Variance in Pneumocystis jirovecii prophylaxis practice for pediatric patients undergoing hematopoietic cell transplantation.

Pneumocystis jirovecii pneumonia (PJP) in hematopoietic cell transplant (HCT) recipients can be prevented by efficient prophylaxis. We surveyed HCT centers in North America to assess their PJP prophylaxis practices. Most institutions used intravenous (IV) pentamidine (29.6%) or inhaled pentamidine (14.8%); 37% institutions changed from trimethoprim/sulfamethoxazole (TMP-SMX) to another medication after conditioning; and 44% administered no PJP prophylaxis during the pre-engraftment period. Most institutions avoided using TMP-SMX during the pre-engraftment period, mainly because of concerns about myelotoxicity, despite this being the preferred PJP prophylaxis agent. There is a need to evaluate the effects of TMP-SMX on engraftment.

Targeting pentamidine towards CD44-overexpressing cells using hyaluronated lipid-polymer hybrid nanoparticles.

Biodegradable nanocarriers possess enormous potential for use as drug delivery systems that can accomplish controlled and targeted drug release, and a wide range of nanosystems have been reported for the treatment and/or diagnosis of various diseases and disorders. Of the various nanocarriers currently available, liposomes and polymer nanoparticles have been extensively studied and some formulations have already reached the market. However, a combination of properties to create a single hybrid system can give these carriers significant advantages, such as improvement in encapsulation efficacy, higher stability, and active targeting towards specific cells or tissues, over lipid or polymer-based platforms. To this aim, this work presents the formulation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles in the presence of a hyaluronic acid (HA)-phospholipid conjugate (HA-DPPE), which was used to anchor HA onto the nanoparticle surface and therefore create an actively targeted hybrid nanosystem. Furthermore, ionic interactions have been proposed for drug encapsulation, leading us to select the free base form of pentamidine (PTM-B) as the model drug. We herein report the preparation of hybrid nanocarriers that were loaded via ion-pairing between the negatively charged PLGA and HA and the positively charged PTM-B, demonstrating an improved loading capacity compared to PLGA-based nanoparticles. The nanocarriers displayed a size of below 150 nm, a negative zeta potential of -35 mV, a core-shell internal arrangement and high encapsulation efficiency (90%). Finally, the ability to be taken up and exert preferential and receptor-mediated cytotoxicity on cancer cells that overexpress the HA specific receptor (CD44) has been evaluated. Competition assays supported the hypothesis that PLGA/HA-DPPE nanoparticles deliver their cargo within cells in a CD44-dependent manner.

A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies-its utility during respiratory virus pandemics.

OBJECTIVES: In hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematologic malignancies. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent; however, its use is not straightforward. Inhaled pentamidine is the recommended second-line agent; however, aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. We evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic hematopoietic stem cell transplantation recipients and patients with hematologic malignancies during COVID-19. RESULTS: A total of 202 unique patients who received 239 courses of IV pentamidine, with a median of three doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The most common reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients developed an infusion reaction or experienced adverse effects from IV pentamidine. CONCLUSIONS: Pentamidine administered IV monthly is safe and effective.

Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone. OBJECTIVES: To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis. METHODS: DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023. STUDY ELIGIBILITY CRITERIA: Comparative randomized controlled trials (RCTs). PARTICIPANTS: PWH. INTERVENTIONS: Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo. ASSESSMENT OF RISK OF BIAS: Cochrane risk-of-bias tool for RCTs 2. METHODS OF DATA SYNTHESIS: Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed. RESULTS: A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups. CONCLUSIONS: TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.

Nebulised pentamidine prophylaxis of pneumocystis pneumonia in adults accessing HIV services at royal free hospital, London.

Receipt of nebulised pentamidine in people with HIV was audited to identify if individuals were appropriately receiving nebulised pentamidine, and whether national guidelines were being followed when prophylaxis was commenced and discontinued. Of 76 people with who received nebulised pentamidine, the main indication for starting nebulised pentamidine was a co-trimoxazole adverse drug reaction. Co-trimoxazole desensitization was not attempted before starting nebulised pentamidine. The main indication for stopping nebulised pentamidine prophylaxis was when immune reconstitution occurred. This single centre audit revealed that national guidelines were being followed in most cases. The lack of information regarding the reason for starting or stopping nebulised pentamidine prophylaxis, or detail of the clinician's concerns about potential poor adherence with oral regimens of prophylaxis as a reason for choosing nebulised pentamidine prophylaxis, identifies a need for improved documentation of clinicians' decision-making. Introduction of pharmacist-led interventions/alerts using patients' electronic records, similar to those used in primary care, would enable the specialist pharmacy team to identify when and if co-trimoxazole desensitization has been offered and discussed/declined before a clinician prescribes nebulised pentamidine as well as enabling identification of those in who pentamidine prophylaxis has been continued, despite "immune reconstitution".

Combination therapy with liposomal amphotericin b (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate in a refractory visceral leishmaniasis case

Abstract Visceral leishmaniasis is a systemic disease that is potentially severe and endemic in Brazil. It clinically manifests as fever, weight loss, swelling, hepatosplenomegaly, paleness, and edema. In this study, we discuss a case of a 1-year-old child diagnosed with refractory visceral leishmaniasis after being treated with liposomal amphotericin B in two distinct occasions. Considering the persistent clinical features and weak response to conventional treatment, a combination therapy with liposomal amphotericin B (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate was initiated, and response to treatment was good.

Treatment of American tegumentary leishmaniasis in special populations: a summary of evidence

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.

Influência do estado nutricional na evolução clínica e terapêutica de adultos e idosos com leishmaniose tegumentar americana / Influence of the nutritional status in the clinical and therapeutical evolution in adults and elderly with american tegumentary leishmaniasis

O objetivo deste estudo foi descrever o estado nutricional de pacientes adultos e idosos com leishmaniose tegumentar americana (LTA). Foi realizado um estudo longitudinal em 68 pacientes adultos e idosos com LTA atendidos no Laboratório de Vigilância em Leishmanioses – Instituto de Pesquisa Clínica Evandro Chagas – Fiocruz, no período de 2009 a 2012. A avaliação nutricional foi realizada através do peso, altura, Índice de Massa Corporal e albumina sérica. A evolução clínica(epitelização e cicatrização das lesões) foi avaliada até dois anos após o tratamento de LTA. A maioria da amostra era composta por homens (71%), adultos (73%), com renda familiar de 1 a 5salários mínimos (79%) e com grau de instrução fundamental incompleto (48,5%). A forma predominante da LTA foi a cutânea (72%) e 39% apresentaram comorbidades, sendo a hipertensão arterial a mais frequente (30,8%). As intercorrências clínicas e nutricionais mais prevalentes foram:redução recente na ingestão de alimentos (23,9%), obstrução nasal (22,1%), úlcera oral (14,7%),anorexia + disfagia (13,2% cada) e odinofagia (10,3%). O tempo de cicatrização foi de 145,50 ±87,84 dias para lesões cutâneas e 172,89 ± 123 dias para lesões mucosas. Foram observados baixo peso em 10% e hipoalbuminemia em 12% dos pacientes...

The objective of this study is to describe the nutritional status of adult and elderly patients with American Tegumentary Leishmaniasis (ATL). It was conducted a longitudinal study in 68 adult andelderly patients with ATL treating at the Laboratório de Vigilância em Leishmanioses (Surveillance Leishmaniasis Laboratory) at the Instituto de Pesquisa Clínica Evandro Chagas (Evandro Chagas Clinical Research Institute)-Fiocruz, from 2009 to 2012. The nutritional assessment was performedusing weight, height, the Body Mass Index (BMI) and blood albumin levels. The clinical evolution(epithelialization, and wound healing) was measured up to two years after ATL treatment. Most ofthe sample was composed of men (71%), adults (73%), with household income of 1-5 minimumwages (79%), and incomplete basic education (48.5%). The predominant ATL form was cutaneous(72%), and 39% presented comorbidities, the most frequent was hypertension (30.8%). The most prevalent clinical and nutritional events were: recent reduction in food intake (23.9%); nasal obstruction (22.1%); oral ulcer (14.7%), anorexia + dysphagia (13.2% each) and odynophagia(10.3%). The healing time was 145.50 ± 87.84 days for skin lesions, and 172.89 ± 123 days formucous membrane lesions. Low weight in 10%, and hypoalbuminemia in 12% of the patients havebeen observed...

Profilaxis de neumonía por Pneumocystis jiroveci en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against Pneumocystis pneumonia in pediatric and adult patients undergoing solid organ or hematopoietic stem cells transplantation

Pneumocystis jiroveci is an important pathogen in patients undergoing SOT and HSCT. Universal prophylaxis is recommended for all adults and children with SOT and HSCT, considering that its use significantly reduces the occurrence and mortality associated with pneumonia by this agent. The drug of choice is cotrimoxazole (A1) three times a week, low-dose scheme, that has proved equally effective and better tolerated than the daily regimen and/or at high doses. Prophylaxis starts 7 to 14 days post transplant in SOT recipients and post-implant in HSCT, with an average duration of 6 months except in liver and lung transplant as in HSCT with significant degree of immunosuppression, that lasts for 1 year. Alternatives for prophylaxis are dapsone (B2), aerosolized pentamidine (B2) and atovaquone (C2).

Pneumocystis jiroveci es un patógeno importante en pacientes sometidos a TOS y TPH. Se recomienda proilaxis universal a todos los pacientes adultos y niños sometidos a TOS o TPH porque su uso reduce signiicati-vamente la ocurrencia y mortalidad asociada a neumonía por este agente. El medicamento de elección es cotrimoxa-zol (A1) tres veces por semana, en dosis bajas, esquema que ha demostrado igual eicacia y mejor tolerancia que el esquema diario y/o con dosis altas. La proilaxis se inicia 7 a 14 días post trasplante en TOS y posterior al implante en TPH, con una duración promedio de 6 meses salvo en trasplante de hígado y pulmón en que se prolonga por 1 año, al igual que en TPH con grado importante de inmunosupresión. Son alternativas de profilaxis dapsona (B2), pentamidina aerosolizada (B2) y atavacuona (C2).

Concomitância de leishmanioses e infecçäo pelo vírus da imunodeficiência humana (HIV): estudo de quatro casos / Concurrent leishmaniasis and human immunodeficiency virus infection: a study of four cases

Säo apresentados quatro casos de leishmaniose em pacientes com SIDA, sendo dois de leishmaniose visceral e dois com forma cutâneo-mucosa. Lesöes cutâneas e de mucosa oral, disseminadas, estavam presentes nos pacientes com a forma tegumentar da doença. Febre prolongada, hepatoesplenomegalia e pancitopenia foram as manifestaçöes principais da forma visceral. A contagem de linfócitos TCD4+ era baixa em todos os casos. A pesquisa de leishmanias foi positiva no aspirado de medula óssea e na biópsia de lesöes cutâneas e mucosas. Os pacientes responderam ao tratamento com antimoniais pentavalentes e com a anfotericina B. Poucos casos de coinfecçäo leishmaniose e HIV têm sido descritos em nosso meio. Apesar da ampla expansäo de ambas, até agora suas áreas de distribuiçäo geográfica teve pouca superposiçäo. Os autores recomendam a inclusäo desta parasitose no diagnóstico diferencial das doenças oportunistas que acometem indivíduos com SIDA

Diabetes mellitus associated with pentamidine isethionate in diffuse cutaneous leishmaniasis

The authors report a case of a male patient from Bacabal, MA with diffuse cutaneous leishmaniasis (DCL), for at least nine years, with 168 lesions on his body. These were tumour-like nodules with some ulceration. He used pentavalent antimonial (glucantime) and an association of gamma interferon plus glucantime with improvement of the lesions but relapsed later. Recently, pentamidine isethionate (pentacarinat) was given a dosage of 4mg/kg/weight/day on alternate days for 20 applications. After 3 months a similar course of 10 application was given 2 times. Later he developed diabetic signs with weight loss of 10kg, polydypsia, polyuria and xerostomia. The lower limbs lesions showed signs of activity. Blood glucose levels normalised and remain like this at moment. Attention is drawn to the fact that pentamidine isethionate should be used as a therapy option with care, obeying rigorous laboratory controls including a glucose tolerance test.

Pentamidina: atualizaçäo e aplicaçöes clínicas / Pentamidine: Up-to-dating and clinical use

Os autores efetuaram uma atualizaçäo sobre a pentamidina e comentam suas aplicaçöes na clínica médica

Tratamento da leishmaniose tegumentar americana com a pentamidina, esquema em dose única endovenosa / Treatment of american cutaneous Leishmaniasis with pentamidine: scheme in single endovenous dosis

Os autores relatam os resultados obtidos no tratamento de 63 casos de leishmaniose tegumentar americana empregando o metanossulfonato de pentamidina (Lomidine) em dose única e endovenosa. Na dose de 120 a 480 mg em 100 a 250 ml de soro glicosado a 5%, a eficâcia foi de 76%. Considerando as reaçöes colaterais e as contra-indicaçöes da pentamidina, recomendam a sua utilizaçäo somente em alguns casos de recidiva ou rebeldes ao tratamento antimonial

Tratamento com pentamidina de seis casos da forma mucosa de leishmaniase tegumentar / Treatment with pentamidine of 6 cases with mucus form of tegumentary leishmaniasis

As principais razöes para a escolha da pentamidina no presente ensaio terapêutico foram a alta taxa de recidiva de casos de forma mucosa de leishmaniose tegumentar com o tratamento pelos antimoniais pentavalentes e o fato deste medicamento ter sido usado com sucesso na forma cutânea da doença. Seis pacientes com forma mucosa de leishmaniose tegumentar diagnosticados clinicamente por exame dermato-otorrinolaringológico, reaçäo intradérmica de Montenegro, cultura inoculaçäo em hamster e esfregaço de material obtido das lesöes, exame histopatológico e pesquisa de anticorpos circulantes, foram tratados com pentamidina na dose de 200 mg em dias alternados, com dose total entre 2,3 a 5,9g, de acordo com a clínica. Houve cura clínica e parasitológica de cinco casos, com acompanhamento variando de 12 a 24 meses após o tratamento. No único caso de falha, tratava-se de um paciente que também näo respondeu ao tratamento com Glucantime. Entre os efeitos colaterais estäo um caso de diabetes mellitus, alteraçöes transitórias de glicemia em dois casos e abscesso glúteo em um, concluindo-se ser boa a resposta terapêutica à pentamidina dos casos da forma mucosa de leishmaniose tegumentar

A pentamidina: excelente terapêutica da leishmaniose cutânea; esquema de tratamento idealizado na Guiana Francesa em dose única / Pentamidine: excelent therapy of cutaneous leishmaniasis: treatment schedule used in French Guiany with single-dose

Apresenta-se a experiência no tratamento da leishmaniose cutânea com a pentamidina, em vários esquemas terapêuticos, assinalando os bons resultados e a regular tolerância ao medicamento. O esquema mais prático, parece ser o da administraçäo em infusäo venosa em dose única de três a quatro ampolas (360 a 480mg). Enfatiza-se a eficácia, tolerabilidade, baixo custo e facilidade de administraçäo em regiöes distantes, onde o paciente ou a equipe médica tem dificuldade de retornar em curto período de tempo