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Guidelines for treatment of resistant Acinetobacter baumannii (AB) are limited, leaving a knowledge gap in best practices for treatment. This study described treatments and outcomes of extensively-drug resistant (XDR) AB.Retrospective cohort study including patients with XDRAB (non-susceptible to at least 1 agent in all but 2 or fewer classes) and antibiotic treatment between 2012 and 2018 at Veterans Affairs Medical Centers. Descriptive statistics summarized antibiotics; propensity score adjusted regression models were fit to compare outcomes.Two hundred and seventy-six patients with 439 XDRAB cultures and Gram-negative targeted antibiotic treatment were included. One hundred and eighteen (43%) patients received monotherapy while 158 (57%) received combination therapy, most commonly including a carbapenem (n = 106, 67%) and polymyxin (n = 66, 42%). One hundred and eighty-four (67%) patients received inadequate treatment. In adjusted models, combination therapy did not decrease the odds of in-hospital (aOR 1.24, 95%CI 0.60-2.59) or 30-day (aOR 1.43, 95%CI 0.86-2.38) mortality, or median postculture length of stay (aIRR 1.11, 95%CI 0.86-1.43). Likewise, receipt of inadequate treatment was not associated with poorer outcomes.In this national cohort of patients with XDRAB, neither combination therapy nor receipt of adequate treatment improved outcomes. Further research is needed on optimal management of this difficult-to-treat pathogen with few effective antibiotic options.

Background Infectious diseases (ID) consultation improves health outcomes for certain infections but has not been well described for Pseudomonas aeruginosa (PA) bloodstream infection (BSI). Therefore, the goal of this study was to examine ID consultation of inpatients with PA BSI and factors impacting outcomes. Methods This was a retrospective cohort study from January 1, 2012, to December 31, 2018, of adult hospitalized veterans with PA BSI and antibiotic treatment 2 days before through 5 days after the culture date. Multidrug-resistant (MDR) cultures were defined as cultures with resistance to at least 1 agent in ≥3 antimicrobial categories tested. Multivariable logistic regression models were fit to assess the impact of ID consults and adequate treatment on mortality. Results A total of 3256 patients had PA BSI, of whom 367 (11.3%) were multidrug resistant (MDR). Most were male (97.5%), over 65 years old (71.2%), and White (70.9%). Nearly one-fourth (n = 784, 23.3%) died during hospitalization, and 870 (25.8%) died within 30 days of their culture. Adjusted models showed that ID consultation was associated with decreased in-hospital (odds ratio [OR], 0.47; 95% CI, 0.39–0.56) and 30-day mortality (OR, 0.51; 95% CI, 0.42–0.62). Conclusions Consultation with ID physicians improves clinical outcomes such as in-hospital and 30-day mortality for patients with PA BSI. ID consultation provides value and should be considered for patients with PA BSI.

Background Acquisition of pathogens into health care settings from prior room occupants has been documented. Hospital room privacy curtains are at high risk for pathogenic bacterial contamination. Antimicrobial impregnated curtains could be effective in reducing contamination. Methods Rooms within an intensive care unit at The University of Iowa Hospitals and Clinics were randomized to 3 arms. The 2 intervention arms: (1) halamine antimicrobial curtains (BioSmart curtain [BSC]) and (2) halamine antimicrobial curtains sprayed twice weekly with a sodium hypochlorite-based disinfecting spray (BSC-pre and BSC-post) and a third control arm (standard curtain [SC]). Samples were collected twice weekly for 3 weeks to assess pathogenic bacterial contamination. Results The likelihood of remaining uncontaminated was 38% for SC, 37% for BSC, and 60% for the BSC-pre group. Time to event (contamination) analysis found no statistically significant difference between pathogenic contamination between the SC, BSC, and BSC-pre groups (P value = .1921). There was a decrease in average colony count for BSC curtains compared with control, however, this difference was not statistically significant. Hypochlorite spray was found to transiently decontaminate curtains, but effects dissipated after 72 hours. Conclusions BSC did not show a significant reduction in pathogenic contamination compared with control. Antimicrobial curtains could have a role in reducing environmental contamination in the health care setting. Future studies should be done to determine the long-term effects of using antimicrobial curtains in health care.

Background Dogs are the primary reservoir for human visceral leishmaniasis due to Leishmania infantum. Phlebotomine sand flies maintain zoonotic transmission of parasites between dogs and humans. A subset of dogs is infected transplacentally during gestation, but at what stage of the clinical spectrum vertically infected dogs contribute to the infected sand fly pool is unknown. Methodology/Principal findings We examined infectiousness of dogs vertically infected with L. infantum from multiple clinical states to the vector Lutzomyia longipalpis using xenodiagnosis and found that vertically infected dogs were infectious to sand flies at differing rates. Dogs with mild to moderate disease showed significantly higher transmission to the vector than dogs with subclinical or severe disease. We documented a substantial parasite burden in the skin of vertically infected dogs by RT-qPCR, despite these dogs not having received intradermal parasites via sand flies. There was a highly significant correlation between skin parasite burden at the feeding site and sand fly parasite uptake. This suggests dogs with high skin parasite burden contribute the most to the infected sand fly pool. Although skin parasite load and parasitemia correlated with one another, the average parasite number detected in skin was significantly higher compared to blood in matched subjects. Thus, dermal resident parasites were infectious to sand flies from dogs without detectable parasitemia. Conclusions/Significance Together, our data implicate skin parasite burden and earlier clinical status as stronger indicators of outward transmission potential than blood parasite burden. Our studies of a population of dogs without vector transmission highlights the need to consider canine vertical transmission in surveillance and prevention strategies., Author summary Sand flies transmit Leishmania parasites between infected dogs and humans leading to the life-threatening tropical disease Visceral Leishmaniasis (VL). Identifying which dogs transmit parasites well to sand flies is important to curb disease spread. The offspring of both dogs and humans can also be infected vertically while in utero. Despite this, the infectiousness of dogs that receive parasites in utero to sand flies has not been thoroughly investigated. Thus, we allowed sand flies to feed on a group of vertically infected dogs at varying stages of VL disease severity and measured sand fly parasite uptake. We found vertically infected dogs were readily able to transmit parasites to the sand flies. Dogs that were most infectious had mild to moderate clinical disease and relatively high levels of parasite infection in their blood and skin. However, the level of skin infection was significantly higher than that observed in the blood, and the skin parasite load had the strongest correlation with sand fly parasite uptake. This implicates the skin may be an underappreciated driver of canine infectiousness to the sand fly vector. In addition, this work highlights that vertically infected dogs are very important parts of the transmission cycle and must be considered in all public health efforts addressing VL.

Background:Clostridioides difficile infection (CDI) is the most frequently reported hospital-acquired infection in the United States. Bioaerosols generated during toilet flushing are a possible mechanism for the spread of this pathogen in clinical settings.Objective:To measure the bioaerosol concentration from toilets of patients with CDI before and after flushing.Design:In this pilot study, bioaerosols were collected 0.15 m, 0.5 m, and 1.0 m from the rims of the toilets in the bathrooms of hospitalized patients with CDI. Inhibitory, selective media were used to detect C. difficile and other facultative anaerobes. Room air was collected continuously for 20 minutes with a bioaerosol sampler before and after toilet flushing. Wilcoxon rank-sum tests were used to assess the difference in bioaerosol production before and after flushing.Setting:Rooms of patients with CDI at University of Iowa Hospitals and Clinics.Results:Bacteria were positively cultured from 8 of 24 rooms (33%). In total, 72 preflush and 72 postflush samples were collected; 9 of the preflush samples (13%) and 19 of the postflush samples (26%) were culture positive for healthcare-associated bacteria. The predominant species cultured were Enterococcus faecalis, E. faecium, and C. difficile. Compared to the preflush samples, the postflush samples showed significant increases in the concentrations of the 2 large particle-size categories: 5.0 µm (P = .0095) and 10.0 µm (P = .0082).Conclusions:Bioaerosols produced by toilet flushing potentially contribute to hospital environmental contamination. Prevention measures (eg, toilet lids) should be evaluated as interventions to prevent toilet-associated environmental contamination in clinical settings.

Background: Ceftazidime/avibactam (C/A), ceftolozane/tazobactam (C/T), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V) combine either a cephalosporin (C/T and C/A) or a carbapenem antibiotic (M/V and I/R) with a β-lactamase inhibitor. They are used to treat carbapenem-resistant Enterobacterales (CRE) and/or multidrug-resistant Pseudomonas aeruginosa (MDRPA). Objective: We compared the pooled clinical success of these medications to older therapies. Methods: PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for C/A, C/T, I/R, and M/V studies. The main outcome was clinical success, which was assessed using random-effects models. Stratified analyses were conducted for study drug, sample size, quality, infection source, study design, and multidrug-resistant gram-negative organism (MDRGNO) population. Microbiological success and 28- and 30-day mortality were assessed as secondary outcomes. Heterogeneity was determined using I2 values. Results: Overall, 25 articles met the inclusion criteria; 8 observational studies and 17 randomized control trials. We detected no difference in clinical success comparing new combination antibiotics with standard therapies for all included organisms (pooled OR, 1.21; 95% CI, 0.96–1.51). We detected a moderate level of heterogeneity among the included studies I2 = 56%. Studies that focused on patients with CRE or MDRPA infections demonstrated a strong association between treatment with new combination antibiotics and clinical success (pooled OR, 2.20; 95% CI, 1.60–3.57). Conclusions: C/T, C/A, I/R, and M/V are not inferior to standard therapies for treating various complicated infections, but they may have greater clinical success for treating MDRPA and CRE infections. More studies that evaluate the use of these antibiotics for drug-resistant infections are needed to determine their effectiveness.

In Leishmania infantum-endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.

Introduction Our aim was to evaluate cost and acute care utilization related to an organized approach to care coordination and transitional care after major acute care hospitalization for children with medical complexities, including cerebral palsy. Methods A retrospective cohort of 32 patients from Ranken Jordan Pediatric Bridge Hospital (RJPBH) who received the Care Beyond the Bedside model was compared with 151 patients receiving standard care elsewhere across Missouri. Claims data (2007–2012) were obtained from MoHealthNet, Missouri's Medicaid program, for all children with moderate to severe cerebral palsy (defined using approximated Gross Motor Function Classification System levels) who had at least one hospital visit during the study period ( N = 183). Risk-adjusted linear and Poisson regression models were used to analyze per-member–per-month costs and three indicators of acute care utilization (emergency department visits, readmissions, and inpatient days). Results RJPBH patients were associated with statistically significant reductions in per-member–per-month costs (−21%), hospital readmissions (−66%), and inpatient days (−57%). Discussion RJPBH's enhanced interprofessional medical home-like model, including intense care coordination, psychosocial therapy, family and caregiver empowerment, and transitional care, may be keys to reducing cost and unnecessary hospital use for children with medical complexities with cerebral palsy who receive Medicaid.

Background: Infections caused by Acinetobacter spp are often healthcare acquired, difficult to treat, and associated with high mortality. Extensively drug-resistant (XDR) Acinetobacter are nonsusceptible to at least 1 agent in all but 2 or fewer antimicrobial classes. Epidemiologic and outcome data for XDR Acinetobacter are limited and have largely been reported outside the United States. This national cohort study describes epidemiology, clinical characteristics, and outcomes for patients with XDR Acinetobacter in VA health care. Methods: This was a retrospective cohort study including microbiology and clinical data from all patients hospitalized between 2012 and 2018 at any VA medical center who had cultures that grew XDR Acinetobacter spp. Performance and reporting of bacterial speciation and antibiotic susceptibility testing were performed by each VA laboratory according to their protocol. Descriptive statistics were used to summarize data. Results: Of 11,541 unique patients with 15,358 cultures that grew Acinetobacter spp during the study period, 410 (3.6%) patients had 670 (4.4%) cultures that grew XDR Acinetobacter. Mean age was 68 years (SD, 12.2 years) and the median Charlson comorbidity index was 3 (IQR, 1–5). The greatest proportion of isolates were from the respiratory tract (n = 235, 35%) followed by urine (n = 184, 28%). The South had the greatest proportion of patients with XDR Acinetobacter (n = 162, 40%); almost all patients were seen at urban VA medical centers (n = 406, 99%). Most patients (n = 335, 82%) had had antibiotic exposure in the prior 90 days, most commonly vancomycin (n = 238, 65%) and third- or fourth-generation cephalosporins (n = 155, 38%). Most patients (n = 334, 81%) also had a hospital or long-term care admission in the prior 90 days. Fig. 1 shows antibiotic susceptibilities of XDR Acinetobacter isolates; polymyxins, tigecycline, and minocycline demonstrated the highest susceptibility. In-hospital mortality occurred in 90 patients (22%), 30-day mortality in 97 patients (24%), and 1-year mortality in 198 patients (48%). Of 93 patients, 23% were readmitted to the hospital within 90 days. Conclusions: Providers should maintain a heightened suspicion for infection with XDR Acinetobacter spp in older patients seen at urban medical centers who have had recent healthcare and antibiotic exposures, particularly if they have respiratory or urinary tract infections. Isolation of XDR Acinetobacter is associated with high in-hospital and 30-day mortality. New antibiotics targeting MDR gram-negative bacteria generally lack activity against Acinetobacter, leaving polymyxins, tigecycline, and minocycline as the only limited treatment options. Therefore, novel antibiotics for XDR Acinetobacter are urgently needed.Funding: NoneDisclosures: None

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are gram-negative bacteria resistant to at least 1 carbapenem and are associated with high mortality (50%). Carbapenemase-producing CRE (CP-CRE) are particularly serious because they are more likely to transmit carbapenem resistance genes to other gram-negative bacteria and they are resistant to all carbapenem antibiotics. Few studies have evaluated risk factors associated with CP-CRE colonization. The goal of this study was to determine the risk factors associated with CP-CRE colonization in a cohort of US veterans. Methods: We conducted a retrospective cohort study of patients seen at VA medical centers between 2013 and 2018 who had positive cultures for CRE from any site, defined by resistance to at least 1 of the following carbapenems: imipenem, meropenem, doripenem, or ertapenem. CP-CRE was defined via antibiotic sensitivity data that coded the culture as being ‘carbapenemase producing,’ being ‘Hodge test positive,’ or ‘KPC producing.’ Only the first positive culture for CRE was included. Patient demographics (year of culture, age, sex, race, major comorbidities, infectious organism, culture site, inpatient status, and CP-CRE status) and facility demographics (rurality, geographic region, and facility complexity) were collected. Bivariate analysis and multiple logistic regression were performed to determine variables associated with CP-CRE versus non–CP-CRE. Results: In total, 3,322 patients were identified with a positive CRE culture: 546 (16.4%) with CP-CRE and 2,776 (83.63%) with non–CP-CRE. Most patients were men (95%) and were older (mean age, 71; SD, 12.5) and were diagnosed at a high-complexity VA medical center (65%). Most of the cultures were urine (63%), followed by sputum (13%), and blood (7%). Most were from inpatients (46%), followed by outpatients (42%), and long-term care facilities (12%). Multivariable analysis showed the following variables to be associated with CP-CRE positive cultures: congestive heart failure (P = .0136), African American (P = .0760), Klebsiella spp (P < .0001), GI cancers (P = .0087), culture collected in 2017 (P = .0004), and culture collected in 2018 (P < .0001). There were also significant differences CP-CRE frequencies by geographic region (P < .001). Discussion: CP-CRE diagnoses are relatively rare; however, the serious complications associated make them important infections to investigate. In our analysis, we found that congestive heart failure and gastric cancer were comorbidities strongly associated with CP-CRE. In 2017, the VA formalized their CP-CRE definition, which led to more accurate reporting. Conclusions: After the guideline was implemented, CP-CRE detection dramatically increased in noncontinental US facilities. More work should be done in the future to determine the different risk factors between non–CP-CRE and CP-CRE infections.Funding: NoneDisclosures: None

Background: Gram-negative bacteria cause a variety of hospital-associated infections (HAIs). Of concern is Pseudomonas aeruginosa, which is a leading cause of HAIs. Early and adequate therapy of P. aeruginosa blood stream infection (BSI) is associated with decreased mortality. Additionally, infectious disease consultation has also shown to improve health outcomes, streamline care, and decrease costs. Therefore, the goal of this study was to describe treatment of P. aeruginosa BSI and impact of infectious disease consultations on health outcomes. Methods: In this retrospective cohort study, we analyzed national VA medical, encounter, pharmacy, microbiology, and laboratory data from January 1, 2012 to December 31, 2018. The cohort included all hospitalized adult veterans (aged ≥18 years) who had a positive blood culture for P. aeruginosa. Only the first P. aeruginosa blood culture per patient was included, and duplicate cultures within 30 days were removed. Treatment was identified within −2 to +5 days of the culture date. Multidrug-resistant (MDR) cultures were identified based on resistance to at least 1 agent in at least 3 or more antimicrobial categories tested. Multivariable logistic regression models were fit to assess infectious disease consultations and adequate treatment on in-hospital mortality and 30-day mortality. Results: In total, 3,256 patients had a BSI with P. aeruginosa, of which 386 (11.5%) were MDR. Most of these patients were male (97.5%), >65 years of age (70.9%), and non-Hispanic white (63.8%). Also, 784 patients (23.3%) died during hospitalization and 870 (25.8%) died within 30 days of their culture. In multivariable regression models, infectious disease consultations were associated with decreased odds of in-hospital mortality (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53–0.77) and 30-day mortality (OR, 0.56, 95% CI, 0.48–0.67) even after adjusting for age, race, care setting, Charlson score, and prior healthcare exposures. Furthermore, inadequate definitive treatment was associated with increased odds of in-hospital mortality (OR, 2.77; 95% CI, 1.35–5.69) and 30-day mortality (OR, 2.37; 95% CI, 1.18–4.79), even after adjusting for age, Charlson score, care setting, and prior healthcare exposures. In addition, carbapenem treatment was associated with increased odds of in-hospital mortality (OR, 1.38; 95% CI, 1.12–1.70) and 30-day mortality (OR, 1.49; 95% CI, 1.22–1.81), whereas fluoroquinolone treatment was associated with lower odds of in-hospital mortality (OR, 0.49; 95% CI, 0.41–0.59) and 30-day mortality (OR, 0.60; 95% CI, 0.50–0.71). Finally, extended-spectrum cephalosporin was also associated with lower odds of in-hospital mortality (OR, 0.82; 95% CI, 0.68–0.98). Conclusions: Use of infectious disease consultations and any adequate definitive treatment for those with P. aeruginosa BSI lowered odds of in-hospital and 30-day mortality. Early consultation with infectious disease physicians regarding adequate treatment has direct positive impact on clinical outcomes for patients with P. aeruginosa BSI.Funding: NoDisclosures: None

Background: Infections caused by Acinetobacter spp are often healthcare acquired and associated with high mortality. Extensively drug-resistant (XDR) Acinetobacter are nonsusceptible to at least 1 agent in all but 2 or fewer antibiotic classes. Few of the new antibiotics targeting multidrug-resistant gram-negative bacteria are effective against XDR Acinetobacter. Recent national guidelines for treatment of resistant gram-negative infections do not include Acinetobacter, leaving a knowledge gap in best practices. Methods: This retrospective cohort study included microbiology, clinical, and pharmacy data from all patients hospitalized between 2012 and 2018 at any Veterans’ Affairs medical center who had cultures that grew XDR Acinetobacter spp. Bivariate unadjusted analyses compared clinical outcomes by monotherapy versus combination therapy. Using mixed-effects ordinal logistic regression, propensity score–adjusted models accounting for severity of illness and other variables associated with treatment were fit to compare outcomes. Results: Of 11,546 patients with 15,364 cultures that grew Acinetobacter spp, 408 patients (3.5%) had 666 cultures (4.3%) with XDR Acinetobacter. Moreover, 276 of these patients (67.6%) had gram-negative targeted antibiotic treatment within −2 to +5 days from the culture. Furthermore, 118 patients (42.8%) received monotherapy, most commonly piperacillin-tazobactam (n = 54, 45.7%) or an anti-Pseudomonas cephalosporin (n = 21, 17.8%). Also, 158 (57.2%) patients received combination therapy, most commonly a carbapenem (n = 93, 58.9%) and/or polymyxin (n = 68, 43.0%). Moreover, 41 patients (25.9%) received both a carbapenem and polymyxin. In both unadjusted and adjusted analyses, there were no significant differences in the odds of 30-day mortality (aOR, 1.43; 95% CI, 0.86–2.38) or 1-year mortality (aOR, 1.04; 95% CI, 0.68–1.60) between combination therapy and monotherapy groups. Among 264 patients (96%) whose cultures occurred during an inpatient or long-term care admission, unadjusted analyses showed increased odds of in-hospital mortality (OR, 1.89; 95% CI, 1.08–3.29) and longer postculture length of stay in the combination therapy group: median, 23 days (IQR, 11–57) versus 14 days (IQR, 7–32) (P = .02). However, with propensity score adjustment, these associations were no longer significant. Furthermore, there was no significant difference in odds of 90-day readmission between groups in either unadjusted or adjusted analyses (aOR, 1.20; 95% CI, 0.74–1.95). Conclusions: In this large national cohort of patients with XDR Acinetobacter cultures, more patients received combination therapy than monotherapy, and carbapenems and polymyxins were the most-used classes. However, there were no significant differences in outcomes between patients receiving combination therapy and monotherapy, suggesting lack of clinical benefit to the common practice of treating XDR Acinetobacter infections with multiple antibiotics. Further research is needed to determine optimal treatment strategies for this pathogen.Funding: NoDisclosures: None

Background Dentists prescribe few broad-spectrum antibiotics but are the primary prescriber of clindamycin in the U.S. Data is scarce on the association of dental antibiotic prescribing and Clostridioides difficile infection (CDI). Here we present results from a longitudinal cohort of patients with a CDI positive diagnostic test 30 days after receiving an antibiotic prescribed by a dentist. Methods A cohort of patients with antibiotic prescriptions within 7 days of a dental visit were identified from 2015-2018. From this cohort, patients with positive C. difficile test 30 days after a dental antibiotic were included. Chart reviews obtained information about the dental visit, antibiotic prescribed, and CDI diagnosis. Descriptive statistics were used to describe characteristics of those with CDI following a dental antibiotic. Results 212,763 Veterans received an antibiotic from a dentist between 2015-2018. Of them, 87 patients had a positive CDI test within 30 days of receiving their dental antibiotic. Over half (57.4%) of these patients had surgical dental visits and 45.9% had an oral infection coded. Dentists documented reasons for prescription was treatment of a local infection (40%) and post procedure prophylaxis (24%). Amoxicillin (54.0%) and clindamycin (40.2%) were the most commonly prescribed antibiotics. 65.7% of the patients that received clindamycin from the dentist had a documented penicillin allergy. 58.6% of patients had a preexisting gastrointestinal condition and 44.8% were taking gastric acid reducer medication. Only 19.5% of the antibiotic prescriptions met ADA guidelines for appropriate antibiotics (presence of gingival manipulation and a cardiac condition). CDI cases were treated with metronidazole (55.2%), or vancomycin (37.9%); 5.7% had no apparent treatment through the VA. The average number of days between the dental visit and CDI diagnosis was 18.9. Conclusion The occurrence of CDI was infrequent after a dental antibiotic. However, clindamycin was prescribed more frequently in this cohort than published literature on dentist prescribing. Approximately half had a gastrointestinal risk factor for CDI. More research is needed to determine the type of patient most at risk for CDI following a dental antibiotic. Disclosures All Authors: No reported disclosures

Background Carbapenem-resistant Enterobacteriaceae (CRE) are a substantial burden, with recent data showing no change in hospital CRE between 2012-2017. All carbapenemases produced by CRE have been identified in the U.S., however trends in testing and detection over time have not been well described. Trends in carbapenemase testing in the VA, 2013-2018 Methods A retrospective cohort study of Veterans hospitalized between 2013-2018 with CRE cultures defined by either 2015 or 2017 VA guidelines. In general, this was Escherichia coli, Klebsiella pneumoniae/oxytoca, or Enterobacter spp. non-susceptible to imipenem, meropenem, and/or doripenem, and to 3rd generation cephalosporins for 2015 definition. Testing for Klebsiella pneumoniae carbapenemase (KPC), New Dehli metallo-β-lactamase (NDM), Verona integron-encoded metallo-β-lactamase (VIM), Imipenemase (IMP), and Oxacillinase-48-like (OXA-48) was summarized with descriptive statistics. Facility characteristics assessed included region, complexity, and rurality. Results Out of 5,778 CRE cultures, 1,900 (32.9%) were tested for carbapenemases and 1,612 (84.8%) of these had carbapenemases detected. Among CP-CRE cultures, 1,042 (64.6%) had testing for ≥1 genetic mechanism; all tests included KPC. Testing for NDM (n=585, 56.1%), VIM (n=102, 9.8%), IMP (n=102, 9.8%), and OXA-48 (n=507, 48.7%) was less frequent. KPC was detected in 915/1,042 cultures (87.8%), while NDM (n=7/585, 1.2%) was rarely detected. There were no cases of VIM, IMP, or OXA-48. Carbapenemase testing increased significantly over the study period; KPC, NDM, and OXA-48 were the predominant mechanisms tested (Figure 1). The South (38.6%) and Northeast (37.2%) had the highest proportion of CRE with carbapenemase testing. High complexity (vs low) and urban (vs rural) facilities were significantly associated with carbapenemase testing (p< 0.001). Conclusion Following publication of initial CRE guidelines in 2015, carbapenemase testing and detection increased in the VA, although tests for non-KPC carbapenemases were less frequent. Surveillance of non-KPC carbapenemases is important due to global dissemination and enhanced antibiotic resistance. Efforts should support carbapenemase testing in low complexity, rural facilities in the Midwest and West. Disclosures All Authors: No reported disclosures

Background Ceftolozane/ Tazobactam (C/T), Ceftazidime/ Avibactam (C/A), Meropenem/ Vaborbactam (M/V) and Imipenem/ Relebactam (I/R) are new combination beta-lactam/ beta-lactamase inhibitor antibiotics primarily used to treat multidrug-resistant (MDR) Gram-negative infections. This study synthesized outcomes of comparative observational studies and randomized control trials (RCTs) that evaluated clinical success of these antibiotics compared to other therapies. Methods PubMed, EMBASE, and Google Scholar were searched from January 1st, 2013 through October 1st, 2019 for comparative observational studies and RCTs of C/T, C/A, M/V and I/R in patients with pneumonia, complicated intra-abdominal and urinary tract infections. Study and patient demographics were collected along with clinical and microbiological success rates. Meta-regression analysis was used to determine the pooled effectiveness of C/T, C/A, M/V, and I/R. Heterogeneity and publication bias were assessed via I2 values and funnel plots, respectively. Results Literature search returned 1,645 results. After exclusion criteria, 21 publications representing 6,246 patients were retained: 16 RCTs (8 C/A, 3 C/T, 3 I/R, 2 M/V) and 5 comparative observational studies (3 C/A, 2 C/T). Pooled risk ratios for clinical success showed that all four antibiotics were non-inferior to comparator antibiotics (0.99 (95% CI (0.97-1.01)). Eleven of the sixteen RCTs evaluated microbiological success; pooled risk ratio was 1.08 (95% CI 1.04-1.13), indicating that older therapies were more successful at microbiological eradication than newer antibiotics. Only 6 of the included studies (3 RCTs and 2 observational studies) focused on patients with MDR infections. Limiting the analysis to MDR RCTs did not change the overall conclusions. Conclusion Although older therapies had slightly higher microbiologic clearance, pooled clinical success rates for C/A, C/T, M/V, and I/R were non-inferior to older therapies, including in studies focused on patients with MDR infections. Additional studies are needed to further evaluate these drugs’ effectiveness for treatment of MDR infections. Disclosures All Authors: No reported disclosures

Background: Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (C/A) are new β-lactam/β-lactamase combination antibiotics that were approved by the FDA in 2014 and 2015, respectively, to treat complicated intra-abdominal and urinary tract infections. They are commonly used to treat multidrug-resistant Pseudomonas aeruginosa (MDRPA) and carbapenem-resistant Enterobacteriaceae (CRE) infections at any site. Both medications are also often used as salvage therapy when empiric therapy has failed or when the infectious organism tests resistant to all other available antibiotics. The purpose of this review is to present the clinical experience and reported clinical success rates of C/T and C/A. Methods: PubMed, EMBASE, and Google Scholar were searched from January 1, 2013, through October 1, 2019, for publications detailing clinical experience with C/T and C/A in patients with CRE and MDRPA infections. Included study designs were extended cases series and clinical observational studies. Information on infection type, bacterial agent, salvage therapy uses, clinical success, and resistance development during treatment were abstracted. Meta-regression analysis was used to determine the pooled effectiveness of C/T and C/A among included studies. Results: The literature search returned 1,645 publications. After exclusion criteria were applied, 16 publications representing 769 patients were retained. The study population was mostly male (pooled average, 62%). The major comorbidities represented in the pooled population were solid organ transplantation (20.0%), kidney disease (19.5%), cardiovascular disease (15.3%), and diabetes (15.3%). Pneumonia was the predominant infection type (41.4%) and MDRPA was the pathogen most frequently evaluated (57.7%). The pooled clinical success rate was 70.2% (95% CI, 64.5%–75.3%). Also, 10 studies explicitly evaluated C/A or C/T as salvage therapy. The pooled clinical success rate for salvage therapy studies was 75.2% (95% CI, 69.7%–80.0%). Development of resistance to C/T or C/A during or after treatment was reported for 2.0% of the population. Conclusion: Overall, these medications have a high clinical success rate in patients with severe and complicated infections and limited treatment options. Pooled clinical success rates were high (70.2%) and the medications were particularly effective as salvage therapy. Resistance rates were low, although this could have been biased by the small percentage of studies that reported on this outcome. More longitudinal studies comparing the effectiveness of C/T and C/A against other antibiotic regimens are needed.Funding: NoneDisclosures: None

Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009–1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185–8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.

In Leishmania infantum–endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec(®) after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.