Dolutegravir is the newest integrase strand transfer inhibitor to be approved for the treatment of human immunodeficiency virus (HIV) infection. Dolutegravir is equivalent or superior to existing ...treatment regimens in both treatment-naïve and treatment-experienced patients including those with previous raltegravir or elvitegravir failure. The consistent efficacy coupled with excellent tolerability and infrequent drug-drug interactions makes the co-formulation of dolutegravir with two nucleotide reverse-transcriptase inhibitors an attractive treatment option. This review summarizes the pharmacokinetics, adverse event profile, and efficacy of dolutegravir in the treatment of HIV.
Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty (TJA). Rifampin is an antibiotic with the ability to penetrate bacterial biofilms, and thus has been ...considered as a potentially important adjunct in the prevention and treatment of PJI. The aim of this systematic review is to evaluate and summarize the use of rifampin in TJA, particularly in the context of PJI.
A literature search of all relevant electronic databases was performed. All comparative studies assessing the use of rifampin in the context of TJA were included. Descriptive data are reported, and a meta-analysis was performed using all studies which compared the addition of rifampin to standard care in treating PJI.
A total of 33 studies met inclusion criteria. A meta-analysis of 22 studies comparing the addition of rifampin to standard care for treating PJI found a significant reduction in failure rates (26.0% vs 35.9%; odds ratio 0.61, 95% confidence interval 0.43-0.86). The protective effect of rifampin was maintained in studies which included exchange arthroplasty as a treatment strategy, but not in studies only using an implant retention strategy. Among studies reporting adverse events of rifampin, there was a 20.5% adverse event rate.
Overall, rifampin appears to confer a protective effect against treatment failure following PJI. This treatment effect is particularly pronounced in the context of exchange arthroplasty. Further high-level evidence is needed to clarify the exact indications and doses of rifampin which can most effectively act as an adjunct in the treatment of PJI.
Level III, Systematic Review and Meta-Analysis of Level I-III Studies.
Large observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have provided limited information on ...other aspects of nirmatrelvir-ritonavir use. Our objective was to evaluate prescribing outcomes such as the prevalence of drug-drug interactions (DDI), adverse drug events (ADE) and treatment adherence in an outpatient community clinic setting. We conducted a single-centre retrospective cohort study of adult outpatients prescribed nirmatrelvir-ritonavir in our community COVID-19 assessment clinic in Toronto, Ontario between March 3 and September 20, 2022. We performed a descriptive analysis of the patient population, DDIs, DDI interventions, treatment adherence, ADEs and clinical outcomes of patients prescribed nirmatrelvir-ritonavir. There were 637 individuals prescribed nirmatrelvir-ritonavir during the study period. The median age was 70, the median number of risk factors for severe disease were 2, 45% were immunocompromised and 82% had received 3 or more COVID-19 vaccine doses. 95% (542/572) completed the 5-day course of therapy with 68% (388/572) having complete symptom resolution by 28-day. Eleven percent (60/572) experienced recurrent symptoms following the completion of nirmatrelvir-ritonavir. Over 70% had one or more clinically significant DDIs requiring mitigation and 62% of patients experienced at least one ADE, which was most commonly dysgeusia or gastrointestinal-related. Ninety-five percent (542/572) of patients completed therapy as prescribed. Overall, hospitalization within 28 days was 3.3% with 1.2% attributed to COVID-19 and there were no deaths.
Among outpatients with coronavirus disease 2019 (COVID-19) due to the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) δ (delta) variant who did and did not receive 2 vaccine doses at 7 days ...after symptom onset, there was no difference in viral shedding (cycle threshold difference 0.59, 95% CI, -4.68 to 3.50;
= .77) with SARS-CoV-2 cultured from 2 (7%) of 28 and 1 (4%) of 26 outpatients, respectively.
Abstract
Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on ...dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P = 0.48), BA.1 (P = 0.21), BA.5 (P = 0.07), BQ.1.1 (P = 0.10), nor XBB.1.5 (P = 0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. This study provides evidence that BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induce similar neutralization against Omicron subvariants, even when antigenically divergent from the circulating variant.
Widely available and easily accessible testing for COVID-19 is a cornerstone of pandemic containment strategies. Nasopharyngeal swabs (NPS) are the currently accepted standard for sample collection ...but are limited by their need for collection devices and sampling by trained healthcare professionals. The aim of this study was to compare the performance of saliva to NPS in an outpatient setting. This was a prospective study conducted at three centers, which compared the performance of saliva and NPS samples collected at the time of assessment center visit. Samples were tested by real-time reverse transcription polymerase chain reaction and sensitivity and overall agreement determined between saliva and NPS. Clinical data was abstracted by chart review for select study participants. Of the 432 paired samples, 46 were positive for SARS-CoV-2, with seven discordant observed between the two sample types (four individuals testing positive only by NPS and three by saliva only). The observed agreement was 98.4% (kappa coefficient 0.91) and a composite reference standard demonstrated sensitivity of 0.91 and 0.93 for saliva and NPS samples, respectively. On average, the Ct values obtained from saliva as compared to NPS were higher by 2.76. This study demonstrates that saliva performs comparably to NPS for the detection of SARS-CoV-2. Saliva was simple to collect, did not require transport media, and could be tested with equipment readily available at most laboratories. The use of saliva as an acceptable alternative to NPS could support the use of widespread surveillance testing for SARS-CoV-2.
Antibiotics and proton pump inhibitors (PPIs) are associated with Clostridium difficile infection (CDI). Both a computer order entry alert to highlight this association as well as antimicrobial ...stewardship directed prospective audit and feedback represent novel interventions to reduce the co-administration of antibiotics and PPIs among hospitalized patients.
Consecutive patients admitted to two General Internal Medicine wards from October 1, 2010 until March 31, 2013 at a teaching hospital in Toronto, Ontario, Canada were evaluated. The baseline observation period was followed by the first phase, which involved the creation of a computerized order entry alert that was triggered when either a PPI or an antibiotic was ordered in the presence of the other. The second phase consisted of the introduction of an antibiotic stewardship-initiated prospective audit and feedback strategy. The primary outcome was the co-administration of antibiotics and PPIs during each phase.
This alert led to a significant reduction in the co-administration of antibiotics and PPIs adjusted for month and secular trends, expressed as days of therapy per 100 patient days (4.99 vs. 3.14, p < 0.001) The subsequent introduction of the antibiotic stewardship program further reduced the co-administration (3.14 vs. 1.80, p <0.001). No change was observed in adjusted monthly CDI rates per 100 patient care days between the baseline and alert cohorts (0.12 vs. 0.12, p = 0.99) or the baseline and antibiotic stewardship phases (0.12 vs. 0.13, p = 0.97).
Decreasing the co-administration of PPIs and antibiotics can be achieved using a simple automatic alert followed by prospective audit and feedback.
Prosthetic hip and knee joint infections (PJIs) are challenging to eradicate despite prosthesis removal and antibiotic therapy. There is a need to understand risk factors for PJI treatment failure in ...the setting of prosthesis removal.
A retrospective cohort of individuals who underwent prosthesis removal for a PJI at 5 hospitals in Toronto, Canada, from 2010 to 2014 was created. Treatment failure was defined as recurrent PJI, amputation, death, or chronic antibiotic suppression. Potential risk factors for treatment failure were abstracted by chart review and assessed using a Cox proportional hazards model.
A total of 533 individuals with prosthesis removal were followed for a median (interquartile range) of 814 (235-1530) days. A 1-stage exchange was performed in 19% (103/533), whereas a 2-stage procedure was completed in 88% (377/430). Treatment failure occurred in 24.8% (132/533) at 2 years; 53% (56/105) of recurrent PJIs were caused by a different bacterial species. At 4 years, treatment failure occurred in 36% of 1-stage and 32% of 2-stage procedures (
= .06). Characteristics associated with treatment failure included liver disease (adjusted hazard ratio aHR, 3.12; 95% confidence interval CI, 2.09-4.66), the presence of a sinus tract (aHR, 1.53; 95% CI, 1.12-2.10), preceding debridement with prosthesis retention (aHR, 1.68; 95% CI, 1.13-2.51), a 1-stage procedure (aHR, 1.72; 95% CI, 1.28-2.32), and infection due to Gram-negative bacilli (aHR, 1.35; 95% CI, 1.04-1.76).
Failure of PJI therapy is common, and risk factors are not easily modified. Improvements in treatment paradigms are needed, along with efforts to reduce orthopedic surgical site infections.
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