Antibiotic therapy is associated with adverse drug events among older adults with advanced cancer: A cohort study.

BACKGROUND: Older adults with advanced cancer are exposed to antibiotics but estimates of adverse drug events associated with antibiotic therapy are lacking. AIM: Evaluate the association of antibiotic therapy with adverse drug events in older adults with advanced cancer. DESIGN: Cohort study where the exposure was the ratio of days of therapy of an oral or intravenous antibiotic per patient-day and the outcome was an adverse drug event, defined as cardiotoxicity, hepatotoxicity, nephrotoxicity, Clostridioides difficile infection, or new detection of a multidrug-resistant organism. SETTING/PARTICIPANTS: Patients aged ⩾65 years with solid tumors from a tertiary care center who received palliative chemotherapy (n = 914). RESULTS: Mean age was 75 ± 6.6 years, and 52% were female. Common tumors were lung (31%, n = 284) and gastrointestinal (26%, n = 234). Mean time from first course of palliative chemotherapy to index admission was 128 days. Five-hundred thirty (58%) patients were exposed to antibiotics during the index admission; of these, 27% (n = 143) met standardized criteria for infection. Patients were commonly exposed to cephalosporins (33%, n = 298) and vancomycin (30%, n = 276). Among patients exposed to antibiotics, 35% (n = 183/530) developed an adverse drug event. In multivariable testing, antibiotic therapy was associated with development of an adverse drug event (>0 to <1 vs 0 days of therapy/patient-day: adjusted odds ratio [aOR] = 1.9; 95% confidence interval [CI], 1.2-2.8; ⩾1 vs 0 days of therapy/patient-day: aOR = 2.1, 95% CI, 1.4-3.0). CONCLUSION: Antibiotic therapy was independently associated with adverse drug events in hospitalized older adults with advanced cancer. These findings may inform antibiotic decision-making among palliative care providers.

Clinical implications of SARS-CoV-2 cycle threshold values in solid organ transplant recipients.

Detection of SARS-CoV-2 viral RNA by RT-PCR assays is the primary diagnostic test for COVID-19. Cycle threshold (CT ) values generated by some of these assays provide inversely proportional proxy measurements of viral load. The clinical implications of CT values are incompletely characterized, particularly in solid organ transplant (SOT) recipients. We conducted a retrospective chart review of 25 adult SOT recipients admitted to the Yale New Haven Health System between March 1 and May 15, 2020, analyzing 50 test results to investigate the clinical implications of SARS-CoV-2 CT values in this population. Initial CT values from upper respiratory tract samples were significantly higher in patients on tacrolimus, but were not associated with admission severity nor highest clinical acuity. Viral RNA was detected up to 38 days from symptom onset with a gradual increase in CT values over time. In five patients with serial testing, CT values <35.0 were detected >21 days after symptom onset in 4/5 and ≥27 days in 2/5, demonstrating prolonged RNA detection. These data describe SARS-CoV-2 viral dynamics in SOT patients and suggest that CT values may not be useful to predict COVID-19 severity in SOT patients. SARS-CoV-2 CT values may be more useful in informing infection prevention measures.

Education needed to improve antimicrobial use during end-of-life care of older adults with advanced cancer: A cross-sectional survey.

BACKGROUND: Antimicrobial use during end-of-life care of older adults with advanced cancer is prevalent. Factors influencing the decision to prescribe antimicrobials during end-of-life care are not well defined. AIM: To evaluate factors influencing medicine subspecialists to prescribe intravenous and oral antimicrobials during end-of-life care of older adults with advanced cancer to guide an educational intervention. DESIGN: 18-item single-center cross-sectional survey. SETTING/PARTICIPANTS: Inpatient medicine subspecialists in 2018. RESULTS: Of 186 subspecialists surveyed, 67 (36%) responded. Most considered withholding antimicrobials at the time of clinical deterioration during hospitalization (n = 54/67, 81%), viewed the initiation of additional intravenous antimicrobials as escalation of care (n = 44/67, 66%), and believed decision-making should involve patients or surrogates and providers (n = 64/67, 96%). Fifty-one percent (n = 30/59) of respondents who conducted advance care planning did not discuss antimicrobials. Barriers to discussing end-of-life antimicrobials included the potential to overwhelm patients or families, challenges of withdrawing antimicrobials, and insufficient training. CONCLUSIONS: Although the initiation of additional intravenous antimicrobials was viewed as escalation of care, antimicrobials were not routinely discussed during advance care planning. Educational interventions that promote recognition of antimicrobial-associated adverse events, incorporate antimicrobial use into advance care plans, and offer communication simulation training around the role of antimicrobials during end-of-life care are warranted.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

Effect of Cranberry Capsules on Bacteriuria Plus Pyuria Among Older Women in Nursing Homes: A Randomized Clinical Trial.

Importance: Bacteriuria plus pyuria is highly prevalent among older women living in nursing homes. Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Objective: To test the effect of 2 oral cranberry capsules once a day on presence of bacteriuria plus pyuria among women residing in nursing homes. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled efficacy trial with stratification by nursing home and involving 185 English-speaking women aged 65 years or older, with or without bacteriuria plus pyuria at baseline, residing in 21 nursing homes located within 50 miles (80 km) of New Haven, Connecticut (August 24, 2012-October 26, 2015). Interventions: Two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (ie, 72 mg total, equivalent to 20 ounces of cranberry juice) vs placebo administered once a day in 92 treatment and 93 control group participants. Main Outcomes and Measures: Presence of bacteriuria (ie, at least 105 colony-forming units [CFUs] per milliliter of 1 or 2 microorganisms in urine culture) plus pyuria (ie, any number of white blood cells on urinalysis) assessed every 2 months over the 1-year study surveillance; any positive finding was considered to meet the primary outcome. Secondary outcomes were symptomatic urinary tract infection (UTI), all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics administered for suspected UTI, and total antimicrobial administration. Results: Of the 185 randomized study participants (mean age, 86.4 years [SD, 8.2], 90.3% white, 31.4% with bacteriuria plus pyuria at baseline), 147 completed the study. Overall adherence was 80.1%. Unadjusted results showed the presence of bacteriuria plus pyuria in 25.5% (95% CI, 18.6%-33.9%) of the treatment group and in 29.5% (95% CI, 22.2%-37.9%) of the control group. The adjusted generalized estimating equations model that accounted for missing data and covariates showed no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1% vs 29.0%; OR, 1.01; 95% CI, 0.61-1.66; P = .98). There were no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths; 20.4 vs 19.1 deaths/100 person-years; rate ratio [RR], 1.07; 95% CI, 0.54-2.12), hospitalization (33 vs 50 admissions; 39.7 vs 59.6 hospitalizations/100 person-years; RR, 0.67; 95% CI, 0.32-1.40), bacteriuria associated with multidrug-resistant gram-negative bacilli (9 vs 24 episodes; 10.8 vs 28.6 episodes/100 person-years; RR, 0.38; 95% CI, 0.10-1.46), antibiotics administered for suspected UTIs (692 vs 909 antibiotic days; 8.3 vs 10.8 antibiotic days/person-year; RR, 0.77; 95% CI, 0.44-1.33), or total antimicrobial utilization (1415 vs 1883 antimicrobial days; 17.0 vs 22.4 antimicrobial days/person-year; RR, 0.76; 95% CI, 0.46-1.25). Conclusions and Relevance: Among older women residing in nursing homes, administration of cranberry capsules vs placebo resulted in no significant difference in presence of bacteriuria plus pyuria over 1 year. Trial Registration: clinicaltrials.gov Identifier: NCT01691430.

A cluster-randomized controlled trial of a multicomponent intervention protocol for pneumonia prevention among nursing home elders.

BACKGROUND: Pneumonia remains an important public health problem among elderly nursing home residents. This clinical trial sought to determine if a multicomponent intervention protocol, including manual tooth/gum brushing plus 0.12% chlorhexidine oral rinse, twice per day, plus upright positioning during feeding, could reduce the incidence of radiographically documented pneumonia among nursing home residents, compared with usual care. METHODS: This cluster-randomized clinical trial was conducted in 36 nursing homes in Connecticut. Eligible residents >65 years with at least 1 of 2 modifiable risk factors for pneumonia (ie, impaired oral hygiene, swallowing difficulty) were enrolled. Nursing homes were randomized to the multicomponent intervention protocol or usual care. Participants were followed for up to 2.5 years for development of the primary outcome, a radiographically documented pneumonia, and secondary outcome, a lower respiratory tract infection (LRTI) without radiographic documentation. RESULTS: A total of 834 participants were enrolled: 434 to intervention and 400 to usual care. The trial was terminated for futility. The number of participants in the intervention vs control arms with first pneumonia was 119 (27.4%) vs 94 (23.5%), respectively, and with first LRTI, 125 (28.8%) vs 100 (25.0%), respectively. In a multivariable Cox regression model, the hazard ratio in the intervention vs control arms, respectively, was 1.12 (95% confidence interval [CI], .84-1.50; P = .44) for first pneumonia and 1.07 (95% CI, .79-1.46, P = .65) for first LRTI. CONCLUSIONS: The multicomponent intervention protocol did not significantly reduce the incidence of first radiographically confirmed pneumonia or LRTI compared with usual care in nursing home residents. CLINICAL TRIALS REGISTRATION: NCT00975780.

Urinary tract infections in older women: a clinical review.

IMPORTANCE: Asymptomatic bacteriuria and symptomatic urinary tract infections (UTIs) in older women are commonly encountered in outpatient practice. OBJECTIVE: To review management of asymptomatic bacteriuria and symptomatic UTI and review prevention of recurrent UTIs in older community-dwelling women. EVIDENCE REVIEW: A search of Ovid (Medline, PsycINFO, Embase) for English-language human studies conducted among adults aged 65 years and older and published in peer-reviewed journals from 1946 to November 20, 2013. RESULTS: The clinical spectrum of UTIs ranges from asymptomatic bacteriuria, to symptomatic and recurrent UTIs, to sepsis associated with UTI requiring hospitalization. Recent evidence helps differentiate asymptomatic bacteriuria from symptomatic UTI. Asymptomatic bacteriuria is transient in older women, often resolves without any treatment, and is not associated with morbidity or mortality. The diagnosis of symptomatic UTI is made when a patient has both clinical features and laboratory evidence of a urinary infection. Absent other causes, patients presenting with any 2 of the following meet the clinical diagnostic criteria for symptomatic UTI: fever, worsened urinary urgency or frequency, acute dysuria, suprapubic tenderness, or costovertebral angle pain or tenderness. A positive urine culture (≥105 CFU/mL) with no more than 2 uropathogens and pyuria confirms the diagnosis of UTI. Risk factors for recurrent symptomatic UTI include diabetes, functional disability, recent sexual intercourse, prior history of urogynecologic surgery, urinary retention, and urinary incontinence. Testing for UTI is easily performed in the clinic using dipstick tests. When there is a low pretest probability of UTI, a negative dipstick result for leukocyte esterase and nitrites excludes infection. Antibiotics are selected by identifying the uropathogen, knowing local resistance rates, and considering adverse effect profiles. Chronic suppressive antibiotics for 6 to 12 months and vaginal estrogen therapy effectively reduce symptomatic UTI episodes and should be considered in patients with recurrent UTIs. CONCLUSIONS AND RELEVANCE: Establishing a diagnosis of symptomatic UTI in older women requires careful clinical evaluation with possible laboratory assessment using urinalysis and urine culture. Asymptomatic bacteriuria should be differentiated from symptomatic UTI. Asymptomatic bacteriuria in older women should not be treated.

Cohort study of patients with advanced cancer: outcomes associated with duration of antibiotic therapy for non-ventilator hospital-acquired pneumonia.

In this single-center observational study of 118 older adults with advanced cancer who developed non-ventilator hospital-acquired pneumonia, prolonged antibiotic durations (8-14 and ≥15 vs ≤7 d) were not associated with reduced adjusted odds of 90-day all-cause readmission or death. These data may inform antimicrobial stewardship efforts in palliative care settings.

National Cohort Study of Homebound Persons Living With Dementia: Antibiotic Prescribing Trends and Opportunities for Antibiotic Stewardship.

Background: Over 7 million older Americans are homebound. Managing infections in homebound persons presents unique challenges that are magnified among persons living with dementia (PLWD). This work sought to characterize antibiotic use in a national cohort of PLWD who received home-based primary care (HBPC) through the Veterans Health Administration. Methods: Administrative data identified veterans aged ≥65 years with ≥2 physician home visits in a year between 2014 and 2018 and a dementia diagnosis 3 years before through 1 year after their initial HBPC visit. Antibiotics prescribed orally, intravenously, intramuscularly, or by enema within 3 days of an HBPC visit were assessed from the initial HBPC visit to death or December 31, 2018. Prescription fills and days of therapy (DOT) per 1000 days of home care (DOHC) were calculated. Results: Among 39 861 PLWD, the median age (interquartile range [IQR]) was 85 (78-90) years, and 15.0% were Black. Overall, 16 956 (42.5%) PLWD received 45 122 prescription fills. The antibiotic use rate was 20.7 DOT per 1000 DOHC. Telephone visits and advanced practice provider visits were associated with 30.9% and 42.0% of fills, respectively. Sixty-seven percent of fills were associated with diagnoses for conditions where antibiotics are not indicated. Quinolones were the most prescribed class (24.3% of fills). The overall median length of therapy (IQR) was 7 (7-10) days. Antibiotic use rates varied across regions. Within regions, the median annual antibiotic use rate decreased from 2014 to 2018. Conclusions: Antibiotic prescriptions were prevalent in HBPC. The scope, appropriateness, and harms of antibiotic use in homebound PLWD need further investigation.

Prevalence and treatment of postobstructive pneumonia among older adults with advanced cancer.

Among 124 older adults with advanced cancer who were hospitalized with pneumonia, 7.3% met criteria for postobstructive pneumonia. There were no differences in antibiotic duration, antibiotic spectrum, 30-day and 90-day readmissions, or mortality between those with and without postobstructive pneumonia. Bacteria were identified in 5 patients with postobstructive pneumonia.

Comparison of traditional instruction versus nontraditional learning to improve trainee knowledge of urine culture practices in catheterized patients.

We surveyed trainees about their urine culture practices and assessed the impact of an educational intervention delivered electronically and in-person. Trainee scores improved across all levels of training and across all questions on the post-intervention survey, but there was no difference in scores by mode of education (P=0.91).

Infectious diseases in the nursing home setting: challenges and opportunities for clinical investigation.

The global population is aging. With the high prevalence of dementia and functional decline in older Americans, many aging adults with disabilities reside in nursing homes in their final stage of life. Immunosenescence, multiple comorbid diseases, and grouped quarter living all coalesce in nursing home residents to increase the risk for infectious disease. The unique issues involved with diagnosis, prognosis, and management of infectious diseases in nursing home residents make research based in the nursing home setting both necessary and exciting for the physician investigator. This review discusses the opportunities and challenges involved with research of the evolving public health problem of infections among nursing home residents.

Increased Length of Stay Associated With Antibiotic Use in Older Adults With Advanced Cancer Transitioned to Comfort Measures.

BACKGROUND: Antibiotic use may increase hospital length of stay (LOS) among older patients with advanced cancer who are transitioned to comfort measures. METHODS: We studied a cohort of patients with advanced cancer aged ≥65 years who were transitioned to comfort measures during admission from July 1, 2014, through November 30, 2016. We evaluated the association between antibiotic exposure and LOS using a Poisson regression model adjusted for age, gender, cancer type, comorbidities, infection, and intensive care unit admission. RESULTS: Among 461 patients with advanced cancer, median age was 74 years (range: 65-99), 49.0% (n = 226) were female, and 20.6% (n = 95) had liquid tumors. Overall, 82.9% (n = 382) received ≥1 antibiotic and 64.6% (n = 298) had ≥1 infection diagnosis during hospitalization. Infection diagnoses commonly included sepsis (35%, n = 161/461), pneumonia (25%, n = 117/461), and urinary tract infection (14%, n = 66/461). Among those receiving antibiotics, the most common choices included vancomycin (79%, n = 300/382), cephalosporins (63%, n = 241/382), and penicillins (45%, n = 172/382). In a multivariable Poisson regression model, LOS was 34% longer (count ratio = 1.34, [95% confidence interval: 1.20-1.51]) among those exposed versus unexposed to antibiotics. CONCLUSIONS: Antibiotic use among patients with advanced cancer who are transitioned to comfort measures is associated with longer LOS. These data illustrate the importance of tradeoffs associated with antibiotic use, such as unintended increased LOS, when striving for goal-concordant care near the end of life.