Exploring variations in recommended first-choice therapy for complicated urinary tract infections in males: Insights from outpatient settings across age, race, and ethnicity.

INTRODUCTION: There are known disparities in the treatment of infectious diseases. However, disparities in treatment of complicated urinary tract infections (UTIs) are largely uninvestigated. OBJECTIVES: We characterized UTI treatment among males in Veterans Affairs (VA) outpatient settings by age, race, and ethnicity and identified demographic characteristics predictive of recommended first-choice antibiotic therapy. METHODS: We conducted a national, retrospective cohort study of male VA patients diagnosed with a UTI and dispensed an outpatient antibiotic from January 2010 through December 2020. Recommended first-choice therapy for complicated UTI was defined as use of a recommended first-line antibiotic drug choice regardless of area of involvement (ciprofloxacin, levofloxacin, or sulfamethoxazole/trimethoprim) and a recommended duration of 7 to 10 days of therapy. Multivariable models were used to identify demographic predictors of recommended first-choice therapy (adjusted odds ratio [aOR] > 1). RESULTS: We identified a total of 157,898 males diagnosed and treated for a UTI in the outpatient setting. The average antibiotic duration was 9.4 days (±standard deviation [SD] 4.6), and 47.6% of patients were treated with ciprofloxacin, 25.1% with sulfamethoxazole/trimethoprim, 7.6% with nitrofurantoin, and 6.6% with levofloxacin. Only half of the male patients (50.6%, n = 79,928) were treated with recommended first-choice therapy (first-line drug choice and appropriate duration); 77.6% (n = 122,590) were treated with a recommended antibiotic choice and 65.9% (n = 104,070) with a recommended duration. Age 18-49 years (aOR 1.07, 95% confidence interval [CI] 1.03-1.11) versus age ≥65 years was the only demographic factor predictive of recommended first-choice therapy. CONCLUSIONS: Nearly half of the patients included in this study did not receive recommended first-choice therapies; however, racial and ethnic disparities were not identified. Underutilization of recommended first-choice antibiotic therapy in complicated UTIs continues to be an area of focus for antimicrobial stewardship programs.

Real-world utilization of ceftazidime/avibactam among inpatients in the national Veterans Affairs Healthcare System.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Multidrug-resistant (MDR) infections are challenging to treat due to underlying patient conditions, pathogen characteristics, and high antibiotic resistance rates. As newer antibiotic therapies come to market, limited data exist about their real-world utilization. METHODS: This was a national retrospective cohort study of ceftazidime/avibactam (approved in 2015) utilization among inpatients from the Veterans Affairs (VA) Healthcare System, from 2015 through 2021. Joinpoint regression was used to estimate time trends in utilization. RESULTS: Ceftazidime/avibactam use increased by 52.3% each year (days of therapy per 1,000 bed days; 95% confidence interval, 12.4%-106.4%). We identified 1,048 unique predominantly male (98.3%) and white (66.2%; Black, 27.7%) patients treated with ceftazidime/avibactam, with a mean (SD) age of 71.5 (11.9) years. The most commonly isolated organisms were Pseudomonas aeruginosa (36.3%; carbapenem resistant, 80.6%; MDR, 65.0%) and Klebsiella species (34.1%; carbapenem resistant, 78.4%; extended-spectrum cephalosporin resistant, 90.7%). Common comorbid conditions included hypertension (74.8%), nervous system disorders (60.2%), diabetes mellitus (48.7%), and cancer (45.1%). Median time to ceftazidime/avibactam initiation from admission was 6 days, with a median of 3 changes in therapy before ceftazidime/avibactam initiation and a subsequent median length of inpatient stay of 14 days (median of 8 days of ceftazidime/avibactam therapy). Treatment heterogeneity was high, both before ceftazidime/avibactam initiation (89.6%) and during ceftazidime/avibactam treatment (85.6%), and common concomitant antibiotics included vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). The inpatient mortality rate was 23.6%, and 20.8% of patients had a subsequent admission with ceftazidime/avibactam treatment. CONCLUSION: Utilization of ceftazidime/avibactam increased from 2015 to 2021 in the national VA Healthcare System. Ceftazidime/avibactam was utilized in complex, difficult-to-treat patients, with substantial treatment heterogeneity and variation in the causative organism and culture site.

Nirmatrelvir/Ritonavir Utilization for the Treatment of Non-hospitalized Adults with COVID-19 in the National Veterans Affairs (VA) Healthcare System.

INTRODUCTION: Limited data exist regarding real-world utilization of nirmatrelvir/ritonavir. We identified predictors of nirmatrelvir/ritonavir use among Veterans Affairs (VA) outpatients nationally. METHODS: We conducted a retrospective cohort study among outpatients with coronavirus disease 2019 (COVID-19) who were eligible to receive nirmatrelvir/ritonavir between January and December of 2022, to identify factors associated with nirmatrelvir/ritonavir use (i.e., demographics, medical history, prior medication and healthcare exposures, frailty, and other clinical characteristics) using multivariable logistic regression. RESULTS: We included 309,755 outpatients with COVID-19 who were eligible for nirmatrelvir/ritonavir, of whom 12.2% received nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir uptake increased from 1.1% to 23.2% over the study period. Factors associated with nirmatrelvir/ritonavir receipt included receiving a COVID-19 booster vs. none (adjusted odds ratio [aOR] 2.19 [95% confidence interval [CI] 2.12-2.26]), age ≥ 50 vs. 18-49 years (aORs > 1.5 for all age groups ≥ 50 years), having HIV (aOR 1.36 [1.22-1.51]), being non-frail vs. severely frail (aOR 1.22 [1.13-1.33]), and having rheumatoid arthritis (aOR 1.12 [1.04-1.21). Those with concomitant use of potentially interacting antiarrhythmics (aOR 0.35 [0.28-0.45]), anticoagulants/antiplatelets (aOR 0.42 [0.40-0.45]), and/or psychiatric/sedatives (aOR 0.84 [0.81-0.87]) were less likely to receive nirmatrelvir/ritonavir. CONCLUSIONS: Despite increases over time, overall utilization of nirmatrelvir/ritonavir was low. Predictors of nirmatrelvir/ritonavir utilization were consistent with known risk factors for progression to severe COVID-19, including older age and underlying medical conditions. Unvaccinated and undervaccinated patients and those receiving potentially interacting medications for cardiovascular or mental health conditions (antiarrhythmic, alpha-1 antagonist, anticoagulant/antiplatelet, sedative/hypnotic/psychiatric) were less likely to receive nirmatrelvir/ritonavir. Further education of prescribers and patients about nirmatrelvir/ritonavir treatment guidelines is needed to improve overall uptake and utilization in certain high-risk subpopulations.

Antibiotics on Demand: Advances in Asynchronous Telemedicine Call for Increased Antibiotic Surveillance.

The rapid growth of telehealth services has brought about direct-to-consumer telemedicine platforms, enabling patients to request antibiotics online without a virtual or face-to-face consultation. While telemedicine aims to enhance accessibility, this trend raises significant concerns regarding appropriate antimicrobial use and patient safety. In this viewpoint, we share our first-hand experience with 2 direct-to-consumer platforms, where we intentionally sought inappropriate antibiotic prescriptions for nonspecific symptoms strongly indicative of a viral upper respiratory infection. Despite the lack of clear necessity, requested antibiotic prescriptions were readily transmitted to our local pharmacy following a simple monetary transaction. The effortless acquisition of patient-selected antibiotics online, devoid of personal interactions or consultations, underscores the urgent imperative for intensified antimicrobial stewardship initiatives led by state and national public health organizations in telehealth settings. By augmenting oversight and regulation, we can ensure the responsible and judicious use of antibiotics, safeguard patient well-being, and preserve the efficacy of these vital medications.

Advancements in Novel Live Biotherapeutic Products for Clostridioides difficile Infection Prevention.

The profound impact of the human microbiome on health and disease has captivated the interest of clinical and scientific communities. The human body hosts a vast array of microorganisms collectively forming the human microbiome, which significantly influences various physiological processes and profoundly shapes overall well-being. Notably, the gut stands out as an exceptional reservoir, harboring the most significant concentration of microorganisms, akin to an organ in itself. The gut microbiome's composition and function are influenced by genetics, environment, age, underlying conditions, and antibiotic usage, leading to dysbiosis and pathogenesis, such as Clostridioides difficile infection (CDI). Conventional CDI treatment, involving antibiotics like oral vancomycin and fidaxomicin, fails to address dysbiosis and may further disrupt gut microbial communities. Consequently, emerging therapeutic strategies are focused on targeting dysbiosis and restoring gut microbiota to advance CDI therapeutics. Fecal microbiota transplantation (FMT) has demonstrated remarkable efficacy in treating recurrent CDI by transferring processed stool from a healthy donor to a recipient, restoring gut dysbiosis and enhancing bacterial diversity. Moreover, 2 newer Food and Drug Administration (FDA)-approved live biotherapeutic products (LBP), namely, Fecal Microbiota Live-JSLM and Fecal Microbiota Spores Live-BRPK, have shown promise in preventing CDI recurrence. This review explores the role of the gut microbiota in preventing and treating CDI, with an emphasis on gut-based interventions like FMT and fecal microbiota-based products that hold potential for gut restoration and prevention of CDI recurrence. Understanding the microbiome's impact on CDI prevention and treatment offers valuable insights for advancing future CDI therapeutics.

Decreasing Antibiotic Resistance Trends Nationally in Gram-Negative Bacteria Across United States Veterans Affairs Medical Centers, 2011-2020.

INTRODUCTION: Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate their threat. The objective of this study was to assess antibiotic resistance trends in Gram-negative bacteria. METHODS: The first cultures of Pseudomonas aeruginosa, Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, and Serratia marcescens per hospitalized patient per month collected from 125 Veterans Affairs Medical Centers (VAMCs) between 2011 to 2020 were included. Time trends of resistance phenotypes (carbapenem, fluoroquinolone, extended-spectrum cephalosporin, multi-drug, and difficult-to-treat) were analyzed with Joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals and p values. A 2020 antibiogram of reported antibiotic percent susceptibilities was also created to evaluate resistance rates at the beginning of the COVID-19 pandemic. RESULTS: Among 40 antimicrobial resistance phenotype trends assessed in 494,593 Gram-negative isolates, there were no noted increases; significant decreases were observed in 87.5% (n = 35), including in all P. aeruginosa, Citrobacter, Klebsiella, M. morganii, and S. marcescens phenotypes (p < 0.05). The largest decreases were seen in carbapenem-resistant phenotypes of P. mirabilis, Klebsiella, and M. morganii (AAPCs: - 22.9%, - 20.7%, and - 20.6%, respectively). In 2020, percent susceptibility was over 80% for all organisms tested against aminoglycosides, cefepime, ertapenem, meropenem, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. CONCLUSION: We observed significant decreases in antibiotic resistance for P. aeruginosa and Enterobacterales over the past decade. According to the 2020 antibiogram, in vitro antimicrobial activity was observed for most treatment options. These results may be related to the robust infection control and antimicrobial stewardship programs instituted nationally among VAMCs.

Staphylococcal biofilm: penetration and bioavailability of vancomycin with or without rifampin.

We measured antibiotic penetration and bioavailability in staphylococcus biofilms using simulated humanized concentrations of fluorescent vancomycin plus or minus rifampin. Vancomycin percent recovery across biofilm layers was:upper = 46%, middle = 40%, and lower = 33%. Vancomycin plus rifampin was not significantly different (P = 0.65). Addition of rifampin did not improve vancomycin penetration across biofilm layers.

Student pharmacists delivering academic detailing on adult pneumococcal vaccination to community pharmacists.

BACKGROUND: Academic detailing is an educational outreach approach to disseminate evidence-based information to health care professionals and improve clinical decision making. Pharmacists and physicians are recognized as the most qualified individuals to perform academic detailing; however, trained student pharmacists may also serve as suitable academic detailers. OBJECTIVES: To describe our academic detailing intervention that used trained student pharmacists to disseminate an updated pneumococcal vaccination clinical pathway (i.e., decision-support tool) and education to community pharmacists in Rhode Island and Massachusetts. METHODS: We updated an academic detailing initiative that included a pneumococcal vaccination clinical pathway and education for community pharmacists in 2021. Two University of Rhode Island (URI) College of Pharmacy pharmacist faculty members trained 6 student pharmacists to perform academic detailing. Student pharmacists visited URI-affiliated community pharmacies throughout Rhode Island and Massachusetts. After each session, each participant received a 6-question anonymous paper survey to assess the effectiveness of the updated pathway and academic detailing session. The survey used a 5-point Likert-type scale. We assessed the percentage agreement with each question. RESULTS: Academic detailing was delivered to 76 community pharmacists from May to August 2021. Most respondents agreed (89.2%, 58/65) that their knowledge of which patient populations met eligibility for the pneumococcal conjugate vaccine or pneumococcal polysaccharide vaccine improved. Respondents were confident they could apply the knowledge gained (93.8%, 61/65) and intended to apply the pathway (93.8%, 61/65) to clinical practice. Most respondents expected vaccination practices to change because of the academic detailing and education materials received (83.6%, 51/61). Almost all respondents (95.4%, 62/65) found the educational materials easy to understand. CONCLUSION: Trained student pharmacists can deliver academic detailing regarding adult pneumococcal vaccination to community pharmacists. Enlisting the help of student pharmacists may be a sustainable approach to academic detailing and provides students with valuable opportunities to practice delivering educational outreach to community pharmacists.

Antibiotic Prescribing in Outpatient Settings: Rural Patients Are More Likely to Receive Fluoroquinolones and Longer Antibiotic Courses.

Suboptimal antibiotic prescribing may be more common in patients living in rural versus urban areas due to various factors such as decreased access to care and diagnostic testing equipment. Prior work demonstrated a rural health disparity of overprescribing antibiotics and longer durations of antibiotic therapy in the United States; however, large-scale evaluations are limited. We evaluated the association of rural residence with suboptimal outpatient antibiotic use in the national Veterans Affairs (VA) system. Outpatient antibiotic dispensing was assessed for the veterans diagnosed with an upper respiratory tract infection (URI), pneumonia (PNA), urinary tract infection (UTI), or skin and soft tissue infection (SSTI) in 2010-2020. Rural-urban status was determined using rural-urban commuting area codes. Suboptimal antibiotic use was defined as (1) outpatient fluoroquinolone dispensing and (2) longer antibiotic courses (>ten days). Geographic variation in suboptimal antibiotic use was mapped. Time trends in suboptimal antibiotic use were assessed with Joinpoint regression. While controlling for confounding, the association of rurality and suboptimal antibiotic use was assessed with generalized linear mixed models with a binary distribution and logit link, accounting for clustering by region and year. Of the 1,405,642 veterans diagnosed with a URI, PNA, UTI, or SSTI and dispensed an outpatient antibiotic, 22.8% were rural-residing. In 2010-2020, in the rural- and urban-residing veterans, the proportion of dispensed fluoroquinolones declined by 9.9% and 10.6% per year, respectively. The rural-residing veterans were more likely to be prescribed fluoroquinolones (19.0% vs. 17.5%; adjusted odds ratio (aOR), 1.03; 95% confidence interval (CI), 1.02-1.04) and longer antibiotic courses (53.8% vs. 48.5%; aOR, 1.19, 95% CI, 1.18-1.20) than the urban-residing veterans. Among a large national cohort of veterans diagnosed with URIs, PNA, UTIs, and SSTIs, fluoroquinolone use and longer antibiotic courses were disproportionally more common among rural- as compared to urban-residing veterans. Outpatient antibiotic prescribing must be improved, particularly for rural-residing patients. There are many possible solutions, of which antibiotic stewardship interventions are but one.

Penicillin-Binding Proteins and Alternative Dual-Beta-Lactam Combinations for Serious Enterococcus faecalis Infections with Elevated Penicillin MICs.

Ampicillin-ceftriaxone has become a first-line therapy for Enterococcus faecalis endocarditis. We characterized the penicillin-binding protein (PBP) profiles of various E. faecalis strains and tested for synergy to better inform beta-lactam options for the treatment of E. faecalis infections. We assessed the affinity of PBP2B from elevated-MIC strain E. faecalis LS4828 compared to type strain JH2-2 using the fluorescent beta-lactam Bocillin FL. We also characterized pbp4 and pbpA structures and PBP4 and PBP2B expression and used deletion and complementation studies to assess the impact of PBP2B on the levels of resistance. We tested penicillin-susceptible and -resistant E. faecalis isolates against ceftriaxone or ceftaroline combinations with other beta-lactams in 24-h time-kill studies. Two penicillin-susceptible strains (JH2-2 and L2052) had identical pbp sequences and similar PBP expression levels. One reduced-penicillin-susceptibility strain (L2068) had pbp sequences identical to those of the susceptible strains but expressed more PBP4. The second decreased-penicillin-susceptibility strain (LS4828) had amino acid substitutions in both PBP4 and PBP2B and expressed increased quantities of both proteins. PBP2B did not appear to contribute significantly to the elevated beta-lactam MICs. No synergy was demonstrable against the strains with both mutated PBPs and increased expression (L2068 and LS4828). Meropenem plus ceftriaxone or ertapenem plus ceftriaxone demonstrated the most consistent synergistic activity. PBP2B of strain LS4828 does not contribute significantly to reduced penicillin susceptibility. Neither the MIC nor the level of PBP expression correlated directly with the identified synergistic combinations when tested at static subinhibitory concentrations.

Trends in Stenotrophomonas maltophilia antibiotic resistance rates in the United States Veterans Affairs Health System.

Introduction. Stenotrophomonas maltophilia is an important multidrug-resistant Gram-negative pathogen. While largely a hospital-acquired pathogen, there have been increasing reports of the pathogen in the community.Gap Statement. Trends in S. maltophilia prevalence and resistance rates that include outpatient isolates are unknown.Aim. We described recent trends in prevalence and resistance of S. maltophilia in the national Veterans Affairs (VA) Healthcare system.Methodology. The study identified positive S. maltophilia clinical cultures among VA adult patients from 2010 to 2018 across all VA hospitals, long-term care facilities/units, and outpatient settings. Annual S. maltophilia resistance rates were evaluated. Multidrug resistant (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95 % confidence intervals using Joinpoint software.Results. Over the 9 year study period, 18 285 S. maltophilia cultures were identified (57 % hospital, 3 % long-term care, 40 % outpatient). The most common source of S. maltophilia cultures were respiratory cultures (34.6 %) followed by urine cultures (30.4 %). In VA hospitals and long-term care facilities, the number of S. maltophilia cultures decreased significantly (by 5.4% and 8.4 % per year respectively). Overall, 3.1 % of isolates were MDR which remained stable over the study period. Resistance to other antibiotics assessed mostly remained stable, except SMX/TMP resistance decreased significantly by 8.5 % (2010, 15 %; 2018, 6 %) per year in VA hospitals.Conclusion. While previous work has recognized S. maltophilia as primarily a nosocomial pathogen, the present study found that 40 % of cultures collected were among outpatients. Between 2010 and 2018, the number of positive S. maltophilia cultures decreased significantly in the national VA Healthcare System. Resistance to SMX/TMP decreased over the study period in VA hospitals and now more closely reflects previously reported resistance rates worldwide (0-10 %). MDR S. maltophilia remained stable and low in the national VA Healthcare System.

Path of least recurrence: A systematic review and meta-analysis of fidaxomicin versus vancomycin for Clostridioides difficile infection.

STUDY OBJECTIVE: Current Clostridioides difficile infection (CDI) treatment guidelines recommend either fidaxomicin or vancomycin as first-line therapy for initial and recurrent CDI. The objective of this study was to compare recurrence rates of fidaxomicin and vancomycin for the treatment of CDI in clinically relevant and real-world subgroups via systematic review and meta-analysis. DESIGN & DATA SOURCES: A systematic literature review was performed by searching PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to September 1, 2021, for randomized and observational studies comparing vancomycin and fidaxomicin for CDI treatment in adults. The meta-analysis was performed with Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) using a random-effects model. The primary end point was CDI recurrence after treatment with fidaxomicin or vancomycin. Subgroup analyses were conducted. PATIENTS, INTERVENTION, MEASUREMENTS & MAIN RESULTS: The literature search identified six randomized controlled trials and eight observational trials, with a total of 3944 patients (fidaxomicin 32%; vancomycin 68%) included in the meta-analysis. The mean age of study patients ranged from 46 to 75 years. The CDI recurrence rate was 22.4% (fidaxomicin 16.1%, vancomycin 25.4%). Compared to vancomycin, treatment with fidaxomicin was associated with a 31% reduction in the risk of recurrence (risk ratio 0.69; 95% confidence interval: 0.52-0.91, I2  = 62%). This reduction in recurrence risk was also seen in subgroup analyses for patients with initial CDI, first recurrent CDI, non-severe and severe CDI, and in both inpatient and outpatient settings. CONCLUSION: Our systematic review and meta-analysis found fidaxomicin was consistently associated with a lower risk of CDI recurrence than vancomycin. These results confirm CDI guideline recommendations and indicate that fidaxomicin may be preferred over vancomycin to minimize CDI recurrence across multiple clinical scenarios, although further studies are warranted.

Meropenem plus Ceftaroline Is Active against Enterococcus faecalis in an In Vitro Pharmacodynamic Model Using Humanized Dosing Simulations.

The standard of care for serious Enterococcus faecalis infections is ampicillin plus ceftriaxone. Ampicillin's inconvenient dosing schedule, drug instability, allergy potential, along with ceftriaxone's high risk for Clostridioides difficile infection and its promotion of vancomycin-resistant enterococci (VRE), led our team to explore alternative options. This work aimed to understand the role of carbapenems in combination with cephalosporins in these infections. We selected two ampicillin and penicillin susceptible E. faecalis strains (AMP-MIC 0.5-2 µg/mL; PCN-MIC 2 µg/mL) and simulated human therapeutic dosing regimens in a 48-h in vitro pharmacodynamic model (IVPD) with ampicillin (2g q4h), ertapenem (1g q24h), meropenem (2g q8h), ceftriaxone (2g q12h), and ceftaroline (600 mg q8h). As expected, ampicillin plus ceftriaxone demonstrated enhanced activity compared with ampicillin monotherapy with no MIC increases in either isolate. Meropenem and ceftaroline demonstrated significant kill against both isolates, with no regrowth or MIC increases occurring. Meropenem plus ceftriaxone also demonstrated significant kill, and while no MIC increases were identified for meropenem, there was minor regrowth and larger standard deviations. Ertapenem combined with either ceftriaxone or ceftaroline enhanced activity at 24 h, but at 48 h, regrowth occurred, and ertapenem MIC increases were noted. Meropenem-based combination therapy against E. faecalis may provide clinicians with another regimen to treat severe E. faecalis infections. Meropenem plus ceftaroline was as active as the standard of care treatment (ampicillin plus ceftriaxone) and may serve as an alternative for serious E. faecalis infections. Further studies are warranted to determine the clinical efficacy.

It's about the patients: Practical antibiotic stewardship in outpatient settings in the United States.

Antibiotic-resistant pathogens cause over 35,000 preventable deaths in the United States every year, and multiple strategies could decrease morbidity and mortality. As antibiotic stewardship requirements are being deployed for the outpatient setting, community providers are facing systematic challenges in implementing stewardship programs. Given that the vast majority of antibiotics are prescribed in the outpatient setting, there are endless opportunities to make a smart and informed choice when prescribing and to move the needle on antibiotic stewardship. Antibiotic stewardship in the community, or "smart prescribing" as we suggest, should factor in antibiotic efficacy, safety, local resistance rates, and overall cost, in addition to patient-specific factors and disease presentation, to arrive at an appropriate therapy. Here, we discuss some of the challenges, such as patient/parent pressure to prescribe, lack of data or resources for implementation, and a disconnect between guidelines and real-world practice, among others. We have assembled an easy-to-use best practice guide for providers in the outpatient setting who lack the time or resources to develop a plan or consult lengthy guidelines. We provide specific suggestions for antibiotic prescribing that align real-world clinical practice with best practices for antibiotic stewardship for two of the most common bacterial infections seen in the outpatient setting: community-acquired pneumonia and skin and soft-tissue infection. In addition, we discuss many ways that community providers, payors, and regulatory bodies can make antibiotic stewardship easier to implement and more streamlined in the outpatient setting.

Assessing Rates of Co-Resistance and Patient Outcomes in Multidrug-Resistant Pseudomonas aeruginosa.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with poor patient outcomes due to complex co-resistance patterns. We described common co-resistance patterns, clinical characteristics, and associated outcomes in patients admitted with an MDR P. aeruginosa. This national, multicenter, retrospective cohort study within the Veterans Affairs included adults hospitalized with a MDR P. aeruginosa infection (January 2015-December 2020) per Centers for Disease Control definition. Clinical outcomes were compared among those with differing MDR P. aeruginosa co-resistance: resistant to carbapenems and extended-spectrum cephalosporins and piperacillin-tazobactam (CARB/ESC/PT) versus without CARB/ESC/PT resistance; resistant to carbapenems and extended-spectrum cephalosporins and fluoroquinolone (CARB/ESC/FQ) versus without CARB/ESC/FQ resistance. We included 3,763 hospitalized patients. Co-resistance to CARB/ESC/PT was observed in 42.7%, and to CARB/ESC/FQ in 40.7%. The lowest co-resistance rates were observed with ceftolozane-tazobactam (6.2%, n = 6/97; 12.5%, n = 10/80, respectively) and ceftazidime-avibactam (5.2%, n = 5/97; 12.5%, n = 10/80, respectively). Overall, 14.2% of patients died during hospitalization, 59.7% had an extended length of stay, and 14.9% had reinfection with hospitalization. Outcomes were similar between patients with MDR P. aeruginosa strains with and without co-resistance to CARB/ESC/PT and CARB/ESC/FQ. Among a national cohort of patients hospitalized with MDR P. aeruginosa infections, co-resistance to three classes of standard of care antibiotics, such as carbapenem, extended-spectrum cephalosporins, and piperacillin-tazobactam or fluoroquinolones, exceeded 40% in our study population, posing great concerns for selecting appropriate empirical therapy. Clinical outcomes were poor for all patients, regardless of different co-resistance patterns. New treatment options are needed for hospitalized patients with suspected or confirmed MDR P. aeruginosa infections. IMPORTANCE We studied antibiotic co-resistance patterns in a national group of hospitalized patients with infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa, a type of bacteria that resists treatment to at least three classes of antibiotics. Co-resistance to antibiotic classes most typically used for treatment was common, which makes selecting appropriate antibiotics to successfully treat the infections difficult. Outcomes, including death, were poor for all patients in our study, regardless of the different patterns of co-resistance to common antibiotic classes. New antibiotics are needed to help treat hospitalized patients with MDR P. aeruginosa infections.

Antimicrobial Prescribing in the Telehealth Setting: Framework for Stewardship During a Period of Rapid Acceleration Within Primary Care.

Antibiotic resistance is a global public health threat. The use of telehealth in primary care presents unique barriers to antimicrobial stewardship, including limited physical examination and changes to the patient-provider relationship. Since the coronavirus disease 2019 (COVID-19) pandemic, there is a need to identify novel antimicrobial stewardship strategies with an explosion in the use of telehealth within primary care. Our review proposes a tailored, sustainable approach to antimicrobial prescribing in the telehealth setting based on the Centers for Disease Control and Prevention's Core Elements of Outpatient Antibiotic Stewardship: commitment, action for policy and practice; tracking and reporting; and education and expertise. The rapid growth of telehealth for all types of primary care visits (not just antibiotic use) is outpacing knowledge associated with strategies for antimicrobial stewardship. Improving antibiotic use within primary care settings is critical as telehealth will remain a priority whether the COVID-19 pandemic recedes, particularly within patient populations with limited access to healthcare.

Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance.

The progressive increase in antibiotic resistance in recent decades calls for urgent development of new antibiotics and antibiotic stewardship programs to help select appropriate treatments with the goal of minimising further emergence of resistance and to optimise clinical outcomes. Three new tetracycline-class antibiotics, eravacycline, omadacycline, and tigecycline, have been approved within the past 15 years, and represent a new era in the use of tetracyclines. These drugs overcome the two main mechanisms of acquired tetracycline-class resistance and exhibit a broad spectrum of in vitro activity against gram-positive, gram-negative, anaerobic, and atypical pathogens, including many drug-resistant strains. We provide an overview of the three generations of tetracycline-class drugs, focussing on the efficacy, safety, and clinical utility of these three new third-generation tetracycline-class drugs. We also consider various scenarios of unmet clinical needs where patients might benefit from re-engagement with tetracycline-class antibiotics including outpatient treatment options, patients with known ß-lactam antibiotic allergy, reducing the risk of Clostridioides difficile infection, and their potential as monotherapy in polymicrobial infections while minimising the risk of any potential drug-drug interaction. KEY MESSAGESThe long-standing safety profile and broad spectrum of activity of tetracycline-class antibiotics made them a popular choice for treatment of various bacterial infections; unfortunately, antimicrobial resistance has limited the utility of the early-generation tetracycline agents.The latest generation of tetracycline-class antibiotics, including eravacycline, tigecycline, and omadacycline, overcomes the most common acquired tetracycline resistance mechanisms.Based on in vitro characteristics and clinical data, these newer tetracycline agents provide an effective antibiotic option in the treatment of approved indications in patients with unmet clinical needs - including patients with severe penicillin allergy, with renal or hepatic insufficiency, recent Clostridioides difficile infection, or polymicrobial infections, and those at risk of drug-drug interactions.

The Comparative Effectiveness of Ceftolozane/Tazobactam versus Aminoglycoside- or Polymyxin-Based Regimens in Multi-Drug-Resistant Pseudomonas aeruginosa Infections.

Pseudomonas aeruginosa infections are challenging to treat due to multi-drug resistance (MDR) and the complexity of the patients affected by these serious infections. As new antibiotic therapies come on the market, limited data exist about the effectiveness of such treatments in clinical practice. In this comparative effectiveness study of ceftolozane/tazobactam versus aminoglycoside- or polymyxin-based therapies among hospitalized patients with positive MDR P. aeruginosa cultures, we identified 57 patients treated with ceftolozane/tazobactam compared with 155 patients treated with aminoglycoside- or polymyxin-based regimens. Patients treated with ceftolozane/tazobactam were younger (mean age 67.5 vs. 71.1, p = 0.03) and had a higher comorbidity burden prior to hospitalization (median Charlson 5 vs. 3, p = 0.01) as well as higher rates of spinal cord injury (38.6% vs. 21.9%, p = 0.02) and P. aeruginosa-positive bone/joint cultures (12.3% vs. 0.7%, p < 0.0001). Inpatient mortality was significantly lower in the ceftolozane/tazobactam group compared with aminoglycosides or polymyxins (15.8% vs. 27.7%, adjusted odds ratio 0.39, 95% confidence interval 0.16−0.93). There were no significant differences observed for the other outcomes assessed. In hospitalized patients with MDR P. aeruginosa, inpatient mortality was 61% lower among patients treated with ceftolozane/tazobactam compared to those treated with aminoglycoside- or polymyxin-based regimens.