Antibiotic resistance in the patient with cancer: Escalating challenges and paths forward.

Infection is the second leading cause of death in patients with cancer. Loss of efficacy in antibiotics due to antibiotic resistance in bacteria is an urgent threat against the continuing success of cancer therapy. In this review, the authors focus on recent updates on the impact of antibiotic resistance in the cancer setting, particularly on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). This review highlights the health and financial impact of antibiotic resistance in patients with cancer. Furthermore, the authors recommend measures to control the emergence of antibiotic resistance, highlighting the risk factors associated with cancer care. A lack of data in the etiology of infections, specifically in oncology patients in United States, is identified as a concern, and the authors advocate for a centralized and specialized surveillance system for patients with cancer to predict and prevent the emergence of antibiotic resistance. Finding better ways to predict, prevent, and treat antibiotic-resistant infections will have a major positive impact on the care of those with cancer.

Urgent, Comprehensive Federal Action Needed To Stem Mortality and Medicare Costs Associated With Antimicrobial Resistance.

This paper is a call to action for the policies necessary to reduce the burden of antimicrobial resistance, including federal investments in antibiotic stewardship, antibiotic innovation, surveillance, research, diagnostics, infection prevention, the infectious diseases workforce, and global coordination.

Mortality, Length of Stay, and Healthcare Costs Associated With Multidrug-Resistant Bacterial Infections Among Elderly Hospitalized Patients in the United States.

BACKGROUND: This study reports estimates of the healthcare costs, length of stay, and mortality associated with infections due to multidrug-resistant bacteria among elderly individuals in the United States. METHODS: We conducted a retrospective cohort analysis of patients aged ≥65 admitted for inpatient stays in the Department of Veterans Affairs healthcare system between 1/2007-12/2018. We identified those with positive cultures for multidrug-resistant bacteria and matched each infected patient to ≤10 control patients. We then performed multivariable regression models to estimate the attributable cost and mortality due to the infection. We also constructed multistate models to estimate the attributable length of stay due to the infection. Finally, we multiplied these pathogen-specific attributable cost, length of stay, and mortality estimates by national case counts from hospitalized patients in 2017. RESULTS: Our cohort consisted of 87 509 patients with infections and 835 048 matched controls. Costs were higher for hospital-onset invasive infections, with attributable costs ranging from $22 293 (95% confidence interval: $19 101-$24 485) for methicillin-resistant Staphylococcus aureus (MRSA) to $57 390 ($34 070-$80 710) for carbapenem-resistant (CR) Acinetobacter. Similarly, for hospital-onset invasive infections, attributable mortality estimates ranged from 14.2% (12.2-16.2%) for MRSA to 24.1% (12.1-36.0%) for CR Acinetobacter. The aggregate cost of these infections was an estimated $1.9 billion ($1.3 billion-$2.5 billion) with 11 852 (8719-14 985) deaths and 448 224 (354 513-541 934) inpatient days in 2017. CONCLUSIONS: Efforts to prevent these infections due to multidrug-resistant bacteria could save a significant number of lives and healthcare resources.

Infectious Diseases Physicians: Improving and Protecting the Public's Health: Why Equitable Compensation Is Critical.

Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of ID, threatening the future of the ID workforce. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees.

The Infectious Diseases Society of America's 10 × '20 Initiative (10 New Systemic Antibacterial Agents US Food and Drug Administration Approved by 2020): Is 20 × '20 a Possibility?

BACKGROUND: Infections caused by antibiotic-resistant bacteria, including carbapenem-resistant Enterobacteriaceae, have increased in frequency, resulting in significant patient morbidity and mortality. The Infectious Diseases Society of America continues to propose legislative, regulatory, and funding solutions to address this escalating crisis. This report updates the status of development and approval of systemic antibiotics in the United States as of late 2018. METHODS: We performed a review of the published literature and on-line clinical trials registry at www.clinicaltrials.gov to identify new systemically acting orally and/or intravenously administered antibiotic drug candidates in the development pipeline, as well as agents approved by the US Food and Drug Administration since 2012. RESULTS: Since our 2013 pipeline status report, the number of new antibiotics annually approved for marketing in the United States has reversed its previous decline, likely influenced by new financial incentives and increased regulatory flexibility. Although our survey demonstrates progress in development of new antibacterial drugs that target infections caused by resistant bacterial pathogens, the majority of recently approved agents have been modifications of existing chemical classes of antibiotics, rather than new chemical classes. Furthermore, larger pharmaceutical companies continue to abandon the field, and smaller companies face financial difficulties as a consequence. CONCLUSIONS: Unfortunately, if 20 × '20 is achieved due to efforts embarked upon in decades past, it could mark the apex of antibiotic drug development for years to come. Without increased regulatory, governmental, industry, and scientific support and collaboration, durable solutions to the clinical, regulatory, and economic problems posed by bacterial multidrug resistance will not be found.

White Paper: Developing Antimicrobial Drugs for Resistant Pathogens, Narrow-Spectrum Indications, and Unmet Needs.

Despite progress in antimicrobial drug development, a critical need persists for new, feasible pathways to develop antibacterial agents to treat people infected with drug-resistant bacteria. Infections due to resistant gram-negative bacilli continue to cause unacceptable morbidity and mortality rates. Antibacterial agents have been historically studied in noninferiority clinical trials that focus on a single site of infection (eg, complicated urinary tract infections, intra-abdominal infections), yet these designs may not be optimal, and often are not feasible, for study of infections caused by drug-resistant bacteria. Over the past several years, multiple stakeholders have worked to develop consensus regarding paths forward with a goal of facilitating timely conduct of antimicrobial development. Here we advocate for a novel and pragmatic approach and, toward this end, present feasible trial designs for antibacterial agents that could enable conduct of narrow-spectrum, organism-specific clinical trials and ultimately approval of critically needed new antibacterial agents.

Faces of Resistance: Using Real-World Patients and Their Advocates to Teach Medical Students About Antimicrobial Stewardship.

We engaged medical students with antimicrobial stewardship (AS) and antimicrobial resistance (AMR) through patient stories and a panel on AMR advocacy with experts from the Centers for Disease Control and Prevention and the Infectious Diseases Society of America. Students were surveyed on their perceptions about AS and AMR (response rate = 139 of 166, 84%).