A Review of Newly Approved Antibiotic Treatment for Community-Acquired Bacterial Pneumonia: Lefamulin

2020 ◽  
Vol 35 (8) ◽  
pp. 349-354
Author(s):  
Hongmei Wang ◽  
Creaque V. Charles
Keyword(s):  
Hepatic Impairment ◽  
Bacterial Pneumonia ◽  
Dosage Adjustment ◽  
Standard Of Care ◽  
Cross Resistance ◽  
Respiratory Pathogens ◽  
Severe Hepatic Impairment ◽  
Current Standard ◽  
Oral Formulations ◽  
Bacterial Protein Synthesis

Lefamulin is a novel systemic, semi-synthetic pleuromutilin class of antimicrobials that has been shown to be effective against common respiratory pathogens associated with community-acquired bacterial pneumonia (CABP). CABP, a common infection among older people, leads to an increase in hospitalizations and mortality. Therefore, the use of lefamulin could be beneficial for CABP treatment in patients who are 65 years of age or older.<br/> The Food and Drug Administration (FDA) approved lefamulin for the treatment of CABP, which is available in both intravenous and oral formulations. This medication offers the benefit of not having any cross-resistance to other antibiotics and is highly concentrated in lung tissues. Lefamulin is unique because it has an induced-fit mechanism of action which inhibits bacterial protein synthesis. The clinical efficacy of lefamulin has demonstrated noninferiority to current standard-of-care for CABP, and patients, generally, have tolerated it well in clinical trials.<br/> Lefamulin does not require dosage adjustment in renal impairment. However, the drug does requires dosage adjustment in severe hepatic impairment, based on Child-Pugh scores and clinical consideration in patients with severe hepatic impairment based on Child-Pugh scores. Though the benefit of adding lefamulin to a formulary is still in question; its potential to be a beneficial treatment for CABP is encouraging.

A Review of Newly Approved Antibiotic Treatment for Community-Acquired Bacterial Pneumonia: Lefamulin

2020 ◽  
Vol 35 (8) ◽  
pp. 349-354
Author(s):  
Hongmei Wang ◽  
Creaque V. Charles
Keyword(s):  
Hepatic Impairment ◽  
Bacterial Pneumonia ◽  
Dosage Adjustment ◽  
Standard Of Care ◽  
Cross Resistance ◽  
Respiratory Pathogens ◽  
Severe Hepatic Impairment ◽  
Current Standard ◽  
Oral Formulations ◽  
Bacterial Protein Synthesis

Lefamulin is a novel systemic, semi-synthetic pleuromutilin class of antimicrobials that has been shown to be effective against common respiratory pathogens associated with community-acquired bacterial pneumonia (CABP). CABP, a common infection among older people, leads to an increase in hospitalizations and mortality. Therefore, the use of lefamulin could be beneficial for CABP treatment in patients who are 65 years of age or older.<br/> The Food and Drug Administration (FDA) approved lefamulin for the treatment of CABP, which is available in both intravenous and oral formulations. This medication offers the benefit of not having any cross-resistance to other antibiotics and is highly concentrated in lung tissues. Lefamulin is unique because it has an induced-fit mechanism of action which inhibits bacterial protein synthesis. The clinical efficacy of lefamulin has demonstrated noninferiority to current standard-of-care for CABP, and patients, generally, have tolerated it well in clinical trials.<br/> Lefamulin does not require dosage adjustment in renal impairment. However, the drug does requires dosage adjustment in severe hepatic impairment, based on Child-Pugh scores and clinical consideration in patients with severe hepatic impairment based on Child-Pugh scores. Though the benefit of adding lefamulin to a formulary is still in question; its potential to be a beneficial treatment for CABP is encouraging.

scholarly journals Preclinical Characterization of GSK2336805, a Novel Inhibitor of Hepatitis C Virus Replication That Selects for Resistance in NS5A

2013 ◽  
Vol 58 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Jill Walker ◽  
Renae Crosby ◽  
Amy Wang ◽  
Ermias Woldu ◽  
Jessica Vamathevan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Standard Of Care ◽  
Cross Resistance ◽  
Current Standard ◽  
Dna Viruses ◽  
Consensus Sequences ◽  
Genotype 1A ◽  
Rna And Dna

ABSTRACTGSK2336805 is an inhibitor of hepatitis C virus (HCV) with picomolar activity on the standard genotype 1a, 1b, and 2a subgenomic replicons and exhibits a modest serum shift. GSK2336805 was not active on 22 RNA and DNA viruses that were profiled. We have identified changes in the N-terminal region of NS5A that cause a decrease in the activity of GSK2336805. These mutations in the genotype 1b replicon showed modest shifts in compound activity (<13-fold), while mutations identified in the genotype 1a replicon had a more dramatic impact on potency. GSK2336805 retained activity on chimeric replicons containing NS5A patient sequences from genotype 1 and patient and consensus sequences for genotypes 4 and 5 and part of genotype 6. Combination and cross-resistance studies demonstrated that GSK2336805 could be used as a component of a multidrug HCV regimen either with the current standard of care or in combination with compounds with different mechanisms of action that are still progressing through clinical development.

Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

2020 ◽  
Vol 26 (28) ◽  
pp. 3468-3496
Author(s):  
Emilio Rodrigo ◽  
Marcio F. Chedid ◽  
David San Segundo ◽  
Juan C.R. San Millán ◽  
Marcos López-Hoyos
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Rescue Therapy ◽  
Standard Of Care ◽  
Rejection Rate ◽  
New Drugs ◽  
High Dose ◽  
Current Standard ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

scholarly journals Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 864
Author(s):  
Christopher L. Cioffi
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Therapeutic Potential ◽  
Opioid Analgesic ◽  
Critical Role ◽  
Analgesic Efficacy ◽  
Standard Of Care ◽  
Current Standard ◽  
Glycine Transporters ◽  
Pathological Pain

Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread interest as a potential class of novel analgesics. The GlyTs are Na+/Cl−-dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a possible mechanism by which to increase spinal extracellular glycine concentrations and enhance GlyR-mediated inhibitory neurotransmission in the dorsal horn. Various inhibitors of both GlyT1 and GlyT2 have demonstrated broad analgesic efficacy in several preclinical models of acute and chronic pain, providing promise for the approach to deliver a first-in-class non-opioid analgesic with a mechanism of action differentiated from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances reported for the field, and discuss the key challenges associated with the development of a GlyT inhibitor into a safe and effective agent to treat pain.

scholarly journals Updated Insights on EGFR Signaling Pathways in Glioma

2021 ◽  
Vol 22 (2) ◽  
pp. 587
Author(s):  
Alexandru Oprita ◽  
Stefania-Carina Baloi ◽  
Georgiana-Adeline Staicu ◽  
Oana Alexandru ◽  
Daniela Elise Tache ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Egfr Signaling ◽  
Current Standard ◽  
Egfr Amplification ◽  
Epidermal Growth ◽  
New Diagnosis ◽  
Clear Clinical Benefit

Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.

A comparison between 25-gauge and 22-gauge Franseen needles for endoscopic ultrasound-guided sampling of pancreatic and peripancreatic masses: a randomized non-inferiority study

Endoscopy ◽  
2021 ◽  
Author(s):  
Dongwook Oh ◽  
Joonseog Kong ◽  
Sung Woo Ko ◽  
Seung-Mo Hong ◽  
Hoonsub So ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Endoscopic Ultrasound ◽  
Care Center ◽  
Tertiary Care ◽  
Standard Of Care ◽  
Fine Needle Biopsy ◽  
Needle Aspiration ◽  
Adverse Event Rate ◽  
Current Standard ◽  
Fine Needle

Abstract Background Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) are the current standard of care for sampling pancreatic and peripancreatic masses. Recently, a 22G EUS-FNB needle with Franseen geometry was developed, and this device was also introduced in a 25G platform. We compared the performance of the 25G and 22G Franseen needles for EUS-guided sampling of pancreatic and peripancreatic solid masses. Methods We conducted a parallel-group randomized non-inferiority trial at a tertiary-care center from November 2018 to May 2019. The primary outcome was the quality of the histologic core assessed using the Gerke score. The optimal histologic core is indicated by a Gerke score of 4 or 5, which enables optimal histologic interpretation. The overall diagnostic accuracy and adverse event rate were also evaluated. Results 140 patients were enrolled and randomized (1:1) to the 25G and 22G groups. Tissue acquisition by EUS-FNB was successful in all patients. The optimal histologic core procurement rate was 87.1 % (61/70) for the 25G needle vs. 97.1 % (68/70) for the 22G; difference −10 % (95 % confidence interval −17.35 % to −2.65 %). High quality specimens were more frequently obtained in the 22G group than in the 25G group (70.0 % [49/70] vs. 28.6 % [20 /70], respectively; P < 0.001). The overall diagnostic accuracy did not differ between the groups (97.4 % for 25G vs. 100 % for 22G). Conclusions The 25G Franseen needle was inferior to the 22G needle in histologic core procurement. Therefore, for cases in which tissue architecture is pivotal for diagnosis, a 22G needle, which procures relatively higher quality specimens than the 25G needle, should be used.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

scholarly journals De-Escalation of Therapy for Patients with Early-Stage Squamous Cell Carcinoma of the Anus

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2099
Author(s):  
Eric Miller ◽  
Jose Bazan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Intensity Modulated Radiation Therapy ◽  
Late Toxicity ◽  
Standard Of Care ◽  
The Elderly ◽  
Current Standard

The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly in the elderly, with increased mortality in this age group. While the current standard of care for localized SCCA remains chemoradiation (CRT), completion of this treatment can be challenging with risks for severe acute and late toxicity. It remains unclear if full course CRT is required for the management of early-stage SCCA or if de-escalation of treatment is possible without compromising patient outcomes. Alternative therapies include radiation therapy alone or local excision for appropriate patients. Modifying standard CRT may also reduce toxicity including the routine use of intensity-modulated radiation therapy for treatment delivery, modification of treatment volumes, and selection and dosing of concurrent systemic therapy agents. Finally, we provide an overview of currently accruing prospective trials focused on defining the role of de-escalation of therapy in patients with early-stage SCCA.

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