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1.
Microbiol Res ; 265: 127206, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2042033

ABSTRACT

COVID-19 (Coronavirus Disease 2019), a life-threatening viral infection, is caused by a highly pathogenic virus named SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Currently, no treatment is available for COVID-19; hence there is an urgent need to find effective therapeutic drugs to combat COVID-19 pandemic. Considering the fact that the world is facing a major issue of antimicrobial drug resistance, naturally occurring compounds have the potential to achieve this goal. Antimicrobial peptides (AMPs) are naturally occurring antimicrobial agents which are effective against a wide variety of microbial infections. Therefore, the use of AMPs is an attractive therapeutic strategy for the treatment of SARS-CoV-2 infection. This review sheds light on the potential of antimicrobial peptides as antiviral agents followed by a comprehensive description of effective antiviral peptides derived from various natural sources found to be effective against SARS-CoV and other respiratory viruses. It also highlights the mechanisms of action of antiviral peptides with special emphasis on their effectiveness against SARS-CoV-2 infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Antimicrobial Peptides , Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Resistance, Multiple , Humans , Pandemics
2.
Int J Mol Sci ; 23(14)2022 Jul 07.
Article in English | MEDLINE | ID: covidwho-1928571

ABSTRACT

Multidrug antimicrobial resistance is a constantly growing health care issue associated with increased mortality and morbidity, and huge financial burden. Bacteria frequently form biofilm communities responsible for numerous persistent infections resistant to conventional antibiotics. Herein, novel nanoparticles (NPs) loaded with the natural bactericide farnesol (FSL NPs) are generated using high-intensity ultrasound. The nanoformulation of farnesol improved its antibacterial properties and demonstrated complete eradication of Staphylococcus aureus within less than 3 h, without inducing resistance development, and was able to 100% inhibit the establishment of a drug-resistant S. aureus biofilm. These antibiotic-free nano-antimicrobials also reduced the mature biofilm at a very low concentration of the active agent. In addition to the outstanding antibacterial properties, the engineered nano-entities demonstrated strong antiviral properties and inhibited the spike proteins of SARS-CoV-2 by up to 83%. The novel FSL NPs did not cause skin tissue irritation and did not induce the secretion of anti-inflammatory cytokines in a 3D skin tissue model. These results support the potential of these bio-based nano-actives to replace the existing antibiotics and they may be used for the development of topical pharmaceutic products for controlling microbial skin infections, without inducing resistance development.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Biofilms , Drug Resistance, Multiple , Farnesol/pharmacology , Humans , Microbial Sensitivity Tests , SARS-CoV-2 , Staphylococcal Infections/drug therapy , Staphylococcus aureus
3.
Microb Drug Resist ; 28(5): 601-610, 2022 May.
Article in English | MEDLINE | ID: covidwho-1864944

ABSTRACT

This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p-value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p-value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p-value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p-value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.


Subject(s)
Bacteremia , Gram-Negative Bacterial Infections , Neoplasms , Neutropenia , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Bacteremia/epidemiology , Child , Drug Resistance, Multiple , Escherichia coli , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/drug therapy , Humans , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/pathology , Neutropenia/complications , Neutropenia/drug therapy , Retrospective Studies
4.
Int J Environ Res Public Health ; 19(8)2022 04 16.
Article in English | MEDLINE | ID: covidwho-1809881

ABSTRACT

In sub-Saharan Africa, there is limited information about the use of microbiology laboratory services in patients with suspected urinary tract infections (UTIs). This cross-sectional study assessed the requests for urine culture in patients with suspected UTI in two tertiary (maternal and paediatric) hospitals-Freetown and Sierra Leone, during May 2017-May 2021-and determined antimicrobial resistance (AMR) patterns among bacterial isolates. One laboratory served the two hospitals, with its electronic database used to extract information. Overall, there were 980 patients, of whom 168 (17%) had cultures requested and performed. Of these, 75 (45%) were culture positive. During 2017-2019, there were 930 patients, of whom 156 (17%) had cultures performed. During 2020-2021, when services were disrupted by the COVID-19 pandemic, there were 50 patients, of whom 12 (24%) had cultures performed. The four commonest isolates were Escherichia coli (36), Klebsiella pneumoniae (10), Staphylococcus aureus (9), and Pseudomonas spp. (6). There were high levels of AMR, especially for trimethoprim-sulfamethoxazole (47%), nalidixic acid (44%), nitrofurantoin (32%) and cefotaxime (36%). Overall, 41 (55%) bacterial isolates showed multidrug resistance, especially E. coli (58%), Pseudomonas spp. (50%), and S. aureus (44%). These findings support the need for better utilization of clinical microbiology services to guide antibiotic stewardship and monitoring of trends in resistance patterns.


Subject(s)
COVID-19 , Urinary Tract Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Child , Cross-Sectional Studies , Drug Resistance, Bacterial , Drug Resistance, Multiple , Escherichia coli , Female , Humans , Male , Microbial Sensitivity Tests , Pandemics , Sierra Leone/epidemiology , Staphylococcus aureus , Tertiary Care Centers , Urinary Tract Infections/drug therapy , Urinary Tract Infections/epidemiology , Urinary Tract Infections/microbiology
5.
Mycoses ; 65(6): 613-624, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1794602

ABSTRACT

BACKGROUND: Candida auris is an emerging multidrug-resistant pathogen in intensive care settings (ICU). During the coronavirus disease 19 (COVID-19) pandemic, ICU admissions were overwhelmed, possibly contributing to the C. auris outbreak in COVID-19 patients. OBJECTIVES: The present systematic review addresses the prevalence, underlying diseases, iatrogenic risk factors, treatment and outcome of C. auris infections in COVID-19 patients. METHODS: MEDLINE, Scopus, Embase, Web of Science and LitCovid databases were systematically searched with appropriate keywords from 1 January 2020 to 31 December 2021. RESULTS: A total of 97 cases of C. auris were identified in COVID-19 patients. The pooled prevalence of C. auris infections (encompassing candidemia and non-candidemia cases) in COVID-19 patients was 14%. The major underlying diseases were diabetes mellitus (42.7%), hypertension (32.9%) and obesity (14.6%), followed by the iatrogenic risk factors such as a central venous catheter (76.8%%), intensive care unit (ICU) stay (75.6%) and broad-spectrum antibiotic usage (74.3%). There were no significant differences in underlying disease and iatrogenic risk factors among C. auris non-candidemia/colonisation and C. auris candidemia cases. The mortality rate of the total cohort is 44.4%, whereas, in C. auris candidemia patients, the mortality was 64.7%. CONCLUSION: This study shows that the prevalence of C. auris infections remains unchanged in the COVID-19 pandemic. Hospital-acquired risk factors may contribute to the clinical illness. Proper infection control practices and hospital surveillance may stop future hospital outbreaks during the pandemic.


Subject(s)
COVID-19 , Candidemia , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , COVID-19/epidemiology , Candida , Candida auris , Candidemia/drug therapy , Candidemia/epidemiology , Drug Resistance, Multiple , Humans , Iatrogenic Disease/epidemiology , Microbial Sensitivity Tests , Pandemics , Prevalence , Risk Factors , Treatment Outcome
6.
Molecules ; 27(3)2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1625062

ABSTRACT

Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID-19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance.


Subject(s)
Drug Resistance, Multiple , Drug Resistance, Neoplasm , Animals , Drug Resistance, Microbial , Humans
7.
Int J Mol Sci ; 22(24)2021 Dec 18.
Article in English | MEDLINE | ID: covidwho-1580689

ABSTRACT

Global reports on multidrug resistance (MDR) and life-threatening pathogens such as SARS-CoV-2 and Candida cruris have stimulated researchers to explore new antimicrobials that are eco-friendly and economically viable. In this context, biodegradable polymers such as nisin, chitin, and pullulan play an important role in solving the problem. Pullulan is an important edible, biocompatible, water-soluble polymer secreted by Aureobasidium pullulans that occurs ubiquitously. It consists of maltotriose units linked with α-1,6 glycosidic bonds and is classed as Generally Regarded as Safe (GRAS) by the Food and Drug Administration (FDA) in the USA. Pullulan is known for its antibacterial, antifungal, antiviral, and antitumor activities when incorporated with other additives such as antibiotics, drugs, nanoparticles, and so on. Considering the importance of its antimicrobial activities, this polymer can be used as a potential antimicrobial agent against various pathogenic microorganisms including the multidrug-resistant (MDR) pathogens. Moreover, pullulan has ability to synthesize biogenic silver nanoparticles (AgNPs), which are remarkably efficacious against pathogenic microbes. The pullulan-based nanocomposites can be applied for wound healing, food packaging, and also enhancing the shelf-life of fruits and vegetables. In this review, we have discussed biosynthesis of pullulan and its role as antibacterial, antiviral, and antifungal agent. Pullulan-based films impregnated with different antimicrobials such as AgNPs, chitosan, essential oils, and so on, forming nanocomposites have also been discussed as natural alternatives to combat the problems posed by pathogens.


Subject(s)
Anti-Infective Agents/pharmacology , Drug Resistance, Multiple/drug effects , Glucans/biosynthesis , Anti-Bacterial Agents , Anti-Infective Agents/chemistry , Antifungal Agents , COVID-19 , Chitin/pharmacology , Chitosan/chemistry , Drug Resistance, Multiple/physiology , Food Packaging , Glucans/metabolism , Glucans/pharmacology , Humans , Metal Nanoparticles/chemistry , Nanocomposites/chemistry , Nisin/pharmacology , Polymers/chemistry , SARS-CoV-2
8.
Front Immunol ; 12: 753849, 2021.
Article in English | MEDLINE | ID: covidwho-1523705

ABSTRACT

Background: CD14+ monocytes present antigens to adaptive immune cells via monocytic human leukocyte antigen receptor (mHLA-DR), which is described as an immunological synapse. Reduced levels of mHLA-DR can display an acquired immune defect, which is often found in sepsis and predisposes for secondary infections and fatal outcomes. Monocytic HLA-DR expression is reliably induced by interferon- γ (IFNγ) therapy. Case Report: We report a case of multidrug-resistant superinfected COVID-19 acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support. The resistance profiles of the detected Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter freundii isolates were equipped with resistance to all four antibiotic classes including carbapenems (4MRGN) and Cefiderocol in the case of K. pneumoniae. A causal therapeutic antibiotic strategy was not available. Therefore, we measured the immune status of the patient aiming to identify a potential acquired immune deficiency. Monocyte HLA-DR expression identified by FACS analysis revealed an expression level of 34% positive monocytes and suggested severe immunosuppression. We indicated IFNγ therapy, which resulted in a rapid increase in mHLA-DR expression (96%), rapid resolution of invasive bloodstream infection, and discharge from the hospital on day 70. Discussion: Superinfection is a dangerous complication of COVID-19 pneumonia, and sepsis-induced immunosuppression is a risk factor for it. Immunosuppression is expressed by a disturbed antigen presentation of monocytes to cells of the adaptive immune system. The case presented here is remarkable as no validated antibiotic regimen existed against the detected bacterial pathogens causing bloodstream infection and severe pneumonia in a patient suffering from COVID-19 ARDS. Possible restoration of the patient's own immunity by IFNγ was a plausible option to boost the patient's immune system, eliminate the identified 4MRGNs, and allow for lung recovery. This led to the conclusion that immune status monitoring is useful in complicated COVID-19-ARDS and that concomitant IFNγ therapy may support antibiotic strategies. Conclusion: After a compromised immune system has been detected by suppressed mHLA-DR levels, the immune system can be safely reactivated by IFNγ.


Subject(s)
Bacteria/immunology , COVID-19/immunology , Drug Resistance, Multiple/immunology , HLA Antigens/immunology , Interferon-gamma/immunology , Monocytes/immunology , Respiratory Distress Syndrome/immunology , Adult , Humans , Receptors, Interferon/immunology
9.
Photochem Photobiol Sci ; 20(11): 1497-1545, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1491552

ABSTRACT

Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Emphasis is placed on the pipeline of photosensitizers that proved effective to inactivate biofilms, showed efficacy in animal models of infectious diseases or reached clinical trials. Novel opportunities resulting from the COVID-19 pandemic are briefly discussed. The molecular features of promising photosensitizers are emphasized and contrasted with those of photosensitizers used in the treatment of solid tumors. The development of photosensitizers has been accompanied by the fabrication of a variety of affordable and customizable light sources. We critically discuss the combination between photosensitizer and light source properties that may leverage PDDI and expand its applications to wider markets. The success of PDDI in the management of infectious diseases will ultimately depend on the efficacy of photosensitizers, affordability of the light sources, simplicity of the procedures, and availability of fast and efficient treatments.


Subject(s)
Communicable Disease Control/methods , Drug Resistance, Microbial/drug effects , Drug Resistance, Multiple/drug effects , Photochemotherapy , Photosensitizing Agents/therapeutic use , Animals , Bacteria/drug effects , Biofilms/drug effects , Fungi/drug effects , Humans , Microbial Sensitivity Tests , Neoplasms/drug therapy , Photosensitizing Agents/pharmacology
10.
Curr Opin Infect Dis ; 34(4): 365-371, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1341151

ABSTRACT

PURPOSE OF REVIEW: The coronavirus disease (COVID-19) pandemic has resulted in necessary modifications of infection control policies and practices in acute healthcare facilities globally. This is often accompanied by infrastructure modifications, ward redesignations, as well as healthcare staff redeployments and changes to infection prevention and control (IPC) practices. We review the potential for both negative and positive impacts these major changes can have on nosocomial transmission of multidrug-resistant organisms (MDROs). RECENT FINDINGS: Healthcare facilities around the world have reported outbreaks of MDROs during the COVID-19 pandemic. In contrast some centres have reported a decrease in baseline rates due to a number of possible factors. SUMMARY: While implementing crucial preventive measures for COVID-19, is it important to consider any collateral effects of changes in IPC and antimicrobial stewardship program (ASP) practices. The disruption caused to IPC and ASP practices during the pandemic are likely to see a counter intuitive increase in transmission of MDROs.


Subject(s)
COVID-19/epidemiology , Cross Infection/epidemiology , Cross Infection/etiology , Cross Infection/transmission , Drug Resistance, Microbial , Drug Resistance, Multiple , SARS-CoV-2 , Acute Disease , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Cross Infection/drug therapy , Disease Outbreaks , Hospitals , Humans , Infection Control/methods , Pandemics , Public Health Surveillance
11.
Infection ; 49(4): 591-605, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1130951

ABSTRACT

BACKGROUND: The incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes. OBJECTIVE: This narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified. METHOD: We perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms. RESULTS: The incidence of secondary pulmonary infections is low at 16% (4.8-42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9-33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2-21 days) from initial hospitalization and 9 days (4-18 days) after ICU admission. The use of antibiotics is high at 60-100% involving the studies included in our review. CONCLUSION: The widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 patients.


Subject(s)
COVID-19/complications , Lung Diseases, Fungal/epidemiology , Pneumonia, Bacterial/epidemiology , SARS-CoV-2 , Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship , COVID-19/epidemiology , Coinfection/diagnosis , Coinfection/drug therapy , Coinfection/epidemiology , Coinfection/microbiology , Drug Resistance, Multiple , Humans , Incidence , Lung Diseases, Fungal/etiology , Lung Diseases, Fungal/microbiology , Pneumonia, Bacterial/etiology , Pneumonia, Bacterial/microbiology , Time Factors
14.
Emerg Infect Dis ; 26(11): 2694-2696, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-734338

ABSTRACT

In New Delhi, India, candidemia affected 15 critically ill coronavirus disease patients admitted to an intensive care unit during April-July 2020. Candida auris accounted for two thirds of cases; case-fatality rate was high (60%). Hospital-acquired C. auris infections in coronavirus disease patients may lead to adverse outcomes and additional strain on healthcare resources.


Subject(s)
Betacoronavirus , Candida , Candidiasis/virology , Coronavirus Infections/microbiology , Cross Infection/microbiology , Pneumonia, Viral/microbiology , Adult , Aged , Antifungal Agents/therapeutic use , COVID-19 , Candidiasis/drug therapy , Candidiasis/epidemiology , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Critical Illness , Cross Infection/drug therapy , Cross Infection/epidemiology , Drug Resistance, Multiple , Female , Humans , India/epidemiology , Male , Microbial Sensitivity Tests , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , SARS-CoV-2
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