Pneumocystis Jirovecii Pneumonia Prophylaxis In Patients Research Articles

EVALUATING PNEUMOCYSTIS JIROVECII PNEUMONIA (PCP) PROPHYLAXIS IN PATIENTS WITH GLIOMA RECEIVING CONCURRENT TEMOZOLOMIDE AND RADIATION – A PATIENT AND PHYSICIAN SURVEY

Abstract Temozolomide (TMZ) given concurrently with radiation (TMZ-RT) is essential in glioma therapy. Pneumocystis jirovecii pneumonia (PCP) prophylaxis is required by provincial and national drug monographs based on two incidents of PCP in a pilot study. There is otherwise limited evidence to inform the need for PCP prophylaxis in this population. METHODS: We conducted a single-centre survey of patients and national survey of physicians on the role of PCP prophylaxis in patients with glioma receiving concurrent TMZ-RT. RESULTS: Fifteen percent (31/212) of physicians and 60% (44/73) of patients completed a survey. The median age of patients was 42 (20-77); 85% (34/40) had completed adjuvant TMZ, and 59% (24/41) were not offered PCP prophylaxis. After reviewing the hypothetical risks of PCP, 13.2% (5/38) of patients were concerned about PCP infection, whereas 26% (10/38) were concerned about potential side effects from prophylactic antibiotics. Physician participants included medical (29%, 9/31) radiation (29%, 9/31), and neuro-oncologists (32%, 10/31). Most physicians (77%, 17/22) felt the evidence informing PCP prophylaxis in this population was weak; 58% (11/19) were not routinely prescribing prophylaxis, and 73% (16/22) felt that PCP prophylaxis should be limited to patients with additional risk factors. Sixty-three percent (22/35) of patients and 57% (12/21) of physicians were interested in a clinical trial to assess the risk of PCP infection in this setting. CONCLUSION: Clinical equipoise exists on the role of PCP prophylaxis during and after TMZ-RT amongst patients and physicians. Rigorous prospective studies need to be conducted to inform and standardize best practices.

P54 Pneumocystis jirovecii prophylaxis in patients on rituximab

Abstract Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab 10 Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months) 7 Number of patients on rituximab monotherapy 2 Number of patients who are 6 months post-treatment 1 Number of patients with other risk factors for PCP 1 (hypogammaglobulinaemia) Number of patients who are eligible for prophylaxis, as per the guideline 8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia) Number of patients on cotrimoxazole 7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest.

A Prospective Study of IV Pentamidine for Pneumocystis Jirovecii Pneumonia Prophylaxis in Adult Patients with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplant or Chemotherapy

Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is routinely administered to patients undergoing hematopoietic stem cell transplantation (SCT) or intensive chemotherapy. There is continued risk of PJP particularly in SCT recipients when they require prolonged immunosuppression or high dose corticosteroids. Trimethoprim-sulfamethoxazole is the drug of choice but its use is limited by hematologic toxicities. Inhaled pentamidine is an alternative, but frequently causes bronchospasm, needs to be given by a respiratory therapist, and requires use of a private room during administration due to its teratogenicity. Intravenous (IV) pentamidine is FDA approved for PJP treatment, and overcomes these challenges. We conducted the first ever prospective study of IV pentamidine for PJP prophylaxis in adult patients undergoing SCT or intensive chemotherapy.Fifty patients were enrolled in a single-arm trial. Patients requiring PJP prophylaxis according to institutional guidelines received pentamidine 4 mg/kg (maximum 300 mg) intravenously with ondansetron pre-medication. Patients were followed for the occurrence of PJP pneumonia. Adverse events were recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4. Patient satisfaction was assessed by conducting the Treatment Satisfaction Questionnaire for Medication (TSQM Version 1.4) survey. Thirty-two (64%) patients were male, and the median age was 55 years (range: 19-72). Twenty-four patients (48%) were undergoing intensive chemotherapy while 26 (52%) were undergoing SCT. Of the latter group, 62% received autologous SCT and 38% allogeneic SCT. At the time of IV pentamidine administration, 58% of patients were neutropenic (absolute neutrophil count < 0.5 thous/µL) and 86% of patients were lymphopenic (absolute lymphocyte count < 1 thous/µL). All patients received at least one dose of IV pentamidine (range: 1-9). There were no cases of PJP documented during the 12 month study period. There were no NCI-CTCAE grade 3/4 events. Seventeen (34%) patients experienced a grade 1 or 2 adverse event. The most common adverse events were nausea (n=4) and hypotension (n=6). Hypotension typically occurred at the end of the infusion, was transient, and asymptomatic. Grade 1/2 acute kidney injury developing within one week of pentamidine occurred in 2 patients (4%). In both patients, serum creatinine increased within 3 days, peaked within 7 days, and normalized within 10 days. Two treatment-related interruptions of drug infusion occurred; one due to infusion-related perioral and facial numbness which resolved as soon as the drug was stopped and one due to nausea which resolved after intravenous ondansetron. IV infusion was resumed successfully in both cases. Engraftment was not adversely affected in patients undergoing SCT. The median time to neutrophil and platelet engraftment was 12 (range: 11-15) and 14 (range: 10-16) days in autologous SCT recipients and 13 (range: 13-31) and 14 (range: 14-31) days in allogeneic SCT recipients.Results from the TSQM questionnaire indicate that the majority of patients found that IV pentamidine was "not at all bothersome" (n=33, 69%), "did not interfere with physical health and ability to function" (n=37, 77%), and was "extremely easy to receive" (n=29, 60%). The most common adverse events reported in the TSQM questionnaire were nausea (n=6), nasal congestion (n=2), and mouth numbness (n=2). However, they had "minimal" or "no effect at all" on patient satisfaction with the drug. Overall patients were satisfied with the administration of IV pentamidine (n=43, 86%, p<0.01).Our study illustrates the safety and feasibility of using IV pentamidine for PJP prophylaxis in patients undergoing SCT or intensive chemotherapy. In SCT patients, IV pentamidine did not delay engraftment. The incorporation of patient centered outcomes showed a high degree of satisfaction with this method of prophylaxis. Thus, although comparative studies are required, IV pentamidine overcomes many of the respiratory and logistic challenges faced when administering inhaled pentamidine and appears to be better tolerated. In particular, patients undergoing SCT who require PJP prophylaxis over a prolonged period may derive benefit from the improved safety and patient satisfaction profile of IV pentamidine. DisclosuresNo relevant conflicts of interest to declare.

Discontinuing Pneumocystis jirovecii Pneumonia Prophylaxis in HIV-Infected Patients With a CD4 Cell Count

To review the evidence for discontinuing primary and secondary Pneumocystis jirovecii pneumonia (PJP) prophylaxis in HIV-infected patients with a CD4 count <200 cells/mm(3). We conducted a literature search in MEDLINE, EMBASE, Cochrane Library, Google Scholar, and the International Aids Society Library (up to August 2015) using the following key search terms: Pneumocystis jirovecii, pneumonia, human immunodeficiency virus, primary prophylaxis, secondary prophylaxis, and discontinuation. All English-language studies that evaluated discontinuation of primary and/or secondary PJP prophylaxis in HIV-infected patients with CD4 count <200 cells/mm(3) were included. Five studies were identified, which varied in design, sample size, outcomes, and duration of follow-up. Three studies examined discontinuation of primary and secondary PJP prophylaxis; 1 study evaluated discontinuing primary PJP prophylaxis; and 1 study evaluated stopping secondary PJP prophylaxis. Two out of the 5 studies pooled data for all opportunistic infections. Overall, there was a low incidence of PJP among HIV-infected patients who discontinued primary PJP prophylaxis and were well controlled on antiretroviral therapy (ART). Discontinuation of primary PJP prophylaxis appears to be safe in patients on combination ART with a suppressed HIV viral load and a CD4 count >100 cells/mm(3). Additional data are needed to support the safety of discontinuing secondary PJP prophylaxis. Decisions to discontinue PJP prophylaxis in patients with a CD4 count <200 cells/mm(3) should be done on an individual patient basis, taking into consideration clinical factors, including ongoing adherence to ART.