White paper on antimicrobial stewardship in solid organ transplant recipients.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a "one-size-fits-all" style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Impact of narrowing perioperative antibiotic prophylaxis for left ventricular assist device implantation.

BACKGROUND: Although infections are a significant potential complication among patients undergoing left ventricular assist device (LVAD) implantation, standardized surgical infection prophylaxis (SIP) regimens are not well defined. At Montefiore Medical Center, a 4-drug SIP regimen containing fluconazole, ciprofloxacin, rifampin, and vancomycin was previously utilized. In January 2020, the antimicrobial stewardship program implemented a 2-drug SIP regimen of vancomycin and cefazolin to limit exposure to broad-spectrum antibiotics. This study evaluated LVAD-associated infection rates prior to and following the SIP revision. METHODS: A retrospective review of patients who underwent LVAD implantation from 1/2018 to 4/2021 was performed. Infections were classified using the International Society for Heart and Lung Transplantation definitions. Infection rates at 2 weeks, 30 days, and 90 days post-implantation in the 4-drug SIP regimen (1/2018-12/2019) and the 2-drug SIP regimen (1/2020 to 4/2021) were compared. RESULTS: A total of 71 patients were included. The number of patients with LVAD-associated infections (including surgical site infections) was not significantly different in either SIP group at 2 weeks (9% vs. 4%, p = .64), 30 days (9% vs. 11%, p = .99), or 90 days (19% vs. 14%, p = .75). There was no statistically significant difference in 30 or 90-day mortality. LVAD-associated gram-negative (7% vs. 7%; p > .99) and fungal (5% vs. 0%; p = .51) infections were uncommon. The most common organism isolated was Staphylococcus aureus, and the most common type of infection was pneumonia in both SIP groups. CONCLUSION: No significant difference in LVAD-associated infections or infection-related mortality was observed with de-escalation of perioperative antibiotics. Additional studies with larger sample sizes are needed to endorse the findings of this study.

Maintaining mask momentum in transplant recipients.

The widespread use of facemasks has been a crucial element in the control of the SARS-CoV-2 pandemic.  With mounting evidence for mask efficacy against respiratory infectious diseases and greater acceptability of this intervention, it is proposed that masking should continue after the pandemic has abated to protect some of our most vulnerable patients, recipients of stem cell and solid organ transplants. This may involve not only masking these high-risk patients, but possibly their close contacts and the healthcare workers involved in their care. We review the evidence for mask efficacy in prevention of respiratory viruses other than SARS-CoV-2 and address the burden of disease in transplant recipients.  Although we acknowledge that there are limited data on masking to prevent infection in transplant recipients, we propose a framework for the study and implementation of routine masking as a part of infection prevention interventions after transplantation.

COVID-19 infection in kidney transplant recipients at the epicenter of pandemics.

We investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, 132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. The prevalence of SARS-CoV-2 infection was 23.4% in the 975 patients tested by either RT-PCR or SARS-CoV-2 IgG. Older patients and patients with higher serum creatinine levels were more likely diagnosed by RT-PCR compared to SARS-CoV-2 IgG. Sixty-nine RT-PCR positive patients were screened for SARS-CoV-2 IgG antibodies at a median of 44 days post-diagnosis (Inter Quartile Range 31-58) and 80% were positive. Overall mortality was 20.5% but significantly higher (37.8%) in the patients who required hospitalization. Twenty-three percent of the hospitalized patients required kidney replacement therapy and 6.3% lost their allografts. In multivariable analysis, older age, receipt of deceased-donor transplantation, lack of influenza vaccination in the previous year and higher serum interleukine-6 levels were associated with mortality. Thus, 42% of patients with a kidney transplant and with COVID-19 were diagnosed on antibody testing without significant clinical symptoms; 80% of patients with positive RT-PCR developed SARS-CoV-2 IgG and mortality was high among patients requiring hospitalization.

Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation.

OBJECTIVES: To use a standardized tool for a multicenter assessment of antibiotic appropriateness in ICUs and identify local antibiotic stewardship improvement opportunities. DESIGN: Pilot point prevalence conducted on October 5, 2016; point prevalence survey conducted on March 1, 2017. SETTING: ICUs in 12 U.S. acute care hospitals with median bed size 563. PATIENTS: Receiving antibiotics on participating units on March 1, 2017. INTERVENTIONS: The Centers for Disease Control and Prevention tool for the Assessment of Appropriateness of Inpatient Antibiotics was made actionable by an expert antibiotic stewardship panel and implemented across hospitals. Data were collected by antibiotic stewardship program personnel at each hospital, deidentified and submitted in aggregate for benchmarking. hospital personnel identified most salient reasons for inappropriate use by category and agent. MEASUREMENTS AND MAIN RESULTS: Forty-seven ICUs participated. Most hospitals (83%) identified as teaching with median licensed ICU beds of 70. On March 1, 2017, 362 (54%) of 667 ICU patients were on antibiotics (range, 8-81 patients); of these, 112 (31%) were identified as inappropriate and administered greater than 72 hours among all 12 hospitals (range, 9-82%). Prophylactic antibiotic regimens and PICU patients demonstrated a statistically significant risk ratio of 1.76 and 1.90 for inappropriate treatment, respectively. Reasons for inappropriate use included unnecessarily broad spectrum (29%), no infection or nonbacterial syndrome (22%), and duration longer than necessary (21%). Of patients on inappropriate antibiotic therapy in surgical ICUs, a statistically significant risk ratio of 2.59 was calculated for noninfectious or nonbacterial reasons for inappropriate therapy. CONCLUSIONS: In this multicenter point prevalence study, 31% of ICU antibiotic regimens were inappropriate; prophylactic regimens were often inappropriate across different ICU types, particularly in surgical ICUs. Engaging intensivists in antibiotic stewardship program efforts is crucial to sustain the efficacy of antibiotics and quality of infectious diseases care in critical care settings. This study underscores the value of standardized assessment tools and benchmarking to be shared with local leaders for targeted antibiotic stewardship program interventions.

Infectious Complications in Lung Transplant Recipients.

Lung transplantation is a lifesaving intervention for patients with advanced lung disease. Due to a combination of immunosuppression, continuous exposure of the lungs to the environment, and complications at the anastomotic sites, lung transplant recipients are at high risk for infectious complications. The aim of this review is to summarize recent developments in the field of infectious diseases as it pertains to lung transplant recipients.

Bring it on again: antimicrobial stewardship in transplant infectious diseases: updates and new challenges.

Advancement in solid organ transplantation and hematopoietic stem cell transplant continues to improve the health outcomes of patients and widens the number of eligible patients who can benefit from the medical progress. Preserving the effectiveness of antimicrobials remains crucial, as otherwise transplant surgeries would be unsafe due to surgical site infections, and the risk of sepsis with neutropenia would preclude stem cell transplant. In this review, we provide updates on three previously discussed stewardship challenges: febrile neutropenia, Clostridioides difficile infection, and asymptomatic bacteriuria. We also offer insight into four new stewardship challenges: the applicability of the "shorter is better" paradigm shift to antimicrobial duration; antibiotic allergy delabeling and desensitization; colonization with multidrug-resistant gram-negative organisms; and management of cytomegalovirus infections. Specifically, data are accumulating for "shorter is better" and antibiotic allergy delabeling in transplant patients, following successes in the general population. Unique to transplant patients are the impact of multidrug-resistant organism colonization on clinical decision-making of antibiotic prophylaxis in transplant procedure and the need for antiviral stewardship in cytomegalovirus. We highlighted the expansion of antimicrobial stewardship interventions as potential solutions for these challenges, as well as gaps in knowledge and opportunities for further research.

Molecular diagnosis of an unusual aetiology of chronic abdominal pain with ascites.

An immigrant woman in her 60s with a complex medical history and remote occupational exposure to patients with tuberculosis (TB) presented with abdominal pain, early satiety, bloating and weight loss. Physical exam showed abdominal distention and ascites. Diagnostic paracentesis revealed low serum ascites albumin gradient and elevated ascitic lymphocytic count. However, fluid cytology, bacterial and mycobacterial cultures were negative. An interferon-gamma release assay for TB was indeterminate. MRI of the abdomen and pelvis showed a thickened endometrial stripe. Endometrial biopsy demonstrated non-caseating granulomatous endometritis. No organisms were identified on Grocott methenamine silver or acid-fast bacilli special stains. A tissue block from the endometrial biopsy submitted for DNA sequencing was positive for mycobacterium tuberculosis (MTB) complex Urine mycobacterial cultures were obtained and the patient was started on isoniazid, rifampin, ethambutol and pyrazinamide, with significant improvement in her symptoms. Urine mycobacterial cultures were eventually positive for pansusceptible MTB.

Real-world effectiveness of fidaxomicin in patients at high risk of Clostridioides difficile recurrence.

Objective: Compare the real-world impact of fidaxomicin (FDX) and vancomycin (VAN) on Clostridioides difficile infection (CDI) recurrence in a high-risk patient population. Design: A retrospective, matched-cohort study evaluating hospitalized patients with CDI from January 1, 2016, to November 1, 2022, within a tertiary academic medical center. Patients: Adult patients with at least 1 prior CDI case who received either FDX or VAN for non-fulminant CDI while admitted, and had at least 1 additional risk factor for recurrence. Risk factors included age >70, solid organ or bone marrow transplant recipients, broad-spectrum antibiotic use within 30 days, or receipt of chemotherapy/immune-modulating agents within 30 days of admission. FDX and VAN patients were matched according to risk factors. Results: A total of 415 patient admissions were identified. After the exclusion of 92 patients for fulminant CDI, diarrhea from another cause, or use of VAN taper therapy, and 15 unmatched patients, 308 patient admissions were included (68 FDX and 240 VAN patients). There were no significant differences in 4-week recurrence (26% vs 23%; OR 1.1; P = .51), 90-day CDI readmission (29% vs 23%; P = .65), or 90-day all-cause readmission (54% vs 53%; P = .91). There was a significant 17% decrease in 90-day mortality associated with the use of FDX (OR .3; P = .04). Conclusions: In a real-world high-risk patient population, the use of FDX compared to oral VAN did not result in decreased CDI recurrence within 4 weeks or fewer hospital readmissions within 90 days. Further research is needed to better assess the value of FDX in this patient population.

Defining the Landscape of Educational Experiences in Transplant Infectious Diseases: A National Survey of Infectious Diseases Fellows in the United States.

Background: Transplant infectious diseases (TID) is a growing area of expertise within infectious diseases (ID), but TID training is not standardized. Previous surveys of fellows identified opportunities to improve TID education resources but did not explore didactic, clinical, and nonclinical experiences comprehensively. Methods: The American Society of Transplantation ID Community of Practice surveyed adult and pediatric fellows in US-based general ID or dedicated TID training programs to explore their didactic exposure, clinical experiences, and non-direct patient care activities in TID. Results: A total of 234 fellows initiated the survey, and 195 (83%) (190 general ID and 19 TID fellows, including 125 adult, 76 pediatric, and 8 combined adult-pediatric fellows) completed the entire survey. More than half of the fellows described receiving no formal curricular content on most foundational topics in transplant medicine. Almost all respondents (>90%) had some inpatient TID experience, but for >60% of fellows this was <12 weeks annually. Clinical exposure varied by fellow and patient type-in an average month rotating on an inpatient TID service, more than half of adult fellows had evaluated ≥10 kidney, liver, or hematopoietic stem cell transplant recipients but <10 heart, lung, pancreas, or intestinal recipients; pediatric fellows saw <10 of all patient types. Nearly half (46%) of general ID fellows had not spent any time in the dedicated TID clinic at their program. Few fellows had participated in protocol development, organ selection meetings, or donor evaluations. Conclusions: This survey highlights important gaps in TID training. Given the increasing need for TID specialists, updated curricula and educational resources are needed.

Meeting the Consultation Surge: A Nationwide Survey of Consult Volume and Mitigation Strategies in Infectious Diseases Fellowship Programs.

High patient volume in fellowship programs can affect learning, wellness, and patient outcomes. Training programs must find ways to mitigate high consultation volume to protect the learning environment. This survey describes average new consults and average censuses for infectious diseases training programs and strategies implemented to mitigate high volume.

What is the role of the clinical microbiology laboratory in the care of diagnostically challenging OPAT patients? Illustrative cases and literature review.

Optimal care of patients requiring long-term outpatient parenteral or oral antimicrobial therapy by infectious diseases (ID) specialists is facilitated by an accurate microbiologic diagnosis. Close collaboration between ID specialists and the clinical microbiology laboratory for routine or specialized molecular testing can result in more accurate diagnoses, streamlined antimicrobial regimens, and improved patient outcomes.

Bring it on: Top five antimicrobial stewardship challenges in transplant infectious diseases and practical strategies to address them.

Antimicrobial therapies are essential tools for transplant recipients who are at high risk for infectious complications. However, judicious use of antimicrobials is critical to preventing the development of antimicrobial resistance. Treatment of multidrug-resistant organisms is challenging and potentially leads to therapies with higher toxicities, intravenous access, and intensive drug monitoring for interactions. Antimicrobial stewardship programs are crucial in the prevention of antimicrobial resistance, though balancing these strategies with the need for early and frequent antibiotic therapy in these immunocompromised patients can be challenging. In this review, we summarize 5 frequently encountered transplant infectious disease stewardship challenges, and we suggest strategies to improve practices for each clinical syndrome. These 5 challenging areas are: asymptomatic bacteriuria in kidney transplant recipients, febrile neutropenia in hematopoietic stem cell transplantation, antifungal prophylaxis in liver and lung transplantation, treatment of left-ventricular assist device infections, and Clostridioides difficile infection in solid-organ and hematopoietic stem-cell transplant recipients. Common themes contributing to these challenges include limited data specific to transplant patients, shortcomings in diagnostic testing, and uncertainties in pharmacotherapy.

Does local matter? Evaluating susceptibility variations between hospital-wide and hematology-oncology unit antibiograms.

Antibiograms are important for guiding empiric antibiotics for febrile neutropenia. However, hospital-wide antibiograms may not capture complexities of patients with hematologic malignancies. We created a hematology-oncology unit-specific antibiogram and found higher resistance among Escherichia coli, Klebsiella pneumonia, and Enterococcus isolates compared to hospital-wide data.

Expanding the scope and visibility of ambulatory stewardship programs with novel coronavirus disease 2019 (COVID-19) therapeutics.

Antimicrobial stewardship programs (ASPs) can be expanded to the outpatient setting to serve as a first line of defense against coronavirus disease 19 (COVID-19) hospitalizations and to reduce the burden on emergency departments and acute-care hospitals. Given the numerous emergency use authorizations of monoclonal antibodies and oral antivirals, ASPs possess the expertise and leadership to direct ambulatory COVID-19 initiatives and transform it into a predominantly outpatient illness. In this review, we summarize the critical role and benefits of an ASP-championed ambulatory COVID-19 therapeutics program.

COVID-19 and Solid Organ Transplantation: A Review Article.

The coronavirus pandemic has significantly impacted solid organ transplantation (SOT). Early in the outbreak period, transplant societies recommended suspending living kidney transplant programs in communities with widespread transmission to avoid exposing recipients to increased risk of immunosuppression, while recommendations were made to reserve deceased-donor kidney transplantation for likely life-saving indications. SOT recipients may be at high risk from COVID-19 disease due to chronic immunosuppressive treatment and other medical comorbidities. Mortality rates reported between 13 to over 30% in SOT recipients. In addition to high rates of complications and mortality attributable to COVID-19 infections, the pandemic has also led to additional complexities in transplantation including new questions regarding screening of donors and recipients, decision making to accept a patient for kidney transplant or wait after pandemic. The clinical implications of COVID-19 infection may also differ depending on the type of the transplanted organ and recipient comorbidities which further impacts decisions on continuing transplantation during the pandemic. Transplant activity during a pandemic should be tailored with careful selection of both donors and recipients. Furthermore, while tremendous strides have been made in treatment strategies and vaccinations, the impact of these in transplant recipients may be attenuated in the setting of their immunosuppression. In this review, we aim to summarize several aspects of COVID-19 in transplantation, including the immune response to SARS-CoV-2, SARS-CoV-2 diagnostics, clinical outcomes in SOT recipients, and end-stage kidney disease patients, transplant activity during the pandemic, and treatment options for COVID-19 disease.

Bacterial and fungal coinfections in COVID-19 patients hospitalized during the New York City pandemic surge.

We observed bacterial or fungal coinfections in COVID-19 patients admitted between March 1 and April 18, 2020 (152 of 4,267, 3.6%). Among these patients, mortality was 57%; 74% were intubated; 51% with bacteremia had central venous catheters. Time to culture positivity was 6-7 days, and 79% had received prior antibiotics. Metallo-ß-lactamase-producing E. cloacae coinfections occurred in 5 patients.

Rapid Implementation of a Multidisciplinary COVID-19 Cytokine Storm Syndrome Task Force.

OBJECTIVE: Patients with coronavirus disease 2019 (COVID-19) can progress to a state of unregulated inflammation called cytokine storm syndrome (CSS). We describe formation and operation of a COVID-19 multidisciplinary consultation service that was allowed to individualize treatment for critically ill patients with COVID-19 during the pandemic. METHODS: Institutional experts from different subspecialties formed a COVID-19 CSS task force at Montefiore Medical Center, Bronx, NY. They agreed on a set of four clinical and six laboratory parameters that can help early identify COVID-19 CSS. We describe the formation and implementation of the COVID-19 task force. The case series description of the COVID-19 CSS consultation cohort highlights consultation volume, baseline characteristics, clinical and laboratory parameters, and how biologic treatments were allocated to these patients. RESULTS: Between April 4,2020, and May 7,2020, the COVID-19 CSS task force was formed, consisting of adult and pediatric rheumatologists and allergy and immunology physicians. The task force evaluated a total of 288 patients, of whom 197 (68%) were male, the median (interquartile range [IQR]) age was 62 (51-70) years, 122 (42%) were Hispanic, and 88 (31%) were Black or African American. The common presenting symptoms in all referred patients were dyspnea (85%) and diarrhea (80%). Thirty-one patients who received biologic therapy were younger, with a median (IQR) age of 53 (32-63) years, as opposed to 62.5 (52-70) years in the nonbiologic group (P = 0.008). A higher proportion receiving biologics was in the critical care setting (26 [84%] vs 151 [59%]; P = 0.006). CONCLUSION: To the best of our knowledge, this is the first multidisciplinary collaborative effort to provide individualized patient recommendations for evaluation and treatment of patients with COVID-19 who may have CSS. This working model helped to devise an approach that may have identified patients who were most likely to benefit from biologic therapy in the absence of evidence-based guidelines.