MtlD as a therapeutic target for intestinal and systemic bacterial infections.

Unlabelled: The ability to treat infections is threatened by the rapid emergence of antibiotic resistance among pathogenic microbes. Therefore, new antimicrobials are needed. Here we evaluate mannitol-1-phosphate 5-dehydrogenase (MtlD) as a potential new drug target.

Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening.

Multidrug-resistant bacterial infections pose an ever-evolving threat to public health. Since the outset of the antibacterial age, bacteria have developed a multitude of diverse resistance mechanisms that suppress the effectiveness of current therapies. New drug entities, such as Novel Bacterial Topoisomerase Inhibitors (NBTIs), can circumvent this major issue.

Synergistic bactericidal effects of phage-enhanced antibiotic therapy against MRSA biofilms.

Unlabelled: Methicillin-resistant (MRSA) causes biofilm-related medical device infections. Phage-antibiotic combinations offer potential therapy due to proven antibiofilm efficacy. We evaluated phage-antibiotic synergy against biofilms using modified checkerboard and 24-h time-kill assays.

Phage-antibiotic synergy against daptomycin-nonsusceptible MRSA in an simulated endocardial pharmacokinetic/pharmacodynamic model.

Phage-antibiotic combinations (PAC) offer a potential solution for treating refractory daptomycin-nonsusceptible (DNS) methicillin-resistant (MRSA) infections. We examined PAC activity against two well-characterized DNS MRSA strains (C4 and C37) and . PACs comprising daptomycin (DAP) ± ceftaroline (CPT) and a two-phage cocktail (Intesti13 + Sb-1) were evaluated for phage-antibiotic synergy (PAS) against high MRSA inoculum (10 CFU/mL) using (i) modified checkerboards (CB), (ii) 24-h time-kill assays (TKA), and (iii) 168-h simulated endocardial vegetation (SEV) models.

Ciprofloxacin in combination with bacteriophage cocktails against multi-drug resistant in simulated endocardial vegetation models.

-associated infective endocarditis represents difficult-to-treat, deep-seated infections. Phage-antibiotic combinations have shown to eradicate multi-drug resistant (MDR) , limit the development of phage resistance, and restore antibiotic sensitivity. The objective of this study was to evaluate the activity of phage-ciprofloxacin (CIP) combinations in 4-day simulated endocardial vegetation (SEV) models against drug-resistant isolates.

Phage-antibiotic combinations against multidrug-resistant in static and dynamic biofilm models.

Biofilm-producing infections pose a severe threat to public health and are responsible for high morbidity and mortality. Phage-antibiotic combinations (PACs) are a promising strategy for combatting multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat infections. Ten MDR/XDR strains and five .

Targeting Dalbavancin Inoculum Effect: Adjunctive Single Dose of Daptomycin.

Introduction: Daptomycin (DAP) has proven to be a viable alternative amid vancomycin resistance; however, the use of DAP post vancomycin treatment has led to the development of DAP non-susceptible (DNS) strains. Dalbavancin (DAL), a novel single-dosed lipoglycopeptide, has shown enhanced activity against highly resistant Staphylococcus aureus strains. However, on the basis of previous reports and our observations, DAL does not demonstrate similar activity at high versus low inoculum levels.

Phage-Antibiotic Cocktail Rescues Daptomycin and Phage Susceptibility against Daptomycin-Nonsusceptible Enterococcus faecium in a Simulated Endocardial Vegetation Model.

Enterococcus faecium is a difficult-to-treat pathogen with emerging resistance to most clinically available antibiotics. Daptomycin (DAP) is the standard of care, but even high DAP doses (12 mg/kg body weight/day) failed to eradicate some vancomycin-resistant strains. Combination DAP-ceftaroline (CPT) may increase β-lactam affinity for target penicillin binding proteins (PBP); however, in a simulated endocardial vegetation (SEV) pharmacokinetic/pharmacodynamic (PK/PD) model, DAP-CPT did not achieve therapeutic efficacy against a DAP-nonsusceptible (DNS) vancomycin-resistant E.

Evaluation of Omadacycline Alone and in Combination with Rifampin against Staphylococcus aureus and Staphylococcus epidermidis in an Pharmacokinetic/Pharmacodynamic Biofilm Model.

Biofilm-associated infections lead to substantial morbidity. Omadacycline (OMC) is a novel aminomethylcycline with potent activity against Staphylococcus aureus and Staphylococcus epidermidis, but data surrounding its use in biofilm-associated infections are lacking. We investigated the activity of OMC alone and in combination with rifampin (RIF) against 20 clinical strains of staphylococci in multiple biofilm analyses, including an pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor (CBR) model (simulating human exposures).

Translating phage therapy into the clinic: Recent accomplishments but continuing challenges.

Phage therapy is a medical form of biological control of bacterial infections, one that uses naturally occurring viruses, called bacteriophages or phages, as antibacterial agents. Pioneered over 100 years ago, phage therapy nonetheless is currently experiencing a resurgence in interest, with growing numbers of clinical case studies being published. This renewed enthusiasm is due in large part to phage therapy holding promise for providing safe and effective cures for bacterial infections that traditional antibiotics acting alone have been unable to clear.

Optimization of Phage-Antibiotic Combinations against Staphylococcus aureus Biofilms.

Phage therapy has gained attention due to the spread of antibiotic-resistant bacteria and narrow pipeline of novel antibiotics. Phage cocktails are hypothesized to slow the overall development of resistance by challenging the bacteria with more than one phage. Here, we have used a combination of plate-, planktonic-, and biofilm-based screening assays to try to identify phage-antibiotic combinations that will eradicate preformed biofilms of Staphylococcus aureus strains that are otherwise difficult to kill.

Current therapies and challenges for the treatment of Staphylococcus aureus biofilm-related infections.

Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and contributes to significant increase in morbidity and mortality especially when associated with medical devices and in biofilm form. Biofilm structure provides a pathway for the enrichment of resistant and persistent phenotypes of S. aureus leading to relapse and recurrence of infection.

Editorial: Special Issue on Pharmacokinetic/Pharmacodynamic Models of Antibiotics.

Pharmacokinetic/pharmacodynamic (PK/PD) modeling is an essential tool for rational drug development and treatment design [...

Activity of the Lactate Dehydrogenase Inhibitor Oxamic Acid against the Fermentative Bacterium : Bactericidal Effects and Prevention of Daptomycin Resistance In Vitro and in an Ex Vivo Model.

is a fermentative bacterium that relies on lactate dehydrogenase to balance its redox poise and keep glycolysis active. Metabolomic analysis of an in vitro-derived daptomycin-resistant (DAP-R) strain (351-D10) revealed differences in glucose catabolism relative to its DAP-susceptible (DAP-S) parental strain, 351. Metabolic changes associated with the transition to this DAP-R phenotype suggested that inhibiting glycolysis could alter DAP susceptibility.

Phage Cocktails with Daptomycin and Ampicillin Eradicates Biofilm-Embedded Multidrug-Resistant with Preserved Phage Susceptibility.

Multidrug-resistant (MDR) is a challenging nosocomial pathogen known to colonize medical device surfaces and form biofilms. Bacterio (phages) may constitute an emerging anti-infective option for refractory, biofilm-mediated infections. This study evaluates eight MDR strains for biofilm production and phage susceptibility against nine phages.

Bacteriophage-antibiotic combination therapy for multidrug-resistant Pseudomonas aeruginosa: In vitro synergy testing.

Aims: Here, we investigate the impact of phage-antibiotic combinations (PAC) on bacterial killing, resistance development and outer membrane vesicle (OMV) production in multidrug-resistant (MDR) P. aeruginosa.

Methods And Results: After screening 10 well-characterized MDR P.

Eradication of Biofilm-Mediated Methicillin-Resistant Staphylococcus aureus Infections : Bacteriophage-Antibiotic Combination.

Bacterial biofilms are difficult to eradicate and can complicate many infections by forming on tissues and medical devices. Phage+antibiotic combinations (PAC) may be more active on biofilms than either type of agent alone, but it is difficult to predict which PAC regimens will be reliably effective. To establish a method for screening PAC combinations against Staphylococcus aureus biofilms, we conducted biofilm time-kill analyses (TKA) using various combinations of phage Sb-1 with clinically relevant antibiotics.

Folate Functionalized Lipid Nanoparticles for Targeted Therapy of Methicillin-Resistant .

Methicillin-resistant (MRSA), commonly called a superbug, is a highly alarming antibiotic-resistant population of bacteria. Vancomycin (VAN) was first approved by the FDA in 1988, and it is still regarded as the treatment of choice for MRSA. The efficacy of VAN treatment has become less effective due to the development of VAN resistance in MRSA and the potential for nephrotoxicity.

Evaluation of Bacteriophage Cocktails Alone and in Combination with Daptomycin against Daptomycin-Nonsusceptible Enterococcus faecium.

Enterococcus faecium is a significant multidrug-resistant pathogen. Bacteriophage cocktails are being proposed to complement antibiotic therapy. After a screen of 8 E.

Biofilm Time-Kill Curves to Assess the Bactericidal Activity of Daptomycin Combinations against Biofilm-Producing Vancomycin-Resistant and .

Introduction: and are responsible for 13.9% of hospital-acquired infections with frequent resistance to vancomycin (82.6% of , 9.

Exebacase in Addition to Daptomycin against MRSA.

Exebacase is a lysin (cell wall hydrolase) with direct lytic activity against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA). Time-kill analysis experiments illustrated bactericidal activity of exebacase-daptomycin against MRSA strains MW2 and 494.

In Vitro Synergy of Colistin in Combination with Meropenem or Tigecycline against Carbapenem-Resistant .

is currently classified as one of six pathogens that contribute to increased patient mortality. Thus, exploratory studies navigating alternative treatment strategies are of supreme interest. Herein, we completed minimum inhibitory concentration (MIC) testing, and time-kill analyses (TKA) on 50 carbapenem-resistant isolates including 28 colistin-resistant isolates.

Antibacterial Activity of Cefiderocol against Multidrug-Resistant Acinetobacter baumannii.

Cefiderocol (CFDC), a novel siderophore cephalosporin, demonstrates strong activity against multidrug-resistant (MDR) Acinetobacter baumannii. Limited studies have evaluated CFDC alone and in combination with other Gram-negative antibiotics against MDR A. baumannii isolates.