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Biomedical subjects

Roberto Manfredi

Publications and source records attributed to Roberto Manfredi.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Nocardiosis as the first opportunistic disease in a patient with missed HIV infection. Pathomorphism of presentation, clinical course, and evolution].

It is reported on the ground of the most updated literature evidences an infrequent case of multiple cavitating pulmonary infiltrates and a probable liver abscess caused by a Nocardia asteroides disseminated infection heralding a HIV-related profound immunodeficiency who remained missed and undiagnosed until the emerging of this severe opportunistic infection.

AIDS-Related Opportunistic Infections↗
PubMed2006

Trend of mortality observed in a cohort of drug addicts of the metropolitan area of Bologna, North-Eastern Italy, during a 25-year-period.

The aim of our study is to evaluate the temporal trend of deaths in a cohort of i.v. drug users (IVDU) followed in a city of Northen Italy (Bologna), and to assess its relationship with HIV infection and AIDS, and availability of potent anti-retroviral therapy. One thousand and 214 IVDUs (mainly heroin addicts), 916 males and 298 females, attending an out-patient service for treatment and prevention of substance abuse between 1977 and November 1996, were enrolled into our observational cohort, and their vital status was ascertained up to December 31, 2002. The large majority of enrolled subjects were born in the Bologna metropolitan area and surroundings; no extra-European immigrants were present. During the observation period, 271 IVDUs (22.3%) died, 211 males (23.0%), and 60 females (20.1%). No death was recorded before 1984. Main death causes result as follows: AIDS (52.8% of episodes), heroin overdose (22.1%), street accidents (7.4%), decompensated liver cirrhosis (6.3%), and suicide (2.9%). The highest absolute number of deaths was observed between years 1991 and 1996. Crude mortality rate caused by AIDS was 10.0 per 1000 for males and 13.2/1000 for females; the rate of death due to other causes proved 11.1/1000 among males and 5.2/1000 among females. In most recent years, a sharp decrease in the number of AIDS-related deaths, attributable to the increased use of potent antiretroviral regimens, was recorded among IVDUs, although overall mortality rate remained appreciable.

Acquired Immunodeficiency Syndrome↗
PubMed2006

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.

Acetamides↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Acidosis, Lactic↗
PubMed2005

Legionnaires' disease associated with macular rash: two cases.

Legionnaires' disease is an acute bacterial infection, generally sustained by Legionella pneumophila, which involves primarily the lower respiratory tract, although it is often associated with multi-systemic extrapulmonary manifestations. Afflicted patients may sometimes have gastrointestinal symptoms, liver function abnormalities, renal failure or central nervous system complications, while cutaneous manifestations are very uncommon and may include erythematous, maculopapular or petechial skin lesions. Pathogenesis of skin involvement in the setting of Legionnaires' disease is still uncertain, but may involve toxic or immunological mechanisms. Two exceptional cases of Legionella pneumonia complicated by diffuse, macular rash in two adult women are described, in association with severe peripheral polyneuropathy and flaccid quadriplegia in one case.

Adult↗
PubMed2005

Advanced acute myelogenous leukaemia (AML) during HAART-treated HIV disease, manifesting initially as a thyroid mass.

A rare case report of acute myelogenous 46 XY, inv(16)(p13q22) leukaemia occurring in a patient with his HIV infection controlled by highly active antiretroviral therapy is reported, in the context of a review of the available literature evidences. The initial localization as an isolated thyroid mass has no clinical equivalents to date. Although at its initial presentation the haematological disease had a very advanced (M5) stage expressing a predominant monocytic phenotype, two 1-week cytotoxic chemotherapy cycles carried out with cytarabin-daunorubicin, achieved complete remission (as assessed by combined diagnostic imaging, and repeated bone marrow studies). At the present 11-month follow-up time, eventual bone marrow transplantation is under evaluation, since the chromosomal translocation was still present. A such favourable clinical response to acute, advanced myelogenous leukaemia with an insidious recognition is considered infrequent, especially in the setting of HIV disease.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Severe staphylococcal knee arthritis responding favourably to linezolid, after glycopeptide-rifampicin failure: a case report and literature review.

A puzzling case report of a septicaemic post-surgical staphylococcal knee arthritis which did not respond to long-term courses of associated rifampicin and teicoplanin or vancomycin, despite apparently favourable in vitro susceptibility assays, but which rapidly resolved after i.v. followed by oral administration of linezolid is presented, and discussed in the context of the most recent literature evidence. The lack of response to a 14-d-long course of glycopeptides does not find explanation from the in vitro minimum 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 bone involvement nor abscess formation was of concern, effective glycopeptide and rifampicin penetration into infectious tissue should have been assured. From a clinical viewpoint, the introduction of a 2-week i.v. linezolid followed by 1 further week of oral linezolid led to complete clinical and microbiological cure, and an unexpected functional success.

Acetamides↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

A re-emerging class of antimicrobial agents: streptogramins (quinupristin/dalfopristin) in the management of multiresistant gram-positive nosocomial cocci in hospital setting.

Multiresistant gram-positive cocci, including Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis and Enterococcus faecium, are emerging pathogens in the setting of immunocompromised, hospitalized patients, especially when surgery or invasive procedures are of concern, and patients are admitted in intensive care units. The spectrum of antimicrobial compounds available for an effective treatment of these infection is significantly threatened by the emerging and spread of glycopeptide-resistant strains. Quinupristin/dalfopristin is a novel streptogramine association, which represents an effective response to most of these problems, due to its innovative mechanim of action, its maintained activity against multiresistant pathogens, and its possibility of synergistic activity with other compounds. Problems related to the epidemiology of multiresistant gram-positive infection, potential clinical indications of quinupristin/dalfopristin, and updated data on efficacy and tolerability of this compound and its derivatives, are outlined on the ground of a review of available literature evidences.

Anti-Infective Agents↗
PubMed2005

[The role of a novel antiretroviral class (fusion inhibitors) in the treatment of advanced HIV infection. Preliminary experience with enfuvirtide].

A preliminary open-label study on the administration of the novel, parenteral HIV fusion inhibitor enfuvirtide as a part of a salvage antiretroviral treatment in a cohort of hardly pretreated and multiresistant patients with advanced HIV disease followed until 30 consecutive months of therapy is presented, and discussed on the ground of available experiences, and an update of literature evidences in this field. Expectations and concerns on the use of this novel anti-HIV compound (belonging to an innovative pharmacological class) in daily practice are debated, since no specific recommendations have been produced until now, and enfuvirtide administration appears significantly more effective when made in conjunction with at least one or two other active antiretroviral agents. The management of the very frequent site injection reactions represents an adjunctive problem in the treatment of these multi-problematic patients.

Adolescent↗
PubMed2005

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.

Acetamides↗
PubMed2005

[H5N1 avian influenza].

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.

Animals↗