Improving the safety of outpatient parenteral antimicrobial therapy for patients with solid tumors.

BACKGROUND AND OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. METHODS: We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the completeness of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. RESULTS: Completeness of ID provider notes improved from a baseline of 77 to 100% (p < .0001) for antimicrobial recommendations, 75 to 97% (p < .0001) for follow-up recommendations, and 19 to 98% (p < .0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24 to 56% (p = .027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. CONCLUSIONS: Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.

Clostridioides difficile Infection in Cancer and Immunocompromised Patients: Relevance of a Two-step Diagnostic Algorithm and Infecting Ribotypes on Clinical Outcomes.

BACKGROUND: Patients with cancer are particularly vulnerable to Clostridioides difficile infection (CDI). Guidelines recommend a two-step diagnostic algorithm to differentiate carriers from CDI; however, there are limited data for this approach while including other confounding risk factors for diarrhea such as radiation, cytotoxic chemotherapy, and adoptive cell based therapies. METHODS: We conducted a prospective, non-interventional, single center, cohort study of cancer patients with acute diarrhea and C. difficile, identified in stools by nucleic acid amplification tests (NAAT) and culture. Fecal toxin A/B was detected by enzyme immunoassay (EIA) and isolates were ribotyped using 16s rRNA fluorescent sequencing. Patients were followed for 90 days to compare outcomes according to malignancy type, infecting ribotype, and EIA status. RESULTS: We followed 227 patients with a positive NAAT. Of these, 87% were hospitalized and 83% had an active malignancy. EIA was confirmed positive in 80/227 (35%) of patients. Those with EIA+ were older (60 ± 18 years vs 54 ± 19 years., P = .01), more likely to fail therapy [24/80 (30%) vs 26/147 (18%), P = .04] and experience recurrence [20/80 (25%) vs 21/147(14%), P < .05]. We found a low prevalence (22%) of ribotypes historically associated with poor outcomes (002, 018, 027, 56, F078-126, 244) but their presence were associated with treatment failure [17/50 (34%) vs 33/177 (19%), P = .02]. CONCLUSIONS: When compared to cancer patients with fecal NAAT+/EIA-, patients with NAAT+/EIA+ CDI are less likely to respond to therapy and more likely to experience recurrence, particularly when due to ribotypes associated with poor outcomes.

Clinical presentation and outcomes of non-typhoidal Salmonella infections in patients with cancer.

BACKGROUND: Non-typhoidal Salmonella (NTS) infection is thought to be more severe in cancer patients, but this has not been studied since the development of new cancer therapies, increasing antibiotic resistance and the introduction of new antibiotics. We sought to describe the demographic characteristics, microbiological findings, clinical manifestations, and outcomes of NTS infections in cancer patients at our institution. METHODS: We reviewed microbiology laboratory records and identified patients who had cancer and from whom NTS organisms were recovered between January 1, 2000 and December 31, 2013, at a comprehensive cancer center in Houston, Texas. Descriptive statistics were used to summarize patient characteristics, clinical presentation and outcomes. RESULTS: We identified 110 isolates from 82 patients with 88 episodes of NTS infection (including five relapses [6%] in four patients, and two consecutive episodes in one patient). Fifty-five patients (67%) had hematologic malignancies. Most NTS isolates were susceptible to the commonly prescribed antimicrobials. Sixty-nine percent of patients had sepsis and one-third had severe sepsis or septic shock. Gastroenteritis, bacteremia, or both were present in 69% of patients, and the rest had focal infection. Mortality at 30 days was low (8%). Relapses occurred only in patients receiving ≤ 10 days of antibiotic therapy. CONCLUSIONS: NTS affects predominantly patients with hematologic malignancies, followed by gastrointestinal and genitourinary cancers. Invasive disease, sepsis, and septic shock are common presentations among admitted patients. Antimicrobial prophylaxis may not prevent NTS infection. Thirty-day mortality and attributable mortality rates were low in our series compared to older case series. Early appropriate antibiotic therapy may have had a role in decreasing mortality. Relapses occurred in patients receiving ≤ 10 days of therapy, suggesting the need for longer duration of antibiotic therapy in cancer patients with uncomplicated NTS infections.

Immune reconstitution and severity of COVID-19 among hematopoietic cell transplant recipients.

Severe acute respiratory syndrome coronavirus 2 can lead to life-threatening coronavirus disease 2019 (COVID-19) infections in patients with hematologic malignancies, particularly among hematopoietic cell transplant (HCT) recipients. We describe two patients with COVID-19 during the pre-engraftment period after HCT and review previous reports of COVID-19 in HCT recipients. Because of significant mortality from COVID-19, primarily after allogeneic HCT, early, preemptive, and optimal directed therapy may improve outcomes and reduce the mortality rate but still needs to be established in clinical trials.

Neutropenic Enterocolitis: Clinical Features and Outcomes.

BACKGROUND: Patients undergoing chemotherapy are at risk for mucosal injury and neutropenia, which facilitate colonic mucosal invasion by the bowel flora and subsequent neutropenic enterocolitis, which has a poor prognosis. OBJECTIVE: This study aimed to assess the clinical features and outcomes of neutropenic enterocolitis in patients at a comprehensive cancer center. DESIGN: This is a retrospective cohort study. SETTING: The study was conducted at the University of Texas MD Anderson Cancer Center. PATIENTS: Neutropenic enterocolitis was defined by the presence of an absolute neutrophil count <1000/mm, compatible abdominal symptoms, and either mucosal thickening on abdominal imaging or mucosal injury on colon biopsy. Patients who had been diagnosed between 2010 and 2018 were included. MAIN OUTCOMES: Complication and survival rates were analyzed using logistic regression and Cox regression analyses, respectively. RESULTS: Of the 49,244 patients who had neutropenia during the study period, 134 (2.7%) were included. The median time from neutropenia onset to neutropenic enterocolitis was 2 days (interquartile range, 1-10 days). Neutropenic enterocolitis symptoms lasted for a median of 11 days (interquartile range, 6-22 days). Most patients received antibiotics (88%) and granulocyte colony-stimulating factor (68%). Complications included sepsis (11%), colonic perforation (2%), pneumatosis intestinalis (2%), and abscess formation (2%). The risks associated with complications included immunosuppressive therapy use within 1 month before neutropenic enterocolitis onset (OR, 3.92; 95% CI, 1.04-14.76) and delayed imaging (OR, 1.10; 95% CI, 1.03-1.17). Older age, severe neutropenia, prolonged neutropenia before and after neutropenic enterocolitis diagnosis, and other concomitant systemic infections were associated with lower survival rates. LIMITATIONS: The performance of this study at a single center and its retrospective nature are limitations of the study. CONCLUSION: The prompt diagnosis and management of neutropenic enterocolitis are critical to prevent complications. The use of granulocyte colony-stimulating factor can be beneficial to shorten the duration of neutropenia. See Video Abstract at http://links.lww.com/DCR/B116. ENTEROCOLITIS NEUTROPÉNICA: CARACTERÍSTICAS CLÍNICAS Y RESULTADOS: Los pacientes sometidos a quimioterapia, están en riesgo de lesión de la mucosa y neutropenia, lo que facilita la invasión de la mucosa colónica por la flora intestinal y la subsecuente enterocolitis neutropénica, con un mal pronóstico.Evaluar las características clínicas y los resultados de la enterocolitis neutropénica de pacientes en un centro integral de cáncer.Estudio de cohorte retrospectivo.El estudio se realizó en el MD Anderson Cancer Center de la Universidad de Texas.Se definió la enterocolitis neutropénica, como la presencia de un recuento absoluto de neutrófilos <1000 / mm3, con síntomas compatibles abdominales y engrosamiento de la mucosa en imagen abdominal o lesión de la mucosa en biopsia de colon. Se incluyeron pacientes diagnosticados entre 2010 y 2018.Se analizaron las tasas de complicaciones y supervivencia mediante análisis de regresión logística y regresión de Cox.De 49,244 pacientes que tuvieron neutropenia durante el período de estudio, 134 (2.7%) fueron incluidos. La media del tiempo desde el inicio de la neutropenia hasta la enterocolitis neutropénica, fue de 2 días (RIC, 1-10 días). Los síntomas de enterocolitis neutropénica duraron una media de 11 días (RIC, 6-22 días). La mayoría de los pacientes recibieron antibióticos (88%) y factor estimulante de colonias de granulocitos (68%). Las complicaciones incluyeron sepsis (11%), perforación colónica (2%), neumatosis intestinal (2%) y formación de abscesos (2%). Los riesgos asociados con las complicaciones incluyeron, uso de terapia inmunosupresora dentro de 1 mes antes del inicio de la enterocolitis neutropénica (razón de probabilidades 3.92; intervalo de confianza del 95% 1.04-14.76) y demora en la obtención de imágenes (razón de probabilidades 1.10; intervalo de confianza del 95% 1.03-1.17), edad avanzada, neutropenia grave, neutropenia prolongada antes y después del diagnóstico de enterocolitis neutropénica y de otras infecciones sistémicas concomitantes, se asociaron con bajas tasas de supervivencia.Centro único y estudio retrospectivo.El rápidodiagnóstico y manejo de la enterocolitis neutropénica, es crítico para prevenir complicaciones. El uso del factor estimulante de colonias de granulocitos puede ser beneficioso para acortar la duración de la neutropenia. Consulte Video Resumen en http://links.lww.com/DCR/B116.

A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation.

Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients. Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. The primary endpoint analysis counted confirmed CDAD, receipt of CDAD-effective medications (for any indication), and missing CDAD assessment (for any reason, including death) as failures; this composite analysis is referred to as "prophylaxis failure" to distinguish from the pre-specified sensitivity analysis, which counted only confirmed CDAD (by toxin immunoassay or nucleic acid amplification test) as failure. Results: Of 611 subjects enrolled, 600 were treated and analyzed. Prophylaxis failure was similar in fidaxomicin and placebo recipients (28.6% vs 30.8%; difference 2.2% [-5.1, 9.5], P = .278). However, most failures were due to non-CDAD events. Confirmed CDAD was lower in fidaxomicin vs placebo recipients (4.3% vs 10.7%; difference 6.4% [2.2, 10.6], P = .0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients. Conclusions: While no difference was demonstrated between arms in the primary analysis, results of the sensitivity analysis demonstrated that fidaxomicin significantly reduced the incidence of CDAD in HSCT recipients. Clinical Trials Registration: NCT01691248.

Emerging Perspectives on mTOR Inhibitor-Associated Pneumonitis in Breast Cancer.

Substantial improvements in the early detection and treatment of breast cancer have led to improvements in survival, but breast cancer remains a significant cause of morbidity and mortality in women. In 2012, the mammalian target of rapamycin (mTOR) inhibitor everolimus was approved by the U.S. Food and Drug Administration for the treatment of advanced breast cancer in patients resistant to endocrine therapy. Although everolimus is generally well tolerated, mTOR inhibitor-associated pneumonitis is one of the most common adverse drug events leading to treatment discontinuation. To date, the underlying pathophysiology of this toxicity is unclear, and this uncertainty may hinder the optimization of management strategies. However, experiences from breast cancer and renal cell carcinoma clinical trials indicate that mTOR inhibitor-associated pneumonitis can be effectively managed by early detection, accurate diagnosis, and prompt intervention that generally involves everolimus dose reductions, interruptions, or discontinuation. Management can be achieved by a multidisciplinary approach that involves the collaborative efforts of nurses, oncologists, radiologists, infectious disease specialists, pulmonologists, clinical pharmacists, and pathologists. Comprehensive education must be provided to all health care professionals involved in managing patients receiving everolimus therapy. Although general recommendations on the management of mTOR inhibitor-associated pneumonitis have been published, there is a lack of consensus on the optimal management of this potentially serious complication. This article provides an overview of mTOR inhibitor-associated pneumonitis, with a focus on the detection, accurate diagnosis, and optimal management of this class-related complication of mTOR inhibitor therapy. IMPLICATIONS FOR PRACTICE: This article summarizes the pathogenesis, clinical presentation, incidence, detection, and optimal management of everolimus-related noninfectious pneumonitis in breast cancer. In particular, this article provides a detailed overview of the important aspects of the detection, accurate diagnosis, and appropriate management of mammalian target of rapamycin inhibitor-associated pneumonitis. In addition, this article emphasizes that effective management of this adverse drug event in patients with breast cancer will require a multidisciplinary approach and collaboration among various health care professionals.

Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa.

A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 µg/mL.

Influence of Minimum Inhibitory Concentration in Clinical Outcomes of Enterococcus faecium Bacteremia Treated With Daptomycin: Is it Time to Change the Breakpoint?

BACKGROUND: Daptomycin has become a front-line antibiotic for multidrug-resistant Enterococcus faecium bloodstream infections (BSIs). We previously showed that E. faecium strains with daptomycin minimum inhibitory concentrations (MICs) in the higher end of susceptibility frequently harbor mutations associated with daptomycin resistance. We postulate that patients with E. faecium BSIs exhibiting daptomycin MICs of 3-4 µg/mL treated with daptomycin are more likely to have worse clinical outcomes than those exhibiting daptomycin MICs ≤2 µg/mL. METHODS: We conducted a multicenter retrospective cohort study that included adult patients with E. faecium BSI for whom initial isolates, follow-up blood culture data, and daptomycin administration data were available. A central laboratory performed standardized daptomycin MIC testing for all isolates. The primary outcome was microbiologic failure, defined as clearance of bacteremia ≥4 days after the index blood culture. The secondary outcome was all-cause in-hospital mortality. RESULTS: A total of 62 patients were included. Thirty-one patients were infected with isolates that exhibited daptomycin MICs of 3-4 µg/mL. Overall, 34 patients had microbiologic failure and 25 died during hospitalization. In a multivariate logistic regression model, daptomycin MICs of 3-4 µg/mL (odds ratio [OR], 4.7 [1.37-16.12]; P = .014) and immunosuppression (OR, 5.32 [1.20-23.54]; P = .028) were significantly associated with microbiologic failure. Initial daptomycin dose of ≥8 mg/kg was not significantly associated with evaluated outcomes. CONCLUSIONS: Daptomycin MICs of 3-4 µg/mL in the initial E. faecium blood isolate predicted microbiological failure of daptomycin therapy, suggesting that modification in the daptomycin breakpoint for enterococci should be considered.

Antibiotic-resistant gram-negative bacterial infections in patients with cancer.

Patients with cancer are at high risk for infections caused by antibiotic resistant gram-negative bacteria. In this review, we summarize trends among the major pathogens and clinical syndromes associated with antibiotic resistant gram-negative bacterial infection in patients with malignancy, with special attention to carbapenem and expanded-spectrum ß-lactam resistance in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia--all major threats to our cancer patients. Optimal therapy for these antibiotic-resistant pathogens still remains to be determined.

Failure of high-dose daptomycin for bacteremia caused by daptomycin-susceptible Enterococcus faecium harboring LiaSR substitutions.

High-dose daptomycin (DAP) therapy failed in a neutropenic patient with bloodstream infection caused by a DAP-susceptible Enterococcus faecium (minimum inhibitory concentration, 3 µg/mL) harboring genetic changes associated with DAP resistance, with persistent bacteremia and selection of additional resistances. Daptomycin monotherapy should be used cautiously against DAP-susceptible E. faecium strains with minimum inhibitory concentrations >2 µg/mL.

The characteristics and outcomes of parainfluenza virus infections in 200 patients with leukemia or recipients of hematopoietic stem cell transplantation.

Community respiratory viruses are significant causes of morbidity and mortality in patients with leukemia and hematopoietic stem cell transplant (HSCT) recipients. Data on characteristics and outcomes of parainfluenza virus (PIV) infections in these patients are limited. We reviewed the records of patients with leukemia and HSCT recipients who developed PIV infections to determine the characteristics and outcomes of such infections. We identified 200 patients with PIV infections, including 80 (40%) patients with leukemia and 120 (60%) recipients of HSCT. At presentation, most patients (70%) had an upper respiratory tract infection and the remaining patients (30%) had pneumonia. Neutropenia, APACHE II score more than 15, and respiratory coinfections were independent predictors of progression to pneumonia on multivariate analysis. Overall mortality rate was 9% at 30 days after diagnosis and 17% among patients who had PIV pneumonia, with no significant difference between patients with leukemia and HSCT recipients (16% vs 17%). On multivariate analysis, independent predictors of death were relapsed or refractory underlying malignancy, APACHE II score more than 15, and high-dose steroid use. Patients with leukemia and HSCT are at risk for serious PIV infections, including PIV pneumonia, with a significant mortality rate. We identified multiple risk factors for progression to pneumonia and death.

Implementation of an Automated Antibiotic Time-out at a Comprehensive Cancer Center.

Background: Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established. Methods: An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed. Results: Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: -0.89 days (95% confidence interval [CI], -1.38 to -.41); linezolid: -0.89 days (95% CI, -1.27 to -.52); meropenem: -0.97 days (95% CI, -1.39 to -.56); tigecycline: -1.41 days (95% CI, -2.19 to -.63); P < .001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (-43.49; 95% CI, -58.61 to -28.37; P < .001), tigecycline (-35.47; 95% CI, -44.94 to -26.00; P < .001), and daptomycin (-9.47; 95% CI, -15.25 to -3.68; P = .002). Discussion: A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.

Nontuberculosis mycobacteria (NTM) infections in patients with leukemia: a single center case series.

Patients with leukemia experience profound immunosuppression both from their underlying disease as well as chemotherapeutic treatment. Little is known about the prevalence and clinical presentation of nontuberculous mycobacteria (NTM) in this patient population. We identified six cases of NTM infection from 29,743 leukemia patients who had acid-fast bacilli (AFB) cultures. Four cases had bloodstream infections and five had disseminated disease, including one who presented with an unusual case of diffuse cellulitis/myositis. All patients were lymphopenic at time of diagnosis, and two patients ultimately died from their NTM infection. NTM infections are a rare, but potentially life-threatening infection in patients with leukemia. Sending AFB cultures early is important to direct appropriate antimicrobial therapy and allow for future leukemia-directed therapy.

Cefazolin high-inoculum effect in methicillin-susceptible Staphylococcus aureus from South American hospitals.

OBJECTIVES: Clinical failures with cefazolin have been described in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) producing type A ß-lactamase. We investigated the prevalence of the cefazolin inoculum effect (InE) in MSSA from South American hospitals, since cefazolin is used routinely against MSSA due to concerns about the in vivo efficacy of isoxazolyl penicillins. METHODS: MSSA isolates were recovered from bloodstream (n = 296) and osteomyelitis (n = 68) infections in two different multicentre surveillance studies performed in 2001-02 and 2006-08 in South American hospitals. We determined standard-inoculum (10(5)cfu/mL) and high-inoculum (10(7) cfu/mL) cefazolin MICs. PFGE was performed on all isolates that exhibited a cefazolin InE. Multilocus sequence typing (MLST) and sequencing of part of blaZ were performed on representative isolates. RESULTS: The overall prevalence of the cefazolin InE was 36% (131 isolates). A high proportion (50%) of MSSA isolates recovered from osteomyelitis infections exhibited the InE, whereas it was observed in 33% of MSSA recovered from bloodstream infections. Interestingly, Ecuador had the highest prevalence of the InE (45%). Strikingly, 63% of MSSA isolates recovered from osteomyelitis infections in Colombia exhibited the InE. MLST revealed that MSSA isolates exhibiting the InE belonged to diverse genetic backgrounds, including ST5, ST8, ST30 and ST45, which correlated with the prevalent methicillin-resistant S. aureus clones circulating in South America. Types A (66%) and C (31%) were the most prevalent ß-lactamases. CONCLUSIONS: Our results show a high prevalence of the cefazolin InE associated with type A ß-lactamase in MSSA isolates from Colombia and Ecuador, suggesting that treatment of deep-seated infections with cefazolin in those countries may be compromised.

Mitigating Burnout: Transition to a Condensed Workweek for Advanced Practice Providers in Infectious Diseases.

Burnout among health-care workers is highly prevalent and profoundly impacts the quality of patient care. In addition to affecting patient safety, burnout results in higher staff turnover, revenue deficits due to decreased productivity, financial risk, and diminished organization viability because of the impact on quality of care, patient satisfaction, and safety. Culmination of external and internal stressors in health-care worker populations is associated with a higher probability of burnout and workers who reported perceived low workplace flexibility. In addition, workplace flexibility is associated with reduced odds of experiencing burnout. Workplace flexibility plays a critical role in potentially reducing the occurrence of burnout in the health-care worker population. Individually focused solutions are important to mitigate burnout, however, comprehensive organizational change ensures durable and sustainable solutions. There is a correlation between a positive employee outlook and reduced stress when there is a perceived level of control over one's work schedule. The goal of this article is to showcase the process of a successful implementation of a condensed work schedule for an advanced practice provider workforce in infectious diseases in response to burnout and workload shifts. This chronicles the steps of design, rationale, procuring buy-in by stakeholders, and operational implementation of the new schedules. Advanced practice provider satisfaction and burnout were measured by periodic surveys at timepoints along the way.

Risk Factors Associated with Severe Clostridioides difficile Infection in Patients with Cancer.

INTRODUCTION: Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer. METHODS: This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome composition was determined by sequencing the V3/V4 region of 16 s rDNA encoding gene. Differential abundance analyses were used to single out significant microbial features which differed across severity levels. RESULTS: On univariate analysis, factors associated with severe CDI included the presence of toxin A/B in stools (odds ratio [OR] 2.14 [1.05-4.36] p = 0.04 and prior 90-day metronidazole use (OR 2.66 [1.09-6.50] p = 0.03). Although alpha and beta diversity was similar between disease severity groups and toxin A/B in stools, increased abundance of Bacteroides uniformis, Ruminococcaceae, and Citrobacter koseri were associated with protection from severe CDI (p < 0.05) and depletion of anaerobes was higher in patients with prior metronidazole exposure. CONCLUSION: Use of metronidazole for non-CDI indications within 90 days prior to diagnosis and presence of toxin A/B in stools were associated with severe CDI. Findings provide valuable insights into risk factors for severe CDI in an underserved population with cancer that warrants further exploration.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

A multicenter study of pandemic influenza A (H1N1) infection in patients with solid tumors in 3 countries: early therapy improves outcomes.

BACKGROUND: Pandemic influenza A (hereafter 2009/H1N1) caused significant morbidity and mortality during the 2009 pandemia. Patients with chronic medical conditions and immunosuppressive diseases had a greater risk of complications. However, data regarding the characteristics and outcome of 2009/H1N1 infection in patients with solid tumors are nonexistent. Herein, the authors describe a series of influenza 2009/H1N1 in patients with solid malignancies at 3 major cancer hospitals worldwide. METHODS: The authors retrospectively reviewed the records of patients with solid organ malignancies and 2009/H1N1 from The University of Texas M. D. Anderson Cancer Center in Houston, Texas; the Mexican National Cancer Institute, Federal District of Mexico; and King Hussein Cancer Center in Amman, Jordan from the period of the 2009 H1N1 pandemia. Data on demographics, disease characteristics, and outcome were extracted. RESULTS: In total, 115 cases were identified during the pandemic influenza among the 3 institutions. High rates of hospitalization (50%), pneumonia (23%), and death (9.5%) were reported. Patients who developed pneumonia and those who died were moderately to severely immunocompromised (P = .001 and P = .006, respectively). A multivariate competing risk analysis demonstrated that a delay >48 hours in starting antiviral therapy was associated significantly with an increased risk of developing pneumonia (P = .013). CONCLUSIONS: The 2009/H1N1 pandemic caused severe illness in immunocompromised patients with cancer who had solid tumors, and heavily immunosuppressed patients were at greater risk of developing pneumonia and death. Early initiation of antiviral therapy is crucial in this patient population to decrease morbidity and probably mortality.