Facility- and patient-level factors associated with implementation of contact precautions in hospitalized VA patients with positive CRE cultures.

Decreasing the time to contact precautions (CP) is critical to carbapenem-resistant Enterobacterales (CRE) prevention. Identifying factors associated with delayed CP can decrease the spread from patients with CRE. In this study, a shorter length of stay was associated with being placed in CP within 3 days.

Prevalence of unnecessary antibiotic prescriptions among dental visits, 2019.

OBJECTIVE: The US National Action Plan for Combating Antibiotic-Resistant Bacteria established a goal to decrease unnecessary outpatient antibiotic use by 50%. However, data to inform this goal have been limited to medical settings and have not included dental prescribing. Thus, we sought to identify the proportion of antibiotics prescribed inappropriately by dentists to inform outpatient stewardship efforts. METHODS: Cross-sectional analysis of 2019 Veterans' Affairs (VA) national electronic health record data. Antibiotics prescribed by dentists were evaluated for appropriateness based on 2 definitions: one derived from current guidelines (consensus-based recommendations) and the other based on relevant clinical literature (nonconsensus). A clustered binomial logistic regression model determined factors associated with discordant prescribing. RESULTS: In total, 92,224 antibiotic prescriptions (63% amoxicillin; mean supply, 8.0 days) were associated with 88,539 dental visits. Prophylaxis for complications in medically compromised patients was associated with the most (30.9%) antibiotic prescriptions, followed by prevention of postsurgical complications (20.1%) and infective endocarditis (18.0%). At the visit level, 15,476 (17.5%) met the consensus-based definition for appropriate antibiotic usage and 56,946 (64.3%) met the nonconsensus definition. CONCLUSIONS: More than half of antibiotics prescribed by dentists do not have guidelines supporting their use. Regardless of definition applied, antibiotics prescribed by dentists were commonly unnecessary. Improving prescribing by dentists is critical to reach the national goal to decrease unnecessary antibiotic use.

Risk factors for oral infection and dry socket post-tooth extraction in medically complex patients in the absence of antibiotic prophylaxis: A case-control study.

INTRODUCTION: Dry socket and infection are complications of tooth extractions. The objective was to determine risk factors for post-extraction complications in patients without antibiotic prophylaxis stratified by early- and late-complications and complication type (oral infection and dry socket). METHODS: Retrospective, case (with complications)-control (without complications) study of patients (n = 708) who had ≥1 extraction performed at any Veterans Health Administration facility between 2015-2019 and were not prescribed an antibiotic 30 days pre-extraction. RESULTS: Early complication cases (n = 109) were more likely to be female [odds ratio (OR) = 2.06; 95% confidence interval (CI):1.05-4.01], younger (OR = 0.29; 95% CI:0.09-0.94 patients ≥ 80 years old, reference:18-44 years), Native American/Alaska Native (OR = 21.11; 95% CI:2.33-191.41) and have fewer teeth extracted (OR = 0.53 3+ teeth extracted; 95% CI:0.31-0.88, reference:1 tooth extracted). Late complication cases (n = 67) were more likely to have a bipolar diagnosis (OR = 2.98; 95% CI:1.04-8.57), history of implant placement (OR = 8.27; 95% CI:1.63-41.82), and history of past smoking (OR = 2.23; 95% CI:1.28-3.88). CONCLUSION: Predictors for post-extraction complications among patients who did not receive antibiotic prophylaxis were similar to prior work in cohorts who received prophylaxis. Unique factors identified in a medically complex population included being younger, Native American/Alaska Native, having mental health conditions, history of a dental implant, and fewer teeth extracted.

Treatment effectiveness of antibiotic therapy in Veterans with multidrug-resistant Acinetobacter spp. bacteremia.

Objective: To describe antimicrobial therapy used for multidrug-resistant (MDR) Acinetobacter spp. bacteremia in Veterans and impacts on mortality. Methods: This was a retrospective cohort study of hospitalized Veterans Affairs patients from 2012 to 2018 with a positive MDR Acinetobacter spp. blood culture who received antimicrobial treatment 2 days prior to through 5 days after the culture date. Only the first culture per patient was used. The association between treatment and patient characteristics was assessed using bivariate analyses. Multivariable logistic regression models examined the relationship between antibiotic regimen and in-hospital, 30-day, and 1-year mortality. Generalized linear models were used to assess cost outcomes. Results: MDR Acinetobacter spp. was identified in 184 patients. Most cultures identified were Acinetobacter baumannii (90%), 3% were Acinetobacter lwoffii, and 7% were other Acinetobacter species. Penicillins-ß-lactamase inhibitor combinations (51.1%) and carbapenems (51.6%)-were the most prescribed antibiotics. In unadjusted analysis, extended spectrum cephalosporins and penicillins-ß-lactamase inhibitor combinations-were associated with a decreased odds of 30-day mortality but were insignificant after adjustment (adjusted odds ratio (aOR) = 0.47, 95% CI, 0.21-1.05, aOR = 0.75, 95% CI, 0.37-1.53). There was no association between combination therapy vs monotherapy and 30-day mortality (aOR = 1.55, 95% CI, 0.72-3.32). Conclusion: In hospitalized Veterans with MDR Acinetobacter spp., none of the treatments were shown to be associated with in-hospital, 30-day, and 1-year mortality. Combination therapy was not associated with decreased mortality for MDR Acinetobacter spp. bacteremia.

Age and beliefs about vaccines associated with COVID-19 vaccination among US Veterans.

This project surveyed Veterans' COVID-19 vaccination beliefs and status. 1,080 (30.8%) Veterans responded. Factors associated with being unvaccinated, identified using binomial logistic regression, included negative feelings about vaccines (OR = 3.88, 95%CI = 1.52, 9.90) and logistical difficulties such as finding transportation (OR = 1.95, 95%CI = 1.01, 3.45). This highlights the need for education about and access to vaccination.

Antimicrobial stewardship strategy implementation and impact in acute care spinal cord injury and disorder units.

CONTEXT: Antimicrobial Stewardship Programs (ASPs) are crucial to optimizing antibiotic use. ASPs are implemented in the Veterans Health Administration (VAs), but they do not target the needs of populations at high risk for resistant infections, such as spinal cord injury and disorder (SCI/D). OBJECTIVE: The goal of this study was to assess key ASP leader and SCI/D clinicians' perceived level of implementation and impact of 33 Antimicrobial Stewardship (AS) strategies. METHOD: SCI/D clinicians and ASP leaders across 24 VA facilities with SCI/D units were surveyed. Participants rated their perceived level of impact ("high", "mild", "low") and perceived level of implementation ("not", "partially", "fully") for 33 AS strategies in SCI/D units in VAs. Strategies were grouped into core elements which they support. We conducted a Fisher's exact test to assess differences between respondent perceptions based on role (SCI/D clinicians versus ASP leaders). RESULTS: AS strategy implementation varied across VA facilities. Of the AS strategies, pre-authorization was perceived to be highly impactful (78%) and fully implemented (82%). SCI/D clinicians and ASP leaders rated AS strategies differently such that SCI/D clinicians were less aware of implementation of AS strategies related to reporting requirements; further, SCI/D clinicians rated strategies which guide treatment duration and which limit C. difficile antibiotic exposure as more impactful than ASP leaders. Ratings for facility-wide and SCI/D unit ratings did not significantly differ for impact or implementation. CONCLUSION: Implementation practices varied across VA facilities. Future work should implement highly impactful AS strategies according to facility and unit needs.

Factors associated with dental implant loss/complications in the Veterans Health Administration, 2015-2019.

OBJECTIVES: Twelve percent of the U.S. population has a dental implant. Although rare, implant loss/complications can impact quality of life. This study evaluated indicators for implant loss/complications. METHODS: Veterans with dental implants placed between 2015 and 2019 were included. Implant loss/complications were defined as implant removal or peri-implant defect treatment within 90 days. Binomial logistic regression identified factors associated with implant loss/complications. RESULTS: From 2015 to 2019, 48,811 dental implants were placed in 38,246 Veterans. Implant loss/complications was identified for 202 (0.4%) implants. In adjusted analyses, Veterans aged 50-64 years (OR = 1.92 (95% confidence interval (CI): 1.06, 3.46)) and ≥65 (OR = 2.01 (95% CI: 1.14, 3.53)) were more likely to have implant loss/complications. History of oral infection, tooth location, and number of implants placed all significantly increased the odds of loss/complications. CONCLUSION: Dental implant loss/complications are rare outcomes. Older age, location of implant, and the number of implants placed during a visit were significant predictors of loss/complication.

Uptake in newly approved antibiotics prescribed to patients with carbapenem-resistant Enterobacterales (CRE).

We assessed trends in treatment of patients with CRE from 2012 through 2018. We detected decreased utilization of aminoglycosides and colistin and increased utilization in extended-spectrum cephalosporins and ceftazidime-avibactam. We found significant uptake of ceftazidime-avibactam, a newly approved antibiotic, to treat CRE infections.

Clostridioides difficile infection following dental antibiotic prescriptions in a cohort of US veterans.

Among 108 (0.05% of cohort) US veterans with a Clostridioides difficile infection (CDI) within 30 days of a dental antibiotic prescription, 80% of patients received guideline-discordant antibiotics. Half had chronic gastrointestinal illness potentially exacerbating their CDI risk. More efforts are needed to improve antibiotic stewardship.

Increased carbapenemase testing following implementation of national VA guidelines for carbapenem-resistant Enterobacterales (CRE).

Objective: To describe national trends in testing and detection of carbapenemases produced by carbapenem-resistant Enterobacterales (CRE) and associate testing with culture and facility characteristics. Design: Retrospective cohort study. Setting: Department of Veterans' Affairs medical centers (VAMCs). Participants: Patients seen at VAMCs between 2013 and 2018 with cultures positive for CRE, defined by national VA guidelines. Interventions: Microbiology and clinical data were extracted from national VA data sets. Carbapenemase testing was summarized using descriptive statistics. Characteristics associated with carbapenemase testing were assessed with bivariate analyses. Results: Of 5,778 standard cultures that grew CRE, 1,905 (33.0%) had evidence of molecular or phenotypic carbapenemase testing and 1,603 (84.1%) of these had carbapenemases detected. Among these cultures confirmed as carbapenemase-producing CRE, 1,053 (65.7%) had molecular testing for ≥1 gene. Almost all testing included KPC (n = 1,047, 99.4%), with KPC detected in 914 of 1,047 (87.3%) cultures. Testing and detection of other enzymes was less frequent. Carbapenemase testing increased over the study period from 23.5% of CRE cultures in 2013 to 58.9% in 2018. The South US Census region (38.6%) and the Northeast (37.2%) region had the highest proportion of CRE cultures with carbapenemase testing. High complexity (vs low) and urban (vs rural) facilities were significantly associated with carbapenemase testing (P < .0001). Conclusions: Between 2013 and 2018, carbapenemase testing and detection increased in the VA, largely reflecting increased testing and detection of KPC. Surveillance of other carbapenemases is important due to global spread and increasing antibiotic resistance. Efforts supporting the expansion of carbapenemase testing to low-complexity, rural healthcare facilities and standardization of reporting of carbapenemase testing are needed.

Comparative effectiveness of antibiotic therapy for carbapenem-resistant Enterobacterales (CRE) bloodstream infections in hospitalized US veterans.

Background: Carbapenem-resistant Enterobacterales bloodstream infections (CRE-BSI) increase mortality three-fold compared with carbapenem-susceptible bloodstream infections. Because these infections are rare, there is a paucity of information on mortality associated with different treatment regimens. This study examines treatment regimens and association with in-hospital, 30 day and 1 year mortality risk for patients with CRE-BSI. Methods: This retrospective cohort study identified hospitalized patients within the Veteran Affairs (VA) from 2013 to 2018 with a positive CRE blood culture and started antibiotic treatment within 5 days of culture. Primary outcomes were in-hospital, 30 day and 1 year all-cause mortality. Secondary outcomes were healthcare costs at 30 days and 1 year and Clostridioides difficile infection 6 weeks post culture date. The propensity for receiving each treatment regimen was determined. Multivariable regression assessed the association between treatment and outcomes. Results: There were 393 hospitalized patients from 2013 to 2018 included in the study. The cohort was male (97%) and elderly (mean age 71.0 years). Carbapenems were the most prescribed antibiotics (47%). In unadjusted analysis, ceftazidime/avibactam was associated with a lower likelihood of 30 day and 1 year mortality. After adjusting, ceftazidime/avibactam had a 30 day mortality OR of 0.42 (95% CI 0.17-1.02). No difference was found in C. difficile incidence at 6 weeks post-infection or total costs at 30 days or 1 year post culture date by any treatments. Conclusions: In hospitalized veterans with CRE-BSI, none of the treatments were shown to be associated with all-cause mortality. Ceftazidime/avibactam trended towards protectiveness against 30 day and 1 year all-cause mortality. Use of ceftazidime/avibactam should be encouraged for treatment of CRE-BSI.

Infectious Disease Consults of Pseudomonas aeruginosa Bloodstream Infection and Impact on Health Outcomes.

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.

Epidemiology and outcomes associated with carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa: a retrospective cohort study.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to describe CRAB and CRPA epidemiology and identify factors associated with mortality and length of stay (LOS) post-culture. METHODS: This was a national retrospective cohort study of Veterans with CRAB or CRPA positive cultures from 2013 to 2018, conducted at Hines Veterans Affairs Hospital. Carbapenem resistance was defined as non-susceptibility to imipenem, meropenem and/or doripenem. Multivariable cluster adjusted regression models were fit to assess the association of post-culture LOS among inpatient and long-term care (LTC) and to identify factors associated with 90-day and 365-day mortality after positive CRAB and CRPA cultures. RESULTS: CRAB and CRPA were identified in 1,048 and 8,204 unique patients respectively, with 90-day mortality rates of 30.3% and 24.5% and inpatient post-LOS of 26 and 27 days. Positive blood cultures were associated with an increased odds of 90-day mortality compared to urine cultures in patients with CRAB (OR 6.98, 95% CI 3.55-13.73) and CRPA (OR 2.82, 95% CI 2.04-3.90). In patients with CRAB and CRPA blood cultures, higher Charlson score was associated with increased odds of 90-day mortality. In CRAB and CRPA, among patients from inpatient care settings, blood cultures were associated with a decreased LOS compared to urine cultures. CONCLUSIONS: Positive blood cultures and more comorbidities were associated with higher odds for mortality in patients with CRAB and CRPA. Recognizing these factors would encourage clinicians to treat these patients in a timely manner to improve outcomes of patients infected with these organisms.

Treatment of extensively-drug resistant (XDR) Acinetobacter and impact on clinical outcomes in U.S. veterans affairs (VA) medical centers.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Leishmania infantum xenodiagnosis from vertically infected dogs reveals significant skin tropism.

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.

Risk Factors Associated With Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Positive Cultures in a Cohort of US Veterans.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) cause approximately 13 100 infections, with an 8% mortality rate in the United States annually. Carbapenemase-producing CRE (CP-CRE) a subset of CRE infections infections have much higher mortality rates (40%-50%). There has been little research on characteristics unique to CP-CRE. The goal of the current study was to assess differences between US veterans with non-CP-CRE and those with CP-CRE cultures. METHODS: A retrospective cohort of veterans with CRE cultures from 2013-2018 and their demographic, medical, and facility level covariates were collected. Clustered multiple logistic regression models were used to assess independent factors associated with CP-CRE. RESULTS: The study included 3096 unique patients with cultures positive for either non-CP-CRE or CP-CRE. Being African American (odds ratio, 1.44 [95% confidence interval, 1.15-1.80]), diagnosis in 2017 (3.11 [2.13-4.54]) or 2018 (3.93 [2.64-5.84]), congestive heart failure (1.35 [1.11-1.64]), and gastroesophageal reflux disease (1.39 [1.03-1.87]) were associated with CP-CRE cultures. There was no known antibiotic exposure in the previous year for 752 patients (24.3% of the included patients). Those with no known antibiotic exposure had increased frequency of prolonged proton pump inhibitor use (17.3%) compared to those with known antibiotic exposure (5.6%). DISCUSSION: Among a cohort of patients with CRE, African Americans, patients with congestive heart failure, and those with gastroesophageal reflux disease had greater odds of having a CP-CRE culture. Roughly 1 in 4 patients with CP-CRE had no known antibiotic exposure in the year before their positive culture.

Meta-analysis of Clinical Outcomes Using Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam for the Treatment of Multidrug-Resistant Gram-Negative Infections.

Ceftolozane-tazobactam (C/T), ceftazidime-avibactam (C/A), and meropenem/vaborbactam (M/V) are new beta-lactam/beta-lactamase combination antibiotics commonly used to treat multidrug-resistant Pseudomonas aeruginosa (MDRPA) and carbapenem-resistant Enterobacteriaceae (CRE) infections. This review reports the clinical success rates for C/T, C/A, and M/V. PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for publications detailing the use of C/T, C/A, and M/V. A meta-analysis determined the pooled effectiveness of C/T, C/A, and M/V. The literature search returned 1950 publications; 29 publications representing 1620 patients were retained. Pneumonia was the predominant infection type (49.8%). MDRPA was the major pathogen treated (65.3%). The pooled clinical success rate was 73.3% (95% CI, 68.9%-77.5%). C/T, C/A, or M/V resistance was reported in 8.9% of the population. These antibiotics had a high clinical success rate in patients with complicated infections and limited treatment options. Larger studies comparing C/T, C/A, and M/V against other antibiotic regimens are needed.

Evaluating the clinical effectiveness of new beta-lactam/beta-lactamase inhibitor combination antibiotics: A systematic literature review and meta-analysis.

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 ß-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.

Carbapenem-resistant Enterobacteriaceae epidemiology in Veterans' Affairs medical centers varies by facility characteristics.

This is an epidemiological study of carbapenem-resistant Enterobacteriaceae (CRE) in Veterans' Affairs medical centers (VAMCs). In 2017, almost 75% of VAMCs had at least 1 CRE case. We observed substantial geographic variability, with more cases in urban, complex facilities. This supports the benefit of tailoring infection control strategies to facility characteristics.