Aetiology and prognosis of bacteraemia in Italy.

A prospective multi-centre study was conducted to assess the microbiological pattern and prognostic factors of bacteraemia and their impact on clinical outcome. All patients admitted to 41 Italian hospitals over 2 months, from whom one or more clinically significant organisms were isolated from blood culture, were studied according to a standardized protocol and case definition. A total of 156 episodes of bacteraemia were identified in 20,601 patients. There were 3.9 episodes of nosocomially acquired bacteraemia and 3.7 episodes of community-acquired bacteraemia per 1000 admissions. The most frequent pathogens isolated were Gram-negative bacteria (44.9%) but Gram-positive species accounted for 40.4 % of episodes. Fungal infections due to Candida spp. were found in 3.8 % of episodes, and multiple pathogens were recovered from 9.6% of episodes. The clinical response to bacteraemia was classified as sepsis in 90 episodes (577%), severe sepsis in 21 (13.5%) and septic shock in 26 (167%); 19 episodes (12.2%) showed no clinical response. The total in-hospital mortality was 25.0%. By multivariate logistic regression, the variables which independently predicted mortality were increasing age, the presence of septic shock, infection with Gram-positive bacteria or fungi and nosocomial acquisition.

Nevirapine or efavirenz combined with two nucleoside reverse transcriptase inhibitors compared to HAART: a meta-analysis of randomized clinical trials.

PURPOSE: A meta-analysis of randomized controlled trials (RCTs) was performed to evaluate effectiveness and tolerability of triple antiretroviral therapy regimens in HIV-infected patients. METHOD: RCTs including the nonnucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine (NVP) or efavirenz (EFV) compared to two nucleoside reverse transcriptase inhibitor (NRTI) regimens and to three-drug regimens based on two NRTIs and one protease inhibitor (PI; highly active antiretroviral therapy [HAART]) were analyzed by Peto's method. RESULTS: A significant virological response was observed in patients treated with NNRTIs (odds ratio [OR] 3.6; 95% CI, 2.2-6.0), particularly in naïve patients (OR 7.4; 95% CI, 4.1-13.5). A fair reduction of HIV disease progression was also observed in patients treated with NNRTIs (OR 0.8; 95% CI, 0.6-1.0). Moreover, a significantly lower rate of HIV progression was observed in patients with a CD4 + lymphocyte count below 100/mm(3). Five RCTs comparing two NRTIs and one NNRTI to HAART were subsequently evaluated. A slightly higher rate of virological response was observed with NNRTIs (OR 1.6; 95% CI, 1.1-2.1), whereas no difference was observed concerning progression of HIV disease. CONCLUSION: Antiretroviral therapy including NVP or EFV was more effective in reducing viral load than therapy with only two NRTIs and was slightly more effective than HAART. Effectiveness in delaying HIV disease progression was less evident, even though lower rate of progression was observed in patients with advanced HIV infection compared to two NRTIs alone.

Evolution of coinfection with human immunodeficiency virus and hepatitis C virus in patients treated with highly active antiretroviral therapy.

A retrospective analysis of data from a cohort of patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were treated with highly active antiretroviral therapy (HAART) at 3 infectious diseases units in northern Italy was performed. While the patients were receiving HAART, CD4(+) cell counts significantly increased and HIV RNA serum levels decreased. However, no significant overall changes in alanine aminotransferase (ALT) levels and HCV RNA serum levels were observed. Fifteen (4.6%) of 323 patients died within 3 years of follow-up; death was related to cirrhosis in 5 patients (1.6%). No significant difference was observed between cirrhosis-related mortality and mortality related to other causes. Patients with ALT levels >4 times the normal values at initiation of HAART showed a significant decrease in ALT levels, whereas patients with normal ALT levels at initiation of HAART showed a significant increase over time, suggesting that HAART may have long-term beneficial or detrimental effects, depending on patient characteristics.

Anti-inflammatory response of IL-4, IL-10 and TGF-beta in patients with systemic inflammatory response syndrome.

The systemic inflammatory response syndrome (SIRS) is an inflammatory process seen in association with a large number of clinical infective and non-infective conditions. The aim of this study was to investigate the role of anti-inflammatory cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta). Serum levels of IL-4, IL-10 and TGF-beta were determined in 45 patients with SIRS: 38 patients had SIRS of infectious origin, whereas seven patients had non-infectious SIRS. Twenty healthy subjects were used as controls. Serum levels of IL-4, IL-10 and TGF-beta were determined by an immunoenzyme assay. A significant increase of IL-4 was observed in these patients at the time of diagnosis and 5 days later. In contrast, serum levels of IL-10 were not increased at the time of diagnosis, but a slight decrease was noted after 5 days. Serum levels of TGF-beta were not increased at time of diagnosis, and a slight increase was observed after 5 days. Serum levels of IL-4 were significantly higher in patients with infectious SIRS at the time of diagnosis, whereas no significant difference between infectious and non-infectious SIRS was noted for serum levels of IL-10 and TGF-beta at the time of diagnosis and 5 days later. During SIRS, serum levels of IL-4 were significantly increased with a significant correlation between IL-4 and mortality, and only levels of IL-4 were significantly increased in the SIRS caused by infectious stimuli.

Acyclovir for treatment of infectious mononucleosis: a meta-analysis.

A meta-analysis of 5 randomized controlled trials (RCT), involving 339 patients with acute infectious mononucleosis (IM) treated with acyclovir (ACV) was performed. ACV was given intravenously in 2 RCTs, which included patients with more severe disease, and orally in the remaining 3 RCTs, which included patients with mild to moderate IM. Both clinical and virological endpoint data available from RCT were evaluated in this study. There was a trend towards clinical effectiveness of ACV treatment, but no statistically significant results were achieved. In contrast, a significant reduction in the rate of oropharyngeal EBV shedding was observed at the end of the therapy (overall OR: 6.62; 95% CI: 3.56-12.29; p < 0.00001). However, no difference in EBV shedding was observed 3 weeks later. There was no significant difference on adverse events in the groups of patients treated with ACV or placebo. In conclusion, clinical data do not support use of ACV for the treatment of acute IM, despite good virological activity of this drug. There is a need for more effective treatment of EBV infection.

A retrospective study on the efficacy and safety of amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients.

To evaluate the efficacy and safety of Amphotericin B dissolved in dextrose (Amb) or in a lipid emulsion (Intralipid, Amb-IL) in AIDS patients with cryptococcal meningitis, we conducted a retrospective study in 30 AIDS patients with cryptococcal meningitis. A clinical complete resolution was obtained in 11 patients (55%) treated with Amb, and in six patients (60%) treated with Amb-IL. Intralipid did not decrease the infusion-related adverse effects, in particular nephrotoxicity and anaemia. Our results indicate that Amb-IL formulation is useful in the treatment of cryptococcal meningitis in AIDS patients, but it does not reduce the infusion-related adverse events.

Fatal aortic Myceliophthora thermophila infection in a patient affected by cystic medial necrosis.

A 22-year-old Italian woman developed fungal aortitis after cardiac surgery for aortic insufficiency. She experienced two episodes of septic embolization and subsequently underwent replacement of the aortic root and initial ascending aorta by a homograft. The lumina of the ascending aorta, aortic arch and the origin of the innominate artery were completely filled with vegetation. From the involved tissue the phaeoid thermophilic hyphomycete Myceliophthora thermophila (Apinis) van Oorschot was isolated in pure culture. This is the second report of isolation of this fungus from humans and the first isolation of a human pathogenic strain of M. thermophila causing fatal vasculitis in a patient affected by cystic medial necrosis. A detailed morphological description of the isolate is also provided.

Detectable levels of IgM antibodies to hepatitis C virus core protein predict breakthrough in patients with chronic hepatitis C treated with interferon-alpha.

The predictive value of IgM antibodies to hepatitis C virus core antigen (HCcAb) is controversial. We studied 79 patients undergoing interferon-alpha (IFN-alpha) treatment and we found that detectable levels of IgM HCcAb could predict breakthrough on treatment.

Interferon-alpha therapy for chronic hepatitis B in children: a meta-analysis.

A meta-analysis of six randomized clinical trials involving 240 children with chronic hepatitis B treated with recombinant interferon-alpha (IFN-alpha) was performed. IFN-alpha treatment was effective in blocking viral replication. Clearance of hepatitis B virus (HBV) DNA from sera occurred in 44 of 127 treated patients (P < .00001), and clearance of hepatitis B e antigen (HBeAg) occurred in seven of 74 treated patients (P = .099). IFN-alpha normalized serum levels of alanine aminotransferase (ALT) in 33 of 85 treated patients (P = .017). At the end of the follow-up period, viral replication was still reduced in IFN-alpha-treated patients, HBV DNA clearance occurred in 36 of 126 patients (P = .014), and HBeAg clearance occurred in 29 of 126 patients (P = .026). Regarding these virological and biochemical endpoints, we found that prolonged therapy (> 6 months) was associated with a better response, whereas high dosages of IFN-alpha were not. These findings could be biased by limited follow-up. Children with high ALT levels had a better response. However, these randomized clinical trials had some methodological flaws, including the lack of information on histologic response to IFN-alpha treatment by pediatric patients and the absence of "hard outcomes" (such as survival or development of cirrhosis or hepatocellular carcinoma).

Possible pathogenic role for Sporothrix cyanescens isolated from a lung lesion in a heart transplant patient.

Sporothrix cyanescens is a fungus rarely isolated from human specimens. Its pathogenic role has never been demonstrated but has been postulated on the basis of its occurrence in normally sterile body sites, its isolation from debilitated individuals and its thermotolerance. A first case of nodular pulmonary lesions developing in an immunosuppressed, heart transplant patient is reported. Sporothrix cyanescens was isolated from a fine needle lung biopsy. The patient failed to respond to itraconazole therapy, whereas he was successfully treated with amphotericin B.

Effects of recombinant human gamma interferon on intracellular survival of Bordetella pertussis in human phagocytic cells.

Several studies have demonstrated that Bordetella pertussis has the ability to enter and survive intracellularly within human polymorphonuclear leukocytes (PMNL) and human monocytes/macrophages. The effects of human recombinant gamma interferon (IFN-gamma) on the survival of B. pertussis in PMNL and human monocytes, and on the oxidative burst activity of PMNL and human monocytes in response to B. pertussis were assessed in this study. IFN-gamma partially increased intracellular killing of phagocytosed B. pertussis in human monocytes, as determined by an orange acridine-crystal violet assay. In contrast, IFN-gamma did not enhance intracellular killing of B. pertussis in PMNL. No significant increase of superoxide production was noted in human monocytes in response to B. pertussis when stimulated with various concentrations of IFN-gamma. The partial increase of B. pertussis killing by IFN-gamma within monocytes, together with poor production of superoxide may explain how B. pertussis can survive within human phagocytic cells, and thus cause a more prolonged course of the disease.

Effect of recombinant IL-1 beta and recombinant gamma interferon on septic acute lung injury in mice.

The effect of recombinant human interleukin 1B (IL-1B) and recombinant human gamma interferon (IFN-g), when given prophylactically, in a mouse model of septic acute lung injury was studied. Mice were treated with various doses of IL-1B and IFN-g for 3 consecutive days prior to administration of lipopolysaccharide of Escherichia coli (1 mg/kg given intraperitoneally). To determine the histologic changes occurring after prophylactic administration of such cytokines, a scoring system was assessed. A significant reduction of edema and neutrophil accumulation into the lungs of mice was observed, especially at doses of 100 U per mouse and 10,000 U per mouse of IL-1B and IFN-g, respectively. Prophylactic administration of IL-1B or IFN-g caused histologic changes, including marked reduction of edema and neutrophil accumulation in the interstitial and alveolar spaces. Combined prophylactic administration of IL-1B and IFN-g provoked a marked decrease of neutrophil accumulation into the lungs, but was not accompanied by significant reduction of edema or hemorrhage. These results provide evidence for the beneficial role of IL-1B and IFN-g in the abnormality of septic acute lung injury by reducing inflammatory lesions.

Serum levels of interleukin-1 alpha, interleukin-1 beta, interleukin-6, and tumor necrosis factor in patients with acute viral hepatitis.

Serum levels of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in patients with acute viral hepatitis were investigated. Twelve patients suffering from acute viral hepatitis were studied; 8 patients presented with acute hepatitis B, 2 patients with acute hepatitis A, and 2 patients with acute hepatitis C. Serum levels of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were significantly increased in all patients with acute viral hepatitis. Decreased serum levels of all cytokines were noted in four patients with acute hepatitis B during the recovery phase of infection. In addition, IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were undetectable at the end of a follow-up period of 6 months. Our study shows that increased levels of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha are probably related to hepatitis activity and thus may have some role in hepatocytic injury.

Production and release of tumor necrosis factor alfa, interleukin-1B and interleukin-6 by human mononuclear leukocytes stimulated with pertussis toxin.

Pertussis toxin (PT) has been previously shown to affect a wide variety of immune responses and to cause lymphocyte proliferation. In this study, we examined the effect of PT on cultured human peripheral blood lymphocytes and monocytes with the regard to the capability of this toxin to stimulate the production and release of various cytokines. PT was found to induce the production and release of Tumor Necrosis Factor alfa (TNF-alfa) and Interleukin-6 (IL-6) by both human lymphocytes and monocytes and IL-1 (IL-1B) beta by human monocytes in culture. Most activities of PT in vitro were achieved at the optimal concentration range of 1-0.01 microgram/ml, which is responsible for the adjuvant effect of PT in vivo. Since TNF-alfa, IL-1 beta and IL-6 are potent mediators of inflammation, the production and release of these cytokines by PT and Bordetella pertussis itself may play an important role in antibacterial defenses against such infection.