Chiara Montrucchio

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.

Transplacental passage of etravirine and maraviroc in a multidrug-experienced HIV-infected woman failing on darunavir-based HAART in late pregnancy

Sir, Although highly active antiretroviral treatment (HAART) in HIV-infected pregnant women has been shown to be effective in reducing mother-to-child-transmission (MTCT), some therapeutic issues remain a concern. Changes in drug pharmacokinetics (PK) in the second and third trimesters could cause reductions in plasma exposure of several antiretrovirals, while for most recent compounds few data are available. Boosted darunavir is widely used in multidrug-experienced pregnant patients, but information in this setting is limited to heterogeneous case reports showing lower trough concentrations (1168–1908 ng/mL) as compared with non-pregnant patients. – 6 The use of inhibitory quotients (IQs) has been proposed to individualize the exposure of drugs in relation to the harboured viruses: our group showed that the darunavir weighted score genotypic IQ (ws gIQ) was the most accurate predictor of virological response in treatmentexperienced patients. Therefore the use of darunavir ws gIQ could help clinicians to manage multidrug-experienced pregnant women. We describe the case of a young woman infected with HIV and hepatitis C virus whose therapeutic history includes suboptimal adherence to several antiretrovirals and virological failures on regimens containing efavirenz, indinavir and saquinavir. HIV polymerase revealed resistance-associated mutations both in the reverse transcriptase (D67N, T69N, K70R, A98G, M184V, K103N and K219Q) and the protease (M46I, I84V and L90M) gene. After successfully receiving tenofovir/emtricitabine and darunavir/ritonavir (800/100 mg once daily) she discontinued every treatment. Two years later she agreed to reinitiate tenofovir/emtricitabine and once-daily darunavir/ritonavir: at this time she presented with 539 CD4+ T lymphocytes/mm (15%, 0.27 CD8/CD4 ratio), 55500 HIV RNA copies/mL and an R5 tropic virus. Three months later (at 10 weeks of gestational age) her pregnancy test was positive and her darunavir/ritonavir dosage was increased to 600/100 mg twice daily. After a net decrease in viral load (252 copies/mL at 16 weeks and 115 copies/mL at

The Effect on Mortality of Fluconazole or Echinocandins Treatment in Candidemia in Internal Medicine Wards

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.

The effect on mortality of fluconazole or echinocandins treatment in internal medicine wards

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.

Diagnostic accuracy of new and old cognitive screening tools for HIV-associated neurocognitive disorders

Considering the similarities between HIV‐associated neurocognitive disorders (HAND) and neurodegenerative dementias and the frequency of executive dysfunctions among HIV‐positive patients, we evaluated the accuracy of the Frontal Assessment Battery and Clock‐Drawing Test together with the Three Questions Test and International HIV Dementia Scale to screen for HAND.

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.

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/&mgr;L) 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.