Antimicrobial Stewardship Strategies Research Articles

Using β-lactam antibiotics in patients with a history of β-lactam allergy: current concepts.

β-lactams are the most widely used antibiotic family, but they are also the most common cause of drug-induced hypersensitivity reactions. The estimated prevalence of reported penicillin allergy ranges between 9% and 12%, although a high percentage of patients with a history of penicillin allergy have no subsequent reactions on reexposure to β-lactams. A self-reported penicillin allergy has been associated with antimicrobial resistance, increased cost, intensive care admission, and death, making it essential to establish an accurate diagnosis. In addition to a thorough clinical history, diagnostic methods include skin tests, in vitro tests, and drug-challenge tests. In this review, the diagnosis and management of patients with self-reported penicillin allergy is discussed, including the recently introduced antimicrobial stewardship strategy.

The impact of antimicrobial stewardship strategies on antibiotic appropriateness and prescribing behaviours in selected countries in the Middle East: a systematic review.

Antimicrobial resistance is a global health problem and antimicrobial stewardship is an essential component of hospital policies worldwide yet little is known regarding effective implementation strategies in the Middle East. We conducted a review of studies carried out in this region that deployed different antimicrobial stewardship strategies to assess antimicrobial appropriateness and prescribing behaviours. A search of MEDLINE, EMBASE, International Pharmaceutical Abstracts, Google and Google Scholar was conducted. Twenty articles met the inclusion criteria; 2 studies evaluated strategies including prospective audit with feedback, while 18 others evaluated strategies including benchmarking antimicrobial utilization against guidelines. Recommendations for implementation of stewardship in the Middle East highlighted the importance of developing and updating local antimicrobial prescribing policies and using collaborative interdisciplinary approaches for success.

Are there any reasons to change our behavior in necrotizing fasciitis with the advent of new antibiotics?

The treatment of necrotizing fasciitis requires a multifaceted approach, consisting of surgical source control with immediate surgical debridement along with life support, clinical monitoring, and antimicrobial therapy. Many drugs are now available for the treatment of this life-threatening infectious disease, and the purpose of this review is to provide the reader with an updated overview of the newest therapeutic options. Because most necrotizing soft tissue infections are polymicrobial, broad-spectrum coverage is advisable. Acceptable monotherapy regimens include piperacillin-tazobactam or a carbapenem. However, drugs such as ceftolozane-tazobactam, ceftazidime-avibactam in association with an antianaerobic agent (metronidazole or clindamycin) are currently available as valuable alternatives. The new cephalosporins active against methicillin-resistant Staphylococcus aureus (MRSA), ceftaroline, and ceftobiprole share similar antibacterial activity against Gram-positive cocci, and they might be considered as an alternative to nonbetalactam anti-MRSA agents for necrotizing fasciitis management. Two new long-acting lypoglycopeptides - oritavancin and dalbavancin - share the indications for acute bacterial skin and skin structure infections and had similar activity against Gram-positive cocci including MRSA and streptococci. Carbapenem-sparing agents are particularly suitable for antimicrobial stewardship strategy. The new long-acting lypoglycopeptides are very effective in treating necrotizing fasciitis and are uttermost attractive for patients requiring short hospital stays and early discharge.

Variability in Antifungal and Antiviral Use in Hospitalized Children.

We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children's hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed. Infect Control Hosp Epidemiol 2017;38:743-746.

The Role of Topical Antiseptic Agents Within Antimicrobial Stewardship Strategies for Prevention and Treatment of Surgical Site and Chronic Open Wound Infection.

Scope and Significance: The topical use of antiseptics for wound care has a role in an antimicrobial stewardship strategy. However, the details of this role need clarification. Further clinical research into the use of topical antiseptics in wound care would lower the risk of furthering antibiotic resistance and contribute to more effective antibiotic use. As part of this research, experimental and surveillance data are needed on the resistance and tolerance patterns associated with topical antiseptic use in wound infections. Objective: The development of antibiotic resistance presents global challenges in terms of patient harm and increased healthcare costs. The treatment of "at risk" and infected wounds contributes to this conundrum. Synergies between antibiotics and antiseptics and their appropriate combined use need exploration. Approach: A review of available evidence on the appropriateness of antiseptics as a fundamental component of antimicrobial stewardship strategies has been undertaken. Innovation: Opening up new ways of thinking and identifying gaps of knowledge will lead to optimizing justification of antimicrobial choices and combinations. This may lead to changes in practice in terms of solutions for the prevention and treatment of wound infection. Conclusion: Antiseptics are an integral part of antimicrobial stewardship strategies for the prevention and treatment of surgical site and chronic open wound infections.

Pharmacists lead bold antimicrobial stewardship strategy at two large hospitals

Pharmacists lead bold antimicrobial stewardship strategy at two large hospitals

Challenges of Antibiotic Stewardship on the Internal Medicine Ward

BackgroundAudit and feedback programs are considered to be one of the most effective antimicrobial stewardship (ASP) strategies to improve antibiotic prescribing; however, resource requirements are a limiting factor.MethodsIn a controlled, quasi-experimental study we evaluated the impact of once weekly ASP rounds conducted with one Medicine teaching team, while two Medicine teams served as controls, at a tertiary care center from November 2014 until November 2015. We assessed process measures and changes in antibiotic utilization (reported as monthly defined daily doses per 1000 patient days from November 2013 to November 2015 using statistical process control charts).ResultsIn total, 249 patients (40% of 627 patients on the team) were on anti-infectives on the day of the rounds and had been discussed, of which 18% (48/249) were already followed by infectious diseases. A total of 79 interventions were made. Reduced duration of therapy comprised over half of the recommendations (39/76, 51%). Discontinuing antibiotics on the same day was the second most common intervention (20/76, 26%). All stewardship suggestions were accepted by the Medicine team. However, no significant changes in antibiotic utilization were observed with a similar reduction in both groups for piperacillin-tazobactam and meropenem while at the same time, an increased use of first and third-generation cephalosporins was observed.ConclusionWhile the process measures demonstrated a change in the treatment plan in 1 out of 3 patients reviewed, this did not translate into a significant change in antibiotic utilization as compared with the control groups. This may be related to the comparably small proportion of patients reviewed by ASP given that rounds occurred only once a week, and were cancelled 28 times within a one year period due to limited Medicine clinician availability. There also could have been cross-contamination between the two study arms with faculty and trainees who received the intervention while on the intervention team continuing their learned practice while on a control team. Process measures are an important means to measure the impact of ASPs, as antibiotic utilization is not a sensitive metric and may not reliably reflect improvement in antibiotic management at the individual patient level.Disclosures All authors: No reported disclosures.

Penicillin Allergy Skin Testing as an Antibiotic Stewardship Intervention in Hematopoietic Cell Transplant Recipients

BackgroundPenicillin allergy de-labeling can be an effective stewardship tool at reducing cost and the use of alternative non-β-lactam antibiotics. This study aimed to determine the effect of a pre-transplant penicillin allergy skin testing (PAST) protocol on antibiotic usage and costs in an immunocompromised hematopoietic cell transplant (HCT) population.MethodsWe conducted a retrospective study of adult HCT patients at the Cleveland Clinic from July 2010-September 2016. Routine AST for HCT patients reporting allergy to β-lactam antibiotics was implemented at our institution in July 2015. We compared days of antibiotic therapy (DOT) and antibiotic costs (AC) before and after the implementation of the AST protocol. Antibiotic usage for empiric treatment of suspected bacterial infection was captured as average DOT per 1000 patient days during the index hospitalization and AC were measured as dollars per 1000 patient days. Utilization of alternative antibiotics was compared with our standard formulary agent (piperacillin/tazobactam).ResultsAmong the 1108 HSCT during the study period (N = 871 pre-and N = 237 post-PAST) β-lactam allergy was reported by 178 patients (141 [16%] pre- and 37 [16%] post-PAST, P = 0.83). PAST was performed on 8% (11/141) and 76% (28/37) of patients pre- and post-implementation. Only 2 positive PAST were noted (one in each group). There were no adverse reactions to PAST. There was no significant difference in the disease and transplant characteristics between the two groups. Average DOT (760 vs. 588; P = 0.03) and AC ($23,559 vs. $14,179; P = 0.012) decreased for all alternative antibiotics except levofloxacin (see Figures 1 and 2). Usage and cost of our institutional empiric formulary agent increased after AST implementation.ConclusionThe use of PAST to adjudicate reported β-lactam allergy in patients undergoing HCT is an effective antimicrobial stewardship strategy to lower usage and cost of alternative antibiotics and can facilitate prescribing of effective standard formulary agents when treating immunocompromised HCT patients at high-risk for infection. The impact of penicillin allergy de-labeling on Clostridium difficile infection and antibiotic resistance merits evaluation in future studies.Disclosures All authors: No reported disclosures.

Antimicrobial stewardship practices in Virginia

The Society of Healthcare Epidemiology of America, the Centers for Disease Control and Prevention, and the President's Council of Advisors on Science and Technology recognize the need to combat antimicrobial resistance through the promotion of antimicrobial stewardship programs. Health care facilities in Virginia were surveyed using a 23-item survey focused on facility characteristics and antimicrobial stewardship strategies. Antimicrobial stewardship activities were highly variable and many are missing key personnel and resources.

Hospital pharmacists take time out for antimicrobial stewardship.

Hospitals large and small are exploring pharmacy-managed antimicrobial therapy “time-outs” as part of antimicrobial stewardship strategies. In Illinois, four Northwestern Medicine hospitals—333-bed Central DuPage Hospital in Winfield, 159-bed Delnor in Geneva, 98-bed Kishwaukee in DeKalb, and 24-bed Valley West in Sandwich—recently presented findings from a study of pharmacist-led antimicrobial therapy time-outs, as did 650-bed University of Nebraska Medical Center in Omaha. The results of the two studies were presented at the October 2016 IDWeek conference in New Orleans. An antimicrobial therapy time-out, according to the Centers for Disease Control and Prevention’s (CDC’s) core elements for hospital antimicrobial stewardship programs, is a systemic evaluation, at a set time point, of the need to continue antimicrobial treatment. Although CDC recommends that hospitals adopt a policy of routinely requiring a time-out 48 hours after the initiation of antimicrobial therapy, that timing isn’t always practical. “It takes about 72 hours to turn around our cultures,” said Radhika Polisetty, clinical and infectious diseases pharmacist at Central DuPage Hospital. Thus, for their study, the pharmacists at the four Northwestern Medicine hospitals performed time-outs 72 hours after initiating therapy so that their recommendations were backed by microbiology test results.

Variability in Antifungal and Antiviral Use in Hospitalized Children

We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children’s hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed. Infect Control Hosp Epidemiol 2017;38:743–746

Antimicrobial susceptibility of long term care facility and general practice urine samples in patients 65 years and older: an observational study.

Antimicrobial resistance in long-term care facilities (LTCFs) poses a risk to elderly residents. The aim of this observational study was to investigate recent patterns of antimicrobial susceptibility in urine samples submitted to the Microbiology Laboratory at Cork University Hospital (CUH) from LTCFs in the greater Cork region. The antimicrobial susceptibilities of LTCF and General Practitioner (GP) urine samples sent to CUH, for patients aged over 65 years of age, were compared. A retrospective analysis of the antimicrobial susceptibilities of urine samples submitted to the microbiology laboratory at CUH in quarter one of 2011-2014 was conducted. LTCF and GP urine sample susceptibilities, for patients over 65 years of age, were compared using Chi square statistics. Overall, the LTCF urine samples were less susceptible than GP urine samples to the antimicrobials recommended in the national urinary tract infection guidelines; trimethoprim, nitrofurantoin, cephalexin, co-amoxiclav, ciprofloxacin and amoxicillin ( P < 0.001). Important trends in antimicrobial susceptibility over the time period were noted. A significant reduction in susceptibility to co-amoxiclav was found between Q1 2011 and Q1 2014 in both settings (GP P = 0.013, LTCF P = 0.005). This study provides important information which will contribute to the revision of antimicrobial prescribing guidelines in the future. This study highlights the need for continuous surveillance of antimicrobial susceptibility trends in LTCFs. Antimicrobial stewardship strategies are urgently required to address antimicrobial resistance and appropriate antimicrobial prescribing in the LTCF setting.

Patient and public understanding and knowledge of antimicrobial resistance and stewardship in a UK hospital: should public campaigns change focus?

The rising global tide of antimicrobial resistance is a well-described phenomenon. Employing effective and innovative antimicrobial stewardship strategies is an essential approach to combat this public health threat. Education of the public and patients is paramount to enable the success of such strategies. A panel of hospital multidisciplinary healthcare professionals was set up and a short quiz containing true/false statements around antimicrobial stewardship and resistance was designed and piloted. An educational leaflet with the correct replies and supporting information was also produced and disseminated. Participants were recruited on a single day (18 November 2015) from the hospital outpatient clinics and the hospital outpatient pharmacy waiting room. One hundred and forty-five completed quizzes were returned, providing a total of 1450 answers. Overall, 934 of 1450 (64%) statements were scored correctly whilst 481 (33%) were scored incorrectly; 35 (3%) statements were left unscored. We speculate that these results may demonstrate that respondents understood the statements, as only a small proportion of statements were left unanswered. The question dealing with the definition of antimicrobial resistance and the question dealing with the definition of antimicrobial stewardship obtained the most incorrect replies (85% and 72%, respectively). However, a specific factual recall question regarding only one microorganism (MRSA) received the most correct responses (99%). We describe a simple, innovative method of engagement with patients and the general public to help educate and disseminate important public health messages around antimicrobial resistance and stewardship. We also identified the need for public health campaigns to address the knowledge gaps found around this topic.

Clinical Impact and Provider Acceptability of Real-Time Antimicrobial Stewardship Decision Support for Rapid Diagnostics in Children With Positive Blood Culture Results.

Rapid diagnostic technologies for infectious diseases have the potential to improve clinical outcomes, but guideline-recommended antimicrobial stewardship (AS) strategies are not currently optimized for rapid intervention. We evaluated the clinical impact and provider acceptability of implementing real-time AS decision support for children with positive blood culture results according to the FilmArray blood culture identification panel (BCID [BioFire Diagnostics]) at Children's Hospital Colorado. A pre-post quasi-experimental design was used to compare the outcomes of 100 postintervention children with positive blood culture results matched with 200 preintervention control children. Causative organisms in the preintervention group were identified using conventional microbiologic techniques and communicated to providers by a microbiology technologist. Postintervention organisms were identified by the BCID and communicated by an AS provider in real time with interpretation and antimicrobial recommendations. The primary outcome was time to optimal antimicrobial therapy (time from blood culture collection to start of predetermined pathogen-specific regimen or antimicrobial discontinuation for contaminants) compared by a log-rank test and Kaplan-Meier analysis. Provider acceptability of the intervention was assessed via E-mailed surveys. The median time to optimal therapy decreased from 60.2 hours before intervention to 26.7 hours after intervention (P = .001). Among children with blood cultures that contained true pathogens, the time to effective antimicrobial therapy decreased from 6.9 to 3.4 hours (P = .03). Unnecessary antibiotic initiation for children with a culture that contained organisms considered to be contaminants decreased from 76% to 26% (P < .001). Providers reported a change in management as a result of BCID results in 73% of the cases and a mean overall satisfaction rating of 4.8 on a 5-point Likert scale. Real-time AS decision support for rapid diagnostics is associated with improved antimicrobial use and high satisfaction ratings by providers.

Antimicrobial stewardship in paediatrics.

BackgroundAntibiotics are among the drugs most commonly prescribed to children in hospitals and communities. Unfortunately, a great number of these prescriptions are unnecessary or inappropriate. Antibiotic abuse and misuse have several negative consequences, including drug-related adverse events, the emergence of multidrug resistant bacterial pathogens, the development of Clostridium difficile infection, the negative impact on microbiota, and undertreatment risks. In this paper, the principle of and strategies for paediatric antimicrobial stewardship (AS) programs, the effects of AS interventions and the common barriers to development and implementation of AS programs are discussed.DiscussionOver the last few years, there have been significant shortages in the development and availability of new antibiotics; therefore, the implementation of strategies to preserve the activity of existing antimicrobial agents has become an urgent public health priority. AS is one such approach. The need for formal AS programs in paediatrics was officially recognized only recently, considering the widespread use of antibiotics in children and the different antimicrobial resistance patterns that these subjects exhibit in comparison to adult and elderly patients. However, not all problems related to the implementation of AS programs among paediatric patients are solved. The most important remaining problems involve educating paediatricians, creating a multidisciplinary interprofessional AS team able to prepare guidelines, monitoring antibiotic prescriptions and defining corrective measures, and the availability of administrative consensuses with adequate financial support. Additionally, the problem of optimizing the duration of AS programs remains unsolved. Further studies are needed to solve the above mentioned problems.ConclusionsIn paediatric patients, as in adults, the successful implementation of AS strategies has had a significant impact on reducing targeted- and nontargeted-antimicrobial use by improving the quality of care for hospitalized patients and preventing the emergence of resistance. Considering that rationalization of antibiotic misuse and abuse is the basis for reducing emergence of bacterial resistance and several clinical problems, all efforts must be made to develop multidisciplinary paediatric AS programs in hospital and community settings.

Gram-Negative Bacilli in Infants Hospitalized in The Neonatal Intensive Care Unit.

Gram-negative bacilli (GNB) account for a significant burden of infection and colonization in neonatal intensive care units (NICUs), and antibiotic resistance among these pathogens is of increasing concern. A prospective cohort study was performed in 4 NICUs between May 2009 and April 2012. The body sites from which GNB were isolated, antimicrobial susceptibilities of the GNB isolated, and antimicrobial therapy were assessed. Attending neonatologists treated 3.0% (188 of 6184) of eligible infants for GNB infection; 23% of 214 GNB isolates were nonsusceptible to antimicrobial agents, including gentamicin (14.8%), piperacillin-tazobactam (9.9%), third-generation cephalosporin (7.0%), and/or carbapenem agents (4.5%). Gentamicin was the most commonly used antibiotic overall, and much of its use was empiric. However, third-generation cephalosporin agents and cefepime were used more commonly as targeted therapy for identified Gram-negative pathogens. One-quarter of the GNB isolates were nonsusceptible to ≥1 antibiotic. Antimicrobial stewardship strategies for reducing antimicrobial use in NICUs should be implemented.

Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-β-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients.

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.

Antimicrobial Resistance and Stewardship in National Action Plans

Tackling Antimicrobial resistance has global focus due to the significant threat resistance poses to human and animal health and its potential impact on the global economy as a result of reduced productivity caused by sickness and higher treatment costs. Therefore, the importance of strengthening health systems ensuring antimicrobial agents are used and accessed appropriately has never been more important. A potential solution to combating antimicrobial resistance globally is implementing comprehensive and sustainably resourced national plans based on a multi-sector approach. In May 2014, the World Health Organisation passed a resolution that reflects global agreement on the huge threat antimicrobial resistance poses to human health; this was followed by publication of a draft global action plan on which all national action plans being developed are expected to be based. The global action plan seeks to preserve and maintain the responsible and accessible use of antimicrobials for all. The main strategic objectives focus on improving the understanding and awareness of antimicrobial resistance, strengthening knowledge via research and surveillance, reducing infection incidence, optimising the use of antimicrobial treatments and countering antimicrobial resistance through sustainable investment. This paper seeks to explore the global adoption and implementation of national action plans and specifically the use of antimicrobial stewardship (AMS) strategies to promote the optimal use of antimicrobials.

Antimicrobial Stewardship Strategies in Nursing Homes: Urinary Tract Infections

Deciding if a nursing home resident should receive an antimicrobial for a suspected urinary tract infection is challenging. One of the most frequently reported reasons nursing home staff suspect presence of a urinary tract infection (UTI) is change in a resident’s mental status. However, a change in mental status may be due to numerous causes, such as presence of underlying conditions like dementia, or reaction to a new medication. The evaluation for a UTI when a resident experiences change in mental status is further confounded by the high prevalence of asymptomatic bacteriuria, which leads to positive urine cultures in nursing home residents. Various organizations recommend testing and/or treating residents for UTIs only when they have presence of localizing signs and symptoms in order to reduce prescribing antimicrobials to residents with asymptomatic bacteriuria. Unnecessary antimicrobial use is contributing to the emergence of multidrug-resistant organisms and the increase in Clostridium difficile infections. Antimicrobial stewardship programs take measures to reduce inappropriate antimicrobial use including monitoring antibiotic use for residents with suspected urinary tract infections and reviewing the use of diagnostic tests as a driver for antibiotic use. Furthermore, additional methods such as educating nursing home staff on hand hygiene, urinary catheter use, and criteria for identifying signs and symptoms of a urinary tract infection along with discussing and including antimicrobial use in end-of-life goals may also aid in reducing antimicrobial use for UTIs. However, determining when a resident should be treated for a urinary tract infection is difficult, and more research is needed to help clinicians distinguish nursing home residents who have bacteriuria from the residents who have true urinary tract infections.

Making a Case for Pediatric Antimicrobial Stewardship Programs.

Although antimicrobials are commonly used in children, it is important to remember that they can have a profound impact on this unique patient population. Inadvertent consequences of antiinfective use in children include antimicrobial resistance, infection caused by Clostridium difficile, increased risk of obesity, and adverse drug events. In addition, compared with adults, children have different dosing requirements, antimicrobial formulation needs, pharmacokinetics, and antimicrobial susceptibility profiles. Therefore, pediatric-specific antimicrobial stewardship efforts are needed to promote appropriate use of antimicrobials in children. The primary purposes of this review article are to provide a rationale behind pediatric-focused antimicrobial stewardship and to describe currently available evidence regarding the initiatives of pediatric antimicrobial stewardship programs (ASPs). A literature search of the Medline database was performed (from inception through March 2015). The studies included in this review focus on antimicrobial stewardship interventions in inpatient pediatric settings. Ten inpatient studies involving pediatric-focused antimicrobial stewardship interventions were identified from the published literature. Four studies used the core strategy of prospective audit with feedback; two used prior approval. The remaining four used supplemental antimicrobial stewardship strategies (guidelines, clinical pathways, and computerized decision support tools). In general, the interventions resulted in decreased antimicrobial use, reduced antimicrobial costs, and fewer prescribing errors. Children have unique medical needs related to antimicrobials and deserve focused ASP efforts. The literature regarding pediatric antimicrobial stewardship interventions is limited, but published interventions may serve as paradigms for developing pediatric ASPs as demonstrated by the general success of these interventions.