Clinical characteristics, management and outcome of patients with invasive candidiasis hospitalized in Internal Medicine Units: findings from a registry by the Italian Scientific Society FADOI.

PURPOSE: Invasive candidiasis (IC) is a challenging clinical condition, burdened by relevant mortality and morbidity. There is limited knowledge on the occurrence and management of IC in Internal Medicine Units (IMUs). Aim of this study was to provide real-world data on this topic. METHODS: Consecutive objectively diagnosed cases of IC were collected in this prospective registry, which involved 18 IMUs in Italy. Patients were followed-up to 90 days from the diagnosis of candidemia. RESULTS: A total of 111 patients were observed (median age 78, IQR 67-83) for an overall incidence of infection of 1.89 cases/1000 hospital admissions. Candida albicans was the most frequent isolated species (62%), followed by Candida parapsilosis (17%) and Candida glabrata (13%). Echinocandins and fluconazole were used as initial therapy in 56.8 and 43.2% of patients, respectively. Antifungal therapy was started within 24 h in 18.9% of patients, in 40.6% in the period 1-3 days, and in 40.5% of patients more than 3 days after blood cultures. Death rate was 19.8% at 30 days and 40.5% at 90 days. At multivariable analysis concomitant bacteremia (i.e. polymicrobial sepsis), and fluconazole as the initial therapy were associated with an increased risk of death at 90 days. CONCLUSIONS: The incidence of IC is not negligible, and our registry confirmed that these patients have a relevant mortality rate at 90 days. Concomitant bacteremia, featuring polymicrobial sepsis, and starting antifungal treatment with fluconazole instead of echinocandins independently increase the risk of death. Efforts are needed to improve the awareness and management of IC in IMUs.

The ratio between kidney volume and function increases with the progression of nephropathy in Type 2 diabetes.

OBJECTIVE: In Type 2 diabetes, it is not clear if renal size is constantly related to the glomerular filtration rate. In addition, it is not known if kidney volume (KV) is associated with an increased urinary albumin and IgG excretion. METHODS: The relationship between kidney volume, creatinine clearance (CrCl), urinary albumin and IgG excretion in 95 Type 2 diabetic patients with different stages of nephropathy (1 - 4 Stage sec NKDF-QD) was elevated and compared to 85 non-diabetic subjects with similar degree of kidney function. RESULTS: In Type 2 diabetic patients the KV/CrCl ratio was increased, in comparison with the control subjects, from about 15% in Stage 1 to 53% in Stage 4. In T2D subjects, significant correlations were found between KV and urinary albumin excretion (r = 0.665, p < 0.05), and between KV and urinary IgG excretion (r = 0.800, p < 0.001). CONCLUSION: The present study finds that Type 2 diabetic subjects, are characterized by an increased ratio between KV/CrCl, throughout the different progressive stages of nephropathy. In Type 2 diabetes relationships between KV and urinary albumin and between KV and IgG excretion also were found to be significant, suggesting a role for the impaired size selectivity of proteinuria as a possible determinant of KV.

Effects of dietary protein restriction on albumin and fibrinogen synthesis in macroalbuminuric type 2 diabetic patients.

AIMS/HYPOTHESIS: Diabetic nephropathy is associated with hypoalbuminaemia and hyperfibrinogenaemia. A low-protein diet has been recommended in patients with diabetic nephropathy, but its effects on albumin and fibrinogen synthesis are unknown. METHODS: We compared the effects of a normal (NPD; 1.38 +/- 0.08 g kg(-1) day(-1)) or low (LPD; 0.81 +/- 0.04 g kg(-1) day(-1)) -protein diet on endogenous leucine flux (ELF), albumin and fibrinogen synthesis (L-[5,5,5,-2H3]leucine infusion), and markers of inflammation in nine type 2 diabetic patients with macroalbuminuria. Six healthy participants on NPD served as control participants. RESULTS: In comparison with healthy participants, type 2 diabetic patients on an NPD had similar ELF, reduced serum albumin (38 +/- 1.1 vs 42 +/- 0.8 g/l; p < 0.05), similar fractional synthesis rates (FSR) and absolute synthesis rates (ASR) of albumin, and both increased plasma fibrinogen concentration [10.7 +/- 0.6 vs 7.2 +/- 0.5 micromol/l (3.64 +/- 0.22 vs 2.45 +/- 0.18 g/l); p < 0.05] and fibrinogen ASR [11.03 +/- 1.17 vs 6.0 +/- 1.8 micromol 1.73 m(-2) day(-1) (3.7 +/- 0.4 vs 1.9 +/- 0.3 g 1.73 m(-2) day(-1)); p < 0.01]. After LPD, type 2 diabetic patients had the following changes in comparison with NPD: reduced proteinuria (2.74 +/- 0.4 vs 4.51 +/- 0.8 g/day; p < 0.05), ELF (1.93 +/- 0.08 vs 2.11 +/- 0.08 micromol kg(-1) min(-1); p < 0.05) and total fibrinogen pool; increased serum albumin (42 +/- 1 vs 38 +/- 1 g/l; p < 0.01) and albumin ASR (14.1 +/- 1 vs 9.9 +/- 1 g 1.73 m(-2) day(-1); p < 0.05); and reduced plasma IL-6 levels, which were correlated with albumin ASR (r = -0.749; p < 0.05). CONCLUSIONS/INTERPRETATION: LPD in type 2 diabetic patients with diabetic nephropathy reduces low-grade inflammatory state, proteinuria, albuminuria, whole-body proteolysis and ASR of fibrinogen, while increasing albumin FSR, ASR and serum concentration.

Neurotoxicity induced by Cefepime in a very old hemodialysis patient.

Neurotoxicity is an unusual complication of cephalosporin therapy. Only few cases of neurotoxicity induced by Cefepime have been described and probably the frequency of Cefepime-induced status epilepticus is underestimated. We report a case of an 82 year-old male, ESRD patient on chronic hemodialysis program affected by pneumonia, who received a treatment with intravenous Cefepime (1 g/day) and developed a seizure 4 days after the starting antibiotic therapy. Cefepime-induced neurotoxicity was suspected and its administration was immediately discontinued. In order to increase Cefepime clearance a hemodialysis session was urgently started and an improvement of his conscious level was observed. On the following day, after a second hemodialysis session his clinical condition and the status of neurotoxicity were completely recovered. The patient was discharged from the hospital in stable clinical condition one week later. At variance with the cases previously reported, the daily dose of Cefepime administrated to our patient was 50% lower and respected drug prescription dosage. Thus, we speculate on the hypothesis that advanced age of our patient and metabolic encephalopathy induced by chronic uremia made him more sensitive to the neurotoxicity induced by the drug. In conclusion, our case suggests that, in very old patients on long-term hemodialysis, it should be considered, to avoid neurotoxicity, to monitor the clinical neurological status, to use Cefepime at lower dosage than that allowed in patients with severe renal impairment (1 g/day) and, when possible, to evaluate Cefepime plasma levels. However, in these patients, other agents of the same class should be considered such as Cefotaxime and Ceftriaxone which are characterized by both an hepatic and renal excretion. In alternative to cephalosporins, antibiotics with the same action spectrum in the absence of neurological toxicity (i.e. Meropenem) should be recommended.