Inclusion, Diversity, Access, and Equity in Infectious Diseases Fellowship Training: Tools for Program Directors.

The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This article represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.

Concurrent pulmonary Aspergillus and non-Aspergillus mold infections in allogeneic hematopoetic cell transplant recipients.

Patients with hematologic malignancies and recipients of hematopoietic cell transplantation (HCT) are at high risk for invasive mold infections (IMIs). However, risk factors and clinical manifestations are similar between Aspergillus spp. and non-Aspergillus spp. IMIs. Herein, we describe three HCT recipients who had probable invasive pulmonary Aspergillus and non-Aspergillus co-infections. Antifungal agents were changed to voriconazole in two cases where, ultimately, non-Aspergillus molds were diagnosed after these patients died. Our cases highlight the need for better fungal diagnostics in immunocompromised patients. Clinicians should be aware that Aspergillus spp. and non-Aspergillus spp. IMIs can occur concurrently.

Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study.

BACKGROUND: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. METHODS: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. RESULTS: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections. CONCLUSIONS: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

The Effect of Neutropenia and Filgrastim (G-CSF) on Cancer Patients With Coronavirus Disease 2019 (COVID-19) Infection.

BACKGROUND: Neutropenia is commonly encountered in cancer patients. Recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim), a cytokine that initiates proliferation and differentiation of mature granulocytes, is widely given to oncology patients to counteract neutropenia, reducing susceptibility to infection. However, the clinical impact of neutropenia and G-CSF use in cancer patients with coronavirus disease 2019 (COVID-19) remains unknown. METHODS: An observational cohort of 379 actively treated cancer patients with COVID-19 was assembled to investigate links between concurrent neutropenia and G-CSF administration on COVID-19-associated respiratory failure and death. These factors were encoded as time-dependent predictors in an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, the degree of response to G-CSF, based on rise in absolute neutrophil count (ANC) 24 hours after growth factor administration, was also incorporated into a similar Cox model. RESULTS: In the setting of active COVID-19 infection, outpatient receipt of G-CSF led to an increased number of hospitalizations (hazard ratio [HR]: 3.54, 95% confidence interval [CI]: 1.25-10.0, P value: .017). Furthermore, among inpatients, G-CSF administration was associated with increased need for high levels of oxygen supplementation and death (HR: 3.56, 95% CI: 1.19-10.2, P value: .024). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 7.78, 95% CI: 2.05-27.9, P value: .004). CONCLUSIONS: The potential risks versus benefits of G-CSF administration should be considered in neutropenic cancer patients with COVID-19, because G-CSF administration may lead to worsening clinical and respiratory status.

Fecal Microbiota Transplantation Is Safe for Clostridiodies difficile Infection in Patients with Solid Tumors Undergoing Chemotherapy.

BACKGROUND: Recurrent Clostridiodies difficile infection (CDI) contributes to morbidity and mortality in cancer patients. Fecal microbiota transplantation (FMT) has been proven to be effective in treatment of recurrent CDI, but immunocompromised patients have been excluded from prospective studies due to safety concerns. The aim of this study was to investigate the safety of FMT for recurrent CDI in immunocompromised patients with solid tumor malignancy undergoing chemotherapy. METHODS: This was a single center, prospective observational study of patients at a tertiary care cancer center of 10 patients with recurrent CDI who were at least 18 years of age, with a solid tumor malignancy who had received chemotherapy within the previous 6 months. Patients received FMT either by upper endoscopy or colonoscopy and were followed for 6 months. Safety was a primary outcome measured by infections occurring within 2 weeks of FMT. Efficacy of FMT was also evaluated. RESULTS: Nineteen patients were evaluated. On applying exclusion criteria, 10 were included in the study. One patient requested to be off study within 2 weeks and was considered a treatment failure. Seven received FMT via upper endoscopy, three via colonoscopy. There were no infectious complications from FMT. Eight patients (80%) were cured after the first FMT. All eight patients went on to restart oncologic treatment with an average of 32.5 days after FMT. CONCLUSIONS: FMT is safe and effective for recurrent CDI in solid tumor patients undergoing chemotherapy. Patients can resume oncologic treatment after FMT.

An inexpensive point-of-care immunochromatographic test for Talaromyces marneffei infection based on the yeast phase specific monoclonal antibody 4D1 and Galanthus nivalis agglutinin.

Talaromyces marneffei is a thermally dimorphic fungus that causes opportunistic systemic mycoses in patients with AIDS or other immunodeficiency syndromes. The purpose of this study was to develop an immunochromatographic strip test (ICT) based on a solid phase sandwich format immunoassay for the detection of T. marneffei antigens in clinical urine specimens. The T. marneffei yeast phase specific monoclonal antibody 4D1 (MAb4D1) conjugated with colloidal gold nanoparticle was used as a specific signal reporter. Galanthus nivalis Agglutinin (GNA) was adsorbed onto nitrocellulose membrane to serve as the test line. Similarly, a control line was created above the test line by immobilization of rabbit anti-mouse IgG. The immobilized GNA served as capturing molecule and as non-immune mediated anti-terminal mannose of T. marneffei antigenic mannoprotein. The MAb4D1-GNA based ICT showed specific binding activity with yeast phase antigen of T. marneffei, and it did not react with other common pathogenic fungal antigens. The limit of detection of this ICT for T. marneffei antigen spiked in normal urine was approximately 0.6 µg/ml. The diagnostic performance of the ICT was validated using 341 urine samples from patents with culture- confirmed T. marneffei infection and from a control group of healthy individuals and patients with other infections in an endemic area. The ICT exhibited 89.47% sensitivity, 100% specificity, and 97.65% accuracy. Our results demonstrate that the urine-based GNA-MAb4D1 based ICT produces a visual result within 30 minutes and that the test is highly specific for the diagnosis of T. marneffei infection. The findings validate the deployment of the ICT for clinical use.

Penicillin Allergy Testing: An Outpatient Nurse-Driven Program for Patients With Cancer.

BACKGROUND: Penicillin allergy testing (PAT) can decrease the use of unnecessary antibiotics by clarifying who is truly allergic. OBJECTIVES: This article describes the development and implementation of an oncology outpatient nurse-driven PAT program. METHODS: A nurse-driven program, initiated with allergy screening at the first encounter, was designed to identify patients with oncologic diagnoses eligible for PAT. Once verified eligible, patients undergo a three-step testing process (scratch test, intradermal injection, and IV challenge dose) administered by the infusion nurse. FINDINGS: From November 2018 to December 2019, 82 outpatients with reported penicillin allergies were screened; 90% were eligible for PAT, and 97% of patients tested were negative for penicillin allergy. A significant reduction in aztreonam use among patients admitted for hematopoietic stem cell transplantation was also noted as compared to before PAT was offered.

Characterization of a novel yeast phase-specific antigen expressed during in vitro thermal phase transition of Talaromyces marneffei.

Talaromyces marneffei is a dimorphic fungus that has emerged as an opportunistic pathogen particularly in individuals with HIV/AIDS. Since its dimorphism has been associated with its virulence, the transition from mold to yeast-like cells might be important for fungal pathogenesis, including its survival inside of phagocytic host cells. We investigated the expression of yeast antigen of T. marneffei using a yeast-specific monoclonal antibody (MAb) 4D1 during phase transition. We found that MAb 4D1 recognizes and binds to antigenic epitopes on the surface of yeast cells. Antibody to antigenic determinant binding was associated with time of exposure, mold to yeast conversion, and mammalian temperature. We also demonstrated that MAb 4D1 binds to and recognizes conidia to yeast cells' transition inside of a human monocyte-like THP-1 cells line. Our studies are important because we demonstrated that MAb 4D1 can be used as a tool to study T. marneffei virulence, furthering the understanding of the therapeutic potential of passive immunity in this fungal pathogenesis.

Determinants of COVID-19 disease severity in patients with cancer.

As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.

Determinants of Severity in Cancer Patients with COVID-19 Illness.

New York State had 180,458 cases of SARS-CoV-2 and 9385 reported deaths as of April 10th, 2020. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher COVID-19 death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19 disease4. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. Since March 10th, 2020 Memorial Sloan Kettering Cancer Center performed diagnostic testing for SARS-CoV-2 in symptomatic patients. Overall, 40% out of 423 patients with cancer were hospitalized for COVID-19 illness, 20% developed severe respiratory illness, including 9% that required mechanical ventilation, and 9% that died. On multivariate analysis, age ≥ 65 years and treatment with immune checkpoint inhibitors (ICI) within 90 days were predictors for hospitalization and severe disease, while receipt of chemotherapy within 30 days and major surgery were not. Overall, COVID-19 illness is associated with higher rates of hospitalization and severe outcomes in patients with cancer. Association between ICI and COVID-19 outcomes will need interrogation in tumor-specific cohorts.

Trends in Invasive Pneumococcal Disease in Cancer Patients After the Introduction of 7-valent Pneumococcal Conjugate Vaccine: A 20-year Longitudinal Study at a Major Urban Cancer Center.

Background: Rates of invasive pneumococcal disease (IPD) declined since routine childhood immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. We studied the impact of PCV7 on the incidence of IPD in cancer patients. Methods: This was a retrospective analysis of adult and pediatric patients treated at Memorial Sloan Kettering Cancer Center from 1992 to 2012. Recovery of Streptococcus pneumoniae from a sterile site defined IPD. IPD incidence was calculated as cases per 1,000 unique patient-visits per year (UPV). IPD incidence was calculated for the periods: "before PCV7" (1992-2000), "after PCV7" (2001-2010) and "after PCV13" (2011-2012). Results: Of 343 IPD cases, 165, 155, and 23 cases occurred "before PCV7," "after PCV7" and "after PCV13" respectively. The IPD incidence declined from 0.43 "before PCV7" to 0.17 "after PCV7" (95% confidence interval [CI]: 0.33-0.46, P < .001) and 0.11 "after PCV13" (95% CI: 0.42-0.96, P = .004). Adults with hematologic malignancies and children had the highest incidence. In patients 1-4 years old, the incidence declined from 11.2 "before PCV7" to 2.38 "after PCV7" (79% decrease, 95% CI: 0.1-0.4, P < .001). In patients with hematologic malignancies, the incidence declined from 2.55 "before PCV7" to 0.92 "after PCV7" (64% decrease, 95% CI: 0.27-0.47, P < .001). Conclusions: The incidence of IPD among cancer patients sharply declined after introduction of PCV7; especially in high risk groups. The decline in adults suggests an indirect effect from PCV7 childhood vaccination.

Two cases of spontaneous remission of non-parasitic chyluria.

OBJECTIVES: Chyluria is a medical condition with presence of chyle in urine. The disease is most prevalent in South East Asian countries mostly caused by parasitic (Wuchereria bancrofti) infections. Our objective was to investigate the spontaneous remission of non-parasitic chyluria. DESIGN AND METHODS: The spontaneous remission of non-parasitic chyluria cases were worked up with diagnostic investigations, clinical assessment and studied in detail with respect to their natural evolution. RESULTS: We present two patients who were evaluated in the nephrology clinic with symptoms of milky urine and painless hematuria. Midnight blood smear was negative for filarial parasites. Urine culture was without mycobacteria. Urine cytology and IgG western blot for cysticercus were negative. Imaging for a lymphatic leak by lymphoscintigraphy was unrevealing. Chyluria resolved spontaneously in both patients. CONCLUSIONS: In our cases, radiologic visualization via lymphoscintigraphy was unrevealing. The patients were managed conservatively and fortunately underwent spontaneous remission marked by the disappearance of chyluria within several months of her initial diagnosis. In our opinion this spontaneous remission could be due to unrevealed lymphatico-renal fistula collapse or sclerosis of lymphatics caused by contrast media.

Nontuberculous Mycobacterial Infections After Silicone Breast Implant Reconstruction Emphasize a Diversity of Infecting Mycobacteria.

Postsurgical skin and soft tissue infections (SSTIs) caused by nontuberculous mycobacteria (NTM) are uncommon, indolent, difficult to treat, and often mimic pyogenic bacterial infections. Here we present 3 cases of NTM infections following placement of silicone implants for reconstructive breast surgery. These cases emphasize the importance of a high index of suspicion for NTM in patients with SSI after a prosthetic reconstruction refractory to conventional antibiotic therapy and the importance of early investigation with mycobacterial-specific diagnostics.

Toxoplasma Encephalitis in Atypical Hosts at an Academic Cancer Center.

Toxoplasma encephalitis is a well recognized complication of acquired immune deficiency syndrome, solid organ transplantation, and allogeneic hematopoietic stem cell transplantation (HSCT). However, patients with hematologic malignancies not treated with allogeneic HSCT may also develop this condition, which requires high clinical suspicion and consideration for prophylactic therapy.

West Nile Virus Central Nervous System Infection in Patients Treated With Rituximab: Implications for Diagnosis and Prognosis, With a Review of Literature.

The spectrum of West Nile virus (WNV) infection continues to be elucidated. Many cases of WNV are asymptomatic; however, in immunocompromised patients, symptoms are more likely to be severe. We describe fatal WNV central nervous system disease in lymphoma patients who received rituximab, blunting the inflammatory response and complicating diagnosis.

Clostridium difficile infection after allogeneic hematopoietic stem cell transplant: strain diversity and outcomes associated with NAP1/027.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are at high risk for developing Clostridium difficile infection (CDI). We studied the incidence, risk factors, NAP1/027 prevalence, and clinical outcomes, including acute lower gastrointestinal graft-versus-host disease (GI GVHD), associated with early CDI in this population. A retrospective review was conducted of patients who underwent allogeneic HSCT at Memorial Sloan Kettering Cancer Center from January 1, 2005 to September 30, 2010. Early CDI was defined as infection occurring from day -10 to day +40 from stem cell infusion. Among 793 patients who received allogeneic HSCTs, early CDI occurred in 11.9%; 56% cases were between day -5 and day +5. Overall incidence was 25.2 cases/10,000 at-risk days. There was a high prevalence of NAP1/027 strains during peak incidence (61% in 2008). NAP1/027 was the most common strain in both adult and pediatric cases (24% and 23%, respectively). CDI was clinically mild, including those due to NAP1/027. Metronidazole was the primary treatment for 91 of 94 patients, 7 of 8 cases refractory to metronidazole had no response to vancomycin, and none was due to NAP1/027. Relapse of CDI was common (31%). The cumulative incidence of GI GVHD in patients with and without early CDI was 6.8% and 8%, respectively (P = .5). Most cases of CDI occurred during conditioning or immediately after transplant. Despite high prevalence of NAP1/027, we found only mild disease. Most patients were treated successfully with metronidazole, irrespective of NAP1/027 status. There was no significant association between early CDI and subsequent development of GI GVHD. This study demonstrates the high incidence of CDI early after allogeneic HSCT with wide diversity among infecting strains. Despite the high prevalence of NAP1/027, the disease is mild but relapses are common. No association was found between CDI and subsequent development of GI GVHD.

Vaccinations for healthcare personnel: update on influenza, hepatitis B, and pertussis.

PURPOSE OF REVIEW: Healthcare personnel (HCP) are at risk for exposure to and transmission of potentially life-threatening vaccine preventable diseases to patients and colleagues. The Centers for Disease Control and Advisory Committee on Immunization Practices (ACIP) recommend routine influenza immunization and maintenance of immunity to hepatitis B and pertussis, among others. In this article, we aim to review recently approved influenza vaccines, as well as address some of the issues regarding hepatitis B and pertussis vaccinations in HCP. RECENT FINDINGS: Several new formulations of influenza vaccines are now available, including quadrivalent vaccines and non-egg-based vaccines; their use in HCP requires further study. An alarming rise in pertussis rates has led to a revision of ACIP guidelines recommending vaccination for women during each pregnancy. Persistent lack of immunity to hepatitis B after vaccine series remains a problem for many HCP. SUMMARY: Inactivated trivalent influenza vaccines remain the safest and most widely studied influenza vaccinations for healthcare workers. A pertussis booster in the form of Tdap is now recommended for most HCP. More studies are needed regarding the issue of nonresponders in HCP who receive the three-dose hepatitis B vaccine series, as there are some promising strategies available that may boost immune responses.

Investigation of inpatient probiotic use at an academic medical center.

OBJECTIVES: Despite the widespread use of probiotics, there are limited data regarding their safety. The aims of this study were to characterize inpatient probiotic use and to determine the incidence of probiotic-related bloodstream infections due to Lactobacillus acidophilus/Lactobacillus bulgaricus. METHODS: This study was a two-part retrospective study conducted at a large academic medical center. The first part was the characterization of probiotic use during 2007-2008, which included the type of prescribing provider, choice of probiotic prescribed, indications for use, and presence of potential risk factors for probiotic infection among recipients; the second part was the determination of the incidence of probiotic-related bloodstream infections due to L. acidophilus/L. bulgaricus for September 2000-August 2008. RESULTS: Probiotic use was uncommon (0.4%). Ninety-six percent of patients received Lactobacillus-based compounds. Use was common in patients at theoretical risk for probiotic infection. The maximum estimated incidence of probiotic-related bacteremia due to L. acidophilus/L. bulgaricus during the 8-year period was 0.2%. CONCLUSIONS: L. acidophilus/L. bulgaricus probiotic use at our institution appeared to be associated with a minimal risk of probiotic-related infection, even though it was used at a high frequency among inpatients who could be considered at high theoretical risk for probiotic-related bloodstream infection.

Community acquired respiratory and gastrointestinal viral infections: challenges in the immunocompromised host.

PURPOSE OF REVIEW: Newer molecular diagnostic techniques have advanced the field of clinical microbiology and infectious diseases, particularly with respect to characterizing the role that community acquired viruses play in the clinical course and outcomes of the immunocompromised host. This review will examine recent studies describing the impact of adenovirus, rhinovirus, hepatitis E and norovirus in the course of solid organ and stem cell transplant recipients, as well as their epidemiology and implications for infection prevention and control. RECENT FINDINGS: Adenovirus transmission is poorly understood; recent studies increasingly point to reactivation of latent infection in the immunocompromised host. Rhinovirus shedding can persist for weeks after acute viral infection, complicating hospital infection control policies. Hepatitis E is increasingly recognized as a potential pathogen in the stem cell and solid organ transplant population, and should be considered in the work-up for unexplained liver function test abnormalities. Similar to rhinovirus, norovirus shedding from the gastrointestinal tract may persist for months in the immunocompromised host; infected patients are at a higher risk for transmitting norovirus compared with infected healthcare workers. SUMMARY: Additional studies are needed, particularly with respect to transmission, for these community acquired viral infections, which often have devastating consequences in the immunocompromised patient population.