Pharmacist-Driven Rapid Initiation of Antiretroviral Therapy Decreases Time to Viral Suppression in People With HIV.

Background: Rapid initiation of antiretroviral therapy (rapid ART) improves clinical outcomes in people with HIV and is endorsed by clinical guidelines. However, logistical challenges limit widespread implementation. We describe an innovative rapid ART model led by pharmacists and its impact on clinical outcomes, including time to viral suppression (TVS). Methods: On 1 January 2019, we implemented Pharmacist-Driven Rapid ART (PHARM-D RAPID ART), including rapid ART initiation by pharmacists. Our retrospective cohort study compared TVS, using a Cox proportional hazards model, and clinical outcomes among individuals with a new HIV diagnosis before (1 January 2017 to 31 December 2017) and after (1 January 2019 to 31 December 2019) implementation. Results: A total of 108 individuals were included. TVS was significantly shorter (P < .001) for the PHARM-D RAPID ART group (n = 51) compared with the preimplementation group (n = 57) (median: 30 days and 66 days, respectively). Those in the PHARM-D RAPID ART group were significantly more likely to achieve VS at any given time during the study period (adjusted hazard ratio: 3.47 [95% confidence interval, 2.25-5.33]). A total of 94.1% (48/51) of patients in the PHARM-D RAPID ART group were retained in care at 1 year. With a median follow-up of 2.4 years in the PHARM-D RAPID ART group, 98% remained suppressed at last recorded viral load. Conclusions: A pharmacist-driven model for rapid ART delivery decreases TVS with high rates of retention in care and durable VS. This model could improve clinical outcomes and increase program feasibility and sustainability.

Statewide Longitudinal Trends in Transmitted HIV-1 Drug Resistance in Rhode Island, USA.

BACKGROUND: HIV-1 transmitted drug resistance (TDR) remains a global challenge that can impact care, yet its comprehensive assessment is limited and heterogenous. We longitudinally characterized statewide TDR in Rhode Island. METHODS: Demographic and clinical data from treatment-naïve individuals were linked to protease, reverse transcriptase, and integrase sequences routinely obtained over 2004-2020. TDR extent, trends, impact on first-line regimens, and association with transmission networks were assessed using the Stanford Database, Mann-Kendall statistic, and phylogenetic tools. RESULTS: In 1123 individuals, TDR to any antiretroviral increased from 8% (2004) to 26% (2020), driven by non-nucleotide reverse transcriptase inhibitor (NNRTI; 5%-18%) and, to a lesser extent, nucleotide reverse transcriptase inhibitor (NRTI; 2%-8%) TDR. Dual- and triple-class TDR rates were low, and major integrase strand transfer inhibitor resistance was absent. Predicted intermediate to high resistance was in 77% of those with TDR, with differential suppression patterns. Among all individuals, 34% were in molecular clusters, some only with members with TDR who shared mutations. Among clustered individuals, people with TDR were more likely in small clusters. CONCLUSIONS: In a unique (statewide) assessment over 2004-2020, TDR increased; this was primarily, but not solely, driven by NNRTIs, impacting antiretroviral regimens. Limited TDR to multiclass regimens and pre-exposure prophylaxis are encouraging; however, surveillance and its integration with molecular epidemiology should continue in order to potentially improve care and prevention interventions.

Elbasvir/grazoprevir administered for 12 weeks via percutaneous endoscopic gastrostomy tube achieves sustained virologic response: A case report and a review of the literature.

Enteral tubes are necessary for certain patients; however, medication absorption can be affected by this route of administration potentially resulting in decreased efficacy. All first-line treatments for Hepatitis C Virus (HCV) infection are only available as tablets and may have decreased absorption if administered via an enteral tube. This report describes the first case of a pegylated interferon and ribavirin treatment-experienced patient who successfully achieved HCV cure after 12 weeks of elbasvir/grazoprevir administered via percutaneous gastrostomy tube. We further review the available pharmacokinetic and clinical literature regarding administration via enteral feeding tubes for all first-line direct-acting antivirals (DAAs). The literature suggests that crushed administration can be considered for DAAs in patients with gastric access. However, caution should be exercised in patients with extragastric enteral tubes and in those with altered gastrointestinal tract anatomy.

Recent Updates to the Advisory Committee On Immunization Practices Recommendations for Pneumococcal and Herpes Zoster Vaccination.

Pneumococcal and herpes zoster - shingles - vaccination prevent a great deal of morbidity, particularly in elderly and immunocompromised hosts. Vaccination of children with conjugate pneumococcal vaccine in recent years has greatly reduced illness in older individuals as well. This article will review the historical and current recommendations for pneumococcal and herpes zoster vaccination and the rationale for changes at the level of the CDC's Advisory Committee on Immunization Practices.

Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study.

AIM: To assess the efficacy and safety of hydroxychloroquine with or without azithromycin) in hospitalized adult patients with COVID-19. METHODS: We utilized a hospital based prospective data registry. The primary end point was to assess the impact of hydroxychloroquine with or without azithromycin, on outcome, length of hospitalization, and time to clinical improvement. We utilized treatment effects with inverse-probability-weighting and Cox proportional hazards models. All analyses accounted for age, gender, race, severity on admission, days from symptoms onset and chronic comorbidities. RESULTS: 36 patients received hydroxychloroquine and were age- and sex-matched to 72 patients with COVID-19 who received supportive care. Compared to supportive care, the use of HCQ did not shorten the time to clinical improvement (+0.23 days; 95% CI: -1.8-2.3 days) nor did it shorten the duration of hospital stay (+0.91 days; 95% CI: -1.1-2.9 days). Additionally, HCQ did not decrease the risk of COVID-19 in-hospital death (aHR 1.67; 95% CI: 0.29-9.36). Finally, we observed a slight QTc prolongation from a baseline of 444 ± 26 ms to 464 ± 32 ms (mean±SD) among patients receiving hydroxychloroquine with or without azithromycin. CONCLUSION: This study did not yield benefits from hydroxychloroquine use in patients with COVID-19 and monitoring for adverse events is warranted. Nevertheless, the treatment was safely studied under the guidance of an antimicrobial stewardship program.

Successful Kidney Transplantation in a Recipient Coinfected with Hepatitis C Genotype 2 and HIV from a Donor Infected with Hepatitis C Genotype 1 in the Direct-Acting Antiviral Era.

Despite significant advances in transplantation of HIV-infected individuals, little is known about HIV coinfected patients with hepatitis C virus (HCV) genotypes other than genotype 1, especially when receiving HCV-infected organs with a different genotype. We describe the first case of kidney transplantation in a man coinfected with hepatitis C and HIV in our state. To our knowledge, this is also the first report of an HIV/HCV/HBV tri-infected patient with non-1 (2a) HCV genotype who received an HCV-infected kidney graft with the discordant genotype (1a), to which he converted after transplant. Our case study highlights the following: (1) transplant centers need to monitor wait times for an HCV-infected organ and regularly assess the risk of delaying HCV antiviral treatment for HCV-infected transplant candidates in anticipation of the transplant from an HCV-infected donor; (2) closer monitoring of tacrolimus levels during the early phases of anti-HCV protease inhibitor introduction and discontinuation may be indicated; (3) donor genotype transmission can occur; (4) HIV/HCV coinfected transplant candidates require a holistic approach with emphasis on the cardiovascular risk profile and low threshold for cardiac catheterization as part of their pretransplant evaluation.

The impact of an automated antibiotic stewardship intervention for the management of Staphylococcus aureus bacteraemia utilizing the electronic health record.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) management bundles have been shown to improve performance measures and clinical outcomes. SAB bundles often require direct intervention by infectious diseases (ID) physicians or antibiotic stewardship programme (ASP) members or pharmacists. The purpose of this study was to evaluate an automated, real-time ASP intervention utilizing clinical decision support (CDS) in the electronic health record (EHR) for the management of SAB. METHODS: A retrospective, single-centre quasi-experimental study of hospitalized patients with known SAB was conducted. The intervention was the implementation of a hard-stop best practice advisory (BPA) alert that would prompt physicians to use an electronic order set, on identification of SAB, with management recommendations, including ID consultation. The primary outcome was overall adherence to six institutional ASP SAB bundle elements. Secondary outcomes included both clinical and process outcomes. RESULTS: A total of 227 patients were included, 111 in the pre-intervention and 116 in the post-intervention period. Completion of all six bundle elements improved by 27.2% in the post-intervention group (29.7% versus 56.9%, P < 0.001). BPA activation and order-set utilization occurred in 95.7% and 57.8% in the post-intervention group, respectively. Composite outcome of 30 day mortality or 90 day readmission with SAB complication decreased in the post-intervention group by 9.6% (24.3% versus 14.7%, P = 0.092). CONCLUSIONS: Optimization of CDS within the EHR, using real-time BPA alert and order set, demonstrated an immediate, sustainable intervention that improved adherence to institutional performance measures for SAB management without direct prospective audit with intervention and feedback.

Integrase Inhibitors: After 10 Years of Experience, Is the Best Yet to Come?

The era of the integrase strand transfer inhibitors (INSTIs) for the treatment of human immunodeficiency virus (HIV) infection began with raltegravir in 2007. Since that time, several other INSTIs have been introduced including elvitegravir, dolutegravir, and, most recently, bictegravir, that have shown great utility as part of antiretroviral regimens in both treatment-naive and treatment-experienced patients. At present, antiretroviral guidelines fully endorse the INSTI class as part of all first-line treatment regimens. After 10 years of experience with INSTIs, newer agents are on the horizon such as cabotegravir and MK-2048 for potential use as either HIV pre-exposure prophylaxis or maintenance therapy. This review provides a brief overview of the INSTI class including agents currently available and those still in development, reviews available data from both completed and ongoing clinical trials, and outlines simplification strategies using INSTIs.

Systematic Review of the Clinical Utility of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screening for MRSA Pneumonia.

OBJECTIVE: To describe the diagnostic performance characteristics of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening for patients with pneumonia. DATA SOURCES: PubMed and Scopus were searched from 1 January 1990 to 12 December 2018 using terms methicillin-resistant Staphylococcus aureus AND (screening OR active surveillance OR surveillance culture OR targeted surveillance OR chromogenic OR PCR OR polymerase chain reaction OR rapid test) AND (nares OR nasal) AND (pneumonia OR respiratory). STUDY SELECTION AND DATA EXTRACTION: Relevant studies in humans and English were considered. DATA SYNTHESIS: In all, 19 studies, including 21 790 patients, were included. Nasal screening for MRSA had a high negative predictive value (NPV; 76% to 99.4% for relevant studies) across all types of pneumonia. Time from nasal screening to culture varied across studies. Relevance to Patient Care and Clinical Practice: MRSA nasal screening has a high NPV for MRSA involvement in pneumonia. Utilizing this test for antimicrobial stewardship program (ASP) purposes can provide a valuable tool for reducing unwarranted anti-MRSA agents and may provide additional cost benefits. A cutoff of 7 days between nasal swab and culture or infection onset seems most appropriate for use of this test for anti-MRSA agent de-escalation for ASP purposes. CONCLUSIONS: Consideration for the inclusion of the utility of MRSA nasal screening in MRSA pneumonia should be made for future pneumonia and ASP guidelines. Additional studies are warranted to fully evaluate specific pneumonia classifications, culture types, culture timing, and clinical outcomes associated with the use of this test in patients with pneumonia.

Efficacy and Safety of the Early Addition of Vasopressin to Norepinephrine in Septic Shock.

BACKGROUND: Delays in achievement of target mean arterial pressure (MAP) have been associated with increased mortality in patients with septic shock. Vasopressin may be added to norepinephrine to raise MAP or decrease norepinephrine dosage. The purpose of this study was to determine whether early initiation of vasopressin to norepinephrine resulted in a reduced time to target MAP compared to norepinephrine monotherapy. METHODS: This retrospective cohort study compared early addition of vasopressin within 4 hours of septic shock onset to norepinephrine versus initial norepinephrine monotherapy in medically, critically ill patients with septic shock admitted from May 2014 to October 2015. Time to goal MAP was compared using Student t test and examined with Kaplan-Meier curves. Changes in Sequential Organ Failure Assessment (SOFA) scores were evaluated with Wilcoxon rank sum test. RESULTS: Each group contained 48 patients. Mean arterial pressure (61.5 vs 58.6 mm Hg) and intravenous fluid volume received at vasopressor initiation (14.3 vs 25.2 hours, P = .014) were similar. Patients started on early vasopressin achieved and maintained goal MAP sooner (6.2 vs 9.9 hours, P = .023), experienced greater reductions in SOFA scores at 72 hours (-4 vs -1, P = .012), and had shorter hospital durations (343 vs 604 hours, P = .014). Not initiating early vasopressin trended toward an association with increased time to goal MAP (P = .067). CONCLUSION: Early initiation of vasopressin in patients with septic shock may achieve and maintain goal MAP sooner and resolve organ dysfunction at 72 hours more effectively than later or no initiation.

Discontinuation of Vasopressin Before Norepinephrine in the Recovery Phase of Septic Shock.

BACKGROUND: Guidance for the discontinuation of vasopressors in the recovery phase of septic shock is limited. Norepinephrine is more easily titrated; however, septic shock is a vasopressin deficient state, which exogenous vasopressin endeavors to resolve. Discontinuation of vasopressin before norepinephrine may result in clinically significant hypotension. METHODS: This retrospective, cohort study compared discontinuation of norepinephrine and vasopressin in medically, critically ill patients in the recovery phase of septic shock from May 2014 to June 2016. Difference in clinically significant hypotension after norepinephrine or vasopressin discontinuation was evaluated with χ2 test. Linear regression was performed, examining the effect of agent discontinuation on clinically significant hypotension. Baseline variables were examined for a bivariate relationship with clinically significant hypotension; those with P < .2 were included in the model. RESULTS: Vasopressin was discontinued first or last in 62 and 92 patients, respectively. Sequential Organ Failure Assessment scores at 72 hours (7.9 vs 7.6, P = .679) were similar. In unadjusted analysis, when vasopressin was discontinued first, more clinically significant hypotension developed (10.9% vs 67.8%, P < .001). There was no difference in intensive care unit (174 vs 216 hours, P = .178) or hospital duration (470 vs 473 hours, P = .977). In adjusted analyses, discontinuing vasopressin first was associated with increased clinically significant hypotension (odds ratio [OR]: 13.837, 95% confidence interval [CI]: 3.403-56.250, P < .001) but not in-hospital (OR: 0.659, 95% CI: 0.204-2.137, P = .488) or 28-day mortality (OR: 0.215, 95% CI: 0.037-1.246, P = .086). CONCLUSION: Adult patients receiving norepinephrine and vasopressin in the resolving phase of septic shock may be less likely to develop clinically significant hypotension if vasopressin is the final vasopressor discontinued.

Metrics of Antimicrobial Stewardship Programs.

Appropriate metrics are needed to measure the quality, clinical, and financial impacts of antimicrobial stewardship programs. Metrics are typically categorized into antibiotic use measures, process measures, quality measures, costs, and clinical outcome measures. Traditionally, antimicrobial stewardship metrics have focused on antibiotic use, antibiotic costs, and process measures. With health care reform, practice should shift to focusing on clinical impact of stewardship programs over financial impact. This article reviews the various antimicrobial stewardship metrics that have been described in the literature, evidence to support these metrics, controversies surrounding metrics, and areas in which future research is necessary.

Prospective Open-label Trial of Early Concomitant Vasopressin and Norepinephrine Therapy versus Initial Norepinephrine Monotherapy in Septic Shock.

PURPOSE: Delays in achieving target mean arterial pressure (MAP) are associated with increased morbidity and mortality in patients with septic shock. This trial was conducted to test the hypothesis that early concomitant treatment with vasopressin and norepinephrine reduces the time to achieve and maintain target MAP compared with initial norepinephrine monotherapy. METHODS: A single-center prospective open-label trial was conducted in patients with septic shock between November 2015 and June 2016 at a medical intensive care unit in an academic medical center. Initial norepinephrine monotherapy was initiated between November 2015 and February 2016. Between March and June 2016, vasopressin was initiated within 4 hours of norepinephrine. The primary outcome was time to achieving and maintaining MAP of 65 mm Hg for at least 4 hours that was compared between groups using the Student t test and examined using the Kaplan-Meier curve (Clinical Trials registration: NCT02454348). RESULTS: Eighty-two patients were included (41 in each group). Patients treated with early concomitant vasopressin and norepinephrine more frequently had a positive culture (59% vs 37%, p=0.05) and grew nonlactose fermenting gram-negative bacilli (34% vs 10%, p=0.01) compared with patients treated with norepinephrine monotherapy, respectively. The median time to achieve and maintain MAP occurred faster in the early concomitant vasopressin and norepinephrine group, at 5.7 hours (interquartile range [IQR] 1.7-10.3 hrs), compared with 7.6 hours (IQR 3.6-16.7 hrs, p=0.058) in the norepinephrine group. Durations of therapy for norepinephrine or vasopressin, amount of norepinephrine received in the first 24 hours, norepinephrine dosage when MAP was achieved and maintained, maximum norepinephrine dosage, and mortality were similar between groups. CONCLUSION: Patients treated with early concomitant vasopressin and norepinephrine achieved and maintained MAP of 65 mm Hg faster than those receiving initial norepinephrine monotherapy, suggesting that overcoming vasopressin deficiency sooner may reduce the time patients spend in the early phase of septic shock.

Propofol for Treatment of Refractory Alcohol Withdrawal Syndrome: A Review of the Literature.

The authors evaluated all available evidence on the use of propofol as an adjuvant for the treatment of resistant alcohol withdrawal syndrome (AWS) in comparison to other therapies. A comprehensive PubMed search (1966-December 2015) was conducted using the search terms propofol, alcohol withdrawal, and drug therapy. Articles were cross-referenced for other citations. Clinical studies, case series, and case reports published in the English language assessing the use of propofol in adult patients for treatment of AWS were reviewed for inclusion. Propofol is a sedative-hypnotic that exerts its actions through agonism of GABAA receptors at a different binding site than benzodiazepines and reduces glutamatergic activity through N-methyl-d-aspartase (NMDA) receptor blockade. Dosages from 5 to 100 µg/kg/minute reduced AWS symptoms with frequent development of hypotension and requirement for mechanical ventilation. Patients on propofol often experienced longer durations of mechanical ventilation and length of stay, which may be attributed to more-resistant cases of AWS. When propofol was compared with dexmedetomidine as adjuncts in AWS, both agents showed similar benzodiazepine- and haloperidol-sparing effects. Dexmedetomidine was associated with more numerical rates of bradycardia, while propofol was associated with more numerical instances of hypotension. Dexmedetomidine was used more frequently in nonintubated patients. The available data assessing the utility of propofol for AWS exhibited significant heterogeneity. Propofol may be useful in a specific population of patients with AWS, limited to those who are not clinically responding to first-line therapy with benzodiazepines. Specifically, propofol should be considered in patients who are refractory to or not candidates for other adjuvant therapies, patients already requiring mechanical ventilation, or those with seizure activity or refractory delirium tremens. In severe, refractory AWS, adjuvant therapy with propofol may be considered but requires further research to recommend its use either preferentially or as monotherapy.