Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant-Associated Infection Surveillance Network (TRANSNET)

Abstract We sought to describe the clinical experience of voriconazole as primary antifungal prophylaxis (AFP) in allogeneic hematopoietic cell transplant recipients (allo-HCTr). This was a single-center retrospective study of adult allo-HCTr (1 January 2014 to 31 December 2016) who received ≥two doses of voriconazole-AFP. Voriconazole-AFP was started on day +7 post-HCT and continued at least through day +60 post-HCT, or longer as clinically indicated. We reviewed the rate, reasons, and risk factors of voriconazole-AFP discontinuation until day-100 post-HCT. A total of 327 patients were included. Voriconazole-AFP was continued for a median of 69 days (mean: 57.9; range 1, 100): for a median of 90 days (mean :84; range 2, 100) in 180/327 (55%) in the standard-of-care (SOC) group and 20 days (mean :25.6 ; range 1, 89; P-value < .001) in 147/327 (45%) patients in the early-discontinuation-group. Early-voriconazole-AFP discontinuation was due to adverse events, drug interactions, insurance coverage, and other reasons in 101/147 (68.7%), 27 (18.4%), 13 (8.8%), and 6 (4.1%) patients, respectively. Early-voriconazole-AFP discontinuation occurred in 73/327 (22.3%) patients due to hepatotoxicity. Important predictors for early-voriconazole-AFP discontinuation included: graft-versus-host disease grade ≥2 (odds ratio [OR]: 1.9, P-value: .02), alanine-aminotransferase ≥75 IU/ml on voriconazole-administration day-14 (OR: 5.6, P-value: .02) and total bilirubin ≥1.3 mg/dl on voriconazole-administration day-7 (OR: 3.0, P-value: .03). There were 13 proven/probable invasive fungal infections by day-180 post-HCT (8/147, 5.4%, and 5/180, 2.8% in the early-discontinuation and SOC-groups, respectively; log-rank:0.13). By day-180 post HCT, 23/147 (15.6%) and 14/180 (7.8%) patients in the early-discontinuation and SOC-groups had died, respectively (log-rank:0.03). Voriconazole-AFP was discontinued in up to 45% of allo-HCTr. Hepatotoxicity during the first 2 weeks post-HCT is a significant predictor of early-voriconazole-AFP discontinuation.

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Clinical considerations on posaconazole administration and therapeutic drug monitoring in allogeneic hematopoietic cell transplant recipients

Medical Mycology ◽

10.1093/mmy/myaa106 ◽

2020 ◽

Author(s):

Mateja Kraljevic ◽

Nina Khanna ◽

Michael Medinger ◽

Jakob Passweg ◽

Stavroula Masouridi-Levrat ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Fungal Infections ◽

Primary Objective ◽

Hematopoietic Cell ◽

Therapeutic Drug ◽

Cell Transplant ◽

Transplant Recipients ◽

Hematopoietic Cell Transplant ◽

Allogeneic Hematopoietic Cell Transplant

Abstract There is a paucity of data on posaconazole (PCZ) dosing and therapeutic-drug-monitoring (TDM) in allogeneic hematopoietic cell transplant recipients (allogeneic-HCTr). This was a 3-year retrospective multicenter study (January 1, 2016 to December 31, 2018) in adult allogeneic-HCTr who received PCZ (intravenously, IV and/or as delayed-release tablet, DRT) as prophylaxis or treatment for ≥7 consecutive days (D) with at least 1-PCZ-level available using data of the Swiss Transplant Cohort Study. The primary objective was to describe the distribution of PCZ-level and identify predictors of therapeutic PCZ-level and associations between PCZ-dosing and PCZ-level. A total of 288 patients were included: 194 (67.4%) and 94 (32.6%) received PCZ as prophylaxis and treatment, respectively, for a median of 90 days (interquartile range, IQR: 42–188.5). There were 1944 PCZ-level measurements performed, with a median PCZ level of 1.3 mg/L (IQR: 0.8-1.96). PCZ-level was <0.7 mg/L in 383/1944 (19.7%) and <1.0 mg/L in 656/1944 (33.7%) samples. PCZ-level was <0.7 mg/L in 260/1317 (19.7%) and <1.0 mg/L in 197/627 (31.4%) in patients who received PCZ-prophylaxis versus treatment, respectively. There were no significant differences in liver function tests between baseline and end-of-treatment. There were nine (3.1%) breakthrough invasive fungal infections (bIFI), with no difference in PCZ levels between patients with or without bIFI. Despite a very intensive PCZ-TDM, PCZ-levels remain below target levels in up to one-third of allogeneic-HCTr. Considering the low incidence of bIFI observed among patients with PCZ levels in the targeted range, our data challenge the clinical utility of routine universal PCZ-TDM.

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Changing epidemiology of respiratory viral infections in hematopoietic cell transplant recipients and solid organ transplant recipients

Current Opinion in Infectious Diseases ◽

10.1097/qco.0b013e3283480440 ◽

2011 ◽

Vol 24 (4) ◽

pp. 333-343 ◽

Cited By ~ 86

Author(s):

Christian Renaud ◽

Angela P. Campbell

Keyword(s):

Viral Infections ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Hematopoietic Cell ◽

Solid Organ ◽

Cell Transplant ◽

Transplant Recipients ◽

Hematopoietic Cell Transplant ◽

Solid Organ Transplant Recipients ◽

Respiratory Viral Infections

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Effectiveness of bezlotoxumab for prevention of recurrent Clostridioides difficile infection among transplant recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab294 ◽

2021 ◽

Author(s):

Tanner M Johnson ◽

Amanda H Howard ◽

Matthew A Miller ◽

Lorna L Allen ◽

Misha Huang ◽

...

Keyword(s):

Organ Transplant ◽

Standard Of Care ◽

Hematopoietic Cell ◽

Solid Organ ◽

Cell Transplant ◽

Transplant Recipients ◽

Hematopoietic Cell Transplant ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Solid Organ Transplant Recipients

Abstract Background Bezlotoxumab significantly reduces the incidence of recurrent Clostridioides difficile infection; however, limited data is available in solid-organ and hematopoietic-cell transplant recipients. Methods We conducted a single-center retrospective analysis comparing recurrent Clostridioides difficile infection in solid-organ and hematopoietic-cell transplant recipients receiving standard of care alone (oral vancomycin, fidaxomicin, or metronidazole) or bezlotoxumab plus standard of care. The primary outcome was 90-day incidence of recurrent Clostridioides difficile infection, and secondary outcomes included 90-day hospital readmission, mortality, and incidence of heart failure exacerbation. Results Overall, 94 patients received bezlotoxumab plus standard of care (n=38) or standard of care alone (n=56). The mean age was 53 years, patients had a median of 3 prior Clostridioides difficile episodes, and 4 risk factors for recurrent infection. Most patients were solid-organ transplant recipients (76%), with median time to index Clostridioides difficile infection occurring 2.7 years post-transplantation. Ninety-day recurrent Clostridioides difficile infection occurred in 16% (6/38) in the bezlotoxumab cohort compared to 29% (16/56) in the standard of care cohort (p=0.13). Multivariable regression revealed bezlotoxumab was associated with significantly lower odds of 90-day recurrent Clostridioides difficile infection (Odds Ratio [95% CI]: 0.28 [0.08-0.91]). There were no differences in secondary outcomes, and no heart failure exacerbations were observed. Conclusions In a cohort of primarily solid-organ transplant recipients, bezlotoxumab was well tolerated and associated with lower odds of recurrent Clostridioides difficile infection at 90-days. Larger, prospective trials are needed to confirm these findings amongst solid-organ and hematopoietic-cell transplant populations.

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Reported β-Lactam and Other Antibiotic Allergies in Solid Organ and Hematopoietic Cell Transplant Recipients

Clinical Infectious Diseases ◽

10.1093/cid/ciz1025 ◽

2019 ◽

Vol 71 (7) ◽

pp. 1587-1594 ◽

Cited By ~ 4

Author(s):

Hannah Imlay ◽

Elizabeth M Krantz ◽

Erica J Stohs ◽

Kristine F Lan ◽

Jacqlynn Zier ◽

...

Keyword(s):

Antibiotic Use ◽

Hematopoietic Cell ◽

Solid Organ ◽

Cell Transplant ◽

Antibiotic Exposure ◽

Transplant Recipients ◽

Hematopoietic Cell Transplant ◽

Antibiotic Allergy ◽

Days Of Therapy ◽

Lactam Antibiotic

Abstract Background Patients with reported β-lactam antibiotic allergies (BLAs) are more likely to receive broad-spectrum antibiotics and experience adverse outcomes. Data describing antibiotic allergies among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients are limited. Methods We reviewed records of adult SOT or allogeneic HCT recipients from 1 January 2013 to 31 December 2017 to characterize reported antibiotic allergies at time of transplantation. Inpatient antibiotic use was examined for 100 days posttransplant. Incidence rate ratios (IRRs) comparing antibiotic use in BLA and non-BLA groups were calculated using multivariable negative binomial models for 2 metrics: days of therapy (DOT) per 1000 inpatient days and percentage of antibiotic exposure-days. Results Among 2153 SOT (65%) and HCT (35%) recipients, 634 (29%) reported any antibiotic allergy and 347 (16%) reported BLAs. Inpatient antibiotics were administered to 2020 (94%) patients during the first 100 days posttransplantation; average antibiotic exposure was 41% of inpatient-days (interquartile range, 16.7%–62.5%). BLA patients had significantly higher DOT for vancomycin (IRR, 1.4 [95% confidence interval {CI}, 1.2–1.7]; P < .001), clindamycin (IRR, 7.6 [95% CI, 2.2–32.4]; P = .001), and aztreonam in HCT (IRR, 9.7 [95% CI, 3.3–35.0]; P < .001), and fluoroquinolones in SOT (IRR, 2.9 [95% CI, 2.1–4.0]; P < .001); these findings were consistent when using percentage of antibiotic exposure-days. Conclusions Transplant recipients are frequently exposed to antibiotics and have a high prevalence of reported antibiotic allergies. Reported BLA was associated with greater use of β-lactam antibiotic alternatives. Pretransplant antibiotic allergy evaluation may optimize antibiotic use in this population.

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