Antimicrobial Stewardship 2.0 Hospitalist Best Practice Eileen Barrett, MD, MPH, FACP Division of Hospital Medicine UNMH

Objectives Promote best practices for reducing complications from antimicrobial use and overuse Review when antibiotics aren’t indicated Discuss duration of therapy as a tool for de-escalation for common infections treated by hospitalists

Reducing Antibiotic Use

Reducing antibiotic use: Asymptomatic UTI 673 women with recurrent UTIs and asymptomatic bacteriuria Most commonly E coli and E faecalis Half treated, half with watchful waiting Followed for 3, 6, 12 months 30% more symptomatic UTIs at 6 months 300% more symptomatic UTIs at 12 monhts

Reducing antibiotic use: Small abscesses “Cure rates with drainage alone are about 85% or higher, and large studies are therefore required to show relatively small differences in response rates.” Talan DA NEJM 2016;374: 823 suggested a benefit but cure rates were still high regardless of treatment strategy (92.9% vs 85.7%) with no difference in invasive infections

Reducing antibiotic use: late positive cultures

Avoiding antibiotics: De-escalating at 48 hours >400 positive blood cultures 48 hours vs >120 hours of incubation By 48 hours, 98% of aerobic Gram-positive and Gram- negative true infections were found 48 hour results were 97% sensitive and had a negative predictive value of 99%

Reducing doses

Reducing doses: CAP RCT comparing beta-lactam plus macroline versus beta-lactam alone vs fluoroquinolone therapy for CAP Both arms with a beta-lactam allowed either 1 or 2 grams of ceftriaxone daily The study protocol, supplemental appendix, and results do not differentiate between 1 or 2 grams of ceftriaxone

Reducing doses: Uncomplicated cystitis in women Nitrofurantoin 100 mg BID x 5 days TMP/SMX 160/800 mg (one DS tablet) BID x 3 days Ciprofloxacin 250 mg BID x 3 days

Reducing treatment duration

Reducing duration: HAP* 1088 patients RCTs 7-8 day treatment did not increase adverse outcomes vs days VAP due to non-fermenting gram negative bacilli should be treated for longer, however

Reducing duration: CAP “The currently recommended duration of antibiotic therapy for community-acquired pneumonia is 5 to 7 days” “There is no evidence that prolonged courses lead to better outcomes, even in severely ill patients, unless they are immunocompromised”

Reducing duration: Pyelonephritis 248 nonpregnant women with pyelonephritis enrolled 153 completed the study 7 days vs 14 days of therapy with cipro Mostly E coli infections About a quarter were bacteremic No difference in cure rate, failure rate, or recurrent infection

Reducing duration: intrabdominal infections 518 patients with complicated intrabdominal infections Source control was achieved for all (usually surgical drainage, resection, percutaneous drainage) Randomized to treatment for 2 days after resolution of sepsis vs fixed course of 4+/- 1 days Median duration of therapy was 4 days vs 8 days No difference in recurrent infection or surgical site infection (21% vs 22%) or death

Summary of Data to Reduce Complications from Antimicrobials Antibiotics for asymptomatic bacteriuria in nonpregnant increases symptomatic infection Consider only local treatment for skin abscesses Late positive blood cultures are unlikely to be true pathogens Patients receiving end of life care may live longer but have worsened quality of life with antimicrobials

Summary (continued) HAP treatment: 7-8 days CAP treatment: 1 g of CTX, 5-7 days Uncomplicated cystitis: 250mg, 3 days Pyelonephritis treatment: 7 days Intrabdominal infection: 4 days

Next steps Looking upstream Novel approaches

Conclusions We should use data to drive our indication, dose, and duration of antimicrobial usage We should challenge our assumptions to help us reduce complications from antibiotic use and prevent antimicrobial resistance