pentamidine oral (VLX103) / Odan Labs - LARVOL DELTA

[VIRTUAL] EPIDEMIOLOGY, PREDICTORS OF MORTALITY AND ROLE OF PROPHYLAXIS FOR PNEUMOCYSTITIS JIROVECI PNEUMONIA AMONG RHEUMATIC PATIENTS: A TERRITORY-WIDE STUDY (EULAR 2021) - "Prophylaxis was defined as prescription of a prophylactic dose of co-trimoxazole for at least 2 weeks and/or inhaled pentamidine. PJP is an uncommon but important infection in rheumatic patients associated with significant mortality. PJP prophylaxis is effective and should be considered in patients with SSc, AAV and IMM, especially in those receiving a steroid dose above P15."

Clinical • Ankylosing Spondylitis • Fibrosis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Myositis • Pneumonia • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Seronegative Spondyloarthropathies • Spondylarthritis • Systemic Lupus Erythematosus • Systemic Sclerosis • Vasculitis

Single-dose pentamidine substantially reduces viability of trypanosomes in human east African trypanosomiasis. (PubMed, J Travel Med) - No abstract available

Journal • Narcolepsy • Sleep Disorder

Comparative assessment of interventions for treating cutaneous leishmaniasis: A network meta-analysis of randomized clinical trials. (PubMed, Acta Trop) - "We observed several interventions to be effective for treating cutaneous leishmaniasis. However, greater caution is required in interpreting the results as the estimates are likely to change with the advent of results from future studies."

Clinical • Journal • Retrospective data • Dermatology • Infectious Disease

S100P Interacts with p53 while Pentamidine Inhibits This Interaction. (PubMed, Biomolecules) - "In addition, we showed that pentamidine treatment of ZR-75-1 breast cancer cells resulted in reduced proliferation and increased p53 and p21 protein levels, indicating that pentamidine is an effective antagonist that interferes with the S100P-p53 interaction, leading to re-activation of the p53-21 pathway and inhibition of cancer cell proliferation. Collectively, our findings suggest that blocking the association between S100P and p53 by pentamidine will prevent cancer progression and, therefore, provide a new avenue for cancer therapy by targeting the S100P-p53 interaction."

Journal • Breast Cancer • Oncology • Solid Tumor • CDKN1A • S100P

"If I cant not use TMP-SMX I go to atovaquone, not particular reason but I dislike dapsone and do not start me on pentamidine" (@IdVilchez)

"Now I want to rename our treatment in holding area where we give the monthly inhaled pentamidine doses for patients on the drug " Pentamidine puff lounge" :)." (@Boghuma)

Clinical

Efficacy and safety of Pentamidine isethionate for tegumentary and visceral human leishmaniasis: a systematic review. (PubMed, J Travel Med) - "Pentamidine isethionate is associated with a similar cure rate of the first line antileishmanial drugs. Severe and irreversible adverse effect appear to be rare. The drug may still have a role in the treatment of any form of human leishmaniasis when the first-line option has failed or in patients who cannot tolerate other drugs also in the context of travellers or migrants. In difficult cases, the drug can also be considered as a component of a combination treatment regimen."

Clinical • Journal • Review • Atrial Fibrillation • Cardiovascular • Dermatology • Diabetes • Infectious Disease • Metabolic Disorders

Blockers of the SARS-CoV-2 3a Channel Identified by Targeted Drug Repurposing. (PubMed, Viruses) - "To that end, using three bacteria-based assays, we screened a library of 2839 approved-for-human-use drugs and identified the following potential channel-blockers: Capreomycin, Pentamidine, Spectinomycin, Kasugamycin, Plerixafor, Flumatinib, Litronesib, Darapladib, Floxuridine and Fludarabine. The stage is now set for examining the activity of these compounds in detailed electrophysiological studies and their impact on the whole virus with appropriate biosafety measures."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Pneumocystis jirovecii: a review with a focus on prevention and treatment. (PubMed, Expert Opin Pharmacother) - "First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole (TMP-SMX), though intolerance or allergy, and rarely treatment failure, may necessitate alternate therapeutics, such as dapsone, pentamidine, atovaquone, clindamycin, primaquine and most recently, echinocandins as adjunctive therapy. Second-line therapies may be better tolerated, but often sacrifice efficacy. Echinocandins show some promise for new combination therapies; however, further studies are needed to define optimal antimicrobial therapy for PJP as well as the role of corticosteroids in those without HIV."

Journal • Review • Allergy • Human Immunodeficiency Virus • Immunology • Infectious Disease • Oncology • Pneumonia • Respiratory Diseases • Rheumatology • Transplantation

Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug. (PubMed, PLoS Negl Trop Dis) - "These results are relevant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine."

Journal • Narcolepsy • Sleep Disorder

Primaquine plus clindamycin as a promising salvage therapy for Pneumocystis jirovecii pneumonia: A retrospective analysis in Japanese patients. (PubMed, J Infect Chemother) - "Prior to the treatment with PQ-CLDM, most of the patients had been treated with trimethoprim-sulfamethoxazole first, all of which being followed by pentamidine and/or atovaquone treatment. Currently in Japan, both PQ and CLDM are licensed drugs but neither of them is approved for treatment of PCP. Considering the potentially fatal nature of PCP, approval of PQ-CLDM for treating this illness should be urged."

Journal • Retrospective data • Hematological Disorders • Hepatology • Infectious Disease • Liver Failure • Malaria • Pneumonia • Respiratory Diseases

Estimation of treatment and prognostic factors of pneumocystis pneumonia in patients with connective tissue diseases. (PubMed, RMD Open) - "Older age and concomitant ILD were poor prognostic factors for CTD-PCP. ST was a reasonable first-line therapy in patients with CTD-PCP, and patients with inadequate response to ST treated with atovaquone tended to have a better prognosis than those treated with pentamidine."

Biomarker • Clinical • Journal • Immunology • Infectious Disease • Inflammation • Interstitial Lung Disease • Pneumonia • Respiratory Diseases • Rheumatology

Deposition of pentamidine analogues in the human body - spectroscopic and computational approaches. (PubMed, Eur J Pharm Sci) - "The studied analogues display very marked activity against Pneumocystis carinii without cytotoxicity that inspired us to perform an in silico analysis of their mode of action based on the hypothesis that the small DNA groove of rich in adenine-thymine pairs is their molecular target. These studies allowed us to classify them as very promising lead molecules."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Pentamidine enhances photosensitization of Acinetobacter baumannii using diode lasers with emission of light at wavelength of ʎ=405 nm and ʎ=635nm. (PubMed, Photodiagnosis Photodyn Ther) - "In the case of laser light of 635 nm, the lethal effect with 5-ALA was attained with energy fluence of 51 J cm (with pentamidine) and 102 J cm (without pentamidine). The possible roles of pentamidine in enhancing photodynamic inactivation of A. baumannii have been discussed."

Journal

Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes. (PubMed, Med Chem) - "The promising antileishmanial activity of three AGH's and three TSC's was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments."

Journal • Infectious Disease

"why don't many centers use IV pentamidine more often?" (@EagleMyeloma)

Targeting the transmembrane domain 5 of latent membrane protein 1 using small molecule modulators. (PubMed, Eur J Med Chem) - "In this study, the interactions of the transmembrane domain 5 (TMD-5) of latent membrane protein 1 (LMP-1) of Epstein-Barr virus (EBV) were disrupted by pentamidine derivatives to curb the committed step of EBV infection...This study explicitly demonstrated that the interaction of small molecule with lipid should be considered alongside interaction with the protein target when designing small molecules targeting the PPIs of TMDs. In all, this study provides proof of concept for the rational design of small molecules targeting transmembrane PPIs."

Journal • Epstein-Barr Virus Infection • Infectious Disease

"Also I hate to say you could use inhaled pentamidine @DrNeilStone @FranciscoMarty_ @transplantID @dktransplant @VBajrovicMD @m_pereiramd @FaiqaCheemaMD @Bweikert3 @maricar_malinis @Doctor_Yiannis @ChongPearlie @TxID_Edu @DocSaimaAslam @MarionHemmersb1 @RicardoLaHozMD" (@IdVilchez)

Transplantation

"If they let you - it'll always be bactrim but they won't let us in the first 100 days ...next would be pentamidine or atovaquone" (@transplantID)

Superficial Thrombophlebitis From Intravenous Pentamidine in Hematopoietic Cell Transplantation Recipient. (PubMed, Mayo Clin Proc) - No abstract available

Journal • Transplantation

Susceptibility to paromomycin in clinical isolates and reference strains of Leishmania species responsible for tegumentary leishmaniasis in Brazil. (PubMed, Acta Trop) - "Treatment of tegumentary leishmaniasis in Brazil is limited to pentavalent antimonial, amphotericin B and pentamidine...Although never exposed to paromomycin, we found variable susceptibility among these isolates and reference strains in promastigotes and intracellular amastigotes, with the drug being more active in the amastigote form of the parasite. This study provides a preclinical dataset that is useful for the evaluation of paromomycin in the treatment of tegumentary leishmaniasis caused by species that are endemic in Brazil."

Clinical • Journal • Dermatology • Infectious Disease

The Role of nitro (NO2-), chloro (Cl), and fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds. (PubMed, Curr Drug Targets) - "Glucantime, pentamidine and miltefosine are commonly used to treat leishmaniasis, whereas nifurtimox, benznidazole are current treatments for Chagas disease...Pharmacokinetic studies, and the mechanism of action of the promising compounds need to be explored. The use of new catalysts and chemical transformation can afford unexplored halogenated compounds with improved antileishmanial and antitrypanosomal activity."

Journal • CNS Disorders • Infectious Disease

[VIRTUAL] Studies on the in vitro effects of pentamidine isethionate on blood coagulation and blood clot fibrinolysis (ASHP 2020) - "Overall, this study provides quantitative mechanistic insights into the in vitro effects of pentamidine isethionate on coagulation and fibrinolysis. The study reveals that those effects are potentially attributed to the disruption of the proteolytic activity of factor Xa and plasmin. These results can be taken into consideration while prescribing the antiprotozoal drug to patients with blood disorders."

Preclinical • Hematological Disorders • Immunology • Inflammation • Thrombosis • ELANE • F13A1

"Can I add some IV Pentamidine in the mix?" (@DrJ_NoRelation)

In Vitro Activity of Pentamidine Alone and in Combination with Antibiotics against Multidrug-Resistant Clinical Pseudomonas aeruginosa Strains. (PubMed, Antibiotics (Basel)) - "The Minimum Inhibitory Concentration (MIC) was determined following standard protocols, and the results were interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints; however, the gentamicin activity was interpreted according to the Clinical and Laboratory Standards Institute (CLSI) recommendations...Pentamidine plus imipenem and meropenem were the combinations that showed synergistic activity against the most strains. At 1/2×MIC, pentamidine plus antibiotics were synergistic with all three analyzed strains. In summary, pentamidine in combination with antibiotics showed in vitro synergy against multidrug-resistant P. aeruginosa clinical strains, which suggests its possible use as adjuvant to antibiotics for the therapy of infections from MDR P. aeruginosa."

Combination therapy • Journal • Infectious Disease