Inpatient Hepatitis C Treatment Coordination and Initiation for Patients Who Inject Drugs.

BACKGROUND: With hepatitis C (HCV) incidence rising due to injection drug use, people who inject drugs (PWID) are a priority population for direct-acting antivirals (DAA). However, significant barriers exist. At our institution, hospitalized PWID were screened for HCV but not effectively linked to care. AIM: To improve retention in HCV care among hospitalized PWID. SETTING: Quaternary academic center in the Southeast US from August 2021 through August 2022. PARTICIPANTS: Hospitalized PWID with HCV. PROGRAM DESCRIPTION: E-consultation-prompted care coordination and HCV treatment with outpatient telehealth. PROGRAM EVALUATION: Care cascades were constructed to assess retention and HCV treatment, with the primary outcome defined as DAA completion or sustained virologic response after week 4. Of 28 patients, 11 started DAAs inpatient, 8 initiated outpatient, and 9 were lost to follow-up or transferred care. Overall, 82% were linked to care and 52% completed treatment. For inpatient initiators, 73% achieved the outcome. Of non-inpatient initiators, 71% were linked to care, 53% started treatment, and 36% achieved the outcome. DISCUSSION: Inpatient HCV treatment coordination, including DAA initiation, and telehealth follow-up, was feasible and highly effective for hospitalized PWID. Future steps should address barriers to inpatient DAA treatment and expand this model to other similar patient populations.

Adherence to National Consensus Guidelines and Association with Clinical Outcomes in Patients with Candidemia.

BACKGROUND: National consensus guidelines outline recommendations for best practices in treating patients with candidemia. This study evaluated the impact of receiving care adherent to the best practice recommendations on clinical outcomes in patients with candidemia. METHODS: This retrospective, multicenter study included patients with candidemia from 2010 to 2015 at 9 hospitals. The primary outcome was the composite of 30-day in-hospital mortality and 90-day candidemia recurrence. Outcomes were compared between those receiving and not receiving care adherent to the guideline recommendations. Inverse probability weights with regression adjustment were utilized to determine the average treatment effect of adherent care on the composite outcome. RESULTS: 295 patients were included with 14.2% meeting criteria for the composite outcome (11.9% mortality and 2.4% recurrence). The average treatment effect of adherent care was not significant (P = .75). However, receiving appropriate initial antifungal treatment and central venous catheter removal were both associated with the composite (average treatment effect of -17.5%, P = .011 and -8.8%, P = .013, respectively). In patients with a source of infection other than the central line, central venous catheter removal was not associated with the composite (P = .95). The most common reason for failure to receive appropriate initial antifungal treatment was omission of the loading dose. CONCLUSIONS: Central venous catheter removal and appropriate initial antifungal treatment were associated with a lower incidence of the composite of mortality and recurrence. Additional studies are needed to determine the optimal duration of therapy following candidemia clearance.

Clinical outcomes of Stenotrophomonas maltophilia infection treated with trimethoprim/sulfamethoxazole, minocycline, or fluoroquinolone monotherapy.

OBJECTIVES: The historical treatment of choice for Stenotrophomonas maltophilia infection is trimethoprim/sulfamethoxazole and this is primarily based on preclinical studies. The objective of this study was to examine the clinical outcomes of patients receiving monotherapy with different agents. METHODS: This was a retrospective study of adult patients receiving monotherapy for S. maltophilia infection with trimethoprim/sulfamethoxazole (TMP/SMX), a fluoroquinolone, or minocycline from 2010 to 2016. The primary outcome was clinical failure, a composite of recurrence, alteration of therapy due to adverse reaction or concern for clinical failure, or 30-day in-hospital mortality. The secondary outcome was 30-day in-hospital mortality. To account for treatment selection bias, multivariate regression and propensity score weighting were conducted. RESULTS: 284 patients were included (217 received TMP/SMX, 28 received a fluoroquinolone, and 39 received minocycline). The TMP/SMX and minocycline groups appeared to include similar patients whereas the fluoroquinolone group appeared to represent a slightly less severely ill population. Clinical failure was similar between groups (36%, 29%, and 31% in the TMP/SMX, fluoroquinolone, and minocycline groups, respectively, P=0.69) as was 30-day mortality (15%, 7%, and 5% in the TMP/SMX, fluoroquinolone, and minocycline groups, respectively, P=0.16). After controlling for confounding factors, receipt of minocycline (adjusted odds ratio [OR]=0.2 [0.1-0.7]) but not a fluoroquinolone (adjusted OR=0.3 [0.1 to 2.1]) was associated with lower mortality compared with TMP/SMX. This association persisted after propensity score weighting. CONCLUSIONS: Outcomes were similar or better with alternatives to TMP/SMX monotherapy, which indicates this may not be the treatment of choice for infections caused by S. maltophilia.

Pharmaceutical approaches to eradication of persistent HIV infection.

Highly active antiretroviral therapy (HAART) has markedly decreased morbidity and mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals in the developed world. Successful therapy often results in stable plasma levels of HIV-1 RNA below the limits of detection of commercial assays. Nonetheless, HIV-1 has not been cured by HAART. The causes of persistence of HIV infection in the face of current therapy appear to be multifactorial: latent but replication-competent provirus in resting CD4+ T cells, cryptic viral expression below the limits of detection of clinical assays, and viral sanctuary sites might all contribute to persistence. Clearance of HIV infection will almost certainly require a multimodality approach that includes potent suppression of HIV replication, therapies that reach all compartments of residual HIV replication and depletion of any reservoirs of persistent, quiescent proviral infection. This review highlights the basic mechanisms for the establishment and maintenance of viral reservoirs and pharmaceutical approaches towards their elimination.

Inhibition of HIV fusion with multivalent gold nanoparticles.

The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diameter gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small molecules on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics.