Plasma trough concentrations of darunavir/ritonavir and raltegravir in older patients with HIV-1 infection.

OBJECTIVES: The aim of the study was to assess plasma concentrations of darunavir/ritonavir and raltegravir in older patients compared with younger patients with HIV-1 infection. METHODS: In this observational, open-label study, adult HIV-infected out-patients aged ≤ 40 years (younger patients) or ≥ 60 years (older patients) and treated with tenofovir/emtricitabine plus darunavir/ritonavir (800/100 mg daily) or raltegravir (400 mg twice daily) were asked to participate. The trough concentrations (Ctrough ) of darunavir/ritonavir and raltegravir were assessed at steady state using a validated high-performance liquid chromatography (HPLC)-tandem mass spectrometry method. RESULTS: A total of 88 HIV-positive patients were enrolled in the study. Forty-six patients were treated with darunavir/ritonavir, and 42 with raltegravir. The geometric mean plasma Ctrough (coefficient of variation) of raltegravir was comparable between the 19 older and 23 younger subjects: 106 ng/mL (151%) and 94 ng/mL (129%), respectively [geometric mean ratio (GMR) 0.85; 95% confidence interval (CI) 0.71-1.57; P = 0.087]. In contrast, the geometric mean plasma Ctrough of darunavir was significantly higher among the 21 older patients [2209 ng/mL (139%)] than among the 25 younger patients [1876 ng/mL (162%); GMR 1.56; 95% CI: 1.22-1.88; P = 0.004]. Similarly, the geometric mean Ctrough of ritonavir was significantly higher among older than among younger individuals. CONCLUSIONS: The mean plasma Ctrough of darunavir and ritonavir was significantly higher in older patients than in younger patients with HIV-1 infection, while the mean plasma level of raltegravir was comparable in the two groups. However, both regimens showed good tolerability in both younger and older subjects.

Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case-control-control study.

OBJECTIVES: The aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis. METHODS: This was a case-control-control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission. RESULTS: During the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09-4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19-4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00-7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26-6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62-9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11-10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19-0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97-2.75) p = 0.06). CONCLUSIONS: We identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.

Follow-up blood cultures are associated with improved outcome of patients with gram-negative bloodstream infections: retrospective observational cohort study.

OBJECTIVES: We examined factors associated with follow-up blood cultures (FUBCs) in patients with monomicrobial Gram-negative (GN) bloodstream infection (BSI) and investigated the impact of FUBCs on therapeutic management and patient outcome. METHODS: A retrospective cohort analysis was conducted of adult patients diagnosed with GN-BSI at a tertiary-care university hospital during 2013-2016. FUBCs performed between 24 hours and 7 days after index BCs was the exposure variable. Risk factors for 30-day mortality were analysed by multivariate Cox analysis on the overall cohort, including FUBCs as a time-varying covariate and on 1:1 matched patients according to Sequential Organ Failure Assessment (SOFA) score and time to FUBC. RESULTS: In 278 (17.6%) of 1576 patients, FUBCs were performed within a median of 3 and 2 days after index BCs and active antibiotic therapy initiation. Persistent BSI was found in 107 (38.5%) of 278 patients. FUBCs were performed in more severely ill patients, with nonurinary sources, difficult-to-treat pathogens and receipt of initial inappropriate therapy. Source control and infectious disease consultation rates were higher among patients with preceding FUBCs and was associated with longer treatment duration. Thirty-day mortality was 10.4%. Independent risk factors for mortality were Charlson comorbidity index (hazard ratio (HR) 1.12) SOFA (HR 1.11), septic shock (HR 2.64), urinary source (HR 0.60), central venous catheter source (HR 2.30), complicated BSI (HR 2.10), carbapenem resistance (HR 2.34), active empiric therapy (HR 0.68), source control (HR 0.34) and FUBCs (HR 0.48). Association between FUBCs and lower mortality was confirmed in the 274 matched pairs. CONCLUSIONS: FUBCs were performed in more severe GN-BSIs, yielding a high rate of persistent BSI. In this context, FUBCs were associated with lower mortality.