Porphyrins and Metalloporphyrins Combined with N-Heterocyclic Carbene (NHC) Gold(I) Complexes for Photodynamic Therapy Application: What Is the Weight of the Heavy Atom Effect?

The photophysical properties of two classes of porphyrins and metalloporphyrins linked to N-heterocyclic carbene (NHC) Au(I) complexes have been investigated by means of density functional theory and its time-dependent extension for their potential application in photodynamic therapy. For this purpose, the absorption spectra, the singlet-triplet energy gaps, and the spin-orbit coupling (SOC) constants have been determined. The obtained results show that all the studied compounds possess the appropriate properties to generate cytotoxic singlet molecular oxygen, and consequently, they can be employed as photosensitizers in photodynamic therapy. Nevertheless, on the basis of the computed SOCs and the analysis of the metal contribution to the involved molecular orbitals, a different influence in terms of the heavy atom effect in promoting the intersystem crossing process has been found as a function of the identity of the metal center and its position in the center of the porphyrin core or linked to the peripheral NHC.

Paradoxical immune reconstitution inflammatory syndrome associated with previous Cryptococcus neoformans infection in an HIV-positive patient requiring neurosurgical intervention.

Immune reconstitution inflammatory syndrome (IRIS) in HIV-1-infected patients is associated with an exaggerated inflammatory response against an opportunistic infection during highly active antiretroviral therapy. The only review on IRIS associated with Criptococcus neoformans reported 21 episodes including lymphadenitis, necrotizing pneumonitis, breast and cutaneous abscess, and cryptococcomas. To our knowledge this is the first report of IRIS associated with previous meningeal criptococcal infection which required neurosurgical intervention with placement of a ventriculo-peritoneal shunt to drain a CSF cyst formed by exclusion of the temporal horn of the right lateral ventricle. We demonstrate that this procedure is possible without complications such as cryptococcal dissemination into the peritoneum.

Prevalence of antiretroviral drug resistance in untreated persons newly diagnosed with HIV-1 infection.

Current knowledge of HIV-primary resistance indicates that the prevalence of transmitted resistant strains has increased to substantial levels over the past few years, with a wide variation depending upon a number of factors. New infections with a virus strain already resistant to antiretroviral drugs, namely non-nucleoside reverse transcriptase inhibitor (NNRTI), have a negative impact on initial treatment response and also shorten the time to first virologic failure. The aim of this study was to determine the prevalence of antiretroviral drug resistance by a genotypic test in a population with newly diagnosed HIV-1 infection at a clinical centre in Bologna between June 2006 and September 2007.

Long-term statin use does not act on the temporal trend of CD4 cell count in patients on virologically effective HAART.

Pleiotropic features are attributed to statins and fibrates, and effects on laboratory markers of HIV disease progression have been claimed. To assess whether statins/fibrates have long-term effects on the immune recovery of patients on virologically effective HAART, a prospective, comparative study was conducted on 267 dyslipidemic patients treated with either statins, fibrates, or on a dietary exercise programme only. Quarterly assessment of CD4 cell counts showed no differences between groups, thus excluding in-vivo negative immunological effects during effective HAART.

Prolonged statin administration does not act on the cell-mediated immunity of HIV-infected dyslipidemic patients treated with a steady and effective highly active antiretroviral therapy. A two-year prospective study of statin versus fibrate administration.

OBJECTIVE: To assess whether statin administration for HIV-associated hyperlipidemia has long-term effects on immune recovery (as expressed by the trend of mean CD4+ lymphocyte count), in patients on a virologically-active HAART regimen since 12 months or more. METHODS: Single-centre, open-label, prospective study of 301 hyperlipidemic patients treated with statins (99 cases, with a predominant hypercholesterolemia), fibrates (116 subjects, when hypertriglyceridemia prevailed), or a isolated dietary/exercise program (86 patients, used as a control group). Neither epidemiological nor clinical, virological, or immunological differences were detected among the three study groups at baseline. During the subsequent follow-up, patients were excluded from evaluation should virological efficacy was not maintained, and/or initial hypolipidemic therapy was modified or interrupted for any reason. RESULTS: The quarterly assessment of mean CD4+ lymphocyte count did not disclose any statistically significant difference among the three study groups, since baseline and until at least 24 consecutive months of follow-up. Our data tend to exclude relevant in vivo negative activities of statins on immune system recovery of HIV-infected individuals who undergo a virologically effective HAART treatment. CONCLUSIONS: Multiple, pleiotropic features have been attributed to both statins and fibrates, and also apparently significant effects on laboratory markers of HIV disease progression have been recently claimed or expected. Despite some preliminary in vitro and ex-vivo models, both the main hypolipidemic classes administered for the management of HIV-related dyslipidemia (both statins and fibrates) do not seem to act significantly on clinical immune response of patients successfully treated with HAART. Multifactorial pathways are expected to interact with the cell-mediated immune system of HIV-infected patients undergoing successful HAART, and further studies are needed to elucidate whether more subtle immune effects might be prompted by a long-term administration of hypolipidemic drugs in this speciasl setting.

Admission of foreign citizens to the general teaching hospital of Bologna, northeastern Italy: an epidemiological and clinical survey.

BACKGROUND: The emergency regarding recent immigration waves into Italy makes continued healthcare monitoring of these populations necessary. METHODS: Through a survey of hospital admissions carried out during the last five years at the S. Orsola-Malpighi General Hospital of Bologna (Italy), all causes of admission of these subjects were evaluated, together with their correlates. Subsequently, we focused on admissions due to infectious diseases. All available data regarding foreign citizens admitted as inpatients or in Day-Hospital settings of our teaching hospital from January 1, 1999, to March 31, 2004, were assessed. Diagnosis-related group (DRG) features, and single discharge diagnoses, were also evaluated, and a further assessment of infectious diseases was subsequently made. RESULTS: Within a comprehensive pool of 339,051 hospitalized patients, foreign citizen discharges numbered 7,312 (2.15%), including 2,542 males (34.8%) and 4,769 females (65.2%). Males had a mean age of 36.8+/-14.7 years, while females were aged 30.8+/-12.2 years. In the assessment of the areas of origin, 34.6% of hospitalizations were attributed to patients coming from Eastern Europe, 15.3% from Northern Africa, 7.3% (comprehensively) from Western Europe and United States, 6.9% from the Indian subcontinent, 5.9% from sub-Saharan Africa, 5.7% from Latin America, 4.1% from China, 2.5% from the Philippines, and 1.1% from the Middle East. Among women, most hospitalizations (58.8%) were due to obstetrical-gynecological procedures or diseases, including assistance with delivery (27.1%), and pregnancy complications (18.7%), followed by psycho-social disturbances (5.9%), malignancies (5.1%), gastrointestinal diseases (4.7%), and voluntary pregnancy interruption (4.4%). Among men, the most frequent causes of admissions were related to trauma (15.9%), followed by gastroenteric disorders (12%), heart-vascular diseases (8.9%), psycho-social disorders (8.4%), respiratory (7.1%), kidney (6.1%), liver (5.2%), and metabolic (4.9%) diseases, and alcohol or substance abuse (4.2%). Infectious diseases (alone or with concurrent disorders) were reported in 881 discharged individuals, representing 12.1% of the 7,312 DRGs attributed to foreign patients. The comprehensive patient population discharged from our hospital with at least one infectious disease diagnosis had lower rates of respiratory tract infections, followed by chronic viral hepatitis, HIV infection and related diseases, enterocolitis, pulmonary tuberculosis, pyelonephritis, severe skin and soft tissue infection, meningoencephalitis, and malaria, as the most frequently-reported disorders. CONCLUSIONS: Our survey, through a combined analysis of both DRGs and discharge diagnoses, allowed us to conclude that 12.1% of foreign citizens hospitalized at our General teaching Hospital of Bologna (Italy) suffered from at least one infectious disease. Respiratory tract, liver, and gastrointestinal infections, and HIV infection, were found with an appreciable frequency among discharge diagnoses, while the frequency of malaria and meningoencephalitis was lower, compared with other series. Among disorders other than infectious diseases, obstetric-gynecological conditions and post-traumatic episodes (for male patients) were the most frequent causes of hospitalization.

A puzzling microbiological and clinical discrepancy in the management of acute, severe skin-soft tissue and joint staphylococcal infection. In vitro antimicrobial susceptibility to glycopeptides, versus in vivo clinical efficacy of linezolid alone.

We present an intriguing case report of a septicemic post-elective surgical staphylococcal knee arthritis and cellulitis which did not respond to long-term courses of associated rifampicin and teicoplanin or vancomycin despite apparently favourable in vitro susceptibility assays, but rapidly resolved after i.v. followed by oral administration of linezolid. The lack of response to a two-week course of glycopeptides cannot be explained by the in vitro mimimum inhibitory concentrations (MIC90) of involved organisms, which showed full susceptibility of Staphylococcus aureus to vancomycin and teicoplanin, and sensitivity of an accompanying Staphylococcus epidermidis isolated from blood cultures to vancomycin and rifampicin, with borderline "intermediate" values found for teicoplanin. Since neither abscess formation nor bone involvement were of concern, effective glycopeptide and rifampicin penetration into infectious tissue should have been ensured. From a clinical point of view, only the introduction of a two-week i.v. linezolid followed by one more week of oral linezolid obtained a complete clinical and microbiological cure, and an unhoped-for functional success. When managing severe multiresistant gram-positive infections, in vitro activity should be carefully evaluated against expected drug penetration rates into the relevant infectious tissues.

[HIV infection: emerging issues and new challenges]. / Infezione da HIV: problematiche emergenti e nuovi obiettivi.

Highly active antiretroviral therapy (HAART) has had a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with clinical and metabolic complications. Fat redistribution syndrome or lipodystrophy, hyperlipidaemia, insulin resistance and diabetes have been extensively reported in subjects treated with new, potent antiretroviral regimens. The potential long-term consequences of HAART-associated metabolic alterations are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIV-positive persons receiving HAART. On the other hand, the use of potent and expensive antiretroviral combinations in developing countries is very restricted and is unlikely to slow the AIDS pandemic, leading to a desperate need for a vaccine. Despite 20 years of effort, it is still a long way off, even also considerable progress has been made in understanding this problem.

[Screening of adult patients with fever of unknown origin. A prospective study on the role of primary cytomegalovirus infection]. / Screening di pazienti adulti con febbre di origine indeterminata. studio prospettico sul ruolo dell'infezione primaria da cytomegalovirus.

PATIENTS AND METHODS: In a three-year prospective survey of 135 consecutive adult patients referred for fever of unknown origin often associated with a broad spectrum of constitutional signs and symptoms, 21 (15.5%) were found to have a primary Cytomegalovirus infection. RESULTS: In the majority of cases, this syndrome was consistently associated with altered white blood cell count, abnormal T-lymphocyte subsets and hepatosplenomegaly. On the other hand, altered white blood cell differential and serum hepatic enzymes, and constitutional signs and symptoms were absent with a rate ranging from 11.1% to 27.4% of cases, and an initial laboratory cross-reaction with anti-Epstein-Barr IgM antibodies was detected in 48.1% of episodes. Non-specific signs and symptoms were the only features in 27.4% of patients, thus confirming that this disorder may be still clinically underestimated in its real frequency, until virologic assays are carried out. An extensive and varied spectrum of subjective disturbances, sometimes of duration prolonged beyond six months involved nearly 30% of subjects, and lasted for 3-15 months after recovery of acute, primary Cytomegalovirus disease. CONCLUSIONS: In a multidisciplinary (clinical, laboratory, and instrumental) workup for a fever of unknown origin, a rapid recognition of a primary Cytomegalovirus disease is useful to exclude alternative diagnoses, avoid unnecessary exposure to antimicrobial agents, and reassure patients of the benign and self-limiting course of their illness.

Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia.

OBJECTIVES: To evaluate simplified protease inhibitor (PI)-sparing antiretroviral treatment versus lipid-lowering therapy for the management of highly active antiretroviral therapy (HAART)-induced hyperlipidaemia. DESIGN: Randomized, open-label clinical trial assessing the efficacy on hyperlipidaemia of a switching therapy from PI to non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine or efavirenz versus a hypolipidaemic treatment (with pravastatin or bezafibrate) added to current, unchanged antiretroviral combination. METHODS: All HIV-infected patients on their first HAART regimen, with stable immuno-virological features, naive to all NNRTIs, and with mixed hyperlipidaemia, were randomized to replace PI with nevirapine (arm A) or efavirenz (arm B), or to receive pravastatin (arm C) or bezafibrate (arm D) with unchanged HAART regimen, and were followed-up for 12 months. RESULTS: One hundred and thirty patients were evaluated: 29 patients were randomized to arm A, 34 to arm B, 36 to arm C, and 31 to arm D. At the end of the 12-month follow-up, a reduction of 25.2, 9.4, 41.2 and 46.6% in mean triglyceridaemia versus respective baseline values was reported in groups A, B, C and D, respectively, with statistically significant difference between arms A-B and C-D (P < 0.01). Similar results were reported for total and low-density lipoprotein cholesterol levels. Viro-immunological efficacy and tolerability profile were comparable in all considered arms. CONCLUSION: Pravastatin and bezafibrate proved significantly more effective in the management of HAART-related hyperlipidaemia than the switching therapy from PI to nevirapine or efavirenz.

Rosuvastatin for the treatment of hyperlipidaemia in HIV-infected patients receiving protease inhibitors: a pilot study.

Sixteen HIV-infected patients with protease inhibitor (PI)-related, persisting hypercholesterolaemia were treated with 10 mg a day rosuvastatin for 24 weeks. At the end of the observation period, the median reductions in total cholesterol and triglyceride levels versus median baseline values were 21.7 and 30.1%, respectively (P < 0.01). In our small pilot study, rosuvastatin was found to be effective for the treatment of PI-associated hyperlipidaemia, in association with a favourable tolerability profile, without significant clinical or laboratory adverse events.

AIDS-related Kaposi's Sarcoma: evaluation of potential new prognostic factors and assessment of the AIDS Clinical Trial Group Staging System in the Haart Era--the Italian Cooperative Group on AIDS and Tumors and the Italian Cohort of Patients Naive From Antiretrovirals.

PURPOSE: To assess potential new prognostic factors and to validate the AIDS Clinical Trials Group (ACTG) for AIDS-related Kaposi's sarcoma (AIDS-KS) staging system in the highly active antiretroviral therapy (HAART) era. PATIENTS AND METHODS: We collected epidemiologic, clinical, staging, and survival data from 211 patients with AIDS-KS enrolled in two prospective Italian human immunodeficiency virus (HIV) cohort studies. We included in the analysis all patients with the diagnosis of KS made from January 1996, the time at which HAART became available in Italy. RESULTS: In the univariate analysis, survival was not influenced by sex, age, level of HIV viremia at KS diagnosis, HAART at KS diagnosis (HAART-naïve v HAART-experienced), or type of HAART combination. Regarding ACTG classification, the 3-year survival rate was 85% for T0 patients and 69% for T1 patients (P =.007), 83% for S0 patients and 63% for S1 patients (P =.003), and 83% for I0 patients and 71% for I1 patients (P =.06). In the multivariate analysis, only the combination of poor tumor stage (T1) and poor systemic disease (S1) risk identified patients with unfavorable prognosis. The 3-year survival rate of patients with T1S1 was 53%, which was significantly lower compared with the 3-year survival rates of patients with T0S0, T1S0, and T0S1, which were 88%, 80%, and 81%, respectively (P =.0001). CONCLUSION: In the era of HAART, a refinement of the original ACTG staging system is needed. CD4 level does not seem to provide prognostic information. Two different risk categories are identified: a good risk (T0S0, T1S0, T0S1) and a poor risk (T1S1).

Prospective, open-label comparative study of liver toxicity in an unselected population of HIV-infected patients treated for the first time with efavirenz or nevirapine.

OBJECTIVE: To compare the two nonnucleoside reverse transcriptase inhibitors (NNRTIs) when first introduced in an antiretroviral regimen, a prospective open-label assessment of the frequency, severity, risk factors, and outcome of hepatotoxicity was performed. METHOD: Liver enzymes were followed-up during 18 months in patients who received efavirenz (EFV; 324 patients) or nevirapine (NVP; 299). RESULTS: The two study groups were comparable, except for the lower baseline CD4+ count found in the EFV group. No differences were found when considering the type and duration of eventual prior anti-HIV therapy; frequency and length of protease inhibitors, methadone, or anti-tubercular drug use; HCV-HBV co-infection; other hepatobiliary disorders; and alcohol-drug abuse. The frequency of overall and first-month drug interruption proved similar in the two study groups. A hepatotoxicity characterized by at least a 2-fold increase of transaminases versus baseline was significantly linked with NVP, and the number of patients showing hepatotoxicity tended to a reduction in the EFV group. Also the time to peak transaminase alterations was shorter in the NVP group. All significant differences regarding liver-pancreatic toxicities were controlled per eventual baseline hepatobiliary-pancreatic diseases, HIV stage, and concurrent drug therapies. DISCUSSION: Hepatotoxicity is a significant concern in the setting of antiretroviral-treated HIV disease. NVP-based HAART may be more hepatotoxic than EFV-based HAART, and a role is played by chronic liver disorders. Although concurrent hepatobiliary disorders and the possible hepatotoxicity of antiretrovirals do not represent contraindications to nonnucleoside inhibitor use, strict monitoring is recommended.

Hyperlactataemia and lactic acidosis in HIV-infected patients receiving antiretroviral therapy.

Nucleoside reverse-transcriptase inhibitors (NRTIs) have been associated with functional and structural mitochondrial abnormalities, leading to several adverse events, such as increased serum lactic acid levels and lactic acidosis. Mild-to-moderate, asymptomatic hyperlactataemia has been frequently reported in human immunodeficiency virus (HIV)-infected patients treated with NRTIs, with an estimated prevalence between 15% and 35%. On the contrary, symptomatic, severe hyperlactataemia and lactic acidosis are less common, with an incidence ranging from 1.7 to 25.2 cases per 1000 person-years of antiretroviral treatment, and are associated with a remarkable mortality rate, which varies from 30% to 60% in different studies. The clinical presentation of lactic acid syndrome is non-specific and includes asthenia, malaise, nausea, vomiting, abdominal pain, weight loss, tachypnoea, dyspnoea, liver steatosis and increased transaminase levels, and risk factors include previous or concurrent therapy with stavudine or didanosine. Management of symptomatic lactic acid alterations involves NRTI-therapy interruption and supportive care, while natural history of hyperlactataemia is still unknown, and it is uncertain whether asymptomatic patients with increased lactate concentrations are at increased risk of developing lactic acidosis.

Neurosyphilis in a young adult: very early tertiary syphilis?

A rare episode of early neurosyphilis occurred in a 34-year-old, otherwise healthy, woman. Based on an isolated positive Borrelia burgdorferi serology (later interpreted as a cross-reaction), early ceftriaxone was initiated, in the suspect of Lyme borreliosis. Even after the diagnosis was corrected into that of a neurosyphilis, ceftriaxone administration was continued, until it achieved complete clinical and microbiological success after 24 days of treatment in a day-hospital setting, and three-weekly penicillin administrations. When considering the differential diagnosis, a luetic aetiology should not be underestimated when facing young patients with signs-symptoms of a meningoencephalitis. Our case report was characterized by an extremely low patient's age, compared with the occurrence of tertiary neurosyphilis, more than three years after the last sexual contacts. The diagnosis was confirmed by highly positive treponemal and non-treponemal serum and cerebrospinal fluid serology, and several suggestive clinical manifestations: seizures, altered mentation, cognitive impairment, lip drop, and anisochoria. These concomitant findings, together with a neuroradiological report indicating a diffuse meningoencephalitis, allowed us to confirm the diagnosis of neurosyphilis, together with a demonstrated cross-reaction of B. burgdorferi serology. Although ceftriaxone benefits from its once-daily administration (and can be easily delivered on outpatient basis), it is not the firstline treatment of neurosyphilis. However, our experience demonstrated a favourable and rapid response to ceftriaxone, in the absence of toxicity and disease sequelae.

Secondary syphilis presenting with acute severe hepatic involvement in a patient with undiagnosed HIV disease.

A case report of acute, massive, prolonged hepatitis related to secondary syphilis in a patient with undiagnosed HIV infection is described together with possible pathogenetic mechanisms. This is a rare occurrence in resource-rich countries in the era of antibiotics. The impaired immune response and the dysregulation of the cytokine network may have played a role in mediating this severe expression of HIV-associated secondary syphilis. An apparently unexplained acute hepatitis should deserve accurate screening for sexually transmitted diseases, including syphilis and HIV infection.

Antiretroviral Therapy in the Real World : Population-Based Pharmacoeconomic Analysis of Administration of Anti-HIV Regimens to 990 Patients.

OBJECTIVE AND METHODS: The aim of our study was to analyse retrospectively the nature and frequency of antiretroviral prescriptions for 990 HIV-infected patients followed at our outpatient centre in Bologna, Italy, from January 2003 to March 2004. The main focus of the study was to identify the most commonly prescribed combinations and their related expenses, in order to identify the most competitive treatment regimens with regard to costs. Prescriptions were given directly to patients at monthly intervals, and drug treatment adherence data was stored in an electronic database. Antiretroviral regimens administered for the longest period to each patient during the 15 months of the study were selected for the study. All patients treated for <9 consecutive months and/or with treatment adherence levels <90% were excluded. Physicians assessed antiretroviral therapy at least quarterly according to efficacy and safety criteria, but not in terms of pharmacoeconomic considerations. Direct pharmacy expenses were obtained for the 24 most commonly used therapeutic regimens, covering 80.1% of patients. RESULTS: The zidovudine-lamivudine-efavirenz combination proved to be the most prescribed combination (7.3%), followed by zidovudine-lamivudine- nevirapine (7.1%), lamivudine-stavudine (6.2%), zidovudine-lamivudine- lopinavir-ritonavir (5.2%), didanosine-stavudine-lopinavir-ritonavir (4.8%), and lamivudine-stavudine-nevirapine (4.7%). Anti-HIV combinations varied from a minimum yearly cost of euro3895.6 for lamivudine-stavudine to euro9422.8 for the zidovudine-lamivudine-lopinavir-ritonavir combination (+241.9%) [year of costing 2003]. There was a significant difference between the two first-line regimens for antiretroviral-naive subjects, with lopinavir-ritonavir-based combinations costing more than euro9000 per patient/year compared with efavirenz-containing combinations, which were 28% less expensive. Mean daily costs varied substantially, from a minimum of euro10.7 per day for lamivudine-stavudine to a maximum of euro25.8 per day (+241.1%) for zidovudine-lamivudine-lopinavir-ritonavir. Regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) were less costly than most of those including protease inhibitors (PIs). The increased expense of each combination was compared with the cheapest therapeutic selection (lamivudine-stavudine), and costs of all triple combinations were also compared. Regimens based on NNRTIs accounted for 29.3% of our cohort (nevirapine-containing therapies 15.1%, and efavirenz-based ones 14.2%), while PIs were used in the majority of cases (37.3%), with lopinavir-ritonavir as the leading combination (13.6% of patients), followed by nelfinavir (9.9%) and indinavir (9.2%). When drug-related costs were examined, dual nucleoside analogues showed the lowest expense (euro10.7-euro11.6 per day), while triple nucleoside/nucleotide analogue combinations cost nearly twice as much (euro18.5-euro20.4 per day). Among the NNRTIs, there were comparable costs for nevirapine-based combinations (euro18.3-euro18.7 per day), while efavirenz-including regimens were 10% more costly (euro19.2-euro20.l per day). A very broad range of combinations and related costs were found with PIs, but apart from indinavir and saquinavir combinations (euro15.7-euro21.7 per day), all other regimens had a higher daily cost (from euro22.0 per day for ritonavir-based regimens to euro23.4-euro24.3 per day for nelfinavir combinations, and up to euro24.9-euro25.8 per day with lopinavir-ritonavir). When considering nelfinavir- and lopinavir-containing combinations, the difference compared with NNRTI-based regimens varied from 41% when nevirapine- and lopinavir-ritonavir were compared, to 11.6% when efavirenz and nelfinavir were compared. CONCLUSIONS: Investigations that link prescribing patterns and related costs in the setting of HIV disease therapy are needed to improve patient management and help with the planning of healthcare resource allocation.

Linezolid in the treatment of severe central nervous system infections resistant to recommended antimicrobial compounds.

The progressive emergence of antimicrobial-resistant Gram-positive cocci especially in the setting of surgery and intensive care, recommends particular attention in making sound therapeutic choices to overcome both microbial resistances and haemato-encephalic barriers to effective local drug penetration. As in other Western countries, the occurrence of methicillin-resistant Staphylococcus aureus is particularly high also in Italy, especially when high-risk patients and/or settings are involved. In treating post-neurosurgical central nervous system infections (cerebral abscess and meningitis), a key issue is represented by the low cerebrospinal fluid concentration of the two available glycopeptide antibiotics (vancomycin and teicoplanin), usually recommended as first-line therapy of resistant Gram-positive cocci. Recent findings have focused on the possible role of linezolid, an oxazolidinone antibiotic, as a suitable candidate for the treatment of severe brain infection (abscesses) and post-neurosurgical infection, where treatment options and efficacy are significantly limited by the low glycopeptide transfer and the spread of glycopeptide-resistant bacterial strains. Three representative case reports (two brain abscesses and one post-surgical meningitis) are presented and discussed in light of the current literature: in all these cases, salvage linezolid treatment proved resolutory.

[Evolution in the hospitalization for infectious diseases among non-EU patients in Emilia Romagna]. / Evoluzione dei ricoveri per malattie infettive nei pazienti extracomunitari nella Regione Emilia Romagna.

In the Emilia Romagna (ER) area, between 1996 and 2000, a progressive increment in hospitalization for TBC, malaria, AIDS and hepatitis in non-EU patients was observed. This study aims to determine whether this trend was confirmed in 2001 and in which cities the increase was most significant. The Hospital Discharge Cards (HDC) registered in ER for non-EU patients in the relevant period were examined. In 2001, of 20,980 hospitalization cases of non-EU patients, 394 (1.87%) were attributed to infectious diseases, amounting to an increase of 1.77% over 2000. Of the 394 patients 250 (63.45%) were male and 144 (36.55%) female. The most represented age group was 20-39 yrs. Male patients more frequently come from Morocco (54), Senegal (45), Brazil (43), females from Nigeria (36), Morocco (26) and Ghana (14). The towns and cities where hospitalization occurred were, in decreasing order: Modena (24.6%), Bologna (19.3%), Reggio Emilia (12.9%), Ravenna (10.4%), Rimini (8.6%), Parma (8.3%), Piacenza (7.3%), Forli (4.8%), Ferrara and Cesena (both 1.8%). The Hospital Departments primarily involved were: Infectious Diseases with 213 hospitalizations (54%), Pneumology 69 (17.5%), Medicine 44 (11.1%), and Paediatrics 39 (9.9 %). Hospitalization causes were, in order of frequency: TBC with 137 cases (34.8%), malaria 75 cases (19%), AIDS 72 cases (18.3%), viral hepatitis 56 cases (14.2%), septicaemia 22 cases (5.6%) and Salmonella spp. infections 18 cases (4.5%).

[H5N1 avian influenza]. / L'influenza aviaria H5N1.

During the last months of 2003, outbreaks of avian flu caused by influenza A (H5N1) virus were described in eight Asian countries, and has paralleled an epidemic of human influenza caused by the same avian virus A (H5N1). Between December 26, 2003 and October 13, 2005, there had been 117 documented human infections and 60 deaths (mortality, 51%) in four Asian countries: Vietnam, Thailand, Cambodia and Indonesia. Human influenza sustained by H5N1 virus is usually characterized by a severe lower respiratory tract infection, leading to a progressive respiratory failure and several extra-respiratory complications. Infected birds have been the primary source of influenza H5N1 infection in humans in Asia, but transmission from poultry to humans is very limited at present, and requires a direct exposure to live birds, whereas there was no significant risk related to eating well-cooked poultry meat. Human-to-human transmission of H5N1 virus has been suggested in several household clusters, but it seems very uncommon at present. All the viral genes of human H5N1 isolates were of avian influenza origin, which indicates absence of reassortment with human influenza viruses, but H5N1 continue to evolve and persistent monitoring is requested to identify any increase in viral adaptation to man, which could lead to a human pandemic.