The Effect of Retained Hardware on Failure Among Prosthetic Joint Infections of the Knee in the Presence and Absence of Staphylococcus aureus.

Background: The risk of failure associated with different surgical strategies for prosthetic joint infections (PJIs) among patients with and without Staphylococcus aureus is uncertain. The purpose of this study was to assess whether S. aureus modifies the association between retained hardware and failure following revision surgery for PJI of the knee. Methods: This was a single-center retrospective cohort study of 106 first PJIs of the knee between 2016 and 2020 at a rural academic medical center. The exposure was retained hardware following revision surgery for PJI, and the outcomes were recurrent infection, any infection, and a composite outcome including any infection, unplanned revision, failure to undergo reimplantation, amputation, or death within 2 years of revision. We used negative binomial regression to quantify the association between the exposure and outcome and to assess the presence of S. aureus as an effect modifier. Results: Retained hardware was significantly associated with failure when defined as recurrent infection among S. aureus PJI (adjusted risk difference [aRD], 0.38; 95% CI, 0.12-0.64) but not in the absence of S. aureus (aRD, -0.02; 95% CI, -0.17 to 0.13), and S. aureus was an effect modifier (P interaction = .01). Conclusions: We report a significant association between the presence of retained hardware and recurrent infection among S. aureus PJI of the knee, but not for non-S. aureus PJI. This could help inform the surgical management of PJI of the knee in cases where the microbiology is known before surgery.

Tafenoquine for Relapsing Babesiosis: A Case Series.

BACKGROUND: Relapsing babesiosis often occurs in highly immunocompromised patients and has been attributed to the acquisition of resistance against drugs commonly used for treatment such as atovaquone, azithromycin, and clindamycin. Tafenoquine, which is approved for malaria prophylaxis and presumptive antirelapse treatment of Plasmodium vivax malaria, has shown activity against Babesia microti in several animal models of acute infection and in a single human case of relapsing babesiosis. Here, we report 5 cases of relapsing babesiosis treated with tafenoquine, including the previous case, and begin to define the conditions for optimal use of tafenoquine in relapsing babesiosis. METHODS: A definitive diagnosis of babesiosis was made by microscopic examination of Giemsa-stained thin blood smears or a real-time polymerase chain reaction (PCR) that targets the parasite 18S rRNA gene. Clearance of B. microti infection was ascertained by use of blood smear and real-time PCR. RESULTS: Tafenoquine was initiated with a loading dose of 600 mg. A weekly maintenance dose consisted of 200 mg or 300 mg; the lower dose was associated with a delayed clearance of B. microti. In 2 cases, all antimicrobial agents but tafenoquine were discontinued prior to clearance of infection. In 2 other cases, clearance was achieved while tafenoquine was administered along with other antimicrobial agents. In 3 of these 4 cases, tafenoquine was used in combination with atovaquone-proguanil. Other agents included atovaquone, azithromycin, and/or clindamycin. In 1 case, tafenoquine was administered alone and failed to prevent relapse. CONCLUSIONS: Tafenoquine can be a useful adjunct for the treatment of highly immunocompromised patients experiencing relapsing babesiosis caused by B. microti.

Safety of Single High-Dose Liposomal Amphotericin B for Induction Treatment of Cryptococcal Meningitis and Histoplasmosis in People With HIV: A Systematic Review and Meta-analysis.

Background: Evidence for efficacy of single, high-dose liposomal amphotericin B (LAmB) in HIV-associated cryptococcal meningitis and histoplasmosis is growing. No systematic review has examined the safety of this regimen across multiple studies. Methods: We systematically searched Medline, Scopus, and the Cochrane Library from inception to April 2023 for studies reporting grade 3 and 4 adverse events (AEs) with single high-dose LAmB vs traditional amphotericin regimens for HIV-associated fungal infections. Results: Three trials (n = 946) were included. Compared with traditional regimens, single high-dose LAmB was associated with equivalent risk of grade 3 and 4 AEs (risk ratio [RR], 0.75; 95% CI, 0.53-1.06) and lower overall risk of grade 4 AEs (RR, 0.68; 95% CI, 0.55-0.86), grade 4 renal (RR, 0.43; 95% CI, 0.20-0.94) and grade 4 hematological AEs (RR, 0.46; 95% CI, 0.32-0.65). Conclusions: Single, high-dose LAmB is associated with a lower risk of life-threatening AEs compared with other World Health Organization-endorsed amphotericin B-based regimens in invasive HIV-related fungal infection.

A comparison of National Healthcare Safety Network surveillance definitions to physician review for central-line-associated bloodstream infections.

For 147 hospital-onset bloodstream infections, we assessed the sensitivity, specificity, positive predictive value, and negative predictive value of the National Healthcare Safety Network surveillance definitions of central-line-associated bloodstream infections against the gold standard of physician review, examining the drivers of discrepancies and related implications for reporting and infection prevention.

Investigating potential drivers of increased central line...associated bloodstream infections during the coronavirus disease 2019 (COVID-19) Omicron surge.

Central line...associated bloodstream infection rates increased during the Omicron surge at our rural academic medical center. To identify potential drivers of this increase, we investigated period- and patient-specific factors associated with the increase in central line...associated bloodstream infection. Increased central line utilization, decreased central line bundle compliance monitoring, increased proportion of traveling nurses, increased short-term venous catheter use in the internal jugular vein, increased multilumen catheter use, decreased port...associated infection, and increased patient acuity were significantly associated with the surge. Our results helped us target our local infection prevention efforts.

Saturable sinusoidal uptake is rate-determining process in hepatic elimination of docetaxel in rats.

Identifying kinetic determinants of hepatic elimination of drugs would be crucial for better understanding its pharmacokinetics and predicting drug interactions. Present study investigated the kinetics of sinusoidal uptake of docetaxel and its impact on the overall hepatic elimination of docetaxel in rats. The non-renal clearance (CL(NR); hepatic elimination) of docetaxel were significantly reduced by co-administration of intravenous rifampicin, a potent inhibitor of organic anion transporting peptides (OATPs; Oatps), at a dose of 20 mg/kg. Docetaxel uptake into isolated rat hepatocytes was found to be temperature/concentration/energy-dependent, saturable, and reduced by Oatps inhibitors (rifampicin and bromosulfophthalein). Moreover, docetaxel uptake into perfused rat liver was significantly reduced in the presence of 10-µM rifampicin. However, docetaxel metabolism in rat hepatic microsome was not affected by rifampicin at less than 50 µM. Based on the comparison of intrinsic clearances related to hepatic clearance, it can be suggested that sinusoidal uptake could be the rate-determining process in the overall hepatic elimination of docetaxel in rats.