derived peptide motif. As expected, ACFP possesses antimicrobial properties derived from the nanonet structure of defensin, as well as the ability to prevent bleeding and effectively promote wound healing. As an injectable biocompatible hydrogel, ACFP successfully treated chronic epidermal wounds associated with multiple bacterial infections, and promoted healing of a complicated intraperitoneal wound involving the cecum and adjacent abdominal walls while preventing tissue adhesion. In addition to providing a comprehensive therapeutic approach with tremendous clinical potential for chronic wound therapy, ACFP may encourage the development of biomimetic peptide hydrogels with multiple functions against a wide range of human diseases.

Formulation development and characterization of dual drug loaded hot-melt extruded inserts for better ocular therapeutic outcomes: Sulfacetamide/prednisolone

The present investigation was intended to formulate and evaluate a hot-melt extruded (HME) bioadhesive ophthalmic inserts containing a fixed-dose combination of Prednisolone Sodium Phosphate (PSP) and Sulfacetamide Sodium (SA) to improve the treatment outcomes of multiple ocular bacterial infections. The inserts were prepared using FDA-authorised biocompatible polymers, including Polyox WSR N10 LEO NF (polyethylene oxide; PEO), Klucel™ HF (hydroxypropyl cellulose; HPC-HF), and Ethocel™ (Ethylcellulose; EC). The inserts were then assessed for physicochemical characteristics, weight variation, surface pH, uniformity of thickness, drug content, swelling index, thermal analysis, drug–excipient compatibility, moisture uptake and loss, surface morphology, mucoadhesive strength, in vitro release, ex-vivo transcorneal permeation and deposition, and stability. The HPC-HF and EC-containing inserts extended the release of both drugs compared to PEO-N10-based inserts that showed the release of the loaded amount of both drugs immediately (<1 h). All fabricated inserts were stable over 90-day storage at room temperature (25 °C) and accelerated conditions (40 °C) for drug content and thermal behavior. The developed PSP-SA inserts exhibited optimum bioadhesive strength and smooth surface favorable for topical ocular application. Ex vivo transcorneal permeation studies using freshly isolated rabbit corneas demonstrated that the extended-release inserts slowed down the transcorneal flux of the drug in comparison to the immediate-release inserts and the commercial solution eyedrops. Overall, the inserts were fabricated using a solvent-free, scalable, and continuous manufacturing process and could reduce the frequency of administration to once-daily application, affording a new topical delivery vehicle with prolonged antibacterial and anti-inflammatory activity during ocular bacterial infections treatment.

Bacteria-targeted combined with photothermal/NO nanoparticles for the treatment and diagnosis of MRSA infection in vivo.

Currently, undeveloped diagnosis and delayed treatment of bacteria-infected sites in vivo not only expand the risk of tissue infection but are also a major clinical cause of multiple drug-resistant bacterial infections. Here, we present an efficient nanoplatform for NIR-light-controlled and bacteria-targeted delivery of nitric oxide (NO) combined with photothermal therapy (PTT). Using maltotriose-decorated mesoporous polydopamine (MPDA-Mal) and BNN6, a smart antibacterial nanoplatform (B@MPDA-Mal NPs) is developed to combine bacterial targeting, gas-controlled release, and photothermal therapy. Utilizing bacteria's unique maltodextrin transport system, the prepared B@MPDA-Mal NPs can accurately distinguish bacterial infection from sterile inflammation and target the bacteria-infected sites for efficient drug enrichment. Moreover, NIR-light causes MPDA to generate heat, which not only effectively induces BNN6 to produce NO, but also raises the temperature to harm the bacteria further. NO/photothermal combination therapy effectively eliminates biofilm and drug-resistant bacteria. The myositis model of MRSA infection is established and indicated that B@MPDA-Mal NPs can successfully eradicate inflammation and abscesses in mice. Meanwhile, MRI imaging technology is used to monitor the treatment procedure and healing outcomes. Given the aforementioned advantages, the smart antibacterial nanoplatform B@MPDA-Mal NPs can be used as a potential therapeutic tool in the biomedical field against drug-resistant bacterial infections in vivo. This article is protected by copyright. All rights reserved.

Thermosensitive PNIPAM-Based Hydrogel Crosslinked by Composite Nanoparticles as Rapid Wound-Healing Dressings.

Chronic wounds are prone to produce excessive reactive oxygen species (ROS), which are the main reason for multiple bacterial infections and ulcers at the wound. Therefore, regulating ROS is the key in the process of wound healing. Herein, a new type of thermosensitive hydrogels is developed to improve the scavenging efficiency of ROS and accelerate wound repair. Nano-CeO2 was uniformly dispersed on the surface of mesoporous silica (MSN). The nanocomposite particles were physically crosslinked with poly(N-isopropylacrylamide) (PNIPAM) to form a MSN-CeO2@PNIPAM thermoresponsive hydrogel (PMCTH). The stability, temperature sensitivity, rheological properties, biocompatibility, and wound healing ability of the PMCTH were evaluated in detail. The results showed that the hydrogel could not only maintain the stability of the system for a long time with low biological toxicity but also have a phase transition temperature close to the human body temperature. In addition, the PMCTH was directly applied onto the skin surface. The MSN-CeO2 nanoparticles would be dispersed in the hydrogel to restrict ROS exacerbation effects and promoted the formation of blood vessels as well as surrounding tissues, accelerating the wound healing. More importantly, animal experiments showed that when the mass ratio of CeO2 to MSN was 40%, the wound healing rate reached up to 78% on the 10th day, which was far higher than that of other experimental groups. This study provides a new strategy and experimental basis for the applications of functional hydrogels in wound repair.

Rapid Identification and Monitoring of Multiple Bacterial Infections Using Printed Nanoarrays.

Fast and accurate detection of microbial cells in clinical samples is highly valuable but remains a challenge. Here, a simple, culture-free diagnostic system is developed for direct detection of pathogenic bacteria in water, urine, and serum samples using an optical colorimetric biosensor. It consists of printed nanoarrays chemically conjugated with specific antibodies that exhibits distinct color changes after capturing target pathogens. By utilizing the internal capillarity inside an evaporating droplet, target preconcentration is achieved within a few minutes to enable rapid identification and more efficient detection of bacterial pathogens. More importantly, the scattering signals of bacteria are significantly amplified by the nanoarrays due to strong near-field localization, which supports a visualizable analysis of the growth, reproduction, and cell activity of bacteria at the single-cell level. Finally, in addition to high selectivity, this nanoarray-based biosensor is also capable of accurate quantification and continuous monitoring of bacterial load on food over a broad linear range, with a detection limit of 10 CFU mL-1 . This work provides an accessible and user-friendly tool for point-of-care testing of pathogens in many clinical and environmental applications, and possibly enables a breakthrough in early prevention and treatment.

Physiological analysis of severe chlamydia psittaci pneumonia and clinical diagnosis after doxycycline-based treatment.

Objective: To describe the clinical spectrum of severe Chlamydia psittaci pneumonia in order to understand the disease better. Methods: Retrospective analysis was made on 31 patients with severe Chlamydia psittaci pneumonia diagnosed in ICU by next-generation sequencing of metagenome Metagenomic next-generation sequencing(mNGS) from January 2019-November 2022, including clinical characteristics, laboratory examination results, imaging characteristics, treatment, and prognosis. Results: We included 31 patients with severe Chlamydia psittaci pneumonia, 15 of whom had a history of virus exposure. There were 12 cases with multiple bacterial infections, and the common symptoms included fever (31/31,100%), dyspnea (31/31, 100%), cough (22/31, 71.0%), and myalgia (20/31, 64.5%). Laboratory data showed that white blood cells were average or slightly increased, but the levels of C-reactive protein and neutrophils were high. CT findings of the lung were consolidation (19/31, 61.3%) and pleural effusion (11/31, 35.5%). Only one lobe was involved in 11 patients (35.5%). Before diagnosis, 22 patients (71.0%) did not have atypical pathogens in their antimicrobial regimen. After diagnosis, 19 patients (61.3%) received single drug treatment, of which doxycycline or moxifloxacin were the most commonly used drugs. Among 31 patients, three died, nine improved, and nineteen were cured. Conclusion: The clinical manifestations of severe Chlamydia psittaci pneumonia are non-specific. The application of mNGS can improve the diagnostic accuracy of Chlamydia psittaci pneumonia, reduce the unnecessary use of antibiotics, and shorten the course of the disease. Doxycycline-based treatment is effective for severe chlamydia psittaci pneumonia, but it is necessary to understand the secondary bacterial infection and other complications in the course of the disease.

Study of the molecular characteristics and homology of carbapenem-resistant Proteus mirabilis by whole genome sequencing.

Introduction. Proteus mirabilis is part of the family Enterobacteriaceae, and is naturally resistant to various antimicrobial drugs. In recent years, outbreaks of severe nosocomial infections caused by carbapenem-resistant P. mirabilis (CR-PMI) have been frequently reported. Few studies exist on the whole-genome molecular characteristics of this bacterium in China and elsewhere, which stimulated the implementation of this study.Hypothesis. CR-PMI strains contained the multiple drug resistance genes and exhibited a high resistance rate to commonly used antimicrobial drugs.Aim. Our goals here were to identify resistance mechanisms and homology of CR-PMI strains and provide a theoretical basis for clinical treatment and controlling nosocomial infections.Methodology. Bacterial species identification was carried out using matrix-assisted laser desorption/ionization time of flight MS (MALDI-TOF-MS). Antimicrobial susceptibility was determined using the VITEK 2 system and Kirby-Bauer (K-B) disc-diffusion method. Whole-genome sequencing (WGS) was conducted by the Illumina platform NovaSeq sequencer. Antibiotic resistance genes (ARGs) were identified using the NCBI database with Abricate. Plasmid replicon types were identified using PlasmidFinder, available at the Center for Genomic Epidemiology.Results. Five CR-PMI strains collected in our hospital from July 2019 to September 2021 were resistant to almost all antimicrobial agents except aztreonam (ATM), amikacin (AMK) and cefotetan (CTT). All CR-PMI strains contained the carbapenem resistance gene New Delhi metallo-β-lactamase 1 (bla NDM-1), and two strains harboured extended-spectrum β-lactamase (ESBL) genes bla PER-4 and bla CTX-M-65. The five CR-PMI strains contained 27, 18, 30, 25 and 24 drug-resistance genes, respectively. Most antimicrobial resistance genes were detected for aminoglycosides (n=14), followed by cephalosporins (n=7). The phylogenetic tree was divided into five evolutionary groups, and the five CR-PMI strains were in the four evolutionary groups B-E.Conclusion Overall, CR-PMI strains exhibited a high resistance rate to commonly used antimicrobial drugs, and contained the carbapenem resistance gene bla NDM-1. The CR-PMI strains showed a polyclonal trend in different wards at different times. Most importantly, all strains identified contained important antimicrobial resistance genes, which may lead to severe drug resistance transmission and fatal multiple resistant bacterial infections.

A Case Report on a Chemotherapy Treatment to a SARSCOV2 PCR Positive, Non-Hodgkins Lymphoma Filipino Patient

SARSCOV2 causing the COVID-19 infection has spread to a pandemic scale and putting the vulnerable population at risk of infection such as those with malignancies. Cancer treatment remains to be controversial in this time of pandemic such that recommendations were either delay treatment, reduce hospital exposure, or to balance the risk of disease progression(e.g. malignancy) and acquiring the disease (COVID-19). Information on COVID-19 positive cancer patients receiving chemotherapy remains to be limited. Thus, this case is reported. The case is a 64 year old male, newly diagnosed, Non-Hodgkins lymphoma who presented with severe anemia and weight loss. He was diagnosed through the bone marrow findings of CD20, Ki67, BCL2 positive B cell Non-Hodgkins lymphoma, NOS. He underwent induction chemotherapy with Prednisone, Cyclophosphamide and Vincristine. Thereafter he diagnosed to have COVID-19 infection, moderate. He remained to be PCR positive but with noted negative IgM Antibody. He showed signs of worsening anemia thus was given succeeding chemotherapy while admitted in the COVID unit of the hospital. Malignancy in general poses greater risk of severe infection with COVID-19 and possibly a worse outcome.8 The decision to proceed with chemotherapy treatment at the time when cases in the Philippines were not clear due to few testing capacity in the different institutions was based on the symptomatic persistence of severe anemia and weight loss as well as reduction in the functional capacity of the patient. The focus of efforts of oncologists and hematologists as recommended by their respective societies was on the reduction of the possibility of acquiring COVID-19 infection. There is paucity of data among those patients who have been diagnosed with COVID-19 and was given chemotherapy. Although, several studies have shown that among patients with COVID-19 and cancer as co-morbidity, the mortality can reach as high as 21% to 33% or can present with severe type of infection. Recommendations given by National Cancer Center Network(NCCN), American Society of Clinical Oncology(ASCO), European Society for Medical Oncology(ESMO, National Institute for Health and Care Excellence(NICE), World Health Organization(WHO), and Center for Disease Control(CDC) consistently revolve around the shifting of follow-up consults via teleconsultation to reduce travel to the hospital, delay or reduction of immunosuppressive treatments if possible, careful and holistic, multidisciplinary individualized approach in chemotherapeutic treatment, and withholding chemotherapy once positive with SARSCOV2 PCR positive test. In this case, the patient remained to be asymptomatic, non-oxygen requiring but remained to be positive on his 3rd PCR test done (20 days from initial positive test). The infectious disease service considered this as a false positive test and only a reflection of SARSCOV2 RNA remnants in the patient's upper airway. The clinical presentation of this cancer patient to the COVID infection is contradictory to those seen in most studies reviewed. Based on the limited knowledge on the pathophysiology of COVID-19, hyperinflammatory response occur in a robust immune system that causes Systemic inflammatory response syndrome(SIRS) and cytokine storm or hypoinflammatory response leading to multiple secondary bacterial infection.10 But neither was seen in this case. It is therefore possible that details of the mechanism of COVID-19 infection and its association with co-morbidities (malignancy) to severity are yet to be elucidated. All of the knowledge that is learned in this time of pandemic stems from a continuous trial and error efforts of clinicians who, through a sound theoretical foundation, first hand clinical experience and outcome endlessly refine approaches to produce the best outcome for those who are infected with the virus, most importantly, to the vulnerable population, such as those who is burdened by malignancies and COVID-19 infection. The treatment of COVID-19 positive patients with hematologic malignancy should be individualized and should focus on the balance between disease severity and risk of worsening COVID-19 infection.

Immune Activated Cellular Therapy for Drug Resistant Infections: Rationale, Mechanisms, and Implications for Veterinary Medicine.

Antimicrobial resistance and biofilm formation both present challenges to treatment of bacterial infections with conventional antibiotic therapy and serve as the impetus for development of improved therapeutic approaches. Mesenchymal stromal cell (MSC) therapy exerts an antimicrobial effect as demonstrated in multiple acute bacterial infection models. This effect can be enhanced by pre-conditioning the MSC with Toll or Nod-like receptor stimulation, termed activated cellular therapy (ACT). The purpose of this review is to summarize the current literature on mechanisms of antimicrobial activity of MSC with emphasis on enhanced effects through receptor agonism, and data supporting use of ACT in treatment of bacterial infections in veterinary species including dogs, cats, and horses with implications for further treatment applications. This review will advance the field's understanding of the use of activated antimicrobial cellular therapy to treat infection, including mechanisms of action and potential therapeutic applications.

The potential roles of interleukin-25 in infectious diseases.

Interleukin-25 (IL-25), also known as IL-17E, is a recently identified cytokine of the IL-17 family. Numerous studies illustrated that the expression of IL-25 is regulated by multiple pathogens, including parasitic, viral, and bacterial infections. IL-25 has a dual function in infectious diseases. On the one hand, IL-25 activates type 2 immunity via the relevant cytokines, including IL-4, IL-5, and IL-13, which are associated with the development of pathogenic infection-related allergic diseases. On the other hand, IL-25 involves in the recruitment of group 2 innate lymphoid cells (ILC2) to enhanced T helper 2 (Th2) cell differentiation, which are important to the clearance of pathogens. However, the precise roles of IL-25 in infectious diseases remain largely unknown. Thus, the current review will shed light on the pivotal roles of IL-25 in infectious diseases.

Antibiotics targeting bacterial protein synthesis reduce the lytic activity of bacteriophages

Combination therapy of bacteriophages and antibiotics requires careful selection of specific antibiotics as it is crucial towards determining the success of phage therapy to treat multiple drug-resistant bacterial infections. So, we examined how different antibiotics can affect phage lytic activity when used in combination against targeted bacteria. Various antibiotics targeting bacterial protein synthesis pathways were tested for their bactericidal action in combination with bacteriophages of Acinetobacter baumannii (φAB145, φAB182), Staphylococcus aureus (φSA115, φSA116) and Salmonella Typhimurium (φST143, φST188). The phages displayed highly significant antagonism with most of the protein/ribosomal machinery targeting antibiotics: φSA115 (13/13); φSA116 (13/13); φST143 (11/13); φAB145 (11/13); φST188 (9/13); φAB182 (7/13). To validate this antagonistic effect, synergy assessment of these phages with gentamicin (GEN) and tetracycline (TE) was performed using time kill curve assays and counting the remaining viable bacterial cells at the end of the experiment. An increase in bacterial turbidity in phage-antibiotic combination groups was observed as compared to the treatment with phages individually. Also, GEN exhibited 4.22, 5.90, 2.02, 3.15, 2.68, and 2.60 log proliferation in viable cell count, respectively, for φSA115, φSA116, φST145, φAB182, φST143 and φAB188 in combination group in comparison to their individual actions. TE supplementation also led to 2.40, 4.90, 1.61, 2.73, 3.93, and 1.81 log increments in viable bacterial count when combined with φSA115, φSA116, φST145, φAB182, φST143 and φAB188, respectively. This study concludes that antibiotics targeting the bacterial protein biosynthetic machinery may lead to a reduction in the lytic activity of bacteriophages, thus lowering their therapeutic potential. Hence, such compounds must be carefully screened before their employment in combination treatment regimens.