scholarly journals Photodynamic Treatment of Staphylococcus aureus Infections

2021 ◽  
Author(s):  
Christian Erick Palavecino ◽  
Camila Pérez ◽  
Tania Zuñiga
Keyword(s):  
Staphylococcus Aureus ◽  
Photodynamic Therapy ◽  
Large Body ◽  
Multidrug Resistant ◽  
Photodynamic Treatment ◽  
Antibiotic Resistant ◽  
Bibliographic Search ◽  
Life Threatening ◽  
Major Producer ◽  
Healthcare Associated

Introduction: Staphylococcus aureus is a Gram-positive coconut that causes various life-threatening infections and, in turn, represents a major producer of healthcare-associated infections. This pathogen is highly resistant to antibiotics, which has made it difficult to eradicate in recent decades. Photodynamic therapy is a promising approach to address the notable shortage of antibiotic options against multidrug-resistant Staphylococcus aureus. This therapy combines the use of a photosensitizing agent, light, and oxygen to eradicate pathogenic microorganisms. The purpose of this study is to provide relevant bibliographic information about the application of photodynamic therapy as an alternative antimicrobial therapy for Staphylococcus aureus infections. Methods: This review was achieved through a bibliographic search in various databases and the analysis of relevant publications on the subject. Results: A large body of evidence demonstrates the efficacy of photodynamic therapy in eliminating biofilm- or biofilm-producing strains of Staphylococcus aureus, as well as antibiotic-resistant strains. Conclusion: We conclude that photodynamic therapy against Staphylococcus aureus is a recommended antibacterial therapy that may complement antibiotic treatment.

scholarly journals Blurred molecular epidemiological lines between the two dominant methicillin-resistant Staphylococcus aureus clones

2018 ◽  
Author(s):  
Amy C. Dupper ◽  
Mitchell J. Sullivan ◽  
Kieran I. Chacko ◽  
Aaron Mishkin ◽  
Brianne Ciferri ◽  
...  
Keyword(s):  
New York ◽  
Staphylococcus Aureus ◽  
Medical Center ◽  
Data Extraction ◽  
Age Groups ◽  
Bloodstream Infections ◽  
Methicillin Resistant ◽  
Peripheral Intravenous Catheter ◽  
Life Threatening ◽  
Healthcare Associated

AbstractBackgroundMethicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections in both community and hospital settings and is a leading cause of healthcare-associated infections (HAIs). We sought to describe the molecular epidemiological landscape of patients with MRSA bloodstream infections (BSIs) at an urban medical center by evaluating the clinical characteristics associated with the two dominant endemic clones.MethodsComprehensive clinical data extraction from the electronic health records of 227 hospitalized patients ≥18 years old with MRSA BSI over a 33-month period in New York City were collected. The descriptive epidemiology and mortality associated with the two dominant clones was compared using logistic regression.ResultsMolecular analysis revealed that 91% of all single-patient MRSA BSIs were due to two equally represented genotypes, clonal complex (CC) 5 (N=117) and CC8 (N=110). MRSA BSIs were associated with a 90-day mortality of 27%. CC8 caused disease more frequently in younger age groups (56 ± 17 vs 67 ± 17 years old; p<0.001) and in non-White race (OR=3.45 95% CI [1.51-7.87]; p=0.003), with few other major distinguishing features. Morbidity and mortality also did not differ significantly between the two clones. CC8 caused BSIs more frequently in the setting of peripheral intravenous catheters (OR=5.96; 95% CI [1.51-23.50]; p=0.01).ConclusionThe clinical features distinguishing dominant MRSA clones continue to converge. The association of CC8 with peripheral intravenous catheter infections underscores the importance of classical community clones causing hospital-onset infections. Ongoing monitoring and analysis of the dynamic epidemiology of this endemic pathogen is crucial to inform management to prevent disease.

scholarly journals Droplet rather than Aerosol Mediated Dispersion is the Primary Mechanism of Bacterial transmission from Contaminated Hand Washing Sink Traps

2018 ◽  
Author(s):  
Shireen Kotay ◽  
Rodney M. Donlan ◽  
Christine Ganim ◽  
Katie Barry ◽  
Bryan E. Christensen ◽  
...  
Keyword(s):  
Patient Care ◽  
Sampling Methods ◽  
Model Organism ◽  
Air Sampling ◽  
Multidrug Resistant ◽  
Hand Washing ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Potential Reservoir ◽  
Healthcare Associated

ABSTRACTAn alarming rise in hospital outbreaks implicating hand-washing sinks has led to widespread acknowledgement that sinks are a major reservoir of antibiotic resistant pathogens in patient-care areas. An earlier study using a GFP-expressing Escherichia coli (GFP-E. coli) as a model organism demonstrated dispersal from drain biofilm in contaminated sinks. The present study further characterizes the dispersal of microorganisms from contaminated sinks. Replicate hand-washing sinks were inoculated with GFP-E. coli, and dispersion was measured using qualitative (settle plates) and quantitative (air sampling) methods. Dispersal caused by faucet water was captured with settle plates and air sampling methods when bacteria were present on the drain. In contrast, no dispersal was captured without or in between faucet events amending earlier theory that bacteria aerosolize from P-trap and disperse. Numbers of dispersed GFP-E. coli diminished substantially within 30 minutes after faucet usage, suggesting that the organisms were associated with larger droplet-sized particles that are not suspended in the air for long periods.IMPORTANCEAmong the possible environmental reservoirs in a patient care environment, sink drains are increasingly recognized as potential reservoir of multidrug resistant healthcare-associated pathogens to hospitalized patients. With increasing antimicrobial resistance limiting therapeutic options for patients, better understanding of how pathogens disseminate from sink drains is urgently needed. Once this knowledge gap has decreased, interventions can be engineered to decrease or eliminate transmission from hospital sink drains to patients. The current study further defines the mechanisms of transmission for bacteria colonizing sink drains.

scholarly journals Engineering of Long-Circulating Peptidoglycan Hydrolases Enables Efficient Treatment of Systemic Staphylococcus aureus Infection

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Anna M. Sobieraj ◽  
Markus Huemer ◽  
Léa V. Zinsli ◽  
Susanne Meile ◽  
Anja P. Keller ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Blood ◽  
Half Life ◽  
Multidrug Resistant ◽  
Life Extension ◽  
Drug Resistant ◽  
Content Type ◽  
Peptidoglycan Hydrolases ◽  
Life Threatening

ABSTRACT Staphylococcus aureus is a human pathogen causing life-threatening diseases. The increasing prevalence of multidrug-resistant S. aureus infections is a global health concern, requiring development of novel therapeutic options. Peptidoglycan-degrading enzymes (peptidoglycan hydrolases, PGHs) have emerged as a highly effective class of antimicrobial proteins against S. aureus and other pathogens. When applied to Gram-positive bacteria, PGHs hydrolyze bonds within the peptidoglycan layer, leading to rapid bacterial death by lysis. This activity is highly specific and independent of the metabolic activity of the cell or its antibiotic resistance patterns. However, systemic application of PGHs is limited by their often low activity in vivo and by an insufficient serum circulation half-life. To address this problem, we aimed to extend the half-life of PGHs selected for high activity against S. aureus in human serum. Half-life extension and increased serum circulation were achieved through fusion of PGHs to an albumin-binding domain (ABD), resulting in high-affinity recruitment of human serum albumin and formation of large protein complexes. Importantly, the ABD-fused PGHs maintained high killing activity against multiple drug-resistant S. aureus strains, as determined by ex vivo testing in human blood. The top candidate, termed ABD_M23, was tested in vivo to treat S. aureus-induced murine bacteremia. Our findings demonstrate a significantly higher efficacy of ABD_M23 than of the parental M23 enzyme. We conclude that fusion with ABD represents a powerful approach for half-life extension of PGHs, expanding the therapeutic potential of these enzybiotics for treatment of multidrug-resistant bacterial infections. IMPORTANCE Life-threatening infections with Staphylococcus aureus are often difficult to treat due to the increasing prevalence of antibiotic-resistant bacteria and their ability to persist in protected niches in the body. Bacteriolytic enzymes are promising new antimicrobials because they rapidly kill bacteria, including drug-resistant and persisting cells, by destroying their cell wall. However, when injected into the bloodstream, these enzymes are not retained long enough to clear an infection. Here, we describe a modification to increase blood circulation time of the enzymes and enhance treatment efficacy against S. aureus-induced bloodstream infections. This was achieved by preselecting enzyme candidates for high activity in human blood and coupling them to serum albumin, thereby preventing their elimination by kidney filtration and blood vessel cells.

scholarly journals Prevalence of Multiple Antibiotic Resistant Infections in Diabetic versus Nondiabetic Wounds

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Urvish Trivedi ◽  
Shamini Parameswaran ◽  
Andrew Armstrong ◽  
Diana Burgueno-Vega ◽  
John Griswold ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Diabetic Patients ◽  
Wound Infections ◽  
Antibiotic Resistant ◽  
Foot Ulceration ◽  
Multidrug Resistant Organisms ◽  
Initial Hypothesis ◽  
The Usa

Diabetes mellitus (DM) affects 23.6 million people in the USA and approximately 20–25% of diabetic patients will develop foot ulceration during the course of their disease. Up to a quarter of these patients will develop infections that will necessitate amputation. Although many studies report that the rates of antibiotic resistant infections have increased dramatically in the DM population over the last decade, to our knowledge there have been no reports directly comparing the rates of antibiotic resistant infections in DM versus non-DM wounds. We performed a retrospective study comparing the wound infections of 41 DM patients to those of 74 non-DM patients to test the hypothesis that infections with multidrug resistant organisms (MDRO) were more prevalent in the DM population. We found that 63.4% of DM and 50% of non-DM patients had MDRO infections, which was not statistically different. However, 61% of the DM patients hadPseudomonasinfections compared to only 18.9% of non-DM patients. Furthermore, DM patients had significantly more coinfections with bothPseudomonasandStaphylococcus aureus. Though our initial hypothesis was incorrect, we demonstrated a significant correlation betweenPseudomonasandPseudomonas/S. aureuscoinfections within DM wounds.

scholarly journals Efficacy of Phage Cocktail AB-SA01 Therapy in Diabetic Mouse Wound Infections Caused by Multidrug-Resistant Staphylococcus aureus

2020 ◽  
Author(s):  
Legesse Garedew Kifelew ◽  
Morgyn S. Warner ◽  
Sandra Morales ◽  
Lewis Vaughan ◽  
Richard Woodman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Wound Healing ◽  
Bacterial Load ◽  
Foot Ulcer ◽  
Diabetic Mouse ◽  
Multidrug Resistant ◽  
Two Phase ◽  
Antibiotic Resistant ◽  
Phage Cocktail ◽  
Vancomycin Treatment

Abstract Background: Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus. Antibiotic-resistant Staphylococcus aureus is frequently isolated from DFU infections. Bacteriophages (“phages”) represent an alternative or adjunct treatment to antibiotic therapy. Here we describe the efficacy of AB-SA01, a cocktail of three S. aureus Myoviridae phages, made to current good manufacturing practice (cGMP) standards, and which has undergone two phase I trials, in treatment of multidrug-resistant (MDR) S. aureus infections.Methods: Using a diabetic mouse model, bilateral six-millimetre excisional deep skin wounds inflicted on the dorsum of Balb/c mice were infected with 6.7 log10 colony-forming units (CFU) of clinical MDR S. aureus. Infections were treated topically with AB-SA01, or controls: saline, or saline plus intraperitoneal (IP) vancomycin. Bacterial load and wound healing parameters were used to assess treatment efficacy.Results: Wounds of saline-treated mice showed no healing, but expanded and became inflamed, ulcerated, and suppurating. In contrast, AB-SA01 treatment decreased the bacterial load with efficacy similar or superior to vancomycin treatment. In phage-treated mice, wound healing was seen similar to vancomycin treatment. No adverse effects related to the application of phages were observed.Conclusion: Our results suggest that topical phage cocktail treatment may be effective in treating antibiotic-resistant S. aureus DFU infections.

scholarly journals Comparison of Transcriptional Responses and Metabolic Alterations in Three Multidrug-Resistant Model Microorganisms, Staphylococcus aureus ATCC BAA-39, Escherichia coli ATCC BAA-196, and Acinetobacter baumannii ATCC BAA-1790, on Exposure to Iodine-Containing Nano-micelle Drug FS-1

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Ilya S. Korotetskiy ◽  
Sergey V. Shilov ◽  
Tatyana V. Kuznetsova ◽  
Aleksandr I. Ilin ◽  
Monique Joubert ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Gene Regulation ◽  
Growth Phase ◽  
Multidrug Resistant ◽  
Genome Sequences ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Reference Strains ◽  
Sublethal Concentrations

ABSTRACT Iodine is one of the oldest antimicrobial agents. Until now, there have been no reports on acquiring resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic-resistant pathogens as a supplement to antibiotic therapy. The mechanisms of the action, however, remain unclear. The aim of this study was to perform a holistic analysis and comparison of gene regulation in three phylogenetically distant multidrug-resistant reference strains representing pathogens associated with nosocomial infections from the ATCC culture collection: Escherichia coli BAA-196, Staphylococcus aureus BAA-39, and Acinetobacter baumannii BAA-1790. These cultures were treated by a 5-min exposure to sublethal concentrations of the iodine-containing drug FS-1 applied in the late lagging phase and the middle of the logarithmic growth phase. Complete genome sequences of these strains were obtained in the previous studies. Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the treatment of bacteria with FS-1 profoundly affected the expression of many genes involved in the central metabolic pathways; however, alterations of the gene expression profiles were species specific and depended on the growth phase. Disruption of respiratory electron transfer membrane complexes, increased penetrability of bacterial cell walls, and osmotic and oxidative stresses leading to DNA damage were the major factors influencing the treated bacteria. IMPORTANCE Infections caused by antibiotic-resistant bacteria threaten public health worldwide. Combinatorial therapy in which antibiotics are administered together with supplementary drugs improving susceptibility of pathogens to the regular antibiotics is considered a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 has been reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug-resistant tuberculosis. The effects of released iodine on metabolic and regulatory processes in bacterial cells remain unexplored. The current work provides an insight into gene regulation in the antibiotic-resistant nosocomial reference strains treated with iodine-containing nanoparticles. This study sheds light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in sublethal concentrations. This knowledge will aid in the future design of new drugs against antibiotic-resistant infections.

scholarly journals The Neutrally Charged Diarylurea Compound PQ401 Kills Antibiotic-Resistant and Antibiotic-Tolerant Staphylococcus aureus

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Wooseong Kim ◽  
Guijin Zou ◽  
Wen Pan ◽  
Nico Fricke ◽  
Hammad A. Faizi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Lipid Bilayers ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Lead Compound ◽  
Neutral Form ◽  
Cationic Form ◽  
Antibiotic Resistant ◽  
Content Type

ABSTRACT Resistance or tolerance to traditional antibiotics is a challenging issue in antimicrobial chemotherapy. Moreover, traditional bactericidal antibiotics kill only actively growing bacterial cells, whereas nongrowing metabolically inactive cells are tolerant to and therefore “persist” in the presence of legacy antibiotics. Here, we report that the diarylurea derivative PQ401, previously characterized as an inhibitor of the insulin-like growth factor I receptor, kills both antibiotic-resistant and nongrowing antibiotic-tolerant methicillin-resistant Staphylococcus aureus (MRSA) by lipid bilayer disruption. PQ401 showed several beneficial properties as an antimicrobial lead compound, including rapid killing kinetics, low probability for resistance development, high selectivity to bacterial membranes compared to mammalian membranes, and synergism with gentamicin. In contrast to well-studied membrane-disrupting cationic antimicrobial low-molecular-weight compounds and peptides, molecular dynamic simulations supported by efficacy data demonstrate that the neutral form of PQ401 penetrates and subsequently embeds into bacterial lipid bilayers more effectively than the cationic form. Lastly, PQ401 showed efficacy in both the Caenorhabditis elegans and Galleria mellonella models of MRSA infection. These data suggest that PQ401 may be a lead candidate for repurposing as a membrane-active antimicrobial and has potential for further development as a human antibacterial therapeutic for difficult-to-treat infections caused by both drug-resistant and -tolerant S. aureus. IMPORTANCE Membrane-damaging antimicrobial agents have great potential to treat multidrug-resistant or multidrug-tolerant bacteria against which conventional antibiotics are not effective. However, their therapeutic applications are often hampered due to their low selectivity to bacterial over mammalian membranes or their potential for cross-resistance to a broad spectrum of cationic membrane-active antimicrobial agents. We discovered that the diarylurea derivative compound PQ401 has antimicrobial potency against multidrug-resistant and multidrug-tolerant Staphylococcus aureus. PQ401 selectively disrupts bacterial membrane lipid bilayers in comparison to mammalian membranes. Unlike cationic membrane-active antimicrobials, the neutral form of PQ401 rather than its cationic form exhibits maximum membrane activity. Overall, our results demonstrate that PQ401 could be a promising lead compound that overcomes the current limitations of membrane selectivity and cross-resistance. Also, this work provides deeper insight into the design and development of new noncharged membrane-targeting therapeutics to combat hard-to-cure bacterial infections.

scholarly journals Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

scholarly journals Protective face mask filter capable of inactivating SARS-CoV-2, and methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis

2020 ◽  
Author(s):  
Miguel Martí ◽  
Alberto Tuñón-Molina ◽  
Finn Lillelund Aachmann ◽  
Yukiko Muramoto ◽  
Takeshi Noda ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Face Mask ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Methicillin Resistant ◽  
Care Workers ◽  
Contact Transmission ◽  
Life Threatening ◽  
Asymptomatic Individuals

AbstractFace masks have globally been accepted to be an effective protective tool to prevent bacterial and viral transmission, especially against indoor aerosol transmission. However, commercial face masks contain filters that are made of materials that are not capable of inactivating neither SARS-CoV-2 nor multidrug-resistant bacteria. Therefore, symptomatic and asymptomatic individuals can infect other people even if they wear them because some viable viral or bacterial loads can escape from the masks. Furthermore, viral or bacterial contact transmission can occur after touching the mask, which constitutes an increasing source of contaminated biological waste. Additionally, bacterial pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex and their resistance to antibiotics in pneumonia treatment is increasing at an alarming rate. In this regard, herein, we report the development of a novel protective non-woven face mask filter fabricated with a biofunctional coating of benzalkonium chloride that is capable of inactivating SARS-CoV-2 in one minute of contact, and the life-threatening methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Nonetheless, despite the results obtained, further studies are needed to ensure the safety and correct use of this technology for the mass production and commercialization of this broad-spectrum antimicrobial face mask filter. Our novel protective non-woven face mask filter would be useful for many health care workers and researchers working in this urgent and challenging field.

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