scholarly journals Ampicillin-sulbactam is effective in prevention and therapy of experimental endocarditis caused by beta-lactamase-producing coagulase-negative staphylococci.

1996 ◽  
Vol 40 (1) ◽  
pp. 97-101 ◽  
Author(s):  
M C Ramos ◽  
M Ing ◽  
E Kim ◽  
M D Witt ◽  
A S Bayer
Keyword(s):  
Dose Regimen ◽  
Optimal Strategies ◽  
Beta Lactamase ◽  
Coagulase Negative Staphylococci ◽  
Prophylactic Efficacy ◽  
Treatment Regimens ◽  
Staphylococcal Strain ◽  
Rifampin Resistance ◽  
Staphylococcal Isolate

Optimal strategies for the prophylaxis and therapy of endocarditis caused by oxacillin-resistant, coagulase-negative staphylococci in patients with native or prosthetic valvular heart disease are not well defined. We compared the in vivo efficacies of ampicillin-sulbactam-based regimens with those of vancomycin-based oxacillin-resistant, beta-lactamase-producing coagulase-negative staphylococcal isolate (Staphylococcus haemolyticus SE220). Ampicillin-sulbactam (100 and 20 mg/kg of body weight, respectively, given intramuscularly in a two-dose regimen) was equivalent to vancomycin (30 mg/kg given intravenously in a two-dose regimen) in its prophylactic efficacy against the coagulase-negative staphylococcal strain (93 and 80%, respectively). The combination of ampicillin-sulbactam plus either rifampin or vancomycin did not enhance the prophylactic efficacy compared with that of ampicillin-sulbactam or vancomycin alone. In the therapy of established aortic valve endocarditis in rabbits caused by this same coagulase-negative staphylococcal strain, animals received 7-day ampicillin-sulbactam-based or vancomycin-based regimens with or without rifampin. All treatment regimens were effective at lowering intravegetation coagulase-negative staphylococcal densities and rendering vegetations culture negative compared with the coagulase-negative staphylococcal densities and vegetations of untreated controls, with ampicillin-sulbactam in combination with rifampin or vancomycin being the most active regimen. However, only the regimen of ampicillin-sulbactam in combination with vancomycin effectively prevented relapse of endocarditis posttherapy after a 5-day antibiotic-free period. For animals receiving rifampin-containing regimens, relapses of endocarditis were associated with the in vivo development of rifampin resistance among coagulase-negative staphylococcal isolates in the vegetation. Ampicillin-sulbactam was highly effective in the prevention of experimental endocarditis caused by a beta-lactamase-producing, oxacillin-resistant coagulase-negative staphylococcal strain. Ampicillin-sulbactam was also efficacious for the therapy of coagulase-negative staphylococcal endocarditis, especially when it was combined with vancomycin to prevent posttherapeutic relapses.

Peculiarities of the course of type I allergic reactions in patients with blood diseases

2020 ◽  
pp. 40-50
Author(s):  
A. Nikitina
Keyword(s):  
Search Engines ◽  
Anaphylactic Shock ◽  
Type I ◽  
Allergic Reactions ◽  
Common Cause ◽  
Blood Diseases ◽  
Treatment Regimens ◽  
Modern Methods

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.

scholarly journals Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yongbing Pan ◽  
Jianhui Du ◽  
Jia Liu ◽  
Hai Wu ◽  
Fang Gui ◽  
...  
Keyword(s):  
Phage Display ◽  
Neutralizing Antibodies ◽  
Variable Region ◽  
Neutralizing Antibody ◽  
Chain Gene ◽  
Prophylactic Efficacy ◽  
Heavy Chains ◽  
Effective Interventions ◽  
Phage Display Libraries

AbstractAs the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

scholarly journals Rifampin Combination Therapy for Nonmycobacterial Infections

2010 ◽  
Vol 23 (1) ◽  
pp. 14-34 ◽  
Author(s):  
Graeme N. Forrest ◽  
Kimberly Tamura
Keyword(s):  
Combination Therapy ◽  
Prosthetic Heart Valve ◽  
Case Series ◽  
Source Control ◽  
Retrospective Case ◽  
Coagulase Negative Staphylococci ◽  
Joint Infections ◽  
Prosthetic Joint Infections

SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

scholarly journals Competition among Nasal Bacteria Suggests a Role for Siderophore-Mediated Interactions in Shaping the Human Nasal Microbiota

2018 ◽  
Vol 85 (10) ◽  
Author(s):  
Reed M. Stubbendieck ◽  
Daniel S. May ◽  
Marc G. Chevrette ◽  
Mia I. Temkin ◽  
Evelyn Wendt-Pienkowski ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Iron Acquisition ◽  
Interference Competition ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Siderophore Production ◽  
Coagulase Negative Staphylococci ◽  
Exploitation Competition ◽  
Content Type

ABSTRACTResources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed coculture inhibition assays between nasalActinobacteriaandStaphylococcusspp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition byActinobacteriabut thatStaphylococcus aureusisolates were resistant to inhibition. AmongActinobacteria, we observed thatCorynebacteriumspp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10Corynebacteriumspecies isolates, including 3Corynebacterium propinquumisolates that strongly inhibited CoNS and 7 otherCorynebacteriumspecies isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that theC. propinquumgenomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitoryCorynebacteriumspecies genomes. Using a chrome azurol S assay, we confirmed thatC. propinquumproduced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition byC. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced byC. propinquumas dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressedin vivoby analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.IMPORTANCEWithin the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasalStaphylococcusspecies strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and posttranslationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by hindering access to or depleting essential nutrients. As the nasal cavity is a nutrient-limited environment, we hypothesized that exploitation competition occurs in this system. We determined thatCorynebacterium propinquumproduces an iron-chelating siderophore, and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Furthermore, we found that the genes required for siderophore production are expressedin vivo. Thus, although siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.

scholarly journals Clinical extended-spectrum beta-lactamase antibiotic resistance plasmids have diverse transfer rates and can spread in the absence of antibiotic selection

2019 ◽  
Author(s):  
Fabienne Benz ◽  
Jana S. Huisman ◽  
Erik Bakkeren ◽  
Joana A. Herter ◽  
Tanja Stadler ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Conjugative Transfer ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Resistance Plasmids ◽  
Serovar Typhimurium ◽  
Spreading Potential

AbstractHorizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global spread of antibiotic resistance. However, the relative contributions of factors that underlie the spread of clinically relevant plasmids are unclear. Here, we quantified conjugative transfer dynamics of Extended Spectrum Beta-Lactamase (ESBL) producing plasmids in the absence of antibiotics. We showed that clinical Escherichia coli strains natively associated with ESBL-plasmids conjugate efficiently with three distinct E. coli strains and one Salmonella enterica serovar Typhimurium strain, reaching final transconjugant frequencies of up to 1% within 24 hours in vitro. The variation of final transconjugant frequencies varied among plasmids, donors and recipients and was better explained by variation in conjugative transfer efficiency than by variable clonal expansion. We identified plasmid-specific genetic factors, specifically the presence/absence of transfer genes, that influenced final transconjugant frequencies. Finally, we investigated plasmid spread within the mouse intestine, demonstrating qualitative agreement between plasmid spread in vitro and in vivo. This suggests a potential for the prediction of plasmid spread in the gut of animals and humans, based on in vitro testing. Altogether, this may allow the identification of resistance plasmids with high spreading potential and help to devise appropriate measures to restrict their spread.

scholarly journals Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections

2020 ◽  
Vol 14 (12) ◽  
pp. e0008930
Author(s):  
Andrea Schiefer ◽  
Marc P. Hübner ◽  
Anna Krome ◽  
Christine Lämmer ◽  
Alexandra Ehrens ◽  
...  
Keyword(s):  
Adult Worm ◽  
Neglected Tropical Diseases ◽  
Combined Treatment ◽  
Wuchereria Bancrofti ◽  
Drug Candidate ◽  
Treatment Regimens ◽  
Short Course ◽  
Filarial Nematodes ◽  
Product Profile

Current efforts to eliminate the neglected tropical diseases onchocerciasis and lymphatic filariasis, caused by the filarial nematodes Onchocerca volvulus and Wuchereria bancrofti or Brugia spp., respectively, are hampered by lack of a short-course macrofilaricidal–adult-worm killing–treatment. Anti-wolbachial antibiotics, e.g. doxycycline, target the essential Wolbachia endosymbionts of filariae and are a safe prototype adult-worm-sterilizing and macrofilaricidal regimen, in contrast to standard treatments with ivermectin or diethylcarbamazine, which mainly target the microfilariae. However, treatment regimens of 4–5 weeks necessary for doxycycline and contraindications limit its use. Therefore, we tested the preclinical anti-Wolbachia drug candidate Corallopyronin A (CorA) for in vivo efficacy during initial and chronic filarial infections in the Litomosoides sigmodontis rodent model. CorA treatment for 14 days beginning immediately after infection cleared >90% of Wolbachia endosymbionts from filariae and prevented development into adult worms. CorA treatment of patently infected microfilaremic gerbils for 14 days with 30 mg/kg twice a day (BID) achieved a sustained reduction of >99% of Wolbachia endosymbionts from adult filariae and microfilariae, followed by complete inhibition of filarial embryogenesis resulting in clearance of microfilariae. Combined treatment of CorA and albendazole, a drug currently co-administered during mass drug administrations and previously shown to enhance efficacy of anti-Wolbachia drugs, achieved microfilarial clearance after 7 days of treatment at a lower BID dose of 10 mg/kg CorA, a Human Equivalent Dose of 1.4 mg/kg. Importantly, this combination led to a significant reduction in the adult worm burden, which has not yet been published with other anti-Wolbachia candidates tested in this model. In summary, CorA is a preclinical candidate for filariasis, which significantly reduces treatment times required to achieve sustained Wolbachia depletion, clearance of microfilariae, and inhibition of embryogenesis. In combination with albendazole, CorA is robustly macrofilaricidal after 7 days of treatment and fulfills the Target Product Profile for a macrofilaricidal drug.

scholarly journals Reversion of antibiotic resistance in multidrug-resistant pathogens using non-antibiotic pharmaceutical benzydamine

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuan Liu ◽  
Ziwen Tong ◽  
Jingru Shi ◽  
Yuqian Jia ◽  
Tian Deng ◽  
...  
Keyword(s):  
Cost Effective ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Treatment Regimens ◽  
Development Of Resistance ◽  
Metabolic States ◽  
Animal Infection ◽  
Life Threatening

AbstractAntimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimens. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing drugs as potent antibiotic adjuvants offers a cost-effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug-resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non‐steroidal anti‐inflammatory drug in clinic, remarkably potentiated broad-spectrum antibiotic-tetracyclines activity against a panel of clinically important pathogens, including MRSA, VRE, MCRPEC and tet(X)-positive Gram-negative bacteria. Mechanistic studies showed that benzydamine dissipated membrane potential (▵Ψ) in both Gram-positive and Gram-negative bacteria, which in turn upregulated the transmembrane proton gradient (▵pH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system-mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline-benzydamine combination against different metabolic states of bacteria involve persister cells. As a proof-of-concept, the in vivo efficacy of this drug combination was evidenced in multiple animal infection models. These findings indicate that benzydamine is a potential tetracyclines adjuvant to address life-threatening infections by MDR bacteria.

Comparison of fluconazole and amphotericin B in prophylaxis of experimental Candida endocarditis caused by non-C. albicans strains.

1996 ◽  
Vol 40 (2) ◽  
pp. 494-496 ◽  
Author(s):  
A S Bayer ◽  
M D Witt ◽  
E Kim ◽  
M A Ghannoum
Keyword(s):  
Body Weight ◽  
Single Dose ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Dose Regimen ◽  
Prophylactic Efficacy ◽  
Endocarditis Prophylaxis ◽  
Prophylactic Dose ◽  
Candida Strain ◽  
Fungistatic Agent

Amphotericin B (1 mg/kg of body weight, intravenous) and fluconazole (100 mg/kg, intraperitoneal) were compared in the prophylaxis of experimental Candida endocarditis caused by drug-susceptible, non-C. albicans strains C. tropicalis and C. parapsilosis. Neither antifungal agent was effective at preventing endocarditis due to either Candida strain when either agent was administered in a single-dose regimen (1 h prior to fungal challenge); the prophylactic efficacy of both agents increased substantially when a second prophylactic dose was given (24 h postchallenge). The excellent prophylactic efficacy of fluconazole, a fungistatic agent, underscores the importance of microbistatic mechanisms in endocarditis prophylaxis.

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