Adjunctive glucocorticoid therapy for Pneumocystis jirovecii pneumonia in solid organ transplant recipients: A multicenter cohort, 2015-2020.

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.

Transplantid.net: A Pilot Crowdsourced, Living, Online Library of Resources for the Teaching and Practice of Transplant Infectious Diseases.

The field of transplant infectious diseases is rapidly evolving, presenting a challenge for clinical practice and trainee education. Here we describe the construction of transplantid.net, a free online library, crowdsourced and continuously updated for the dual purpose of point-of-care evidence-based management and teaching.

Noroviral diarrhea in solid organ transplant recipients: An analysis of interventions and outcomes.

INTRODUCTION: Noroviral infection can lead to chronic diarrhea in solid organ transplant (SOT) recipients with significant morbidity and mortality. Existing literature has described a wide spectrum of illness and has not come to a consensus on the optimal management of this condition. METHODS: We undertook a retrospective review of all adult SOT recipients between 1/1/2018 and 12/31/2020 who were diagnosed with their first episode of noroviral diarrhea (NVD). Demographic, clinical interventions, and outcomes within 6 months of diagnosis were recorded. Patients' outcomes were classified as either resolved, improved or persistent at 6 months. RESULTS: Seventy-nine SOT recipients were included. Thirty-eight patients (48%) had chronic diarrhea at baseline (CDB). Thirty-two patients (40%) received nitazoxanide, 28 patients (35%) had their immunosuppression adjusted and seven patients (9%) received intravenous immunoglobulin. Diarrhea improved or resolved in 68 patients (85%). Improvement or resolution of diarrhea was observed in 98% of those who did not have history of chronic diarrhea versus 74% in those who did (p = .002). NVD improved in all 12 patients who had mycophenolate discontinued, although this was not statistically significant (p = .131). CONCLUSION: CDB was associated with worse outcomes regardless of intervention. A low threshold to test for NVD in SOT recipients with chronic diarrhea is prudent to prevent delayed diagnosis.

Early Clostridioides difficile infection characterizations, risks, and outcomes in allogeneic hematopoietic stem cell and solid organ transplant recipients.

BACKGROUND: Clostridioides difficile infection (CDI) frequently complicates allogeneic hematopoietic stem cell (allo-HCT) and solid organ transplantation (SOT). METHODS: We retrospectively analyzed risk factors and outcomes of CDI occurring within 30 days of transplant. RESULTS: Between March 2010 and June 2015, 466 allo-HCT and 1454 SOT were performed. The CDI cumulative incidence (95% CI) was 10% (8-13) and 4% (3-5), following allo-HCT and SOT, respectively (p < .01), occurring at a median (range) 7.5 days (1-30) and 11 (1-30), respectively (p = .18). In multivariate analysis, fluoroquinolones use within 14 days pre-transplantation was a risk factor for CDI following allo-HCT (HR 4.06 [95% CI 1.31-12.63], p = .02), and thoracic organ(s) transplantation was a risk factor for CDI following SOT (HR 3.03 [95% CI 1.31-6.98]) for lung and 3.90 (1.58-9.63) for heart and heart/kidney transplant, p = .02. Compared with no-CDI patients, the length of stay (LOS) was prolonged in both allo-HCT (35 days [19-141] vs. 29 [13-164], p < .01) and SOT with CDI (16.5 [4-101] vs. 7 [0-159], p < .01), though not directly attributed to CDI. In allo-HCT, severe acute graft-versus-host disease (aGVHD) occurred more frequently in patients with CDI (33.3% vs. 15.8% without CDI, p = .01) and most aGVHD (87.5%) followed CDI. Non-relapse mortality or overall survival, not attributed to CDI, were also similar in both allo-HCT and SOT. CONCLUSIONS: Early post-transplant CDI is frequent, associated with fluoroquinolones use in allo-HCT and the transplanted organ in SOT, and is associated with longer LOS in both the groups without difference in survival but with increased aGVHD in allo-HCT.

Clostridioides difficile infection in solid organ and hematopoietic stem cell transplant recipients: A prospective multinational study.

BACKGROUND: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT. METHODS: Adults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow-up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited. RESULTS: A total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post-transplant (interquartile range, IQR: 6-133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6 weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty-three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p = .009) and recurrence (p = .014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p = .01). CONCLUSIONS: Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence.

Hemophagocytic lymphohistiocytosis induced by Toxoplasma gondii infection diagnosed by a bone marrow biopsy and DNA next-generation sequencing in an allogeneic hematopoietic stem cell transplant recipient.

In the United States, toxoplasmosis following allogeneic hematopoietic stem transplant (allo-HCT) is very rare with a rate only between 0.5% and 2%. The reported rates of hemophagocytic lymphohistiocytosis (HLH) following allo-HCT range between 0.3% and 17%. Secondary HLH due to toxoplasmosis infection is extremely rare. Herein, we report a case of secondary HLH due to toxoplasmosis following allo-HCT. The diagnosis was reached by a bone marrow biopsy and confirmed by DNA next generation sequencing and immunohistochemical (IHC) staining. The IHC staining included CD1a, a stain previously known to react with cells infected by Leishmania, here we show CD1a staining of macrophages infected with Toxoplasma gondii. Our report highlights the utility of bone marrow biopsy in diagnosing parasitic infection underlying HLH in post-transplant settings. The pre-transplant evaluation of patients from low endemic countries, is a great opportunity to obtain a travel history to determine the risks and the preventative measures against opportunistic infections including toxoplasmosis.

Long-Term Infectious and Noninfectious Outcomes of Monthly Alemtuzumab as a Calcineurin Inhibitor- and Steroid-Free Regimen for Pancreas Transplant Recipients.

Multiple doses of alemtuzumab for immunosuppressive therapy of patients with hematologic malignancies and hematopoietic stem cell transplant have been associated with a high rate of infection. In transplantation, limited alemtuzumab dosing has been successfully used as induction immunosuppression. The effect of multiple doses of alemtuzumab, used as maintenance therapy to minimize steroid and/or calcineurin inhibitor toxicity in solid organ transplant recipients, is unknown. We evaluated the infectious and noninfectious outcomes of 179 pancreas transplant recipients treated with alemtuzumab for induction and maintenance therapy (extended alemtuzumab exposure (EAE)) from 2/28/2003 through 8/31/2005, compared with 159 pancreas transplant recipients with standard induction and maintenance (SIM) therapy performed before (1/1/2002 until 12/31/2002) and after (1/1/2006 until 12/31/2006) the implementation of EAE. EAE was associated with higher risk of overall infections (hazard ratio (HR) 1.33 (1.06-1.66), P=0.01), bacterial infections (HR 1.33 (1.05-1.67), P=0.02), fungal infections (HR 1.86 (1.28-2.71), P < 0.01), and cytomegalovirus infections (HR 2.29 (1.39-3.77), P < 0.01). In addition, EAE was associated with higher risk of acute cellular rejection (HR 2.09 (1.46-2.99), P < 0.01). In conclusion, while a limited alemtuzumab dosing is safe and effective for induction therapy in pancreas transplantation, EAE combined with steroid and calcineurin minimization is associated with a high risk of infectious complications and acute cellular rejection.

Infections with DNA Viruses, Adenovirus, Polyomaviruses, and Parvovirus B19 in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies.

Infections due to adenovirus, polyomaviruses (BK and JC viruses), and parvovirus B19 may not be as common as infections due to other DNA viruses, such as cytomegalovirus in patients with hematological malignancies and the recipients of hematopoietic stem cell transplantation. However, these infections may result in life-threatening diseases that significantly impact patients' recovery, morbidity, and mortality. Treating physicians should be aware of the diseases associated with these viruses, the patient populations at increased risk for complications due to these infections, and the available diagnostic and therapeutic approaches.

Trichosporon loubieri Fungemia in a 39-Year-Old Caucasian Woman With B-Cell Lymphoblastic Leukemia.

We report a case of Trichosporon loubieri (T. loubieri) fungemia with likely liver involvement in a 39-year-old Caucasian patient with relapsed B-cell acute lymphoblastic leukemia after an allogeneic hematopoietic cell transplant. This is the fifth published case of T. loubieri infection and only the third case of T. loubieri fungemia, to our knowledge. All 3 cases of T. loubieri infection with fungemia had liver involvement.

Decreasing incidence of Staphylococcus aureus bacteremia over 9 years: greatest decline in community-associated methicillin-susceptible and hospital-acquired methicillin-resistant isolates.

BACKGROUND: The impact of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) emergence on the epidemiology of S aureus bacteremia (SAB) is not well documented. METHODS: This was an observational study of adult (aged ≥18 years) inpatients with SAB in a single 808-bed teaching hospital during 2002-2003, 2005-2006, 2008-2009, and 2010 with period-stratified SAB rate, onset mode, patient characteristics, and outcome. RESULTS: We encountered a total of 1,098 cases over the entire study period. The rate decreased steadily over time (from 6.64/10(3) discharges in 2002-2003 to 6.49/10(3) in 2005-2006, 5.24/10(3) in 2008-2009, and 5.00/10(3) in 2010; P = .0001), with a greater decline in community-associated cases (0.99/10(3), 0.77/10(3), 0.58/10(3), and 0.40/10(3), respectively; P = .0005) compared with health care-associated cases (5.65/10(3), 5.72/10(3), 4.66/10(3), and 4.60/10(3), respectively; P = .005). The decline was principally in MSSA (3.11/10(3), 2.21/10(3), 2.24/10(3), and 1.75/10(3), respectively; P = .00006), including both community-associated (P = .0002) and health care-associated cases (P = .006). Although overall rate changes in MRSA were not significant (P = .09), hospital-onset MRSA decreased markedly (P < .00001), whereas CA-MRSA increased (P = .03). The all-cause 100-day mortality rate did not change significantly (25.6% for 2002-2003, 25.2% for 2005-2006, 28.1% for 2008-2009, and 32.2% for 2010; P = .10). Differences in MSSA/MRSA-associated mortality decreased (20.1% vs 30.6%, P = .03 for 2002-2003; 18.1% vs 28.9%, P = .05 for 2005-2006; 21.7% vs 32.9%, P = .05 for 2008-2009; and 29.3% vs 34.9, P = .5 for 2010). CONCLUSIONS: SAB incidence is decreasing, with the greatest decline in community-associated MSSA and hospital-onset MRSA cases. Most health care-associated cases currently are community-onset. MRSA/MSSA-related mortality is comparable. These changes are likely related to the emergence of CA-MRSA and the inpatient-to-outpatient shift in health care.

Gemcitabine-associated "pseudocellulitis" and "pseudosepsis": a case report and review of the literature.

Chemotherapeutic agents have been associated with sepsis and a variety of opportunistic and nonopportunistic infections. This was attributed to their immunosuppressive effects. Like all other chemotherapeutic agents, the use of gemcitabine has been associated with different infectious processes, yet many conditions that mimic infections have also been linked to its use. Pseudosepsis is a condition that should be added to these previously described conditions, such as gemcitabine-induced pseudocellulitis. We describe a patient who suffered from 2 different gemcitabine-induced adverse events including pseudocellulitis that was not related to prior lymphedema or radiation recall phenomenon and pseudosepsis wherein antibiotics have no role in the treatment, and the discontinuation of the offending agent resulted in the resolution of the patient's symptoms.

Long-term outcomes of cardiovascular implantable electronic devices in patients with Staphylococcus aureus bacteremia.

BACKGROUND: The use of cardiovascular implantable electronic devices (CIEDs) is increasing. Staphylococcus aureus bacteremia (SAB) poses a risk for hematogenous seeding of the device. Our aim is to identify risk factors associated with secondary CIED infection, due to hematogenous seeding, during SAB from an unrelated primary focus. METHODS: All patients with SAB and CIED were screened. Patients with SAB due to a primary source unrelated to the CIED were included. Patients were classified into cases if CIED infection was documented and controls without CIED infection during a minimum of 12 weeks follow-up. A retrospective review of patients' charts was done. RESULTS: Thirty patients with CIED and SAB from an unrelated focus were identified. CIED infection developed in 11 patients (36.7%). No significant differences were noted between cases and controls in the source, time-to-therapy, and time-to-intervene but infected devices were more likely to be implantable cardioverter-defibrillators (ICD) versus permanent pacemakers (PPMs) (9/11 [81.8%] vs 2/11 [18.2%] respectively, crude odds ratio 12.6, 95% confidence interval 10.8-14.4; P = 0.003). CONCLUSION: Hematogenous seeding of a CIED during SAB from an unrelated focus is not uncommon. The risk factors for CIED seeding are unknown but ICD devices seem to be at greater risk when compared to PPM. The reasons are not yet clear. Larger studies are needed to better define risk factors and design preventive measures.

Delayed peripheral venous catheter-related Staphylococcus aureus bacteremia: onset ≥ 24 hours after catheter removal.

Peripheral venous catheter (PVC)-associated bacteremia usually develops during the indwelling period. We present a review of 14 patients who developed delayed onset Staphylococcus aureus bacteremia (D-SAB), 1-6 days after PVC removal, and compare them to 29 patients with early onset PVC-related S. aureus bacteremia (E-SAB). At the time of removal, the catheter site exhibited inflammation in 8 (57.1%) cases. At SAB onset, PVC site inflammation developed in all patients. Compared to E-SAB, patients with D-SAB were more often aged ≥ 65 y (71.4% vs. 34.5%; p = 0.03) and on corticosteroids (35.7% vs. 6.9%; p = 0.02). D-SAB was more complicated with persistent (> 3 days) bacteremia (42.9% vs. 13.8%; p = 0.04), metastatic infections (35.7% vs. 6.9%; p = 0.02), and slightly higher mortality (21.4% vs. 10.3%; p = 0.3). Logistic regression revealed that the predictors of D-SAB were corticosteroids (odds ratio (OR) 2.10, 95% confidence intervals (CI) 1.16-58.61) and age ≥ 65 y (OR 1.63, 95% CI 1.12-23.30). These patients may have impaired local/systemic defenses that lead to D-SAB, or a blunted host response with delayed recognition.

Risk factors for Pneumocystis jirovecii pneumonia in patients with lymphoproliferative disorders.

BACKGROUND: Guidelines for primary Pneumocystis jirovecii pneumonia (PCP) prophylaxis for patients with hematologic malignancy (HM) are still lacking. Our objective was to identify risk factors for PCP among patients with HM to help recognize patients who would benefit from primary PCP prophylaxis. MATERIAL AND METHODS: We performed a case-control study of adult patients with HM and negative for human immunodeficiency virus and with confirmed PCP by using cytology or histopathology from 2 medical centers over an 11-year period. Each case was matched with 4 patients without PCP by type of HM and year of treatment. We compared demographic, clinical, and laboratory data among cases and controls. Data were analyzed by using SPSS version 18.0. RESULTS: Fourteen cases and 56 controls were included in the study period. No significant differences were seen in demographics between both groups. All identified patients had lymphoproliferative HM, the majority of patients (93%) had either non-Hodgkin lymphoma or chronic lymphocytic leukemia. Autoimmune diseases were more frequent in cases vs. controls (28.6% vs. 5.4% P = .01). The receipt and duration of chemotherapy were similar in both groups. Among chemotherapeutic agents, including steroids, only fludarabine was associated with increased risk for PCP (50% vs. 17.9%; P = .02). No difference was found in total or lymphocyte percentage in cases at the time of PCP diagnosis vs. nadir values in controls. CONCLUSION: Patients with lymphoproliferative HM, specifically chronic lymphocytic leukemia and non-Hodgkin lymphoma, who are receiving fludarabine and with autoimmune disorders are at increased risk for PCP and should be considered for PCP primary prophylaxis.

Long-Term Resolution of Viral Breakthrough after Changing HIV Viral Load Assay.

BACKGROUND: Viral load (VL) measurement assays differ in their sensitivity with polymerase chain reaction assays (PCR) being more sensitive than branched DNA (bDNA) assays. We evaluated virologic outcomes of patients and physicians' response to increased VL after a switch from bDNA to PCR assay. METHOD: Retrospective, case-control study on 65 HIV+ patients receiving highly active antiretroviral therapy (HAART). Cases included patients with undetectable VL by bDNA that became detectable after the switch; controls were patients that remained undetectable. Records were reviewed up to 1 year after the switch. RESULTS: A total of 58.5% patients had detectable VL after the switch. Repeat VL testing and resistance testing were ordered in 15.4% and 23.1% of these patients, respectively. By 1 year, VL was undetectable in 82.8% of cases and 92% of controls (P = .30), without change in HAART. CONCLUSION: Transient viremia after changing VL assay reflects the different sensitivity of these assays with no impact on patients' outcomes compared to controls.

Association of parvovirus B19 infection with glomerulonephritis in an immunocompetent host: a case report.

We present the case of an immunocompetent host with acute glomerulonephritis following parvovirus B19 infection. Renal biopsy demonstrated immune-mediated disease; parvovirus B19 DNA was detected in renal tissue and blood. The patient improved with corticosteroid therapy. Repeat serology 3 months later confirmed recovery from the acute viral infection, although viraemia persisted.