Use Of Broad-spectrum Antimicrobials Research Articles

Septic shock due to Candida famata (Debaryomyces hansenii) candidemia in an ICU immunocompetent trauma-patient

Sepsis related to Candida famata (C. famata) fungemia is extremely rare in immunocompetent patients. Moreover, septic shock has not been reported due to this yeast.A previously healthy young multi-trauma male, presented septic shock from C. famata, after he had been admitted in the Intensive Care Unit (ICU) due to haemorrhagic shock. Risk factors for candidemia in ICU patients are the presence of a central venous catheter (CVC), Total Parenteral Nutrition (TPN), use of broad-spectrum antimicrobials, immunosuppression and the length of ICU stay. The presence of CVCs, prior use of antibiotics, prolonged hospitalization, disruption of skin flora and immunocompromised states have been identified as predisposing risk factors for C. famata fungemia. It is worth noting that the present case concerns a non-immunocompromised patient, but long ICU stay and brain injury may indicate a state of immunoparalysis.Identification of the yeast was performed by partial amplification and sequencing of the 26S ribosomal DNA gene [hypervariable region D1/D2; partial sequencing of the act1 gene confirmed the identity of the strain as Debaryomyces hansenii (GenBank submission ID: 1688297)]The patient quickly recovered from sepsis after initiation of amphotericin B and was discharged on the 60th day.

Principles of antimicrobial therapy in urosepsis - an approach from the perspective of the infectious diseases physician

Background: This topic is aimed to review the treatment approach in adult patients diagnosed with urosespsis, in order to decrease mortality and to maximize the outcome of the antibiotic stewardship efforts. Methods: We present an approach of antibiotic therapy in urosepsis from an infectious diseases physician perspective, based on the recently published data integrating the epidemiology of the urinary tract infections in a multidisciplinary hospital from Romania. Results: The principles of therapy in urosepsis should have five goals, but not limited to rapid diagnosis, specific intensive care unit treatment, obtaining urine and blood cultures, anti-infective treatment and identifying and correction of underlying risk factors. Due to the higher prognostic value, the antimicrobial therapy in urosepsis should consist in “two steps” regimen: initial antimicrobial therapy, based on “empirical” approach for the first 48 - 72 hours and directed or “definitive” antimicrobial therapy adapted to the susceptibility profile of the isolated pathogens, the penetration into the urinary tract and the patient clinical response. Clinicians should be aware of the different antibiotic susceptibility profile of the bacteria from the hospital compared to the community. Thus, the initial choice of antimicrobial agents depends on several criteria like the severity of illness and the risk factors for multidrug resistant pathogens: the immune status of the patient (age, debilitating chronic illnesses, immunosuppressive treatment or uncontrolled malignancies), broad-spectrum antimicrobial use and health care environment exposures in the previous 3 to 6 months, susceptibility of prior urinary isolates, and local community resistance prevalence of bacteria. Conclusions: Our important messages highlighted the need of a holistic approach of urosepsis, in a multidisciplinary team, with integration of risk factors for AMR, focusing on the first phase of antibiotic treatment as the main driven of the survival rate.

Regional Variation of Antimicrobial Use in Japan from 2013-2016, as Estimated by the Sales Data.

The National Action Plan on Antimicrobial Resistance in Japan aims to achieve a 50% reduction in the use of broad-spectrum oral antimicrobials (cephalosporins, macrolides, and quinolones) from 2013 to 2020. Based on the national sales data for antimicrobials, we estimated the regional antimicrobial use (AMU) from 2013-2016 and evaluated the differences in the use of broad-spectrum oral antimicrobials among three regions in which differences had been identified previously. The AMU was standardized based on the defined daily dose (DDD) and described as the DDDs/1,000 inhabitants/day (DID). Annual combined total oral and parenteral AMU during 2013-2016 was 14.9, 14.5, 14.7, and 14.6 DID, respectively. The change in mean ± standard deviation in the total AMU at the prefectural level was - 0.2 ± 0.8 DID. Among the 47 prefectures, decreasing trends were observed in 34, while in the remaining 13 prefectures increasing trends were recorded. In 2016, no significant differences in the mean usage of oral cephalosporins among the three regions were observed. The mean usage of oral macrolides in the eastern (4.1 DID) was significantly lower than that in the central region (4.7 DID) (p = 0.009) and the western (4.8 DID) (p = 0.002). The mean usage of oral quinolones in the western (3.2 DID) was significantly higher than that in the eastern (2.3 DID) (p ＜ 0.001) and central (2.7 DID) (p = 0.001) regions. To determine appropriate targets for the implementation of antimicrobial stewardship for reducting the use of broad-spectrum oral antimicrobials, further studies are required to identify the reasons underlying these differences.

Direct Detection of Pathogens in Bloodstream During Sepsis: Are We There Yet?

Advances in medicine have improved our understanding of sepsis, but it remains a major cause of morbidity and mortality. The detection of pathogens that cause sepsis remains a challenge for clinical microbiology laboratories. Routine blood cultures are time-consuming and are negative in a large proportion of cases, leading to excessive use of broad-spectrum antimicrobials. Molecular testing direct from patient blood without the need for incubation has the potential to fill the gaps in our diagnostic armament and complement blood cultures to provide results in a timely manner. Currently available platforms show promise but have yet to definitively address gaps in sensitivity and specificity. Significant strides have been made in the detection of pathogens directly from blood. A number of hurdles, however, remain before this technology can be adapted for routine use.

1785. Regional Variation of Antimicrobial Use in Japan From 2013 to 2016

BackgroundSince antimicrobial resistance (AMR) is a global threat, judicious antimicrobial usage is required. Compared with European countries, antimicrobial use (AMU) is relatively low in Japan; however, the use of oral broad-spectrum antimicrobials is relatively high. Although the Japanese national action plan on AMR targets a 50% reduction in use of these oral broad-spectrum antimicrobials by 2020 from the level in 2013, regional variation in AMU in Japan is not well known.MethodsNational antimicrobial sales data from 2013 to 2016 was obtained from IQVIA Japan (Tokyo, Japan), which captures 99% of total sales in Japan. Antimicrobials were classified by the World Health Organization (WHO) defined Anatomical Therapeutic Chemicals (ATC) classification. WHO measures the number of antimicrobial use by Defined Daily Dose per 1,000 inhabitant-days (DID). From 2013 to 2016, the difference in DID amongst each prefecture was analyzed, and comparison amongst the three major regions of East, Central, and West Japan was performed using Mann–Whitney U test.ResultsFrom 2013 to 2016, the median (max, min) AMU (DID) change was −0.4 (2.8, −1.6). During the study period, 34 prefectures showed increasing trends and 13 prefectures showed decreasing trends. Median (max, min) AMU (DID) for total antimicrobials, oral cephalosporins, macrolides, and quinolones in 2016 was 14.4 (18.7, 11.2), 3.5 (6.9, 2.5), 4.5 (6.3, 3.2), and 2.8 (3.7, 1.9), respectively. The median total AMU (DID) in East, Central, and West Japan in 2016 was 13.2, 14.4, and 15.8, respectively. Median oral cephalosporins AMU (DID) in Central Japan (3.69) was significantly higher than that in East Japan (3.33) (P = 0.025). Median oral macrolides AMU (DID) in East Japan (4.11) was significantly smaller than that in Central (4.61) and West Japan (4.70) (P < 0.01). Median oral quinolones AMU (DID) in West Japan (3.28) was significantly higher than that in East (2.29) and Central Japan (2.73) (P < 0.01) (figure).ConclusionFrom 2013 to 2016, significant regional variations of oral AMU were observed in Japan. Further studies are needed to specify the appropriate targets of antimicrobial stewardship intervention to reduce oral broad-spectrum AMU in Japan. Disclosures All authors: No reported disclosures.

1855. Antimicrobial Stewardship (AMS) and the Outpatient Parenteral Antimicrobial Therapy (OPAT) Setting

BackgroundAntimicrobial resistance is a major threat to human health. In the OPAT setting broad-spectrum once daily antimicrobials may be chosen in preference to other agents requiring multiple daily doses for reasons of convenience. The role and effectiveness of antimicrobial stewardship (AMS) in the Australian hospital-in-the-home (OPAT) setting have not previously been studied.MethodsThe National Antimicrobial Prescribing Survey (NAPS) was developed in 2011 to provide an audit of antimicrobial prescribing in Australian hospitals and is conducted by The Australian National Centre for Antimicrobial Stewardship (NCAS). The Hospital NAPS was modified for the OPAT setting, trialed in 2016 in five health services and rolled out to all Australian OPAT services as a pilot in 2017.ResultsTwenty-three OPAT services throughout Australia participated in the OPAT NAPS pilot. In total, 1,154 prescriptions for 722 patients (63% male) were included. Patients ranged in age from 1 month to 101 years; median age was 58 years.The most common indications for parenteral antimicrobials were; cellulitis (30%), osteomyelitis (8%), pneumonia (7%), abscess (6%), Cystic Fibrosis exacerbation (5%), endocarditis (4%), septic arthritis (4%), prosthetic joint infection (4%), and exacerbation of bronchiectasis (2%). Piperacillin–tazobactam or ceftriaxone were prescribed in 20% of cases. The majority of prescriptions for antimicrobials to treat community-acquired pneumonia and exacerbations of chronic obstructive airways disease were not compliant with guidelines.The median duration of parenteral therapy for cellulitis was 4 days; however, duration ranged overall from 1 to 44 days for this indication. Prescriptions were compliant with guidelines in 43% of cases, and appropriateness of antimicrobial prescribing was assessed as optimal in 74%, adequate in 13%, suboptimal in 8.5% and inadequate in 3%. Antimicrobial therapy duration was incorrect in 9% of cases.ConclusionOpportunities exist for improving AMS interventions in the OPAT setting, specifically in regards to the use of broad-spectrum antimicrobials and in the treatment of respiratory tract infection. Importantly, not all OPAT services have the same access to AMS.Disclosures All authors: No reported disclosures.

268. Cardiothoracic Surgery Antimicrobial Prophylaxis in Pediatric Patients: Reducing Antimicrobial Exposure

BackgroundPediatric cardiothoracic (CT) surgery poses significant infectious risks, mitigated by antimicrobial prophylaxis and standardized infection control practices. Little is known about the most appropriate postoperative antimicrobial regimen and duration of therapy. In efforts to decrease exposure to broad-spectrum (BS) antimicrobial prophylaxis while preventing postoperative infection, we implemented a risk-stratified algorithm CT surgery prophylaxis algorithm (Figure 1) at our institution.MethodsThis quasi-experimental study included pediatric CT surgery patients at an urban academic medical center. Algorithm implementation in conjunction with daily prospective audit-with-feedback started simultaneously in September 2017, with retrospective review of pre- and postintervention groups. Data related to length of hospital admission, narrow and BS antimicrobial days and appropriateness, infectious complications, and drug toxicity were collected. The preliminary preintervention arm was compared with the postintervention arm using descriptive statistics via SPSS.ResultsPreliminary data suggest a trend toward decreased BS antimicrobial use in the postintervention group by 27%, with a significant decrease in the rate of inappropriate use during the postintervention period. There were no episodes of drug-related nephrotoxicity. ConclusionContinued review is ongoing; however, risk-based limited-spectrum antimicrobial therapy for pediatric CT surgery patients appears efficacious and safe while limiting antimicrobial exposure. Figure 1: Process map for pediatric cardiothoracic surgery algorithmDisclosures All authors: No reported disclosures.

Novel diagnostics of respiratory infection in the intensive care unit

Pneumonia is one the leading causes of a critical care admission and is associated with substantial mortality and morbidity. Despite this, the diagnosis of pneumonia and identifying the causative pathogen is not always straight forward, particularly in the immunocompromised or those already receiving antibiotics. Medical belief today encourages the use of broad spectrum antimicrobials in all patients that may have pneumonia. This approach invariably leads to overtreatment of many patients, with consequent side effects. These side effects may lead to an insidious impact on organ function or overgrowth of harmful organisms (e.g., Clostridium difficile ) which in turn can adversely affect outcome, reduce institutional efficiency and increase healthcare costs. At a society level, it is this over-use of broad spectrum antimicrobials that is helping drive the spread of anti-microbial resistance. Clinicians, urgently need reliable diagnostic aids to inform them that their patient does or does not have an infection and to reliably and rapidly identify the pathogen with any associated resistance genes. Only then can we confidently withhold or prescribe the appropriate antimicrobial.

Inhibition of Streptococcus mutans Biofilms by the Natural Stilbene Piceatannol Through the Inhibition of Glucosyltransferases.

Removal of oral biofilms involves the use of broad-spectrum antimicrobials, which eradicate both pathogenic and protective oral commensal species. Ideal therapeutics for dental caries should be able to selectively inhibit pathogenic biofilms caused by Streptococcus mutans. S. mutans extracellular glucosyltransferases (Gtfs), particularly GtfB and GtfC, synthesize predominantly water-insoluble glucans, which contribute to the structural scaffold of biofilms. The lead stilbene identified through our docking study against the catalytic domain of GtfC is a natural product known as piceatannol, which inhibited S. mutans biofilm formation in a dose-dependent manner, with considerable selectivity over growth inhibition of S. mutans and commensal streptococci. Binding kinetic analysis of piceatannol was performed using Octet RED against both GtfB and GtfC, which produced low micromolar KD values. Piceatannol inhibited S. mutans colonization in an in vivo drosophila model and a rat model of dental caries.

Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit.

BackgroundThe potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU).MethodsAmong all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission.ResultsAmong the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile. The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes.ConclusionsThe prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.

Identifying priorities to improve paediatric in-hospital antimicrobial use by cross-sectional evaluation of prevalence and appropriateness of prescription

IntroductionInformation about paediatric in-hospital antimicrobial usage and prescribing patterns to guide improvement strategies is scant. We aim to use an evaluation of the prevalence and appropriateness of antimicrobial prescription to identify antimicrobial stewardship priorities in children. MethodsA cross-sectional point study was performed on hospitalised paediatric patients in a Spanish tertiary hospital, assessing the prevalence of antimicrobial prescription (PAP) and appropriateness of antimicrobial prescription (AAP). AAP was defined as a correct indication plus an appropriate prescribing pattern (dose, spectrum and interval). Evaluation was performed using established antimicrobial guidelines. Other factors that may have a bearing on antimicrobial prescription were also analysed. ResultsA total of 171 patients were included. PAP was 49.7% (85/171) and AAP was 60.9% (91/161). The most common indications for antimicrobial use were antimicrobial prophylaxis (28.3%, 32/113) and pneumonia (8.2%, 8/113). Overall, 161 antimicrobials were prescribed (1.9 antimicrobials per patient): 55.3% (89/161) were empiric, 16.1% (26/161) were targeted and 28.6% (46/161) were prophylactic. Amoxicillin/clavulanate (8.2%, 14/171) and sulfamethoxazole/trimethoprim (8.2%, 14/171) were the most prescribed antimicrobials. The prescription of antifungals (11.7%, 20/171) and antivirals (1.8%, 3/171) was analysed. Major causes of inappropriate antibiotic use were prolonged prescriptions (21.7%, 35/161) and use of agents with an excessively broad coverage spectrum (21.1%, 34/161). PAP and AAP varied between wards and antimicrobials. ConclusionsMeasurement of PAP and AAP offers valuable information for detecting priorities in hospital settings and monitoring antimicrobial usage prior to the development of antimicrobial stewardship programmes. In our setting, the main areas for improvement are duration of therapy and proper use of broad-spectrum antimicrobials.

Can Consideration of the Microbiome Improve Antimicrobial Utilization and Treatment Outcomes in the Oncology Patient?

The need to provide effective and timely antimicrobial treatment to cancer patients with infections is well recognized but tempered by preliminary, but accumulating, evidence that antibiotic-induced microbiome dysbiosis affects cancer therapy response, noninfectious toxicities, and infectious complications. Given only a minority of empirically treated cancer patients are proven to have a true bacterial infection, it is important to consider the potential negative consequences of extensive broad-spectrum antimicrobial use on the commensal microbiota. Herein, we review the literature substantiating the dilemma oncologists face when treating suspected or documented infections with respect to the interaction between the host microbiome, antibiotics, and cancer-related clinical outcomes. We propose microbiome-based explorations that could assist oncologists in optimizing treatment strategies for cancer-related infections as well as the cancer itself. In addition, we discuss knowledge gaps and challenges in this nascent field that must be addressed to deliver medically relevant, translational applications. We anticipate that the emerging knowledge regarding the role of the microbiota in the health of cancer patients may cause a reappraisal of the manner in which antibiotics are used in the oncologic setting and how microorganisms are viewed by oncologists. Clin Cancer Res; 23(13); 3263-8. ©2017 AACRSee related commentary by Fessler and Gajewski, p. 3229.

Antimicrobial consumption, costs and resistance patterns: a two year prospective study in a Romanian intensive care unit

BackgroundDue to the vulnerable nature of its patients, the wide use of invasive devices and broad-spectrum antimicrobials used, the intensive care unit (ICU) is often called the epicentre of infections. In the present study, we quantified the burden of hospital acquired pathology in a Romanian university hospital ICU, represented by antimicrobial agents consumption, costs and local resistance patterns, in order to identify multimodal interventional strategies.MethodsBetween 1st January 2012 and 31st December 2013, a prospective study was conducted in the largest ICU of Western Romania. The study group was divided into four sub-samples: patients who only received prophylactic antibiotherapy, those with community-acquired infections, patients who developed hospital acquired infections and patients with community acquired infections complicated by hospital-acquired infections. The statistical analysis was performed using the EpiInfo version 3.5.4 and SPSS version 20.ResultsA total of 1596 subjects were enrolled in the study and the recorded consumption of antimicrobial agents was 1172.40 DDD/ 1000 patient-days.The presence of hospital acquired infections doubled the length of stay (6.70 days for patients with community-acquired infections versus 16.06/14.08 days for those with hospital-acquired infections), the number of antimicrobial treatment days (5.47 in sub-sample II versus 11.18/12.13 in sub-samples III/IV) and they increased by 4 times compared to uninfected patients. The perioperative prophylactic antibiotic treatment had an average length duration of 2.78 while the empirical antimicrobial therapy was 3.96 days in sample II and 4.75/4.85 days for the patients with hospital-acquired infections. The incidence density of resistant strains was 8.27/1000 patient-days for methicilin resistant Staphylococcus aureus, 7.88 for extended spectrum β-lactamase producing Klebsiella pneumoniae and 4.68/1000 patient-days for multidrug resistant Acinetobacter baumannii.ConclusionsSome of the most important circumstances collectively contributing to increasing the consumption of antimicrobials and high incidence densities of multidrug-resistant bacteria in the studied ICU, are represented by prolonged chemoprophylaxis and empirical treatment and also by not applying the definitive antimicrobial therapy, especially in patients with favourable evolution under empirical antibiotic treatment. The present data should represent convincing evidence for policy changes in the antibiotic therapy.

Microbiological Etiology and Treatment of Complicated Skin and Skin Structure Infections in Diabetic and Nondiabetic Patients in a Population-Based Study.

BackgroundDiabetes is a major risk factor for skin and skin structure infection (SSSI), and the global burden of diabetics with SSSI is enormous. The more complex microbiology of diabetic foot infection (DFI) is well established, but it is not known whether microbiological etiology differs between diabetics and nondiabetics in other disease entities under the umbrella of complicated SSSI (cSSSI).MethodsThis retrospective, population-based study included patients with cSSSI, and it was conducted in 2 Nordic cities with a low prevalence of antimicrobial resistance. In analyses, patients (N = 460) were separated into 3 groups: diabetics (n = 119), nondiabetics (n = 271), and patients with DFI (n = 70).ResultsAfter exclusion of patients with DFI, there was no difference in the microbiological etiology or initial antimicrobial treatment of cSSSI between diabetics and nondiabetics. Gram-positive bacteria encountered 70% of isolations in diabetics and 69% in nondiabetics, and the empirical treatment covered initial pathogens in 81% and 86% of patients, respectively. However, diabetes was the only background characteristic in the propensity score-adjusted analysis associated with broad-spectrum antimicrobial use and longer antibiotic treatment duration. Patients with DFI had Gram-negative and polymicrobial infection more often than nondiabetics.ConclusionsThese observations suggest that diabetics without DFI are not different in the causative agents of cSSSI, although they are more exposed to antimicrobial therapy of inappropriate extended spectrum and long duration. Broad-spectrum coverage was clearly needed only in DFI. A clear opportunity for antimicrobial stewardship was detected in the rapidly growing population of diabetic patients with cSSSI.

Identifying priorities to improve paediatric in-hospital antimicrobial use by cross-sectional evaluation of prevalence and appropriateness of prescription

IntroductionInformation about paediatric in-hospital antimicrobial usage and prescribing patterns to guide improvement strategies is scant. We aim to use an evaluation of the prevalence and appropriateness of antimicrobial prescription to identify antimicrobial stewardship priorities in children. MethodsA cross-sectional point study was performed on hospitalised paediatric patients in a Spanish tertiary hospital, assessing the prevalence of antimicrobial prescription (PAP) and appropriateness of antimicrobial prescription (AAP). AAP was defined as a correct indication plus an appropriate prescribing pattern (dose, spectrum and interval). Evaluation was performed using established antimicrobial guidelines. Other factors that may have a bearing on antimicrobial prescription were also analysed. ResultsA total of 171 patients were included. PAP was 49.7% (85/171) and AAP was 60.9% (91/161). The most common indications for antimicrobial use were antimicrobial prophylaxis (28.3%, 32/113) and pneumonia (8.2%, 8/113). Overall, 161 antimicrobials were prescribed (1.9 antimicrobials per patient): 55.3% (89/161) were empiric, 16.1% (26/161) were targeted and 28.6% (46/161) were prophylactic. Amoxicillin/clavulanate (8.2%, 14/171) and sulfamethoxazole/trimethoprim (8.2%, 14/171) were the most prescribed antimicrobials. The prescription of antifungals (11.7%, 20/171) and antivirals (1.8%, 3/171) was analysed. Major causes of inappropriate antibiotic use were prolonged prescriptions (21.7%, 35/161) and use of agents with an excessively broad coverage spectrum (21.1%, 34/161). PAP and AAP varied between wards and antimicrobials. ConclusionsMeasurement of PAP and AAP offers valuable information for detecting priorities in hospital settings and monitoring antimicrobial usage prior to the development of antimicrobial stewardship programmes. In our setting, the main areas for improvement are duration of therapy and proper use of broad-spectrum antimicrobials.

Necessity of carbapenem use when prescribed per infectious diseases specialists

Preauthorization strategies, including restricting broad-spectrum antimicrobials such as carbapenems to infectious diseases physicians (ID) are commonly employed by stewardship programs. The appropriateness, or “necessity” of empiric carbapenem therapy by ID, defined as an isolated organism sensitive to the carbapenem and resistant to cefepime, was evaluated over a 6month span and included 84 patients. Additionally, 30 patients followed by ID who were not prescribed a carbapenem until final susceptibilities were included as a definitive therapy group. Differences in multi-drug resistant organism (MDRO) risk factors between groups were non-significant. Carbapenem therapy was necessary for only 6 (7%) empiric therapy patients, while four times as many definitive group patients required a carbapenem but did not receive one empirically. Overall, ID's ability to accurately gauge which patients required carbapenems appeared poor in this study. Alternative risk stratification strategies may better guide broad-spectrum antimicrobial use than ID judgment alone.

Risk factors for excessively prolonged meropenem use in the intensive care setting: a case-control study

BackgroundInappropriate use of broad-spectrum antimicrobials affects adversely both the individual patient and the general public. The aim of the study was to identify patients at risk for excessively prolonged carbapenem treatment in the ICU as a target for antimicrobial stewardship interventions.MethodsCase–control study in a network of 11 ICUs of a university hospital. Patients with uninterrupted meropenem therapy (MT) > 4 weeks were compared to controls. Controls were defined as patients who stayed on the ICU > 4 weeks and received meropenem for ≤ 2 weeks. Associations between case–control status and potential risk factors were determined in a multivariate logistic regression model.ResultsBetween 1st of January 2013 and 31st of December 2015, we identified 36 patients with uninterrupted MT > 4 weeks. Patients with prolonged MT were more likely to be surgical patients (72.2% of cases vs. 31.5% of controls; p ≤ 0.001) with peritonitis being the most common infection (n = 16, 44.4%). In the multivariate logistic regression model colonization with multidrug-resistant (MDR) Gram-negative bacteria (OR 7.52; 95% CI 1.88–30.14, p = 0.004) and the type of infection (peritonitis vs. pneumonia: OR 16.96, 95% CI 2.95–97.49) were associated with prolonged MT.ConclusionSurgical patients with peritonitis and patients with known colonization with MDR Gram-negative bacteria are at risk for excessively prolonged carbapenem therapy and represent an important target population for antimicrobial stewardship interventions.

Surveillance of antimicrobial use in Dutch long-term care facilities.

: Residents living in a long-term care facility (LTCF) are more susceptible to infections. Treatment with antimicrobials is sometimes necessary; however, antibiotic use is considered one of the most important drivers of the development of antibiotic resistance. Surveillance data on antibiotic use in these LTCFs are necessary to get more insight into these patterns. The objective of this study was to describe antibiotic use in LTCFs in the Netherlands. : One hundred and seventy-seven LTCFs in the Netherlands were contacted and asked to participate in a study concerning antibiotic resistance and antibiotic use. Associated pharmacies were asked to provide data about systemic antibiotic use for each participating LTCF location over 1 year. Results on antibiotic use are reported here. : Antibiotic use data from 96 LTCFs were collected from the pharmacies, and 68 of these LTCFs completed additional questionnaires on general characteristics of their location. Mean total use of systemic antimicrobials was 73 DDDs/1000 residents per day (range 2-197 DDDs/1000 residents per day). Co-amoxiclav (23 DDDs/1000 residents/day, range 0-70) was used the most, followed by nitrofurantoin derivatives (12 DDDs/1000 residents/day, range 0-38) and fluoroquinolones (12 DDDs/1000 residents/day, range 0-52). Statistical analysis revealed no significant correlations between the LTCF characteristics and the level of antibiotic use. There was a high use of broad-spectrum antimicrobials, with a large variation in total antibiotic use between individual locations. Further analysis of more in-depth data and possible influencing factors is needed.

A Hospitalist-Led Initiative to Promote Antibiotic Citizenship on Internal Medicine Teaching Services

BackgroundHospitalists are critical partners in antimicrobial stewardship program (ASP) efforts to improve antimicrobial use, but limited data exists on the effectiveness of ASP-hospitalist collaboration. We performed a hospitalist-led quality improvement project with pharmacy collaboration to improve antimicrobial prescribing practices on general internal medicine teaching services at an urban academic medical center.MethodsWe conducted a 3-arm intervention study on internal medicine teaching services from September-December 2016. Three services received an educational (Ed) intervention consisting of an antibiotic rationale checklist, a templated progress note to promote trainee critical thinking about antibiotic management, and a pocket card with institutional guidelines. In addition, 1 team received twice weekly stewardship rounds with an infectious disease clinical pharmacist (Ed+ID-PharmDx2) while another team received 5x week stewardship rounds with a generalist clinical pharmacist (Ed+PharmDx5). The primary outcome was broad-spectrum antibiotic use calculated as days of therapy (DOT) per 1000 patient days compared with historical data from the corresponding months. Secondary outcomes included duration of inpatient therapy, antibiotic costs, length of stay, 30-day readmission, ICU transfer and in-hospital mortality.ResultsBroad-spectrum antibiotic use significantly decreased by 26% (415 vs. 306 DOT/1000 patient days) and 32% (425 vs. 287 DOT per 1000 patient days) on the Ed and Ed+PharmDx5 teams, respectively (P <0.01). Broad-spectrum use on the ED+ID-PharmDx2 team decreased by 9% but was not statistically significant. There was a significant improvement in median length of stay among patients receiving antibiotics for Ed only (-1.5 days; P < 0.001) and Ed+PharmDx5 (-1 day; P < 0.001) and no significant change in 30 day readmissions, ICU transfer and in-hospital mortality for any team. Direct antibiotic costs were reduced by $80,000 during the study period.ConclusionA hospitalist-led initiative to improve inpatient antimicrobial prescribing led to reductions in broad-spectrum antimicrobial use and reduced length of stay. ASPs should target hospitalists and pharmacists as partners in programmatic efforts to improve inpatient antimicrobial prescribing.Disclosures All authors: No reported disclosures.

The projected effectiveness of Clostridium difficile vaccination as part of an integrated infection control strategy

BackgroundEarly clinical trials of a Clostridium difficile toxoid vaccine show efficacy in preventing C. difficile infection (CDI). The optimal patient group to target for vaccination programmes remains unexplored. This study performed a model-based evaluation of the effectiveness of different CDI vaccination strategies, within the context of existing infection prevention and control strategies such as antimicrobial stewardship. MethodsAn individual-based transmission model of CDI in a high-risk hospital setting was developed. The model incorporated data on patient movements between the hospital, and catchment populations from the community and long-term care facilities (LTCF), using English national and local level data for model-parameterisation. We evaluated vaccination of: (1) discharged patients who had an CDI-occurrence in the ward; (2) LTCF-residents; (3) Planned elective surgical admissions and (4) All three strategies combined. ResultsWithout vaccination, 10.9 [Interquartile range: 10.0–11.8] patients per 1000 ward admissions developed CDI, of which 31% were ward-acquired. Immunising all three patient groups resulted in a 43% [42–44], reduction of ward-onset CDI on average. Among the strategies restricting vaccination to one target group, vaccinating elective surgical patients proved most effective (35% [34–36] reduction), but least efficient, requiring 146 [133–162] courses to prevent one ICU-onset case. Immunising LTCF residents was most efficient, requiring just 13 [11–16] courses to prevent one case, but considering this only comprised a small group of our hospital population, it only reduced ICU-onset CDI by 9% [8–11]. Vaccination proved most efficient when ward-based transmission rates and antimicrobial consumption were high. ConclusionsStrategy success depends on the interaction between hospital and catchment populations, and importantly, consideration of importations of CDI from outside the hospital which we found to substantially impact hospital dynamics. Vaccination may be most desirable in settings or patient groups where levels of broad-spectrum antimicrobial use are high and difficult to reduce.