Filippo Trapani

Klebsiella pneumoniae bloodstream infection: epidemiology and impact of inappropriate empirical therapy.

AbstractMultidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniae bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42%) KPC-positive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo-beta-lactamase-positive isolates. Adequate empirical therapy was administered in 74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23% of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment outcomes, we compared several different models comprised of non-antibiotic treatment-related factors predictive of patients’ 30-day survival status. Acute Physiology and Chronic Health Evaluation (APACHE) II score determined at the time of positive blood culture was superior to other investigated models, correctly predicting survival status in 83% of the study cohort. In multivariate analysis accounting for APACHE II, receipt of inadequate empirical therapy was associated with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95% confidence interval 1.1–3.4; p = 0.02). Multidrug-resistant K. pneumoniae accounted for two-thirds of all K. pneumoniae BSIs, high rates of inappropriate empirical therapy, and twofold higher rates of patient death irrespective of underlying illness.

Prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection

Metabolic complications of antiretroviral therapy in HIV-infected patients include insulin resistance, diabetes mellitus, dyslipidaemia and lipodystrophy syndrome. Metabolic syndrome is an aggregation of central obesity with glucose and lipid metabolism alterations that confers an increased risk of cardiovascular disease, which reproduces the antiretroviral-associated metabolic and morphological abnormalities. In this study, we report the prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection referred to our outpatients unit. The prevalence of diabetes mellitus and metabolic syndrome was 4.5% and 9.1%, respectively. A longer exposure to antiretroviral therapy and a diagnosis of lipodystrophy syndrome were significantly associated with both metabolic disturbances.

Statin therapy decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in HIV-infected patients treated with ritonavir-boosted protease inhibitors.

Abstract Background: Statins are lipid-lowering drugs that exhibit anti-inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. Objective: Because very limited data are available today, our objective was to assess the lipid-lowering effects of statins and their capacity to decrease selected soluble markers of inflammation in HIV-infected patients. Methods: Retrospective cohort study of HIV-infected adult patients with hypercholesterolemia who were receiving a stable antiretroviral regimen including a ritonavir-boosted protease inhibitor and who started a lipid-lowering therapy with rosuvastatin (10 mg daily), atorvastatin (10 mg daily), or pravastatin (40 mg daily) and were followed-up for at least 12 months. One hundred and fifty-one patients were enrolled in the study: 51 in the rosuvastatin group, 47 in the atorvastatin group, and 53 in the pravastatin group. The primary observation was change in plasma lipid levels and serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF- α]), while secondary observations include immunovirological parameters and safety profile of statins. Results: One year after starting the statin therapy, patients treated with rosuvastatin had significantly greater decreases in total cholesterol and LDL cholesterol than subjects on atorvastatin or pravastatin. All statins led to a similar, significant reduction in serum levels of hsCRP and TNF-α, without correlation between biomarkers and lipid values, and toxicity rates were similar for all 3 statins. Conclusion: Our findings suggest that rosuvastatin has a significantly greater lipid-lowering effect than atorvastatin or pravastatin, but all 3 statins exert a similar effect in lowering markers of inflammation as hsCRP and TNF-α.

Tenofovir-induced renal toxicity in 324 HIV-infected, antiretroviral-naïve patients

Abstract To better evaluate the renal safety profile of tenofovir, we performed a retrospective study of HIV-infected antiretroviral-naïve patients starting a first antiretroviral therapy between July 2004 and July 2008, and followed-up for 24 months. The glomerular filtration rate (GFR) was calculated using the MDRD formula, and tubular dysfunction was diagnosed with 2 or more of the following: proteinuria, glucosuria, hypouricemia, hypophosphatemia and hypokalemia. Overall, 324 patients were enrolled: 201 were tenofovir-exposed and were compared with 123 tenofovir-unexposed subjects. In both the unadjusted and adjusted analyses, tenofovir-exposed subjects had a significantly greater decline in GFR and a significantly higher incidence of proximal tubular dysfunction through 24 months. Reduced glomerular and tubular functions were significantly associated with older age, diabetes, hypertension and concomitant therapy with a protease inhibitor.

Incidence of renal toxicity in HIV-infected, antiretroviral-naïve patients starting tenofovir/emtricitabine associated with efavirenz, atazanavir/ritonavir, or lopinavir/ritonavir

Abstract Objectives: We performed a retrospective cohort study of HIV-infected antiretroviral-naïve patients starting a first antiretroviral therapy with tenofovir/emtricitabine plus efavirenz (EFV), atazanavir/ritonavir (ATV/r), or lopinavir/ritonavir (LPV/r). Methods: The incidence of renal impairment or proximal tubular dysfunction was evaluated during a 12-month follow-up. Renal impairment was diagnosed by a reduced estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula, and tubular dysfunction was diagnosed when ≥ 2 among proteinuria, glucosuria, hypouricaemia, hypophosphataemia, and hypokalaemia, were identified. Results: A total of 235 patients were enrolled: 82 taking EFV, 78 ATV/r, and 75 LPV/r. The mean decline in eGFR after the 12-month follow-up was significantly greater in subjects treated with ATV/r (−10.4 ml/min/1.73 m2) than in those receiving EFV (− 5.1; p = 0.002) or LPV/r (−4.8; p = 0.003). Similarly, a significantly higher incidence of proximal tubulopathy was observed among ATV/r-treated patients (14.1%) compared with patients receiving EFV (4.9%) or LPV/r (5.3%). Conclusions: In our retrospective study, naïve patients receiving tenofovir/emtricitabine and ATV/r for 12 months showed a significantly higher decline in eGFR and a significantly higher incidence of proximal tubulopathy than those receiving tenofovir/emtricitabine plus EFV or LPV/r, even though clinically evident renal toxicity associated with tenofovir-based treatment is a very uncommon event.

An Antimicrobial Stewardship Program Based on Systematic Infectious Disease Consultation in a Rehabilitation Facility

OBJECTIVE To assess the impact of an antimicrobial stewardship program (ASP) on antibiotic consumption, Clostridium difficile infections (CDI), and antimicrobial resistance patterns in a rehabilitation hospital. DESIGN Quasi-experimental study of the periods before (from January 2011 to June 2012) and after (from July 2012 to December 2014) ASP implementation. SETTING 150-bed rehabilitation hospital dedicated to patients with spinal-cord injuries. INTERVENTION Beginning in July 2012, an ASP was implemented based on systematic bedside infectious disease (ID) consultation and structural interventions (ie, revision of protocols for antibiotic prophylaxis and education focused on the appropriateness of antibiotic prescriptions). Antibiotic consumption, occurrence of CDI, and antimicrobial resistance patterns of selected microorganisms were compared between periods before and after the ASP implementation. RESULTS Antibiotic consumption decreased from 42 to 22 defined daily dose (DDD) per 100 patient days (P<.001). The main reductions involved carbapenems (from 13 to 0.4 DDD per 100 patient days; P=.01) and fluoroquinolones (from 11.8 to 0.99 DDD per 100 patient days; P=.006), with no increases in mortality or length of stay. The incidence of CDI decreased from 3.6 to 1.2 cases per 10,000 patient days (P=.001). Between 2011 and 2014, the prevalence of extensively drug-resistant (XDR) strains decreased from 55% to 12% in P. aeruginosa (P<.001) and from 96% to 73% in A. baumannii (P=.03). The prevalence of ESBL-producing strains decreased from 42% to 17% in E. coli (P=.0007) and from 62% to 15% in P. mirabilis (P=.0001). In K. pneumoniae, the prevalence of carbapenem-resistant strains decreased from 42% to 17% (P=.005), and the prevalence of in methicillin-resistant S. aureus strains decreased from 77% to 40% (P<.0008). CONCLUSIONS An ASP based on ID consultation was effective in reducing antibiotic consumption without affecting patient outcomes and in improving antimicrobial resistance patterns in a rehabilitation hospital. Infect Control Hosp Epidemiol. 2016;1-7.

Lopinavir/ritonavir trough concentrations with the tablet formulation in HIV-1-infected women during the third trimester of pregnancy

Abstract Objectives: An observational, open-label study was performed to assess changes of lopinavir/ritonavir plasma concentrations during pregnancy. Methods: Adult HIV-1-infected women during the third trimester of pregnancy and on stable antiretroviral treatment including zidovudine/lamivudine plus lopinavir/ritonavir tablets (400/100 mg twice daily) were asked to participate. This group was compared with a group of non-pregnant HIV-1-infected women receiving the same antiretroviral regimen. The trough plasma concentration (Ctrough) of lopinavir and ritonavir was assessed at steady-state by a validated high-performance liquid chromatography (HPLC)-tandem mass spectrometry method. Results: A total of 41 HIV-positive female patients were enrolled in the study, with a median age of 28 y (range 20–37 y). These patients were stratified into 2 groups: 21 women in the third trimester of pregnancy (group A) and 20 non-pregnant women (group B). The geometric mean (95% confidence interval (CI)) plasma Ctrough of lopinavir was 4205 (2418–6896) ng/ml in group A and 5098 (3187–8084) ng/ml in group B. The reduction in lopinavir plasma levels observed in group A was not significant (geometric mean ratio 0.87, 95% CI 0.62–1.32; p = 0.411). No correlation was found between lopinavir plasma levels and adverse events (such as diarrhoea and hyperlipidaemia) or immunological parameters of HIV disease, and no changes in plasma HIV viral load were reported. Conclusion: In this study, a slight but not significant decrease in the plasma lopinavir Ctrough was found during the third trimester of pregnancy, suggesting that standard dosing of the tablet formulation is also appropriate during the later stages of pregnancy.

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department

Background The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. Methods A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Results Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Conclusion Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival.

Potential role of T2Candida in the management of empirical antifungal treatment in patients at high risk of candidaemia: a pilot single-centre study

Objectives We estimated the diagnostic accuracy of T2Candida, with blood culture (BC) as the gold standard, and compared turnaround time between these two techniques in order to investigate the potential role of T2Candida in the management of empirical antifungal treatment (EAT). Methods We performed a single-centre prospective observational study in patients with severe sepsis or septic shock and multiple risk factors for candidaemia. Results We analysed 46 out of 50 screened patients. All patients received an echinocandin as EAT; the median EAT duration was 7 days (IQR 4-13 days). BCs were negative in 31 (67.4%) patients, positive for bacteria in 14 (30.4%) patients and positive for Candida albicans in 1 (2.2%) patient. T2Candida was negative, invalid and positive in 37, 5 and 4 patients, respectively. T2Candida and BC results were concordant in all but three patients, where T2Candida was positive and BCs were negative. Two of them were on antifungal prophylaxis at the time of enrolment. T2Candida reduced time to a negative result by 5 days. T2Candida performance was: sensitivity = 100% (95% CI 2.5%-100%), specificity = 91.8% (95% CI 78%-98%), positive predictive value = 25% (95% CI 0.63%-80.6%) and negative predictive value = 100% (95% CI 89.7%-100%). Conclusions In patients with multiple risk factors for candidaemia and severe sepsis or septic shock, T2Candida may be helpful to reduce the length of EAT.