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Expert Opinion on Pharmacotherapy Aug 2021: (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts. Risk factors for pneumonia (PJP) include HIV, organ transplant,... (Review)
Review
: (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts. Risk factors for pneumonia (PJP) include HIV, organ transplant, malignancy, certain inflammatory or rheumatologic conditions, and associated therapies and conditions that result in cell-mediated immune deficiency. Clinical signs of PJP are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue. 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. In people living with HIV (PLWH), adjunctive corticosteroid use in treatment has shown a mortality benefit.: This review article covers the epidemiology, pathophysiology, diagnosis, microbiology, prophylaxis indications, prophylactic therapies, and treatments.: TMP-SMX has been first-line therapy for treating and preventing pneumocystis for decades. However, its adverse effects are not uncommon, particularly during treatment. 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.
Topics: Humans; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33870843
DOI: 10.1080/14656566.2021.1915989 -
Chest Dec 2020Patients with autoimmune and/or inflammatory diseases (AIIDs) are prone to serious infectious complications such as Pneumocystis jirovecii pneumonia (PJP). In non-HIV... (Review)
Review
Patients with autoimmune and/or inflammatory diseases (AIIDs) are prone to serious infectious complications such as Pneumocystis jirovecii pneumonia (PJP). In non-HIV patients, the prognosis is poorer, and diagnostic tests are of lower sensitivity. Given the low incidence of PJP in AIIDs, with the exception of granulomatosis with polyangiitis, and the non-negligible side effects of chemoprophylaxis, routine prescription of primary prophylaxis is still debated. Absolute peripheral lymphopenia, high doses of corticosteroids, combination with other immunosuppressive agents, and concomitant lung disease are strong predictors for the development of PJP and thus should warrant primary prophylaxis. Trimethoprim-sulfamethoxazole is considered first-line therapy and is the most extensively used drug for PJP prophylaxis. Nevertheless, it may expose patients to side effects. Effective alternative drugs such as atovaquone or aerosolized pentamidine could be used when trimethoprim-sulfamethoxazole is not tolerated or contraindicated. No standard guidelines are available to guide PJP prophylaxis in patients with AIIDs. This review covers the epidemiology, risk factors, and prevention of pneumocystis in the context of AIIDs.
Topics: Antifungal Agents; Autoimmune Diseases; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors
PubMed: 32502592
DOI: 10.1016/j.chest.2020.05.558 -
Avicenna Journal of Medicine Jan 2023pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has... (Review)
Review
pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has been a decline in pneumonia incidence in HIV since the introduction of antiretroviral medications. However, its incidence is increasing in non-HIV immunocompromised patients including those with solid organ transplantation, hematopoietic stem cell transplantation, solid organ tumors, autoimmune deficiencies, and primary immunodeficiency disorders. We aim to review and summarize the etiology, epidemiology, clinical presentation, diagnosis, and management of pneumonia in HIV, and non-HIV patients. HIV patients usually have mild-to-severe symptoms, while non-HIV patients present with a rapidly progressing disease. Induced sputum or bronchoalveolar lavage fluid can be used to make a definitive diagnosis of pneumonia. Trimethoprim-sulfamethoxazole is considered to be the first-line drug for treatment and has proven to be highly effective for pneumonia prophylaxis in both HIV and non-HIV patients. Pentamidine, atovaquone, clindamycin, and primaquine are used as second-line agents. While several diagnostic tests, treatments, and prophylactic regimes are available at our disposal, there is need for more research to prevent and manage this disease more effectively.
PubMed: 36969352
DOI: 10.1055/s-0043-1764375 -
Iranian Journal of Parasitology 2021are a causative agent of keratitis (AK) in immunocompetent individuals. Since access to propamidine isethionate (Brolene®) as a first-line treatment has been limited...
BACKGROUND
are a causative agent of keratitis (AK) in immunocompetent individuals. Since access to propamidine isethionate (Brolene®) as a first-line treatment has been limited in recent years, in the current study, we examined the effects of pentamidine isethionate against trophozoite and cyst forms of .
METHODS
This experimental study was conducted in the Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran, during 2019-2020. Pentamidine isethionate at concentrations of 50, 100, 200, 400, 600, 800, and 1000 μM were tested against trophozoites and cyst stages of T4 genotype, at 24- and 48-hour incubation period, and the viability was determined by trypan blue staining. In addition, the cytotoxic effect of the drug was examined in cells using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.
RESULTS
The 50% inhibitory concentration (IC50) of pentamidine isethionate on trophozoite after 24 and 48h were 97.4 μM and 60.99 μM. These results on cyst after 24 and 48h were 470 μM and 175.5 μM, respectively. In MTT assay, the drug showed an inhibitory effect on cell growth with IC50 values of 115.4 μM and 87.42 μM after 24h and 48h, respectively.
CONCLUSION
Pentamidine isethionate exhibited an inhibitory effect on trophozoite and cyst. Given that the trophozoicidal activity of the drug is in the safe dose, it could be suggested as an alternative in patients with AK; however, further investigation is needed in an animal model to confirm the data.
PubMed: 35082884
DOI: 10.18502/ijpa.v16i4.7868 -
Drug Delivery and Translational Research Aug 2022Pentamidine (PTM), which is a diamine that is widely known for its antimicrobial activity, is a very interesting drug whose mechanism of action is not fully understood.... (Review)
Review
Pentamidine (PTM), which is a diamine that is widely known for its antimicrobial activity, is a very interesting drug whose mechanism of action is not fully understood. In recent years, PTM has been proposed as a novel potential drug candidate for the treatment of mental illnesses, myotonic dystrophy, diabetes, and tumors. Nevertheless, the systemic administration of PTM causes severe side effects, especially nephrotoxicity. In order to efficiently deliver PTM and reduce its side effects, several nanosystems that take advantage of the chemical characteristics of PTM, such as the presence of two positively charged amidine groups at physiological pH, have been proposed as useful delivery tools. Polymeric, lipidic, inorganic, and other types of nanocarriers have been reported in the literature for PTM delivery, and they are all in different development phases. The available approaches for the design of PTM nanoparticulate delivery systems are reported in this review, with a particular emphasis on formulation strategies and in vitro/in vivo applications. Furthermore, a critical view of the future developments of nanomedicine for PTM applications, based on recent repurposing studies, is provided. Created with BioRender.com.
Topics: Administration, Cutaneous; Drug Carriers; Drug Delivery Systems; Nanomedicine; Nanoparticles; Pentamidine; Pharmaceutical Preparations
PubMed: 35217992
DOI: 10.1007/s13346-022-01127-4 -
Journal of Travel Medicine Aug 2021We performed a systematic review of the literature to investigate the efficacy and safety of pentamidine isethionate for the treatment of human tegumentary and visceral...
RATIONALE FOR REVIEW
We performed a systematic review of the literature to investigate the efficacy and safety of pentamidine isethionate for the treatment of human tegumentary and visceral leishmaniasis.
KEY FINDINGS
A total of 616 papers were evaluated, and 88 studies reporting data on 3108 cases of leishmaniasis (2082 patients with tegumentary leishmaniasis and 1026 with visceral leishmaniasis) were finally included. The majority of available studies were on New World cutaneous leishmaniasis and visceral leishmaniasis caused by Leishmania donovani. At the same time, few data are available for Old World cutaneous leishmaniasis, mucosal leishmaniasis, and visceral leishmaniasis caused by L. infantum. Pooled cure rate for tegumentary leishmaniasis was 78.8% (CI 95%, 76.9-80.6%) and 92.7% (CI 95%, 88.3-97.1%) according to controlled randomized trial and observational studies and case report and case series respectively. Pooled cure rate for visceral leishmaniasis was 84.8% (CI 95%, 82.6-87.1%) and 90.7% (CI 95%, 84.1-97.3%) according to controlled randomized trial and observational studies and case report and case series, respectively. Comparable cure rate was observed in recurrent and refractory cases of visceral leishmaniasis. Concerning the safety profile, among about 2000 treated subjects with some available information, the most relevant side effects were six cases of arrhythmia (including four cases of fatal ventricular fibrillation), 20 cases of irreversible diabetes, 26 cases of muscular aseptic abscess following intramuscular administration.
CONCLUSIONS/RECOMMENDATIONS
Pentamidine isethionate is associated with a similar cure rate of the first-line anti-leishmanial 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 setting of travel medicine. In difficult cases, the drug can also be considered as a component of a combination treatment regimen.
Topics: Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Leishmaniasis, Visceral; Pentamidine
PubMed: 33890115
DOI: 10.1093/jtm/taab065 -
Current Medicinal Chemistry 2022Pentamidine, an FDA-approved human drug for many protozoal infections, was initially synthesized in the late 1930s and first reported to be curative for parasitosis in... (Review)
Review
Pentamidine, an FDA-approved human drug for many protozoal infections, was initially synthesized in the late 1930s and first reported to be curative for parasitosis in the 1940s. After ninety years of sometimes quiet growth, pentamidine and its derivatives have gone far beyond antibacterial agents, including but not limited to the ligands of DNA minor groove, modulators of PPIs (protein-protein interactions) of the transmembrane domain 5 of lateral membrane protein 1, and the blockers of the SARS-CoV-2 3a channel. This mini-review highlights the development and applications of pentamidine and its analogs, aiming to provide insights for further developing pentamidine derivatives in the following decades.
Topics: DNA; Humans; Ligands; Pentamidine; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35289252
DOI: 10.2174/0929867329666220314121446 -
Antibiotics (Basel, Switzerland) Mar 2023The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria has spread. Due to... (Review)
Review
The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria has spread. Due to antibiotics' availability over the counter in many nations, antibiotic resistance is linked to overuse, abuse, and misuse of these drugs. The World Health Organization (WHO) recognized 12 families of bacteria that present the greatest harm to human health, where options of antibiotic therapy are extremely limited. Therefore, this paper reviews possible new ways for the development of novel classes of antibiotics for which there is no pre-existing resistance in human bacterial pathogens. By utilizing research and technology such as nanotechnology and computational methods (such as in silico and Fragment-based drug design (FBDD)), there has been an improvement in antimicrobial actions and selectivity with target sites. Moreover, there are antibiotic alternatives, such as antimicrobial peptides, essential oils, anti-Quorum sensing agents, darobactins, vitamin B6, bacteriophages, odilorhabdins, 18β-glycyrrhetinic acid, and cannabinoids. Additionally, drug repurposing (such as with ticagrelor, mitomycin C, auranofin, pentamidine, and zidovudine) and synthesis of novel antibacterial agents (including lactones, piperidinol, sugar-based bactericides, isoxazole, carbazole, pyrimidine, and pyrazole derivatives) represent novel approaches to treating infectious diseases. Nonetheless, prodrugs (e.g., siderophores) have recently shown to be an excellent platform to design a new generation of antimicrobial agents with better efficacy against multidrug-resistant bacteria. Ultimately, to combat resistant bacteria and to stop the spread of resistant illnesses, regulations and public education regarding the use of antibiotics in hospitals and the agricultural sector should be combined with research and technological advancements.
PubMed: 36978495
DOI: 10.3390/antibiotics12030628