scholarly journals 415: Antimicrobial resistance—Modeling of prolonged treatment in vitro

2021 ◽  
Vol 20 ◽  
pp. S195
Author(s):  
E. Garcia ◽  
M. Muhlebach ◽  
R. Sharma ◽  
A. Khoei ◽  
G. Rao
2020 ◽  
Vol 15 ◽  
Author(s):  
Manasi M. Chogale ◽  
Sujay S. Gaikwad ◽  
Savita P. Kulkarni ◽  
Vandana B. Patravale

Background: Tuberculosis (TB) continues to be among the leading causes for high mortality among developing countries. Though a seemingly effective treatment regimen against TB is in place, there has been no significant improvement in the therapeutic rates. This is primarily owing to the high drug doses, their associated sideeffects, and prolonged treatment regimen. Discontinuation of therapy due to the severe side effects of the drugs results in the progression of the infection to the more severe drug-resistant TB. Objectives: Reformulation of the current existing anti TB drugs into more efficient dosage forms could be an ideal way out. Nanoformulations have been known to mitigate the side effects of toxic, high-dose drugs. Hence, the current research work involves the formulation of Isoniazid (INH; a first-line anti TB molecule) loaded chitosan nanoparticles for pulmonary administration. Methods: INH loaded chitosan nanoparticles were prepared by ionic gelation method using an anionic crosslinker. Drugexcipient compatibility was evaluated using DSC and FT-IR. The formulation was optimized on the principles of Qualityby-Design using a full factorial design. Results: The obtained nanoparticles were spherical in shape having an average size of 620±10.97 nm and zeta potential +16.87±0.79 mV. Solid state characterization revealed partial encapsulation and amorphization of INH into the nanoparticulate system. In vitro release study confirmed an extended release of INH from the system. In vitro cell line based safety and efficacy studies revealed satisfactory results. Conclusion: The developed nanosystem is thus an efficient approach for antitubercular therapy.


Author(s):  
Ewa A. Burian ◽  
Lubna Sabah ◽  
Klaus Kirketerp-Møller ◽  
Elin Ibstedt ◽  
Magnus M. Fazli ◽  
...  

Acute wounds may require cleansing to reduce the risk of infection. Stabilized hypochlorous acid in acetic buffer (HOCl + buffer) is a novel wound irrigation solution with antimicrobial properties. We performed a first-in-man, prospective, open-label pilot study to document preliminary safety and performance in the treatment of acute wounds. The study enrolled 12 subjects scheduled for a split-skin graft transplantation, where the donor site was used as a model of an acute wound. The treatment time was 75 s, given on 6 occasions. A total of 7 adverse events were regarded as related to the treatment; all registered as pain during the procedure for 2 subjects. One subject had a wound infection at the donor site. The mean colony-forming unit (CFU) decreased by 41% after the treatment, and the mean epithelialization was 96% on both days 14 (standard deviation [SD] 8%) and 21 (SD 10%). The study provides preliminary support for the safety, well-tolerance, and efficacy of HOCl + buffer for acute wounds. The pain was frequent although resolved quickly. Excellent wound healing and satisfying antimicrobial properties were observed. A subsequent in vitro biofilm study also indicated good antimicrobial activity against Pseudomonas aeruginosa with a 96% mean reduction of CFU, when used for a treatment duration of 15 min ( P < .0001), and a 50% decrease for Staphylococcus aureus ( P = .1010). Future larger studies are needed to evaluate the safety and performance of HOCl + buffer in acute wounds, including the promising antimicrobial effect by prolonged treatment on bacterial biofilms.


Author(s):  
Muhammad Faris Adrianto ◽  
Febri Annuryanti ◽  
Clive G. Wilson ◽  
Ravi Sheshala ◽  
Raghu Raj Singh Thakur

AbstractThe delivery of drugs to the posterior segment of the eye remains a tremendously difficult task. Prolonged treatment in conventional intravitreal therapy requires injections that are administered frequently due to the rapid clearance of the drug molecules. As an alternative, intraocular implants can offer drug release for long-term therapy. However, one of the several challenges in developing intraocular implants is selecting an appropriate in vitro dissolution testing model. In order to determine the efficacy of ocular implants in drug release, multiple in vitro test models were emerging. While these in vitro models may be used to analyse drug release profiles, the findings may not predict in vivo retinal drug exposure as this is influenced by metabolic and physiological factors. This review considers various types of in vitro test methods used to test drug release of ocular implants. Importantly, it discusses the challenges and factors that must be considered in the development and testing of the implants in an in vitro setup. Graphical abstract


Microbiology ◽  
2021 ◽  
Vol 167 (11) ◽  
Author(s):  
Alberto Gonçalves Evangelista ◽  
Jessica Audrey Feijó Corrêa ◽  
João Vitor Garcia dos Santos ◽  
Eduardo Henrique Custódio Matté ◽  
Mônica Moura Milek ◽  
...  

The genus Salmonella is closely associated with foodborne outbreaks and animal diseases, and reports of antimicrobial resistance in Salmonella species are frequent. Several alternatives have been developed to control this pathogen, such as cell-free supernatants (CFS). Our objective here was to evaluate the use of lactic acid bacteria (LAB) CFS against Salmonella in vitro. Seventeen strains of LAB were used to produce CFS, and their antimicrobial activity was screened towards six strains of Salmonella . In addition, CFS were also pH-neutralized and/or boiled. Those with the best results were lyophilized. MICs of lyophilized CFS were 11.25–22.5 g l–1. Freeze-dried CFS were also used to supplement swine and poultry feed (11.25 g kg–1) and in vitro simulated digestion of both species was performed, with Salmonella contamination of 5×106 and 2×105 c.f.u. g−1 of swine and poultry feed, respectively. In the antimicrobial screening, all acidic CFS were able to inhibit the growth of Salmonella . After pH neutralization, Lactobacillus acidophilus Llorente, Limosilactobacillus fermentum CCT 1629, Lactiplantibacillus plantarum PUCPR44, Limosilactobacillus reuteri BioGaia, Lacticaseibacillus rhamnosus ATCC 7469 and Pediococcus pentosaceus UM116 CFS were the only strains that partially maintained their antimicrobial activity and, therefore, were chosen for lyophilization. In the simulated swine digestion, Salmonella counts were reduced ≥1.78 log c.f.u. g–1 in the digesta containing either of the CFS. In the chicken simulation, a significant reduction was obtained with all CFS used (average reduction of 0.59±0.01 log c.f.u. ml–1). In general, the lyophilized CFS of L. fermentum CCT 1629, L. rhamnosus ATCC 7469 and L. acidophilus Llorente presented better antimicrobial activity. In conclusion, CFS show potential as feed additives to control Salmonella in animal production and may be an alternative to the use of antibiotics, minimizing problems related to antimicrobial resistance.


2021 ◽  
Vol 2 ◽  
Author(s):  
Anushree Vijaykumar ◽  
Mina Mina

Wnt/β-catenin signaling is known to play essential roles in odontoblast differentiation and reparative dentin formation. Various Wnt activators including LiCl have been increasingly studied for their effectiveness to induce repair of the dentin-pulp complex. LiCl is a simple salt thought to activate Wnt/β-catenin signaling by inhibiting GSK3β. Previous in vitro and in vivo studies showed that LiCl increased odontoblast differentiation and enhanced reparative dentin formation. However, the underlying molecular and cellular mechanisms by which LiCl regulates odontoblast and osteoblast differentiation during reparative dentinogenesis are not well-understood. Our in vitro studies show that exposure of early dental pulp progenitors to LiCl increased the survival and the pool of αSMA+ progenitors, leading to enhanced odontoblast and osteoblast differentiation. The positive effects of LiCl in the differentiation of osteoblasts and odontoblasts from αSMA+ progenitors are mediated by Wnt/β-catenin signaling. Our results also showed that continuous and late exposure of dental pulp cells to LiCl increased the expression of odontoblast markers through Wnt/β-catenin signaling, and the number of odontoblasts expressing DMP1-Cherry and DSPP-Cerulean transgenes. However, unlike the early treatment, both continuous and late treatments decreased the expression of Bsp and the expression of BSP-GFPtpz transgene. These observations suggest that prolonged treatment with LiCl in more mature cells of the dental pulp has an inhibitory effect on osteoblast differentiation. The inhibitory effects of LiCl on osteogenesis and Bsp were not mediated through Wnt/β-catenin signaling. These observations suggest that the effects of LiCl, and GSK3β antagonists on reparative dentinogenesis involve multiple pathways and are not specific to Wnt/β-catenin signaling.


2018 ◽  
Vol 146 (4) ◽  
pp. 409-422 ◽  
Author(s):  
D. Mueller-Doblies ◽  
K. C. R. Speed ◽  
S. Kidd ◽  
R. H. Davies

AbstractIn this retrospective study, we describe and analyse Salmonella data from four livestock species in Great Britain between 1983 and 2014, focusing on Salmonella Typhimurium. A total of 96 044 Salmonella isolates were obtained during the study period. S. Typhimurium was the predominant serovar isolated from cattle and pigs and represented 40.7% (18 455/45 336) and 58.3% (4495/7709) of isolates from these species respectively, while it only accounted for 6.7% (2114/31 492) of chicken isolates and 8.1% (926/11 507) of turkey isolates. Over the study period, DT104 was the most common phage type in all four species; however, DT104 peaked in occurrence between 1995 and 1999, but is currently rare.Monophasic strains of S. Typhimurium represented less than 3% of all Salmonella isolates in cattle and chickens in 2014, but accounted for 10.4% of all turkey isolates and 39.0% of all pig isolates in the same year.Salmonella isolates were tested for their in vitro susceptibility to 16 antimicrobials. Antimicrobial resistance of S. Typhimurium isolates is largely influenced by the dominance of specific phage types at a certain time, which are commonly associated with particular resistance patterns. Changes in resistance patterns over time were analysed and compared between species.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S488-S489
Author(s):  
Joy Yong ◽  
Ka Lip Chew ◽  
Paul Tambyah

Abstract Background Infections caused by the multi-drug-resistant Mycobacterium abscessus complex (MabsC) are challenging to treat and often require multiple antimicrobials for a prolonged treatment course and still have poor outcomes. Clofazimine, an oral anti-leprosy drug, has demonstrated good in vitro susceptibility and is being increasingly employed in treatment regimens for MabsC infections. We performed a drug-use-evaluation of clofazimine in the treatment of MabsC infections. Methods A retrospective review was performed for all patients with MabsC infections treated with clofazimine-containing regimens from January 2014 to June 2017. Results Twenty-nine patients were included. Twelve patients had pulmonary MabsC infections and seventeen had extrapulmonary infections. All isolates had clofazimine minimum-inhibitory-concentration of ≤0.5 mg/L as tested by broth microdilution. Clofazimine was prescribed at initiation of therapy in 31.0% (9/29), as a companion drug during maintenance therapy after initial intravenous therapy in 44.8% (13/29) and as part of salvage therapy due to disease progression or drug intolerance in 24.1% (7/29) of patients. Dosing of clofazimine for the pediatric patients was prescribed at 1–2 mg/kg/day while the adult patients received a range of 50–200 mg/day. Clofazimine was given for a median duration of 148.5 days (range: 14–1212) and most commonly in combination with clarithromycin (82.8%), amikacin (58.6%), and cefoxitin (24.1%). Twelve patients had documented adverse reactions attributable to clofazimine: skin hyperpigmentation (66.7%), abnormal liver function tests (16.7%), and gastrointestinal disturbance (16.7%). Table 1 describes the patients who had clofazimine ceased due to an adverse effect. Nine patients with pulmonary MabsC infections and 16 with extrapulmonary MabsC infections had documented improvement in symptoms. Conclusion Clofazimine as a companion drug in the treatment of MabsC infections was reasonably tolerated over a prolonged period of time. Its availability as an oral active agent makes it an attractive alternative to IV companion drugs and potentially improves compliance to the protracted treatment courses for patients with MabsC infections. Disclosures All authors: No reported disclosures.


Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2661-2667
Author(s):  
J Mysliwietz ◽  
S Thierfelder

Abstract A hamster antimouse CD3 monoclonal antibody (MoAb) opened the way to experimental studies on the suppression of allograft rejection and cytokine-related morbidity after treatment with antibodies modulating the CD3/T-cell receptor complex (CD3/TCR). Because earlier attempts to suppress graft-versus-host disease (GVHD) in patients by in vitro treatment of donor marrow with anti-CD3 MoAb had remained inconclusive, we used a rat IgG2b antimouse CD3 MoAb (17A2) with fewer side effects to analyze suppression of GVHD in the mouse model. Detailed phenotyping of blood, spleen, and lymphnode T cells after the injection of 400 micrograms 17A2 in C57BL/6 mice showed 60% CD3 downmodulation and 50% T- cell depletion for spleen cells. Injection of these spleen cells, together with bone marrow cells, in fully mismatched preirradiated CBA mice delayed GVHD by only 6 days. Ex vivo treatment of donor cells with 17A2 was not effective. In contrast, conditioning of marrow recipients with a single injection of 17A2 delayed 50% GVHD mortality by 100 days and prevented GVHD altogether after prolonged treatment, with survivors showing complete chimerism and specific transplantation tolerance. This difference in antibody effect contrasts with earlier experiences with nonmodulating but more strongly T-cell-depleting MoAbs of the same isotype, which prevent GVHD no matter whether applied in vitro or injected into donor or recipient mice. Our data indicate that CD3/TCR reexpression in marrow recipients with no circulating 17A2 is the reason why ex vivo donor cell treatment with anti-CD3 MoAb is comparatively ineffective. Our data, which allow separate evaluation of cell-depleting and cell-modulating antibody activity, help to explain previous clinical failure to suppress GVHD and provide evidence in favor of conditioning the marrow recipient with anti-CD3 MoAb as a therapeutic alternative.


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