Pneumocystis jiroveci pneumonia in kidney and simultaneous pancreas kidney transplant recipients in the present era of routine post-transplant prophylaxis: risk factors and outcomes

Garg, Neetika; Jorgenson, Margaret R.; Descourouez, Jillian L.; Saddler, Christopher M; Parajuli, Sandesh; Astor, Brad C.; Mandelbrot, Didier A.

doi:10.1186/s12882-018-1142-8

Cited by 16 publications

(34 citation statements)

References 19 publications

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“…In recipients of kidney and/or kidney/pancreas transplants, cytomegalovirus (CMV) viremia (median viral load 3685 IU/ ml) was a risk factor for PCP, with 90% of patients having CMV 1 year prior to PCP and 89% had active CMV infection when diagnosed with PCP [26]. The association with CMV was not seen in HSCT patients, where lymphopenia, acute graft-versus-host disease and the use of immunosuppressive agents were significantly associated with PCP post-allogeneic HSCT [5].…”

Section: Clinical Manifestationmentioning

confidence: 99%

Pneumocystis jirovecii Pneumonia: Epidemiology, Clinical Manifestation and Diagnosis

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2019

Curr Fungal Infect Rep

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Purpose of Review The purpose of this study is to provide an understanding of the increased range of patient cohorts at risk of Pneumocystis jirovecii pneumonia (PCP) and describe typical clinical presentations together with advances in diagnostic assays and strategies. Recent Findings The range of immuno-compromised patients at risk of PCP continues to expand. Apart from human immunodeficiency virus (HIV)-positive patients, those with solid tumours or suffering from haematological malignancy, solid organ transplant recipients or with autoimmune and inflammatory conditions receiving immuno-modulating therapies and patients diagnosed with primary immune deficiencies are all at increased risk of PCP. The clinical presentation of respiratory distress may be mild/moderate in the HIV-positive patient, but fulminant in HIV-negative. While typical clinical signs of PCP, along with underlying risk factors and the absence of alternative diagnoses, may be sufficient to commence therapy, every effort should be made to achieve a mycological diagnosis. With the advent of modern diagnostics techniques (real-time polymerase chain reaction (PCR) and (1-3)-β-D-Glucan), a laboratory-based diagnosis should always be attempted, although microscopic identification of Pneumocystis within respiratory samples remains the reference method. By combining different assays, it may be possible to both exclude and confirm PCP, without the need for invasive samples. Summary This review will summarize the epidemiology, clinical manifestations and diagnostic options for PCP, and also briefly cover therapeutic management, the emerging issue of resistance and PCP in paediatric age group.

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Section: Clinical Manifestationmentioning

confidence: 99%

Pneumocystis jirovecii Pneumonia: Epidemiology, Clinical Manifestation and Diagnosis

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2019

Curr Fungal Infect Rep

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“…6 Immunosuppressant agents, CMV infection, allograft rejection, and a low lymphocyte count have been proposed as risk factors for PCP in KTRs after post-transplantation prophylaxis. 3,5,7 In a meta-analysis of 15 studies, allograft rejection and CMV infection were identified as risk factors for PCP development. The study further suggested that extended prophylaxis targeting allograft rejection and CMV infection may reduce the risk of PCP.…”

Section: Introductionmentioning

confidence: 99%

“…Median time from transplant to CMV infection was 2.2 months (IQR 1.7-3.6), time from transplant to rejection 5.0 months (IQR 0.6-25.0). Time to PCP development after rejection (median [IQR], 6[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] months) was slightly shorter than after CMV infection (median [IQR], 9[5][6][7][8][9][10][11][12]), although this difference was not statistically significant (P = .18) (Table 3,…”

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confidence: 99%

Epidemiology and risk factors associated with Pneumocystis jirovecii pneumonia in kidney transplant recipients after 6‐month trimethoprim‐sulfamethoxazole prophylaxis: A case‐control study

Park

Jung

Kwon

et al. 2020

Transplant Infectious Dis

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Background: Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in kidney transplant recipients (KTRs), and prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is recommended. The aim of this study was to investigate incidence and risk factors for PCP in KTRs after 6-month TMP-SMX prophylaxis. Methods:We conducted a case-control study of patients with PCP who received 6-month PCP prophylaxis with TMP-SMX after kidney transplantation (KT). In cases of rejection, PCP prophylaxis was provided for six additional months after anti-rejection therapy. Cytomegalovirus (CMV) infection was not considered an indication for PCP prophylaxis due to concerns of nephrotoxicity associated with TMP-SMX.Results: Among 3941 kidney or pancreas-kidney transplant recipients, 67 (1.7%) developed PCP after discontinuing TMP-SMX. A total of 47 patients with KT PCP and 94 controls were included. Duration of PCP prophylaxis was similar between cases and controls (median 6 months, P = .53). In multivariate analysis, rejection (OR 3.9; 95% CI 1.4-11.1) and CMV infection (OR 2.4; 95% CI 1.0-5.8) were independently associated with PCP development after TMP-SMX. Rejection or CMV infection was observed in 70% of patients with PCP. Time to PCP development after rejection (median [IQR] 6 [5-19] months) was slightly shorter than after CMV infection (median [IQR] 9 [5-12] months; P = .18). Conclusion:Post-prophylaxis PCP occurred in <2% of KTRs, and about two-thirds of these experienced rejection or CMV infection. These data suggest that at least 6 to 9-month additional chemoprophylaxis may be needed to prevent PCP in KTRs with transplant rejection or CMV infection. K E Y W O R D Scytomegalovirus, Pneumocystis jirovecii pneumonia, rejection

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“…Indeed, we found patients who experienced CMV infection preceded by acute rejection had a twofold increased risk of graft loss and mortality compared to those with CMV without precedent rejection. CMV is an immunomodulating virus that has been associated with increased incidence of other concomitant infections, and subsequent increased mortality . Indeed, this has been described in the setting of rejection treatment .…”

Section: Discussionmentioning

confidence: 99%

The risk of cytomegalovirus infection after treatment of acute rejection in renal transplant recipients

Jorgenson

Descourouez

Lyu

et al. 2019

Clinical Transplantation

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The risk of cytomegalovirus infection (CMV) after rejection treatment is poorly understood. To investigate this, we conducted a case/control (1:2) analysis of adult renal transplant recipients between January 1, 2005 and December 31, 2015, via incidence density sampling and survival analysis. Our objective was to evaluate the association of prior acute rejection with subsequent CMV, including epidemiology and outcomes. There were 2481 eligible renal transplants within the study period and 251 distinct CMV infections. Despite the use of antiviral prophylaxis rejection was a significant risk factor for CMV on unadjusted (HR 1.73 [1.34, 2.24] P < 0.05) and adjusted analysis (HR 1.46 [1.06, 2.04] P < 0.05). When matching cases to controls patients with CMV had significantly more rejection prior to CMV diagnosis (26.7% vs 14.2%, P < 0.01). CMV was associated with a twofold increased risk of prior rejection on unadjusted (OR 1.94, 95%CI: 1.28‐2.96, P < 0.01) and adjusted analysis (OR 2.16, 95% CI: 1.31‐3.58, P < 0.01). Patients with rejection preceding CMV had significantly increased graft loss (HR 2.89, 95% CI: 1.65‐5.09, P < 0.01) and mortality (HR 1.82, 95% CI: 1.12‐4.24, P = 0.03) as compared to those CMV cases without rejection. In conclusion, rejection is a risk factor for CMV infection that appears to persist for 1 year. Preceding rejection events increased risk of graft loss and mortality in CMV patients. Given this, prolonged surveillance monitoring for CMV after rejection may be warranted. Studies are needed investigating optimal monitoring strategies.

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Pneumocystis jiroveci pneumonia in kidney and simultaneous pancreas kidney transplant recipients in the present era of routine post-transplant prophylaxis: risk factors and outcomes

Cited by 16 publications

References 19 publications

Pneumocystis jirovecii Pneumonia: Epidemiology, Clinical Manifestation and Diagnosis

Pneumocystis jirovecii Pneumonia: Epidemiology, Clinical Manifestation and Diagnosis

Epidemiology and risk factors associated with Pneumocystis jirovecii pneumonia in kidney transplant recipients after 6‐month trimethoprim‐sulfamethoxazole prophylaxis: A case‐control study

The risk of cytomegalovirus infection after treatment of acute rejection in renal transplant recipients

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