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.

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.

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.

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.

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.

Association of macrophage migration inhibitory factor (MIF) polymorphisms with risk of meningitis from Streptococcus pneumoniae.

Macrophage migration inhibitory factor (MIF) is an upstream proinflammatory cytokine encoded by a functionally polymorphic locus. This study of 119 patients explored the potential relationship between MIF genotype and invasive Streptococcus pneumoniae infections. We observed an association between a high-expression MIF allele and occurrence of pneumococcal meningitis.

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.

Clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Diseases Society of America.

Residents of long-term care facilities (LTCFs) are at great risk for infection. Most residents are older and have multiple comorbidities that complicate recognition of infection; for example, typically defined fever is absent in more than one-half of LTCF residents with serious infection. Furthermore, LTCFs often do not have the on-site equipment or personnel to evaluate suspected infection in the fashion typically performed in acute care hospitals. In recognition of the differences between LTCFs and hospitals with regard to hosts and resources present, the Infectious Diseases Society of America first provided guidelines for evaluation of fever and infection in LTCF residents in 2000. The guideline presented here represents the second edition, updated by data generated over the intervening 8 years. It focuses on the typical elderly person institutionalized with multiple chronic comorbidities and functional disabilities (e.g., a nursing home resident). Specific topic reviews and recommendations are provided with regard to what resources are typically available to evaluate suspected infection, what symptoms and signs suggest infection in a resident of an LTCF, who should initially evaluate the resident with suspected infection, what clinical evaluation should be performed, how LTCF staff can effectively communicate about possible infection with clinicians, and what laboratory tests should be ordered. Finally, a general outline of how a suspected outbreak of a specific infectious disease should be investigated in an LTCF is provided.

Pandemic influenza H1N1 2009, innate immunity, and the impact of immunosenescence on influenza vaccine.

Seasonal and pandemic strains of influenza have widespread implications for the global economy and global health. This has been highlighted recently as the epidemiologic characteristics for hospitalization and mortality for pandemic influenza H1N1 2009 are now emerging. While treatment with neuraminidase inhibitors are effective for seasonal and pandemic influenza, prevention of morbidity and mortality through effective vaccines requires a rigorous process of research and development. Vulnerable populations such as older adults (i.e., > age 65 years) suffer the greatest impact from seasonal influenza yet do not have a consistent seroprotective response to seasonal influenza vaccines due to a combination of factors. This short narrative review will highlight the emerging epidemiologic characteristics of pandemic H1N1 2009 and focus on immunosenescence, innate immune system responses to influenza virus infection and vaccination, and influenza vaccine responsiveness as it relates to seasonal and H1N1 pandemic influenza vaccines.

Antimicrobial therapy for asymptomatic bacteriuria or candiduria in advanced cancer patients transitioning to comfort measures.

Among 300 advanced cancer patients with potential urinary tract infection (UTI), 19 had symptomatic UTI. Among remaining patients (n = 281), 21% had asymptomatic bacteriuria or candiduria, and 14% received inappropriate therapy for 279 antimicrobial days. Bacteriuria or candiduria predicted antimicrobial therapy. At 10,000 to <100,000 CFU/mL, the incidence rate ratio [IRR] was 16.9 (95% confidence interval [CI], 6.0-47.2), and at ≥100,000 CFU/mL, the IRR was 27.9 (95% CI, 10.9-71.2).

Interobserver variability in the assessment of clinical criteria for suspected urinary tract infection in nursing home residents.

We determined the interobserver variability in the assessment of clinical criteria for urinary tract infection (UTI) in nursing home residents. Pairs of nursing home staff caring for 30 residents were interviewed at the time UTI was suspected. At least one measure from each of 7 clinical criteria categories was reliably assessed by nursing home staff members.

Frequency of Infection during Fever Episodes among Long-Term Care Residents.

BACKGROUND: Empirical data regarding the frequency of infection during fever episodes among women in long-term care facilities are lacking. METHODS: We conducted a case-series analysis of women long-term care residents enrolled in a randomized trial evaluating cranberry capsules to reduce bacteriuria plus pyuria across twenty-one long-term care facilities in CT, USA. Fever episodes identified during adverse event surveillance were assessed using established guidelines for older adults. Among fever episodes, infections were classified using standardized infection surveillance definitions in long-term care residents. RESULTS: We identified 123 fever episodes among 80 women long-term care residents. Median age was 88 years (range, 65-101), and 81% (N=65) had dementia. Among 123 fever episodes, 79 (64%) met criteria for 86 total infections (lower respiratory tract, N=43; pneumonia, N=27; gastroenteritis, N=9; urinary tract, N=7). CONCLUSION: Data from this study suggest that approximately two-thirds of fever episodes involve infection among women in long-term care facilities. These data may guide provider assessments of fever in older adult women in long-term care facilities.