Association of genetic polymorphisms in glucocorticoid pathway with dexamethasone treatment in COVID-19 patients

Background/Objectives: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19 caused by SARS-CoV- 2 as they attenuate the immune response with their antiinflammatory properties. Genetic polymorphisms of glucocorticoid receptor, metabolizing enzymes or transporters may affect treatment response to dexamethasone. The aim of this study was to evaluate the association of polymorphisms in glucocorticoid pathway with disease severity and duration of dexamethasone treatment in COVID-19 patients. Method(s): Our study included 107 hospitalized COVID-19 patients treated with dexamethasone. We isolated DNA from peripheral blood and genotyped all samples for polymorphisms in NR3C1 (rs6198, rs33388), CYP3A4 (rs35599367), CYP3A5 (rs776746), GSTP1 (rs1695, rs1138272), GSTM1/GSTT1 deletions and ABCB1 (1045642, rs1128503, rs2032582 Fisher's and Mann- Whitney tests were used in statistical analysis. Result(s): The median (min-max) age of the included patients was 62 (26-85) years, 69.2 % were male and 30.8 % female and they had moderate (1.9 %), severe (83 %) or critical (15.1 %) disease. NR3C1 rs6198 polymorphism was associated with more severe disease in additive genetic model (P = 0.022). NR3C1 rs6198, ABCB1 rs1045642 and ABCB1 rs1128503 polymorphisms were associated with a shorter duration of dexamethasone treatment in additive (P = 0.048, P = 0.047 and P = 0.024, respectively) and dominant genetic models (P = 0.015, P = 0.048 and P = 0.020, respectively), while carriers of the polymorphic CYP3A4 rs35599367 allele required longer treatment with dexamethasone (P = 0.033). Other polymorphisms were not associated with disease severity or dexamethasone treatment duration. Conclusion(s): Genetic variability of glucocorticoid pathway genes was associated with the duration of dexamethasone treatment of COVID-19 patients.

Efflux-Related Carbapenem Resistance in Acinetobacter baumannii Is Associated with Two-Component Regulatory Efflux Systems' Alteration and Insertion of ΔAbaR25-Type Island Fragment.

The efflux pumps, beside the class D carbapenem-hydrolysing enzymes (CHLDs), are being increasingly investigated as a mechanism of carbapenem resistance in Acinetobacter baumannii. This study investigates the contribution of efflux mechanism to carbapenem resistance in 61 acquired blaCHDL-genes-carrying A. baumannii clinical strains isolated in Warsaw, Poland. Studies were conducted using phenotypic (susceptibility testing to carbapenems ± efflux pump inhibitors (EPIs)) and molecular (determining expression levels of efflux operon with regulatory-gene and whole genome sequencing (WGS)) methods. EPIs reduced carbapenem resistance of 14/61 isolates. Upregulation (5-67-fold) of adeB was observed together with mutations in the sequences of AdeRS local and of BaeS global regulators in all 15 selected isolates. Long-read WGS of isolate no. AB96 revealed the presence of AbaR25 resistance island and its two disrupted elements: the first contained a duplicate ISAba1-blaOXA-23, and the second was located between adeR and adeA in the efflux operon. This insert was flanked by two copies of ISAba1, and one of them provides a strong promoter for adeABC, elevating the adeB expression levels. Our study for the first time reports the involvement of the insertion of the ΔAbaR25-type resistance island fragment with ISAba1 element upstream the efflux operon in the carbapenem resistance of A. baumannii.

Impact of COVID-19 on healthcare-associated infections: Antimicrobial consumption does not follow antimicrobial resistance.

BACKGROUND: This study aimed to analyze the Healthcare-Associated Infections (HAI) rates and antimicrobial consumption in Intensive Care Units (ICU) in São Paulo city during the COVID-19 pandemic and compare them with the pre-pandemic period. METHODS: This cohort included all hospitals that reported HAI rates (Central-Line-Associated Bloodstream Infection ‒ CLABSI and Ventilator-Associated Pneumonia ‒ VAP), the proportion of microorganisms that caused CLABSI, the proportion of resistant microorganisms, and antimicrobial consumption from January 2017 ‒ December 2020. Hospitals were stratified by the number of beds, Central Venous Catheter (CVC) utilization rate, Mechanical-Ventilation (MV) utilization rate, and type of funding. Statistical analyses were based on time-series plots and regression models. RESULTS: 220 ICUs were included. The authors observed an abrupt increase in CLABSI rates after the pandemic onset. High CLABSI rates during the pandemic were associated with hospital size, funding (public and non-profit private), and low CVC use (≤ 50%). An increase in VAP rates was associated with public hospitals, and high MV use (> 35%). The susceptibility profile of microorganisms did not differ from that of the pre-pandemic period. polymyxin, glycopeptides, and antifungal use increased, especially in COVID-19 ICUs. CONCLUSIONS: HAI increased during COVID-19. The microorganisms' susceptibility profile did not change with the pandemic, but the authors observed a disproportionate increase in large-spectrum antimicrobial drug use.

Biapenem, a Carbapenem Antibiotic, Elicits Mycobacteria Specific Immune Responses and Reduces the Recurrence of Tuberculosis.

Tuberculosis (TB) still tops the list of global health burdens even after COVID-19. However, it will sooner transcend the current pandemic due to the prevailing risk of reactivation of latent TB in immunocompromised individuals. The indiscriminate misuse and overuse of antibiotics have resulted in the emergence of deadly drug-resistant variants of Mycobacterium tuberculosis (M.tb). This study aims to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM) in generating long-lasting immunity against TB. BPM treatment significantly boosted the activation status of the innate immune arm-macrophages by augmenting p38 signaling. Macrophages further primed and activated the adaptive immune cells CD4+ and CD8+ T-cells in the lung and spleen of the infected mice model. Furthermore, BPM treatment significantly amplified the polarization of T lymphocytes toward inflammatory subsets, such as Th1 and Th17. The treatment also helped generate a long-lived central memory T-cell subset. The generation of central memory T lymphocyte subset upon BPM treatment in the murine model led to a significant curtailing in the recurrence of TB due to reactivation and reinfection. These results suggest the potentiality of BPM as a potent adjunct immunomodulator to improve host defense against M.tb by enriching long-term protective memory cells. IMPORTANCE Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) tops the list of infectious killers around the globe. The emergence of drug-resistant variants of M.tb has been a major hindrance toward realizing the "END TB" goal. Drug resistance has amplified the global burden toward the quest for novel drug molecules targeting M.tb. Host-directed therapy (HDT) offers a lucrative alternative to tackle emerging drug resistance and disease relapse by strengthening the host's immunity. Through our present study, we have tried to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM). BPM treatment significantly augmented long-lasting immunity against TB by boosting the innate and adaptive immune arms. The generation of long-lived central memory T lymphocyte subset significantly improved the disease outcome and provided sterilizing immunity in the murine model of TB. The present investigation's encouraging results have helped us depict BPM as a potent adjunct immunomodulator for treating TB.

Patient-Centered Surveillance of Drug-Resistant Infections

Drug resistance or multidrug resistance is multidimensional and complex. Over the past decade and especially during the covid-19 pandemic, the incidence of drug resistant infections increased despite the implementation of infection control precautions. This was most commonly seen in low- and middle-income countries, due to the higher burden of infectious diseases, lack of proper infrastructure, unregulated antimicrobial prescriptions over the counter, limited surveillance of antimicrobial use and resistance patterns. This was further compounded by the dearth of healthcare personnel trained in appropriate infectious disease management. Strategies in high income countries to prevent and manage drug resistant infections are unfortunately, not implementable in LMICs due to differences in antimicrobial resistance (AMR) burden, access to newer antibiotics, limited infrastructure and human resources with requisite expertise with lack of economic investment by regulatory authorities to tackle AMR. During the covid-19 pandemic, the lack of therapeutic options and the similar clinical picture initially led to rampant antimicrobial use which in turn contributed to rise in multi-drug resistant infections (MDR). Along with inappropriate antimicrobial use, redistribution of staff assigned to enforce infection control practices, shortage of personnel protective equipment, overcrowded healthcare settings, use of prolonged broad-spectrum antimicrobials in patients requiring during intensive care and mechanical ventilation contributed to the rise in hospital transmission of multidrug resistant infections during the pandemic. To mitigate the effects of drug resistance, healthcare systems must ensure effective implementation of surveillance of antimicrobials, AMR patterns especially in MDR HAIs and antimicrobial stewardship interventions to promote optimal antimicrobial use. National level investment to improve diagnostics must be given priority as it can limit drug resistance and promote the role of biomarkers in streamlining antimicrobial use. These need to be planned to facilitate future integration with any future pandemic surveillance.Copyright © 2023

BEMNIFOSBUVIR HAS LOW POTENTIAL TO INHIBIT P-gp, BCRP, AND OATP1B1 MEDIATED TRANSPORT

Background: Bemnifosbuvir (BEM, AT-527) is a guanosine nucleotide prodrug candidate for the treatment of COVID-19 and chronic HCV. BEM was identified in vitro as an inhibitor of drug transporters P-glycoprotein, breast cancer resistant protein (BCRP) and organic anion transporting polypeptide 1B1 (OATP1B1). Ph 1 studies in healthy participants were conducted to assess the clinical implications of these results using digoxin (DIG) and rosuvastatin (ROSU) as P-gp and BCRP/ OATP1B1 index drugs, respectively. Method(s): Both studies employed a similar design with 2 groups of 14 healthy participants: Day 1/period 1, all participants received a single dose of DIG 0.25mg or ROSU 10mg alone. In period 2, participants received DIG 0.25mg or ROSU 10mg with BEM 1100mg, simultaneously (n=14) or staggered by 2h (n=14). Serial plasma samples were collected and quantitated for DIG or ROSU concentrations. Result(s): A single dose of BEM 1100mg simultaneously administered slightly increased the Cmax of DIG (78%), yet had no effect on its AUC, consistent with the transient nature of BEM plasma PK. When dosed staggered, BEM did not affect the PK of DIG. A single dose (simultaneous or staggered) of BEM 1100mg slightly increased the plasma exposure of ROSU (20%-40%). There was no effect on vital signs, ECG, and no SAEs or drug discontinuations. Conclusion(s): A single high dose of BEM 1100mg only slightly increased the plasma exposure of the P-gp and BCRP/OATP1B1 index drugs DIG and ROSU. BEM has low potential to exhibit clinical meaningful inhibition of these transporters. No dose adjustment will be needed for drugs that are sensitive substrates of P-gp or BCRP/OAT1B1 when co-administered with BEM, staggered dosing may lessen any DDI risk.

Bacterial resistance, a current crisis

Bacterial resistance is a constant battle representing a Public Health trouble. So much, that the World Health Organization consi-derate Public Health as a priority in health, due to the impact that generates as much as in health (giving that recent projections indicate that by 2050 it???ll be produced more deaths because of this than the ones occasioned because of cancer) as its economic impact (which, according to a recent study in the United Kingdom(1), it???ll cost the world???s economy an estimated of 100 trillion dollars). The quick appearance of multidrug-resistant and pandrug-resistant bacteria is a world nature phenomenon, questioning the antibiotics efficiency. Implement protocols and recommendations is essential, just as essential and necessary as give aware-ness to health personnel, taking as base the knowledge of resistance generation and its impact through the years, empowered by the actual pandemic of COVID 19.

A Retrospective Assessment of Sputum Samples and Antimicrobial Resistance in COVID-19 Patients.

Data on bacterial or fungal pathogens and their impact on the mortality rates of Western Romanian COVID-19 patients are scarce. As a result, the purpose of this research was to determine the prevalence of bacterial and fungal co- and superinfections in Western Romanian adults with COVID-19, hospitalized in in-ward settings during the second half of the pandemic, and its distribution according to sociodemographic and clinical conditions. The unicentric retrospective observational study was conducted on 407 eligible patients. Expectorate sputum was selected as the sampling technique followed by routine microbiological investigations. A total of 31.5% of samples tested positive for Pseudomonas aeruginosa, followed by 26.2% having co-infections with Klebsiella pneumoniae among patients admitted with COVID-19. The third most common Pathogenic bacteria identified in the sputum samples was Escherichia coli, followed by Acinetobacter baumannii in 9.3% of samples. Commensal human pathogens caused respiratory infections in 67 patients, the most prevalent being Streptococcus penumoniae, followed by methicillin-sensitive and methicillin-resistant Staphylococcus aureus. A total of 53.4% of sputum samples tested positive for Candida spp., followed by 41.1% of samples with Aspergillus spp. growth. The three groups with positive microbial growth on sputum cultures had an equally proportional distribution of patients admitted to the ICU, with an average of 30%, compared with only 17.3% among hospitalized COVID-19 patients with negative sputum cultures (p = 0.003). More than 80% of all positive samples showed multidrug resistance. The high prevalence of bacterial and fungal co-infections and superinfections in COVID-19 patients mandates for strict and effective antimicrobial stewardship and infection control policies.

New Aspect of Candida spp. Infections

Candidiasis is an opportunistic fungal infection resulting from an imbalance between the host immune system and crucial virulence factors of Candida species. The Candida spp., are one of the major constituents of the human mycobiome as well as the main cause of invasive fungal infections, particularly in immunocompromised patients. They affect the cases who consume a wide-spectrum antibiotic/steroid and those who have prolonged ICU stays and central venous catheters, transplant patients, chemotherapy/ radiotherapy, patients under invasive or noninvasive ventilation, and diabetic individuals with high-rate mortality. In recent decades, Candida species are considered the fourth cause of bloodstream infections;however, the epidemiology of candidemia has been linked to different geographical areas. On the other hand, the emergence of multidrug-resistant Candida spp. named Candia auris, as a global challenge in different countries over recent years in the world, leads to lethal as well as invasive infections with a high rate of spread among patients. At the beginning of the novel coronavirus disease 2019 (COVID-19) pandemic with causative agent of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), invasive yeast infections (IYFs), especially Candidiasis, are dramatically increasing in those individuals as the major groups under immunosuppressed condition. Although echinocandins and azoles are the most common antifungals used for the treatment of IYFs, the increased therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata, calling for the discovery of novel antifungal agents with therapeutic approaches seems necessary. Here, we attempt to focus on the acquisition of knowledge associated with pathogenicity of Candida spp., particularly the indispensable role of virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production), genes that contribute to drug resistance and the related mechanisms, new therapeutic strategies for the treatment of Candidiasis includes combination therapies, application of biomaterials for drug delivery, antibodies, and vaccination, photodynamic therapy, probiotics, and new antifungal products to overcome Candida infections. © 2023 Nova Science Publishers, Inc.

Ayurvedic Herbs Advised for COVID-19 Management: Therapeutic Potential and Clinical Relevance

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. There is no effective medication for COVID-19 as of now, so it would be good to take preventive measures that not only boost our immunity but also fight against infections. The use of traditional Chinese medicine in China to treat COVID-19 patients sets the prototype demonstrating that traditional medicines can contribute to prevention and treatment successfully. In India, the Ministry of AYUSH (Ayurveda, Yoga, Unani, Siddha, Homeop-athy) released a self-care advisory during the COVID-19 crisis as a preventive aspect. This review article discusses the therapeutic potential and clinical relevance of some herbs [(Tulsi (Ocimum sanctum), Haridra (Curcuma longa), Tvaka (Cinnamon), Maricha (Piper longum), Shunthi (Zingi-ber officinale), Munakka (Dried grapes), Lavang (Syzigiumaromaticum), Pudina (Mentha arvensis), and Ajwain (Trachyspermum ammi)] advised by AUYSH to take during COVID-19 infection. They are effective in COVID-19 management, therefore, authors have discussed their detailed traditional uses as therapeutics and spotted scientific insight and clinical significance of the herbs mentioned above along with their mechanistic viewpoint, adequately, on a single platform. Provided information could be a treasure to open up a new research arena on natural products to manage human health crises effectively, caused not only by COVID-19 but also by other infectious diseases.Copyright © 2023 Bentham Science Publishers.

Using Real World Evidence (Rwe) to Assess Drug-Drug Interaction (Ddi) between Paxlovid and the Top 100 Prescribed Drugs in the Us

BACKGROUND: Paxlovid (nirmatrelvir/ritonavir) has received a US Emergency Use Authorization for patients >=12 years with mild-to- moderate COVID-19 at high-risk of progression to severe disease. DDI studies conducted with Paxlovid implicate the PK enhancer ritonavir as the main perpetrator of DDIs. Ritonavir is a potent inhibitor of CYP3A4, CYP2D6, and P-gp. The Paxlovid Fact Sheet1 identifies contraindicated drugs and those with a potentially important interaction. METHOD(S): A retrospective analysis was conducted using RWE from the Optum Clinformatics Data Mart. Patients were identified based on CDC criteria for high-risk COVID-19 and confirmed continuous insurance enrollment from Jan 1 to Dec 31, 2019 with >=1 prescription claim. Excluding non-drug claims (e.g., vaccines), the top 100 drugs were selected and ranked based on total patient counts. DDI potential with Paxlovid was evaluated using US Prescribing and DailyMed Information or relevant literature for each drug. RESULT(S): Of the top 100, 70 drugs are not expected to have a DDI with Paxlovid. These drugs are eliminated unchanged in urine, cleared by enzymes other than CYP3A4 or CYP2D6, are not P-gp substrates, or are cleared by multiple pathways. The remaining 30 drugs expected to have a DDI are represented in the Paxlovid Fact Sheet. The top four drug classes expected to interact with Paxlovid include corticosteroids, narcotic analgesics, anticoagulants, and statins. One drug, simvastatin, is contraindicated. The mechanism of interaction with Paxlovid, or lack thereof, will be presented in detail for each drug. CONCLUSION(S): Paxlovid DDI management is important to ensure the right patients receive this antiviral. This analysis provides an understanding of Paxlovid interactions with the top 100 drugs likely to be used in high-risk COVID-19 patients and serves as an additional DDI management resource.

Antimicrobial peptide antibiotics against multidrug-resistant ESKAPE pathogens

The ongoing COVID-19 pandemic reminds human beings of the challenging nature of the virus SARS-CoV-2. Likewise, bacterial resistance constitutes another potential threat to human health globally. It is the time to prepare for the worst scenario that antibiotic-resistant pathogens could cause 10 million deaths by 2050. Six major types of bacterial pathogens are abbreviated as ESKAPE (i.e., gram-positive Enterococcus faecium, Staphylococcus aureus, gram-negative Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) due to their capability of escaping the action of conventional antibiotics. These pathogens utilize different mechanisms to mitigate the killing effects of antibiotics. To identify potent antimicrobials, numerous approaches are under exploration. This chapter summarizes antimicrobial peptides (AMPs), their engineered analogs, synthetic mimics, conjugates, combinations, formulated nanoparticles, and surface immobilized forms that have demonstrated activity against the ESKAPE pathogens. Also discussed are mechanisms of bacterial killing, and the potential of AMPs as future antibiotics. © 2023 Elsevier Inc. All rights reserved.

The Prevalence and Clinical Characteristics of Multidrug-resistant Hospital-acquired Staphylococcus aureus in Medina, Saudi Arabia

Hospital acquired-Staphylococcus aureus (HA-Staphylococcus aureus), particularly methicillin-resistant Staphylococcus aureus (MRSA), are an important source of nosocomial infections with high morbidity and mortality rates. Few reports showed that infections due to HA-Staphylococcus aureus in Saudi Arabia is increasing, particularly infections attributed to HA-MRSA. The study aimed to explore the prevalence and clinical characteristics of HA-Staphylococcus aureus for the first time in Medina, Saudi Arabia. A total of 1262 clinical samples of hospitalized patients were examined for the presence of Staphylococcus aureus through selective culturing on mannitol salt agar. Vitek Compact System and conventional methods were followed to confirm the isolates. Vitek Compact System tested the antimicrobial susceptibility of isolates whereas the standard PCR was employed to detect the genes encoding antimicrobial resistance (mecA and vanA) and virulence factors (tst, et, and LukS-PV). The overall HA-Staphylococcus aureus prevalence was low (6.58%, n = 1262) of which 84.34% (n = 83) were MRSA. Approximately, 57 samples of the 70 MRSA (81.5%) exhibited a multidrug-resistance (MDR) pattern. All the 83 HA-Staphylococcus aureus isolates were negative for the genes encoding toxic shock syndrome toxin, exfoliative toxin, and Panton-Valentine leukocidin. The study was conducted during the Covid-19 pandemic under partial lockdown, restricted hospitalization, and increased disinfection and infection control measures. Therefore, the low prevalence of HA-Staphylococcus aureus should be carefully interpreted and further multicenter investigations could reveal its true incidence in the city. The high prevalence of MDR HA-MRSA is alarming as it highlights inappropriate antibiotic prescriptions to counter staphylococcal infections. HA-Staphylococcus aureus investigated in this study might lack certain virulence factors. However, their MDR traits and invasive nature could worsen the situation if not properly handled. Copyright © 2023 The Author(s).

Identification of Multi Drug Resistant Bacteria from Drinking Water Samples - A Microbial Survey

Antimicrobial resistance may result from rising resistance patterns of commercially available antibiotics, which is one of the most serious threats to global health and should not be overlooked while the world is focused on the COVID-19 disaster. Waterborne resistant bacteria have been shown to be capable of spreading to people in a lot of circumstances, particularly crowded places in urban living environment with heavy human behavior, such as drinking in public systems and swimming pools. Four hundred drinking water samples were collected from different zones in district Lahore, Pakistan. Multidrug resistance bacterial strains of waterborne pathogens have been isolated and characterized on the basis of colony characteristics, microscopic visuality and biochemical tests. The outcomes of this project revealed that Staphylococcus aureus was (26%), Escheria coli was (45%), Salmonella typhi (15%), Shigella dysenteriae (10%) and Enterococcus faecalis (4%) in district Lahore, Pakistan. These multidrug resistance bacteria showed high resistant patterns against amoxicillin, penicillin, streptomycin, tetracycline, erythromycin, gentamycin, amikacin whereas susceptible for chloramphenicol, cefixime, ofloxacin and ciprofloxacin. The prevalence of associated risk factors such as polluted drinking water (32%), children<5year age (22%), adults >45year age (18%), excessive use of antibiotics (8%), health status of individual (5%), smoking habits (6%), and emotional variables (6%) were observed in this research. These investigations have demonstrated infectious bacterial contamination in surface and groundwater, which caused significant bowel syndrome.Copyright © 2022 Indian Veterinary Assocaition. All rights reserved.

Effects of physicochemical changes (temperature, pH, and culture media) on strong biofilm formation of Acinetobacter baumannii isolated from patients with respiratory infection in Iraq

Introduction and Aim: The ability of Acinetobacter baumannii to form biofilms on biotic and abiotic surfaces is regulated by several pathogens' virulence factors, and this is thought to be at the root of the bacteria's resistance to antibiotics. We hope to learn how temperature, pH, and iron concentrations influence the development of biofilms in A. baumannii isolated from COVID-19 and non-COVID-19 individuals, and which genes are relevant for biofilm formation and antibiotic resistance. Material(s) and Method(s): Eight strong adherent isolates of A. baumannii from respiratory tract infection Iraqi patients (4 from COVID-19 and the other from non-COVID-19 just respiratory patients) had been used in this study which conducted from 10/1/2021 to 10/2/2022. The antibiotic sensitivity of all isolates was determined using the VITEK-2 system. The biofilm associated genes OXA-51, bap, Chaperone Usher (CsuE) and Integron-1, was detected using PCR. Isolates of A. baumainni were put through a battery of tests to determine whether they possessed the capacity to produce robust biofilms under a wide range of both physical (temperature, pH) and chemical circumstances. Result(s): A. baumannii showed that all isolates were multidrug resistant and positive for the biofilm genes studied. Effect on temperature on biofilm formation showed at 44C biofilm formation was significantly lower than that at 37C (mean differences of 0.178000 (t= 8.355, df:3, P=0.004) and 0.204000 (t=26.521, df:3, P=0.000) respectively). The adhesion factor value in the COVID-19 positive and negative groups decreased significantly because of the pH change. Iron concentration of 60 microM significantly lowered biofilm formation among COVID-19 group and non-COVID-19 group. Conclusion(s): A. baumanni are multidrug resistance isolates with a capacity to form biofilms. The ability to form biofilms by A. baumannii is strongly influenced by physical and chemical factors.Copyright © 2023, Indian Association of Biomedical Scientists. All rights reserved.

Treatment of post-COVID-19 patients with chronic recurrent prostatitis: efficacy of recombinant interferon alpha-2b medications.

Introduction. The tactics of managing and treating patients with chronic recurrent bacterial prostatitis (CRBP) in some cases is a difficult-to-treat condition for a practicing urologist. This circumstance occurs because the disease has several predisposing factors, a complex and multifaceted pathogenesis, and certain difficulties in diagnosis and treatment. Objective. To study the effectiveness of recombinant interferon alpha-2b medications in post-COVID-19 patients with chronic recurrent prostatitis against the background of antibiotic multi-drug resistance of microorganisms verified in prostate secretion. Materials and methods. The treatment of 52 post-COVID-19 patients with CRBP was analyzed, divided into three therapy-dependent groups. Group 1 patients (n = 18) received antibiotic therapy (ABT): Levofloxacin 500 mg q.d. PO for 28 days. Group 2 patients (n = 18) underwent combined therapy: ABT supplemented with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C ("Viferon" rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. Group 3 patients (n = 16) received monotherapy with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C ("Viferon"rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. The follow-up period was 6 months with monitoring of clinical and laboratory parameters assessed before treatment, after 1, 3 and 6 months from the start of therapy. Results. Based on the monitoring of the clinical picture and laboratory parameters, after 1 follow-up month, there was a significant decrease in the symptoms of the disease in all study groups. However, after 3 and 6 follow-up months, this trend was observed only in patients of groups 2 and 3 receiving recombinant interferon alfa-2b with an antioxidant complex (vitamins E and C). Conclusions. Strengthening the standard CRBP-therapy with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C makes it possible to normalize both clinical and laboratory parameters in most patients.Copyright © Rostovskii Gosudarstvennyi Meditsinskii Universitet. All rights reserved.

Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study.

Objectives: High frequency of antimicrobial prescription and the nature of prolonged illness in COVID-19 increases risk for complicated bacteriuria and antibiotic resistance. We investigated risk factors for bacteriuria in the ICU and the correlation between antibiotic treatment and persistent bacteria. Methods: We conducted a prospective longitudinal study with urine from indwelling catheters of 101 ICU patients from Uppsala University Hospital, Sweden. Samples were screened and isolates confirmed with MALDI-TOF and whole genome sequencing. Isolates were analyzed for AMR using broth microdilution. Clinical data were assessed for correlation with bacteriuria. Results: Length of stay linearly correlated with bacteriuria (R2 = 0.99, p ≤ 0.0001). 90% of patients received antibiotics, primarily the beta-lactams (76%) cefotaxime, piperacillin-tazobactam, and meropenem. We found high prevalence of Enterococcus (42%) being associated with increased cefotaxime prescription. Antibiotic-susceptible E. coli were found to cause bacteriuria despite concurrent antibiotic treatment when found in co-culture with Enterococcus. Conclusion: Longer stays in ICUs increase the risk for bacteriuria in a predictable manner. Likely, high use of cefotaxime drives Enterococcus prevalence, which in turn permit co-colonizing Gram-negative bacteria. Our results suggest biofilms in urinary catheters as a reservoir of pathogenic bacteria with the potential to develop and disseminate AMR.

Whole-Genome Sequencing-Based Resistome Analysis of Nosocomial Multidrug-Resistant Non-Fermenting Gram-Negative Pathogens from the Balkans.

Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas aeruginosa and Acinetobacter baumannii, are among the major opportunistic pathogens involved in the global antibiotic resistance epidemic. They are designated as urgent/serious threats by the Centers for Disease Control and Prevention and are part of the World Health Organization's list of critical priority pathogens. Also, Stenotrophomonas maltophilia is increasingly recognized as an emerging cause for healthcare-associated infections in intensive care units, life-threatening diseases in immunocompromised patients, and severe pulmonary infections in cystic fibrosis and COVID-19 individuals. The last annual report of the ECDC showed drastic differences in the proportions of NFGNB with resistance towards key antibiotics in different European Union/European Economic Area countries. The data for the Balkans are of particular concern, indicating more than 80% and 30% of invasive Acinetobacter spp. and P. aeruginosa isolates, respectively, to be carbapenem-resistant. Moreover, multidrug-resistant and extensively drug-resistant S. maltophilia from the region have been recently reported. The current situation in the Balkans includes a migrant crisis and reshaping of the Schengen Area border. This results in collision of diverse human populations subjected to different protocols for antimicrobial stewardship and infection control. The present review article summarizes the findings of whole-genome sequencing-based resistome analyses of nosocomial multidrug-resistant NFGNBs in the Balkan countries.

The COVID-19 Pandemic Sparked Off a Large-Scale Outbreak of Carbapenem-Resistant Acinetobacter baumannii from the Endemic Strains at an Italian Hospital.

Acinetobacter baumannii is a nosocomial pathogen that poses a serious threat due to the rise of incidence of multidrug-resistant (MDR) strains. During the COVID-19 pandemic, MDR A. baumannii clones have caused several outbreaks worldwide. Here, we describe a detailed investigation of an MDR A. baumannii outbreak that occurred at Policlinico San Matteo (Pavia, Italy). A total of 96 A. baumannii strains, isolated between January and July 2020 from 41 inpatients (both SARS-CoV-2 positive and negative) in different wards, were characterized by phenotypic and genomic analyses combining Illumina and Nanopore sequencing. Antibiotic susceptibility testing revealed that all isolates were resistant to carbapenems, and the sequence analysis attributed this to the carbapenemase gene blaOXA-23. Virulence factor screening unveiled that all strains carried determinants for biofilm formation, while plasmid analysis revealed the presence of two plasmids, one of which was ~100 kbp long and encoded a phage sequence. A core genome-based phylogeny was inferred to integrate outbreak strain genomes with background genomes from public databases and the local surveillance program. All strains belonged to the globally disseminated sequence type 2 (ST2) clone and were mainly divided into two clades. Isolates from the outbreak clustered with surveillance isolates from 2019, suggesting that the outbreak was caused by two strains that were already circulating in the hospital before the start of the pandemic. The intensive spread of A. baumannii in the hospital was enhanced by the extreme emergency situation of the first COVID-19 pandemic wave that resulted in reduced attention to infection prevention and control practices. IMPORTANCE The COVID-19 pandemic, especially during the first wave, posed a great challenge to the hospital management and generally promoted nosocomial pathogen dissemination. MDR A. baumannii can easily spread and persist for a long time on surfaces, causing outbreaks in health care settings. Infection prevention and control practices, epidemiological surveillance, and microbiological screening are fundamental in order to control such outbreaks. Here, we sequenced the genomes of 96 isolates from an outbreak of MDR A. baumannii strains using both short- and long-read technology in order to reconstruct the outbreak events in fine detail. The sequence data demonstrated that two endemic clones of MDR A. baumannii were the source of this large hospital outbreak during the first COVID-19 pandemic wave, confirming the effect of COVID-19 emergency disrupting the protection provided by the use of the standard prevention procedures.

Healthcare-Associated Bloodstream Infections Due to Multidrug-Resistant Acinetobacter baumannii in COVID-19 Intensive Care Unit: A Single-Center Retrospective Study.

Healthcare-associated infections are an emerging cause of morbidity and mortality in COVID-19 intensive care units (ICUs) worldwide, especially those caused by multidrug-resistant (MDR) pathogens. The objectives of this study were to assess the incidence of bloodstream infections (BSIs) among critically ill COVID-19 patients and to analyze the characteristics of healthcare-associated BSIs due to MDR Acinetobacter baumannii in an COVID-19 ICU. A single-center retrospective study was conducted at a tertiary hospital during a 5-month period. The detection of carbapenemase genes was performed by PCR and genetic relatedness by pulsed-field gel electrophoresis (PFGE) and multilocus-sequence typing. A total of 193 episodes were registered in 176 COVID-19 ICU patients, with an incidence of 25/1000 patient-days at risk. A. baumannii was the most common etiological agent (40.3%), with a resistance to carbapenems of 100%. The blaOXA-23 gene was detected in ST2 isolates while the blaOXA-24 was ST636-specific. PFGE revealed a homogeneous genetic background of the isolates. The clonal spread of OXA-23-positive A. baumannii is responsible for the high prevalence of MDR A. baumannii BSIs in our COVID-19 ICU. Further surveillance of resistance trends and mechanisms is needed along with changes in behavior to improve the implementation of infection control and the rational use of antibiotics.