Prognostic Potential of the Panfungal Marker (1 → 3)-ß-D-Glucan in Invasive Mycoses Patients.

We analyze the prognostic potential of (1 → 3)-ß-D-glucan (BG) levels in predicting clinical outcomes in patients with invasive fungal infections, on a population undergoing 253 episodes (177 with positive and 76 with negative outcome). Using linear regression analysis, we assessed the prognostic potential of kinetically evaluated BG levels and we found an overall sensitivity and specificity of 68 and 82%, respectively. Moreover, using an interpretative algorithm based on two distinct cutoff values, we were able to predict the outcome in 84% of the studied population with a diagnostic accuracy of 82%.

Evaluation of serum (1 → 3)-ß-D-glucan clinical performance: kinetic assessment, comparison with galactomannan and evaluation of confounding factors.

PURPOSE: We investigated the clinical performance of (1 → 3)-ß-D-glucan (BG), as an early marker of invasive fungal infections (IFI), in different clinical settings. METHODS: BG serum levels were assessed by Fungitell (Associates of Cape Cod, Inc), in parallel with galactomannan (GM) when requested by clinicians. By a prospective monocentric study, 270 episodes at risk or with suspect of IFI were enrolled, namely 58 proven-probable invasive aspergillosis (IA), 27 proven invasive candidiasis (IC), 11 possible IC, 16 P.jirovecii pneumonia (PJP), 4 episodes of other IFI and 154 non-IFI controls. RESULTS: We found that (a) the BG overall sensitivity, specificity, positive predictive value and negative predictive value (NPV) were 87.9, 80.5, 76.7 and 89.9 %, respectively; (b) the highest sensitivity was found in the IC groups, followed by PJP, IA and other IFI groups; (c) an association was observed between BG kinetics and patients outcome; (d) in the IA episodes, the combination of BG or GM vs GM alone increased sensitivity from 60.0 to 83.3 % in the haematological patients; (e) false-positive BG results were related to Gram-negative infections or infusion of polyclonal IgM-enriched immunoglobulins, where high levels of BG were indeed detected. CONCLUSION: Besides strengthening its overall good clinical performance, we provide evidence that serum BG correlates with clinical outcome and that, once used in combination with GM, BG allows to enhance IFI diagnosis rate. The high sensitivity and NPV, observed in the Intensive Care Unit setting, open to BG validation as a marker for assessment of antifungal treatment.

Clinical performance of a commercial real-time PCR assay for Aspergillus DNA detection in serum samples from high-risk patients: comparison with a galactomannan enzyme immunoassay.

We investigated the clinical performance of a polymerase chain reaction (PCR)-based commercial platform, the Myconostica MycAssay™ Aspergillus (MAP), for fungal DNA detection in the serum of patients at risk of invasive aspergillosis (IA). Sixty-four hospitalized patients were prospectively enrolled and a total of 71 different episodes were investigated (30 episodes were clinically/microbiologically classified as IA and 41 as control episodes). When MAP was compared to the galactomannan (GM) assay, no significant differences were found in terms of sensitivity (46.7% vs. 50.0%), specificity (97.6% vs. 95.1%), positive predictive value (PPV) (93.3% vs. 88.2%), and negative predictive value (NPV) (71.4% vs. 72.2%). The corresponding areas under the curve (AUC) of the receiver operating characteristic (ROC) curves were also superimposable. Overall, because of the good agreement between the two assays and considering the high specificity and PPV of the MAP, we suggest the use of this PCR-based platform as a second-level examination for the evaluation of clinically undefined cases where culture or GM have provided positive results.

Changing Italian nosocomial-community trends and heteroresistance in Staphylococcus aureus from bacteremia and endocarditis.

Bloodstream infections due to Staphylococcus aureus (BSI) are serious infections both in hospitals and in the community, possibly leading to infective endocarditis (IE). The use of glycopeptides has been recently challenged by various forms of low-level resistance. This study evaluated the distribution of MSSA and MRSA isolates from BSI and IE in 4 Italian hospitals, their antibiotic susceptibility--focusing on the emergence of hVISA--and genotypic relationships. Our results demonstrate that the epidemiology of MRSA is changing versus different STs possessing features between community-acquired (CA)- and hospital-acquired (HA)-MRSA groups; furthermore, different MSSA isolated from BSI and IE were found, with the same backgrounds of the Italian CA-MRSA. The hVISA phenotype was very frequent (19.5%) and occurred more frequently in isolates from IE and in both the MSSA and MRSA strains. As expected, hVISA were detected in MRSA with vancomycin minimum inhibitory concentrations (MICs) of 1-2 mg/l, frequently associated with the major SCCmec I and II nosocomial clones; this phenotype was also detected in some MSSA strains. The few cases of MR-hVISA infections evaluated in our study demonstrated that 5 out of 9 patients (55%) receiving a glycopeptide, died. Future studies are required to validate these findings in terms of clinical impact.

Aedes albopictus (Diptera: Culicidae) population size survey in the 2007 chikungunya outbreak area in Italy. II: Estimating epidemic thresholds.

Our study compared different estimates of adult mosquito abundance (Pupal Demographic Survey [PDS], Human Landing Collection [HLC], Number of Bites declared by Citizens during interviews [NBC]) to the mean number of eggs laid in ovitraps. We then calculated a disease risk threshold in terms of number of eggs per ovitrap above which an arbovirus epidemic may occur. The study was conducted during the summers of 2007 and 2008 in the Emilia-Romagna region of Italy where a chikungunya epidemic occurred in 2007. Ovitrap monitoring lasted from May to September, while adult sampling by means of PDS, HLC, and NBC was repeated three times each summer. Based on calculated rate of increase of the disease (R(0)) and the number of bites per human per day measured during the outbreak, we estimated that only 10.1% of the females transmitted the chikungunya virus in the principal focus. Under our conditions, we demonstrated that a positive correlation can be found between the females' density estimated by means of PDS, HLC, and NBC and the mean number of eggs in the ovitraps. We tested our hypothesis during the 2007 secondary outbreak of CHIKV in Cervia, and found that R(0) calculated based on the number of biting females estimated from the egg density was comparable to the R(0) calculated based on the progression of the human cases. The identification of an epidemic threshold based on the mean egg density may define the high risk areas and focus control programs.

Aedes albopictus (Diptera: Culicidae) population size survey in the 2007 Chikungunya outbreak area in Italy. I. Characterization of breeding sites and evaluation of sampling methodologies.

The population of Aedes albopictus (Skuse) (Diptera: Culicidae) was measured in four towns in northern Italy by means of Stegomyia indices (house index: percentage of houses with at least one active breeding site; container index: percentage of containers with larvae; and Breteau index: number of active breeding sites per premises), pupae per premises index (PPI), pupae per hectare index (PHI), and ovitrap monitoring. A detailed investigation on types and number of productive or potential larval habitats in the inspected premises was performed. Catch basins were the most productive breeding sites in both private and public areas. The influence of the premises maintenance and premises shading indices (PMI and PSI) on the population indices and the correlations between the latter and egg density were assessed. The highest PPI was found in badly maintained premises, most times combined with shady coverage. Stegomyia indices and PPI were well correlated with each other, but not with the PHI, which also included the pupae collected in public areas. We obtained a highly positive correlation (R = 0.86) between the PHI and weekly mean egg density estimated 7-14 d after inspection of the premises. The number of females per hectare, calculated using the Focks model, was correlated with the mean egg density of the week after sampling (R = 0.79), and we propose that ovitrap monitoring can be used to evaluate the efficiency of the control activities or to determine a mean egg density threshold for epidemic risk evaluation.

[Atheroembolic renal disease]. / La malattia renale ateroembolica.

Atheroembolic renal disease can be defined as renal failure due to occlusion of the renal arterioles by cholesterol crystal emboli usually dislodged from ulcerated atherosclerotic plaques of the aorta. Atheroembolic renal disease is part of multisystem disease, since the embolization usually involves other organ systems such as the gastrointestinal system, central nervous system, and lower extremities. The kidney is frequently involved because of the proximity of the renal arteries to the abdominal aorta, where erosion of atheromatous plaques is most likely to occur. Embolization may occur spontaneously or after angiographic procedures, vascular surgery, and anticoagulation. In the last decade, atheroembolic renal disease has become a recognizable cause of renal disease. An ante-mortem diagnosis of the disease is possible in a significant proportion of cases as long as the level of diagnostic suspicion is high. The disease can severely affect kidney and patient survival. Although no specific treatment has been proven efficacious, use of statins may be justifiable and such therapy would be a reasonable choice for future treatment trials.

[Controversial issues in the Giornale Italiano di Nefrologia: how to treat patients with focal segmental glomerular sclerosis]. / Le contoversie del Giornale Italiano di Nefrologia: come trattare i pazienti con glomerulosclerosi focale segmentaria?

Primary focal segmental glomerular sclerosis (FSGS) commonly presents with nephrotic syndrome. Spontaneous remission is rare and persistent nephrotic syndrome is a marker of poor prognosis. For this reason, obtaining remission using drugs with minimal side effects is desirable. The treatment of FSGS, however, represents a challenge. Not only is there a lack of prospective controlled trials, but FSGS is a syndrome of unknown pathophysiology, generally treated with drugs having a mechanism of action that is poorly understood in this setting, the use of which has often drawn criticism because it is based on empirical assumptions rather than pathogenetic evidence. At present, corticosteroids are the standard first-line approach in patients with idiopathic FSGS. Cytotoxic agents and cyclosporin A constitute a good therapeutic option for steroid-dependent patients or frequent relapsers. Mycophenolate mofetil, rituximab and plasmapheresis should be used as rescue treatment because further studies are required to determine their safety and efficacy. Clearly, real progress in FSGS treatment can only be obtained by research focused on the pathophysiology of this disease, so that a therapeutic approach can be defined that is based on reason rather than chance.

Chikungunya epidemic outbreak in Emilia-Romagna (Italy) during summer 2007.

During summer 2007, an outbreak due to the local transmission of CHIKV by Aedes albopictus mosquitoes occurred moreover in Italy, Emilia-Romagna Region, in the areas of Ravenna, Forli-Cesena, Rimini and Bologna cities. The original outbreak developed in Castiglione di Cervia and Castiglione di Ravenna, two small villages divided by a river. The first case was recorded on August 9th the epidemic outbreak then spread out, thus giving rise to smaller secondary outbreaks and further sporadic cases in the same area, for a total of 337 suspected cases, 217 of which confirmed by blood analysis. CHIKV has been isolated and characterized on both blood and mosquito samples.

A regional plan of the Emilia-Romagna regional bureau for Aedes albopictus control--year 2008.

Following the outbreak of Chikungunya virus fever occurred in the summer 2007 in Emila Romagna (an administrative region located along the Adriatic (East) coast of Italy) a regional plan for Aedes albopicus control has been implemented. The major items of the plan are here reported and discussed.

Gram-positive bloodstream infections in liver transplant recipients: incidence, risk factors, and impact on survival.

The objective of the study was to assess the incidence, risk factors, and survival of gram-positive bloodstream infections (GP-BSI(s)) among liver transplant recipients during the first year after transplantation. Between October 2000 and September 2006, 42 episodes of GP-BSI(s) occurred in 205 patients with an overall incidence of 0.20 episodes/patient. Coagulase-negative staphylococci were detected in 45.2% of cases, Enterococcus species in 42.9% (E faecalis, eight; E faecium, seven; E avium, two; E gallinarum, one) and Staphylococcus aureus in 11.9%. Retransplantation was the only independent risk factor for GP-BSI (odds ratio [OR], 0.253; 95% confidence interval (CI), 0.089 to 0.715; P = .009). Thirty-day mortality rate was 28.5% and S aureus infections were related to a poorer outcome. It is noteworthy that all the isolates of S aureus were methicillin-resistant. Ampicillin was inactive against all the strains of E faecium and 50% of E avium isolates, but active against all E faecalis and E gallinarum strains. All the isolates were glycopeptide-susceptible. No significant differences in mortality rate were observed in relation to sex, etiologies of end-stage liver disease, cytomegalovirus infection/reinfection, type of donor, rejection, or retransplantation. GP-BSI, the only independent risk factor for death (OR, 0.262; 95% CI, 0.106 to 0.643; P = .003), reduced the survival rate by 26% in the first year posttransplant. In conclusion, GP-BSI(s) impact significantly on morbidity and mortality posttransplant, particularly among retransplantations. Control measures are required to reduce the incidence of GP-BSI(s) in liver transplant recipients. These findings must be considered when empirical antimicrobial therapy is indicated while awaiting blood-culture results.

[Renal involvement in systemic sclerosis]. / Sclerosi sistemica e coinvolgimento renale.

Systemic sclerosis is an autoimmune disease characterized by fibrosis of the skin and internal organs. Raynaud's phenomenon generally precedes other disease manifestations. The distribution of skin lesions and the internal organ involvement are the basis for the classification into limited and diffuse forms of the disease. Clinically evident renal disease is observed in 10-40% of patients. The most common renal presentation is renal crisis, characterized by acute onset of renal failure and severe hypertension; some patients remain normotensive, showing microangiopathic hemolytic anemia. Renal complications due to penicillamine may occur in some patients. Finally, ANCA-associated glomerulonephritis is a rare complication of the disorder. In spite of treatment with ACE inhibitors, 20-50% of patients with renal crisis progress to end-stage renal disease. In the absence of a specific therapy, there is accumulating evidence supporting the effectiveness of prostacyclin derivatives, antifibrotic and immunosuppressive drugs. The evidence is strong that the ACE inhibitors that are used in renal crisis are disease modifying. In our series including 193 patients with systemic sclerosis, renal involvement was observed in 19 patients; 11 presented renal crisis (hypertensive in 8; normotensive in 3); 5 had chronic nephropathy; 2 developed penicillamine-induced nephrotic syndrome, and 1 ANCA-associated glomerulonephritis. Renal disease occurs in a minority of patients with systemic sclerosis, and may have a variable clinicopathological picture. As renal involvement is associated with a worse prognosis, careful monitoring of blood pressure, urine chemistry and renal function is required, particularly in patients with diffuse skin disease.

Epidemiology of candidaemia and antifungal susceptibility patterns in an Italian tertiary-care hospital.

The epidemiological and antifungal susceptibility data for 94 episodes of candidaemia in an Italian tertiary-care hospital between January 2000 and August 2003 were evaluated by prospective laboratory-based surveillance. The incidence of fungaemia was 0.90 episodes/10 000 patient-days, and the most common species isolated were Candida albicans (40.4%), Candida parapsilosis (22.3%), Candida tropicalis (16.0%) and Candida glabrata (12.8%). Among 24 patients who received antifungal prophylaxis, non-albicans Candida spp. were more prevalent than C. albicans (p 0.012). The 30-day mortality rate was high (38.2%), particularly for haematological (71.4%) and solid-organ transplant patients (50.0%), and in individuals with C. tropicalis and C. glabrata bloodstream infections (60.0% and 50.0%, respectively). In-vitro susceptibility tests demonstrated that 95% of the isolates were susceptible to amphotericin B (MIC < 2 mg/L), 98.1% to posaconazole (MIC < 1 mg/L), 95.8% to flucytosine (MIC < 32 mg/L) and fluconazole (MIC < 64 mg/L), and 94.7% to itraconazole (MIC < 1 mg/L). Posaconazole was active (MIC 0.5 mg/L) against all three isolates of Candida krusei, which had reduced susceptibility to both fluconazole and itraconazole. Overall, non-albicans Candida spp. accounted for 60% of the episodes of candidaemia, which could be related to the use of antifungal prophylaxis. Resistance is still uncommon in Candida spp. recovered from blood cultures. The in-vitro activity of posaconazole is encouraging, and this agent could play an important role in the management of invasive candidiasis, including episodes caused by inherently less susceptible species such as C. krusei.

A simultaneous outbreak of Serratia marcescens and Klebsiella pneumoniae in a neonatal intensive care unit.

We describe two concurrent outbreaks of Serratia marcescens and Klebsiella pneumoniae in a neonatal intensive care unit (NICU). Over a 16-month period, a total of 27 infants were either colonized (N=14) or infected (N=13). There were 15 cases of S. marcescens and 11 cases of K. pneumoniae. Both micro-organisms were involved in one fatal case. Seven preterm babies developed septicaemia, two had bacteraemia, three had respiratory infections and one had purulent conjunctivitis. The S. marcescens and K. pneumoniae isolates were investigated by three molecular methods: enterobacterial repetitive intergenic consensus polymerase chain reaction (PCR), arbitrary primed PCR with M13 primer, and random amplification of polymorphic DNA. Different patterns were found in the 16 S. marcescens epidemic isolates from 16 newborn infants. The major epidemic-involved genotype was linked to the first nine cases and this was subsequently replaced by different patterns. Eight different typing profiles were also determined for the 13 K. pneumoniae isolates from 12 newborn infants. Four K. pneumoniae bacteraemic strains proved to be identical. In conclusion, the typing results revealed that two different micro-organisms (S. marcescens and K. pneumoniae) were simultaneously involved in invasive nosocomial infections in preterm newborns. Two simultaneous clusters of cases were documented. Heterogeneous genotypes among both species were also demonstrated to be present in the NICU at the same time. A focal source for both micro-organisms was not identified but cross-transmission through handling was probably an important route in this outbreak. Strict adherence to handwashing policies, cohorting, isolation of colonized and infected patients, and rigorous environmental hygiene were crucial measures in the containment of the epidemic.

Atherosclerotic renovascular disease: medical therapy versus medical therapy plus renal artery stenting in preventing renal failure progression: the rationale and study design of a prospective, multicenter and randomized trial (NITER).

BACKGROUND: Many studies suggest a major prevalence of atherosclerotic renovascular disease (ARVD), caused by mono or bilateral renal artery stenosis (RAS). Unfortunately, there is no definite therapy to cure this disease to date; therefore, ARVD is burdened by important clinical complications with high social and economic costs. The last few years have seen important advancements in both medical therapy and in interventional radiology (for example, percutaneous transluminal renal artery stenting (PTRS)). All of them could affect, in some way, the natural history of ARVD, but to date the optimal strategy has not been established. METHODS: The protocol of a prospective, multicenter, randomized trial "Nephropathy Ischemic Therapy (NITER)" is presented. It enrolls patients with stable renal failure (glomerular filtration rate (GFR) >or=30 ml/min) and hypertension, and hemodynamically significant atherosclerotic ostial RAS (>or=70%) diagnosed by duplex Doppler (DD) ultrasonography and confirmed by magnetic resonance angiography (MRA). This study aims to evaluate whether medical therapy plus interventional PTRS is superior to medical therapy alone according to the following combined primary endpoint: death or dialysis initiation or reduction by >20% in estimated GFR after 0.5, 1, and 2 yrs of follow-up and an extended follow-up until the 4th year. Medical therapy means drugs to control hypertension, improve dyslipidemia and optimize platelet anti-aggregant therapy. The sample size is estimated in 50 patients per group to achieve a statistical significance of 0.05 in case of a reduction by 50% in the combined endpoints.

Outcome, incidence, and timing of infections in small bowel/multivisceral transplantation.

The objective of this study was to assess the timing, incidence, and outcome of infections in patients with small bowel/multivisceral transplants (SB/MV Tx). A 180-day follow-up was obtained on 13 SB/MV patients transplanted from January 2001 to June 2002. Fifty-six documented infections were observed. By Kaplan-Meier analysis for time to infection, most of which were of bacterial origin (more than 86%), revealed most events to have occurred within the first month post-Tx. Viral infections were equally distributed after the 30th postoperative day.

[Head injuries in the pediatric emergency department: a 5-year experience at the Pediatric Clinic of Modena]. / Il trauma cranico in accettazione pediatrica: esperienza di cinque anni nella clinica pediatrica di Modena.

We re-evaluated the cases of 436 children with minor head injury admitted in the paediatric department of Modena University Hospital in the years 1991-1995 in order to revise diagnostic and therapeutic protocols. The external lesions, the presence of loss consciousness, vomiting, vegetative reactions, late complications, skull X ray, TC scan and EEG were considered. Signs and symptoms at admission have been faced with instrumental findings and eventual late complications to evaluate the prognostic significance. External lesions and vomiting did not correspond to TC scan and EEG positivity or significant sequelae. A more close connection to these parameters was found when an history of immediate loss of consciousness after trauma, or presence of vegetative reactions. Skull X ray appeared useless both to judge the seriousness of the lesion and to formulate a prognosis. EEG appeared a sensible tool to evaluate the gravity of the trauma and its late consequences. TC has confirmed to be the unique instrument able to solve any diagnostic or prognostic doubt. When symptoms suggest a bad prognosis, diagnostic procedures should be limited to TC and EEG. By our point of view, patients that at admission have a normal neurological examination at the Glasgow Coma Scale, no significant symptoms and signs, an history of a minor impact dynamic and no signs of child abuse, can be discharged from the emergency department; in this case parents should be instructed how to do an observation at home in order to evaluate eventual complications.

[Migrant polyarthritis and EBV infection]. / Poliartrite migrante ed infezione da EBV.

A twelve-years-old boy developed fever, pharyngitis and acute migrant polyarthralgia. An increasing ASO titre was observed, so that rheumatic fever was firstly diagnosed. Finally splenomegaly and positive IgG and IgM against Epstein Barr virus led to the diagnosis of acute EBV infection with polyarthritis. EBV infection should be considered into the differential diagnosis of migrant polyarthritis.

Characteristics and outcome predictors of patients involved in an outbreak of Burkholderia cepacia complex.

A Burkholderia cepacia complex outbreak occurred among ventilated non-cystic fibrosis patients in an intensive care unit (ICU) in Italy: 33 colonized and 13 infected patients were included in a retrospective study aimed at investigating factors related to clinical infection and mortality. Demographic/clinical conditions and mortality did not vary significantly between colonized and infected patients, both groups showing high mortality rates compared with the overall ICU population and similar to that observed in patients with other infections. In multivariate regression analysis, disease severity (defined by the Simplified Acute Physiology Score II) and age were the only independent predictors of early mortality (odds ratio: 1.12; 95% confidence interval: 1.02-1.26; and 1.07; 1.01-1.15, respectively).