Jason G. Newland

Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011

IMPORTANCE The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient antibiotic use is unknown. OBJECTIVE To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States. DESIGN, SETTING, AND PARTICIPANTS Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated. EXPOSURES Ambulatory care visits. MAIN OUTCOMES AND MEASURES Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population. RESULTS Of the 184,032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions [95% CI, 48-64]), followed by suppurative otitis media (47 antibiotic prescriptions [95% CI, 41-54]), and pharyngitis (43 antibiotic prescriptions [95% CI, 38-49]). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions. CONCLUSIONS AND RELEVANCE In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.

Variability in Antibiotic Use at Children's Hospitals

BACKGROUND: Variation in medical practice has identified opportunities for quality improvement in patient care. The degree of variation in the use of antibiotics in childrens hospitals is unknown. METHODS: We conducted a retrospective cohort study of 556 692 consecutive pediatric inpatient discharges from 40 freestanding childrens hospitals between January 1, 2008, and December 31, 2008. We used the Pediatric Health Information System to acquire data on antibiotic use and clinical diagnoses. RESULTS: Overall, 60% of the children received at least 1 antibiotic agent during their hospitalization, including >90% of patients who had surgery, underwent central venous catheter placement, had prolonged ventilation, or remained in the hospital for >14 days. Even after adjustment for both hospital- and patient-level demographic and clinical characteristics, antibiotic use varied substantially across hospitals, including both the proportion of children exposed to antibiotics (38%–72%) and the number of days children received antibiotics (368–601 antibiotic-days per 1000 patient-days). In general, hospitals that used more antibiotics also used a higher proportion of broad-spectrum antibiotics. CONCLUSIONS: Childrens hospitals vary substantially in their use of antibiotics to a degree unexplained by patient- or hospital-level factors typically associated with the need for antibiotic therapy, which reveals an opportunity to improve the use of these drugs.

Executive Summary: Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Consensus Guidelines for the Prevention and Treatment of Catheter-related Infections and Peritonitis in Pediatric Patients Receiving Peritoneal Dialysis: 2012 Update

Infectious complications remain the most significant cause for morbidity in pediatric patients receiving chronic peritoneal dialysis (PD). Although prophylactic measures have led to improved results in some centers, the frequency of peritonitis in children on PD continues to exceed that seen in adults, and peritonitis remains the most common reason for changing dialysis modality in children (1,2). The serious nature of this infection led to the creation and publication in 2000 of the Consensus Guidelines for the Treatment of Peritonitis in Pediatric Patients Receiving Peritoneal Dialysis (3), under the auspices of the International Society for Peritoneal Dialysis (ISPD). Those largely opinion-based guidelines were composed by an international committee of experts in the field of pediatric dialysis and served as the first such set of recommendations specific to the pediatric PD population. After the publication of those guidelines, the International Pediatric Peritoneal Dialysis Registry (IPPR) was established to support evaluations of the impact of implementing the guidelines on a global basis and to collect data to serve as evidence upon which future guidelines could be based. Data generated from 501 episodes of peritonitis were collected by the IPPR and serve as a foundation for many of the recommendations made in the present publication (4,5). As with the earlier publication, an international group of experts consisting of pediatric nephrologists, a pediatric dialysis nurse, and a pediatric infectious disease specialist collaborated in the effort. Committee discussions took place face-to-face, during conference calls, and by e-mail. The strength of each guideline statement is graded as Level 1 or 2, or Not Graded, and the quality of the supporting evidence as A, B, C, or D in accordance with the rating scheme used in the KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Care of the Kidney Transplant Recipient (6). Table 1 describes the scheme. TABLE 1 Guideline Rating Scheme Finally, wherever possible, efforts were made to achieve harmonization between the recently published adult treatment recommendations and those designed for children (7). In addition, supporting information (for example, reporting of peritonitis rates, definitions) that is included in the publication pertaining to adults and that is equally applicable to pediatric populations was included in the present publication.

A complete course of intravenous antibiotics vs a combination of intravenous and oral antibiotics for perforated appendicitis in children: a prospective, randomized trial

INTRODUCTION In a previous prospective randomized trial, we found a once-a-day regimen of ceftriaxone and metronidazole to be an efficient, cost-effective treatment for children with perforated appendicitis. In this study, we evaluated the safety of discharging patients to complete an oral course of antibiotics. METHODS Children found to have perforated appendicitis at the time of laparoscopic appendectomy were enrolled in the study. Perforation was defined as a hole in the appendix or fecalith in the abdomen. Patients were randomized to antibiotic treatment with either once daily dosing of ceftriaxone and metronidazole for a minimum of 5 days (intravenous [IV] arm) or discharge to home on oral amoxicillin/clavulanate when tolerating a regular diet (IV/PO arm) to complete 7 days. RESULTS One hundred two patients underwent laparoscopic appendectomy for perforated appendicitis. On presentation, there were no differences in age, weight, sex distribution, days of symptoms, maximum temperature, or leukocyte count between the 2 groups. There was no difference in the postoperative abscess rate between the two treatment groups. Discharge was possible before day 5 in 42% of the patients in the IV/PO arm. CONCLUSIONS When patients are able to tolerate a regular diet, completing the course of antibiotics orally decreases hospitalization with no effect on the risk of postoperative abscess formation.

Impact of a Guideline on Management of Children Hospitalized With Community-Acquired Pneumonia

OBJECTIVES: We sought to describe the impact a clinical practice guideline (CPG) had on antibiotic management of children hospitalized with community-acquired pneumonia (CAP). PATIENTS AND METHODS: We conducted a retrospective study of discharged patients from a children’s hospital with an ICD-9-CM code for pneumonia (480–486). Eligible patients were admitted from July 8, 2007, through July 9, 2009, 12 months before and after the CAP CPG was introduced. Three-stage least squares regression analyses were performed to examine hypothesized simultaneous relationships, including the impact of our institution\x{2019}s antimicrobial stewardship program (ASP). RESULTS: The final analysis included 1033 patients: 530 (51%) before the CPG (pre-CPG) and 503 (49%) after the CPG (post-CPG). Pre-CPG, ceftriaxone (72%) was the most commonly prescribed antibiotic, followed by ampicillin (13%). Post-CPG, the most common antibiotic was ampicillin (63%). The effect of the CPG was associated with a 34% increase in ampicillin use (P < .001). Discharge antibiotics also changed post-CPG, showing a significant increase in amoxicillin use (P < .001) and a significant decrease in cefdinir and amoxicillin/clavulanate (P < .001), with the combined effect of the CPG and ASP leading to 12% (P < 0.001) and 16% (P < .001) reduction, respectively. Overall, treatment failure was infrequent (1.5% vs 1%). CONCLUSIONS: A CPG and ASP led to the increase in use of ampicillin for children hospitalized with CAP. In addition, less broad-spectrum discharge antibiotics were used. Patient adverse outcomes were low, indicating that ampicillin is appropriate first-line therapy for otherwise healthy children admitted with uncomplicated CAP.

Association of neutropenia in systemic lupus erythematosus (SLE) with anti-Ro and binding of an immunologically cross-reactive neutrophil membrane antigen

SLE is associated with the production of autoantibodies to self‐constituents. In particular, certain ribonucleoprotein particles are targeted. Despite the multitude of autoantibodies produced and the remarkable concentrations of these antibodies in the sera of SLE patients, there have been little data that the autoantibodies found in SLE are involved in the pathogenesis of disease or its manifestations. The present work demonstrates that anti‐Ro (or SSA) is associated with granulocytopenia, binds the surface of granulocytes and fixes complement to this membrane surface. Binding is a property of anti‐Ro Fab fragments and can be inhibited by 60‐kD Ro. However, the antigen bound on the surface of granulocytes is a 64 000 mol. wt protein that is a novel autoantigen in SLE. As suggested by inhibition studies, sequence identity between 60‐kD Ro and eight tandem repeats in the 64‐kD antigen may be responsible for the observed serologic cross‐reactivity . These data imply that anti‐Ro antibodies that also bind the 64‐kD protein mediate neutropenia in patients with SLE.

Antimicrobial Stewardship Programs in Pediatrics

OBJECTIVE To describe the prevalence, characteristics, and barriers to implementation of antimicrobial stewardship programs (ASPs) in pediatrics. DESIGN AND PARTICIPANTS In December 2008, we surveyed the pediatric members of the Emerging Infections Network, a network of infectious diseases consultants located throughout North America. Participants responded regarding whether their hospital had or planned to develop an ASP, its characteristics, barriers to improvement or implementation, and perceptions about antimicrobial resistance. RESULTS Of 246 pediatric infectious disease consultants surveyed, 147 (60%) responded. Forty-five respondents (33%) reported having an ASP, and 25 (18%) were planning a program. The percentage of respondents from freestanding childrens hospitals who were planning ASPs was higher than the percentage of respondents from other settings who were planning ASPs (P = .04). Most existing programs were developed before 2000 and had a limited number of full-time equivalent staff, and few programs used a prospective audit-and-feedback structure. Many programs were not monitoring important end points associated with ASPs, including cost and number of antibiotic-days. The major barriers to implementation of an ASP were lack of resources, including funding, time, and personnel, noted by more than 50% of respondents. Regardless of the presence of an ASP, respondents perceived antibiotic resistance as a more significant problem nationally than at their local hospital (P < .001). CONCLUSIONS The prevalence of ASPs in pediatrics is limited, and opportunities exist to improve current programs.

Antibiotic Management of Staphylococcus aureus Infections in US Children's Hospitals, 1999–2008

OBJECTIVES: The objective of this study was to describe trends in antibiotic management for Staphylococcus aureus infections among hospitalized children from 1999 to 2008. METHODS: A retrospective study was conducted by using the Pediatric Health Information Systems database to describe antibiotic treatment of inpatients with S aureus infection at 25 childrens hospitals in the United States. Patients who were admitted from 1999 to 2008 with International Classification of Diseases, Ninth Revision, Clinical Modification codes for S aureus infection were included. Trends in the use of vancomycin, clindamycin, linezolid, trimethoprim-sulfamethoxazole, cefazolin, and oxacillin/nafcillin were examined for percentage use and days of therapy per 1000 patient-days. RESULTS: A total of 64813 patients had a discharge diagnosis for S aureus infection. The incidence of methicillin-resistant S aureus (MRSA) infections during this period increased 10-fold, from 2 to 21 cases per 1000 admissions, whereas the methicillin-susceptible S aureus infection rate remained stable. Among patients with S aureus infections, antibiotics that treat MRSA increased from 52% to 79% of cases, whereas those that treat only methicillin-susceptible S aureus declined from 66% to <30% of cases. Clindamycin showed the greatest increase, from 21% in 1999 to 63% in 2008. Similar trends were observed by using days of therapy per 1000 patient-days. CONCLUSIONS: Antibiotic prescribing patterns for the treatment of S aureus infections have changed significantly during the past decade, reflecting the emergence of community-associated MRSA. Clindamycin is now the most commonly prescribed antibiotic for S aureus infections among hospitalized children. The substantial use of clindamycin emphasizes the importance of continuous monitoring of local S aureus susceptibility patterns.