IV pentamidine for primary PJP prophylaxis in adults undergoing allogeneic hematopoietic progenitor cell transplant

Lim, Matthew J.; Stebbings, A; Lim, Sara J.; Foor, K; Hou, Jing Zhou; Farah, Rafic; Raptis, Anastasios; Marks, Stanley; Weber, David R.; Im, Annie; Dorritie, Kathleen A.; Sehgal, Alison R.; Agha, Mounzer; Lim, Seah H.

doi:10.1038/bmt.2015.131

Cited by 13 publications

(8 citation statements)

References 7 publications

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“…Although concerns had been raised in the past regarding reduced lung penetration of IV pentamidine, many of these studies demonstrated clinically equivalent efficacy compared with the aerosolized route, and thus, IV pentamidine is often preferred in the very young because of ease of delivery. 3,7,20,22,29,30 Weintrub et al 31 reported breakthrough of 14% in a small national survey about monthly IV pentamidine in pediatric HIV, and Gupta et al 32 reported 6% PCP breakthrough for q3-q4 weeks dosing in 30 children with HIV; both groups concluded IV pentamidine was acceptable as second-line prophylaxis for their populations with comparable breakthrough rates to other available options.…”

Section: Discussionmentioning

confidence: 99%

Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the Pediatric Hematopoietic Stem Cell Transplant Population

Levy

Musick

Zinter

et al. 2016

Pediatric Infectious Disease Journal

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Background: Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients with mortality above 50%. Trimethoprim-sulfamethoxazole is a standard PCP prophylaxis; pentamidine is frequently used as second-line prophylaxis because of trimethoprim-sulfamethoxazole's potential for cytopenias. Monthly intravenous (IV) pentamidine has variable efficacy with PCP infection rates of 0%-10% in pediatric patients, and higher breakthrough rates in those younger than 2 years. We hypothesized that bimonthly (twice monthly) pentamidine might have equivalent safety and improved efficacy; therefore, we conducted a retrospective analysis of bimonthly pentamidine PCP prophylaxis. Methods: We retrospectively reviewed records of all pediatric HCT patients who received bimonthly IV pentamidine between December 2006 and June 2013, and collected data regarding demographics, clinical course, prophylaxis rationale, laboratory values and adverse events. Results: Between December 2006 and June 2013, 111 pediatric HCT patients received bimonthly IV pentamidine (574 doses, 8758 patient-days); 31 patients were younger than 2 years at initiation. In the majority (53% of courses), pentamidine was initiated because of cytopenias. Fourteen patients (12.6% of patients, 2.4% of doses) experienced a side-effect prompting discontinuation, including 3 patients with infusion-related hypotension/anaphylaxis and 3 with acute pancreatic dysfunction. No patients [0% (95% confidence interval: 0-3.2)] developed PCP during or after bimonthly IV pentamidine prophylaxis. Conclusions: Bimonthly IV pentamidine for PCP prophylaxis in the HCT pediatric population has comparable safety to monthly IV pentamidine and was highly effective, including in the very young. Bimonthly IV pentamidine should be considered in pediatric patients as second-line PCP prophylaxis.Key Words: pediatric, stem cell transplant, PCP prophylaxis, intravenous pentamidine (Pediatr Infect Dis J 2016;35:135-141) I n the absence of prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients and has a mortality rate higher than 50%.1-3 Trimethoprim-sulfamethoxazole (TMP-SMZ) is standard and validated prophylaxis in the vast majority of adult and pediatric oncologic patients. [4][5][6][7][8] Recent meta-analyses have demonstrated high efficacy of TMP-SMZ prophylaxis in pediatric HCT populations with disease risk reduction of 0.09 and very low PCP breakthrough (0%-0.2%).7 However, some pediatric patients cannot tolerate TMP-SMZ because of bone marrow suppression, allergy, side effects or inability to use oral medications; in these patients, atovaquone, dapsone or pentamidine are considered acceptable second-line prophylaxis. 7,8 Because of the lack of high-quality data, national recommendations conflict regarding second-line prophylaxis in pediatric patients, and consequently, practice varies according to institutional preference. [7][8][9][10][11]...

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Section: Discussionmentioning

confidence: 99%

Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the Pediatric Hematopoietic Stem Cell Transplant Population

Levy

Musick

Zinter

et al. 2016

Pediatric Infectious Disease Journal

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“…All patients underwent screening for vancomycin-resistant enterococcus colonization on the day of admission and they received antimicrobial prophylaxis with oral ciprofloxacin, fluconazole, and acyclovir starting Day-2 of transplant. They also received a dose of intravenous pentamidine (4 mg/kg) on admission to the hospital, as prophylaxis against Pneumocystis jirovecii pneumonia, and the intravenous pentamidine was repeated every 28 days, as described previously [12].…”

Section: Introductionmentioning

confidence: 99%

Peri‐transplant clostridium difficile infections in patients undergoing allogeneic hematopoietic progenitor cell transplant

et al. 2016

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Clostridium difficile infections (CDI) remain the leading cause of infectious diarrhea among hospitalized patients in this country. Patients with hematologic malignancies, especially those who undergo hematopoietic progenitor cell transplants are particularly at risk for developing CDI. One hundred and forty seven consecutive allogeneic hematopoietic progenitor cell transplants were analyzed for peri-transplant Clostridium difficile infections (PT-CDI). Sixteen patients (11%) developed PT-CDI (Median time 5 7 days after transplant). The probability for developing PT-CDI during the peri-transplant period was 12.3%. History of CDI was strongly associated with the development of PT-CDI (P 5 0.008) (OR 5 5.48) (P 5 0.017). These patients also developed PT-CDI much earlier than in those without a history (median 1 day vs. 8 days, P 5 0.03). The probability for developing PT-CDI for those with a history was 39%. There was a trend toward significance (P 5 0.065) between matched related donor grafts and the development of PT-CDI (OR 5 0.245) (P 5 0.08). Age, sex, diagnosis, transplant preparative regimens, Graft-versus-host disease (GVHD) prophylaxis, grade 3/4 acute GVHD, or use of antimicrobials within 8 weeks of transplant were not associated with PT-CDI. Non-CDI-related deaths occurred in one patient in the PT-CDI group and nine in the group without PT-CDI. In the remaining 139 patients, the length of hospital stay for those with PT-CDI was significantly longer than those without (mean 27 days vs. 22 days; P 5 0.02).

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“…While TMP–SMX remains the gold standard for PJP prophylaxis, bone marrow toxicity is a limiting factor for its use in pediatric patients receiving tandem ASCT, who require adequate hematologic recovery between them. American and European guidelines suggest second‐line drugs such as inhaled pentamidine, dapsone, or atovaquone, with limited evidence . Some practicalities should be considered, related to equipment and facilities that may make using inhaled pentamidine difficult …”

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confidence: 99%

“…American and European guidelines suggest second‐line drugs such as inhaled pentamidine, dapsone, or atovaquone, with limited evidence . Some practicalities should be considered, related to equipment and facilities that may make using inhaled pentamidine difficult …”

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confidence: 99%

“…American and European guidelines suggest secondline drugs such as inhaled pentamidine, dapsone, or atovaquone, with Abbreviations: ASCT, autologous stem cell transplant; IVP, intravenous pentamidine; PJP, Pneumocystis jirovecii pneumonia; TMP-SMX, trimethoprim-sulfamethoxazole limited evidence. 1,6,7 Some practicalities should be considered, related to equipment and facilities that may make using inhaled pentamidine difficult. 2,6 Our series of ACST pediatric patients treated with IVP is homogeneous in indication and dosage regimen.…”

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confidence: 99%

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Intravenous pentamidine for Pneumocystis pneumonia prophylaxis in children undergoing autologous hematopoietic stem cell transplant

Tamayo

Busquets

Genestar

et al. 2017

Pediatric Blood & Cancer

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IV pentamidine for primary PJP prophylaxis in adults undergoing allogeneic hematopoietic progenitor cell transplant

Abstract: Abbreviations: ARA-C = cytosine arabinoside; ATG = antithymocyte globulins; Bu = busulfan; Clo = clofarabine; Cy = cyclophosphamide; Flu = fludarabine; Mel = melphalan.

Cited by 13 publications

References 7 publications

Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the Pediatric Hematopoietic Stem Cell Transplant Population

Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the Pediatric Hematopoietic Stem Cell Transplant Population

Peri‐transplant clostridium difficile infections in patients undergoing allogeneic hematopoietic progenitor cell transplant

Intravenous pentamidine for Pneumocystis pneumonia prophylaxis in children undergoing autologous hematopoietic stem cell transplant

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