The New Era of Long-Acting Antiretroviral Therapy: When and Why to Make the Switch.

PURPOSE OF REVIEW: Despite the availability of safe and effective oral combination antiretroviral therapy, barriers to maintaining viral suppression remain a challenge to ending the HIV epidemic. Long-acting injectable antiretroviral therapy was developed as an alternative to daily oral therapy. This review summarizes the current literature on the efficacy of long-acting cabotegravir plus rilpivirine for the treatment of HIV-1, reasons to switch to injectable therapy, and barriers to switching. RECENT FINDINGS: Long-acting cabotegravir plus rilpivirine is safe and effective in maintaining HIV-1 virologic suppression. Ideal candidates for switching to long-acting cabotegravir plus rilpivirine are virologically suppressed on oral regimens with good adherence and no history of virologic failure or baseline resistance. Indications to switch to injectable therapy include patient preference, the potential for improved adherence, and avoidance of adverse effects. Implementation research is needed to assess and overcome system barriers. Long-acting cabotegravir plus rilpivirine is a novel alternative to oral antiretrovirals, with the potential to improve adherence and quality of life in people with HIV.

The Five Ds of Outpatient Antibiotic Stewardship for Urinary Tract Infections.

Urinary tract infections (UTI) are one of the most common indications for antibiotic prescriptions in the outpatient setting. Given rising rates of antibiotic resistance among uropathogens, antibiotic stewardship is critically needed to improve outpatient antibiotic use, including in outpatient clinics (primary care and specialty clinics) and emergency departments. Outpatient clinics are in general a neglected practice area in antibiotic stewardship programs, yet most antibiotic use in the United States is in the outpatient setting. This article provides a comprehensive review of antibiotic stewardship strategies for outpatient UTI in the adult population, with a focus on the "five Ds" of stewardship for UTI, including right diagnosis, right drug, right dose, right duration, and de-escalation. Stewardship interventions that have shown success for improving prescribing for outpatient UTI are discussed, including diagnostic stewardship strategies, such as reflex urine cultures, computerized decision support systems, and modified reporting of urine culture results. Among the many challenges to achieving stewardship for UTI in the outpatient setting, some of the most important are diagnostic uncertainty, increasing antibiotic resistance, limitations of guidelines, and time constraints of stewardship personnel and front-line providers. This article presents a stewardship framework, built on current evidence and expert opinion, that clinicians can use to guide their own outpatient management of UTI.

Genome-wide transcription start site mapping of Bradyrhizobium japonicum grown free-living or in symbiosis - a rich resource to identify new transcripts, proteins and to study gene regulation.

BACKGROUND: Differential RNA-sequencing (dRNA-seq) is indispensable for determination of primary transcriptomes. However, using dRNA-seq data to map transcriptional start sites (TSSs) and promoters genome-wide is a bioinformatics challenge. We performed dRNA-seq of Bradyrhizobium japonicum USDA 110, the nitrogen-fixing symbiont of soybean, and developed algorithms to map TSSs and promoters. RESULTS: A specialized machine learning procedure for TSS recognition allowed us to map 15,923 TSSs: 14,360 in free-living bacteria, 4329 in symbiosis with soybean and 2766 in both conditions. Further, we provide proteomic evidence for 4090 proteins, among them 107 proteins corresponding to new genes and 178 proteins with N-termini different from the existing annotation (72 and 109 of them with TSS support, respectively). Guided by proteomics evidence, previously identified TSSs and TSSs experimentally validated here, we assign a score threshold to flag 14 % of the mapped TSSs as a class of lower confidence. However, this class of lower confidence contains valid TSSs of low-abundant transcripts. Moreover, we developed a de novo algorithm to identify promoter motifs upstream of mapped TSSs, which is publicly available, and found motifs mainly used in symbiosis (similar to RpoN-dependent promoters) or under both conditions (similar to RpoD-dependent promoters). Mapped TSSs and putative promoters, proteomic evidence and updated gene annotation were combined into an annotation file. CONCLUSIONS: The genome-wide TSS and promoter maps along with the extended genome annotation of B. japonicum represent a valuable resource for future systems biology studies and for detailed analyses of individual non-coding transcripts and ORFs. Our data will also provide new insights into bacterial gene regulation during the agriculturally important symbiosis between rhizobia and legumes.

Case-based audit and feedback around a decision aid improved antibiotic choice and duration for uncomplicated cystitis in primary care clinics.

OBJECTIVES: The objective of our study was to evaluate the impact of a multifaceted stewardship intervention on adherence to the evidence-based practice guidelines on treatment of uncomplicated cystitis in primary care. We hypothesised that our intervention would increase guideline adherence in terms of antibiotic choice and duration of treatment. DESIGN: A preintervention and postintervention comparison with a contemporaneous control group was performed. During the first two study periods, we obtained baseline data and performed interviews exploring provider prescribing decisions for cystitis at both clinics. During the third period in the intervention clinic only, the intervention included a didactic lecture, a decision algorithm and audit and feedback. We used a difference-in-differences analysis to determine the effects of our intervention on the outcome and guideline adherence to antibiotic choice and duration. SETTING: Two family medicine clinics (one intervention and one control) were included. PARTICIPANTS: All female patients with uncomplicated cystitis attending the study clinics between 2016 and 2019. RESULTS: Our sample included 932 visits representing 812 unique patients with uncomplicated cystitis. The proportion of guideline-adherent antibiotic regimens increased during the intervention period (from 33.2% (95% CI 26.9 to 39.9) to 66.9% (95% CI 58.4 to 74.6) in the intervention site and from 5.3% (95% CI 2.3 to 10.1) to 17.0% (95% CI 9.9 to 26.6) in the control site). The increase in guideline adherence was greater in the intervention site compared with the control site with a difference-in-differences of 22 percentage points, p=0.001. CONCLUSION: A multifaceted intervention increased guideline adherence for antibiotic choice and duration in greater magnitude than similar trends at the control site. Future research is needed to facilitate scale-up and sustainability of case-based audit and feedback interventions in primary care.

Organizational readiness assessment in acute and long-term care has important implications for antibiotic stewardship for asymptomatic bacteriuria.

BACKGROUND: Prior to implementing an antibiotic stewardship intervention for asymptomatic bacteriuria (ASB), we assessed institutional barriers to change using the Organizational Readiness to Change Assessment. METHODS: Surveys were self-administered on paper in inpatient medicine and long-term care units at 4 Veterans Affairs facilities. Participants included providers, nurses, and pharmacists. The survey included 7 subscales: evidence (perceived strength of evidence) and six context subscales (favorability of organizational context). Responses were scored on a 5-point Likert-type scale. RESULTS: One hundred four surveys were completed (response rate = 69.3%). Overall, the evidence subscale had the highest score; the resources subscale (mean 2.8) was significantly lower than other subscales (P < .001). Scores for budget and staffing resources were lower than scores for training and facility resources (P < .001 for both). Pharmacists had lower scores than providers for the staff culture subscale (P = .04). The site with the lowest scores for resources (mean 2.4) also had lower scores for leadership and lower pharmacist effort devoted to stewardship. CONCLUSIONS: Although healthcare professionals endorsed the evidence about nontreatment of ASB, perceived barriers to antibiotic stewardship included inadequate resources and leadership support. These findings provide targets for tailoring the stewardship intervention to maximize success.

Impact of an assay that enables rapid determination of Staphylococcus species and their drug susceptibility on the treatment of patients with positive blood culture results.

OBJECTIVE: To determine whether an earlier determination of staphylococcal species and their antibiotic susceptibility decreases unnecessary antistaphylococcal treatment and/or facilitates earlier appropriate treatment. METHODS: We used the Xpert MRSA/SA BC system (Cepheid) for immediate determination of species and their drug susceptibility in patients whose blood cultures revealed gram-positive cocci in clusters. We compared the treatment of patients whose physicians received early notification of these results (group 1) with the treatment of patients in a historical cohort with delayed reporting after traditional microbiological studies (group 2). Outcomes were analyzed according to whether blood culture was positive for Staphylococcus species other than S. aureus, methicillin-susceptible S. aureus (MSSA), or methicillin-resistant S. aureus (MRSA) and whether the drugs used were appropriate for methicillin-susceptible or methicillin-resistant staphylococci (hereafter referred to as "MSS drug" or "MRS drug" therapy, respectively). RESULTS: There were 44 (76%) of 58 patients with bacteremia due to Staphylococcus species other than S. aureus in group 1 and 58 (55%) of 106 patients with bacteremia due to Staphylococcus species other than S. aureus in group 2 who received no antistaphylococcal antibiotics (P < .01). Five (6%) of 89 patients in group 1 and 31 (25%) of 123 patients in group 2 received 0-168 hours (0-7 days) of MRS drug therapy (P < .01). Among patients with MSSA bacteremia, the mean time to initiation of appropriate therapy was 5.2 hours in group 1 and 49.8 hours in group 2 (P = .007). Excluding patients who received MRS drug therapy for unrelated conditions, the mean duration of treatment was 19.7 hours in group 1 and 80.7 hours in group 2 (P = .003). Six (50%) of the 12 patients in group 1 and 39 (81%) of the 48 patients in group 2 received MRS drug therapy for MSSA bacteremia (P = .025). Time to initiation of therapy for MRSA bacteremia did not differ between groups. CONCLUSIONS: The use of an assay with rapid results reduced the use of antistaphylococcal therapy among patients who did not have S. aureus bacteremia; it also decreased the use of MRS drug therapy and led to earlier appropriate therapy among patients with MSSA bacteremia.