Pentamidine 300mg powder for solution for injection vials

Pentamidine is an alternative treatment for Pneumocystis pneumonia (PCP) in patients who are intolerant to sulfamethoxazole-trimethoprim; however, its use is limited by serious adverse effects, including glycemic fluctuations. Herein, we report a case in which intermittently scanned continuous glucose monitoring (isCGM) was used to monitor real-time glycemic fluctuations during pentamidine therapy, enabling successful completion of treatment. To contextualize this case, we also conducted a targeted literature review of pentamidine-induced glucose dysregulation. An 86-year-old Japanese man undergoing immunosuppressive therapy for rheumatoid arthritis was diagnosed with PCP and initially treated with sulfamethoxazole-trimethoprim. Because of suspected adverse effects of sulfamethoxazole-trimethoprim, the patient was switched to intravenous pentamidine as second-line therapy. Given the risks associated with advanced age, abnormal kidney function, and concomitant use of clopidogrel, an organic cation transporter 1 (OCT1) inhibitor that may affect pentamidine disposition, glycemic monitoring was initiated using isCGM. The patient experienced nocturnal hypoglycemia soon after initiating pentamidine treatment, which persisted after pentamidine discontinuation. He subsequently developed marked hyperglycemia associated with impaired endogenous insulin secretion, necessitating temporary regular insulin administration and sitagliptin combination therapy. His glycemic control gradually stabilized, and recovery of pancreatic β-cell function was confirmed by increased urinary C-peptide levels. In a literature review of 83 reports published between 1995 and 2025, only nine cases of pentamidine-associated dysglycemia were identified, and this was the only case that demonstrated biphasic glucose dysregulation with both hypoglycemia and hyperglycemia. This case demonstrates that biphasic glucose dysregulation associated with pentamidine (early hypoglycemia followed by delayed-onset hyperglycemia) can be captured using isCGM. Real-time glucose monitoring during pentamidine therapy enabled early intervention and safe completion of treatment. Glycemic monitoring using isCGM may be beneficial in patients receiving pentamidine, especially those with abnormal kidney function, older patients, or those receiving concomitant OCT1 inhibitor therapy.

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Several infectious pulmonary diseases affect the eye. An understanding of the association between infectious pulmonary and ocular diseases is pivotal to their successful management. We aimed to review the infections affecting both the lungs and the eye. The electronic database PubMed and the search engine Google Scholar were searched for relevant articles. Ocular tuberculosis (TB), usually not associated with clinical evidence of pulmonary TB, can affect almost all the ocular structures. Confirmation of the diagnosis of ocular TB requires demonstration of Mycobacterium tuberculosis in ocular fluids/tissues. Among the drugs used to treat TB, ethambutol, isoniazid, and linezolid may cause toxic optic neuropathy. The elderly, those with renal disease, diabetes mellitus, malnourished, alcoholics, and those who will receive ethambutol at doses greater than 15 mg/kg/day and for prolonged periods are at high risk of developing toxic optic neuropathy. These individuals should be referred to an ophthalmologist before initiating anti-tuberculous treatment for a baseline ophthalmic evaluation. Linezolid may also cause toxic retinal neuropathy. Rifampicin may cause yellowish-orange discoloration of tears and contact lenses. Adenovirus, coronavirus, influenza virus, respiratory syncytial virus, and rhinovirus exhibit both pulmonary and ocular tropism. Pneumocystis jirovecii choroiditis is rare and mainly seen when aerosolized pentamidine is used for pneumocystis pneumonia prophylaxis. Further research is needed to develop non-interventional strategies to diagnose ocular TB. Biomarkers for early detection of toxic optic neuropathy are a need of the hour. Genetic factors and mechanisms behind the development of ethambutol, isoniazid, and linezolid-induced toxic optic neuropathy need further study.

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(CL). Among the available agents, amphotericin B (AmB) and pentamidine (PTM) showed promising result against CL. However, monotherapy is associated with incidences of reoccurrence and resistance. Combination therapy is therefore recommended. Thin film hydration method was employed for amphotericin B-pentamidine loaded niosomes (AmB-PTM-NIO) preparation followed by their incorporation into chitosan gel. The optimization of AmB-PTM-NIO was done via Box Behnken Design method and in vitro and ex vivo analysis was performed. The optimized formulation indicated 226 nm particle size (PS) with spherical morphology, 0.173 polydispersity index (PDI), -36 mV zeta potential (ZP) and with entrapment efficiency (EE) of 91% (AmB) and 79% (PTM), respectively. The amphotericin B-pentamidine loaded niosomal gel (AmB-PTM-NIO-Gel) showed desirable characteristics including physicochemical properties, pH (5.1 ± 0.15), viscosity (31870 ± 25 cP), and gel spreadability (280 ± 26.46%). In vitro release of the AmB and PTM from AmB-PTM-NIO and AmB-PTM-NIO-Gel showed more prolonged release behavior as compared to their respective drug solution. Higher skin penetration, greater percentage inhibition and lower IC50 against the promastigotes shows that AmB-PTM-NIO has better antileishmanial activity. The obtained findings suggested that the developed AmB-PTM-NIO-Gel has excellent capability of permeation via skin layers, sustained release profile and augmented anti-leishmanial outcome of the incorporated drugs.

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The second-line antileishmanial compound pentamidine is administered intramuscularly or, preferably, by intravenous infusion, with its use limited by severe adverse effects, including diabetes, severe hypoglycemia, myocarditis and renal toxicity. We sought to test the potential of phospholipid vesicles to improve the patient compliance and efficacy of this drug for the treatment of leishmaniasis by means of aerosol therapy. The targeting to macrophages of pentamidine-loaded liposomes coated with chondroitin sulfate or heparin increased about twofold (up to ca. 90%) relative to noncoated liposomes. The encapsulation of pentamidine in liposomes ameliorated its activity on the amastigote and promastigote forms of Leishmania infantum and Leishmania pifanoi, and it significantly reduced cytotoxicity on human umbilical endothelial cells, for which the concentration inhibiting 50% of cell viability was 144.2 ± 12.7 µM for pentamidine-containing heparin-coated liposomes vs. 59.3 ± 4.9 µM for free pentamidine. The deposition of liposome dispersions after nebulization was evaluated with the Next Generation Impactor, which mimics human airways. Approximately 53% of total initial pentamidine in solution reached the deeper stages of the impactor, with a median aerodynamic diameter of ~2.8 µm, supporting a partial deposition on the lung alveoli. Upon loading pentamidine in phospholipid vesicles, its deposition in the deeper stages significantly increased up to ~68%, and the median aerodynamic diameter decreased to a range between 1.4 and 1.8 µm, suggesting a better aptitude to reach the deeper lung airways in higher amounts. In all, nebulization of liposome-encapsulated pentamidine improved the bioavailability of this neglected drug by a patient-friendly delivery route amenable to self-administration, paving the way for the treatment of leishmaniasis and other infections where pentamidine is active.

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Immunotherapy has emerged as an effective therapeutic approach to several cancer types. The reinvigoration of tumor-infiltrating lymphocyte-mediated immune responses via the blockade of immune checkpoint markers, such as program cell death-1 (PD-1) or its cognate ligand PD-L1, has been the basis for developing clinically effective anticancer therapies. We identified pentamidine, an FDA-approved antimicrobial agent, as a small-molecule antagonist of PD-L1. Pentamidine enhanced T-cell-mediated cytotoxicity against various cancer cells in vitro by increasing the secretion of IFN-γ, TNF-α, perforin, and granzyme B in the culture medium. Pentamidine promoted T-cell activation by blocking the PD-1/PD-L1 interaction. In vivo administration of pentamidine attenuated the tumor growth and prolonged the survival of tumor-bearing mice in PD-L1 humanized murine tumor cell allograft models. Histological analysis of tumor tissues showed an increased number of tumor-infiltrating lymphocytes in tissues derived from pentamidine-treated mice. In summary, our study suggests that pentamidine holds the potential to be repurposed as a novel PD-L1 antagonist that may overcome the limitations of monoclonal antibody therapy and can emerge as a small molecule cancer immunotherapy.

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against the problem carbapenem-resistant Enterobacteriaceae (CRE). Pentamidine is often used as an antiprotozoal and antifungal agent, and linezolid is a defensive Gram-positive bacteria (GPB) antimicrobial. Their combination expands the treatment range to GNB. Hence, the pentamidine-linezolid pair may be an effective treatment for complex infections that are mixed by GPB, GNB, and even fungi. In terms of mechanism, pentamidine inhibited the outer membranes, membrane potentials, and efflux pumps of CRE. This might be a universal mechanism by which pentamidine, as an adjuvant, potentiates other drugs, similar to linezolid, thereby having synergistic antibacterial effects on CRE.

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Combining pentamidine with Gram-positive-targeting antibiotics has been proven to be a promising strategy for treating infections from Gram-negative bacteria (GNB). However, which antibiotics pentamidine can and cannot synergize with and the reasons for the differences are unclear. This study aimed to identify the possible mechanisms for the differences in the synergy of pentamidine with rifampicin, linezolid, tetracycline, erythromycin, and vancomycin against GNB. Checkerboard assays were used to detect the synergy of pentamidine and the different antibiotics. To determine the mechanism of pentamidine, fluorescent labeling assays were used to measure membrane permeability, membrane potential, efflux pump activity, and reactive oxygen species (ROS); the LPS neutralization assay was used to evaluate the target site; and quantitative PCR was used to measure changes in efflux pump gene expression. Our results revealed that pentamidine strongly synergized with rifampicin, linezolid, and tetracycline and moderately synergized with erythromycin, but did not synergize with vancomycin against E. coli, K. pneumoniae, E. cloacae, and A. baumannii. Pentamidine increased the outer membrane permeability but did not demolish the outer and inner membranes, which exclusively permits the passage of hydrophobic, small-molecule antibiotics while hindering the entry of hydrophilic, large-molecule vancomycin. It dissipated the membrane proton motive force and inactivated the efflux pump, allowing the intracellular accumulation of antimicrobials that function as substrates of the efflux pump, such as linezolid. These processes resulted in metabolic perturbation and ROS production which ultimately was able to destroy the bacteria. These mechanisms of action of pentamidine on GNB indicate that it is prone to potentiating hydrophobic, small-molecule antibiotics, such as rifampicin, linezolid, and tetracycline, but not hydrophilic, large-molecule antibiotics like vancomycin against GNB. Collectively, our results highlight the importance of the physicochemical properties of antibiotics and the specific mechanisms of action of pentamidine for the synergy of pentamidine–antibiotic combinations. Pentamidine engages in various pathways in its interactions with GNB, but these mechanisms determine its specific synergistic effects with certain antibiotics against GNB. Pentamidine is a promising adjuvant, and we can optimize drug compatibility by considering its functional mechanisms.

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There are little data on pentamidine as a treatment for paediatric cutaneous leishmaniasis (CL). The objective of this study was to describe the effectiveness and safety of pentamidine over a 10-year period. Every child seen in French Guiana between 2010 and 2020 with proven CL and treated with pentamidine was included. In total, 55 children met the inclusion criteria - 23 girls and 32 boys. There were 38 patients (38/55, 69%) with a > 50% improvement at 1 month after pentamidine treatment and a complete cure at 3 months; 16 children had a < 50% improvement at 1 month and were given a second dose. Of these 16, 8 showed a complete cure at 3 months, 5 were lost to follow-up and 3 showed therapeutic failure at 3 months. The overall cure rate was 84% (46/55) after one or two doses. In terms of the safety of pentamidine, no severe adverse events (grade ≥ 3) were reported.

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