Duration Of Antimicrobial Therapy Research Articles

Bloodstream Infections Caused by Carbapenem-Resistant Enterobacterales: Risk Factors for Mortality, Antimicrobial Therapy and Treatment Outcomes from a Prospective Multicenter Study.

PurposeCarbapenem-resistant Enterobacterales bloodstream infections (CRE BSIs) have a high mortality. However, an optimal antimicrobial treatment has not been determined. This study was conducted to evaluate the risk factors for mortality and provided potential therapeutic options for treatment of CRE infection.Patients and MethodsWe investigated patients with CRE BSIs from 18 hospitals across nine Chinese provinces from January to December 2019. Data were collected from the medical records according to a pre-established questionnaire. Antimicrobial susceptibility testing and DNA sequencing were performed to investigate the characteristics of isolates.ResultsA total of 208 patients enrolled; the overall 30-day mortality rate was 46.2%. The causative pathogen was carbapenem-resistant Klebsiella pneumoniae (CRKP) (85.6%). Patients infected by ST11-KL64 CRKP had a high sepsis/septic shock incidence rate (p < 0.05). Sepsis/septic shock, short duration of antimicrobial therapy and empirical using tigecycline were independent risk factors for mortality (p < 0.05 for each risks). Appropriate therapy had better survival benefit than inappropriate therapy (p = 0.003). No difference was identified between monotherapy and combination therapy (p = 0.105). Tigecycline as a frequently used antimicrobial had poor therapeutic effect on BSI patients (p < 0.001). Carbapenem-based treatment had a better therapeutic effect on patients infected by isolates with meropenem MIC ≤ 8 mg/L (p = 0.022). The patients who received short duration of antimicrobial therapy had poorer prognosis (p < 0.001) than the patients who received long duration of antimicrobial therapy.ConclusionReducing the mortality of CRE BSIs need to comprehensively consider whether the antimicrobials were used appropriately, together with infection severity and CRE strains.

Predictors of mortality among adult, old and the oldest old patients with bloodstream infections: An age comparison

BackgroundBloodstream infections (BSIs) are a major cause of mortality in elderly. Objective of the study is to identify factors predictive of mortality in old and oldest old patients. MethodsThis is a single centre retrospective observational study, including all patients admitted to Fondazione Policlinico A. Gemelli university hospital and diagnosed with BSI. Patients were stratified into three groups according to age: adult (A), younger than 65; old (O), aged between 65 and 80; oldest old (OO), older than 80. Primary outcome was 30-day in-hospital mortality. Secondary outcomes were duration of antimicrobial therapy (DOT) and length of hospital stay (LOS). ResultsOf the 1034 patients included in the study, 346 were in group A, 447 in group O and 241 in group OO. The rate of 30-day mortality raised from 6.9% (24/346) in group A to 10.8% (84/447) in group O and 33.2% (80/241) in group OO (p<0.01), while DOT and LOS significantly decreased moving from adults to oldest old (p<0.01). Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus spp were both independently correlated to an increased 30-day mortality risk selectively in patients older than 80 (MRSA: HR 2.37, p=0.03; Enterococcus spp: HR 2.44, p=0.01). ConclusionsBSIs have a high impact on survival in old and oldest old patients. BSIs by gram-positive pathogens, in particular MRSA and Enterococcus spp, should be a wake-up call for physicians, who should focus efforts on adequate and prompt antibiotic and support treatment.

Drug utilisation in adult, paediatric and neonatal intensive care units, with an emphasis on systemic antimicrobials.

Critically ill adults, children and neonates receive drugs that are often administered parenterally and in infusions. Considering patient illness severity, empirical broad-spectrum antimicrobials are commonly used. We conducted the present study to evaluate the drug use in this population, with aspecial focus on antimicrobials. Aprospective cross-sectional study was implemented in adult, paediatric and neonatal intensive care units. Various prescribing and supplemental indicators were used for drug comparisons. The World Health Organisation's list of essential drugs, the national drug formulary and critically important antimicrobial drugs were assessed. Proportions and median (range) were used to represent categorical and numerical values. Four hundred and ninety-six critically ill patients were enrolled in the study, with 5,636 prescribed drugs used for 31,993 patient-days. Critically ill adults received significantly more drugs compared to children and the neonatal population (11 [8-16], 9 [6-17] and 5 [3-12] respectively). Critically ill neonates received significantly fewer of the drugs listed in the national formulary compared to older children and adults (94.1% [10.1], 92.4% [32.4] and 80.1% [20.4]). Critically ill neonates received fewer antimicrobials (82% compared to 91.3% in adults and 98% in children). Furthermore, critically ill adults received more broad-spectrum antimicrobials compared to neonates. Prolonged empirical antimicrobial use was observed more in critically ill children (52%) compared to adults (29.8%). Alarge majority of the antimicrobials were critically important for 87.7%, 83.9% and 86.5% of patients in the adult, paediatric and neonatal intensive care units. We observed significant differences in terms of drug classes predominantly used in various age groups of critically ill patients, particularly regarding the nature and type of antimicrobial drugs and the duration of antimicrobial therapy.

Bovhyaluronidaze azoximer as an antimicrobial alternative in companion animals

Antimicrobial resistance formation in various bacteria is a serious biosafety threat. In this regard, the important issue in medical and veterinary fields is not only the rational use of antibacterial drugs, but also the search for ways to significantly reduce the need for antibiotics. Three studies designed to research into these challenges are described. The results indicated that (1) the bacteriuria presences in 62.4 +/-4.1% of urine samples obtained from companion animals (the microflora count in urine samples is estimated from ’++’ to ’Entire Field-of-View’); (2) 16.3 +/-4.0% of samples from companion animals showed bacteria with low antibiotics sensitivity, and 8.1 +/-3.0% of samples contained bacteria resistant to 30 antibiotics included in the susceptibility test; (3) the Bovhyaluronidaze azoximer reduce antimicrobial therapy duration statistically significant (p=0.0089). The studies were conducted at the facilities of St. Petersburg State University of Veterinary Medicine and Bars veterinary clinic chain in St. Petersburg, Russia. A randomized clinical trial of Bovhyaluronidaze azoximer effect on course of disease and treatment duration of acute and chronic prostatitis and urocystitis, including complicated by urolithiasis, was conducted in 54 dogs. Animals were randomly assigned to intervention (n=34) and control (n=20) groups. Animals of both groups received the antimicrobial therapy. Interventional group patients additionally received Bovhyaluronidaze azoximer in the form of rectal suppositories. The antimicrobial therapy mean duration in intervention group animals took 14.88 +/-4.98 days, in control group animals — 18.65 +/-5.40 days. The study findings imply that bacteriuria is widely prevalent in companion animals and antimicrobial resistance is increasing issue in veterinary medicine. Bovhyaluronidaze azoximer contributes to microcirculation restore and increases the bioavailability of antibacterial drugs at the site of infection. This makes its relevant for use in the complex treatment for septic and inflammatory processes. This allows to reduce the antimicrobial course duration (and completely decline antibiotic therapy in some cases) and prevent the formation of chronic inflammation and infection sites.

254. Review of Clinical Outcomes in Patients Treated with Beta-lactam vs Non-beta-lactam Therapy for AmpC Producing Bacterial Bloodstream Infections

BackgroundAmpC beta-lactamase producing organisms are traditionally treated with carbapenem or fluoroquinolone antibiotics. Recent studies, however, describe similar clinical outcomes in patients that receive cefepime or piperacillin/tazobactam. We sought to assess outcomes in patients with bloodstream infections caused by AmpC-producing organisms that received beta-lactams compared non-beta-lactam therapy.MethodsData was obtained retrospectively from the electronic health record (EHR) from January 2012 to February 2020. The primary objective was 30-day mortality from the day of first positive blood cultures with Enterobacter spp., Citrobacter spp., or Serratia spp. in patients who received non-beta-lactam therapy (carbapenem, fluoroquinolone, trimethoprim/sulfamethoxazole) to those who received beta-lactam therapy (cefepime, piperacillin/tazobactam). Secondary objectives included 30-day recurrence of bacteremia, pathogen isolated, source of bacteremia, hospital length of stay, and duration of antimicrobial therapy.ResultsA total of 90 patients were included, 50 in the non-beta lactam group and 40 in the beta-lactam group. Demographics were similar between groups. Thirty-day mortality was significantly higher in the beta-lactam group (20% vs 2%, p=0.009). Enterobacter spp. was the most frequently identified pathogen (67%), most commonly isolated from a urinary (31%) or intra-abdominal source (22%). The average duration of antibiotic therapy was significantly higher in the non-beta lactam group (18 vs 12 days, p=0.001). In contrast, there was no significant difference found in hospital length of stay, recurrence of bacteremia, pathogen isolated or source of bacteremia between groups.ConclusionBeta-lactam therapy for the treatment of bloodstream infections caused by Amp-C producing organisms was associated with significantly greater 30-day mortality compared to patients that received non-beta-lactam therapy.Disclosures All Authors: No reported disclosures

19. A Global Point Prevalence Survey of Antimicrobial Use in Neonatal Intensive Care Units

BackgroundAntimicrobials are one of the most commonly used medications in the NICU. We aimed to gather baseline global data on antimicrobial use to facilitate subsequent antimicrobial stewardship efforts.MethodsWe conducted a one-day global NICU point prevalence study on July 1, 2019 with a 30-day follow up. Data collection included patient demographics, antimicrobial therapy, site location, antimicrobial stewardship (AS) practices as well as the duration of antimicrobial therapy and in-hospital mortality were recorded.ResultsEighty-one NICUs from twenty-eight different countries identified 2,163 admitted patients of which 570 (26%) were prescribed at least one antimicrobial. Three NICUs did not have any patients on antimicrobial therapy, all had less than 20 patients admitted. Level 3 and Level 4 NICUs comprised 51% and 48% respectively. Delivery units comprised 74%, the rest were referral centers. AS programs were in place in 62% of the hospitals and 47% of the units had NICU specific initiatives. Patients were on average 32.5 weeks gestational age (+/-5.3 SD), with birth weight of 1976 grams (+/- 1022 SD), and were 32 days (+/-65 SD) postnatal age at the time of the study.Antibiotics were the most frequently used medication in 92% of patients with 931 antibiotics prescribed on the assessment day. Hospitals with any NICU AS initiative had significantly lower rates of antibiotic utilization compared to NICUs without AS (21% and 32%; p-value: < 0.01). Of those on antibiotic therapy, ampicillin, gentamicin and amikacin were prescribed to 41%, 34%, and 21% of patients respectively. When only definitive treatment was evaluated, vancomycin, amikacin, and meropenem were the highest prescribed antibacterial agents at 25%, 19%, and 19% respectively. At the initial assessment, study participants indicated either 3 or 7 days (37% and 26%) for planned duration. Actual treatment duration for empiric and definitive treatment, was 7 and 14 days (29% and 19%) When comparing patients who had an established treatment course at the time of the initial assessment, the final length of treatment for culture negative sepsis was 7 (IQR:5–10) and culture positive sepsis was 11 days (IQR:10–14; p-value: 0.07).ConclusionBenchmarking global antimicrobial use is crucial for improving NICU-AS practices.Disclosures Pavel Prusakov, PharmD, Merck (Research Grant or Support) Debra A. Goff, PharmD, Merck (Research Grant or Support)

379. Epidemiology of Antimicrobial Use Among SARS-CoV-2 Positive and Negative Admissions in the US: A Multicenter Evaluation

BackgroundSARS-CoV-2, a novel coronavirus, emerged in Wuhan, China in December of 2019, and became a pandemic. Increases in bacterial/fungal co-infections have occurred during influenza pandemics and early data from this pandemic indicate high utilization of antimicrobial therapy. We compared the utilization of antimicrobials and health outcomes between SARS-CoV-2 positive and negative patients.MethodsPatients hospitalized at 271 US acute care facilities from 3/1/20–5/30/20 with ≥1 day length of stay (LOS) and ≥24 hours of antimicrobial therapy tested for SARS-CoV-2 were included in the study (BD Insights Research Database [Becton, Dickinson & Company, Franklin Lakes, NJ]). Demographics, antimicrobial utilization, duration of antimicrobial therapy, hospital LOS and ICU LOS data were analyzed by SARS-CoV-2 test results.Results142,054 patients were tested for SARS CoV-2 and 12% (n=17,075) were SARS-CoV-2 positive. SARS-CoV-2 negative and positive patients did not differ regarding presence of a positive bacterial culture. Total LOS, % ICU admission, and ICU LOS were higher among SARS-CoV-2 positive patients (Table). In total 48% of admissions were prescribed antimicrobial therapy; rates were higher in SARS-CoV-2 positive versus negative admissions (68% vs. 46%). The most common antimicrobials and classes are in Table.Antimicrobial therapy and outcomes in hospitalized SARS-CoV-2 tested patients. ConclusionAlmost half of patients tested for SARS-CoV-2 were prescribed antimicrobials, with antimicrobial use higher among those with SARS-CoV-2, despite similar rates of positive cultures. On average, antimicrobials were prescribed within 10 hours from the time to admission among patients tested. These treatment patterns may highlight the difficulties in making treatment decisions and concerns over potential bacterial superinfection in SARS-CoV-2, but also indicate potential overuse of antimicrobials. Collateral damage from antimicrobial overuse include increase selection of antimicrobial resistance, adverse effects of drugs, and unnecessary treatment costs. It will be important to continue to evaluate the utilization and appropriateness of antimicrobial use among SARS-CoV-2 patients.DisclosuresLaura A. Puzniak, PhD, Merck (Employee) Karri A. Bauer, PharmD, Merck Research Laboratories (Employee) Lyn Finelli, DrPH, MS, Merck & Co Inc, (Employee) Carisa De Anda, PharmD, Merck & Co Inc, (Employee) Pamela Moise, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Latha Vankeepuram, MS, BD (Employee) Prashant Parikh, n/a, Becton, Dickinson and Company (Employee) Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)GlaxoSmithKline plc. (Other Financial or Material Support, Funding)

64. Impact of a Duration Bundle on Antimicrobial Use in a Pediatric Hospital

BackgroundLimiting antibiotic durations to the shortest effective duration is a strong recommendation with moderate-quality evidence in the 2016 IDSA Antimicrobial Stewardship Program (ASP) guidelines. An ASP bundle including a decrease in antimicrobial automatic stop dates from 14 days to 10 days along with a guideline for standard durations for 48 specific indications was implemented at a tertiary pediatric hospital in November 2019. The purpose of this review and was to assess the impact of this ASP initiative on patient outcomes and hospital cost-savings by comparison of pre-intervention and post-intervention data.MethodsA set of antimicrobial duration recommendations for pediatric patients was created by the Antimicrobial Stewardship Program, Pediatric Hospital Medicine providers, and Infectious Disease providers specific to indication, agent, or pathogen. After education of medical care providers and distribution of the recommendations, automatic stop dates in the Electronic Medical Record (EMR) were updated from 14 days to 10 days for all antimicrobials. Concomitant advertising campaigns were shown on all hospital screensavers. Data were collected for a one month pre-intervention period of Nov.15 - Dec.15, 2018 including 133 patients and a one month intervention period of Nov.15 - Dec.15, 2019 including 125 patients.ResultsThe average length of stay decreased from an average of 8.3 days pre-implementation to 6.7 days (p=0.043) post implementation. The ratio of actual to recommended duration also decreased from 1.56 to 1.30 (p< 0.001) when comparing pre vs. post initiative. Balancing measures did not change for restarting treatment within 48 hours of stopping or readmission within 30 days for the same infection. The decrease in inpatient therapy translated to more than $10,000 per year in direct drug cost.ConclusionThis intervention lead to a significant reduction in average length of stay per admission and significantly reduced the secondary outcomes of the total duration of antimicrobial therapy and the ratio of actual duration compared to recommended duration. This lead to cost savings and decreased inappropriate antibiotic exposure.Disclosures All Authors: No reported disclosures

The role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in assessment of complex invasive fungal disease and opportunistic co-infections in patients with acute leukemia prior to allogeneic hematopoietic cell transplant.

Individuals diagnosed with acute lymphoid and myeloid malignancies are at significant risk of invasive fungal and bacterial infections secondary to their marked immunocompromised states with a significant high risk of mortality. The role of metabolic imaging with 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) has been increasingly recognized in optimizing the diagnosis of invasive infection, monitoring the response to therapy and guiding the duration of antimicrobial therapy or need to escalate to surgical intervention. Two distinct cases of pulmonary co-infection of rare fungal and bacterial pathogens are explored in severely immunocompromised individuals where FDG PET/CT aided both patients to make a full recovery and transition to HCT. The first case explores mixed Scedosporium apiospermum and Rhizomucor pulmonary infection on a background of T cell/myeloid mixed phenotype acute leukemia ultimately warranting long-term antifungal therapy and lobectomy prior to HCT. The second case explores Fusarium and Nocardia pulmonary infection on a background of relapsed AML also warranting surgical resection with lobectomy and long-term antimicrobials prior to transition to HCT. The cases highlight the utility of FDG PET/CT to support the diagnosis of infections, including the presence or absence of disseminated infection, and to provide highly sensitive monitoring of the infection over time. FDG PET/CT played a key role in directing therapy duration decisions and prompted the necessity for surgical intervention. Ultimately, the use of FDG PET/CT allowed for a successful transition to HCT highlighting its value in this clinical setting. FDG PET/CT has an emerging role in the diagnostic and monitoring pathway for complex infections in high-risk immunocompromised patients.

Abdominal sepsis

Background. Sepsis is a life-threatening acute organ dysfunction that occurs as a result of dysregulation of the macroorganism’s response to infection. Septic shock is a variant of sepsis characterized by the circulatory failure, manifested by hypotension and increased lactate levels &gt;2 mmol/L despite adequate infusion, which requires the administration of vasopressors to maintain average blood pressure &gt;65 mm Hg.&#x0D; Objective. To describe the management of patients with abdominal sepsis.&#x0D; Materials and methods. Analysis of literature data on this topic.&#x0D; Results and discussion. Complicated intra-abdominal infection (IAI) is the growth of pathogenic microorganisms in a usually sterile abdominal cavity, usually due to the perforation of the hollow organs. Uncomplicated IAI involves transmural inflammation of the digestive tract, which does not spread beyond the hollow organ. If uncomplicated IAI are not treated, there is a possibility that they will progress to complicated ones. Measures to control the source of infection include the drainage of abscesses or places of accumulation of infected fluid, removal of necrotic infected tissues and restoration of the anatomy and functions of the affected area. Several multivariate studies have found that failure to adequately control the source of infection is a risk factor for adverse outcomes and death in patients with IAI. Surviving sepsis and other recommendations also support the need for early control of the source of infection. In a study by B. Tellor et al. (2012) mortality was 9.5 % among individuals with adequate control of the infection source and 33.3 % among patients who failed to achieve such control. In some situations, it is advisable to manage patients conservatively. Thus, in appendicular infiltration, most studies have demonstrated the benefits of conservative management (Andersson R.E., Petzold M.G., 2007). Management of IAI without final control of the primary source is possible in cases where the organism has already overcome the infection, and surgery can only increase the number of complications. In general, patients with localized infections may need less invasive management. Thus, percutaneous drainage can be used for localized accumulations of fluid in the abdominal cavity. 80-92 % of drainage procedures are successful on the first attempt. &lt;5 % of patients require surgical treatment. Such drainage procedures are used in infected pancreatic necrosis, and the final debridement of the infection source may be delayed. In critically ill patients, damage control laparotomy and limited intervention (resection without reanastomosis or stoma formation, temporary drainage and tamponade of the abdominal cavity if necessary, temporary closure of the abdominal cavity) are performed to control the infection. Indications for damage control laparotomy include inability to achieve adequate control of the source of IAI during primary laparotomy, hemodynamic instability, the need to re-evaluate the condition of the problematic anastomosis, and diffuse peritonitis. A prospective study of staged laparotomies revealed a shorter length of stay in the intensive care unit, a lower incidence of complications and lower treatment costs using this method compared to the standard one. Antibacterial support of surgical interventions is an important aspect of treatment. In conditions of increasing antibiotic resistance, antibiotics should be prescribed strictly in accordance with the recommendations and for as short effective period as possible.&#x0D; Conclusions. 1. Despite the fact that approaches are changing, control of the IAI source remains the main method of treatment of most patients with IAI. 2. The choice of empirical antibacterial therapy should be based on the risk assessment and potential of resistant bacteria. 3. The duration of antimicrobial therapy can be significantly reduced (4 days).

Prostatic abscess: clinical features, management, and outcomes of a “Stealth” infection: retrospective case series and review of the literature

Prostatic abscess (PA) is uncommon and may be difficult to distinguish from acute prostatitis which often leads to delayed or missed diagnoses. Although gram-negative bacilli are the traditional etiology of PA, Staphylococcus aureus is an emerging cause. The goals of this study were to characterize the current clinical features, microbiology, management, and outcomes of PA at a US academic center. A retrospective review of adult patients hospitalized with an ICD-9/10 diagnosis of PA between January 2013 and July 2018 was conducted. Inclusion criteria included age ≥18 years, a compatible genitourinary (GU) infection syndrome, and imaging consistent with PA. Relevant data were extracted and analyzed by univariate analysis as appropriate. Twenty-two patients with PA were identified with median age 57 years. Five patients (23%) were immunosuppressed and 11 (50%) had diabetes. No patient had prior PA but 3 had past prostatitis. Only 1 patient had recent GU instrumentation and none had indwelling urinary catheters. The most common presenting symptoms were fever (59%), dysuria (45%), and urinary retention (32%). Only 7 out of 18 (39%) patients had prostate tenderness on exam and none had fluctuance. As demonstrated by computed tomography, PAs were multifocal in 8 (36%) patients and 16 (73%) had PAs >2 cm in diameter. The median abscess size was 3.2 cm. S. aureus was isolated in 60% of positive urine cultures and 78% of positive blood cultures; 46% were methicillin-resistant. Nine patients (41%) received antibiotics alone whereas 13 (59%) required antibiotics plus drainage. The median duration of antimicrobial therapy was 34.5 days. Four week mortality was 9%. When comparing S. aureus PA to other causes, S. aureus patients tended to have higher fevers, more often had diabetes, and received longer durations of antibiotic therapy (median 35 days vs 31 days, P = 0.04) but age, abscess size, and mortality did not differ. PA is relatively uncommon and often clinically unsuspected. Imaging may be critical to accurate diagnosis. Optimal management usually requires antibiotics and sometimes drainage depending on abscess size. We found a significant proportion of cases due to S. aureus which might be relevant when deciding empiric antimicrobial therapy.

Duration of antimicrobial therapy for Gram-negative infections.

The potential benefits on antimicrobial resistance emergence, incidence of antibiotic-related adverse effects, and health costs have pushed to shorten therapeutic courses for Gram-negative bacilli (GNB) infections. However, the safety of this approach is still under investigation. This review gathers recent contributions to the evaluation of the impact on antimicrobial resistance and clinical outcome of shorter therapeutic courses against GNB infections, and highlights data on the modern approach of adjustable antibiotic duration. Recent advances include data on the safety of 7-day treatment of uncomplicated Enterobacteriaceae bloodstream infections with favorable early 48-h evolution. A promising innovative approach with individualized treatment duration arises, supported by recently published results on GNB bacteremia evaluating fixed antibiotic durations and an adaptive antibiotic duration driven by blood levels of C-reactive protein. Recent literature illustrates a strong trend towards shortened antibiotic durations in GNB infections, illustrated by lately published data in GNB bacteremia and ongoing studies in GNB ventilator-associated pneumonia. However, short antibiotic course for specific situations, such as immunodeficiency, drug-resistance, and inadequate source control should be handled with caution because of lack of supportive data.

Improving Prescribing Practices at Hospital Discharge With Pharmacist-Led Antimicrobial Stewardship at Transitions of Care

Background: Antimicrobial stewardship (AMS) is recommended in hospital, postacute, and outpatient settings. Transitions of care (TOC) are important in each of these settings; however, AMS efforts during TOC have been limited. Beginning in October 2018, we sequentially implemented a pharmacist-led multidisciplinary review of oral antimicrobial therapy prescribed at hospital discharge from general and specialty medicine wards across a health system. Pharmacists facilitated data input of discharge prescriptions following early identification and collaborative discussion of patients to be discharged on oral antimicrobials The purpose of this study was to evaluate the impact of AMS during TOC. Methods: This project was an IRB-approved stepped-wedge, quasi-experimental study in a 5-hospital health system that included hospitalized adults with skin, urinary, intra-abdominal, and respiratory tract infections who had been discharged from general and specialty wards with oral antimicrobials. Patients with complicated infections, neutropenia, or who were transferred from an outside hospital were excluded. The primary end point was optimization of antimicrobial therapy at time of hospital discharge, defined by correct selection, dose, and duration according to institutional guidance. Outcomes were compared before and after the intervention. Results: In total, 800 patients were included: 400 in the preintervention period and 400 in the postintervention period. Among this cohort, 252 (63%) received the intervention by a pharmacist per protocol during TOC. Patients had similar comorbid conditions before and after the intervention. Preintervention patients were more likely to be discharged from community hospitals. Before the intervention, 36% of discharge regimens were considered optimized, compared to 81.5% after the intervention (P &lt; .001); this difference was largely driven by a reduction in patients receiving a duration of therapy beyond the clinical indication (44.5 vs 10%; P &lt; .001). We observed similar clinical resolution, 30-day readmission, and adverse drug events (ADEs) between the pre- and postintervention periods. Postdischarge antimicrobial duration of therapy was reduced from 4 days (range, 3–5) to 3 days (range, 2–4) (P &lt; .001) Severe ADEs occurred more frequently in the preintervention group (9 vs 3.3%; P = .001), which was driven by isolation of multidrug-resistant pathogens (7 vs 2.5%; P = .003) and Clostridioides difficile (1.8 vs 0.5%; P = .094). Patients who received optimal therapy at discharge were less likely to develop an ADE (aOR, 0.530; 95% CI, 0.363–0.773). Conclusions: Implementation of an AMS TOC protocol reduced antimicrobial days, optimized therapy selection, and reduced duration. This intervention was associated with improved safety without compromise of clinical effectiveness. To increase patient safety, AMS programs should target antimicrobial optimization during TOC.Funding: This work was completed under CDC contract number 200-2018-02928.Disclosures: None

Antibiotic Use at the End-of-Life in Patients with Advanced Dementia: A Systematic Literature Review

Background: Improving the use of antibiotics across the care continuum will be necessary as we strive to protect our patients from antimicrobial resistance. One potential target for antimicrobial stewardship is during end-of-life care of patients with advanced dementia. We aimed to perform a systematic literature review measuring the burden of antibiotic use during end-of-life care in patients with dementia. Methods: We searched PubMed, CINAHL, and Embase through July 2019 for studies with the following inclusion criteria in the initial analysis: (1) end-of-life patients (ie, dementia, cancer, organ failure, frailty or multi-morbidity); (2) antibiotic use in the end-of-life care; with the final analysis restricted to (3) patients with advanced dementia. Only randomized controlled trials (RCTs) and cohort studies were included. Results: Of the 93 full-text articles, 17 studies (18.3%) met the selection criteria for further analysis. Most of the included studies were retrospective (n = 8) or prospective (n = 8) cohort studies. These studies in combination included 2,501 patients with advanced dementia. Also, 5 studies (698 patients, [27.9%]) were restricted to patients with Alzheimer’s disease. In 5 studies in which data were available, fewer than one-quarter of patients (19.9%, 498) with advanced dementia were referred to palliative care. In 12 studies &gt;50% of patients received antibiotics during the end-of-life period. Also, 15 studies did not report the duration of antimicrobial therapy. Only 2 studies reported the antimicrobial consumption in days of therapy per 1,000 resident days. Only 6 studies studied whether the use of antibiotics was associated with beneficial outcomes (survival or comfort), and none of them evaluated potential adverse effects associated with antibiotic use. Conclusions: There are significant gaps in the literature surrounding antimicrobial use at the end of life in patients with advanced dementia. Future studies are needed to evaluate the benefits and harms of using antibiotics for patients during end-of-life care in this patient population.Acknowledgement. We thank Jennifer Deberg from Hardin Library for the Health Sciences, University of Iowa Libraries on the search methods.Disclosures: NoneFunding: None

Specific and non-specific prevention of nosocomial infections in ICU of Burn Centre and their place in multimodal control system

The aim of the study is to evaluate the effectiveness of a number of technologies for controlling purulent-septic infections in a multi-modal system for the prevention of ICP in the ICU of a burn center. Materials and methods . Research on the basis of the ICU of burn center of City Clinical Hospital No. 40 (Yekaterinburg, Russia). To evaluate the effectiveness of the Pseudovac vaccine, a single-center, pilot, prospective, randomized, and parallel study was performed. The observation group consisted of 48 patients, of which 24 patients were included in the experimental group, and 24 – in the control group. The effectiveness was evaluated based on the frequency of hospital infections and colonization caused by P. aeruginosa. We also evaluated the characteristics of antimicrobial therapy with an assessment of the duration of antimicrobial therapy, the number of days free from antibiotic therapy, and the consumption of antibiotics. In order to evaluate the effectiveness of using detergents with probiotic effect and aerosol high-dispersion aerosol of the air-cleaning agent, the number of positive seeding of microorganisms, including pathogens with altered biochemical characteristics before and after treatment of air and hospital environment objects was analyzed. The McNemar test was used to compare relative indicators that characterize related populations. Results and discussions . In the group of unvaccinated patients, there were more hospital infections (83.0 %) than in the experimental group (70.8 %), p = 0.4936. Patients in the control group were infected and colonized with P. aeruginosa strains – 62.5 %, while in the experimental group there were 37.5 %; p = 0.1489. The need to prescribe antibiotics in the groups occurred with approximately the same frequency and was 75.0 and 79.2 % respectively; p = 1.0000. The need for prescribing anti-sinus medications was lower in the experimental group (20.8 %) compared to the control group (41.7 %); p = 0.2129. The consumption of drugs aimed at treating Pseudomonas infection in the experimental group was significantly lower and amounted to 103 compared to 190 NDDD per 1,000 bed days in the control group; p < 0.001. After aerosolization, the number of positive findings on ICU environmental objects decreased by more than two times; p < 0.001. The percentage of microorganisms with altered biochemical characteristics on the significant objects of the Department before treatment was 11.8 % (4), after treatment such microorganisms were not sown. After general cleaning with the use of cleaning probiotics, the share of positive findings in flushes from the Department’s external environment decreased by three times, or from 27 (45.8 %) to 11 (17.2 %), p < 0.001; and the share of microorganisms with altered biochemical characteristics almost four times, or from 9 (15.3 %) to 1 (1.6 %), p = 0.275. Conclusions . 1. In the system of epidemiological control of ICP in the ICU, indoor air aerosolization and cleaning of the hospital environment with the use of probiotics showed high efficiency in reducing the microbial load in the Department. 2. The Pseudovac vaccine did not significantly affect the prevalence of hospital infections in the experimental group. Most notable was a decrease in the consumption of antibacterial drugs and reduce the intake of antibiotics with antidiagonal activity in the vaccinated patients.

The optimal duration of antimicrobial therapy for lower respiratory tract infection in patients with neuromuscular disorders based on a clone library analysis of the bacterial 16S rRNA gene sequence

ObjectivesThe aim of this study is to determine the optimal duration of antimicrobial therapy for lower respiratory tract infection (LRTI) in neuromuscular disorder (NMD) patients. MethodsThis prospective study included 13 episodes from 9 NMD patients hospitalized for bacterial LRTI. Sputum samples were collected from these patients during the three consecutive days after their admission. Bacterial cell counts and the proportion of the most predominant bacterium identified by a clone library analysis of the bacterial 16S rRNA gene sequence in the samples obtained before antimicrobial therapy were serially investigated. ResultsAll episodes were initially treated with ampicillin/sulbactam. In 12 episodes with a therapeutic effect, the bacterial cell counts in the samples obtained on the third day of therapy were significantly lower than those before therapy (P = 0.0013). In most of these episodes, the most predominant bacterium in the sample obtained before therapy was undetectable by the third day of therapy. In the one patient without a therapeutic effect, neither the bacterial cell counts nor the proportion of the most predominant bacterium in the sample obtained before therapy decrease after therapy. ConclusionShort-term antimicrobial therapy is sufficiently effective for LRTI in NMD patients if the initial therapy is effective.

Bacterial pneumonia coinfection and antimicrobial therapy duration in SARS-CoV-2 (COVID-19) infection.

BackgroundBacterial respiratory coinfection in the setting of SARS-CoV-2 infection remains poorly described. A description of coinfection and antimicrobial usage is needed to guide ongoing antimicrobial stewardship.ObjectivesTo assess the rate of empirical antimicrobial treatment in COVID-19 cases, assess the rate and methods of microbiological sampling, assess the rate of bacterial respiratory coinfections and evaluate the factors associated with antimicrobial therapy in this cohort.MethodsInpatients with positive SARS-CoV-2 PCR were recruited. Antibiotic prescription, choice and duration were recorded. Taking of microbiological samples (sputum culture, blood culture, urinary antigens) and culture positivity rate was also recorded. Linear regression was performed to determine factors associated with prolonged antimicrobial administration.ResultsA total of 117 patients were recruited; 84 (72%) were prescribed antimicrobial therapy for lower respiratory tract infections. Respiratory pathogens were identified in seven (6%) patients. The median duration of antimicrobial therapy was 7 days. C-reactive protein level, oxygen requirement and positive cultures were associated with prolonged duration of therapy. ConclusionsThe rate of bacterial coinfection in SARS-CoV-2 is low. Despite this, prolonged courses of antimicrobial therapy were prescribed in our cohort. We recommend active antimicrobial stewardship in COVID-19 cases to ensure appropriate antimicrobial prescribing.

Infective Endocarditis Guidelines: The Challenges of Adherence-A Survey of Infectious Diseases Clinicians.

BackgroundGuidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown.MethodsAn electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America’s Emerging Infections Network.ResultsFive hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The duration of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double β-lactam therapy was “usually” or “almost always” employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians.ConclusionsThe finding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double β-lactam regimens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed.

Responsible antimicrobial use in critically ill adult horses

SummaryDue to increasing antimicrobial resistance, pressure on veterinarians is mounting to adhere to responsible use of antimicrobial drugs. Antimicrobials are frequently included in the treatment of systemically ill horses due to the strong likelihood of an infection and the innate difficulties in differentiating systemic inflammation secondary to noninfectious from infectious causes. In light of increasing antimicrobial drug resistance and the potential negative impact of antimicrobials on equine patients, every attempt should be made to identify noninfectious disease, choose first‐line antimicrobials and discontinue treatment as soon as possible. In most cases, a short duration of antimicrobial therapy ranging from a single dose (e.g. preoperatively) to 24–72 h might be sufficient with long‐term treatment being rarely required. This article aims to provide practical guidelines for antimicrobial drug usage in critically ill adult horses by describing ancillary diagnostic aids that can help establishing whether or not an infection is present, discussing commonly encountered pathogens and their typical antimicrobial drug sensitivity patterns, and providing some guidance how to safely shorten the duration of antimicrobial therapy.

A quick stone component analysis matters in postoperative fever: a propensity score matching study of 1493 retrograde intrarenal surgery.

To evaluate the role of stone components in postoperative fever following RIRS, and to investigate the role of quick stone component analysis during RIRS procedure. 1493 patients with RIRS were retrospectively reviewed. Propensity score matching (PSM) analysis was performed as infection stones (IS) vs. calcium-containing stones (CS) and IS vs. other compositions (OS). Independent risk factors of postoperative fever were identified by logistic analysis and nomogram was constructed. A total of 73 patients suffered postoperative fever (4.9%), 8 patients with sepsis (0.5%), 4 patients with septic shock (0.3%). In IS vs. CS, the incidence of positive urine test (28.4% vs. 14.7%, p = 0.001), residual stone (48.2% vs. 37.6%, p = 0.04), and postoperative fever (9.1% vs. 2.0%, p = 0.004) was significantly higher in IS. In IS vs. OS, IS had a higher incidence of positive urine test (30.9% vs. 9.3%, p < 0.001) and residual stone (47.4% vs. 18.6%, p < 0.001), while there was no significant difference in postoperative fever (10.3% vs. 4.1%, p = 0.17). Multivariate regression analysis revealed that gender (OR 1.82, CI 1.09-3.07, p < 0.001), stone components (OR 0.6, CI 0.37-0.97, p = 0.038), urine test (OR 3.72, CI 2.23-6.20, p < 0.001), and neutrophil ratio > 75% (OR 5.17, CI 3.03-9.16, p < 0.001) were independent risk factors for postoperative fever. A nomogram with moderate discriminative ability (c-index: 0.813) was constructed to predict postoperative fever. Infection stones were closely associated with postoperative fever following RIRS, as well as female gender, preoperative positive urine test, and postoperative neutrophil ratio > 75%. A quick stone component analysis would help in prevention of infectious complications. Early and longer duration of antimicrobial therapy was recommended for patients with infection stones.