Examining Antimicrobial Stewardship in Specific Patients Demographics

As a result of retrospective identification of inappropriate use of antibiotics, antimicrobial stewardship is a growing area of concern and research in medicine. The need and importance of this effort was clearly demonstrated by a plethora of poster presentations on this topic at IDWeek 2019, held from October 2 to October 6, 2019, in Washington, DC

Several teams of researchers identified patient populations who are at high risk for infection or harm from inappropriate antibiotic usage, including patients near end of life, those with cystic fibrosis, those with acute myelogenous leukemia (AML), and those at risk of developing Clostridioides difficile infection , meningitis, or candidemia.

Vyas, et al¹ conducted a retrospective cohort study using electronic medical records of 133 patients who were admitted to a palliative care unit at a tertiary care hospital between 2017 and 2018, and of patients who received antibiotic treatment in the last 14 days of life. Using chi-squared analyses and Mann-Whitney test, researchers found that 67% of patients received antimicrobial treatment; documentation for the goals of such treatment occurred in 77.5% of these patients. There was no statistically significant difference in frequencies of documented symptoms among patients who received antibiotics and those who did not, although dyspnea and lethargy were more common among patients who received antibiotics at end of life. Because there were no differences noted between the 2 subsets of patients, the investigators concluded that the risks associated with the use of antimicrobial medications at end of life may outweigh potential benefits, and therefore, clinicians should engage in discourse on use of these therapies.

In another high-need and high-risk population, Fuller, et al² conducted a retrospective chart review of patients with AML receiving chemotherapy between 2009 and 2017 at a hospital in New York who experienced neutropenic fever. Of 390 patients with AML, 135 patients experienced neutropenic fever, 77 had no identifiable infectious etiologies, and among whom 38 were de-escalated from broad-spectrum antibiotics or discontinued from treatment before recovery of absolute neutrophil counts. Results showed that the risk for recurrent fever was 46% lower in this group compared with patients who were not deescalated from antibiotics until absolute neutrophil count recovery or discharge (hazard ratio, 0.54; 95% CI, 0.34-0.88; P =.01). No significant difference was noted in the need for transfer to intensive care units or in-hospital mortality in both groups. Overall, de-escalation of antibiotics in patients with AML with neutropenic fever was associated with a reduced rate of recurrent fever. Therefore, the investigators highlighted the need for de-escalation of broad-spectrum antibiotics in appropriate clinical settings.

Another retrospective review of an antibiotics stewardship program was conducted in the neurology department of Singapore General Hospital between January 2014 and December 2017.³ It demonstrated that across 184 interventions from these programs, those that were accepted and implemented translated into a shorter length of antibiotic treatment and hospital stay, as well as no difference in 14-day mortality and readmission rates for patients with neurologic conditions compared with nonaccepted interventions. Patients with neurologic conditions are often started on antimicrobial therapies for changes in mental status or isolated fevers, although suboptimal parameters and research have established the need for this. Further, Woodbury et al⁴ elucidated that in neurologic conditions in which the use of antibiotics is established as beneficial and necessary, such as in meningitis, the implementation of antimicrobial stewardship bundles, including an order set, provider education, and the real-time alerts, can result in a 44% increase in the de-escalation of treatment ≤48 hours after lumbar puncture (P =.005); median time to de-escalation of antimicrobial decreased by 35 hours (P =.002). Although these results did not demonstrate a relationship with decreased length of treatment or length of stay in the hospital, reducing the administration of unnecessary broad-spectrum antibiotics has been well-established and beneficial to patients.

Adherence to antimicrobial stewardship programs were also shown to improve cure rates for patients with C difficile infection. Using a retrospective cohort of 188 adult patients with C difficile infection who had received treatment for at least 5 days at a large academic medical center in New York, Begnoche et al⁵ found that the cure rate was significantly higher in patients whose care was adherent to the institution’s C difficile infection antimicrobial stewardship program compared with those whose care was nonadherent (89% vs 78%; P =.048). In addition, the global cure rate and 30-day recurrence rates were higher in patients in the adherent group compared with patients in the nonadherent group; however, these data were not significant. But, with an overall 53% protocol adherence rate to the stewardship program, there was still a substantial positive effect on patient outcomes.

Antimicrobial stewardship programs may also mitigate recent excesses in the use of antipseudomonal beta-lactam therapies, according to study results from Krill and colleagues.⁶ Using a syndrome-based guideline and prospective audit and feedback by direct communication with an infectious disease physician at an urban community hospital, researchers evaluated the effect on days of therapy, cost, and C difficile rates. Results from the stewardship and audit program led to changes in antibiotic treatment to guideline adherence that occurred in 62% of the 916 eligible patients, followed by change to de-escalate that occurred in 30%. Although days of treatment increased with this program (392.5 vs 404.0 days), the use of parental antimicrobials decreased (71% vs 65%). Expenditures on antibacterial treatments decreased from $172,897 to $132,053. Statistically significant reductions were shown for antipseudomonal beta-lactam use in nonintensive care units (P =.0139), and increases in non-antipseudomonal beta-lactam settings occurred (P =.0001). Although certain critical infections warrant the use of antipseudomonal beta-lactams, the application of stewardship programs allows for the judicious use of the medication for potentially successful implementation in community settings.

Incorporating the need for syndrome-specific antimicrobial stewardship programs was highlighted by Bullington, et al in patients with cystic fibrosis.⁷ Using a 6-question email survey, researchers attempted to determine the perception of antimicrobial stewardship programs among clinicians who care for patients with cystic fibrosis. A total of 378 clinicians from 30 countries responded to the survey, 39% of whom reported an antimicrobial stewardship program being available for them. Clinicians identified accurate selection, duration, and dosage of antibiotics that had minimal effects on the development of antimicrobial resistance as the main goals of existing or potential stewardship programs; in cases of cystic fibrosis exacerbation, survey respondents also identified therapeutic dose monitoring and reduction of drug-drug interactions as additional areas that needed stewardship. As the development of an exacerbation is inherently part of the relapsing and remitting nature of cystic fibrosis, the development of desired stewardship programs could have significant positive effects in clinical practice and patient outcomes.

In an interrupted time-series before-after study conducted from 2007 to 2018 at an Italian tertiary-care hospital, Bedini, et al⁸ demonstrated that the implementation of an antimicrobial stewardship program allowed for a consistent decrease in antibiotic consumption over a period of 5 years post-implementation. Using an active and computerized surveillance of all carbapenem prescriptions, researchers conducted an audit of cases where this class of antibiotics were used, followed by a validation with an infectious disease specialist. Results demonstrated that the defined daily dose of total antibiotic consumption decreased by 38.476 per 100patient-days per quarter, and carbapenem use decreased by 4.452 defined daily dose person 100 patient-days per quarter. Further, 5 years after the implementation of this stewardship program the incidence of candidemia decreased by 2.034 episodes per 1000 patient-days (P =.003); this demonstrated a 53% decrease compared with the expected number of episodes of candidemia had the program not been implemented.

The neonatal intensive care unit, an ideal breeding ground for the development and transmission of antimicrobial-resistant bacteria, and as such has unique needs in antimicrobial stewardship programs. To inform the creation of sustainable neonatal intensive care unit-specific antimicrobial stewardship programs, Akinboyo and colleagues⁹ conducted a prospective electronic survey to assess the knowledge, attitudes, and perceptions of such programs among neonatology fellows. Across 99 programs and 700 fellows, 87% (n=139) provided complete responses to the survey, of whom 72% reported the existence of a stewardship program at their institution; however, 33% of the fellows were able to identify the components of the program and 66% either did not or were unsure whether they received training in antimicrobial stewardship during their fellowship. Further, 51% of survey respondents were able to identify the empiric treatment for neonatal meningitis, and 12% were able to identify the optimal treatment for methicillin-susceptible Staphylococcus aureus. On the basis of the results, researchers of the study stressed the importance antibiotic stewardship in physician training.

With so much conflicting data across many demographics of patients, it is becoming increasingly important to have specific guidelines in place to allow for ease of clinical practice, as overall, adherence to appropriate antimicrobial stewardship programs/guidelines has demonstrated consistently optimal outcomes for patients. Further, appropriate training by a dedicated curriculum for illness-specific stewardship programs are paramount; having an antimicrobial stewardship program is inefficient if it is not applicable to common high-risk cases or if clinicians cannot effectively apply it.

References

1. Vyas P, Finuf K, Lopez S, Malhotra P, Hirsh B. Use of antimicrobials at the end of life (EOL): a retrospective cohort study analyzing providers’ reasons for prescribing antimicrobials at the EOL, their benefits and adverse effects. Presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1081.

2. Fuller R, Moshier E, Jacobs SE, et al. Practicing antimicrobial stewardship: de-escalating empiric antibiotics in patients with acute myelogenous leukemia and neutropenic fever. Presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1090.

3. Kwa LHA, Loo LW, Liew Y, Chlebicki MP. Impact of antimicrobial stewardship program (ASP) on patients with neurological conditions. Presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1079.

4. Woodbury K, Seddon M, McMahon A, Kisgen J. Impact of a multiplex polymerase chain reaction meningitis/encephalitis panel and antimicrobial stewardship bundle on antimicrobial use in patients with suspected meningitis or encephalitis. Presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1400.

5. Begnoche BR, Chen V, Saraiya N, Guo Y. Adherence versus non-adherence: clinical outcomes of an antimicrobial stewardship directed treatment protocol for Clostridioides difficile infection. Presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1983.

6. Krill C, Takhsh E, Coleman Y, et al. Impact of a syndrome-based antimicrobial stewardship intervention on anti-pseudomonal beta-lactam use, C difficile rates and cost in an urban community hospital. Presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1059.

7. Bullington W, Smyth A, Elborn S, Drevinek P, Hempstead S, Muhlebach M. Expectations and attitudes toward antimicrobial stewardship among cystic fibrosis care providers. Presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1078.

8. Bedini A, Meschiari M, Franceschini E, Mussini C. Five year impact of an antimicrobial stewardship program on nosocomial candidemia: an interrupted time-series analysis study. Presented at:IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1979.

9. Akinboyo IC, Mukhopadhyay S, Dukhovny D, Young RR, Puopolo K, Guzman-Cottrill J. Knowledge, attitudes and perceptions about antibiotic stewardship (AS) programs among neonatology trainees. Presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1128.