Publications by authors named "Carolyn D Alonso"

28 Publications

  • Page 1 of 1

Ultrasensitive and quantitative toxin measurement correlates with baseline severity, severe outcomes, and recurrence among hospitalized patients with Clostridioides difficile infection.

Clin Infect Dis 2021 Sep 19. Epub 2021 Sep 19.

Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

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 (≥ 18y) with CDI (acute diarrhea, positive stool NAAT, and decision to treat). Baseline stool toxin A and B concentrations were measured by Single Molecule Array. Subjects were classified by baseline CDI severity (four scoring methods) and outcomes within 40 days (death, ICU 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<0.01). 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 (IQR 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=0.003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2-4 (60.5-66.1%)(P=0.02). 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<0.001) and higher rates of detectable toxin (85.7% versus 64.0%, P=0.004).

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.
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http://dx.doi.org/10.1093/cid/ciab826DOI Listing
September 2021

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

J Antimicrob Chemother 2021 Jul 29. Epub 2021 Jul 29.

Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland.

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 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL; P < 0.001), but improved by 2 weeks (0.91 ± 0.84 mg/dL; P = 0.007) and 4 weeks (0.96 ± 0.89 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.
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http://dx.doi.org/10.1093/jac/dkab259DOI Listing
July 2021

Humoral Immune Response to Toxins A and B in Hospitalized Immunocompromised Patients With Infection.

Open Forum Infect Dis 2021 Jul 1;8(7):ofab286. Epub 2021 Jun 1.

Harvard Medical School, Boston, Massachusetts, USA.

Background: The humoral immune response to toxins in infection (CDI) is incompletely characterized in immunocompromised hosts (ICHs).

Methods: We conducted a prospective study of hospitalized adults with CDI, with and without immunosuppression (hematologic malignancy, active solid tumor, solid organ or stem cell transplant, inflammatory bowel disease, autoimmune disease, congenital or acquired immunodeficiency, asplenia, chronic receipt of high-dose steroids, or receipt of immunosuppressing medications within 12 months). Serum and stool antibody concentrations of immunoglobulin (Ig)M, IgG, and IgA to toxins A and B at treatment days 0, 3, and 10-14 were compared.

Results: Ninety-eight subjects (47 ICH; 51 non-ICH) were enrolled. Baseline serum antitoxin A and B antibody levels were similar. At day 3, ICHs demonstrated lower serum levels of antitoxin A IgG, antitoxin A IgA, and antitoxin B IgA (all < .05). At day 10-14, lower antitoxin A IgG concentrations were observed in ICHs (ICH, 21 enzyme-linked immunosorbent assay [ELISA] units; interquartile range [IQR], 16.4-44.6) compared with non-ICH subjects (49.0 ELISA units; IQR, 21.5-103; = .045). In stool, we observed lower concentrations of antitoxin B IgA antibodies at baseline and at day 3 for ICH subjects, with a notable difference in concentrations of antitoxin B IgA at day 3 (ICH, 6.7 ELISA units [IQR, 1.9-13.9] compared with non-ICH, 18.1 ELISA units [IQR, 4.9-31.7]; = .003).

Conclusions: The ICHs with CDI demonstrated lower levels of antitoxin antibodies in serum and stool during early CDI therapy compared with non-ICHs. These data provide insight into the humoral response to CDI in ICHs.
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http://dx.doi.org/10.1093/ofid/ofab286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271131PMC
July 2021

Case Report: Refractory Cryptosporidiosis after CAR T-Cell Therapy for Lymphoma.

Am J Trop Med Hyg 2021 Jul 8. Epub 2021 Jul 8.

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Cryptosporidial diarrhea is uncommon in immunocompetent individuals, more often seen in severely immunocompromised patients. Severe refractory cases have been described in patients with HIV/AIDS before the advent of modern antiretroviral therapy due to an inability to mount an adequate cellular immune response. We describe an 85-year-old patient post-chimeric antigen receptor T-cell therapy relapsed lymphoma who developed refractory Cryptosporidium spp. diarrhea in the setting of persistent CD4+ cytopenia. Despite receiving multiple antiparasitic agents, including failure of a prolonged course of nitazoxanide, the patient experienced persistent symptoms for 9 months with repeatedly positivity stool Cryptosporidium spp. direct fluorescent antibody (DFA) test. We highlight this case of refractory Cryptosporidium spp. and the importance of recognizing the pathogen in a non-HIV-infected immunosuppressed host.
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http://dx.doi.org/10.4269/ajtmh.21-0246DOI Listing
July 2021

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

JAMA 2021 04;325(15):1535-1544

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

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.
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http://dx.doi.org/10.1001/jama.2021.3645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953339PMC
April 2021

Casting a wider protective net: Anti-infective vaccine strategies for patients with hematologic malignancy and blood and marrow transplantation.

Blood Rev 2021 05 17;47:100779. Epub 2020 Nov 17.

Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, 110 Francis Street, Suite GB, Boston, MA 02215, USA. Electronic address:

Patients who have hematologic malignancies are at high risk for infections but vaccinations may be effective prophylaxis. The increased infection risk derives from immune defects secondary to malignancy, the classic example being CLL, and chemotherapies and immunotherapy used to treat the malignancies. Therapy of hematologic malignancies is being revolutionized by introduction of novel targeted agents and immunomodulatory medications, improving the survival of patients. At the same time those agents uniquely change the infection risk and response to immunizations. This review will summarize current vaccine recommendations for patients with hematologic malignancies including patients who undergo hematopoietic cell transplant.
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http://dx.doi.org/10.1016/j.blre.2020.100779DOI Listing
May 2021

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

Dig Dis Sci 2021 Oct 8;66(10):3303-3306. Epub 2020 Nov 8.

Divisions of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center & Harvard Medical School, Dana 617D, 330 Brookline Avenue, Boston, MA, 02215, USA.

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.
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http://dx.doi.org/10.1007/s10620-020-06683-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105423PMC
October 2021

Beyond the Superficial: Disseminated Infection in a Kidney Transplant Recipient.

Open Forum Infect Dis 2020 Jul 5;7(7):ofaa281. Epub 2020 Jul 5.

Harvard Medical School, Boston, Massachusetts, USA.

Superficial dermatophyte infections are common in the general population and are readily treated with topical antifungals. Deeper invasion is rare, and dissemination to visceral organs is extremely uncommon. We describe a 66-year-old renal transplant recipient who developed disseminated infection while undergoing treatment for acute humoral rejection. The infection presented as a facial rash with subsequent dissemination to the lungs and chest wall. All sites of infection improved with combination administration of oral posaconazole and terbinafine. In this work, we review the available literature regarding management of disseminated infection and discuss therapeutic interventions for disseminated dermatophytosis in immunosuppressed hosts.
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http://dx.doi.org/10.1093/ofid/ofaa281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566364PMC
July 2020

Identification of a norovirus outbreak on a hematopoietic stem cell transplant unit and development and implementation of a novel infection prevention algorithm for controlling transmission.

Infect Control Hosp Epidemiol 2020 04 24;41(4):472-476. Epub 2020 Feb 24.

Harvard Medical School, Boston, Massachusetts, United States.

Controlling norovirus transmission in units with immunocompromised patients is challenging. We present a cluster of norovirus cases that occurred on a stem-cell transplant unit and the prevention efforts that were implemented to limit the outbreak. Protocols developed to control this cluster may provide a model for other facilities.
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http://dx.doi.org/10.1017/ice.2020.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483699PMC
April 2020

Recent developments in the management of recurrent Clostridioides difficile infection.

Anaerobe 2020 Apr 10;62:102108. Epub 2019 Oct 10.

Department of Medicine, Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.anaerobe.2019.102108DOI Listing
April 2020

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

Clin Infect Dis 2020 09;71(6):1472-1478

Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

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.
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http://dx.doi.org/10.1093/cid/ciz978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486840PMC
September 2020

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

Anaerobe 2020 Feb 4;61:102098. Epub 2019 Sep 4.

Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

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.
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http://dx.doi.org/10.1016/j.anaerobe.2019.102098DOI Listing
February 2020

Bezlotoxumab for the prevention of infection: a review of current evidence and safety profile.

Infect Drug Resist 2019 17;12:1-9. Epub 2018 Dec 17.

Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USA.

infection (CDI) is a leading nosocomial disease estimated to cause nearly half a million cases in the United States annually. Recurrent CDI (rCDI) affects ~25% of patients after completion of standard of care therapy and is associated with substantial health care costs and a negative impact on patient's overall markers of quality of life. Bezlotoxumab is the first of its kind monoclonal antibody directed against toxin B and indicated for prevention of rCDI in at-risk patients. For the present review, we assessed English-language studies evaluating the clinical efficacy, safety, and pharmacokinetics of bezlotoxumab in humans. Relevant studies were obtained through PubMed, Embase, Cochrane database library, Web of Science, and clinicaltrials.gov. Overall, bezlotoxumab demonstrated a 40% relative reduction rate (absolute rate reduction of ~10%) and a number needed to treat of 10 patients with a favorable safety profile. Special populations, including the elderly, immunocompromised, and patients with end-stage renal disease were evaluated in post hoc analyses with a similarly favorable reduction in rCDI. This review presents and interprets the most recent safety data and the clinical application of bezlotoxumab, highlighting specific high-risk patient populations.
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http://dx.doi.org/10.2147/IDR.S159957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301304PMC
December 2018

Adjunctive Use of Cidofovir and Intravenous Immunoglobulin to Treat Invasive Adenoviral Disease in Solid Organ Transplant Recipients.

Pharmacotherapy 2018 12 26;38(12):1260-1266. Epub 2018 Nov 26.

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Background: Infections with adenoviruses (ADVs) can result in considerable mortality and morbidity in solid organ transplant (SOT) recipients. Standard therapy for ADV infections in transplant recipients is not established. At our institution, intravenous cidofovir and immunoglobulin have been used to treat disseminated or invasive ADV in SOT and hematopoietic stem cell transplant recipients.

Methods: A retrospective case series of SOT recipients treated with cidofovir and intravenous immunoglobulin was performed.

Results: Five SOT recipients (four renal and one heart transplant) with adenovirus infection were treated successfully with cidofovir and immunoglobulin. Cidofovir was discontinued after the first negative ADV viral load and resolution of clinical symptoms, given the concern for nephrotoxicity in renal transplant recipients. Renal tubular acidosis type 2 and iritis were observed in two patients receiving therapy.

Conclusion: Symptom resolution and a single negative ADV viral load may be indicators for cidofovir discontinuation.
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http://dx.doi.org/10.1002/phar.2194DOI Listing
December 2018

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

Transpl Infect Dis 2018 Dec 31;20(6):e12967. Epub 2018 Jul 31.

Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

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.
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http://dx.doi.org/10.1111/tid.12967DOI Listing
December 2018

Clinical characteristics and treatment outcomes among respiratory syncytial virus (RSV)-infected hematologic malignancy and hematopoietic stem cell transplant recipients receiving palivizumab.

Leuk Lymphoma 2019 01 27;60(1):85-91. Epub 2018 Jun 27.

a Department of Medicine , Beth Israel Deaconess Medical Center and Harvard Medical School , Boston , MA , USA.

Palivizumab has been used to treat respiratory syncytial virus (RSV)-infected hematologic malignancy patients at our institution based on limited published data. We conducted this retrospective study to evaluate clinical outcomes and mortality rates of RSV-infected hematologic malignancy patients from 2007 to 2016. A total of 67 patients (19 received palivizumab and 47 received supportive care) were identified. Palivizumab-treated patients had a significantly higher proportion of underlying ischemic heart disease, graft-versus-host-disease, hypogammaglobulinemia, and concomitant pulmonary infections. There were no significant differences in mortality rates or readmission rates between the two groups. The estimated odds ratio for death in patients receiving palivizumab after adjusting for propensity scores and covariates were 0.12 ([0.01, 1.32], p = .08) and 0.09 ([0.01, 1.03], p = .05) respectively. After adjustment for factors associated with severity of illness, there was no difference in mortality among patients treated with palivizumab.
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http://dx.doi.org/10.1080/10428194.2018.1468896DOI Listing
January 2019

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

Transpl Infect Dis 2017 Aug 12;19(4). Epub 2017 Jul 12.

Harvard Medical School, Boston, MA, USA.

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.
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http://dx.doi.org/10.1111/tid.12728DOI Listing
August 2017

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

Ann Pharmacother 2017 Sep 6;51(9):804-810. Epub 2017 May 6.

1 Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USA.

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.
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http://dx.doi.org/10.1177/1060028017706374DOI Listing
September 2017

Does Adjunctive Tigecycline Improve Outcomes in Severe-Complicated, Nonoperative Infection?

Open Forum Infect Dis 2017 10;4(1):ofw264. Epub 2017 Feb 10.

Division of Infectious Diseases and.

Severe infection is associated with a high rate of mortality; however, the optimal treatment for severe- complicated infection remains uncertain for patients who are not candidates for surgical intervention. Thus, we sought to evaluate the benefit of adjunctive tigecycline in this patient population using a retrospective cohort adjusted for propensity to receive tigecycline. We found that patients who received tigecycline had similar outcomes to those who did not, although the small sample size limited power to adjust for comorbidities and severity of illness.
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http://dx.doi.org/10.1093/ofid/ofw264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413996PMC
February 2017

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

Transpl Infect Dis 2017 Feb 11;19(1). Epub 2017 Jan 11.

Department of Infectious Diseases and Medical Microbiology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, QC, 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.
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http://dx.doi.org/10.1111/tid.12648DOI Listing
February 2017

An Unusual Cause of a Breast Mass in a Patient from China.

Am J Trop Med Hyg 2015 Aug 1;93(2):347-9. Epub 2015 Jun 1.

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of Breast Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Sparganosis is a parasitic infection caused by Spirometra spp. and often presents as a subcutaneous swelling, most commonly noticed in the abdominal wall or extremities. Amphibians such as frogs ingest infected copepods (crustaceans that have ingested coracidia, i.e., Spirometra spp. embryos) and serve as a secondary intermediate host. Complete surgical excision is recommended for definitive diagnosis and treatment. Granulomatous inflammation is the most common histologic finding. Although dissemination can occur, most cases are localized. Serum enzyme-linked immunosorbent assay (ELISA) has been suggested as a potential surveillance tool. Medical therapy with antiparasitic agents, such as praziquantel, is not typically recommended but may be effective at high doses. Preventing recurrence thus depends on adequate surgical removal of the parasite. We report a case of a breast mass caused by sparganosis infection in a Chinese female whose likely exposure was due to frog consumption. The diagnosis was confirmed on surgical excision and no systemic antiparasitic therapy was required.
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http://dx.doi.org/10.4269/ajtmh.15-0235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530759PMC
August 2015

Recurrent Clostridium difficile infection: From colonization to cure.

Anaerobe 2015 Aug 27;34:59-73. Epub 2015 Apr 27.

Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.anaerobe.2015.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492812PMC
August 2015

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

Transfusion 2015 Apr 11;55(4):719-25. Epub 2014 Nov 11.

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

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 β-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.
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http://dx.doi.org/10.1111/trf.12908DOI Listing
April 2015

Clostridium difficile Infection (CDI) in Solid Organ and Hematopoietic Stem Cell Transplant Recipients.

Curr Infect Dis Rep 2014 Aug;16(8):414

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Lowry Medical Office Building, Suite GB, 110 Francis Street, Boston, MA, 02215, USA,

Patients undergoing solid organ and stem cell transplantation are at increased risk of Clostridium difficile infection (CDI) compared with nontransplant patients. CDI may be associated with significant morbidity in this population including prolonged hospitalization, increased hospital charges, and complications in the transplanted organ. A combination of host factors, including both B-cell and T-cell immunosuppression, in addition to traditional risk factors for CDI such as broad-spectrum antibacterial exposure, are likely to contribute to the elevated risk in this population. This article addresses the current epidemiology and risk factors for CDI in transplant recipients, the downstream complications following this infection, and current management strategies, with an emphasis on novel approaches for primary and recurrent disease including fecal microbiota transplantation.
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http://dx.doi.org/10.1007/s11908-014-0414-0DOI Listing
August 2014

Clostridium difficile infection after adult autologous stem cell transplantation: a multicenter study of epidemiology and risk factors.

Biol Blood Marrow Transplant 2013 Oct 1;19(10):1502-8. Epub 2013 Aug 1.

Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address:

We sought to describe the epidemiology of Clostridium difficile infection (CDI) among adult recipients of autologous hematopoietic stem cell transplantation (auto-HSCT) within the first year after HSCT in centers with variable epidemiology of hypertoxigenic strains. A multicenter, retrospective nested case-control study was conducted among 873 auto-HSCT recipients at Johns Hopkins Hospital (JHH) and Hôpital Maisonneuve-Rosemont (HMR) between January 2003 and December 2008. Despite center differences in the prevalence of NAP-1 strains during the study period (21% to 43% at JHH versus 80% to 84% in HMR), the 1-year incidence of CDI was similar in the 2 hospitals (6.2% at JHH versus 5.7% at HMR). The median time to infection was 11 days (interquartile range, 1 to 27 days). In case-control analyses, grade ≥2 mucositis (odds ratio [OR], 3.00; P = .02) and receipt of a fourth-generation cephalosporin (OR, 2.76; P = .04) were identified as predictors for CDI. Mucositis was the strongest predictor of risk for CDI in multivariate analysis (adjusted OR, 2.77; P = .03). CDI is a common and early complication of auto-HSCT. Treatment-related gastrointestinal mucosal damage, along with the potentially modifiable risk of antimicrobial exposure, influence the risk for CDI early after auto-HSCT.
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http://dx.doi.org/10.1016/j.bbmt.2013.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806308PMC
October 2013

Clostridium difficile infection among hematopoietic stem cell transplant recipients: beyond colitis.

Curr Opin Infect Dis 2013 Aug;26(4):326-31

Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

Purpose Of Review: To review the most recent data regarding the epidemiology, risks factors, and outcomes among hematopoietic stem cell transplant recipients with Clostridium difficile infection (CDI).

Recent Findings: With the emergence of an epidemic strain of C. difficile known as NAP1 in the early 2000s, rates of this infection have escalated globally. Hematopoietic stem cell transplant recipients appear to be one of the most vulnerable populations for the development of CDI. Traditional risk factors for CDI including antimicrobial exposure and older age are likely only a piece of the overall risk profile, with recent study results also emphasizing other factors such as transplant type, conditioning regimen, and graft-versus-host disease (GVHD). The relationship between CDI and subsequent development of GVHD, particularly of the gastrointestinal tract, is of specific interest. A bidirectional relationship of association has been highlighted in a number of recent studies and underscores the need for further prospective studies to address the potential indirect effects of alloreactivity induced by CDI.

Summary: CDI has emerged as one of the most common infections in the early transplant period. Recent studies have begun to address the epidemiology of disease, risk factors for, and outcomes after infection in the stem cell transplant. However, more research is needed to unravel the observed relationship between CDI and GVHD.
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http://dx.doi.org/10.1097/QCO.0b013e3283630c4cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222064PMC
August 2013

Epidemiology and outcomes of Clostridium difficile infections in hematopoietic stem cell transplant recipients.

Clin Infect Dis 2012 Apr 12;54(8):1053-63. Epub 2012 Mar 12.

Department of Medicine, The Johns Hopkins Hospital, Baltimore, MD 21205, USA.

Background. Clostridium difficile is the leading cause of infectious diarrhea among hospitalized patients and is a major concern for patients undergoing hematopoietic stem cell transplantation (HSCT). Risk factors and the natural history of C. difficile infection (CDI) are poorly understood in this population. Methods. We performed a retrospective nested case-control study to describe the epidemiology, timing, and risk factors for CDI among adult patients who received HSCTs at our center from January 2003 through December 2008. Results. The overall 1-year incidence of CDI was 9.2% among HSCTs performed (n = 999). The median time to diagnosis of CDI was short among both autologous and allogeneic HSCT recipients (6.5 days and 33 days, respectively). Risk factors for CDI in allogeneic HSCT recipients included receipt of chemotherapy prior to conditioning for HSCT, broad-spectrum antimicrobial use, and acute graft-versus-host disease (GVHD; adjusted odds ratio [AOR], 4.45; 95% confidence interval [CI], 1.54-12.84; P = .006). There was a strong relationship between early CDI and subsequent development of gastrointestinal tract GVHD in the year following allogeneic HSCT (P < .001). Gastrointestinal GVHD was also strongly associated with an increased risk for recurrent CDI (AOR, 4.23 [95% CI, 1.20-14.86]; P = .02). Conclusions. These results highlight the high incidence and early timing of CDI after HSCT. Early timing, coupled with the noted risk of pretransplant chemotherapy, suggests that the natural history of disease in some patients may involve colonization prior to HSCT. A potentially important interplay between CDI and GVHD involving the gastrointestinal tract was observed.
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http://dx.doi.org/10.1093/cid/cir1035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309884PMC
April 2012

Increasing incidence of iliopsoas abscesses with MRSA as a predominant pathogen.

J Infect 2011 Jul 18;63(1):1-7. Epub 2011 May 18.

Department of Medicine, Division of Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.

Objectives: Iliopsoas abscesses (IPAs) are rare infections involving purulence within the muscles of the iliopsoas compartment, seldom due to Methicillin-resistant Staphylococcus aureus (MRSA) historically. This study was designed to evaluate the clinical characteristics and outcomes of patients with IPAs.

Methods: A retrospective analysis of the demographics, clinical presentation, microbiologic data and treatment modalities among patients with IPAs from 1993 to 2007 at The Johns Hopkins Hospital was performed.

Results: Among 61 patients with IPAs, infection rates increased from 0.5 cases/10,000 admissions (1993-2004) to 6.5 cases/10,000 admissions (2005-2007) (P < 0.001). An adjacent infectious focus was identified in 80% of patients, from skeletal (48%), intra-abdominal (23%), vascular (5%), genitourinary (3%), and cutaneous sources (2%). During 2005-2007, MRSA became a predominant pathogen, accounting for 25% of all cases and 37% of cases with a definitive microbiologic diagnosis (P = 0.006). Patients with IPAs >2 cm were more likely to undergo drainage, with trends toward longer hospitalizations, longer antibiotic courses, and increased odds of securing a definitive microbiologic diagnosis.

Conclusions: Since 2005, rates of IPA have dramatically increased, with MRSA now the leading cause of infection. Knowledge of common pathogens should guide antimicrobial therapy including empiric coverage for MRSA in institutions with similar populations, especially if culture data are not available.
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http://dx.doi.org/10.1016/j.jinf.2011.05.008DOI Listing
July 2011
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