Mortality in patients with early- or late-onset candidaemia.

OBJECTIVES: Although candidaemia is a well-known complication of hospital stay and has a crude mortality of ∼40%, few data are available for episodes diagnosed within 10 days after hospital admission. In this paper, we compared the risk factors for mortality according to the onset of candidaemia. METHODS: This was a retrospective study of hospitalized patients with early-onset candidaemia (EOC; ≤ 10 days) or late-onset candidaemia (LOC; >10 days) to identify any distinct clinical characteristics and risk factors for 30 day mortality in two Italian academic centres. RESULTS: A total of 779 patients were included in the study: 183 EOC and 596 LOC. Mortality was significantly lower in EOC (71/183, 38.8% versus 283/596, 47.5%, P=0.03). In EOC, multivariate analysis showed that inadequate initial antifungal therapy (IIAT) (P=0.005, OR 3.02, 95% CI 1.40-6.51), Candida albicans aetiology (P=0.02, OR 2.17, 95% CI 1.11-4.26) and older age (P<0.001, OR 1.05, 95% CI 1.02-1.07) were independent risk factors for mortality. In LOC, liver disease (P=0.003, OR 2.46, 95% CI 1.36-4.43), IIAT (P=0.002, OR 2.01, 95% CI 1.28-3.15) and older age (P<0.001, OR 1.03, 95% CI 1.02-1.04) were independently associated with a fatal outcome, while treatment with caspofungin was associated with survival (P<0.001, OR 0.42, 95% CI 0.26-0.67). CONCLUSIONS: EOC has different clinical characteristics and risk factors for mortality compared with LOC. Although EOC mortality is significantly lower, the rate of inappropriate antifungal treatment is higher. Treatment with caspofungin is significantly associated with survival in patients with LOC. Efforts are needed to improve the diagnosis and treatment of EOC.

In-hospital and long-term outcomes of HIV-positive patients undergoing PCI according to kind of stent: a meta-analysis.

BACKGROUND: Pathogenesis of cardiovascular disease in HIV-positive patients is related to the interaction between traditional and HIV-specific factors. Limited data are available regarding the prognosis of HIV-positive patients undergoing percutaneous coronary intervention (PCI). METHODS: All observational studies evaluating the prognosis of HIV-positive patients treated with PCI were included. In-hospital and long-term major adverse cardiac events (MACE) [composite endpoint of all-cause death or myocardial infarction (MI)] were the primary endpoints, whereas in-hospital and long-term all-cause death, cardiovascular death, MI, stent thrombosis, target vessel revascularization (TVR), target lesion revascularization (TLR), and bleeding complications were the secondary ones. FINDINGS: In all, 1243 patients in nine studies were included, with a mean age of 54 years. Among them, 12% were female and 91% were admitted for acute coronary syndromes. In-hospital MACE occurred in 6.0% (5.4-6.6), death in 4.2% (2.6-5.9), and MI in 1.3% (0-2.8), whereas major bleeding occurred in 2.0% (1.7-2.3) of the patients. After 2 years (1.6-3.1), long-term MACE occurred in 17.4% (11.9-22.3), all-cause death in 8.7% (3.2-14.2), and MI in 7.8% (5.5-10.1) of the patients, whereas stent thrombosis and TVR in 3.4% (1.5-5.3) and 10.5% (7.5-13.4), respectively. In patients treated with drug-eluting stents (DES), the rate of long-term MACE was 22.3% (10.1-34.4), with an incidence of 4.9% (0.0-11.4) of MI and 5.7% (2.3-13.7, all 95% confidence intervals of TLR. INTERPRETATION: HIV-positive patients have a high risk of in-hospital and long-term MACE after PCI, partially reduced by the use of DES. Further studies on the risk of recurrent ischemic events with current generation stents are needed, to offer a tailored therapy in this high-risk population.

The outcome of HIV-positive late presenters according to detectable CMV DNA and anti-CMV treatment.

BACKGROUND: HIV late presenters are at high risk of cytomegalovirus (CMV) reactivation and end-organ disease. CMV viraemia has been associated with poor survival but the effect of anti-CMV treatment has not been studied in this setting. METHODS: HIV-positive patients were included in a retrospective study if presenting with <350 CD4+ T-cells/µl and starting an antiretroviral treatment within 3 months of the diagnosis. Primary end point was 5-year survival according to the presence of CMV viraemia, CMV end-organ disease and anti-CMV treatment. RESULTS: 302 patients were included. 157 patients (52%) presented CMV viraemia (CMV-V) and 44 (14.6%) CMV end-organ disease (CMV-EOD). 5-year mortality was higher in CMV-EOD and CMV-V patients than in CMV-negative patients (11.4 versus 9.6 versus 0%; P=0.002). In patients with CMV-V, 5-year mortality was numerically higher in untreated patients (12.9% versus 6.9%; P=0.257) without reaching statistical significance. At univariate analysis the diagnosis of serious opportunistic infections (cryptococcosis, progressive multifocal leukoencephalopathy, lymphoma; P=0.001) and the absence of a negative CMV DNA in the follow-up (P<0.001) were associated with poor outcome. At multivariate analysis HCV coinfection (P=0.016; aOR 6.98, 95% CI 1.50, 32.59), the absence of a negative CMV DNA in the follow-up (P<0.001; aOR 19.40, 95% CI 3.70, 101.64) and marginally the absence of anti-CMV treatment (P=0.052; aOR 4.944, 95% CI 0.99, 24.73) were independent predictors of poor outcome. CONCLUSIONS: CMV reactivation in HIV-positive patients with poor immunity is associated with worse prognosis: the pre-emptive use of anti-CMV therapy was associated with a better outcome in patients with CMV-V.

Evaluation of coronary features of HIV patients presenting with ACS: The CUORE, a multicenter study.

BACKGROUND AND AIMS: The risk of recurrence of myocardial infarction (MI) in HIV patients presenting with acute coronary syndrome (ACS) is well known, but there is limited evidence about potential differences in coronary plaques compared to non-HIV patients. METHODS: In this multicenter case-control study, HIV patients presenting with ACS, with intravascular-ultrasound (IVUS) data, enrolled between February 2015 and June 2017, and undergoing highly active antiretroviral therapy (HAART), were retrospectively compared to non-HIV patients presenting with ACS, before and after propensity score with matching, randomly selected from included centers. Primary end-point was the prevalence of multivessel disease. Secondary end-points were the prevalence of abnormal features at IVUS, the incidence of major-acute-cardiovascular-events (MACE), a composite end point of cardiovascular death, MI, target lesion revascularization (TLR), stent thrombosis (ST), non-cardiac death and target vessel revascularization (TVR). For each end-point, a subgroup analysis was conducted in HIV patients with CD4 cell count <200/mm3. RESULTS: Before propensity score, 66 HIV patients and 120 non-HIV patients were selected, resulting in 20 and 40 after propensity score. Patients with multivessel disease were 11 and 17, respectively (p = 0.56). IVUS showed a lower plaque burden (71% vs. 75%, p < 0.001) and a higher prevalence of hyperechoic non-calcified plaques (100% vs. 35%, p < 0.05) in HIV patients; a higher prevalence of hypoechoic plaques (7% vs. 0%, p < 0.05), a higher incidence of MACE (17.4% vs. 9.1% vs. l'8.0%, p < 0.05), MI recurrence (17.2% vs. 0.0% vs. 2.3%, p < 0.05), and ST (6.7% vs. 0.3% vs. 03%, p < 0.05) in HIV patients with CD4 < 200/mm3. CONCLUSIONS: Our study may provide a part of the pathophysiological basis of the differences in coronary arteries between HIV-positive and HIV-negative patients, suggesting that the former present with peculiar morphological features at IVUS, even after adjustment for clinical variables. Furthermore, we confirmed that an advanced HIV infection is associated with a high risk of non-calcific plaques and with a worse prognosis, including cardiovascular events and ACS recurrence.

Role of Normalized T-Cell Subsets in Predicting Comorbidities in a Large Cohort of Geriatric HIV-Infected Patients.

BACKGROUND: Adults aging with HIV are at greater risk for several comorbidities. The CD4 cell count and CD4/CD8 ratio often fail to normalize in elderly patients despite prolonged antiretroviral therapy; this has been associated with concomitant diseases and poor prognosis. METHODS: A cross-sectional analysis in antiretroviral-treated HIV-positive patients aged 65 years and older. The aim of the study was to describe the predictors of normalized T-cell subsets ("nT", CD4/CD8 ratio ≥1 and CD4 ≥500 cells/µL) in a cohort of geriatric HIV-positive patients and its association with HIV-associated non-AIDS conditions (HANA). RESULTS: One thousand ninety-two patients were included: nT was observed in 340 patients (31.1%). Multivariate binary logistic analysis showed that plasma HIV RNA <50 copies/mL (P = 0.004), female sex (P = 0.002), and nadir CD4 cell count (P < 0.001) were independent predictors of nT. Age and sex-adjusted prevalence of hypertension (P = 0.037), lipid abnormalities (P = 0.040), and multimorbidity (P = 0.034) were higher in subjects with nT, whereas chronic obstructive pulmonary disease (COPD) and cancer were lower (respectively, P = 0.028 and P = 0.005). Multivariate analysis showed that HIV duration was an independent predictor of several comorbidities, whereas nT was protective for cancer and COPD. HIV duration and nT were simultaneously predictors of multimorbidity. CONCLUSIONS: Normalized T-cell subsets were observed in approximately one-third of geriatric HIV-positive subjects, and they were predicted by female sex and immunovirological features. HIV-associated non-AIDS conditions were more prevalent in patients with longer HIV duration, whereas nT represented a protective factor for cancer and COPD.

Raltegravir Plus Nevirapine as Maintenance Antiretroviral Therapy in HIV-Positive Patients: Safety, Efficacy and Pharmacokinetics.

BACKGROUND: Tolerability, long-term toxicities and selection of resistant variants limit the use and efficacy of antiretroviral drugs in HIV-positive patients. Novel combinations are needed for mantaining long-term control of HIV replication; nevertheless scarse data are available on protease inhibitor-free dual antiretroviral therapies. METHODS: A multi-centric retrospective study was conducted including HIV-1-positive patients on raltegravir/nevirapine dual regimens. Plasma concentrations were measured as therapeutic drug monitoring while a subset of patients underwent intensive 12-hour pharmacokinetic evaluation. RESULTS: A total of 77 patients switching from successful regimens (76.6% male, median age 52 years) was included; 10 patients on raltegravir plus nevirapine once-daily while 67 subjects on twice-daily schedule. After a median follow-up of 32 months 69 patients (89.6%) were still successfully on treatment. Three patients discontinued for side effects (skin rash or hepatoxicity). Virological failure was observed in five patients (6.5%, 3 on once-daily schedule): in 4 patients (80%) resistance-associated mutations were observed (4 reverse transcriptase, 2 integrase). Triglycerides decreased in patients switching with lipid abnormalities (n=52) and estimated creatinine clearance increased in those with less than 60 ml/min (n=13). Median trough raltegravir and nevirapine concentrations were 83 ng/ml (32-227) and 5460 ng/ml (4037-7221); intensive 12-hours pharmacokinetic parameters (n=7) were similar to published data. CONCLUSION: Dual therapy with raltegravir/nevirapine in selected patients was highly effective over a 32-month follow up: virological failure was infrequent (6.5%), most common with once-daily schedule (60%) and often associated with the selection of resistance-associated mutations (80%). Twice-daily raltegravir plus nevirapine deserves further clinical evaluation as an NRTI- and PI-sparing strategy in selected patients.

Candidemia, and infections by Clostridium difficile and carbapenemase-producing Enterobacteriaceae: new enteropathogenetic opportunistic syndromes?

In this paper we analyze three enteropathogenetic opportunistic infections represented by Candida spp., C. difficile and carbapenemase-producing K. pneumoniae. The common pathogenetic pathway is based on an alteration of the intestinal flora, now mainly referred as the human microbiome, with secondary opportunism for infections caused by Candida, C. difficile and carbapenemase-producing Enterobacteriaceae ("CCC"). We highlight the epidemiology, risk factors, clinical syndromes associated with the pathogens and we propose some new issues related to the epidemiology and diagnosis of candidemia, also using hierarchical cluster analysis, definitions of levels of interventions in patients colonized or infected by carbapenemase-producing bacteria. The "enteropathogenetic" opportunistic syndromes are best prevented with antimicrobial stewardship programs aiming at increasing diagnostic specificity of infectious syndromes to reduce the antimicrobial use and costs. Appropriate guidelines for infection control should also be implemented to reduce the nosocomial spread of enteropathogenetic microbes.

The Effect on mortality of fluconazole or echinocandins treatment in candidemia in internal medicine wards [corrected].

The incidence of candidemia has increased over the past two decades, with an increased number of cases in Internal Medicine and a prevalence ranging from 24% to 57%. This single-center retrospective study was performed to evaluate the epidemiology and the risk factors associated with mortality of candidemia in patients admitted to Internal Medicine wards (IMWs) of the City of Health and Sciences, Molinette Hospital, Turin, from January 2004 to December 2012. For each patient, demographic, clinical and microbiological data were collected. A case of candidemia was defined as a patient with at least one blood culture positive for Candida spp. Amongst 670 episodes of candidemia, 274 (41%) episodes occurred in IMWs. The mortality was 39% and was associated at multivariate analysis with sepsis, cirrhosis and neurologic diseases, whilst removal of central venous catheter ≤48h was significantly associated with survival. In the 77 patients treated with early antifungal therapy the mortality was 29% and was not significantly different with caspofungin or fluconazole, whilst in patients with definitive therapy the mortality was significantly lower with echinocandins compared to fluconazole (11.7% Vs. 39%; p=0.0289), a finding confirmed by multivariate analysis. The mortality was significantly associated with sepsis, cirrhosis and neurologic diseases, whilst CVC removal ≤48h was associated with survival. In patients with early therapy, fluconazole or caspofungin were equally effective. However, echinocandins were significantly more effective as definitive treatment, a finding not explained by differences in treatment delays. Further studies are needed to understand the full potential of these different therapeutic strategies in IMWs.

Transcatheter aortic valve implantation in a 54-year-old patient with aggressive HIV.

We report a case of a 54-year-old patient who was denied surgical replacement for severe aortic stenosis because of complicated acquired immunodeficiency syndrome and who successfully underwent transcatheter aortic valve implantation at our institution.