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1.
J Infect Chemother ; 28(7): 978-981, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1851523

ABSTRACT

Netherton's syndrome, a rare congenital disorder, is clinically characterized by chronic dermatologic disorders such as ichthyosiform erythroderma and ichthyosis linearis circumflexa. Curable treatment is yet to be established, and corticosteroid ointment is required to maintain good dermatological condition. Because of the permanent skin barrier impairment, patients with Netherton's syndrome are considered to be vulnerable to cutaneous infections. However, its clinical characteristics are yet to be elucidated due to the limited number of reported cases. Herein, we describe the clinical course of a patient who developed persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A 19-year-old Japanese woman who had been diagnosed with Netherton's syndrome in her infancy and had been applying topical corticosteroid agents all over her body since her then, was referred to our hospital because of persistent MRSA bacteremia and secondary adrenal insufficiency. The patient was diagnosed with a central line-associated bloodstream infection and was appropriately treated with antibiotics and corticosteroid therapies. We assume that the damaged skin barrier due to the congenital dermatological disorder causes a disruption in the normal bacterial flora of the skin, leading to the invasion of harmful bacteria, such as S. aureus. In addition, internal (humoral immunodeficiency by decreased antibody against bacterial polysaccharide antigens) and external (prolonged and systemic use of corticosteroid ointment) factors bring about an immunodeficiency state in such patients. We highlight that in the absence of radical treatment, clinicians need to recognize that patients with Netherton's syndrome are vulnerable to bacterial infections owing to the mixture of immunosuppressive factors.


Subject(s)
Bacteremia , Methicillin-Resistant Staphylococcus aureus , Adult , Bacteremia/drug therapy , Female , Humans , Ointments , Staphylococcus aureus , Syndrome , Young Adult
2.
Int J Mol Sci ; 23(9)2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1847340

ABSTRACT

In this study, humidified air dielectric barrier discharge (DBD) plasma was used to inactivate Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and bacteriophages in biofilms containing DNA, NaCl, carbohydrates, and proteins. The humidified DBD plasma was very effective in the inactivation of microbes in the (≤1.0 µm) biofilms. The number of surviving E. coli, S. aureus, and bacteriophages in the biofilms was strongly dependent on the constituent and thickness of the biofilms and was greatly reduced when the plasma treatment time increased from 5 s to 150 s. Our analysis shows that the UV irradiation was not responsible for the inactivation of microbes in biofilms. The short-lived RONS generated in the humidified air DBD plasma were not directly involved in the inactivation process; however, they recombined or reacted with other species to generate the long-lived RONS. Long-lived RONS diffused into the biofilms to generate very active species, such as ONOOH and OH. This study indicates that the geminated NO2 and OH pair formed due to the homolysis of ONOOH can cause the synergistic oxidation of various organic molecules in the aqueous solution. Proteins in the biofilm were highly resistant to the inactivation of microbes in biofilms, which is presumably due to the existence of the unstable functional groups in the proteins. The unsaturated fatty acids, cysteine-rich proteins, and sulfur-methyl thioether groups in the proteins were easily oxidized by the geminated NO2 and OH pair.


Subject(s)
Bacteriophages , Escherichia coli Infections , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Biofilms , Escherichia coli/physiology , Humans , Nitrogen Dioxide , Staphylococcus aureus/physiology
3.
Drugs ; 82(5): 533-557, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1827389

ABSTRACT

Sulopenem (formerly known as CP-70,429, and CP-65,207 when a component of a racemic mixture with its R isomer) is an intravenous and oral penem that possesses in vitro activity against fluoroquinolone-resistant, extended spectrum ß-lactamases (ESBL)-producing, multidrug-resistant (MDR) Enterobacterales. Sulopenem is being developed to treat patients with uncomplicated and complicated urinary tract infections (UTIs) as well as intra-abdominal infections. This review will focus mainly on its use in UTIs. The chemical structure of sulopenem shares properties of penicillins, cephalosporins, and carbapenems. Sulopenem is available as an oral prodrug formulation, sulopenem etzadroxil, which is hydrolyzed by intestinal esterases, resulting in active sulopenem. In early studies, the S isomer of CP-65,207, later developed as sulopenem, demonstrated greater absorption, higher drug concentrations in the urine, and increased stability against the renal enzyme dehydropeptidase-1 compared with the R isomer, which set the stage for its further development as a UTI antimicrobial. Sulopenem is active against both Gram-negative and Gram-positive microorganisms. Sulopenem's ß-lactam ring alkylates the serine residues of penicillin-binding protein (PBP), which inhibits peptidoglycan cross-linking. Due to its ionization and low molecular weight, sulopenem passes through outer membrane proteins to reach PBPs of Gram-negative bacteria. While sulopenem activity is unaffected by many ß-lactamases, resistance arises from alterations in PBPs (e.g., methicillin-resistant Staphylococcus aureus [MRSA]), expression of carbapenemases (e.g., carbapenemase-producing Enterobacterales and in Stenotrophomonas maltophilia), reduction in the expression of outer membrane proteins (e.g., some Klebsiella spp.), and the presence of efflux pumps (e.g., MexAB-OprM in Pseudomonas aeruginosa), or a combination of these mechanisms. In vitro studies have reported that sulopenem demonstrates greater activity than meropenem and ertapenem against Enterococcus faecalis, Listeria monocytogenes, methicillin-susceptible S. aureus (MSSA), and Staphylococcus epidermidis, as well as similar activity to carbapenems against Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes. With some exceptions, sulopenem activity against Gram-negative aerobes was less than ertapenem and meropenem but greater than imipenem. Sulopenem activity against Escherichia coli carrying ESBL, CTX-M, or Amp-C enzymes, or demonstrating MDR phenotypes, as well as against ESBL-producing Klebsiella pneumoniae, was nearly identical to ertapenem and meropenem and greater than imipenem. Sulopenem exhibited identical or slightly greater activity than imipenem against many Gram-positive and Gram-negative anaerobes, including Bacteroides fragilis. The pharmacokinetics of intravenous sulopenem appear similar to carbapenems such as imipenem-cilastatin, meropenem, and doripenem. In healthy subjects, reported volumes of distribution (Vd) ranged from 15.8 to 27.6 L, total drug clearances (CLT) of 18.9-24.9 L/h, protein binding of approximately 10%, and elimination half-lives (t½) of 0.88-1.03 h. The estimated renal clearance (CLR) of sulopenem is 8.0-10.6 L/h, with 35.5% ± 6.7% of a 1000 mg dose recovered unchanged in the urine. An ester prodrug, sulopenem etzadroxil, has been developed for oral administration. Initial investigations reported a variable oral bioavailability of 20-34% under fasted conditions, however subsequent work showed that bioavailability is significantly improved by administering sulopenem with food to increase its oral absorption or with probenecid to reduce its renal tubular secretion. Food consumption increases the area under the curve (AUC) of oral sulopenem (500 mg twice daily) by 23.6% when administered alone and 62% when administered with 500 mg of probenecid. Like carbapenems, sulopenem demonstrates bactericidal activity that is associated with the percentage of time that free concentrations exceed the MIC (%f T > MIC). In animal models, bacteriostasis was associated with %f T > MICs ranging from 8.6 to 17%, whereas 2-log10 kill was seen at values ranging from 12 to 28%. No pharmacodynamic targets have been documented for suppression of resistance. Sulopenem concentrations in urine are variable, ranging from 21.8 to 420.0 mg/L (median 84.4 mg/L) in fasted subjects and 28.8 to 609.0 mg/L (median 87.3 mg/L) in those who were fed. Sulopenem has been compared with carbapenems and cephalosporins in guinea pig and murine systemic and lung infection animal models. Studied pathogens included Acinetobacter calcoaceticus, B. fragilis, Citrobacter freundii, Enterobacter cloacae, E. coli, K. pneumoniae, Proteus vulgaris, and Serratia marcescens. These studies reported that overall, sulopenem was non-inferior to carbapenems but appeared to be superior to cephalosporins. A phase III clinical trial (SURE-1) reported that sulopenem was not non-inferior to ciprofloxacin in women infected with fluoroquinolone-susceptible pathogens, due to a higher rate of asymptomatic bacteriuria in sulopenem-treated patients at the test-of-cure visit. However, the researchers reported superiority of sulopenem etzadroxil/probenecid over ciprofloxacin for the treatment of uncomplicated UTIs in women infected with fluoroquinolone/non-susceptible pathogens, and non-inferiority in all patients with a positive urine culture. A phase III clinical trial (SURE-2) compared intravenous sulopenem followed by oral sulopenem etzadroxil/probenecid with ertapenem in the treatment of complicated UTIs. No difference in overall success was noted at the end of therapy. However, intravenous sulopenem followed by oral sulopenem etzadroxil was not non-inferior to ertapenem followed by oral stepdown therapy in overall success at test-of-cure due to a higher rate of asymptomatic bacteriuria in the sulopenem arm. After a meeting with the US FDA, Iterum stated that they are currently evaluating the optimal design for an additional phase III uncomplicated UTI study to be conducted prior to the potential resubmission of the New Drug Application (NDA). It is unclear at this time whether Iterum intends to apply for EMA or Japanese regulatory approval. The safety and tolerability of sulopenem has been reported in various phase I pharmacokinetic studies and phase III clinical trials. Sulopenem (intravenous and oral) appears to be well tolerated in healthy subjects, with and without the coadministration of probenecid, with few serious drug-related treatment-emergent adverse events (TEAEs) reported to date. Reported TEAEs affecting ≥1% of patients were (from most to least common) diarrhea, nausea, headache, vomiting and dizziness. Discontinuation rates were low and were not different than comparator agents. Sulopenem administered orally and/or intravenously represents a potentially well tolerated and effective option for treating uncomplicated and complicated UTIs, especially in patients with documented or highly suspected antimicrobial pathogens to commonly used agents (e.g. fluoroquinolone-resistant E. coli), and in patients with documented microbiological or clinical failure or patients who demonstrate intolerance/adverse effects to first-line agents. This agent will likely be used orally in the outpatient setting, and intravenously followed by oral stepdown in the hospital setting. Sulopenem also allows for oral stepdown therapy in the hospital setting from intravenous non-sulopenem therapy. More clinical data are required to fully assess the clinical efficacy and safety of sulopenem, especially in patients with complicated UTIs caused by resistant pathogens such as ESBL-producing, Amp-C, MDR E. coli. Antimicrobial stewardship programs will need to create guidelines for when this oral and intravenous penem should be used.


Subject(s)
Bacteriuria , Methicillin-Resistant Staphylococcus aureus , Prodrugs , Urinary Tract Infections , Adenosine Monophosphate/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteriuria/chemically induced , Bacteriuria/drug therapy , Carbapenems/pharmacology , Cephalosporins/pharmacology , Ciprofloxacin/pharmacology , Ertapenem , Escherichia coli , Female , Fluoroquinolones/pharmacology , Gram-Negative Bacteria , Guinea Pigs , Humans , Imipenem/pharmacology , Lactams , Male , Membrane Proteins/pharmacology , Meropenem/pharmacology , Mice , Probenecid/pharmacology , Prodrugs/pharmacology , Staphylococcus aureus , Urinary Tract Infections/drug therapy , beta-Lactamases/pharmacology
4.
ACS Chem Biol ; 17(5): 1239-1248, 2022 May 20.
Article in English | MEDLINE | ID: covidwho-1805550

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health, as the US mortality rate outweighs those from HIV, tuberculosis, and viral hepatitis combined. In the wake of the COVID-19 pandemic, antibiotic-resistant bacterial infections acquired during hospital stays have increased. Antibiotic adjuvants are a key strategy to combat these bacteria. We have evaluated several small molecule antibiotic adjuvants that have strong potentiation with ß-lactam antibiotics and are likely inhibiting a master regulatory kinase, Stk1. Here, we investigated how the lead adjuvant (compound 8) exerts its effects in a more comprehensive manner. We hypothesized that the expression levels of key resistance genes would decrease once cotreated with oxacillin and the adjuvant. Furthermore, bioinformatic analyses would reveal biochemical pathways enriched in differentially expressed genes. RNA-seq analysis showed 176 and 233 genes significantly up- and downregulated, respectively, in response to cotreatment. Gene ontology categories and biochemical pathways that were significantly enriched with downregulated genes involved carbohydrate utilization, such as the citrate cycle and the phosphotransferase system. One of the most populated pathways was S. aureus infection. Results from an interaction network constructed with affected gene products supported the hypothesis that Stk1 is a target of compound 8. This study revealed a dramatic impact of our lead adjuvant on the transcriptome that is consistent with a pleiotropic effect due to Stk1 inhibition. These results point to this antibiotic adjuvant having potential broad therapeutic use in combatting MRSA.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Carbazoles/pharmacology , Humans , Methicillin-Resistant Staphylococcus aureus/genetics , Microbial Sensitivity Tests , Pandemics , Staphylococcus aureus , Transcriptome
5.
Molecules ; 27(7)2022 Mar 24.
Article in English | MEDLINE | ID: covidwho-1785835

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen and responsible for causing life-threatening infections. The emergence of hypervirulent and multidrug-resistant (MDR) S. aureus strains led to challenging issues in antibiotic therapy. Consequently, the morbidity and mortality rates caused by S. aureus infections have a substantial impact on health concerns. The current worldwide prevalence of MRSA infections highlights the need for long-lasting preventive measures and strategies. Unfortunately, effective measures are limited. In this study, we focus on the identification of vaccine candidates and drug target proteins against the 16 strains of MRSA using reverse vaccinology and subtractive genomics approaches. Using the reverse vaccinology approach, 4 putative antigenic proteins were identified; among these, PrsA and EssA proteins were found to be more promising vaccine candidates. We applied a molecular docking approach of selected 8 drug target proteins with the drug-like molecules, revealing that the ZINC4235426 as potential drug molecule with favorable interactions with the target active site residues of 5 drug target proteins viz., biotin protein ligase, HPr kinase/phosphorylase, thymidylate kinase, UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase, and pantothenate synthetase. Thus, the identified proteins can be used for further rational drug or vaccine design to identify novel therapeutic agents for the treatment of multidrug-resistant staphylococcal infection.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Vaccines , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Genomics , Humans , Ligases , Methicillin-Resistant Staphylococcus aureus/genetics , Molecular Docking Simulation , Staphylococcal Infections/prevention & control , Staphylococcus aureus , Vaccinology
6.
J Infect Chemother ; 28(3): 465-468, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1778294

ABSTRACT

Dalbavancin is a lipoglycopeptide antibiotic used off-label to treat serious gram-positive infections, including infections secondary to methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin has unique pharmacokinetic parameters and has a role in therapy for treating vulnerable patients, including intravenous drug users, who have challenges complying with typical care plans for serious infections. While there is data indicating successful clinical use of dalbavancin in patients with history of intravenous drug use as well as pharmacokinetic-pharmacodynamic data assessing dalbavancin in obesity, there is a lack of information regarding clinical effects of dalbavancin in patients with extreme obesity, especially in patients with concomitant drug use. This case report describes a 40-year-old morbidly obese female actively using intravenous drugs who developed prolonged MRSA bacteremia without a recognizable focus. Despite partial treatment with dalbavancin, the patient developed osteomyelitis and discitis of the spine with associated epidural phlegmon, likely complications of the MRSA bacteremia.


Subject(s)
Bacteremia , Methicillin-Resistant Staphylococcus aureus , Obesity, Morbid , Adult , Anti-Bacterial Agents/adverse effects , Bacteremia/drug therapy , Female , Humans , Obesity, Morbid/complications , Obesity, Morbid/drug therapy , Teicoplanin/adverse effects , Teicoplanin/analogs & derivatives
7.
Front Public Health ; 10: 853757, 2022.
Article in English | MEDLINE | ID: covidwho-1776076

ABSTRACT

Background: The rising prevalence of multi-drug resistant organisms (MDROs), such as Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococci (VRE), and Carbapenem-resistant Enterobacteriaceae (CRE), is an increasing concern in healthcare settings. Materials and Methods: Leveraging data from electronic healthcare records and a unique MDRO universal screening program, we developed a data-driven modeling framework to predict MRSA, VRE, and CRE colonization upon intensive care unit (ICU) admission, and identified the associated socio-demographic and clinical factors using logistic regression (LR), random forest (RF), and XGBoost algorithms. We performed threshold optimization for converting predicted probabilities into binary predictions and identified the cut-off maximizing the sum of sensitivity and specificity. Results: Four thousand six hundred seventy ICU admissions (3,958 patients) were examined. MDRO colonization rate was 17.59% (13.03% VRE, 1.45% CRE, and 7.47% MRSA). Our study achieved the following sensitivity and specificity values with the best performing models, respectively: 80% and 66% for VRE with LR, 73% and 77% for CRE with XGBoost, 76% and 59% for MRSA with RF, and 82% and 83% for MDRO (i.e., VRE or CRE or MRSA) with RF. Further, we identified several predictors of MDRO colonization, including long-term care facility stay, current diagnosis of skin/subcutaneous tissue or infectious/parasitic disease, and recent isolation precaution procedures before ICU admission. Conclusion: Our data-driven modeling framework can be used as a clinical decision support tool for timely predictions, characterization and identification of high-risk patients, and selective and timely use of infection control measures in ICUs.


Subject(s)
Drug Resistance, Multiple, Bacterial , Intensive Care Units , Methicillin-Resistant Staphylococcus aureus , Vancomycin-Resistant Enterococci , Electronic Health Records , Humans , Models, Theoretical , Patient Admission
8.
Front Cell Infect Microbiol ; 12: 806077, 2022.
Article in English | MEDLINE | ID: covidwho-1775644

ABSTRACT

Background: Mobile phones of healthcare workers (HCWs) can act as fomites in the dissemination of microbes. This study was carried out to investigate microbial contamination of mobile phones of HCWs and environmental samples from the hospital unit using a combination of phenotypic and molecular methods. Methods: This point prevalence survey was carried out at the Emergency unit of a tertiary care facility. The emergency unit has two zones, a general zone for non-COVID-19 patients and a dedicated COVID-19 zone for confirmed or suspected COVID-19 patients. Swabs were obtained from the mobile phones of HCWs in both zones for bacterial culture and shotgun metagenomic analysis. Metagenomic sequencing of pooled environmental swabs was conducted. RT-PCR for SARS-CoV-2 detection was carried out. Results: Bacteria contamination on culture was detected from 33 (94.2%) mobile phones with a preponderance of Staphylococcus epidermidis (n/N = 18/35), Staphylococcus hominis (n/N = 13/35), and Staphylococcus haemolyticus (n/N = 7/35). Two methicillin-sensitive and three methicillin-resistant Staphylococcus aureus, and one pan-drug-resistant carbapenemase producer Acinetobacter baumannii were detected. Shotgun metagenomic analysis showed high signature of Pseudomonas aeruginosa in mobile phone and environmental samples with preponderance of P. aeruginosa bacteriophages. Malassezia and Aspergillus spp. were the predominant fungi detected. Fourteen mobile phones and one environmental sample harbored protists. P. aeruginosa antimicrobial resistance genes mostly encoding for efflux pump systems were detected. The P. aeruginosa virulent factor genes detected were related to motility, adherence, aggregation, and biofilms. One mobile phone from the COVID-19 zone (n/N = 1/5; 20%) had positive SARS-CoV-2 detection while all other phone and environmental samples were negative. Conclusion: The findings demonstrate that mobile phones of HCWs are fomites for potentially pathogenic and highly drug-resistant microbes. The presence of these microbes on the mobile phones and hospital environmental surfaces is a concern as it poses a risk of pathogen transfer to patients and dissemination into the community.


Subject(s)
COVID-19 , Cell Phone , Methicillin-Resistant Staphylococcus aureus , Humans , Methicillin-Resistant Staphylococcus aureus/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics
9.
J Hosp Infect ; 123: 52-60, 2022 May.
Article in English | MEDLINE | ID: covidwho-1757533

ABSTRACT

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections are rampant in hospitals and residential care homes for the elderly (RCHEs). AIM: To analyse the prevalence of MRSA colonization among residents and staff, and degree of environmental contamination and air dispersal of MRSA in RCHEs. METHODS: Epidemiological and genetic analysis by whole-genome sequencing (WGS) in 12 RCHEs in Hong Kong. FINDINGS: During the COVID-19 pandemic (from September to October 2021), 48.7% (380/781) of RCHE residents were found to harbour MRSA at any body site, and 8.5% (8/213) of staff were nasal MRSA carriers. Among 239 environmental samples, MRSA was found in 39.0% (16/41) of randomly selected resident rooms and 31.3% (62/198) of common areas. The common areas accessible by residents had significantly higher MRSA contamination rates than those that were not accessible by residents (37.2%, 46/121 vs. 22.1%, 17/177, P=0.028). Of 124 air samples, nine (7.3%) were MRSA-positive from four RCHEs. Air dispersal of MRSA was significantly associated with operating indoor fans in RCHEs (100%, 4/4 vs. 0%, 0/8, P=0.002). WGS of MRSA isolates collected from residents, staff and environmental and air samples showed that ST 1047 (CC1) lineage 1 constituted 43.1% (66/153) of all MRSA isolates. A distinctive predominant genetic lineage of MRSA in each RCHE was observed, suggestive of intra-RCHE transmission rather than clonal acquisition from the catchment hospital. CONCLUSION: MRSA control in RCHEs is no less important than in hospitals. Air dispersal of MRSA may be an important mechanism of dissemination in RCHEs with operating indoor fans.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Aged , COVID-19/epidemiology , Carrier State/epidemiology , Humans , Methicillin , Methicillin-Resistant Staphylococcus aureus/genetics , Pandemics , Staphylococcal Infections/epidemiology
10.
Pediatr Infect Dis J ; 41(4): e142-e145, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1752202

ABSTRACT

We reviewed all cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) bacteremia in Danish children between 2016 and 2021. We found 2 fatal cases with preceding viral prodrome due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the usual benign course of SARS-CoV-2 infection in children, awareness of possible superinfection with PVL-SA in a child with rapid deterioration is crucial to ensure adequate treatment, including antimicrobial drugs with antitoxin effect.


Subject(s)
Bacteremia , Bacterial Toxins/biosynthesis , COVID-19/complications , Exotoxins/biosynthesis , Leukocidins/biosynthesis , SARS-CoV-2 , Staphylococcal Infections/etiology , Staphylococcal Infections/mortality , Staphylococcus aureus/genetics , Adolescent , COVID-19/virology , Child , Child, Preschool , Coinfection , Comorbidity , Denmark/epidemiology , Female , Humans , Infant , Male , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Public Health Surveillance , Severity of Illness Index , Staphylococcal Infections/diagnosis , Staphylococcal Infections/therapy , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolism
11.
Sci Rep ; 12(1): 2803, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1735270

ABSTRACT

The COVID-19 pandemic has demonstrated the real need for mechanisms to control the spread of airborne respiratory pathogens. Thus, preventing the spread of disease from pathogens has come to the forefront of the public consciousness. This has brought an increasing demand for novel technologies to prioritise clean air. In this study we report on the efficacy of novel biocide treated filters and their antimicrobial activity against bacteria, fungi and viruses. The antimicrobial filters reported here are shown to kill pathogens, such as Candida albicans, Escherichia coli and MRSA in under 15 min and to destroy SARS-CoV-2 viral particles in under 30 s following contact with the filter. Through air flow rate testing, light microscopy and SEM, the filters are shown to maintain their structure and filtration function. Further to this, the filters are shown to be extremely durable and to maintain antimicrobial activity throughout the operational lifetime of the product. Lastly, the filters have been tested in field trials onboard the UK rail network, showing excellent efficacy in reducing the burden of microbial species colonising the air conditioning system.


Subject(s)
Air Filters/microbiology , Anti-Infective Agents/chemistry , Antiviral Agents/chemistry , Air Filters/virology , Anti-Infective Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/epidemiology , COVID-19/virology , Candida albicans/drug effects , Chlorhexidine/analogs & derivatives , Chlorhexidine/chemistry , Chlorhexidine/pharmacology , Escherichia coli/drug effects , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , SARS-CoV-2/drug effects , Time Factors
12.
Talanta ; 243: 123352, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1730116

ABSTRACT

Accurate identification of mutant pathogens derived from genetic polymorphisms is highly desired in clinical diagnosis. However, current detection methods based on Watson-Crick hybridization suffers from false positives due to the cross-reactivity of wild-type sequences. In this study, we developed an accurate identification of mutant pathogens by combining programmable DNAzyme and target nucleic acid sequence-triggered transcription. Single nucleotide variants (SNVs) are the most plentiful type of mutations in the genome. High specificity to discriminate SNV was first achieved by rational design of dual-hairpin DNA structure and DNAzyme's capability of site-specific cleavage. T7 RNA polymerase-mediated transcription amplification was introduced to exponentially increase the sensitivity by encompassing T7 promoter sequence into the dual-hairpin DNA structure. The design of this biosensor is fast and straightforward without many computational steps, and the highly sensitive biosensor can detect not only SNVs but also occasional insertions and large deletions in the genome. We showed that the assay could rapidly detect COVID-19 variant and methicillin-resistant Staphylococcus aureus (MRSA), and the limit of detection is 0.96 copy/µL. The modular design of functional DNA enables this biosensor be easily reconfigured and is useful diagnosis of emerging infectious diseases caused by mutant pathogens.


Subject(s)
Biosensing Techniques , DNA, Catalytic , Biosensing Techniques/methods , COVID-19/diagnosis , DNA, Catalytic/chemistry , DNA, Catalytic/genetics , Humans , Limit of Detection , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Nucleic Acid Amplification Techniques/methods , Nucleic Acid Hybridization , SARS-CoV-2/isolation & purification
13.
BMJ Case Rep ; 15(3)2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1723594

ABSTRACT

A man fully mRNA-vaccinated against COVID-19 presented to our hospital with an acute febrile illness, respiratory symptoms and a positive test for SARS-CoV-2. He was later found early into hospitalisation to have two morbid bacterial co-infections: Legionella pneumophila serogroup 1 and methicillin-resistant Staphylococcus aureus (MRSA). Although this patient was initially admitted for COVID-19 management, his initial presentation was remarkable for lobar pneumonia, hyponatraemia and rhabdomyolysis more compatible with Legionnaire's disease than severe COVID-19. On discovery of MRSA pneumonia as a second bacterial infection, immunosuppressive COVID-19 therapies were discontinued and targeted antibiotics towards both bacterial co-infections were initiated. The patient's successful recovery highlighted the need to have high suspicion for bacterial co-infections in patients presenting with community-acquired pneumonia and a positive SARS-CoV-2 test, as patients with serious bacterial co-infections may have worse outcomes with use of immunosuppressive COVID-19 therapies.


Subject(s)
COVID-19 , Coinfection , Community-Acquired Infections , Legionella pneumophila , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/therapeutic use , COVID-19/complications , Coinfection/diagnosis , Community-Acquired Infections/microbiology , Humans , Male , SARS-CoV-2 , Staphylococcal Infections/complications , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcus aureus
14.
ACS Appl Mater Interfaces ; 14(7): 8718-8727, 2022 Feb 23.
Article in English | MEDLINE | ID: covidwho-1683917

ABSTRACT

Transparent antimicrobial coatings can maintain the aesthetic appeal of surfaces and the functionality of a touch-screen while adding the benefit of reducing disease transmission. We fabricated an antimicrobial coating of silver oxide particles in a silicate matrix on glass. The matrix was grown by a modified Stöber sol-gel process with vapor-phase water and ammonia. A coating on glass with 2.4 mg of Ag2O per mm2 caused a reduction of 99.3% of SARS-CoV-2 and >99.5% of Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus compared to the uncoated glass after 1 h. We envisage that screen protectors with transparent antimicrobial coatings will find particular application to communal touch-screens, such as in supermarkets and other check-out or check-in facilities where a number of individuals utilize the same touch-screen in a short interval.


Subject(s)
Anti-Infective Agents/chemistry , Bacterial Infections/prevention & control , COVID-19/prevention & control , Oxides/chemistry , Silver Compounds/chemistry , Ammonia/chemistry , Anti-Infective Agents/pharmacology , Bacterial Infections/microbiology , COVID-19/virology , Glass/chemistry , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Oxides/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/pathogenicity , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Silicates/chemistry , Silver Compounds/pharmacology , Water/chemistry
17.
Curr Opin Infect Dis ; 35(2): 149-162, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1672443

ABSTRACT

PURPOSE OF REVIEW: Some patients with coronavirus disease 2019 (COVID-19) may develop pulmonary bacterial coinfection or superinfection, that could unfavorably impact their prognosis. RECENT FINDINGS: The exact burden of methicillin-resistant Staphylococcus aureus (MRSA) lung infection in peculiar populations such as patients with COVID-19 remains somewhat elusive, possibly because of wide heterogeneity in methods and endpoints across studies. SUMMARY: There was important heterogeneity in the retrieved literature on the epidemiology of MRSA lung infection in patients with COVID-19, both when considering all other bacteria as the denominator (relative prevalence ranging from 2% to 29%) and when considering only S. aureus as the denominator (relative prevalence ranging from 11% to 65%). Overall, MRSA is among the most frequent causative agents of pulmonary infection in patients with COVID-19. Improving our ability to rapidly reach etiological diagnosis of bacterial lung infection in COVID-19 patients remains fundamental if we are to improve the rates of appropriate antibiotic therapy in patients with COVID-19 and concomitant/superimposed MRSA infection, at the same time avoiding antibiotic overuse in line with antimicrobial stewardship principles.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/therapeutic use , COVID-19/complications , Humans , Lung , SARS-CoV-2 , Staphylococcal Infections/complications , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology , Staphylococcus aureus
18.
PLoS One ; 17(2): e0260580, 2022.
Article in English | MEDLINE | ID: covidwho-1666746

ABSTRACT

Healthcare-associated infections (HAIs) remain a serious public health problem. In previous work, two models of an intensive care unit (ICU) showed that differing population structures had markedly different rates of Staphylococcus aureus (MRSA) transmission. One explanation for this difference is the models having differing long-term equilbrium dynamics, resulting from different basic reproductive numbers, R0. We find in this system however that this is not the case, and that both models had the same value for R0. Instead, short-term, transient dynamics, characterizing a series of small, self-limiting outbreaks caused by pathogen reintroduction were responsible for the differences. These results show the importance of these short-term factors for disease systems where reintroduction events are frequent, even if they are below the epidemic threshold. Further, we examine how subtle changes in how a hospital is organized-or how a model assumes a hospital is organized-in terms of the admission of new patients may impact transmission rates. This has implications for both novel pathogens introduced into ICUs, such as Ebola, MERS or COVID-19, as well as existing healthcare-associated infections such as carbapenem-resistant Enterobacteriaceae.


Subject(s)
Cross Infection/transmission , Disease Outbreaks , Intensive Care Units , Methicillin-Resistant Staphylococcus aureus , Models, Statistical , Patient Admission , Staphylococcal Infections/epidemiology , Staphylococcal Infections/transmission , Humans , Nurses , Physicians , Staphylococcal Infections/microbiology , Stochastic Processes
19.
J Infect Chemother ; 28(5): 616-622, 2022 May.
Article in English | MEDLINE | ID: covidwho-1649513

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has greatly impacted medical care practices. Although the effects on infectious disease treatment and infection control, such as antimicrobial resistance, have been specified, very few reports exist on the specific effects of COVID-19. METHODS: We investigated the effects of COVID-19 on daily medical practices at a tertiary hospital in Japan by comparing the use of hand sanitizers, the detection of bacteria from blood cultures, and the amount dose of antibacterial drugs used for one year before (April 2019 to March 2020, fiscal year 2019.) and after COVID-19 admissions began (April 2020 to March 2021, fiscal year 2020). RESULTS: The use of hand sanitizers increased by 1.4-3 times during the year after COVID-19 admissions began; the incidence of methicillin-susceptible Staphylococcus aureus and all S. aureus detected in blood cultures reduced in all departments. No decrease was observed in the usage of all antibacterial drugs; rather, the usage of all antibacterial drugs tended to increase in all departments. Therefore, no significant change was observed in the detection of drug-resistant bacteria and the trends of antibacterial drug use based on the acceptance of COVID-19 patients. CONCLUSIONS: The prevalence of drug-resistant bacteria and trends of antibacterial drug use remained unchanged despite the increased use of hand sanitizers due to the admission of patients with COVID-19.


Subject(s)
COVID-19 , Communicable Diseases , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Communicable Diseases/drug therapy , Drug Resistance, Bacterial , Humans , Infection Control , Japan/epidemiology , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Staphylococcus aureus , Tertiary Care Centers
20.
J Antimicrob Chemother ; 77(1): 38-48, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1621627

ABSTRACT

OBJECTIVES: Increasing spread of resistance could jeopardize the use of antifolates against MRSA infections. METHODS: We compared the prevalence of phenotypic trimethoprim/sulfamethoxazole resistance in 20 534 clinical Staphylococcus aureus isolates (19 096 MSSA and 1438 MRSA) of non-redundant patients at Heidelberg University Hospital over 8 years and performed WGS on trimethoprim/sulfamethoxazole-resistant MRSA. RESULTS: From 2012 to 2019, trimethoprim/sulfamethoxazole resistance in MSSA (674/19 096; 3.5%) ranged between 1.5% and 7.2% and in MRSA (135/1438; 9.4%) between 0.5% and 20.2%, reaching a peak in 2016 and 2018, respectively (Ptrend < 0.001). Trimethoprim/sulfamethoxazole resistance was more likely in outpatients than inpatients (P = 0.005), younger patients (P < 0.001), skin and soft tissue infections (SSTIs) (MRSA only, P = 0.05), submissions from pulmonology (MRSA only, P = 0.001), the upper respiratory tract (MSSA only, P < 0.001) and general surgery (MSSA only, P = 0.001). WGS of 76 trimethoprim/sulfamethoxazole-resistant MRSA revealed that 59% belonged to major pandemic CA-MRSA clones (ST22, ST8, ST398, ST772, ST30), 47% harboured Panton-Valentine leucocidin (PVL), 97% SCCmec IV/V, 71% dfrG and 28% dfrA. SNP-based phylogeny of trimethoprim/sulfamethoxazole-resistant MRSA core genomes favoured independent introduction over clonal expansion as the source, most prominently of dfrA+ trimethoprim/sulfamethoxazole-resistant ST22 MRSA from the Gaza Strip. CONCLUSIONS: The presented results support that trimethoprim/sulfamethoxazole-resistant S. aureus, formerly associated with SSTI from outpatients and S. aureus in the (sub)tropics, is on the rise in the temperate zone, potentially due to migration. Closer monitoring of trimethoprim/sulfamethoxazole resistance in S. aureus is recommended to safeguard the effectiveness of antifolate compounds.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Trimethoprim, Sulfamethoxazole Drug Combination , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Exotoxins , Germany/epidemiology , Humans , Leukocidins , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Tertiary Care Centers , Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology
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