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Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel β-lactam-β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.).We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy.Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P 0.001). The number needed to harm with best alternative therapy was 3.Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI.

Background Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4–8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns. Methods This was a retrospective cohort study of hospitalized patients with E. cloacae, K. aerogenes, or C. freundii bacteremia from January 2015 to March 2022 receiving high-dose cefepime or a carbapenem. Cox regression models were used with incorporation of inverse probability of treatment weighting and time-varying covariates. Results Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79–2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52–1.77). Multivariable weighted Cox models identified Pitt bacteremia score >4 (aHR, 1.41; 95% CI, 1.04–1.92), deep infection (aHR, 2.27; 95% CI, 1.21–4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03–1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40–0.89). Conclusions Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy.

Background A prior study demonstrated suboptimal antibiotic prescribing in the emergency department (ED) at 77.4% for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). This study measured the effect of indication-based antibiotic order sentences (AOS) on prescribing. Methods IRB-approved quasi-experiment of adults prescribed antibiotics in ED for uncomplicated LRTI, UTI, or ABSSSI from January - June 2019 (pre-group) or September - December 2021 (post-group). Exclusion: hospital admission, immunocompromised, active cancer, or prophylactic antibiotics. AOS are lean process, electronic discharge prescriptions retrievable by name or indication; AOS implementation occurred July 2021. Optimal prescribing was defined as the correct antibiotic selection, dose, and duration per local and national guidelines. Seven-day endpoints: antibiotic escalation, ED or hospital readmission, any outpatient contact, and reported adverse drug event (ADE). Descriptive and bivariate statistics performed. Variables considered for multivariable logistic regression had p< 0.2 or plausible association with optimal prescribing. Results 294 patients included: 147-pre and 147-post. Patient characteristics are in Table 1. Overall optimal prescribing improved from 12 (8.2%) to 34 (23.1%) (p< 0.001). Breakdown of optimal prescribing in pre- and post-groups: selection 90 (61.2%) vs 117 (79.6%) (p< 0.001), dose 99 (67.3%) vs 115 (78.2%) (p=0.036), duration 38 (25.9%) vs 50 (34%) (p=0.126). After adjustment, AOS were independently associated with optimal prescribing (Table 2). Secondary endpoints: antibiotic escalation 10 (6.8%) vs 7 (4.8%) (p=0.662), hospital or ED readmission 12 (8.2%) vs 10 (6.8%) (p=0.658), outpatient contact 31 (21.1%) vs 28 (19%) (p=0.662), and ADE 2 (1.4%) vs 4 (2.7%) (p=0.684). Post-hoc analysis showed suboptimal uptake of AOS by ED prescribers. Table 1:Baseline and Clinical CharacteristicsTable 2:Bivariable and Multivariable Regression Analysis of Factors Associated with Optimal Prescribing†Covaries with intervention group; Hosmer and Lemeshow p = 0.68; Method: backwards logistic regression; No variables removed Conclusion AOS is an efficient and promising antimicrobial stewardship strategy; provider re-education is needed to increase AOS uptake. Disclosures All Authors: No reported disclosures.

Background Multi-drug resistant (MDR) pathogens are a continuously evolving threat for which there are limited effective treatment modalities. Omadacycline (OMC) is a novel oral and intravenously administered aminomethylcycline with potent in-vitro activity against MDR gram-negative and gram-positive pathogens. Post-marketing data investigating its potential place in the antibiotic armamentarium is limited. This study aimed at describing the clinical success and tolerability of patients receiving OMC for various infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to March 30, 2022. We included all patients ≥ 18 years of age that received OMC for any infection not related to Mycobacterium spp. for ≥72 hours. The primary outcome was clinical success at 30 days, defined as survival, the absence of persistence or re-emergence of infection during or after therapy, and the absence of escalation or alteration of OMC. Incidence of adverse effects while on OMC and reasons for OMC utilization were also analyzed. Results This analysis included 19 patients from 10 distinct academic centers. The median age was 50 years (IQR, 37-63), 58% were male, 63% were Caucasian, and the median APACHE II, Charlson and SOFA scores were 10 (IQR 5-12.5), 4 (IQR 2-6.3), and 1 (IQR 0 – 2.25), respectively. Most patients had a bone and joint (8/19, 42.1%) or intra-abdominal infections (4/19, 21.1%), all with positive cultures. Eight patients (44.1%) had a polymicrobial infection and 4 (22.2%) had bacteremia. The most common pathogens encountered were Carbapenem-resistant A. baumannii (5/19, 27.8%), E. coli (5/19, 27.8%), Vancomycin-resistant Enterococcus spp. (4/19, 22.2%), and K. pneumoniae (3/19, 16.7%). Clinical success was observed in 14 patients (74%) and 7 (36.8%) received combination therapy. Adverse drug reactions were reported in 3 patients (15.8%) and of those patients, none discontinued therapy. Reasons for prescribing OMC were mostly attributed to oral availability (12/14, 85.7%) and resistance to other agents (7/14, 50%). Conclusion OMC demonstrated clinical effectiveness and safety against a large number of MDR pathogens. More robust, prospective, comparative studies are needed to confirm our preliminary findings. Disclosures P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.

Background Comparative effectiveness studies to guide treatment decisions for infections caused by carbapenem-resistant P. aeruginosa (CRPA) susceptible to traditional agents (non-carbapenem β-lactams and fluoroquinolones) are unavailable. This study aims to compare clinical outcomes between patients treated with traditional and alternative treatment regimens for lower respiratory tract infection (LRTI) caused by CRPA that remain susceptible to traditional agents. Methods Multi-center, retrospective cohort from January 2016 to December 2019. We included adults with CRPA (resistant to ≥ 1 carbapenem; meropenem or imipenem) that were susceptible to ≥1 traditional agent (piperacillin-tazobactam, cefepime, ceftazidime, ciprofloxacin, or aztreonam) by CLSI breakpoints isolated from an LRTI sample. All other antibiotics were considered alternative agents. We excluded patients with known colonization, cystic fibrosis, or who expired ≤24 hours after antibiotic receipt. Primary outcome was 30-day mortality and secondary outcomes included 30-day readmission and 30-day recurrence. Results In total, 87 patients, ‘traditional’ treatment (n=53) and ‘alternative’ treatment (n=34), were included from 2 institutions in Detroit, MI, USA: median(IQR) age 59(20) years, 64.4% male, and 59.8% African American. Median(IQR) APACHE II and Charlson Comorbidity index scores were 24(10) and 4(5), respectively. Most patients received traditional therapy (n=53), most commonly with cefepime (60.4%) or piperacillin-tazobactam (41.5%). While 34(39.0%) were treated with alternative agents, most commonly ceftolozane-tazobactam (64.7%) or an aminoglycoside (29.4%) alone or in combination. Thirty-day mortality was not significantly different between traditional and alternative therapy groups (22.6% and 11.8%), respectively. There was no significant difference between 30-day recurrence (17.0% and 20.6%) or 30-day readmission (22.6% and 17.6%) between groups. Conclusion Clinical outcomes did not differ significantly between patients receiving traditional vs. alternative agents for LRTI caused by CRPA susceptible to traditional agents. Traditional agents may be considered for these infections. Further comparative studies are needed to guide treatment decisions for CRPA. Disclosures All Authors: No reported disclosures.

Background Diabetic foot infections (DFIs) are commonly associated with antibiotic overuse. Empiric DFI treatment often includes coverage for Pseudomonas aeruginosa (PsA), but the frequency of PsA DFIs is poorly understood. The study objectives were to quantify the prevalence of and determine predictors for PsA DFIs. Methods This multicenter, retrospective cohort included hospitalized patients with DFI from 2013 through 2020 who were age ≥18 years; diabetes mellitus diagnosis; and DFI based on International Classification of Diseases, Tenth Revision coding, antibiotic treatment, and DFI culture with organism growth. Osteomyelitis was excluded. Patient characteristics were described and compared; the primary outcome was presence of PsA on DFI culture. Predictors of PsA DFI were identified using multivariable logistic regression. Results Two hundred ninety-two patients were included. The median age was 61 (interquartile range [IQR], 53–69) years; the majority were men (201 [69%]) and White (163 [56%]). The most commonly isolated organisms were methicillin-susceptible Staphylococcus aureus (35%) and streptococci (32%); 147 (54%) cultures were polymicrobial. Two hundred fifty-seven (88%) patients received empiric antibiotics active against PsA, but only 27 (9%) patients had PsA DFI. Immunocompromised status (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 1.3–16.7]) and previous outpatient DFI antibiotic treatment failure (aOR, 4.8 [95% CI, 1.9–11.9]) were associated with PsA DFI. Conclusions PsA DFI is uncommon, but most patients receive empiric antipseudomonal antibiotics. Empiric broad-spectrum antibiotics are warranted given the frequency of mixed infections, but patient-specific risk factors should be considered before adding antipseudomonal coverage.

Background Candida spp. infective endocarditis (CIE) although rare is associated with high morbidity and mortality. Risk factors include prosthetic heart valves and injection drug use (IDU). We reviewed all cases of CIE at our institution to describe the microbiology, treatment and outcomes of patients focusing on IDU as a predisposing factor. Methods Retrospective cohort of patients with definite CIE between 2013 and 2019 at a university hospital was analysed. Demographic data collected included IDU, microbiologic, treatment and mortality. The primary outcome of interest was 12-month, all-cause mortality. Results Twenty patients were included (one had two separate episodes of CIE); CIE accounted for 4% of total infective endocarditis (IE) cases during the study period. The median (IQR) age was 38 (30-58) years, 10 (50%) had a previous history of IE, and 4 (20%) patients had prosthetic heart valves or an implanted cardiac device. Thirteen (65%) patients were IDU. The tricuspid valve was the primary valve involved (8/18, 44%), and C albicans was the most frequently isolated organism (8, 36%). Echinocandin was the most common treatment strategy (8, 40%). Only three (15%) patients underwent valve replacement during hospitalisation. There were no in-hospital fatalities, and 5 (25%) patients died at one year; all were IDU (39% to 0%, p = .11). Conclusion CIE is a rare infectious disease seen more commonly in the IDU population. Cardiac surgery was rarely performed, and long-term mortality was 25%. Additional data are needed to identify ideal management strategies in this population.

Background People who inject drugs (PWID) are at increased risk of deleterious sequelae due to infective endocarditis (IE). A standardized, hospital-wide drug use–associated infection protocol targeting medication safety, pain management, and limiting external risk factors was implemented at an academic medical center to improve outcomes in PWID with IE. Methods A quasi-experimental study included patients with active injection drug use and definite IE from January 2013 to July 2017 (preintervention group) and from September 2017 to January 2019 (intervention group). The primary outcome of interest was the 90-day all-cause readmission rate. Secondary outcomes included infection-related readmission rates, in-hospital and all-cause mortality rates, and the frequency of patients leaving against medical advice. Results A total of 168 patients were included, in the 100 preintervention and 68 in the intervention group. Patients in the intervention group had reduced odds of 90-day all-cause readmission (adjusted odds ratio, 0.2; 95% confidence interval, 0.08–0.6) after adjustment for confounding variables. The 12-month all-cause mortality rate was also significantly reduced in the intervention group (adjusted odds ratio, 0.25; 95% confidence interval, .07–.89). The intervention group had a higher proportion of patients leaving against medical advice (6% for the preintervention group vs 35% for the intervention group, P Conclusions A drug use–associated infection protocol demonstrated reduced 90-day all-cause readmission and 12-month all-cause mortality rates in PWID with IE. This study highlights the importance of standardized care processes for improving care in this specialized patient population.

Antibiotic-resistant Gram-negative bacteria have been associated with substantial morbidity and mortality and have limited treatment options available. Omadacycline (OMC) is an aminomethylcycline antibiotic that has been shown to exhibit broad in vitro activity against antibiotic-resistant Gram-negative bacteria. Given the lack of real-world data, the primary objective of our report was to describe early experience with OMC for the treatment of resistant Gram-negative infections.This was a real-world, multicenter, observational cases series/pilot study conducted in the USA. Inclusion criteria included any adult patient aged ≥ 18 years who received OMC for ≥ 72 h either in the inpatient and/or outpatient setting. Clinical success was defined as a composite of 90-day survival from initiation of OMC, lack of alteration in treatment/addition of other antibiotic due to concerns of OMC failure, and lack of microbiologic recurrence within 30 days from the end of therapy.Oral OMC was used in nine cases primarily for multidrug-resistant (MDR)/extensively drug-resistant (XDR) Gram-negative bacterial infections (55.6% XDR and/or carbapenem-resistant Acinetobacter baumannii [CRAB]). The majority of infections were of bone/joint (55.6%) origin, followed by intra-abdominal (33.3%) origin. Clinical success occurred in 66.7% of cases, with 80.0% success each in infections of bone/joint origin or those caused by CRAB. One patient experienced an adverse effect that was not treatment limiting while on therapy (gastrointestinal).The use of oral OMC in MDR/XDR Gram-negative infections exhibited a relatively high success rate with minimal adverse effects. Real-world studies with larger case numbers are needed to confirm our initial findings.

Background Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). Methods We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan–Meir analysis to assess the time to nephrotoxicity between the 2 groups. Results We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560–6.993). Results of the stratified Kaplan–Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). Conclusions Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Background Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. Methods Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. Results Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001). Conclusions No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.

The objective of this study was to quantify incidence and determine predictors of Gram-negative bacilli (GNB) in people who inject drugs (PWID) with injection-drug use (IDU)-related infections. The investigation was a retrospective cohort of hospitalized PWID from January 2017 to December 2019. Inclusion criteria were age of ≥18 years, active IDU, treated IDU-attributable infection, and organism growth from microbiology cultures. Infection types included infective endocarditis (IE), acute bacterial skin/skin structure infection (ABSSSI), osteoarticular infection (OAI), and other bloodstream infections (BSI). Primary outcome was GNB identification from microbiologic culture; descriptive statistics were used to describe the cohort. Multivariable regression was used to identify variables associated with GNB infection. A total of 230 PWID were included, 65 (28%) with GNB infections and 165 (72%) with Gram-positive infections. The median (interquartile range [IQR]) population age was 38 (31 to 45) years. Most patients were women (56%); 37% had no insurance. Infection types were as follows: IE, 41%; ABSSSI, 37%; OAI, 20%; and other BSI, 2%. A total of 278 organisms were isolated from 230 patients. The most common organisms were methicillin-resistant Staphylococcus aureus (43%), Streptococcus spp. (19%), methicillin-susceptible S. aureus (17%), and Serratia marcescens (8%); 10% of infections were mixed GNB and Gram-positive infections. A total of 80% of patients received empirical Pseudomonas aeruginosa coverage; only 7% had P. aeruginosa infections. In multivariable regression, age of >50 years (adjusted odds ratio [adjOR], 2.9; 95% confidence interval [CI], 1.2 to 7.2), prior hospitalization within 90 days (adjOR, 2.2; 95% CI, 1.2 to 4.3), and OAI (adjOR, 3.2; 95% CI, 1.5 to 6.6) were associated with GNB infection. GNB in PWID with IDU-attributable infections were more frequently observed in recently hospitalized, older patients with OAI. The majority of patients received empirical antipseudomonal antibiotic coverage, but P. aeruginosa was infrequent. PWID are a potential population to target improved empirical antibiotic use.

BackgroundCeftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown.MethodsA retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality.ResultsA total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31–5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03–0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4.ConclusionsThese data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.

STUDY OBJECTIVE Ceftarolinefosamil is a cephalosporin with broad clinical utility; however, limited data suggest that prolonged ceftaroline exposure may be associated with neutropenia. The objective was to determine drug and patient factors associated with neutropenia in patients receiving ceftaroline or ceftriaxone for deep-seated infections. DESIGN Retrospective, ratio-matched cohort study. SETTING Four acute-care hospitals within an urban health care system. PATIENTS A total of 176 hospitalized adults who received definitive ceftaroline (44 patients) or ceftriaxone (132 patients) therapy for at least 7 days between January 2013 and April 2017 for any of the following indications: bone and joint infections (BJI), infective endocarditis (IE), or bloodstream infections (BSI). MEASUREMENTS AND MAIN RESULTS The primary outcome was development of neutropenia while receiving cephalosporin therapy, defined as an absolute neutrophil count (ANC)

Background We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). Methods This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). Results Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081–0.941). Conclusions Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs.

Background PLWHA commonly suffer from chronic pain that is often treated with opioids, leading to subsequent opiate use disorders. As the majority of Americans live in close proximity to a pharmacy, community pharmacists are well equipped to interact with PLWHA. Few data quantify the needs of PLWHA with OUD, or how they utilize community pharmacists. Objectives To characterize the perceptions of Persons Living with HIV/AIDS (PLWHA) and using opioid medications on the interaction with pharmacists. Methods For this study, a qualitative approach was used. A key purpose of interviews is to encourage and inspire the subject to share a significant event of his/her life with the interviewer. Recruitment for face-to-face interviews with PLWHA continued until saturation was achieved. The Theory of Planned Behavior was used to assess the findings from this study. Sixteen interviews were transcribed verbatim and content analysis was performed by two researchers using Dedoose®, a qualitative software. Codes were grouped based on similarities into categories that facilitated the emergence of themes. Results Content analysis revealed two major themes. The first theme presents the subjects' beliefs and opinions about pharmacists' interactions when picking up their opioid prescriptions. Several subjects described encounters with the pharmacists that facilitated a trustful relationship. In the second theme, the analysis showed that the relationship with community pharmacists could be improved by having a more in-depth counseling about opioid medication and abuse. Conclusions These data highlight how PLWHA would like to interact with pharmacists when picking up opioid prescriptions. These results depicted how some subjects are using the pharmacists as a vital resource for medication information. These findings also demonstrated how for some subjects a more detailed counseling session when they receive opioid medications could be crucial in changing their behavior. Thus, community pharmacists are well positioned to reduce the usage of opioid medications and change PLWHA behavior and attitudes toward opioid prescriptions.

Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen for Mycobacterium abscessus. The majority of infections were of pulmonary origin (7/12; 58.3%). The median (interquartile range) duration of OMC was 6.2 (4.2–11.0) months. Clinical success occurred in 9/12 (75.0%) patients. Three patients experienced a possible adverse effect while on therapy.

The opioid epidemic has had a significant, negative impact in the United States, and people living with HIV/AIDS (PLWHA) represent a vulnerable sub-population that is at risk for negative sequela from prolonged opioid use or opioid use disorder (OUD). PLWHA are known to suffer from HIV-related pain and are commonly treated with opioids, leading to subsequent addictive disorders. PLWHA and OUD are at an increased risk for attrition in the HIV care continuum, including suboptimal HIV laboratory testing, delayed entry into HIV care, and initiation or adherence to antiretroviral therapy. Barriers to OUD treatment, such as medication-assisted therapy, are also apparent for PLWHA with OUD, particularly those living in rural areas. Additionally, PLWHA and OUD are at a high risk for serious drug–drug interactions through antiretroviral-opioid metabolic pathway-related inhibition/induction, or via the human ether-a-go-go-related gene potassium ion channel pathways. HIV-associated neurocognitive disorders can also be potentiated by the off-target inflammatory effects of opioid use. PLWHA and OUD might require more intensive, individualized protocols to sustain treatment for the underlying opioid addiction, as well as to provide proactive social support to aid in improving patient outcomes. Advancements in the understanding and management of PLWHA and OUD are needed to improve patient care. This review describes the effects of prescription and non-prescription opioid use in PLWHA.

Objectives: Pharmacists play a vital role in serving patients during the ongoing nationwide opioid epidemic, and so it is also critical to educate the next generation of pharmacists on opioids and opioid use disorder (OUD). The primary objective of this study was to quantitatively characterize student perceptions of opioid use and the stigma associated with OUD. Secondary aims were to determine whether differences in perceptions exist based upon the student&rsquo, s year in the Doctor of Pharmacy program or employment in a community pharmacy. Methods: First-, second-, third-, and fourth-year student pharmacists voluntarily completed an electronic survey regarding perceptions of opioid use and stigma associated with OUD. Results: Of the 9 survey items, students were most uncomfortable referring patients to community resources for addiction support and/or treatment (25.3% comfortable or very comfortable). Students working in a community pharmacy were significantly more comfortable talking to patients attempting to refill opioids early and providing opioid counseling as compared to their peers not working in community pharmacy. Fourth-year students reported a higher level of comfort talking to a patient attempting to refill an opioid prescription early, counseling a patient on an opioid prescription, and providing information about alternatives to opioids. Third-year students responded most favorably to the items regarding how well the curriculum has prepared them to interact with patients taking opioids and those with OUD. Conclusions: These findings reveal that students are comfortable counseling on opioids and discussing alternative options. Differences in perceptions were observed based upon the student&rsquo, s year in the program and whether or not they were employed in a community pharmacy setting.

Purpose of Review The looming threat of antimicrobial resistance requires robust stewardship and new developments in infectious diseases pharmacotherapy. This review discusses the pertinent spectrum and clinical data of lefamulin (Xenleta®), with a focus on potential real-world use. Recent Findings Lefamulin is a novel pleuromutilin antibiotic that obtained Food and Drug Administration labeling for community-acquired bacterial pneumonia (CABP) in 2019. Lefamulin is available in both intravenous and oral formulations, and it inhibits bacterial protein synthesis inhibition through interactive binding to unique sites of the peptidyl transferase center of the 50s bacterial ribosome subunit. Resistance, including cross-resistance with other antibiotics, is infrequent. Lefamulin demonstrates activity against most Gram-positive pathogens and other organisms commonly associated with CABP, i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae. Lefamulin may also be an option for serious public health threats like methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and multi-drug-resistant organisms associated with sexually transmitted infections, e.g., Neisseria gonorrhoeae, Mycoplasma genitalium. Lefamulin lacks activity against Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacterales, most anaerobes, and E. faecalis. In Phase III trials, lefamulin monotherapy was non-inferior to moxifloxacin with or without linezolid for CABP. Summary Lefamulin is a well-tolerated agent with a unique mechanism, availability in both IV and PO formulations, and it has been rigorously studied for safety and efficacy for CABP.

Background Valve surgery in tricuspid valve infective endocarditis (TVIE) is controversial in people who inject drugs (PWID) due to perceived risks of reinfection because of recidivism. The study objective was to compare outcomes of percutaneous mechanical aspiration (PMA) using the Penumbra Indigo system to valve surgery in PWID with TVIE. Methods Retrospective cohort of adult PWID hospitalized with definite TVIE and received PMA or valve surgery from January 2014 to April 2019. Primary endpoint was all-cause 12-month mortality; secondary endpoints included in-hospital mortality and all-cause 12-month readmission. Results In total, 85 patients were included: 42 undergoing PMA and 43 undergoing valve surgery. Baseline patient demographics were similar between groups; 62 (73%) patients were women, and the median age was 31 (interquartile range, 27-41) years. Seventy-four (86%) patients had a previous history of infective endocarditis and received long-term antibiotic therapy before surgical intervention; 33 (38%) patients presented with septic shock on admission. The most commonly organism was methicillin-resistant Staphylococcus aureus (n = 32 of 84, 38%). Five (12%) PMA patients died in hospital compared with 1 (2%) patient who received valve surgery (P = .11). All-cause 12-month mortality was 24% and 19% for the PMA and surgery groups, respectively (P = .57). When considering confounders, there was no difference in all-cause 12-month mortality between the PMA and valve surgery groups (adjusted odds ratio, 1.5; 95% confidence interval, 0.48-4.8); no significant differences in secondary outcomes were identified. Conclusions PMA was associated with similar outcomes to valve surgery for management of TVIE in PWID. PMA may be an alternative to valve surgery as a treatment or bridging strategy to surgery while PWID undergo addiction treatment.

Background Sepsis is an important cause of morbidity and mortality in the pregnant patient. Injection drug use in pregnant populations has led to increased cases of bacteremia and infective endocarditis (IE) due to Staphylococcus aureus. We describe all cases of S. aureus bacteremia and IE among admitted pregnant patients at our hospital over a 6-year period. Methods This was a retrospective review of pregnant patients hospitalized with S. aureus bacteremia between April 2013 and November 2019. Maternal in-hospital mortality and fetal in-hospital mortality were the primary outcomes measured; the secondary outcome was the rate of 6-month maternal readmission. Results Twenty-seven patients were included; 15 (56%) had IE. The median (interquartile range [IQR]) age was 29 (25–33) years; 22 (82%) patients had methicillin-resistant S. aureus. Infection onset occurred at a median (IQR) of 29 (23–34) weeks’ gestation. Twenty-three (85%) mothers reported active injection drug use, and 21 (78%) were hepatitis C seropositive. Fifteen (56%) mothers required intensive care unit (ICU) care. Twenty-two (81%) patients delivered 23 babies; of the remaining 5 mothers, 3 (11%) were lost to follow-up and 2 (7%) terminated pregnancy. Sixteen (73%) babies required neonatal ICU care, and 4/25 (16%) infants/fetuses died during hospitalization. One (4%) mother died during hospitalization, and 7/26 (27%) mothers were readmitted to the hospital within 6 months for infectious complications. Conclusions Injection drug use is a modifiable risk factor for S. aureus bacteremia in pregnancy. Fetal outcomes were poor, and mothers were frequently readmitted secondary to infection. Future targeted interventions are needed to curtail injection drug use in this population.

Objective: To assess the efficacy and safety of dalbavancin compared to standard-of-care (SOC) or vancomycin and daptomycin in invasive infections due to suspected or confirmed Gram-positive organisms. Methods: Retrospective cohort of adults who received dalbavancin or SOC on discharge or as an outpatient from 12/2016 to 11/2019. Indications were osteoarticular infection (OAI), infective endocarditis (IE), or other bloodstream infection (BSI). Primary endpoint was 90-day infection-related readmission (IRR); secondary endpoints included time-to-IRR, frequency of adverse drug events (ADEs), and all-cause readmission and mortality. Results: 215 patients were included: 70 (33%) receiving dalbavancin, and 145 (67%) receiving SOC. Indications were OAI (47%), IE (27%), and other BSI (26%). OAI was more common in patients on dalbavancin compared with those receiving SOC (70% vs. 37%, P [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] vs. 13 [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , P=0.021). IRR incidence was 17% for dalbavancin patients and 28% for SOC patients. Dalbavancin use was independently associated with lower IRR (adjusted odds ratio [adjOR], 0.10; 95% confidence interval [CI], 0.04-0.31). There was longer median (IQR) time-to-IRR in the dalbavancin group (43 [30-87] vs. 23 [11 -63] days, P=0.039), but no differences in all-cause readmission or mortality. Treatment-related ADE incidence was 3% and 14% for the dalbavancin and SOC groups, respectively (P=0.013). Infusion reactions (1/2) and catheter-related complications (1/2) were the most common dalbavancin ADEs; catheter-related complications (14/21), nephrotoxicity (3/21), rhabdomyolysis (2/21), and rash (2/21) were the most common SOC ADEs. Conclusions: Dalbavancin use was associated with lower 90-day IRR, a shorter hospital LOS prior to therapy, and longer time-to-IRR compared with SOC.

Objectives Infective endocarditis (IE) with non-HACEK Gram-negative (GN) organisms is rare, but associated with poor outcomes. The purpose of this study was to quantify the microbiology, treatment strategies, and frequency of poor outcomes in patients with non-HACEK GN IE. Materials Retrospective cohort of adults with definite non-HACEK GN IE from 1/11-1/19. The primary endpoint was poor patient outcome, defined as a composite of all-cause death or infection-related readmission within 90-days of index infection. Results 43 patients were included: 51% patients were men, and the median (IQR) age was 40 (31-50) years. Forty patients reported injection drug use. The most common organisms were Pseudomonas aeruginosa (68%) and Serratia marcescens (9%). Seventy-six percent of patients received definitive combination therapy; the most common antibiotics used in combination with a β-lactam were aminoglycosides (50%) and fluoroquinolones (34%). Three patients discontinued combination therapy due to toxicity. Twelve-month, all-cause mortality and readmission was 30% and 54%, respectively. In multivariable logistic regression, variables independently associated with composite poor outcome were receipt of fluoroquinolone-based IE combination therapy and septic shock. Conclusions Long-term mortality and readmission rates were high. Patients who received fluoroquinolone-based IE combination therapy more frequently developed poor outcomes than those who did not.

Background The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac death (SCD) in persons living with HIV (PLWH). Methods A systematic literature search using PubMed and Google Scholar databases was performed using the following search terms: ‘HIV and prolonged QTc’ and ‘managing HIV-patients with prolonged QTc’. References within articles of interest were also evaluated. Results/Discussion PLWH are at an increased risk of having a prolonged QTc interval. Some risk factors for this include the virus itself, concomitant medications, comorbid conditions, addictions and electrolyte disturbances. PLWH who have an increased HIV RNA viral load or decreased CD4+ T-cell count are at further risk for progressing to sudden cardiac death (SCD). Many medications commonly prescribed in the PLWH population, such as antiretrovirals and antimicrobials used in opportunistic infection prophylaxis, have also been shown to promote QTc prolongation through inhibition of human ether-a-go-go potassium channels or through drug metabolism inhibition of other QTc prolonging drugs. Conclusions Due to the high number of risk factors associated with QTc prolongation, clinicians should incorporate baseline and routine ECG monitoring for PLWH to potentially lower the increased risk of SCD in PLWH.