A toolkit for the management of infection or colonization by extended-spectrum beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome of a European project.

Among European countries, prevalence rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering the Mediterranean. This is the case for Italy, with 26% of Escherichia coli displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E toolkit designed to assist clinicians in managing patients harboring ESBL-E was favorably implemented in Southern France. In a context of lack of specific Italian recommendations, its extension to an adjacent region of Italy was made possible through a cross-border EU cooperation program. Italian infectious disease (ID) specialists, microbiologists, and community-based general practitioners from three districts in Liguria were offered a toolkit consisting in a warning system and detailed procedures for the management of patients harboring ESBL-E, including seeking advice from an ID specialist, and were trained during 52 video conferences by an experienced French team. Indications and trends in antimicrobial prescription were studied following implementation of the toolkit. Between November 2013 and November 2014, 476 patients were identified as harboring ESBL-E and expert advice was sought for 364 of these; all patients and/or their caregivers were advised on appropriate hygiene measures and 209/341 with documented management received antimicrobial treatment, while asymptomatic carriers (39%) were not prescribed antibiotics. The ESBL-E toolkit was well received by the healthcare staff. A specific, simple tool consisting in a care-bundle approach to manage ESBL-E carriers can restrict antimicrobial prescription to symptomatic patients while raising awareness among caregivers of the importance of seeking expert advice and implementing appropriate hygiene measures.

Conserved T cell and natural killer cell function in treatment-experienced adults receiving tenofovir plus didanosine as nucleoside reverse transcription inhibitor backbone.

Anti-retroviral treatment (ART) usually results in efficient control of virus replication and in immune reconstitution. Among potential adverse effects, impairment of immune responses in terms of CD4(+) T cell counts has been attributed to some ART regimens, as with didanosine-tenofovir. We studied the functional integrity of adaptive and innate immunity during didanosine-tenofovir-containing ART. Two groups of extensively pretreated patients completing at least 48 weeks of ART containing either lamivudine-didanosine (n = 21) or tenofovir-didanosine (n = 25) were identified. In addition to standard clinical immune and virological parameters, we performed a flow cytometric analysis of natural killer (NK) cells, of memory and naive CD4(+) T cells and of T cell receptor alphabeta(+) T cells co-expressing inhibitory NK receptors. Functional analysis consisted in specific and total interferon-gamma production by NK cells and of recall antigen proliferation of peripheral blood mononuclear cells. Comparable clinical immunological reconstitution and virological control were confirmed in the two groups of patients in the absence of clinically relevant adverse effects. The proportion of CD4(+)CD45RA(+) T cells and of functionally inhibited killer immunoglobulin-like receptor T cell receptor alphabeta(+) cells, the proliferation to recall antigens as well as NK cell phenotype and function as determined by interferon-gamma production in patients treated with tenofovir-didanosine were comparable to those treated with a different regimen. Thus, no differences in functional innate or adaptive immune reconstitution are detected in drug-experienced human immunodeficiency virus-infected patients on tenofovir-didanosine nucleoside reverse transcription inhibitor regimens.

Emerging and re-emerging infectious disease in otorhinolaryngology.

SUMMARY: Emerging and re-emerging infectious disease in otorhinolaryngology (ENT) are an area of growing epidemiological and clinical interest. The aim of this section is to comprehensively report on the epidemiology of key infectious disease in otorhinolaryngology, reporting on their burden at the national and international level, expanding of the need of promoting and implementing preventive interventions, and the rationale of applying evidence-based, effective and cost- effective diagnostic, curative and preventive approaches. In particular, we focus on i) ENT viral infections (HIV, Epstein-Barr virus, Human Papilloma virus), retrieving the available evidence on their oncogenic potential; ii) typical and atypical mycobacteria infections; iii) non-specific granulomatous lymphadenopathy; iv) emerging paediatric ENT infectious diseases and the prevention of their complications; v) the growing burden of antimicrobial resistance in ENT and the strategies for its control in different clinical settings. We conclude by outlining knowledge gaps and action needed in ENT infectious diseases research and clinical practice and we make references to economic analysis in the field of ENT infectious diseases prevention and care.

[Kidney toxicity's "HAART" therapy]. / Nefrotossicità della "Terapia Antiretrovirale Altamente Efficace".

Human immunodeficiency virus (HIV) and antiretroviral therapy can damage the kidney. Highly active antiretroviral therapy (HAART) generally improves the renal function as it reduces the viral replication, although the renal function may be reduced by certain antiretroviral drugs. HAART causes acute tubular necrosis, acute interstitial nephritis, calculi, Fanconi Syndrome, crystal nephropathy, elevated lipid levels as well as calcium and phosphorus alteration. The physician must estimate renal function before and during antiretroviral therapy, especially when HIV-infected patients have some risk factors for renal damage such as high-blood pressure or hepatitis B or C infections.

Listeria monocytogenes brain abscesses in a girl with acute lymphoblastic leukaemia after late central nervous system relapse.

A case of Listeria monocytogenes bacteraemia and meningitis with intracerebral abscesses in a girl with acute lymphoblastic leukaemia in relapse is reported. The clinical features included subacute onset with fever and marked irritability followed by seizures, meningism and confusion. The pathogen was isolated from blood and cerebrospinal fluid. Computerised tomography of the brain showed two intracerebral parenchymal localisations, in the left frontal lobe and in the right occipital lobe, respectively. The patient survived this severe infection without neurological sequelae. 2 months later she underwent allogeneic bone marrow transplantation without major complications. This case report should alert pediatric oncologists about the possible occurrence of severe intracerebral listerial infections in the immunocompromised child and suggests that this infection can be treated successfully and should not necessarily preclude continuation of antineoplastic treatments.

In vitro activity of a Combretum micranthum extract against herpes simplex virus types 1 and 2.

The authors demonstrate in vitro antiviral activity of a methanolic extract of Combretum micranthum leaves against HSV-1 and HSV-2. This activity is present only in the extract dissolved 7 days before the assay, but not in the freshly prepared extract, thus indicating the presence of inactive precursors which undergo spontaneous transformations into active compounds. The alkaline autooxidation of the methanolic extract promotes this rapid transformation. The precursors have been identified as condensed catechinic tannins, which, under alkaline conditions, suffer rapid cleavage, intramolecular rearrangement to catechinic acid and autooxidation. The alkaline autooxidation products of the methanolic extract of C. micranthum and those of the synthetic catechinic acid show similar I.R. and U.V. absorption curves, as well as similar anti-HSV-1 and -HSV-2 activities. EC50s of catechinic acid autooxidation products against HSV-1 and HSV-2 replication were 2 micrograms/ml and 4 micrograms/ml, respectively, when cell cultures were treated with the compound during virus infection.

Plasma and tonsillar tissue pharmacokinetics of teicoplanin following intramuscular administration to children.

The population pharmacokinetics of teicoplanin in plasma and tonsillar tissue in children was determined following intramuscular administration. Thirty seven patients in all received either a single 5 mg/kg dose; 2 doses of 5 mg/kg, 12 h apart; 3 doses of 5 mg/kg, 12 h apart; or, a single 10 mg/kg dose. Limited data, comprising a maximum of 2 blood samples and 1 tonsillar sample were taken from each patient, with the maximum time being 48 h after the first dose of teicoplanin (in the 3 x 5 mg/kg dosing schedule). All plasma data were analyzed simultaneously by a maximum likelihood method employing a modified EM algorithm. A first-order absorption, one-compartment disposition model was fitted to the data. Mean parameter values (with lower and upper 95% confidence intervals) were: clearance/bioavailability, 0.024 L h(-1) kg(-1) (0.020-0.027); volume of distribution/bioavailability, 0.61 L kg(-1) (0.54-0.70); absorption rate constant, 0.43 h(-1) (0.31-0.61). A first-order transfer model for distribution of teicoplanin between plasma and tonsillar tissue was fitted to the tonsil data. The mean parameter values (95% confidence intervals) were: transfer rate constant between plasma and tonsils 0.49 h(-1) (0.35-0.67); transfer rate constant between tonsils and plasma 0.73 h(-1) (0.52-1.03). These rate constants correspond to a distribution half-life of 0.95 h and an equilibrium distribution concentration ratio between tonsillar tissue and plasma of 0.67. After normalising clearance and volume of distribution for body weight, there was no further influence of body weight on the pharmacokinetic parameters. Also, there was no effect of dose, and as two formulations were used, one for the 5 mg/kg dose and the other for the 10 mg/kg dose, no effect of formulation on the pharmacokinetics of teicoplanin after im (intramuscular) administration was found.

[Cefotiam, a new cephalosporin. Microbiological research, preliminary evaluation of its effect on phagocytosis and clinical multicenter research]. / Cefotiam, nuova cefalosporina. Ricerca microbiologica, valutazione preliminare dell'interferenza sulla fagocitosi e ricerca clinica policentrica.

After a brief review of the data on cefotiam in the literature the report presents the results of microbiological research, a preliminary study into the drug's possible actions on phagocytosis and a polycentric clinical study of 93 cases of broncho-pleuro-pulmonary pathology and one sinusitis of the jaw. In vitro cefotiam was found to have an excellent inhibitory effect on gram positive and gram negative bacteria with MICs50 and 90 respectively 0.2 and 0.8 mcg/ml V. Staph. aureus, Str. pyogenes. E. Coli, K. pneumoniae and Pr. mirabilis. A dose-dependent increase in phagocytosis was noted. The clinical response was excellent with 90.43% (88/94) of the cases achieving clinical and radiological cure or very much improved. Cefotiam was very well tolerated with the appearance of 2/94 skin rashes (2.12%). The liver and kidney parameters showed no change at the end of treatment. No increase in enzymuria was noted during treatment with cefotiam.

[Hereditary fructose intolerance]. / L'intolleranza ereditaria al fruttosio.

Two cases of hereditary fructose intolerance are reported. In the first one the symtomatology has started with an acute hepatic failure; the second one has come to our observation with a diagnosis of intrahepatic biliary duct atresia. It is underlined the difficulty of a differential diagnosis, in infants with serious hepatic failure, between infectious, metabolic and others illnesses.

[Granulomatous hepatitis. Apropos of a case with difficult etiological diagnosis]. / Le epatiti granulomatose. A proposito di un caso di difficile inquadramento eziologico.

Hepatic granulomatosis is an anatomo-pathologic feature, rising from the aspecific answer of the liver to various antigenic, toxic and infectious noxae. One of the most frequent symptoms of this disease is a some weeks lasting fever. The most frequent etiology is proved to be infectious, particularly tuberculosis, and sarcoidosis. In this paper an analysis of the various diseases which can produce hepatic granulomas is presented, as well as the clinical case of patient with fever and hepatic disease for whom it has been possible to get to an etioilogic diagnosis of tuberculosis only through an hepatic biopsy and culture of liver tissue.

[Liver cirrhosis in childhood. Considerations on 22 cases with different etiology]. / La cirrosi epatica in età pediatrica. Considerazioni su ventidue casi a differente eziologia.

Although rather uncommon and multifactorial in etiology, liver cirrhosis is a severe and often rapidly fatal disease in pediatrics. In our institution, during the last 15 years, 22 children with liver cirrhosis have been followed. The underlying predisposing condition was HBV infection (8 cases), CMV perinatal infection (2 cases), Wilson's disease (4 cases), chronic cholestasis (2 cases) and alcohol abuse (2 cases); in 4 cases no predisposing condition was evident. In all cases the histological examination of the liver was the diagnostic cornerstone. The mean age at diagnosis was 6 years and 8 months, with an early onset especially in the posthepatitis cirrhosis. In 10 out of 22 patients, cirrhosis was not preceded by an history of chronic liver disease. Poor subjective symptomatology was present in 13 of the cases, hepatomegaly in all, splenomegaly in 18 cases, signs of hepatic failure in 13 cases. In all patients various impairments of hepatocellular synthesis were detectable, especially during the period preceding the development of hepatic insufficiency. The mean time to cirrhosis was 5 years. The average duration of the follow up was 3 years and 4 months: during the follow up 6 patients improved, 5 patients showed no clinical or functional modifications of their hepatic disease, 3 patients worsened and 8 died. In order to perform suitable treatment of liver cirrhosis the need of early diagnosis and etiological definition should be emphasized.

An unusual CT presentation of congenital cerebral toxoplasmosis in an 8 month-old boy with AIDS.

We report on a 8-month-old boy with AIDS, born of an asymptomatic mother with positive HTLV-III serology. He was hospitalized in the Intensive Care Unit because of anemia, fever and hepatosplenomegaly. Chest X-ray showed pneumonia and subsequent blood cultures were positive for Candida albicans. After 3 days of Amphotericin B treatment, the patient was transferred to Infectious Disease Department. After 30 days of hospitalization, the patient developed a rapid neurological impairment evolving into coma. CT scan showed a round, ring-shaped low density lesion with hyperdense and enhancing haemorrhagic centre in the left basal ganglia and a smaller hypodense lesion on the right. There was also evidence of cortical atrophy and mild ventricular dilatation. Such lesions are more commonly described in children with AIDS and congenital cytomegalic inclusion virus (CMV) encephalitis. In this case toxoplasma cysts were shown microscopically reinforcing the contention that in patients with AIDS, toxoplasma gondii infection may occur with atypical manifestation.

Computed tomography (CT) in children with herpes simplex encephalitis.

Computed Tomography (CT) scans were obtained from nine infants with herpes simplex virus encephalitis (HSE). The early CT findings were generalized or localized edematous change and a mass effect was also seen in two cases. In the follow-up study two patients showed bilateral gyriform calcification, a rare occurrence in association with intracranial infection. The appearance of multicystic encephalomalacia was evident in one patient 3 months after the onset of disease. It is shown that the CT findings of neonates and young children with HSE are different from those of adults.

Pharmacokinetics of teicoplanin in pediatric patients.

The pharmacokinetics of teicoplanin have been studied in 13 pediatric male patients from 2 to 12 years of age. Patients were given a single 3-mg/kg intravenous dose of teicoplanin for prophylaxis. Blood and urine samples were collected for 8 days after administration, and teicoplanin levels were determined by microbiological assay. Pharmacokinetic parameters were estimated from a three-compartment open pharmacokinetic model and from a noncompartmental analysis. Levels in plasma 1 h after the administration averaged 14.8 mg/liter. The half-lives of the two distribution phases were 1.3 and 9.7 h. The half-life of the terminal phase averaged 57.9 h, with similar estimates obtained from the noncompartmental analysis and from data from urine. The volume of distribution of the central compartment was 0.15 liter/kg, whereas the volume of distribution at steady state and during the elimination phase were 0.80 and 1.25 liters/kg. The total teicoplanin clearance averaged 14.8 ml/h per kg, with renal clearance accounting for about 60% of the total. The average cumulative recovery of teicoplanin in urine over 8 days was 59% of the dose, similar to the value obtained in adult volunteers. There was no significant linear correlation between elimination half-life and age. Preliminary data after repeated administration support the reliability of the model used and the validity of the mean estimated parameters. There were no local or systemic adverse reactions to teicoplanin.

EBNA-negative polyclonal B cells derived from a long-term culture of unclassified acute lymphoblastic leukemia: IL-2-like activity of culture's supernatant.

A long-term culture of bone marrow lymphoblasts in a case of unclassified acute lymphoblastic leukemia is described. Cells lacking any lymphocytic marker in the early phase of the culture were gradually substituted by B cells showing a pattern of polyclonality. The culture supernatant contained high levels of immunoglobulins also showing interleukin 2 activity. Search for antigens related to the Epstein-Barr virus was negative. A clonal expansion of B cells versus spontaneous differentiation of unclassified leukemic cells is discussed; the long-term culture technique as a tool for a better evaluation of leukemic cells is suggested and discussed.

Serum concentrations and safety of single daily dosing of amikacin in children undergoing bone marrow transplantation.

The serum concentrations and safety of single daily dosing of amikacin were studied in 16 episodes of fever and granulocytopenia in children undergoing bone marrow transplantation. Amikacin (20 mg/kg) was administered as a 20 min iv infusion once daily for 7 to 19 days; all patients received concomitant therapy with ceftazidime. Peak amikacin concentrations measured immediately after infusion on day 1 and 4 of therapy averaged 72.29 +/- 11.6 mg/l and 74.02 +/- 19.29 mg/l respectively. A slight but statistically significant increase 30 minute post-infusion concentrations was observed in most patients during therapy. Serum amikacin were less than 3 mg/l in all trough samples and within 6 h post-infusion in most patients. A significant increase in serum creatinine was observed in one patient, who was also receiving cyclosporin A. Auditory function was evaluated in 10 patients and showed no changes. Although other drugs were added to cover Gram-positive or fungal pathogens, all patients survived. These data combined with the recent experience of single daily dose amikacin in adults supports further evaluation of novel dosage regimens of aminoglycosides in children.