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.

Epidemiology and outcomes associated with enterococcal blood stream infection among liver and kidney transplant recipients.

Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus accounts for up to 20% of BSIs in this population, with vancomycin-resistant enterococcus (VRE) posing a particular risk. This is a retrospective, case-control study of adult liver and kidney transplant recipients between 01/01/2016 and 06/30/2021 that characterizes the epidemiology and outcomes of enterococcal BSIs in liver and kidney transplantations at a single institution. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.3%). Cases were mostly liver transplant recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14-43); controls included 14 KT recipients (50%). Groups differed significantly (all p < .05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p < .0001). There were no differences in 1-year mortality between the groups. Enterococcus faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. In our liver and kidney transplants, enterococcal BSIs occurred early among liver transplant recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period.

Influence of induction therapy and antiretroviral regimen on outcomes in kidney transplant recipients living with human immunodeficiency.

PURPOSE: Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes. METHODS: We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. RESULTS: Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations. CONCLUSIONS: In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs.

How Would You Manage This Patient With Clostridioides difficile Infection? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and the American College of Gastroenterology recently released updated guidelines on management of patients with Clostridioides difficile infection. Although these 2 guidelines generally agree, there are a few important differences in their advice to clinicians. In these rounds, 2 experts, an infectious diseases specialist and a gastroenterologist, discuss antibiotic treatment options for nonsevere disease, the role of fecal microbiota transplantation for fulminant disease, and the use of bezlotoxumab to prevent recurrence in the context of Ms. C, a 48-year-old woman with fulminant C difficile infection.

Stool Interleukin-1ß Differentiates Clostridioides difficile Infection (CDI) From Asymptomatic Carriage and Non-CDI Diarrhea.

BACKGROUND: Despite advances in the understanding and diagnosis of Clostridioides difficile infection (CDI), clinical distinction within the colonization-infection continuum remains an unmet need. METHODS: By measuring stool cytokines and antitoxin antibodies in well-characterized cohorts of CDI (diarrhea, nucleic acid amplification test [NAAT] positive), non-CDI diarrhea (NCD; diarrhea, NAAT negative), asymptomatic carriers (ASC; no diarrhea, NAAT positive) and hospital controls (CON; no diarrhea, NAAT negative), we aim to discover novel biological markers to distinguish between these cohorts. We also explore the relationship of these stool cytokines and antitoxin antibody with stool toxin concentrations and disease severity. RESULTS: Stool interleukin (IL) 1ß, stool immunoglobulin A (IgA), and immunoglobulin G (IgG) anti-toxin A had higher (P < .0001) concentrations in CDI (n = 120) vs ASC (n = 43), whereas toxins A, B, and fecal calprotectin did not. Areas under the receiver operating characteristic curve (ROC-AUCs) for IL-1ß, IgA, and IgG anti-toxin A were 0.88, 0.83, and 0.83, respectively. A multipredictor model including IL-1ß and IgA anti-toxin A achieved an ROC-AUC of 0.93. Stool IL-1ß concentrations were higher in CDI compared to NCD (n = 75) (P < .0001) and NCD + ASC+ CON (CON, n = 75) (P < .0001), with ROC-AUCs of 0.83 and 0.86, respectively. Stool IL-1ß had positive correlations with toxins A (ρA = +0.55) and B (ρB = +0.49) in CDI (P < .0001) but not in ASC (P > .05). CONCLUSIONS: Stool concentrations of the inflammasome pathway, proinflammatory cytokine IL-1ß, can accurately differentiate CDI from asymptomatic carriage and NCD, making it a promising biomarker for CDI diagnosis. Significant positive correlations exist between stool toxins and stool IL-1ß in CDI but not in asymptomatic carriers.

Ultrasensitive and Quantitative Toxin Measurement Correlates With Baseline Severity, Severe Outcomes, and Recurrence Among Hospitalized Patients With Clostridioides difficile Infection.

BACKGROUND: Stool toxin concentrations may impact Clostridioides difficile infection (CDI) severity and outcomes. We correlated fecal C difficile toxin concentrations, measured by an ultrasensitive and quantitative assay, with CDI baseline severity, attributable outcomes, and recurrence. METHODS: We enrolled 615 hospitalized adults (≥18 years) with CDI (acute diarrhea, positive stool nucleic acid amplification testing, and decision to treat). Baseline stool toxin A and B concentrations were measured by single molecule array. Subjects were classified by baseline CDI severity (4 scoring methods) and outcomes within 40 days (death, intensive care unit stay, colectomy, and recurrence). RESULTS: Among 615 patients (median, 68.0 years), in all scoring systems, subjects with severe baseline disease had higher stool toxin A+B concentrations than those without (P < .01). Nineteen subjects (3.1%) had a severe outcome primarily attributed to CDI (group 1). This group had higher median toxin A+B (14 303 pg/mL [interquartile range, 416.0, 141 967]) than subjects in whom CDI only contributed to the outcome (group 2, 163.2 pg/mL [0.0, 8423.3]), subjects with severe outcome unrelated to CDI (group 3, 158.6 pg/mL [0.0, 1795.2]), or no severe outcome (group 4, 209.5 pg/mL [0.0, 8566.3]) (P = .003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2-4 (60.5%-66.1%) (P = .02). Individuals with recurrence had higher toxin A+B (2266.8 pg/mL [188.8, 29411]) than those without (154.0 pg/mL [0.0, 5864.3]) (P < .001) and higher rates of detectable toxin (85.7% versus 64.0%, P = .004). CONCLUSIONS: In CDI patients, ultrasensitive stool toxin detection and concentration correlated with severe baseline disease, severe CDI-attributable outcomes, and recurrence, confirming the contribution of toxin quantity to disease presentation and clinical course.

Higher In Vivo Fecal Concentrations of Clostridioides difficile Toxins A and B in Patients With North American Pulsed-Field Gel Electrophoresis Type 1/Ribotype 027 Strain Infection.

Ultrasensitive, quantitative Clostridioides difficile stool toxin measurement demonstrated significantly higher concentrations of toxins A and B in patients infected with the North American pulsed-field gel electrophoresis type 1/ribotype 027 (NAP-1/027) strain compared with other strains, providing in vivo confirmation of the in vitro association between NAP-1/027 and elevated toxin production.

Safety and efficacy of intravenously administered cidofovir in adult haematopoietic cell transplant recipients: a retrospective multicentre cohort study.

OBJECTIVES: To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). METHODS: This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). RESULTS: We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115; 69.7%), 1 mg/kg/week (18; 10.9%), 3 mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ±â€Š0.95 mg/dL) compared with baseline (0.91 ±â€Š0.39 mg/dL; P < 0.001), but improved by 2 weeks (0.91 ±â€Š0.84 mg/dL; P = 0.007) and 4 weeks (0.96 ±â€Š0.89 mg/dL; P = 0.03) post-EOT. Median viral load significantly declined for patients with adenovirus DNAaemia by EOT (P < 0.0001) and for patients with CMV DNAaemia by EOT + 4 weeks (P = 0.003), but not for patients with BK virus DNAaemia. CONCLUSIONS: One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.

Absence of Toxemia in Clostridioides difficile Infection: Results from Ultrasensitive Toxin Assay of Serum.

Clostridioides difficile infection (CDI) is caused by Toxins A and B, secreted from pathogenic strains of C. difficle. This infection can vary greatly in symptom severity and in clinical presentation. Current assays used to diagnose CDI may lack the required sensitivity to detect the exotoxins circulating in blood. The ultrasensitive single molecule array (Simoa) assay was modified to separately detect toxin A and toxin B in serum with a limit of detection at the low picogram level. When applied to a diverse cohort, Simoa was unable to detect toxins A or B in serum from patients with CDI, including many classified as having severe disease. The detection of toxin may be limited by the inference of antitoxin antibodies circulating in serum. This result does not support the hypothesis that toxemia occurs in C. difficile infection, conflicting with the findings of other published reports.

Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19.

Importance: Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines. Objective: To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses. Design, Setting, and Participants: Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S. Interventions: Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010 viral particles or 1 × 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group). Main Outcomes and Measures: Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses. Results: Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced. Conclusion and Relevance: In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine. Trial Registration: ClinicalTrials.gov Identifier: NCT04436276.

Laxative Use Does Not Preclude Diagnosis or Reduce Disease Severity in Clostridiodes difficile Infection.

BACKGROUND: To optimize utility of laboratory testing for Clostridiodes difficile infection (CDI), the 2017 Infectious Diseases Society of America-Society for Healthcare Epidemiology of America (IDSA-SHEA) clinical practice guidelines recommend excluding patients from stool testing for C. difficile if they have received laxatives within the preceding 48 hours. Sparse data support this recommendation. METHODS: Patients with new-onset diarrhea (≥3 bowel movements in any 24-hour period in the 48 hours before stool collection) and a positive stool C. difficile nucleic acid amplification test were enrolled. Laxative use within 48 hours before stool testing, severity of illness (defined by 4 distinct scoring methods), and clinical outcomes were recorded. RESULTS: 209 patients with CDI were studied, 65 of whom had received laxatives. There were no significant differences in the proportion of patients meeting severe CDI criteria by 4 severity scoring methods in patients receiving versus not receiving laxatives (66.2% vs 56.3%, respectively; P = .224) by IDSA-SHEA, the primary scoring system. Similar rates of serious outcomes attributable to CDI, including death, intensive care unit admission, and colectomy, were observed in the laxative and no laxative groups. CONCLUSIONS: Our study found similar rates of severe CDI and serious CDI-attributable clinical outcomes in CDI-diagnosed patients who did or did not receive laxatives. Precluding recent laxative users from CDI testing, as proposed by the IDSA-SHEA guideline, carries a potential for harm due to delayed diagnosis and treatment.

Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials.

Recurrent Clostridioides (formerly Clostridium) difficile infection (rCDI) is common, and patients who have had one recurrence are more likely to have multiple recurrences. Frequent recurrences have been associated with increased morbidity and mortality, high healthcare costs, and lower quality of life. In this review, we compare the efficacy of interventions designed to prevent rCDI. We performed a systematic review of the English literature, including randomized controlled trials (RCTs) that evaluated rCDI as an outcome. Studies were included irrespective of patient demographics, disease severity, type of intervention, comparator used, or time-point of outcome evaluation. We performed a comprehensive literature search with the assistance of a research librarian. Two reviewers independently extracted data and assessed risk of bias. Our search yielded 38 RCTs (8,102 participants). Nineteen RCTs (3,743 subjects) evaluated antibiotics, eight fecal microbiota transplantation (FMT) (582 subjects), three monoclonal antibodies (MAbs) (2,805 subjects), and eight probiotics, prebiotics, or non-antibiotic polymers (972 subjects). The antibiotic and FMT therapies that demonstrated efficacy in rCDI prevention included: fidaxomicin (when compared to a ten-day vancomycin course) and FMT administered by nasogastric tube (when compared to a fourteen-day vancomycin course and a fourteen-day vancomycin course plus bowel lavage). Actoxumab (MAb against C. difficile toxin A; CDA1) plus bezlotoxumab (MAb against C. difficile toxin B; CDB1) in combination or bezlotoxumab alone appeared to be more effective in preventing rCDI compared to actoxumab alone. Of the prebiotics, probiotics, and nonantibiotic polymers, oligofructose, Saccharomyces boulardii, and the nontoxigenic C. difficile strain M3 were the most efficacious for rCDI prevention. Thirty-eight RCTs (>8,000 participants) evaluating treatment modalities for CDI were examined for efficacy in prevention of rCDI. Several CDI-specific antibiotics, FMT modalities, monoclonal antibodies, and various prebiotics and probiotics demonstrated a reduction in risk of rCDI with the greatest risk reduction observed with FMT and monoclonal antibody therapy. It is notable that the comparators in these studies were very different from one another and the relative risk reduction of rCDI may not be directly comparable from one study to the next.

Recent developments in the management of recurrent Clostridioides difficile infection.

Clostridioides (formerly Clostridium) difficile is responsible for a substantial burden of nosocomial infection. Recurrent C. difficile infection (rCDI) remains a concern due to its high morbidity, mortality, and cost. Despite the updated 2017 IDSA C. difficile treatment guidelines, there remains a lack of well-studied preventive control measures and treatment modalities for rCDI. There are ongoing efforts to develop novel therapies, such as new antibiotics with a lesser impact on gut microbiota and more targeted therapies, such as bacteriotherapy. This mini review highlights key rCDI management updates, preventive measures and ongoing research on novel treatment strategies including bacteriotherapy.

Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with solid organ transplants: an institutional experience and review of the literature.

Clostridium difficile, an anaerobic gram-positive, spore-forming bacillus, has become the most common cause of nosocomial infectious diarrhea, and is associated with increased mortality in all populations. Patients who have received solid organ transplants (SOT) are at increased risk of Clostridium difficile infection (CDI) and CDI recurrence (rCDI). This may be related to chronic immunosuppression, frequent antibiotic exposure, and increased or prolonged hospitalizations. Increased morbidity and mortality from CDI is well-described in SOT patients. Conventional treatments for index and recurrent CDI include vancomycin and fidaxomicin. Fecal microbiota transplantation has emerged as an effective and safe alternative for treating rCDI in the general population. Reports of its safety in certain immunocompromised populations, such as those with inflammatory bowel disease, appear reassuring, but outcomes among SOT patients are less well known. Here, we summarize the experiences published to date on the treatment of rCDI with FMT in SOT patient, and also describe our detailed FMT protocol and experience in treating a series of SOT patients with rCDI. In addition to reporting the safety and efficacy of our FMT experience, we also discuss the diagnostic challenges and considerations in this population of solid organ transplant recipients.

Bezlotoxumab: Could This be the Answer for Clostridium difficile Recurrence?

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of bezlotoxumab (BEZ), a novel monoclonal antibody against Clostridium difficile toxin B. DATA SOURCES: A PubMed search was conducted for data between 1946 and April 2017 using MeSH terms bezlotoxumab, MK-6072, or MDX-1388 alone and the terms Clostridium difficile combined with monoclonal antibody or antitoxin. STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to English-language studies that described clinical efficacy, safety, and pharmacokinetics in humans and animals. Abstracts featuring prepublished data were also evaluated for inclusion. DATA SYNTHESIS: BEZ is indicated for adult patients receiving standard-of-care (SoC) antibiotics for C difficile infection (CDI) to prevent future recurrence. Two phase III trials-MODIFY I (n = 1452) and MODIFY II (n = 1203)-demonstrated a 40% relative reduction in recurrent CDI (rCDI) with BEZ compared with placebo (16.5% vs 26.6%, P < 0.0001). The most common adverse drug events associated with BEZ were mild to moderate infusion-related reactions (10.3%). CONCLUSIONS: In patients treated with SoC antibiotics, BEZ is effective in decreasing rCDI. BEZ has no apparent effect on treatment of an initial CDI episode. In light of increasing rates of CDI, BEZ is a promising option for preventing recurrent episodes. The greatest benefit has been demonstrated in high-risk patients, though the targeted patient population is yet to be defined.

Risk factors for the development of Clostridium difficile infection in adult allogeneic hematopoietic stem cell transplant recipients: A single-center study in Québec, Canada.

BACKGROUND: Clostridium difficile infection (CDI) is a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our primary objective was to determine risk factors for the development of CDI during the first year following allo-HSCT. METHODS: A matched case-control study nested in a cohort of allo-HSCT at a single hospital in Montréal, Québec, Canada, was conducted from 2002 through 2011. RESULTS: Sixty-five of 760 patients who underwent allo-HSCT between 2002 and 2011 developed CDI, representing an incidence of 8.6%. We selected 123 controls matched for year of transplant for risk factor analyses. In the multivariable analysis, receipt of trimethoprim-sulfamethoxazole (TMP-SMX) prior to transplantation (adjusted odds ratio [aOR] 0.07, 95% confidence interval [CI] 0.02-0.27), mucositis (aOR 5.90, 95% CI 2.08-16.72), and reactivation of cytomegalovirus (CMV) (aOR 6.17, 95% CI 2.17-17.57) and of other Herpesviridae viruses (aOR 3.04, 95% CI 1.13-8.16) were the variables that remained statistically associated with CDI. High-risk antibiotic use in the late post-transplant period (aOR 7.63, 95% CI 2.14-27.22) was associated with development of late CDI. CONCLUSION: This study revealed reactivation of CMV and other Herpesviridae viruses as novel risk factors for CDI. Administration of TMP-SMX prior to transplantation was independently associated with a decreased risk of CDI. Early and late CDI after HSCT may have distinct risk factors.

A multicenter, retrospective, case-cohort study of the epidemiology and risk factors for Clostridium difficile infection among cord blood transplant recipients.

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of health-care associated infectious diarrhea. The aim of this study was to evaluate the epidemiology and risk factors for CDI in the 100 days following umbilical cord blood transplantation (UCBT) at three Boston hospitals. METHODS: We performed a multicenter, retrospective, case-cohort study of 226 UCBT recipients at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, and Dana Farber/Brigham and Women's Cancer Center from 2003 to 2012. CDI was defined as diarrhea (≥3 unformed bowel movements for at least 2 days) plus a positive stool test for toxinogenic C. difficile and not attributed to any other cause. RESULTS: Among 226 UCBT recipients, 22 patients (9.7%) developed CDI within the first 100 days of transplant (corresponding to an infection rate of 10.8 cases per 10 000 person-days). The 100-day and 1-year rates were stable across the time period and between institutions. UCBT recipients with CDI were more likely than non-CDI patients to be older, with higher body mass indices, and to have received an antipseudomonal penicillin agent. In a time-dependent case-cohort analysis of the risk factors associated with CDI in the first 100 days after UCBT, bacterial infection after UCBT was the strongest risk factor for CDI (hazard ratio 2.8; 95% confidence interval 1.08-7.24; P=.03), after adjustment for transplant variables including antibiotic exposure. CONCLUSION: This study verifies the previously reported risk factors for CDI including older age and antibiotic exposure and identifies a novel association between bacterial infections and risk for CDI.

Transfusion-associated Anaplasma phagocytophilum infection in a pregnant patient with thalassemia trait: a case report.

BACKGROUND: Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile illness caused by the bacterium Anaplasma phagocytophilum. Although usually transmitted via tick bite, HGA may rarely also be acquired through transfusion. HGA during pregnancy may pose significant gestational risks due to altered maternal immune status and the potential for perinatal transmission. CASE REPORT: A pregnant 34-year-old Massachusetts woman with ß-thalassemia trait was diagnosed at 32 weeks of gestation with transfusion-associated HGA (TAHGA) after receiving nine leukoreduced red blood cell transfusions. She was successfully treated with rifampin therapy and gave birth to a healthy child who tested negative for HGA after delivery. An implicated blood donor was subsequently identified through physician collaboration with the regional American Red Cross and Massachusetts Department of Public Health. DISCUSSION: This is the 11th reported case of HGA in pregnancy and is at least the sixth known case in which leukoreduction did not prevent TAHGA. As seen in this case, nonspecific symptomatology of variable onset can impede diagnosis and treatment. This may increase risk of poor outcomes in maternal HGA patients. Cases of TAHGA, although currently uncommon, may increase as the incidence of HGA in certain parts of the country increases. CONCLUSION: Heightened cross-institutional awareness of the potential risk of TAHGA is warranted. Clinicians need to consider transfusion-associated infections when fever occurs in a transfusion recipient. This case provides additional evidence that leukoreduction does not obviate risk of A. phagocytophilum contamination of donated blood components.

Recurrent Clostridium difficile infection: From colonization to cure.

Clostridium difficile infection (CDI) is increasingly prevalent, dangerous and challenging to prevent and manage. Despite intense national and international attention the incidence of primary and of recurrent CDI (PCDI and RCDI, respectively) have risen rapidly throughout the past decade. Of major concern is the increase in cases of RCDI resulting in substantial morbidity, morality and economic burden. RCDI management remains challenging as there is no uniformly effective therapy, no firm consensus on optimal treatment, and reliable data regarding RCDI-specific treatment options is scant. Novel therapeutic strategies are critically needed to rapidly, accurately, and effectively identify and treat patients with, or at-risk for, RCDI. In this review we consider the factors implicated in the epidemiology, pathogenesis and clinical presentation of RCDI, evaluate current management options for RCDI and explore novel and emerging therapies.