Percutaneous ablation in perivascular-HCC: impact of liver parenchyma and characteristics of vascular structures on the outcomes.

AIM: Percutaneous radiofrequency ablation (RFA) is a standard treatment for small-HCC (<3 cm). However, some features such as proximity to intrahepatic vascular structures (perivascular location) seem to be related to short- and long-term outcomes. The aims of the study were to investigate the features related to ablation success and local tumor progression (LTP) in patients submitted to percutaneous ablation for perivascular-HCC. MATERIALS AND METHODS: From January 2010 to May 2021, 132 perivascular-HCC nodules ablated with US-guided single probe percutaneous RFA were retrospectively analyzed. Univariate analysis and multivariable Cox regression model were used to identify factors that were independently related to ablation success and LTP-free survival. RESULTS: The overall ablation success rate was 71.9% (n=95). Morbidity and mortality rates were 4.0% and 0.0%. The features related to ablation success: nodule size (≤20 mm vs. >20 mm) (OR 2.442, p=0.031), major vascular structures diameter (3-5 mm vs ≥ 5 mm) (OR 2.167, p=0.037) and liver parenchyma (cirrhosis vs no-cirrhosis) (OR 2.373, p=0.033). The following features resulted independently related to better LTP-free survival: nodule size ≤20 mm (HR 2.802, p=0.003), proximity to glissonean pedicles (HR 1.677, p=0.028), and major vascular structure diameter <5 mm (HR 1.987, p=0.041). CONCLUSIONS: Perivascular location confirmed to be a difficult and unfavorable indication for percutaneous ablation for HCC nodules. However, perivascular nodules not suitable for surgery with low-risk features (size <20 mm, proximity to glissonian pedicles and vascular diameter <5 mm) may be treated with RFA with satisfactory outcomes.

Previous bloodstream infections due to other pathogens as predictors of carbapenem-resistant Klebsiella pneumoniae bacteraemia in colonized patients: results from a retrospective multicentre study.

INTRODUCTION: the purpose of this retrospective multicenter study was to assess whether the risk of developing bloodstream infections (BSI) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in colonized patients is influenced by the occurrence of BSI due to other pathogens. METHODS: from January 2012 to March 2014, all patients with at least one rectal swab positive for CRKP and at least 30 days of previous hospital stay were included in the study. The primary outcome measure was CRKP BSI, defined as a time-to-event endpoint. The role of potential predictors was evaluated through univariable and multivariable Cox regression analyses, considering previous BSI as a time-dependent variable. RESULTS: during the study period, 353 patients met the inclusion criteria. Thirty-seven developed a CRKP BSI (11%). A higher incidence of CRKP BSI was observed in presence rather than in absence of previous BSI. In the final multivariable model of risk factors for CRKP BSI, multisite colonization (hazard ratio [HR] 13.73, 95% confidence intervals [CI] 3.29-57.32, p < 0.001), ICU stay (HR 3.14, 95% CI 1.19-8.31, p = 0.021), and previous BSI (p = 0.026, with the overall effect being mainly due to Enterococcus spp. BSI vs absence of BSI, HR 6.62, 95% CI 2.11-20.79) were associated with the development of CRKP BSI, while an inverse association was observed for age (HR 0.98, 95% CI 0.95-1.00, p = 0.027). CONCLUSIONS: previous BSI due to other pathogens were associated with an increased risk of CRKP BSI that was independent of other factors in colonized patients with prolonged hospital exposure.

The ghost dead: ethical and medico legal analysis on the Mediterranean tragedies.

Background: Cadaveric identification represents a legal, moral and medico-legal obligation and also fulfills the ethical function to allow the living to offer their dead a merciful burial. In the Mediterranean basin we have been witnessing for years a struggle for life where hundreds of migrants die in an attempt to reach Europe. For these people right to be recognized is not easy because of ante-death biological data are not always available for comparison, and DNA analysis is not always feasible cause for the absence of data with which to compare. In Italy a multidisciplinary protocol has been adopted that involves the acquisition of data provided by family members present in the countries of origin. Materials and Methods: Between August 2015 and December 2021, bodies of 879 migrants of various nationalities washed up on the shores of Sicily and Calabria. These men, women, and children, in various states of preservation, were examined. Each body underwent a multidisciplinary approach. External examination and autopsy aimed to determine the cause of death for judicial purposes and to facilitate individual identification. Whenever possible bodies underwent total body post-mortem computed tomography examination to identify fractures and prosthetic implants. including inspection of the third molar to provide an estimate of the age. Conclusions: The activity carried out in cooperation with Prefecture, Scientific Police, and National and International Red Cross highlighted the importance of employing multiple scientific skills to compensate for the lack of biological information. The importance of appropriate behaviors to avoid contamination and ensure proper preservation underlines the importance of the establishment of a dedicated database.

Defect detection in additively manufactured AlSi10Mg and Ti6Al4V samples using laser ultrasonics and phase shift migration.

Laser ultrasonics (LU) is a non-contact and non-destructive method with a high data acquisition rate, making it a promising candidate for in-situ monitoring of defects in different additive manufacturing (AM) processes, including laser powder bed fusion (LPBF) and directed energy deposition, as well as final part inspection. In order to see the effect of various artificial defect types on an LU sub-surface reconstruction, AlSi10Mg samples with side through-holes, as well as Ti6Al4V samples with bottom blind holes and trapped powder were printed using LPBF, and then ultrasound B-scans of the samples were obtained using an LU system. The resulting scan data was processed using a custom frequency domain phase shift migration (PSM) algorithm, to reconstruct the defects and their locations. Novel ways of pre-processing the B-scan, used as an input to PSM, and taking advantage of its frequency representation, are demonstrated. Newton's method was used to find a stationary phase approximation, used to account in the frequency domain for the fixed offset emitter-receiver arrangement within the PSM calculation. The Newton's method calculation time was reduced by 33%, by using an approximation of the phase function to find an initial guess. The smallest defects that were detected using this method were in the size range between 200 to 300µm for the bottom hole defects, using an 8 ns laser pulse duration. The effect of the laser on the surface of a part being built, and the challenges and further work needed to integrate LU in a LPBF machine for in-situ inspection are discussed.

DNA bacterial load in children with bacteremic pneumococcal community-acquired pneumonia.

This study was conducted to evaluate the association between pneumococcal DNA load and parapneumonic pleural effusion (PPE) in children with community-acquired pneumonia. Bacterial load was quantified and related to the presence of PPE with or without empyema in 72 otherwise healthy children aged ≤5 years who were hospitalised because of radiographically confirmed CAP and showed a real-time polymerase chain reaction that was positive for Streptococcus pneumoniae. The proportion of children with a high bacterial load (i.e. ≥265 DNA copies/mL) was larger among the subjects with PPE than those without it. Multivariate analysis showed that a high bacterial load was significantly associated with PPE (OR 8.65; 95% CI 1.10-67.8 vs a bacterial load of <125 copies/mL). Children with infection due to pneumococcal serotype 19A were at highest risk of developing PPE (OR 7.44; 95% CI 1.10-50.4 vs all other typeable serotypes). The patients with CAP due to pneumococcal serotypes that are not included in the 13-valent conjugate vaccine (PCV13) were more frequently affected by PPE than those with infections associated with serotypes included in the vaccine, except for serotype 19A. Bacterial loads of ≥265 DNA copies/mL are significantly associated with PPE, and serotype 19A is significantly associated with a high bacterial load and the development of PPE. The mean bacterial load of the patients with empyema was higher than that of patients with simple PPE. Although further studies are required, it seems that serotypes not included in PCV13 can play a major role in causing a higher bacterial load and PPE.

Jet or intensive care unit ventilator during simulated percutaneous transtracheal ventilation: a lung model study.

BACKGROUND: Percutaneous transtracheal ventilation (PTV) via a jet ventilator (PTJV) is considered a rescue technique in difficult airway management. However, whether a conventional ventilator can generate adequate ventilation via PTV is not known. Our goal was to evaluate the tidal volume (V(T)) generated by a conventional ventilator during simulated PTV compared with PTJV in a lung model. METHODS: A lung model simulating an adult lung was used. A catheter was inserted through the artificial trachea and connected to either a jet ventilator or a conventional ventilator. The direction of catheter insertion was perpendicular to the trachea, pointing towards the lung and away from the lung. The jet ventilator was operated at 344.7 kPa. The conventional ventilator was operated in the pressure mode at peak inspiratory pressures of 40-90 cm H(2)O. RESULTS: The jet ventilator generated larger V(T) [817 (336) ml] when the catheter was pointing towards the lung than when pointing away from the lung or perpendicular to the trachea [121 (41) and 69 (24) ml, respectively, P<0.01]. With the conventional ventilator, changes in V(T) at different direction of catheter insertion were much less [222 (81) ml catheter pointing towards the lung, 229 (121) ml perpendicular to the trachea, and 187 (97) ml away from the lung]. CONCLUSIONS: Our result demonstrated that PTJV was effective only when the catheter was pointing towards the lung and requires high operating pressure. A conventional ventilator can generate reasonable minute ventilation through the transtracheal catheter less dependent on directions of catheter insertion and should be considered during emergent PTV.

On the application of sound radiation force for focusing of powder stream in directed energy deposition.

One of the challenges in directed energy deposition via powder feeding (DED-PF) is the powder stream divergence that results in low catchment efficiency (i.e., the fraction of particles added to the melt pool). This article introduces a new ultrasound-based powder focusing method referred to as ultrasound particle lensing (UPL), tailored for powder used in DED-PF. The method uses an ultrasound phased array to produce a small volume of high-intensity ultrasound with the required period averaged sound intensity profile. UPL was used to acoustically focus streams of Ti64 and SS 316L particles with an average size of 89µm and a particle speed of 0.6 m/s, exiting from a DED-PF nozzle analog. The e-1 powder stream widths downstream of the resulting force fields for both materials were reduced by 30%. The experimental results closely match Lagrangian and Eulerian simulations of the process. This novel setup offers the possibility of fast control of the powder stream divergence angle and effective diameter in the process zone during the DED-PF process. This will in turn improve the feature resolution and catchment efficiency of the process.

Cytokine genetic profile in Whipple's disease.

Whipple's disease (WD) is a very rare chronic systemic condition characterised by a Th2/T regulatory (Treg) dysregulated immune response versus Tropheryma whipplei, a bacterium widely diffuse in the environment. To investigate whether this Th2/Treg polarised response has a genetic background, we investigated the Th1, Th2, Th17 and Treg cytokine genetic profile of 133 patients with WD. Thanks to the European Consortium on WD (QLG1-CT-2002-01049), the polymorphism of 13 cytokine genes was analysed in 111 German and 22 Italian patients using the polymerase chain reaction with sequence-specific primers (PCR-SSP) technique. The frequencies of the genotypes, haplotypes and functional phenotypes were compared with those obtained in 201 German and 140 Italian controls. Clinical heterogeneity was also considered. Functionally, WD patients may be considered as low producers of TGF-ß1, having an increased frequency of the genotype TGF-ß1+869C/C,+915C/C [12.3 % vs. 3.81 %, odds ratio (OR) = 4.131, p = 0.0002] and high secretors of IL-4, carrying the genotype IL-4-590T/T (5.34 % vs. 1.17 %, OR = 5.09, p = 0.0096). No significant association was found between cytokine polymorphism and clinical variability. Analogously to the recent cellular findings of a Th2/Treg polarised response, we showed that the cytokine genetic profile of WD patients is skewed toward a Th2 and Treg response. This was similar in both German and Italian populations. However, the significant deviations versus the controls are poorer than that expected on the basis of these recent cellular findings.

Needs and challenges of daily life for people with Down syndrome residing in the city of Rome, Italy.

BACKGROUND: Population-based surveys on the quality of life of people with Down syndrome (DS) are difficult to perform because of ethical and legal policies regarding privacy and confidential information, but they are essential for service planning. Little is known about the sample size and variability of quality of life of people with DS living in the city of Rome, which has a population of 2.7 million inhabitants. The aim of the present study is to explore the needs and challenges in health, social integration and daily life, of people with DS living in Rome. METHODOLOGY: A cross-sectional, census-based survey was conducted in 2006. All family doctors (3016 in total) of the National Health Service were involved by the Statistical Bureau of the Municipality of Rome. As per the census, every resident citizen is registered with a family doctor and every person with disabilities is coded. Associations for Down Syndrome encouraged their members to participate in the research. Questionnaires were completed by families of people with DS, in accordance with privacy laws. FINDINGS: An initial survey, conducted via a letter and a telephone contact with family doctors, identified 884 people with DS residing in the city of Rome. Data on the medical and social conditions of 518 people with DS, ranging in age from 0 to 64 years, were collected. Some 88% of these were living with their original family; 82.1% had one or more siblings, and 19.5% had lost one or both parents. A full 100% of children with DS were enrolled in the public school system. This ensures that they are fully occupied and entirely integrated in society. After secondary school there is a lack of opportunities. Thus, only 10% of adults were working with a regular contract. A mere 42.2% of people with DS aged 25-30 were involved in some form of regular activity (although not always on a daily basis). After the age of 30, the percentage of people demonstrating decline in function increased sharply, while disability-related support decreased. In other words, as people with DS age, daily life evolves increasingly around the home, with only occasional outdoor activities. CONCLUSION: The health, employment and social needs of the majority of people with DS in the city of Rome are not being met. The findings of this study underscore the urgent need for more comprehensive inclusion in society of adults with DS and for the provision of support services to create an enabling environment for inclusion. Because of the variability of performance among individuals with DS, there is a need to create more case-specific options in terms of work, living arrangements, social networking and medical services. Schooling and social inclusion in childhood alone do not guarantee a satisfactory quality of life in adulthood. It is argued herewith that policy of inclusion and support should extend over the entire lifetime of people with DS.

Pyogenic granuloma after cosmetic eye whitening. / Granuloma piogénico tras blanqueamiento ocular cosmético.

CLINICAL CASE: A 46-year-old caucasian male with a history of chronic conjunctival hyperemia, presented at our clinic 5 years after he underwent the surgical procedure of cosmetic eye whitening. On examination we observed pyogenic granuloma in the right eye; besides acute nongranulomatous anterior uveitis and necrotizing scleritis in both eyes. RESULT: Complete clinical evaluation and full work-up exclusion of systemic diseases was done. The pyogenic granuloma was treated with surgical resection, as well as anterior uveitis and necrotizing scleritis were successfully treated with systemic corticoesteroids and methotrexate. CONCLUSION: The surgical cosmetic eye whitening could have as complication the pyogenic granuloma in addition to necrotizing scleritis and nongranulomatous anterior uveitis; and be present 5 years after the procedure. The surgical resection is a successful treatment for this presentation of pyogenic granuloma.

Burden of an educational program on end of life management in a Internal Medicine ward: a real life report.

BACKGROUND AND AIM: Appropriate end of life (EOL) management in Internal Medicine wards is challanging. The aim of this study was to analyze the burden of an educational program on EOL management in a Internal Medicine ward. Materials and methods: We retrospectively analysed characteristics and management of patients consecutively died in an italian Internal Medicine ward along one year. We compared demographic, co-morbidity, pharmacological treatment in the last 48-hours of life and procedures during hospital stay in patients died six months before and after an educational program on palliative cares and EOL management addressed to a team of physicians and nurses. RESULTS: Study population was composed by 354 patients (190 females), with mean age ± DS 83.5 ± 10.6 years, one half admitted after the educational program. Eighty-four percent of deaths was exepected in the last 48 hours before exitus. Demographic characteristics and causes of hospitalization were not different before and after educational program. After the educational program the sharing of palliative care program with patient, relatives and/or caregivers (97.7% vs 85.8%, p=0.0001) and written order to withdrawal vital parameters relevation (39.5% vs 22%, p=0.0005) significantly increased, while difference in pharmacological classes prescribed in the last 48 hours of life was not find. Blood (54.8% vs 67.2%, p=0.0219) and arterial gas analysis (28.8% vs 39.5%, p=0.0435) samples in the last 48 hours of life were significantly reduced. Radiological and/or endoscopic examinations, red cells or platelets transfusion were reduced and palliative therapy was increased, despite difference between the two periods was not statistically significant. CONCLUSION: Educational program in Internal Medicine wards aimed to improve skills could contribute to make EOL management more appropriate and patient-oriented and it should be strongly encour-aged.

Rapid microbiological tests for bloodstream infections due to multidrug resistant Gram-negative bacteria: therapeutic implications.

BACKGROUND: Treating severe infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) is one of the most important challenges for clinicians worldwide, partly because resistance may remain unrecognized until identification of the causative agent and/or antimicrobial susceptibility testing (AST). Recently, some novel rapid test for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with bloodstream infections (BSIs) have become available. OBJECTIVES: The objective of this narrative review is to discuss the advantages and limitations of different rapid tests for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with BSI, as well as the available evidence on their possible role to improve therapeutic decisions and antimicrobial stewardship. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The present review is structured in the following way: (a) rapid tests on positive blood cultures; (b) rapid tests directly on whole blood; (c) therapeutic implications. IMPLICATIONS: Novel molecular and phenotypic rapid tests for identification and AST show the potential for favourably influencing patients' outcomes and results of antimicrobial stewardship interventions by reducing both the time to effective treatment and the misuse of antibiotics, although the interpretation about their impact on actual therapeutic decisions and patients' outcomes is still complex. Factors such as feasibility and personnel availability, as well as the detailed knowledge of the local microbiological epidemiology, need to be considered very carefully when implementing novel rapid tests in laboratory workflows and algorithms. Providing high-level, comparable evidence on the clinical impact of rapid identification and AST is becoming of paramount importance for MDR-GNB infections, since in the near future rapid identification of specific resistance mechanisms could be crucial for guiding rapid, effective, and targeted therapy against specific resistance mechanisms.

Activity of daptomycin on biofilms produced on a plastic support by Staphylococcus spp.

The aim of this study was to assess whether the novel lipopeptide daptomycin might be capable of disrupting or inhibiting the synthesis of biofilms produced by staphylococci. Fourteen recently isolated slime-producing methicillin-susceptible (MET-S) and methicillin-resistant (MET-R) strains (three MET-S Staphylococcus aureus, three MET-R S. aureus, three MET-S Staphylococcus epidermidis, three MET-R S. epidermidis and two vancomycin-intermediate S. aureus (VISA)) were tested. Slime formation on polystyrene plates was quantified spectrophotometrically. Daptomycin (2-64 mg/L) inhibited slime synthesis by > or =80% in MET-S strains, by 60-80% in MET-R S. aureus and by 70-95% in MET-R S. epidermidis. At 64 mg/L, biofilm synthesis decreased by 80% in the VISA isolates. Daptomycin also disrupted pre-formed biofilm: >50% breakdown of initial biofilm (5h) was observed in all strains. Disruption of mature biofilms (48 h), in terms of percentage, was more variable depending on the strain, ranging from ca. 20% in a MET-R S. epidermidis strain to almost 70% in two MET-S strains (one S. aureus and one S. epidermidis). Daptomycin at concentrations achievable during therapy promoted a statistically significant inhibition of slime synthesis (preventing biofilm building) and induced slime disruption (disaggregating its structure) both in initial and mature biofilms on a plastic support in all staphylococcal strains studied.

Tigecycline in vitro activity against gram-negative and gram-positive pathogens collected in Italy.

BACKGROUND: In this study (part of the global TEST program), the in vitro activity of tigecycline, a member of a new class of antimicrobial agents, the glycylcyclines, against clinical isolates collected in Italy was evaluated. METHODS: A total of 200 clinical isolates were collected and identified in our institution during 2005. Minimum inhibitory concentrations (MICs) of the antimicrobial agents were determined by the broth microdilution method recommended by the CLSI in 2005. RESULTS: Globally, 135 Gram-negative and 65 Gram-positive pathogens were evaluated. Tigecycline demonstrated excellent inhibitory activity against Acinetobacter spp., Haemophilus influenzae, Escherichia coli, Enterococcus spp., Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae with MIC(90)

Multimodal retinal imaging in central serous chorioretinopathy treated with oral eplerenone or photodynamic therapy.

PurposeTo correlate function and structural optical coherence tomography (OCT) to optical coherence tomography angiography (OCT-A) measures in patients affected by central serous chorioretinopathy (CSC) and to describe their changes after treatments (ie oral eplerenone, half-fluence photodynamic therapy (PDT)).Patients and methodsTwenty eyes of 16 consecutive patients with treatment-naïve CSC undergoing either eplerenone or PDT were enrolled in this prospective, observational study. All patients underwent structural OCT and OCT-A at baseline and after therapy at months 1 and 3.ResultsEleven eyes of nine patients and nine eyes of seven patients underwent eplerenone or PDT treatment, respectively. Central macular thickness (CMT) and subretinal fluid (SRF) correlated to fovea avascular zone (FAZ) area (r=0.74 and r=0.71, P=0.01) and vessel density (r=0.77 and r=0.68, P=0.01) at deep capillary plexus (DCP). CMT (P=0.0011), SRF (P=0.0005), SFCT (P=0.0016), FAZ area at DCP (P=0.0334) improved at 3-month visit. A significant reduction of deep FAZ area was appreciated in eplerenone (P=0.0204) but not in PDT (P=0.5) group. SFCT reduction was significantly higher in PDT than eplerenone group (P=0.0347).ConclusionStructural and vascular parameters are correlated in CSC and they improve after different treatments. Both half-fluence PDT and oral eplerenone do not permanently damage choriocapillaris or other choroidal layers as evaluated by OCT-A.

Activity of moxifloxacin on biofilms produced in vitro by bacterial pathogens involved in acute exacerbations of chronic bronchitis.

The aim of this study was to assess whether moxifloxacin is able to inhibit the synthesis of and to disrupt biofilms produced in vitro by bacterial pathogens involved in acute bacterial exacerbations of chronic bronchitis. Three strains each of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli recently isolated from clinical respiratory specimens and capable of slime production were used. Biofilm formation on polystyrene plates was quantified spectrophotometrically by established methodologies. Moxifloxacin (0.5 mg/L) inhibited slime synthesis by >70% in S. aureus, H. influenzae and S. pneumoniae, 45-70% in E. coli and 35-70% in M. catarrhalis. Disruption of pre-formed structures was also promoted by moxifloxacin both for initial (5h) and mature (48 h) biofilms. Drug concentrations reached during therapy (0.5-4 mg/L) resulted in a breakdown of initial biofilm of 60-80% in H. influenzae and S. pneumoniae, 48-86% in S. aureus, 37-69% in M. catarrhalis and 51-71% in E. coli. Mature biofilms were less susceptible to degradation. Moxifloxacin at concentrations that can be achieved in the bronchial mucosa during therapy therefore promotes a significant inhibition of biofilm synthesis and induces slime disruption, a feature that may be instrumental in reducing the exacerbations so frequently observed in this condition.

In vitro activity of prulifloxacin against Escherichia coli isolated from urinary tract infections and the biological cost of prulifloxacin resistance.

Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of prulifloxacin against 30 strains of Escherichia coli isolated from urinary tract infections as well as the 'biological cost' related to acquisition of resistance to the same drug in 10 uropathogenic E. coli were assessed. In terms of MIC(90), prulifloxacin was more potent than ciprofloxacin and levofloxacin. Prulifloxacin produced lower or equal MPC values than the other two fluoroquinolones (93.3% and 73.3% compared with levofloxacin and ciprofloxacin, respectively). Compared with susceptible strains, prulifloxacin-resistant mutants showed a reduced rate of growth (ranging from 20.0% to 98.0% in different culture media and incubation conditions) and a decreased fitness index (ranging from 0.959 to 0.999). They were also impaired in their ability to adhere to uroepithelial cells and urinary catheters (11.7-66.4% and 16.3-78.3% reduction, respectively) and showed a lower surface hydrophobicity (51.2-76.0%). They were more susceptible to ultraviolet irradiation (30.6-93.8% excess mortality), showed increased resistance to colicins and diminished transfer of plasmids (<1-8.5x10(-8) vs. 3.3x10(-7)-2.4x10(-4)). Synthesis of haemolysin and type I fimbriae and production of flagella were also adversely affected. This study demonstrates a strict relationship between acquisition of prulifloxacin resistance and loss of important virulence traits. In this transition, E. coli pays a severe biological cost that entails a general reduction of fitness, thus compromising competition with susceptible wild-type strains in the absence of the drug.

Antifungal resistance in Candida spp. isolated in Italy between 2002 and 2005 from children and adults.

The activity of amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole was tested in vitro against 618 clinical Candida spp. isolates, using the broth microdilution or the disk diffusion method (voriconazole). Amphotericin B and voriconazole were the most potent antifungal agents assayed (100% of susceptible strains). Resistance to fluconazole and itraconazole was detected in three (0.7%) and 11 (2.7%) isolates of Candida albicans and in four (3.7%) isolates of Candida glabrata. Flucytosine intermediate, resistant strains, or both, were observed in C. albicans (0.3% and 0.7%), C. glabrata (2.8% intermediate) and C. tropicalis (15.2% and 15.2%). C. krusei was the least susceptible species to azoles. No statistically significant differences in the rates of resistant isolates depending on site of infection and age of the patient were observed, with the exception of C. albicans and itraconazole (higher percentage of resistance in children). At present, acquired antifungal resistance represents an uncommon finding in most Candida spp. circulating in Northern Italy.

Ideal microbiological and pharmacological characteristics of a quality antimicrobial agent: comparing original and generic molecules.

This article critically evaluates the main in vitro and in vivo studies published which compare generic with the original molecules, both those administered orally and parenterally. The authors indicate that caution should be used in assuming bioequivalence of the generic drug with its clinical efficacy in clinical practice. In fact, mild differences in the content of the active ingredient, less relevant in healthy volunteers, may have an impact in the actual population, which is heterogeneous for age, sex, weight, concomitant risk factors and severity of the underlying disease, as in critically ill patients, with consequences for the patient and ecosystem. Nowadays the requirements for authorization to commercialize a generic antimicrobial agent are focused on demonstration of bioequivalence to the original molecule, with a range variability of +/-20%. However this kind of trial is not sufficient to predict the actual profile in clinical practice, particularly in critically ill patients. Thus while generics can represent an opportunity for physicians, patients and healthcare systems the regulatory procedures do not seem exhaustive, and it is probably necessary to define an ad hoc technical standard of quality before their commercialization and to perform adequate clinical trials regarding efficacy and safety of the "equivalent molecule", especially for drugs used in critically ill patients.

In vitro activity of ceftibuten at sub-inhibitory concentrations in comparison with other antibiotics against respiratory and urinary tract pathogens.

Some new features of the in vitro activity of ceftibuten, an oral third generation cephalosporin, have been studied in reference to respiratory and urinary tract pathogens included in its antibacterial spectrum. At 0.25XMIC (minimum inhibitory concentration) and 0.5XMIC levels, ceftibuten was able to affect the biofilm production in 2/3 of both Escherichia coli and Proteus mirabilis strains, and reduced the number of strains capable of adhering to epithelial cells by about 35% in comparison to the control. Surface hydrophobicity was also influenced by ceftibuten and the other drugs at 0.25-0.5XMIC. In general, no marked variation in the virulence traits of the pathogens studied were found by exposing bacteria to sub-MICs of ceftibuten. Plasmid loss (from 1.8 to 37.2%), and Flac transfer inhibition (about 30-50% reduction in the number of recombinants) were detected under the experimental conditions used. This study confirms the excellent antibacterial properties of ceftibuten by adding new information about the effects of this antibiotic against pathogens often involved in respiratory and urinary tract infections that may be treated with this compound, supporting the appropriate use of this cephalosporin.