Publications

An online consultation tool, the Sexually Transmitted Diseases Clinical Consultation Network is a new resource for sexually transmitted disease clinicians and clinic managers. An initial evaluation shows that most requests (29%) were from medical doctors, followed by nurse practitioners (22%). Syphilis queries comprised 39% of consults followed by gonorrhea (12%) and chlamydia (11%).

BACKGROUND: Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhoea and colitis. This review is an update of a previously published Cochrane review.

OBJECTIVES: The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile-associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms.

SEARCH METHODS: We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials.

SELECTION CRITERIA: Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review.

DATA COLLECTION AND ANALYSIS: Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed-effect model, except where significant heterogeneity was detected, at which time a random-effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost.

MAIN RESULTS: Twenty-two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy-two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy-one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly-seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo-controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co-morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co-morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary).

AUTHORS' CONCLUSIONS: No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest.

Growing antimicrobial resistance and a dwindling antibiotic pipeline have resulted in an emerging postantibiotic era, as patients are now dying from bacterial infections that were once treatable. The fast-paced "Golden Age" of antibiotic development that started in the 1940s has lost momentum; from the 1980s to the early 2000s, there was a 90% decline in the approval of new antibiotics as well as the discovery of few new novel classes. Many companies have shifted away from development due to scientific, regulatory, and economic hurdles that proved antibiotic development to be less attractive compared with more lucrative therapeutic areas. National and global efforts are focusing attention toward potential solutions for reinvigorating the antibiotic pipeline and include "push" incentives such as public-private partnerships and "pull" incentives such as reimbursement reform and market exclusivity. Hybrid models of incentives, global coordination among stakeholders, and the appropriate balance of antibiotic pricing, volume of drug used, and proper antimicrobial stewardship are key to maximizing efforts toward drug development to ensure access to patients in need of these therapies.

Improving the use of antibiotics across the continuum of care is a national priority. Data outlining the misuse of antibiotics in the outpatient setting justify the expansion of antibiotic stewardship programs (ASPs) into this health care setting; however, best practices for outpatient antibiotic stewardship (AS) are not yet defined. In a companion article, we focused on recommendations to overcome challenges related to the implementation of an outpatient ASP (e.g., building the AS team and defining program metrics). In this document, we outline AS interventions that have demonstrated success and highlight opportunities to enhance AS in the outpatient arena. This article summarizes examples of point-of-care testing, policies and interventions, and education strategies to improve antibiotic use that can be used in the outpatient setting.

OBJECTIVES: To address the public health threat of antibiotic resistance, there has been an enhanced call for antibiotic stewardship programs throughout the health care continuum.

SUMMARY: While antibiotic stewardship programs have been well described in the inpatient setting, data on effectiveness and guidance on implementing outpatient programs is scarce. Establishing stewardship practices in the outpatient setting is necessary because more than 60% of human antibiotic use occurs in this setting.

CONCLUSION: In this article, we highlight the importance and need for stewardship in the outpatient setting, discuss strategies for the development of stewardship teams, and discuss potential metrics that can be used to assess effectiveness of antibiotic stewardship interventions.

STUDY DESIGN: Retrospective cohort studyObjectives:To identify independent risk factors associated with community-associated multidrug-resistant Psedomonas aeruginosa (MDRPA) in a population of veterans with spinal cord injury and disorders (SCI/D).

SETTING: A total of 127 Veterans Affairs healthcare facilities.

METHODS: Laboratory results from 1 January 2012 to 31 December 2013 were collected, and MDRPA cultures were compared with non-MDRPA cultures.

RESULTS: One thousand four hundred forty-one cultures were collected from Veterans with SCI/D, including 227 cultures with MDRPA isolates. Characteristics associated with an increased odds of MDRPA include age 50-64 (adjusted odds ratio (aOR)=1.80, 95% confidence interval (CI)=1.13-2.87), MDRPA culture in the past 365 days (aOR=9.12, 95% CI=5.88-14.15) and carbapenem exposure in the past 90 days (aOR=2.56, 95% CI=1.35-4.87). In contrast, paraplegia was associated with a 53% decreased odds of MDRPA compared with those with tetraplegia (aOR=0.47, 95% CI=0.32-0.69).

CONCLUSIONS: Risk factors for community-associated MDRPA include prior history of MDRPA and exposure to carbapenems. Awareness of these factors is important for targeted prevention and treatment of MDRPA in patients with SCI/D.

OBJECTIVES: Pain is the most prevalent problem among veterans, who receive pain diagnoses 5 times more frequently than the general population. Opioids are commonly prescribed for pain, but they have potential for misuse and serious adverse events. The study objective was to evaluate opioid dispensing patterns and predictors for overlap in veterans who are eligible for Medicare Part D benefits.

METHODS: A sample of male and all female veterans aged 66 years and older without cancer in 2005-2009 was included. Overlapping days' supply of opioids were evaluated within the U.S. Department of Veterans Affairs (VA), within Part D, and in cross-system users of VA and Part D-reimbursed pharmacies during 2007-2009. Dispensing patterns were analyzed with t tests and chi-square tests. Predictors of overlap were identified with general estimating equations.

RESULTS: At least 1 opioid was dispensed to 88.5% of the sample. In 2006 after Part D implementation, 55.2% of opioids were dispensed by VA, decreasing to 44.3% in 2009 (P <0.0001). Opioids dispensed from Part D-reimbursed pharmacies had a higher frequency of overlap compared to those filled at a VA facility (P <0.0001). While overlapping days' supply for opioids filled at VA decreased, overlap increased for prescriptions filled at Part D-reimbursed pharmacies (P <0.0001). There was minimal overlap in opioids between systems, but cross-system use increased over the study period. Predictors for overlap include females, Part D enrollment, no VA medication copay, sleep disorders, psychiatric diagnoses, and substance or alcohol abuse (all P <0.01). Veterans who were Hispanic, older, and had higher incomes had lower overlap odds (all P <0.0001).

CONCLUSIONS: Opioids dispensed from Part D-reimbursed pharmacies had a higher frequency of overlapping days' supply as compared to those filled by the VA, but there was minimal overlap between systems. While overlapping opioid prescriptions filled by the VA decreased from 2007 to 2009, overlap increased for prescriptions filled at Part D-reimbursed pharmacies. Tools, such as drug monitoring programs, should be used by VA and non-VA providers to decrease opioid-related harms and misuse.

Background: This study aims to evaluate the treatment and follow-up of bacteriuria in the emergency department (ED). Objective: The primary objective was to determine the frequency of patients discharged from the ED with antibiotics for symptomatic and asymptomatic bacteriuria, and the secondary objectives were to determine the frequency of patients receiving postdischarge antibiotic interventions and antibiotic-related adverse drug reactions (ADRs). Methods: This retrospective study evaluated patients with ED urine cultures sent between October 1, 2015, and November 24, 2015. Patients with indwelling catheters, concurrent antibiotics, and admission for inpatient care were excluded. T tests and contingency tables were applied in SAS; P < .05 was considered significant. Results: Of 429 unique patients with urine cultures drawn in the ED, 13.1% (n = 56) received treatment for a bacteriuria. The majority of patients discharged from the ED with antibiotics had urinary tract infection (UTI) symptoms documented in the medical record (76.8%; n = 43). Of those patients who required postdischarge interventions, 4 out of 13 had appropriate antibiotic adjustments based on culture and sensitivity results at follow-up. In a subset of patients with inappropriately ordered urine cultures (no UTI symptoms documented or antibiotic prescribed), a higher percentage of patients had normal urinalyses (UA) compared to abnormal UAs (83.3% vs 10.4%, P = .0008). No significant ADRs were identified. Conclusions: The majority of patients treated for bacteriuria in the ED had documented symptoms consistent with UTIs and appropriate empiric antibiotics. However, incorporating antimicrobial stewardship activities in the ED targeting unnecessary urine cultures and assuring postdischarge follow-up if treatment modification is needed based on culture results can improve antibiotic prescribing.