A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis.

BACKGROUND: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).

Methods of conservative antibiotic treatment of acute uncomplicated appendicitis: A systematic review.

BACKGROUND: Meta-analyses and a recent guideline acknowledge that conservative management of uncomplicated appendicitis with antibiotics can be successful for patients who wish to avoid surgery. However, guidance as to specific management does not exist. METHODS: PUBMED and EMBASE search of trials describing methods of conservative treatment was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. RESULTS: Thirty-four studies involving 2,944 antibiotic-treated participants were identified. The greatest experience with conservative treatment is in persons 5 to 50 years of age. In most trials, imaging was used to confirm localized appendicitis without evidence of abscess, phlegmon, or tumor. Antibiotics regimens were generally consistent with intra-abdominal infection treatment guidelines and used for a total of 7 to 10 days. Approaches ranged from 3-day hospitalization on parenteral agents to same-day hospital or ED discharge of stable patients with outpatient oral antibiotics. Minimum time allowed before response was evaluated varied from 8 to 72 hours. Although pain was a common criterion for nonresponse and appendectomy, analgesic regimens were poorly described. Trials differed in use of other response indicators, that is, white blood cell count, C-reactive protein, and reimaging. Diet ranged from restriction for 48 hours to as tolerated. Initial response rates were generally greater than 90% and most participants improved by 24 to 48 hours, with no related severe sepsis or deaths. In most studies, appendectomy was recommended for recurrence; however, in several, patients had antibiotic retreatment with success. CONCLUSION: While further investigation of conservative treatment is ongoing, patients considering this approach should be advised and managed according to study methods and related guidelines to promote informed shared decision-making and optimize their chance of similar outcomes as described in published trials. Future studies that address biases associated with enrollment and response evaluation, employ best-practice pain control and antibiotic selection, better define cancer risk, and explore longer time thresholds for response, minimized diet restriction and hospital stays, and antibiotic re-treatment will further our understanding of the potential effectiveness of conservative management. LEVEL OF EVIDENCE: Systematic review, level II.

Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment.

INTRODUCTION: Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%-15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficiently large and pragmatic to incorporate usual variations in care and measures the patient experience is needed to determine whether antibiotics are as good as appendectomy. OBJECTIVES: The Comparing Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial for acute appendicitis aims to determine whether the antibiotic treatment strategy is non-inferior to appendectomy. METHODS/ANALYSIS: CODA is a randomised, pragmatic non-inferiority trial that aims to recruit 1552 English-speaking and Spanish-speaking adults with imaging-confirmed appendicitis. Participants are randomised to appendectomy or 10 days of antibiotics (including an option for complete outpatient therapy). A total of 500 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary analytic outcome is quality of life (measured by the EuroQol five dimension index) at 4 weeks. Clinical adverse events, rate of eventual appendectomy, decisional regret, return to work/school, work productivity and healthcare utilisation will be compared. Planned exploratory analyses will identify subpopulations that may have a differential risk of eventual appendectomy in the antibiotic treatment arm. ETHICS AND DISSEMINATION: This trial was approved by the University of Washington's Human Subjects Division. Results from this trial will be presented in international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02800785.

Antibiotics-First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management.

STUDY OBJECTIVE: Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy. METHODS: Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate. RESULTS: Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/µL (range 6,200 to 23,100/µL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group. CONCLUSION: A multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.

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.

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.

Use of a Hospital-Wide Screening Program for Early Detection of Sepsis in General Surgery Patients.

Sepsis remains a significant source of mortality among hospitalized patients. This study examines the usage of a vital sign-based screening protocol in identifying postoperative patients at risk for sepsis at an academic-affiliated medical center. We identified all general surgery inpatients undergoing abdominopelvic surgery from January to June 2014, and compared those with positive screening tests to a sample of screen-negative controls. Multivariate logistic regression was used to identify predictors of positive screening tests and progression to severe sepsis. In total, 478 patients underwent abdominopelvic operations, 59 had positive screening tests, 33 qualified for sepsis, and six progressed to severe sepsis. Predictors of a positive screening test were presence of cancer [odds ratio (OR) 30.7, 95% confidence interval (CI) 2.2-420], emergency operation (OR 6.5, 95% CI 1.7-24), longer operative time (OR 2.2/h, 95% CI 1.2-4.1), and presence of postoperative infection (OR 6.4, 95% CI 1.5-27). The screening protocol had sensitivity 100 per cent and specificity 88 per cent for severe sepsis. We identified no predictors of severe sepsis. In conclusion, vital sign-based screening provides value by drawing early attention to patients with potential to develop sepsis, but escalation of care for these patients should be based on clinical judgment.

Inability of polymerase chain reaction, pyrosequencing, and culture of infected and uninfected site skin biopsy specimens to identify the cause of cellulitis.

BACKGROUND: The cause of cellulitis is unclear. Streptococcus pyogenes, and to a lesser extent, Staphylococcus aureus, are presumed pathogens. METHODS: We conducted a study of adults with acute cellulitis without drainage presenting to a US emergency department research network. Skin biopsy specimens were taken from the infected site and a comparable uninfected site on the opposite side of the body. Microbiology was evaluated using quantitative polymerase chain reaction (PCR), pyrosequencing, and standard culture techniques. To determine the cause, the prevalence and quantity of bacterial species at the infected and uninfected sites were compared. RESULTS: Among 50 subjects with biopsy specimens from infected and uninfected sites, culture rarely identified a bacterium. Among 49 subjects with paired specimens from infected and uninfected sites tested with PCR, methicillin-susceptible S. aureus was identified in 20 (41%) and 17 (34%), respectively. Pyrosequencing identified abundant atypical bacteria in addition to streptococci and staphylococci. Among 49 subjects with paired specimens tested by pyrosequencing, S. aureus was identified from 11 (22%) and 15 (31%) and streptococci from 15 (31%) and 20 (41%) of the specimens, respectively. Methicillin-resistant S. aureus was not found by culture or PCR, and S. pyogenes was not identified by any technique. CONCLUSIONS: The bacterial cause of cellulitis cannot be determined by comparing the prevalence and quantity of pathogens from infected and uninfected skin biopsy specimens using current molecular techniques. Methicillin-susceptible S. aureus was detected but not methicillin-resistant S. aureus or S. pyogenes from cellulitis tissue specimens. For now, optimal treatment will need to be guided by clinical trials. Noninfectious causes should also be explored.

Factors associated with decision to hospitalize emergency department patients with skin and soft tissue infection.

INTRODUCTION: Emergency department (ED) hospitalizations for skin and soft tissue infection (SSTI) have increased, while concern for costs has grown and outpatient parenteral antibiotic options have expanded. To identify opportunities to reduce admissions, we explored factors that influence the decision to hospitalize an ED patient with a SSTI. METHODS: We conducted a prospective study of adults presenting to 12 U.S. EDs with a SSTI in which physicians were surveyed as to reason(s) for admission, and clinical characteristics were correlated with disposition. We employed chi-square binary recursive partitioning to assess independent predictors of admission. Serious adverse events were recorded. RESULTS: Among 619 patients, median age was 38.7 years. The median duration of symptoms was 4.0 days, 96 (15.5%) had a history of fever, and 46 (7.5%) had failed treatment. Median maximal length of erythema was 4.0cm (IQR, 2.0-7.0). Upon presentation, 39 (6.3%) had temperature >38°C, 81 (13.1%) tachycardia, 35 (5.7%), tachypnea, and 5 (0.8%) hypotension; at the time of the ED disposition decision, these findings were present in 9 (1.5%), 11 (1.8%), 7 (1.1%), and 3 (0.5%) patients, respectively. Ninety-four patients (15.2%) were admitted, 3 (0.5%) to the intensive care unit (ICU). Common reasons for admission were need for intravenous antibiotics in 80 (85.1%; the only reason in 41.5%), surgery in 23 (24.5%), and underlying disease in 11 (11.7%). Hospitalization was significantly associated with the following factors in decreasing order of importance: history of fever (present in 43.6% of those admitted, and 10.5% discharged; maximal length of erythema >10cm (43.6%, 11.3%); history of failed treatment (16.1%, 6.0%); any co-morbidity (61.7%, 27.2%); and age >65 years (5.4%, 1.3%). Two patients required amputation and none had ICU transfer or died. CONCLUSION: ED SSTI patients with fever, larger lesions, and co-morbidities tend to be hospitalized, almost all to non-critical areas and rarely do they suffer serious complications. The most common reason for admission is administration of intravenous antibiotics, which is frequently the only reason for hospitalization. With the increasing outpatient intravenous antibiotic therapy options, these results suggest that many hospitalized patients with SSTI could be managed safely and effectively as outpatients.

Diagnosis and management of urinary tract infection in the emergency department and outpatient settings.

Emergency physicians encounter urinary tract infections (UTIs) in a wide spectrum of disease severity and patient populations. The challenges of managing UTIs in an emergency department include limited history, lack of follow-up, and lack of culture and susceptibility results. Most patients do not require an extensive diagnostic evaluation and can be safely managed as outpatients with oral antibiotics. The diagnostic approach to and treatment of adults presenting to emergency departments with UTIs are reviewed.

International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.

A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.

Urinary tract infections in the emergency department.

Urinary tract infection (UTI) is a commonly encountered clinical condition in the emergency department. Emergency physicians evaluate and treat UTIs in a wide spectrum of disease severity and patient populations. This article is written from the perspective of evaluating and managing UTIs in the emergency department. It highlights the pitfalls and clinical dilemmas pertinent to emergency physicians that are not often encountered by infectious disease specialists.

Neurocysticercosis in radiographically imaged seizure patients in U.S. emergency departments.

Neurocysticercosis appears to be on the rise in the United States, based on immigration patterns and published cases series, including reports of domestic acquisition. We used a collaborative network of U.S. emergency departments to characterize the epidemiology of neurocysticercosis in seizure patients. Data were collected prospectively at 11 university-affiliated, geographically diverse, urban U.S. emergency departments from July 1996 to September 1998. Patients with a seizure who underwent neuroimaging were included. Of the 1,801 patients enrolled in the study, 38 (2.1%) had seizures attributable to neurocysticercosis. The disease was detected in 9 of the 11 sites and was associated with Hispanic ethnicity, immigrant status, and exposure to areas where neurocysticercosis is endemic. This disease appears to be widely distributed and highly prevalent in certain populations (e.g., Hispanic patients) and areas (e.g., Southwest).