November 17, 2014
Another GetSmart week is here: the CDC’s annual “observance to raise awareness of antibiotic resistance and the importance of appropriate antibiotic prescribing and use”. Last fall’s threat report by the agency cast an unprecedented amount of attention to the issue, yielding commendable policy actions in less than a year: most notably, the President’s recent Executive Order mandates antibiotic stewardship programs in all healthcare facilities by the end of 2016.
Better oversight of prescribing in hospitals is clearly needed: a recent Vital Signs report found over a third of UTI prescriptions and vancomycin starts may be inappropriate; a point-prevalence survey by Magill and colleagues showed that over 50% of inpatients in EIP sites receive antibiotics, most frequently broad-spectrum agents like vancomycin, ceftriaxone and piperacillin/tazobactam. Vexingly, there has been little research on how cultures and other diagnostic data – pivot to any stewardship program – are used to guide therapy for the duration of a patient’s stay.
To address this gap, we undertook a chart review study at six institutions – two teaching centers, three community hospitals and one VA – looking at the indications for starting antimicrobials, the use of culture and radiology results and the patterns of modifying empiric therapy in the first five days of treatment. The study team of leading ID specialists, led by CDDEP’s Ramanan Laxminarayan and sponsored by CDC’s DHQP, abstracted data from 1,200 charts. After some exclusions shown in the graph, we categorized empiric therapy as escalated, deescalated or discontinued, and unchanged.
Consistent with prior research, we found nearly 2/3rds of inpatients were receiving antibiotics, with empiric starts dominated by combinations of vancomycin, piperacillin/tazobactam and fluoroquinolones. It is likely that a lot f those initial prescriptions were unnecessary, as 30% of patients lacked fever or abnormal white blood cell counts at the start.
Appropriate cultures (on or before start of therapy) were collected from 59% of patients, and although 60% came back negative, only 22% of all evaluated patients and had their antibiotics narrowed or stopped (Figure). More specifically, 22/59 (37%) of patients with negative urine culture and 11/22 (50%) of those with negative blood culture had antimicrobials stopped or narrowed. Of pneumonia patients with negative chest imaging that proportion was 12/50 (24%).
When adjusting for other covariates, narrowing or discontinuation was more likely when cultures were collected at the start of therapy and no infection was noted on an initial radiological study. In turn, escalation was associated with multiple infection sites and a positive culture (see table below).
It seems like diagnostic uncertainty drives a lot of possibly unnecessary antibiotic use. These results underscore not only the need for rapid diagnostics, but also the importance of mechanisms to assure tests are ordered in time and their results are actually used to optimize therapy – goals attainable through better stewardship programs and physician education.
Unfortunately, our paper could not analyze the effect of stewardship programs: of the six sites three had programs in place, but these were recently established and, with the exception of one community hospital that did informal prospective audits, usually limited to restricting certain antimicrobials (not vancomycin or zosyn).
This leaves several goals for future research. In light of the president’s executive order, there is a clear need for large-scale studies examining the effectiveness of various approaches, particularly in community hospitals or outpatient setting. The experience of mandatory stewardship in California showed staffing is one of the main barriers to stewardship, especially for rural community hospitals.
What can be done to resolve the dearth of stewards? A great point made in this blog is that the government’s resistance action plans should include steps to incentivize and expand the training of more ID physicians. Although the threat drug resistance gets more public attention each year, “getting smart” about antibiotics, including their timely withdrawal and adjustment, ultimately requires the buy-in of current and future prescribers.
Nikolay Braykov is a former CDDEP researcher and current Emory University graduate student and co-author of “Assessment of empirical antibiotic therapy optimisation in six hospitals: an observational cohort study“, published in the Lancet Infectious Diseases in December 2014.
