A shortened course of Amoxicillin/Clavulanate is the preferred antibiotic treatment after surgery for perforated appendicitis in children.

BACKGROUND/PURPOSE: Despite evidence supporting short course outpatient antibiotic treatment following appendectomy for perforated appendicitis, evidence of real-world implementation and consensus for antibiotic choice is lacking. We therefore aimed to compare outpatient antibiotic treatment regimens in a national cohort. METHODS: We identified children who underwent surgery for perforated appendicitis between 2010 and 2018 using the PearlDiver database and compared 45-day disease-specific readmission between children who received shortened (5-8 days) versus prolonged (10-14 day) total antibiotic courses (inpatient intravenous and/or oral) completed with outpatient Amoxicillin/Clavulanate versus Ciprofloxacin/Metronidazole, and compared antibiotic type (5-14 days) to each other. RESULTS: 4916 children were identified, 2001 (90.0%) treated with Amoxicillin/Clavulanate (5-14 days), 381 (19.0%) with shortened (5-8 days), 1464 (73.2%) with prolonged (10-14 days) courses. 222 (10.0%) were treated with Ciprofloxacin/Metronidazole, 44 (19.8%) with shortened, 174 (78.4%) with prolonged courses. Freedom from readmission was not different between prolonged and shortened course whether they received Amoxicillin/Clavulanate (adjusted hazard ratio [AHR] 1.54, 95%CI 0.95-2.5) or Ciprofloxacin/Metronidazole (AHR 3.49, 95%CI 0.45-27.3). Antibiotic type did not affect readmission rate (Amoxicillin/Clavulanate versus Ciprofloxacin/Metronidazole, AHR 1.21, 95%CI 0.71-2.05). CONCLUSION: Prolonged antibiotic regimens are routinely prescribed despite evidence suggesting shorter courses and antibiotic choice are not associated with greater treatment failure. As it is better tolerated, we recommend a shortened course of Amoxicillin/Clavulanate for oral management of perforated appendicitis. STUDY DESIGN: Retrospective. LEVEL OF EVIDENCE: Level III.

The Growing Role of CDK4/6 Inhibitors in Treating Hormone Receptor-Positive Advanced Breast Cancer.

OPINION STATEMENT: Single-agent endocrine therapy has been the standard therapeutic choice for the management of hormone receptor (HR)-positive, Her2-negative advanced breast cancer (ABC) for decades. However, the rapidly accumulating data regarding the biological role and safety of CDK4/6 inhibitors and the first-in-class approval of palbociclib have made these novel agents an essential component of treatment for HR-positive ABC. In the frontline setting, palbociclib in combination with endocrine therapy showed an improvement in progression-free survival (PFS) by 10 months to nearly 25 months when compared with endocrine therapy alone and a clinical benefit rate (CBR = stable disease >24 weeks + partial response + complete response) of 85%. Furthermore, clinically meaningful improvements in PFS were seen in combination with fulvestrant for patients with prior endocrine therapy, including premenopausal women. While neutropenia is experienced by most patients, it is typically uncomplicated and palbociclib is otherwise well tolerated. Recent analysis also demonstrated improved quality of life and reassuring evidence of no compromise in benefit from subsequent therapies after progression on palbociclib. Along with palbociclib, the CDK4/6 inhibitors ribociclib and abemaciclib are being evaluated in a variety of settings (metastatic, neoadjuvant, and adjuvant), alone and in combination with endocrine therapy, chemotherapy, and targeted therapies. Future research is needed to address challenges regarding the potential competition of these agents as the preferred partner in endocrine-sensitive disease, their use as single agents or in combination in the endocrine-refractory setting, and the clinical and molecular criteria for use as an alternative to chemotherapy. Unfortunately, despite efforts to determine predictive biomarkers for response, RB1 expression and HR-positive disease have been the only clear predictors of therapeutic benefit. Once more mature data become available, we hope to confirm a significant impact on long-term survival. Meanwhile, given the multiple therapies patients with ABC will receive, prolonged PFS with a well-tolerated oral regimen is a clinically meaningful endpoint. Palbociclib's impact on PFS, high CBR, and tolerability have made its use a preferred option for treating many HR-positive, Her2-negative ABC patients.