Use Of Broad-spectrum Antimicrobials Research Articles

Activity of Cannabidiol on Ex Vivo Amino Acid Fermentation by Bovine Rumen Microbiota

Amino-acid-fermenting bacteria are wasteful organisms within the rumens of beef cattle that remove dietary amino nitrogen by producing ammonia, which is then excreted renally. There are currently no on-label uses for the control of this microbial guild, but off-label use of broad-spectrum antimicrobials has shown efficacy, which contributes to antimicrobial resistance. Plant-derived antimicrobials supplemented into the diets of cattle may offer worthwhile alternatives. This study sought to investigate the role of cannabidiol (CBD) as a terpenophenolic antimicrobial. Ex vivo cell suspensions were harvested from the rumen fluid of Angus × Holstein steers in non-selective media with amino acid substrates. The suspensions were treated with five concentrations of CBD (860 μg mL−1–0.086 μg mL−1) and incubated (24 h), after which ammonia production and viable number of cells per substrate and treatment were measured. The data demonstrated a ~10–15 mM reduction in ammonia produced at the highest concentration of CBD and negligible changes in the viable number of amino-acid-fermenting bacteria. CBD does not appear to be a biologically or economically viable terpenophenolic candidate for the control of amino acid fermentation in beef cattle.

Antimicrobial stewardship and molecular diagnostics: a symbiotic approach to combating resistance in the ED and ICU.

This review aims to evaluate the incorporation of rapid molecular diagnostics (RMD) in antimicrobial stewardship programs (ASPs) in the management of patients in the emergency department (ED) and intensive care unit (ICU), highlighting a shift from conventional microbiological diagnostic tests to RMD strategies to optimize antimicrobial use and improve patient outcomes. Recent advances in RMD have demonstrated the superior accuracy of RMD in identifying pathogens, combined with shorter turnaround times. RMD allows speeding up of antimicrobial decision making in the ED and facilitates faster escalation when empirical therapy was inappropriate, as well as more efficient de-escalation of empirical therapy later in the course of the treatment. Implementation of RMD however may be challenging. RMD hold great value in simplifying patient management and mitigating antimicrobial exposure, particularly in settings with high levels of antimicrobial resistance where the use of broad-spectrum antimicrobials is high. While the impact on the use of antimicrobials is significant, the impact on patient outcomes is not yet clear. Successful integration of RMD in clinical decision making in the ED and ICU requires a team approach and continued education, and its use should be adapted to the local epidemiology and infrastructure.

Healthcare-associated infections and antimicrobial use in acute care hospitals in Greece, 2022; results of the third point prevalence survey

BackgroundThe burden of healthcare-associated infections (HAIs) and the extent of antimicrobial use (AU) are periodically recorded through Point Prevalence Surveys (PPS) in acute care hospitals coordinated by the European Centre for Disease Prevention and Control (ECDC). In previous PPSs, Greece demonstrated increased HAI and AU prevalence: 9% and 54.7% in 2011–2012, and 10% and 55.6% in 2016–2017, respectively. The 2022 PPS aimed to estimate HAIs and AU indicators among inpatients, especially amid the COVID-19 pandemic.MethodsA cross-sectional study was conducted in 50 hospitals during October-December 2022, in Greece. Patients admitted before 8.00 a.m. of the survey day were observed. Patients with at least one HAI or receiving at least one antimicrobial agent were included. Data were collected by hospital infection control teams. Hospital and ward-level variables were analysed.ResultsFrom 9,707 inpatients, 1,175 had at least one HAI (12.1%), and 5,376 were receiving at least one antimicrobial (55.4%). Intensive care unit patients had the highest HAI (45.7%) and AU (71.3%) prevalence. Of the 1,408 recorded HAIs, lower respiratory tract (28.9%), bloodstream (20%), and urinary tract infections (13.1%) were the most common. Among 1,259 isolates, Klebsiella (20.5%) and Acinetobacter (12.8%) were most frequently identified. Resistance to first-level antibiotic markers was 69.3%. Among the 9,003 antimicrobials, piperacillin-tazobactam (10.9%), and meropenem (7.7%) were frequently prescribed. The ratio of broad-spectrum to narrow-spectrum antibiotics was 1.4. As defined by the 2021 WHO AWaRe (Access, Watch, Reserve) classification, restricted classes of Watch and Reserve agents comprised 76.7% of antibiotics. Usual indications were treatment of community-acquired infections (34.6%) and HAIs (22.9%). For surgical prophylaxis, cefoxitin was commonly used (20.2%), and typical courses (75.7%) lasted more than one day. HAI and AU prevalence were positively associated with bed occupancy (p = 0.027) and secondary hospitals (p = 0.014), respectively.ConclusionsThe 2022 PPS highlighted the increasing trend of HAI prevalence and high AU prevalence in Greece, the emergence of difficult-to-treat pathogens, and the extensive use of broad-spectrum antimicrobials. Strengthening infection control and antimicrobial stewardship programs in hospital settings is essential.

P25 Nowhere to hide: broad-spectrum antimicrobial guideline adherence in outpatients

Abstract Background The NHS Acute Trusts Standard1 contract requires a 10% reduction in broad-spectrum antibiotics by 10% by March 2024 from a 2017 baseline. Co-amoxiclav is a broad-spectrum antibacterial that comprises 30% of broad-spectrum consumption at University Hospitals Birmingham. It is widely used across all specialities and is a perfect candidate to review to influence downward trend in consumption. Outpatient prescriptions do not receive the same level of scrutiny from pharmacy or antimicrobial stewardship team as inpatient prescriptions. If deviations from guidelines are identified, then this could be a potential area to address to reduce consumption. Methods Sixty outpatient co-amoxiclav prescriptions were reviewed to assess appropriateness of prescribing during December 2022. Parameters assessed included the indication and duration of co-amoxiclav therapy and adherence to Trust antimicrobial guidelines. The speciality prescribing outpatient co-amoxiclav was also documented to identify whether prescribing trends could be identified. Results Of 60 reviewed outpatient prescriptions written in December 2022, 54 were issued by acute medicine with other specialities including cardiothoracic, renal medicine, elderly care, ENT, urology and cardiology. All prescriptions had a documented indication and duration, however only three were adherent to Trust antimicrobial guidelines. The graph below represents the different indications co-amoxiclav was prescribed for to outpatients across all three hospital sites. Co-amoxiclav was most frequently prescribed for respiratory tract infections, followed by skin and then urinary tract infections. Conclusions This audit has highlighted that outpatient co-amoxiclav is commonly prescribed inappropriately and does not comply with Trust antimicrobial guidelines. The speciality most frequently prescribing outpatient co-amoxiclav inappropriately was acute and emergency medicine. The lack of clarity regarding the infection indication is a potentially important factor in this setting, resulting in broad-spectrum antimicrobial use to cover multiple potential bacterial infections. A limitation of this audit is it was carried out over a short and busy winter period.

A quasi-experimental study of a bundled diagnostic stewardship intervention for ventilator-associated pneumonia

ObjectivesDiagnostic error in the use of respiratory cultures for ventilator-associated pneumonia (VAP) fuels misdiagnosis and antibiotic overuse within intensive care units. In this prospective quasi-experimental study (NCT05176353), we aimed to evaluate the safety, feasibility, and efficacy of a novel VAP-specific bundled diagnostic stewardship intervention (VAP-DSI) to mitigate VAP over-diagnosis/overtreatment. MethodsWe developed and implemented a VAP-DSI using an interruptive clinical decision support tool and modifications to clinical laboratory workflows. Interventions included gatekeeping access to respiratory culture ordering, preferential use of non-bronchoscopic bronchoalveolar lavage for culture collection, and suppression of culture results for samples with minimal alveolar neutrophilia. Rates of adverse safety outcomes, positive respiratory cultures, and antimicrobial utilization were compared between mechanically ventilated patients (MVPs) in the 1-year post-intervention study cohort (2022–2023) and 5-year pre-intervention MVP controls (2017–2022). ResultsVAP-DSI implementation did not associate with increases in adverse safety outcomes but did associate with a 20% rate reduction in positive respiratory cultures per 1000 MVP days (pre-intervention rate 127 [95% CI: 122–131], post-intervention rate 102 [95% CI: 92–112], p < 0.01). Significant reductions in broad-spectrum antibiotic days of therapy per 1000 MVP days were noted after VAP-DSI implementation (pre-intervention rate 1199 [95% CI: 1177–1205], post-intervention rate 1149 [95% CI: 1116–1184], p 0.03). DiscussionImplementation of a VAP-DSI was safe and associated with significant reductions in rates of positive respiratory cultures and broad-spectrum antimicrobial use. This innovative trial of a VAP-DSI represents a novel avenue for intensive care unit antimicrobial stewardship. Multicentre trials of VAP-DSIs are warranted.

Plant Extracts: Potential Alternative Treatment for Bovine Mastitis Causing Pathogen Staphylococcus aureus

Bovine mastitis is a significant disease affecting dairy herds worldwide. Mastitis can be characterized by physical, chemical, and bacteriological changes in milk and various pathological changes in the glandular tissues. This disease can invariably affect the health status of cattle and eventually have a direct economic impact on the dairy industry. Mastitis can be caused by the interaction of pathogens and their environment, and one of the disease-causing pathogens, Staphylococcus aureus, remains the leading cause of mastitis. Treatment is directed towards the use of broad-spectrum antimicrobials. However, with the threat of antibiotic-resistant pathogens, alternative treatments are being explored. The use of plants with ethnoveterinary origins can be promising in the search for novel therapeutic regimens. This review focuses on various studies using plant extracts as a possible alternative treatment for this specific bovine-causing pathogen, Staphylococcus aureus. Several studies that were conducted will serve as preliminary data in the development of alternative treatments for bovine mastitis.

Implementation and Perceived Effectiveness of Prospective Audit and Feedback and Preauthorization by US Pediatric Antimicrobial Stewardship Programs.

Antimicrobial stewardship programs (ASPs) promote optimal antimicrobial use to prevent resistance, improve outcomes, and reduce costs. We explored how pediatric ASPs enact prospective audit and feedback (PAF) and preauthorization and characterized programs' perceptions of how these choices affected attainment of stewardship goals. We conducted focus groups with US pediatric ASP practitioners, organized by predominant strategy: PAF, preauthorization, or a hybrid. We asked open-ended questions about organization, staffing, and operation of these strategies, as well as rationales for and perceived advantages and disadvantages of these choices. We used applied thematic analysis to analyze transcripts, organizing coded text into themes and categories. We formulated a conceptual model for how the design and performance of PAF and preauthorization affect stewardship goals and stewards' work experiences. Eighteen physicians and 14 pharmacists from 24 hospitals participated in five focus groups. Stewards described myriad advantages and limitations of PAF and preauthorization that support or detract from stewardship goals. For example, PAF uncovered institutional trends in antibiotic use and fostered relationship building but was time-consuming. Preauthorization efficiently reduced broad-spectrum antimicrobial use, yet offered limited educational opportunities. How these strategies facilitated or impeded appropriate antimicrobial use in turn affected stewards' professional satisfaction, creating a feedback loop that could reinforced positive or negative outcomes. ASPs reported differing emphasis on and implementation of PAF and preauthorization. Each strategy entailed contrasting benefits and trade-offs for steward satisfaction and perceived efficacy, suggesting that a hybrid approach could enable ASPs to maximize strengths of each to mitigate drawbacks of the other.

Prevalence of Candida species and their Susceptibility to Triazoles in Clinical Isolates from a Tertiary Care Hospital

In the recent past, the incidence of Candidiasis has witnessed a concerning upsurge, resulting in a significant healthcare challenge. These infections are further exacerbated by factors like the widespread use of broad-spectrum antimicrobials, chemotherapy-induced neutropenia, and the presence of medical devices. The present study is designed to address the critical need for identifying the Candida species responsible for clinical infections and assessing their susceptibility to key antifungal drugs Fluconazole, Voriconazole, and Itraconazole. Two hundred clinical samples from Rohilkhand Medical College &amp; Hospital, Bareilly were analyzed. Using Vitek-2 Compact (Biomerieux, France), the Candida spp. and the antifungal drug sensitivities were identified for Fluconazole and Voriconazole. E-test was done to identify Itraconazole sensitivity. This study found that C. albicans accounted for 21.5% while Non-albicans Candida (NAC) constituted 78.5%. Prolonged medication was the most common factor making susceptible for Candidiasis (43.5%), followed by indwelling biomedical devices (23%), Diabetes mellitus (16%), surgical causes (5.5%), trauma (5%), pregnancy (5%), and HIV (2%). Antifungal susceptibility testing showed that 68.5%, 72%, and 69.5% of Candida spp. isolates were sensitive to Fluconazole, Voriconazole, and Itraconazole, respectively. In conclusion, non-albicans Candida infections are increasing due to predisposing conditions, and some of these species are inherently resistant to the routinely used antifungal drugs. The study emphasizes the importance of identifying Candida spp. and their susceptibility to antifungals. This can limit the indiscriminate use of antifungal drugs, aid in selecting appropriate treatments, and reduce treatment costs, hospital stays, and patient morbidity and mortality.

689. Significant Improvement in Hand Hygiene Compliance and Decline in Clostridioides difficile Infections with Implementation of Infection Prevention Interventions

Abstract Background Per CDC, C. difficile is an urgent microbial threat. Despite use of CDC diagnostic criteria, 2-step testing protocol and antimicrobial stewardship interventions limiting broad spectrum antimicrobial use, we witnessed an increase in infections in 2022, therefore, additional interventions were implemented. Methods A multifaceted QI intervention program to improve IPC (infection prevention and control) practices was implemented in July 2022 at a 160-bed tertiary care center serving the tristate area of Iowa, South Dakota and Nebraska. Interventions included: auditing and real time observations for health care personnel (HCP) hand hygiene compliance; monitoring soap/sanitizer usage; educational interventions including posters posted throughout the hospital emphasizing hand hygiene, “A clean in and clean out” approach and contact precautions reminders posted in patient rooms/nursing stations, weekly nursing huddles focused on nursing and ancillary staff education, provider counseling and continued coaching. Pre-intervention period (P1: 1/10/2021- 6/30/2022) was compared with Intervention period (P2: 07/01/2022-3/31/2023) for hand hygiene compliance and C. difficile infection rates. Results Overall adequate hand hygiene compliance rates for all health care personnel (HCP) increased from 71% during P1 to 85% during P2 (P&amp;lt; 0.05). All categories of HCP showed a significant improvement in hand hygiene compliance from P1 to P2, with rates for physicians increasing from 74% to 92% (p&amp;lt; 0.05), nurses from 68% to 94% (p&amp;lt; 0.001); nurse practitioners/physician assistants from 75% to 90% (p&amp;lt; 0.05), ancillary staff (chaplain, medical technicians, social workers) from 60% to 89% (p&amp;lt; 0.01)]. Hand hygiene product use increased significantly and soap usage alone increased from 45% to 75% in P2 (p&amp;lt; 0.05). C. difficile infections declined significantly from a mean of 1.9 infections per 1000 patient days during P1 to 0.5 infections per 1000 patient days during P2 (p&amp;lt; 0.001); SIR (Standardized infection ratio) decreased from 1.14 during P1 to 0.4 during P2 (p&amp;lt; 0.01). No C. difficile related mortality was observed. Conclusion With implementation of multifaceted IPC interventions, significantly improved hand hygiene rates and a significant decline in C. difficile infections were observed. Disclosures All Authors: No reported disclosures

Examining the Veterinary Electronic Antimicrobial Prescriptions for Dogs and Cats in the Campania Region, Italy: Corrective Strategies Are Imperative.

Companion animals are increasingly being recognised as important contributors to the spread of antimicrobial-resistant bacteria. The present work aimed to measure the antimicrobial drug prescribing in dogs and cats in the Campania Region, Italy by analysing the Veterinary Electronic Prescriptions (VEPs) between 2019 and 2020. The medical records associated with antimicrobial drug prescriptions were collected according to the drug administration (systemic or topical) and the rationale for the treatment chosen. In the period under investigation, 166,879 drugs were prescribed of which 129,116 (73.4%) were antimicrobial. A total of 83,965 (65%) antibiotics were prescribed to dogs, 40,477 (31.4%) to cats, and 4674 (3.6%) to other companion animals. In dogs, 90.5% of VEPs prescribed for systemic treatment included an antimicrobial Critically Important or Highly Important or Important for human medicine (WHO, 2018). The most widely prescribed class was fluoroquinolones. The antimicrobials prescribed were mainly metronidazole-spiramycin (29.7%), amoxicillin-clavulanic (19.6%), enrofloxacin and cephalexin in dogs (16.5%) and enrofloxacin (22.6%) and amoxicillin-clavulanic acid (21.4%) in cats. Based on the results, the widespread use of broad-spectrum antimicrobials and the use of molecules for which limitations should be observed according to the EMA guidelines has emerged.

Improving the management of medical emergency team calls due to suspected infections: A before–after study

ObjectiveTo introduce a management guideline for sepsis-related MET calls to increase lactate and blood culture acquisition, as well as prescription of appropriate antibiotics. DesignProspective before (Jun–Aug 2018) and after (Oct–Dec 2018) study was designed. SettingA public university linked hospital in Melbourne, Australia. ParticipantsAdult patients with MET calls related to sepsis/infection were included. Main outcome measuresThe primary outcome measure was the proportion of MET calls during which both a blood culture and lactate level were ordered. Secondary outcomes included the frequency with which new antimicrobials were commenced by the MET, and the presence and class of administered antimicrobials. ResultsThere were 985 and 955 MET calls in the baseline and after periods, respectively. Patient features, MET triggers, limitations of treatment and disposition after the MET call were similar in both groups. Compliance with the acquisition of lactates (p = 0.101), respectively. There was a slight reduction in compliance with lactate acquisition in the after period (97% vs 99%; p = 0.06). In contrast, there was a significant increase in acquisition of blood cultures in the after period (69% vs 78%; p = 0.035). ConclusionsIntroducing a sepsis management guideline and enhanced linkage with an AMS program increased blood culture acquisition and decreased broad spectrum antimicrobial use but didn't change in-hospital mortality.

VRE acquisition in hospital and its association with hospital antimicrobial usage -a non-linear analysis of an extended time series.

Vancomycin resistant enterococci (VRE) have become endemic pathogens in many Australian hospitals causing significant morbidity. There are few observational studies that have evaluated the effect of antibiotic usage on VRE acquisition. This study examined VRE acquisition and its association with antimicrobial use. The setting was a NSW tertiary hospital with 800 beds over a 63 month period up to March 2020, straddling piperacillin-tazobactam (PT) shortages that occurred from in September 2017. The primary outcome was monthly inpatient hospital onset Vancomycin-resistant Enterococci (VRE) acquisitions. Multivariate adaptive regression splines (MARS) were used to estimate hypothetical thresholds, where antimicrobial use above threshold is associated with increased incidence of hospital onset VRE acquisition. Specific antimicrobials and categorised usage (broad, less broad and narrow spectrum) were modelled. There were 846 hospital onset VRE detections over the study period. Hospital onset vanB and vanA VRE acquisitions fell significantly by 64% and 36% respectively after the PT shortage. MARS modelling indicated that PT usage was the only antibiotic found to exhibit a meaningful threshold. PT usage greater than 17.4 defined daily doses/1000 occupied bed-days (95%C I: 13.4, 20.5) was associated with higher onset of hospital VRE. This paper highlights the large, sustained impact that reduced broad spectrum antimicrobial use had on VRE acquisition and showed that PT use in particular was a major driver with a relatively low threshold. It raises the question as to whether hospitals should be determining local antimicrobial usage targets based on direct evidence from local data analysed with non-linear methods.

Emerging fungal infections of man

Many fungi are now emerging as important causes of superficial and deep seated infections of man. The indiscriminate use of broad spectrum antimicrobials by oral and topical routes and prolonged hospital stay have led to emergence of many new fungal pathogens like Candida auris, Histoplasma spp. and Emergomyces spp.. Of these, C. auris is an established nosocomial pathogen now and can colonize hospital surfaces very commonly. Immunocompromised status of the patients due to various causes like HIV infection, Diabetes mellitus and anticancer chemotherapy, have added to the problems of emerging mycoses. Other risk factors can be exposure to soil and vegetation, and aquatic animals, in case of Lobomycosis. Some of these emerging mycoses are caused by dimorphic fungi. Also, some of these pathogens are really not fungi but algae, like Prototheca spp. Many a times these fungal pathogens are very difficult to identify accurately and treat. Treatment options are limited and surgical excision may have to be tried. Some of them may not be culturable at all, and need histopathology to confirm diagnosis. Their taxonomy is also being revised and reviewed constantly. These aspects are very important and should be studied and reviewed. Here we have reviewed available information in this aspect.

P05 Introducing new laboratory equipment for blood culture tests to improve the timeliness of antimicrobial susceptibility results in sepsis patients: a quality improvement project

Abstract Background Blood culture tests are crucial for identifying microorganisms causing sepsis and planning targeted antimicrobial therapy based on susceptibility results. However, the traditional testing method has remained unchanged for the last 60 years, resulting in a delay of approximately four days for final antimicrobial susceptibility results. This delay contributes to increased antimicrobial resistance, broad-spectrum antimicrobial use and healthcare costs. This project aims to reduce the time taken for antimicrobial susceptibility results. Methods An initial pilot study trial of 100 samples with a new system will be conducted, followed by a qualitative and quantitative evaluation strategy, keeping the existing system as a gold standard. The project scope was defined to avoid scope creep, and a detailed SWOT analysis was conducted to identify the best equipment available on the market. Interventions A process map was created, and a detailed fish bone (Ishikawa) problem analysis was done to identify key issues and potential bottlenecks. A robust stakeholder analysis has been planned, and a detailed GANTT chart has been prepared. Implementing effective communication, leadership and nudge theory can engage stakeholders and mitigate risks. A cost-benefit analysis predicted a cost savings of nearly a million pounds within one hospital of seven within the Trust. Conclusions The introduction of new laboratory equipment for blood culture tests has the potential to reduce the turnaround time for antimicrobial susceptibility results significantly to less than 24 h, leading to early diagnosis and treatment of sepsis with targeted antimicrobial therapy. This initiative also counters various problems, including antimicrobial resistance, broad-spectrum antimicrobial use and healthcare costs. This project proposal is an important step towards improving blood culture testing and the timeliness of antimicrobial susceptibility results. Organizations like the NHS must seek to improve continuously for long-term effectiveness, and this project is one such change that will reap many long-term benefits.

P36 Using the Australian National Antimicrobial Prescribing Survey portal (NAPS) to benchmark antibiotic prescribing within an Integrated Care Board (ICB): a pilot point prevalence survey (PPS) of two NHS Trusts

Abstract Background PPS is useful in evaluating volume and appropriateness of antimicrobial prescribing to guide specific antimicrobial stewardship (AMS) interventions. Integrated care systems enable collaboration within an ICB and benchmarking of antimicrobial prescribing in constituent trusts to identify disparities and learn from sharing best practice. NAPS is a web-based qualitative auditing platform which is used to conduct an annual Australia-wide PPS. To assess the suitability of NAPS in benchmarking antimicrobial prescribing practices, we piloted the NAPS platform in the acute admission ward areas in two NHS Trusts within an ICB. Methods In OUHFT, admissions to 2 acute medicine wards on a single day were extracted using the Cerner electronic prescribing system. Antimicrobial prescriptions were anonymized, reviewed using NAPS protocol and uploaded to the NAPS platform. In BHT, antimicrobial prescriptions on 2 admission wards were collected manually using the NAPS parameters and audit standards and entered directly into Excel®. Ethical approval was not required due to the anonymized nature of this audit. Results A total of 124 patients at OUHFT and 53 patients at BHT were included. The proportion of patients prescribed antimicrobials varied, with a prevalence of 23% (n = 29) at OUHFT and 54% (n = 28) at BHT. The total number of antimicrobial prescriptions was approximately 40 per trust. Compliance with guidelines for OUHFT and BHT (88% versus 83%) and stewardship appropriateness (73% versus 80%) were similar. The main indication for antimicrobials was pneumonia. The most common reasons for inappropriateness were ‘incorrect duration’ and ‘spectrum too broad’. The most prescribed antimicrobials differed, with co-amoxiclav and amoxicillin (43%) at OUHFT and metronidazole and clarithromycin (24%) at BHT. Non-compliance with guidelines was frequently associated with the use of doxycycline and co-amoxiclav (47%) at OUHFT and amoxicillin and piperacillin/tazobactam (72%) at BHT. Conclusions Benchmarking of antimicrobial prescribing was possible as both PPSs were conducted using the NAPS parameters and standards. Focusing efforts on antibiotic prescribing for pneumonia, the use of broad-spectrum antimicrobials and reducing duration of courses will be taken forward as a key focus for AMS efforts. NAPS is a suitable tool for benchmarking, sharing best practice and facilitating discussion of AMS interventions across an ICB. This model should be considered as a template for national benchmarking of antimicrobial prescribing.

Metabolic syndrome is independently associated with improved overall survival to first-line therapy with immune checkpoint inhibitors in non-small cell lung cancer.

Many co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC). We carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC. One hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival. Our results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.

Candida lipolytica Bloodstream Infection in an Adult Patient with COVID-19 and Alcohol Use Disorder: A Unique Case and a Systematic Review of the Literature.

Candida lipolytica is an uncommon Candida species causing invasive fungemia. This yeast is mainly associated with the colonisation of intravascular catheters, complicated intra-abdominal infections, and infections in the paediatric population. Here, we report a case of C. lipolytica bloodstream infection in a 53-year-old man. He was admitted for an alcohol withdrawal syndrome and mild COVID-19. Among the primary risk factors for candidemia, only the use of broad-spectrum antimicrobials was reported. The empiric treatment was commenced with caspofungin and then targeted with intravenous fluconazole. Infective endocarditis was ruled out using echocardiography, and PET/TC was negative for other deep-seated foci of fungal infection. The patient was discharged after blood culture clearance and clinical healing. To the best of our knowledge, this is the first case of C. lipolytica candidemia in a patient with COVID-19 and alcohol use disorder. We performed a systematic review of bloodstream infections caused by C. lipolytica. Clinicians should be aware of the possibility of C. lipolytica bloodstream infections in patients with alcohol use disorder, especially in a COVID-19 setting.

Antimicrobial consumption and drug utilization patterns among COVID-19 and non-COVID-19 patients.

To understand differences in antimicrobial use between COVID-19 and non-COVID-19 patients. To compare two metrics commonly used for antimicrobial use: Defined Daily Dose (DDD) and Days of Therapy (DOT). To analyse the order in which antimicrobials were prescribed to COVID-19 patients using process mining techniques. We analysed data regarding all ICU admissions from 1 January 2018 to 14 September 2020, in 17 Brazilian hospitals. Our main outcome was the antimicrobial use estimated by the DDD and DOT (Days of Therapy). We compared clinical characteristics and antimicrobial consumption between COVID-19 and non-COVID-19 patients. We used process mining to evaluate the order in which the antimicrobial schemes were prescribed to each COVID-19 patient. We analysed 68 405 patients admitted before the pandemic, 12 319 non-COVID-19 patients and 3240 COVID-19 patients. Comparing those admitted during the pandemic, the COVID-19 patients required advanced respiratory support more often (42% versus 12%). They also had longer ICU length of stay (6 versus 3 days), higher ICU mortality (18% versus 5.4%) and greater use of antimicrobials (70% versus 39%). Most of the COVID-19 treatments started with penicillins with ß-lactamase inhibitors (30%), third-generation cephalosporins (22%), or macrolides in combination with penicillins (19%). Antimicrobial prescription increased in Brazilian ICUs during the COVID-19 pandemic, especially during the first months of the epidemic. We identified greater use of broad-spectrum antimicrobials by COVID-19 patients. Overall, the DDD metric overestimated antimicrobial use compared with the DOT metric.

Nasopharyngeal rapid diagnostic testing to reduce unnecessary antibiotic use and individualize management of acute otitis media.

Acute otitis media (AOM) is the most common indication for antibiotics in children. The associated organism can influence the likelihood of antibiotic benefit and optimal treatment. Nasopharyngeal polymerase chain reaction can effectively exclude the presence of organisms in middle-ear fluid. We explored the potential cost-effectiveness and reduction in antibiotics with nasopharyngeal rapid diagnostic testing (RDT) to direct AOM management. We developed 2 algorithms for AOM management based on nasopharyngeal bacterial otopathogens. The algorithms provide recommendations on prescribing strategy (ie, immediate, delayed, or observation) and antimicrobial agent. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life day (QALD) gained. We used a decision-analytic model to evaluate the cost-effectiveness of the RDT algorithms compared to usual care from a societal perspective and the potential reduction in annual antibiotics used. An RDT algorithm that used immediate prescribing, delayed prescribing, and observation based on pathogen (RDT-DP) had an ICER of $1,336.15 per QALD compared with usual care. At an RDT cost of $278.56, the ICER for RDT-DP exceeded the willingness to pay threshold; however, if the RDT cost was <$212.10, the ICER was below the threshold. The use of RDT was estimated to reduced annual antibiotic use, including broad-spectrum antimicrobial use, by 55.7% ($4.7 million for RDT vs $10.5 million for usual care). The use of a nasopharyngeal RDT for AOM could be cost-effective and substantially reduce unnecessary antibiotic use. These iterative algorithms could be modified to guide management of AOM as pathogen epidemiology and resistance evolve.

1807. Tracking antibiotic de-escalation using a novel metric, days of antibiotic spectrum coverage (DASC)

Abstract Background In the United States, days of therapy (DOT) is the currently preferred method for measuring antibiotic consumption. A major disadvantage of DOT is that it does not account for the antimicrobial’s spectrum. Antibiotic de-escalation is therefore not well-captured by DOT. To overcome the limitation of DOT, we recently proposed a new metric, days of antibiotic spectrum coverage (DASC). DASC is calculated by multiplying DOT and the antibiotic spectrum coverage (ASC) score, which was assigned based on the activities of each antibiotic agent for 11 wild type bacteria and 5 acquired resistance patterns. Here we evaluate the performance of DASC using antibiotic consumption data where the main antimicrobial stewardship program (ASP) activity is daily prospective audit-and-feedback of all inpatients on antibiotics. Methods We analyzed the retrospective cohort of inpatient antibiotic use at Iowa City VA Health Care System from 2017 to 2021. Total monthly DOT was the aggregation of monthly DOT for each antibiotic. DASC for each antibiotic was calculated by multiplying ASC for each antibiotic to DOT. DASC for each antibiotic was aggregated to total monthly DASC. Days-present was used as a denominator for both metrics. Trends of total monthly DOT and DASC were analyzed by simple linear regression. Results There was no significant trend in monthly DOT (Figure A: beta= 0.30, 95%CI: -0.67 to 1.27, p=0.55), but there was a significant downward trend in monthly DASC (Figure B: beta= -6.89, 95%CI: -12.7 to -0.98, p=0.03). Conclusion While a significant downward trend was seen using monthly DASC, no trend was observed using monthly DOT. In contrast to DOT, which captures antibiotic consumption without considering the spectrum, DASC captures both antibiotic consumption and spectrum, suggesting DASC can add another dimension in tracking inpatient antibiotic use. DASC is easily calculated if DOT for each antibiotic is available. Metrics that don’t capture antimicrobial spectrum may not be able detect improvements in avoiding unnecessary use of broad-spectrum antimicrobials, an important target of ASPs. Disclosures Daniel J. Livorsi, MD, Merck &amp; Co.: Grant/Research Support Michihiko Goto, MD MSCI, Merck &amp; Co.: Grant/Research Support.