Delving into the Latest Updates on PATH Drug Solutions with Synapse

Overview

Oral cephalosporins and mecillinam are used to treat Shigella infections, but are compromised by extended-spectrum β-lactamases (ESBLs) and plasmid AmpC β-lactamases. Potential solutions include combining an oral or intravenous cephalosporin with a β-lactamase inhibitor (BLI) or using an oral penem. These strategies were examined using Escherichia coli transconjugants and clinical isolates with ESBLs or AmpC, as a proxy for shigellae. The Clinical and Laboratory Standards Institute agar dilution method was used with inocula of 10(4) and 10(6) colony-forming units/spot. ESBLs conferred resistance to the cephalosporins and mecillinam, at least at high inoculum, although: (i) ceftibuten was significantly compromised only by SHV and CTX-M-15 ESBLs, but not by TEM or CTX-M-9 and -14; (ii) cefdinir was little affected by TEM-type ESBLs, and mecillinam was little affected by CTX-M-9 group enzymes. The BLI clavulanic acid reduced the minimum inhibitory concentrations (MICs) of cephalosporins and mecillinam to ≤2 mg/L for ESBL-producers, even at high inocula; sulbactam in particular and tazobactam were less effective, especially against SHV types. Strains with AmpC were resistant to all cephalosporins±inhibitors, but mecillinam remained active (MIC=1 mg/L) against a strain with AmpC alone, whereas strains with TEM-1+AmpC were susceptible to mecillinam+clavulanic acid at ≤2 mg/L. Faropenem was active against all ESBL- and AmpC-producers at 4 mg/L, with little inoculum effect or inhibitor potentiation. In conclusion, cephalosporin+clavulanic acid combinations overcame ESBLs, with ceftibuten+clavulanic acid being particularly promising. Mecillinam+clavulanic acid and faropenem overcame both ESBLs and AmpC enzymes. Clinical utility will depend also on a drug's ability to reach intracellular shigellae in the intestinal epithelium and this deserves exploration for clavulanic acid and faropenem.

01 Jan 2011·Kala Azar in South Asia

Post-kala-azar Dermal Leishmaniasis: Facing the Challenge of Eliminating Kala-Azar from South Asia

Author: V. Ramesh ; Philippe Desjeux

Post-kala-azar dermal leishmaniasis (PKDL) is a cutaneous complication of visceral leishmaniasis (VL) which usually appears after treatment of a VL episode. The incidence of PKDL varies across countries and no up-to-date global estimate is available. Parasitological diagnostic tests show either low sensitivity or are difficult to decentralize in the field (e.g., polymerase chain reaction). Available treatments are long, costly, and frequently toxic. It is believed that PKDL has a multi-factorial and complex origin. It is widely accepted that persons with PKDL harbor Leishmania parasites in the skin and, therefore, act as reservoirs of infection in VL transmission, especially during interepidemic periods. PKDL poses a serious threat to the success of the VL elimination program in South Asia, and requires an immediate and focused strategy from the health authorities in charge of the national programs in India, Nepal, and Bangladesh. Control and research efforts are urgently needed to improve PKDL surveillance and case management in order to reduce delays in diagnosis and treatment and, hence, reduce morbidity and the risk of transmission.

01 Jan 2011·Global Clinical Trials

Background

Author: Richard Chin

Publisher Summary The chapter explains the One World Health by World Health Organization (WHO). Prior to the International Conference on Harmonization (ICH), which brought the Global Cooperation Group (GCP) regulations in line across the USA, Europe, and Japan, the varied regulatory requirements for each country made international trials very onerous. The WHO is not a regulatory agency, but for many countries that cannot afford a robust regulatory system or have not yet developed one, the WHO is a very important source of validation for drugs and vaccines. The original intent was to help agencies such as UNAIDS, UNICEF, UNFPA, and the World Bank determine which drugs were of high and dependable quality. The packaging and labeling must meet the specific WHO requirements as outlined in the WHO International Guideline on Packaging and Shipping of Vaccine. The WHO's target is to complete the initial review of the application within three months. If the application is adequate, the WHO will test samples of the vaccine and perform site visits. Once the evaluation is complete, the WHO informs the sponsor, the NRA, and the UN agencies. In emergency cases, a fast-track process expedites the process. After the prequalification, reassessments are performed, usually every two years. The reassessment usually requires submission of information detailing changes to the product or manufacturing, retesting of samples, and a site visit, among other actions. There is, in addition, continual random testing of vaccine samples, as well as monitoring of complaints about the vaccines from the field.

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News (Medical) associated with PATH Drug Solutions

27 Sep 2007

·www.biospace.com

Dr. Victoria Hale to Build Upon Institute for OneWorld Health's Success for Broader Global Health Impact; Founder Steps Down as CEO; Remains Chair of the Board of Directors

SAN FRANCISCO--(BUSINESS WIRE)--The Institute for OneWorld Health, the first nonprofit pharmaceutical company in the United States, announced today that its Founder, Chief Executive Officer, and Chair of the Board of Directors, Victoria G. Hale, Ph.D., will step down from the CEO position later this year, after serving in the role since OneWorld Health’s inception in 2000

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Pipeline

Pipeline Snapshot as of 23 Dec 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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