Patient diversity and author representation in clinical studies supporting the Surviving Sepsis Campaign guidelines for management of sepsis and septic shock 2021: a systematic review of citations.

BACKGROUND: The generalizability of the Surviving Sepsis Campaign (SSC) guidelines to various patient populations and hospital settings has been debated. A quantitative assessment of the diversity and representation in the clinical evidence supporting the guidelines would help evaluate the generalizability of the recommendations and identify strategic research goals and priorities. In this study, we evaluated the diversity of patients in the original studies, in terms of sex, race/ethnicity, and geographical location. We also assessed diversity in sex and geographical representation among study first and last authors. METHODS: All clinical studies cited in support of the 2021 SSC adult guideline recommendations were identified. Original clinical studies were included, while editorials, reviews, non-clinical studies, and meta-analyses were excluded. For eligible studies, we recorded the proportion of male patients, percentage of each represented racial/ethnic subgroup (when available), and countries in which they were conducted. We also recorded the sex and location of the first and last authors. The World Bank classification was used to categorize countries. RESULTS: The SSC guidelines included six sections, with 85 recommendations based on 351 clinical studies. The proportion of male patients ranged from 47 to 62%. Most studies did not report the racial/ ethnic distribution of the included patients; when they did so, most were White patients (68-77%). Most studies were conducted in high-income countries (77-99%), which included Europe/Central Asia (33-66%) and North America (36-55%). Moreover, most first/last authors were males (55-93%) and from high-income countries (77-99%). CONCLUSIONS: To enhance the generalizability of the SCC guidelines, stakeholders should define strategies to enhance the diversity and representation in clinical studies. Though there was reasonable representation in sex among patients included in clinical studies, the evidence did not reflect diversity in the race/ethnicity and geographical locations. There was also lack of diversity among the first and last authors contributing to the evidence.

The Impact of Pharmacist-Led Antimicrobial Stewardship Review of Cultures in the Ambulatory Setting at a Comprehensive Cancer Center.

Background: Several antimicrobial stewardship interventions have demonstrated improved clinical outcomes. Though the impact of a pharmacist-led antimicrobial stewardship review of cultures has been described, studies have not evaluated such an intervention in institutions that primarily serve cancer patients. Aim: To describe the impact of the antimicrobial stewardship pharmacist's review of microbiological cultures from adult cancer patients in the ambulatory setting. Method: A retrospective study at a comprehensive cancer center that included adult cancer patients with positive microbiological cultures treated in the ambulatory setting, between August 2020 and February 2021. The cultures were reviewed in real time by the antimicrobial stewardship pharmacist, and were assessed for appropriateness of treatment. The number of antimicrobial modifications made, type of modifications, and physicians' acceptance rate were recorded. Results: A total of 661 cultures from 504 patients were reviewed by the pharmacist. The mean age of patients was 58 years ± 16 (SD); most had solid tumors (95%), and 34% were recent recipients of chemotherapy. Among the reviewed cultures, 175 (26%) required antimicrobial therapy modification, with an acceptance rate of 86%. The modifications consisted of changing from non-susceptible to susceptible antimicrobials (n = 95, 54%), initiation (n = 61, 35%), discontinuation (n = 10, 6%), de-escalation (n = 7, 4%), and dose modification (n = 2, 1%) of antimicrobials. Conclusion: Around one fourth of the cultures reviewed by the antimicrobial stewardship pharmacist in the ambulatory setting required interventions to optimize therapy. Future studies should evaluate the impact of these interventions on clinical outcomes.

All-cause mortality in cancer patients treated for sepsis in intensive care units: a systematic review and meta-analysis.

PURPOSE: Sepsis is a common complication in patients with cancer, but studies evaluating the outcomes of critically ill cancer patients with sepsis on a global scale are limited. We aimed to summarize the existing evidence on mortality rates in this patient population. METHODS: Prospective and retrospective observational studies evaluating critically ill adult cancer patients with sepsis, severe sepsis, and/or septic shock were included. Studies published from January 2010 to September 2021 that reported at least one mortality outcome were retrieved from MEDLINE (Ovid), Embase (Ovid), and Cochrane databases. Study selection, bias assessment, and data collection were performed independently by two reviewers, and any discrepancies were resolved by a third reviewer. The risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled intensive care unit (ICU), hospital, and 28/30-day mortality rates. The heterogeneity of the data was tested using the chi-square test, with a P value < 0.10 indicating significant heterogeneity. RESULTS: A total of 5464 citations were reviewed, of which 10 studies met the inclusion criteria; these studies included 6605 patients. All studies had a Newcastle-Ottawa scale score of 7 or higher. The mean patient age ranged from 51.4 to 64.9 years. The pooled ICU, hospital, and 28/30 day mortality rates were 48% (95% CI, 43- 53%; I2 = 80.6%), 62% (95% CI, 58-67%; I2 = 0%), and 50% (95% CI, 38- 62%; I2 = 98%), respectively. Substantial between-study heterogeneity was observed. CONCLUSION: Critically ill cancer patients with sepsis had poor survival, with a hospital mortality rate of about two-thirds. The substantial observed heterogeneity among studies could be attributed to variability in the criteria used to define sepsis as well as variability in treatment, the severity of illness, and care across settings. Our results are a call to action to identify strategies that improve outcomes for cancer patients with sepsis.

Prevalence and Predictors of Multi-Drug Resistant Organisms Among Ambulatory Cancer Patients with Urinary Tract Infections.

Purpose: Urinary tract infections (UTIs) are among the most common community-acquired infections in patients with cancer. Though the prevalence of multi-drug resistant organisms (MDROs) has increased, there are limited studies on MDROs among ambulatory cancer patients with UTIs. Therefore, we aimed to evaluate the prevalence and predictors of MDROs in this patient population. Patients and Methods: A retrospective study of adult cancer patients treated for bacterial UTIs in the ambulatory setting at King Hussein Cancer Center. The medical laboratory's system was used to identify positive urine cultures taken in the ambulatory setting, between Aug 2020 and March 2021. UTIs were defined as a positive urine culture along with the initiation of antibiotics empirically or as definitive therapy. Patient characteristics, as well as the type and sensitivity of the bacterial organisms, were recorded. MDROs were defined as intrinsic or acquired non-susceptibility to at least one agent in three or more antimicrobial categories. Logistic regression was used to identify predictors that were independently associated with MDROs. Results: A total of 376 patients had UTIs that met the inclusion criteria; mean age 60.5±15.1 (SD) years and 330 (87.8%) had solid tumors. Gram-negative bacteria was recorded in the majority of UTIs (n = 368, 97.9%), the most common being Escherichia-coli (n = 220, 59.8%) and Klebsiella-pneumonia (n = 68, 18.5%). MDROs were recorded in 226 (60.1%) of urine cultures, with the majority being extended-spectrum-beta-lactamase producing organisms (n = 142, 62.8%). The only significant predictor was having had a UTI with MDRO within the past 6 months (OR 5.6, 95% CI 2.1-15.2). Conclusion: More than half of the positive urine cultures of cancer patients treated for UTIs in the ambulatory setting were MDROs. A subsequent UTI due to MDROs is more likely to occur in patients who had a UTI with an MDRO within the past 6 months.

Vancomycin therapeutic monitoring by measured trough concentration versus Bayesian-derived area under the curve in critically ill patients with cancer.

The updated vancomycin guideline and recent studies suggested that trough concentrations may result in underestimation of the actual area under the curve (AUC), leading to excessive dosing and nephrotoxicity. With limited data available on critically ill cancer patients, this study aimed to compare the two methods in this patient population. This was a 5-year retrospective study on patients treated with vancomycin in the intensive care unit (ICU) of a comprehensive cancer center. The measured trough concentration was compared to Bayesian-derived AUC/minimum-inhibitory-concentration (MIC), considering MIC as 1. Trough concentrations of 15-20 mg/L and AUC of 400-600 mg h/L were considered the targeted goal. Multivariate analysis was performed to identify factors associated with an AUC below the targeted goal. During the study period, 316 patients were included. The mean age was 54 years ±16 (SD); most patients had solid tumors (75%), and 11% had neutropenia. A targeted goal AUC and trough were recorded in 128 (41%) patients and in 64 (20%) patients, respectively. Of the 128 patients with targeted goal AUC, 31 (24%) had targeted goal trough concentrations and 91 (71%) had trough concentrations below 15 mg/L. Furthermore, among the patients with targeted goal trough concentration (n = 64), 33 (52%) had higher than targeted goal AUC. Augmented renal clearance (ARC), defined as a calculated creatinine-clearance ≥130 ml/min, was associated with an AUC below the targeted goal. In a cohort of critically ill patients with cancer, over two-thirds of the patients with a targeted goal Bayesian AUC/MIC had trough concentrations below the targeted goal. ARC was associated with AUC below the targeted goal.

Augmented renal clearance in critically ill patients with cancer (ARCCAN Study): A prospective observational study evaluating prevalence and risk factors.

Augmented renal clearance (ARC) is a phenomenon that has been associated with enhanced excretion of renally eliminated drugs, such as antimicrobials, which may result in subtherapeutic levels and potentially therapeutic failure. There has been limited data on ARC in critically ill patients with cancer. This study aimed to evaluate the prevalence of ARC and to identify risk factors associated with ARC in this patient population. This was a prospective study at an oncologic intensive care unit (ICU) which included adult patients with normal renal function, defined as serum creatinine ≤1 mg/dl and urine output >0.5 ml/kg/hr. The 24-hour creatinine clearance (ClCr) study was used to determine ClCr, starting on day 1 of ICU admission, for 5 days or until ICU transfer or death. ARC was defined as ClCr >130 ml/min/1.73 m2 . Univariate and multivariate logistic regression analyses were performed to identify risk factors for ARC. Over the study period, 363 patients were enrolled who completed an average of 2.8 ± 1.5(SD) days in the study and contributed 977 ClCr measurements. The mean age was 52 ± 16(SD) years old, the majority had solid tumors (n = 264, 73%), mean APACHE II was 21 ± 8(SD), and the major admission diagnosis was respiratory failure (n = 165, 45%). ARC was reported in 116 (32%) patients on at least one of the study days. Over the study period, the incidence of ARC ranged between 15.6% and 24.3%. Age was the only risk factor significantly associated with ARC (OR 1.028, 95% CI 1.005-1.051).

Establishing a Structured Pharmacy Training Program in Sterile Compounding.

The objective of this study was to describe a structured pharmacy training program in sterile compounding in a comprehensive cancer center in Jordan. A previously performed gap analysis showed a degree of non-compliance with the international standards in certain elements of sterile compounding. A structured training program with theoretical and practical domains was developed and implemented. The trainees were required to complete a compounding competency assessment at the end of the training. A questionnaire was distributed to evaluate the trainees' satisfaction. At one year of implementation, 25 pharmacists and 7 pharmacy technicians were enrolled into the training program. A questionnaire was conducted on 26 trainees. Based on the questionnaire results, 100% of the trainees were satisfied regarding the training objectives and the instructors' performance; 11.5% of the trainees stated that more time is needed for each trainee; and 3.8% said that more time is needed for the discussion. The development and implementation of a pharmaceutical sterile compounding training program in a comprehensive cancer care center was achieved by incorporating theoretical and practical techniques, with documented competency of trainees who reported satisfaction with the program. The optimal time dedicated for this program should be evaluated in future studies.

ICU readmission of patients with cancer: Incidence, risk factors and mortality.

PURPOSE: Few studies evaluated ICU readmission in cancer patients. This study aimed to describe the incidence and risk factors for ICU readmission in cancer patients and the association with mortality. MATERIALS AND METHODS: A retrospective cohort study at a comprehensive cancer center, which included cancer patients who were discharged after their initial ICU admission over a 5-year period. The characteristics and outcomes of patients who required ICU readmission within 30 days of discharge were compared to those who did not require readmission during the study period. Multivariate analyses were performed to identify factors associated with readmission and to evaluate the association between readmission and mortality. RESULTS: Among 1582 patients discharged from the ICU, 313(19.8%) were readmitted after a median of 6 days. The most common readmission diagnoses were respiratory failure and sepsis. Mechanical ventilation (OR 5.80; 95% CI 4.29-7.84) and thrombocytopenia (OR 1.66; 95% CI 1.16-2.38), on the first ICU admission were associated with readmission. Readmission was associated with a higher risk of 28-day and 90-day mortality, (OR 3.02; CI 2.3-4.00) and (OR 3.47; 95% CI 2.69-4.49), respectively. CONCLUSIONS: ICU readmission was associated with increased mortality. Mechanical ventilation and thrombocytopenia at the first admission were associated with ICU readmission.