Changes in Streptococcus pneumoniae Susceptibility in Wisconsin: Implications for Clinical Treatment Decisions for Respiratory Infections.

Objective: In 2019, the American Thoracic Society and Infectious Diseases Society of America updated clinical practice guidelines for community-acquired pneumonia (CAP). In contrast to guidelines published in 2007, macrolide monotherapy for outpatients was made a conditional recommendation based on resistance levels. Local knowledge of current antimicrobial susceptibility is needed to guide management of CAP and other bacterial respiratory pathogens. The purpose of this study was to investigate antimicrobial susceptibility profiles and trending for Wisconsin Streptococcus pneumoniae isolates.Design: Multi-center laboratory surveillance, with testing at a central location utilizing standardized susceptibility testing protocols.Methods: Data published by the Wisconsin Department of Health Services (DHS) were augmented with data from the Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) program. Data were stratified by invasive or non-invasive sources, as well as DHS region and compared to data compiled from 2006-2010.Results: Susceptibility rates for ≥ 916 invasive S. pneumoniae assessed from 2016-2020 were greater than 91% for ceftriaxone, tetracycline, and fluoroquinolone agents and were generally higher than those from 354 non-invasive isolates. Low susceptibility rates were observed for invasive isolates of penicillin (78.7%) and erythromycin (64.8%) and were even lower for non-invasive isolates (73.8% and 59.9%, respectively). This erythromycin susceptibility rate was a significant reduction from that observed in 2006-2010 (80.4; P < 0.0002). 24.8% of isolates generated an erythromycin MIC ≥ 8 µg/mL. Statewide geographic variability was noted.Conclusions: Rates of S. pneumoniae susceptibility to parenteral penicillins and cephems, and oral tetracycline and fluoroquinolone agents, remain high throughout Wisconsin. However, low oral penicillin susceptibility rates, taken together with declining macrolide susceptibility rates, should cause clinicians to consider alternative treatment options for respiratory tract infections, especially with macrolides.

Surveillance of Fluoroquinolone Resistance in Wisconsin: Geographic Variation and Impact of Revised CLSI Breakpoints.

Objective: Many clinical microbiology laboratories procure antimicrobial susceptibility testing data using guidelines established by Clinical and Laboratory Standards Institute (CLSI). When necessary, CLSI revises interpretive breakpoints in efforts to improve clinical correlation, with two revisions relative to fluoroquinolone agents occurring in 2019. The purpose of this investigation was to determine the impact of fluoroquinolone breakpoint revisions on Wisconsin clinical isolates of Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa.Design: Multi-center laboratory surveillance, with testing at a single location utilizing standardized media and susceptibility testing protocols.Methods: From the Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) program, levofloxacin and ciprofloxacin minimum inhibitory concentration (MIC) values for 1911, 1521, and 1463 Wisconsin isolates of E. coli, P. mirabilis, and P. aeruginosa, respectively, were determined by broth microdilution testing. In separate data analyses, all MIC data were interpreted using CLSI breakpoints published prior to 2019, then secondarily by using CLSI breakpoints published since 2019 (which reflect lower breakpoints for both levofloxacin and ciprofloxacin resistance). Findings were further stratified by Wisconsin Department of Health Services region.Results: Up to 3.2% decreased statewide fluoroquinolone susceptibility was observed for E. coli isolates, while 5.1% and 6.3% decreases in levofloxacin susceptibility were noted for P. aeruginosa and P. mirabilis isolates, respectively, when revised breakpoints were applied. E. coli isolates from the Western region and P. mirabilis isolates from the Southeastern region demonstrated significant shifts toward decreased fluoroquinolone susceptibility upon application of revised breakpoints. Northern region P. mirabilis isolates exhibited consistently decreased fluoroquinolone susceptibility.Conclusions: Fluoroquinolone resistance has been underreported in Wisconsin as a whole, yet geographic variability continues to exist. Targeted annual surveillance is important to identify and monitor resistance trending. Compilations of SWOTARE surveillance data can be utilized to predict the impact of future CLSI interpretive breakpoint revisions in Wisconsin.

Implementation of telehealth antimicrobial stewardship through partnership of an academic medical center and a community hospital.

PURPOSE: Small community hospitals often lack the human, financial, and technological resources necessary to implement and maintain successful antimicrobial stewardship programs now required by national regulatory and accrediting bodies. Creative solutions are needed to address this problem. SUMMARY: A 3-stage, quasi-experimental study including patients receiving antibiotics for pneumonia, skin and soft tissue infections, and urinary tract infections at a community hospital in Wisconsin from June 2013 to December 2015 was conducted. Remote telehealth prospective audit and feedback, guideline and order set management, and staff education targeting pharmacists, nurses, and physicians were provided during the 7-month intervention phase; these services were then removed for the postintervention period. Antimicrobial utilization (days of therapy [DOT] per 1,000 patient-days), hospital length of stay, and readmission and 30-day mortality rates were assessed to determine the impact of telehealth services on these outcomes. During the preintervention (baseline), intervention, and postintervention periods, 1,037 patients received antibiotics for the targeted infectious disease conditions. Patient demographics and rates of infectious disease conditions were similar among the different periods. Telehealth antimicrobial stewardship reduced broad-spectrum antibiotic use, including use of imipenem (from 83 to 31 DOT, P < 0.001), levofloxacin (from 123 to 99 DOT, P < 0.001), and vancomycin (from 104 to 85 DOT, P < 0.001), compared to utilization during the baseline period; mean (SD) length of stay also decreased (from 4.6 [2.8] days to 4.2 [2.6] days, P = 0.02). After nonrenewal of telehealth stewardship, vancomycin and piperacillin/tazobactam usage returned to or exceeded baseline levels. CONCLUSION: The partnership between an academic medical center and a small community hospital improved antimicrobial utilization and clinical outcomes. Successful telehealth antimicrobial stewardship models should be explored further as a means to provide optimal patient care.

Antibiotic utilization variability among training services at an academic medical center: An observational study.

OBJECTIVE: Evaluate the difference in antibiotic prescribing between various levels of resident training or attending types. DESIGN: Observational, retrospective study. SETTING: Tertiary-care, academic medical center in Madison, Wisconsin. METHODS: We measured antibiotic utilization from January 1, 2016, through December 31, 2018, in our general medicine (GM) and hospitalist services. The GM1 service is staffed by outpatient internal medicine physicians, the GM2 service is staffed by geriatricians and hospitalists, and the GM3 service is staffed by only hospitalists. The GMA service is led by junior resident physicians, and the GMB service is led by senior resident physicians. We measured utilization using days of therapy (DOT) per 1,000 patient days (PD). In a secondary analysis based on antibiotic spectrum, we used average DOT per 1,000 PD. RESULTS: Teaching services prescribed more antibiotics than nonteaching services (671.6 vs 575.2 DOT per 1,000 PD; P < .0001). Junior resident-led services used more antibiotics than senior resident-led services (740.9 vs 510.0 DOT per 1,000 PD; P < .0001). Overall, antibiotic prescribing was numerically similar between various attending physician backgrounds. A secondary analysis showed that GM services prescribed more broad-spectrum, anti-MRSA, and anti-pseudomonal antibiotics than the hospitalist services. GM junior resident-led services prescribed more broad-spectrum, anti-MRSA, and antipseudomonal therapy compared to their senior counterparts. CONCLUSIONS: Antibiotics were prescribed at a significantly higher rate in services associated with trainees than those without. Services led by a junior resident physician prescribed antibiotics at a significantly higher rate than services led by a senior resident. Interventions to reduce unnecessary antibiotic exposure should be targeted toward resident physicians, especially junior trainees.

In vitro evaluation of meropenem-vaborbactam against clinical CRE isolates at a tertiary care center with low KPC-mediated carbapenem resistance.

The in vitro activity of meropenem-vaborbactam was examined against clinical carbapenem-resistant Enterobacteriaceae isolates collected over 3 years at our medical center. Only 3 KPC-producers were identified. Susceptibility to meropenem-vaborbactam was noted in 15/16 (94%) isolates (MIC90 2 mg/L) that were nonsusceptible to meropenem. Meropenem-vaborbactam may have utility at centers where non-KPC-producers are more frequent.

Prophylactic Antibiotics for Enucleation and Evisceration: A Retrospective Study and Systematic Literature Review.

PURPOSE: To report surgical site infection (SSI) rates of eviscerations and enucleations with implants performed without perioperative intravenous (IV) antibiotics or postoperative oral antibiotics, and to give SSI prevention recommendations. METHODS: A single-center retrospective chart review was performed after obtaining institutional review board approval. Charts were found by Current Procedural Terminology codes. Demographics, surgical indication, procedure, implant, antibiotic use, and postoperative course were recorded. SSIs occurring within 30 days after surgery were reviewed and postoperative infection rates were determined. RESULTS: Four hundred eighty-one cases from January 1999 to December 2015 were analyzed. There were 102 eviscerations with implants, 314 enucleations with implants, 23 enucleations without implants, 23 implant exchanges, 15 implants placed secondarily after enucleation, and 4 implant removals. Seventy cases (14.6%) were given perioperative IV antibiotics, and in this group one periorbital infection occurred unrelated to orbital surgery (1.4%). Of the 411 cases (85.4%) not given perioperative IV antibiotics, 1 of 87 eviscerations with implants developed an SSI (1.1%), 2 of 273 enucleations with implants developed SSIs (0.7%), and none of the 13 enucleations without implants developed SSIs. CONCLUSIONS: To our knowledge, this is the first published case series reporting SSI rates of enucleations and eviscerations with implants performed without perioperative IV antibiotics or postoperative oral antibiotics. With infection rates comparing favorably to other case series where antibiotics were given, the routine use of perioperative IV antibiotics and postoperative oral antibiotics for enucleations and eviscerations may not be indicated.

Top 10 Myths Regarding the Diagnosis and Treatment of Cellulitis.

BACKGROUND: Cellulitis is commonly treated in the emergency department (ED). Patients who present with cellulitis incur significant health care costs and may be overtreated with antibiotics. The accurate diagnosis and treatment of cellulitis plays an important role in cost-effective, high-quality medical care, as well as appropriate antibiotic utilization. OBJECTIVE: We aim to describe common fallacies regarding cellulitis. We present 10 myths that result in misdiagnosis, overtreatment, or inappropriate empiric management of cellulitis. Clinical presentation, including swelling and redness, is explored in depth, along with incidence of community-acquired methicillin-resistance Staphylococcus aureus, management of tick bites, and effective antibiotic therapy for cellulitis. DISCUSSION: Patients are often treated for cellulitis unnecessarily or inappropriately. Awareness of these myths will help guide providers in clinical decision making in order to effectively tailor treatment for these infections. CONCLUSIONS: Cellulitis is not as simple as it might seem, and is commonly misdiagnosed in the ED. Noninfectious causes of local symptoms, including lymphedema, venous stasis, and deep vein thrombosis need to be considered. Cellulitis should be treated with empiric antimicrobial therapy based on patient risk factors and regional susceptibility patterns. This review will assist providers in managing cellulitis and avoiding treatment errors that lead to high costs, unwanted side effects for patients, and overuse of antibiotics.

Optimizing Inpatient Urine Culture Ordering Practices Using the Electronic Medical Record: A Pilot Study.

A prospective quasi-experimental before-and-after study of an electronic medical record-anchored intervention of embedded education on appropriate urine culture indications and indication selection reduced the number of urine cultures ordered for catheterized patients at an academic medical center. This intervention could be a component of CAUTI-reduction bundles. Infect Control Hosp Epidemiol 2017;38:486-488.

Top 1% of Inpatients Administered Antimicrobial Agents Comprising 50% of Expenditures: A Descriptive Study and Opportunities for Stewardship Intervention.

OBJECTIVE To characterize the top 1% of inpatients who contributed to the 6-month antimicrobial budget in a tertiary, academic medical center and identify cost-effective intervention opportunities targeting high-cost antimicrobial utilization. DESIGN Retrospective cohort study. PATIENTS Top 1% of the antimicrobial budget from July 1 through December 31, 2014. METHODS Patients were identified through a pharmacy billing database. Baseline characteristics were collected through a retrospective medical chart review. Patients were presented to the antimicrobial stewardship team to determine appropriate utilization of high-cost antimicrobials and potential intervention opportunities. Appropriate use was defined as antimicrobial therapy that was effective, safe, and most cost-effective compared with alternative agents. RESULTS A total of 10,460 patients received antimicrobials in 6 months; 106 patients accounted for $889,543 (47.2%) of the antimicrobial budget with an antimicrobial cost per day of $219±$192 and antimicrobial cost per admission of $4,733±$7,614. Most patients were immunocompromised (75%) and were followed by the infectious disease consult service (80%). The most commonly prescribed antimicrobials for treatment were daptomycin, micafungin, liposomal amphotericin B, and meropenem. Posaconazole and valganciclovir accounted for most of the prophylactic therapy. Cost-effective opportunities (n=71) were present in 57 (54%) of 106 patients, which included dose optimization, de-escalation, dosage form conversion, and improvement in transitions of care. CONCLUSION Antimicrobial stewardship oversight is important in implementing cost-effective strategies, especially in complex and immunocompromised patients who require the use of high-cost antimicrobials. Infect Control Hosp Epidemiol 2017;38:259-265.

Top Ten Myths Regarding the Diagnosis and Treatment of Urinary Tract Infections.

BACKGROUND: Urinary tract infections (UTI) are the most common type of infection in the United States. A Centers for Disease Control and Prevention report in March 2014 regarding antibiotic use in hospitals reported "UTI" treatment was avoidable at least 39% of the time. The accurate diagnosis and treatment of UTI plays an important role in cost-effective medical care and appropriate antimicrobial utilization. OBJECTIVE: We summarize the most common misperceptions of UTI that result in extraneous testing and excessive antimicrobial treatment. We present 10 myths associated with the diagnosis and treatment of UTI and succinctly review the literature pertaining to each myth. We explore the myths associated with pyuria, asymptomatic bacteriuria, candiduria, and the elderly and catheterized patients. We attempt to give guidance for clinicians facing these clinical scenarios. DISCUSSION: From our ambulatory, emergency department, and hospital experiences, patients often have urine cultures ordered without an appropriate indication, or receive unnecessary antibiotic therapy due to over-interpretation of the urinalysis. CONCLUSIONS: Asymptomatic bacteriuria is common in all age groups and is frequently over-treated. A UTI diagnosis should be based on a combination of clinical symptoms with supportive laboratory information. This review will assist providers in navigating common pitfalls in the diagnosis of UTI.

Daptomycin dosing based on ideal body weight versus actual body weight: comparison of clinical outcomes.

Daptomycin use at our institution changed to ideal body weight dosing based on a published analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. Patients were treated for documented Enterococcus species, Staphylococcus aureus, or coagulase-negative Staphylococcus infections, including bloodstream, intraabdominal, skin and soft tissue, urinary, and bone. There was no statistically significant difference in clinical success between the groups (88.9% for actual body weight compared to 89.1% for ideal body weight, P = 0.97). After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups. Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all patients and types of infections and organisms.

The use of best practice alerts with the development of an antimicrobial stewardship navigator to promote antibiotic de-escalation in the electronic medical record.

OBJECTIVE: Develop a clinical decision support tool comprised of an electronic medical record alert and antimicrobial stewardship navigator to facilitate antimicrobial stewardship. DESIGN: We analyzed alerts targeting antimicrobial de-escalation to assess the effectiveness of the navigator as a stewardship tool. The alert provides antimicrobial recommendations, then directs providers to the navigator, which includes order management, relevant patient information, evidence-based clinical information, and bidirectional communication capability. SETTING: Academic, tertiary care medical center with an electronic medical record. INTERVENTION: Alerts containing stewardship recommendations and immediate access to the navigator were created. RESULTS: Antibiotic use and response data were collected 1 day before stewardship recommendation via the best practice alert (BPA) tool and 1 day after the BPA tool response. A total of 1,285 stewardship BPAs were created. Two hundred and forty-four (18.9%) of the BPAs were created and acted upon within 72 hours for the purpose of de-escalation: 169 (69%) were accepted, 30 (12%) were accepted with modification, and 45 (18%) were rejected. Statistically significant decreases in total antibiotic use as well as in use of broad-spectrum (anti-methicillin-resistant Staphylococcus aureus and anti-pseudomonal) agents occurred when accepted recommendations were compared with rejected recommendations. CONCLUSIONS: We describe the successful development of a clinical decision support tool to perform prospective audit and feedback comprised of an alert and navigator system featuring evidence-based recommendations and clinical and educational information. We demonstrate that this tool improves antibiotic use through our example of de-escalation.

The "epic" challenge of optimizing antimicrobial stewardship: the role of electronic medical records and technology.

Antimicrobial stewardship programs (ASPs) are established means for institutions to improve patient outcomes while reducing the emergence of resistant bacteria. With the increased adoption and evolution of electronic medical records (EMRs), there is a need to assimilate the tools of ASPs into EMRs, using decision support and feedback. Third-party software vendors provide the mainstay for integration of individual institutional EMR and ASP efforts. Epic is the leading implementer of EMR technology in the United States. A collaboration of physicians and pharmacists are working closely with Epic to provide a more comprehensive platform of ASP tools that may be institutionally individualized. We review the historical relationship between ASPs and the EMR, cite examples of Epic stewardship tools from 3 academic medical centers' ASPs, discuss limitations of these Epic tools, and conclude with the current process in evolution to integrate ASP tools and decision support capacities directly into Epic's EMR.

Can the antibiogram be used to assess microbiologic outcomes after antimicrobial stewardship interventions? A critical review of the literature.

Hospitals are implementing antimicrobial stewardship programs (ASPs) in response to national guidelines to improve the use and to extend the utility of antiinfective drugs. An often implied purpose of ASPs is to curb or reverse the emergence of resistant bacteria. Because antibiotic use causes antibiotic resistance, there is a natural tendency to link local measures of antibiotic use to local measures of bacterial resistance, and the hospital antibiogram is a readily available measure of resistance. We performed a literature review to identify published reports that used hospitalwide and unit-specific antibiograms to assess the relationship of ASP interventions to changes in resistance. Eight studies were identified and reviewed. The relationship between hospital antibiotic use and resistance is complex, and the existing literature has several limitations. Furthermore, the antibiogram itself is neither designed nor well suited to reflect changes in hospital antimicrobial drug use. The literature on the effectiveness of ASPs in reducing resistance continues to emerge, but at this time the antibiogram bears an inconsistent relationship with changes in hospital antibiotic use and cannot be recommended to reliably evaluate an ASP intervention. Interrupted time series analysis is a superior strategy to assess the effect of an ASP intervention on bacterial resistance, but it is not widely used because of its complexity and greater data requirements. Nevertheless, before ASP efforts can be convincingly demonstrated to have a favorable impact on resistance, a more sophisticated approach that links drug use to resistance should become a priority, at least for hospitals that have sufficient resources.

Separating the influences of environment and species interactions on patterns of distribution and abundance: competition between large herbivores.

1. Much recent research has focused on the use of species distribution models to explore the influence(s) of environment (predominantly climate) on species' distributions. A weakness of this approach is that it typically does not consider effects of biotic interactions, including competition, on species' distributions. 2. Here we identify and quantify the contribution of environmental factors relative to biotic factors (interspecific competition) to the distribution and abundance of three large, wide-ranging herbivores, the antilopine wallaroo (Macropus antilopinus), common wallaroo (Macropus robustus) and eastern grey kangaroo (Macropus giganteus), across an extensive zone of sympatry in tropical northern Australia. 3. To assess the importance of competition relative to habitat features, we constructed models of abundance for each species incorporating habitat only and habitat + the abundance of the other species, and compared their respective likelihoods using Akaike's information criterion. We further assessed the importance of variables predicting abundance across models for each species. 4. The best-supported models of antilopine wallaroo and eastern grey kangaroo abundance included both habitat and the abundance of the other species, providing evidence of interspecific competition. Contrastingly, models of common wallaroo abundance were largely influenced by climate and not the abundance of other species. The abundance of antilopine wallaroos was most influenced by water availability, eastern grey kangaroo abundance and the frequency of late season fires. The abundance of eastern grey kangaroos was most influenced by aspects of climate, antilopine wallaroo abundance and a measure of cattle abundance. 5. Our study demonstrates that where census and habitat data are available, it is possible to reveal species' interactions (and measure their relative strength and direction) between large, mobile and/or widely-distributed species for which competition is difficult to demonstrate experimentally. This allows discrimination of the influences of environmental factors and species interactions on species' distributions, and should therefore improve the predictive power of species distribution models.