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Biomedical subjects

F Baldelli

Publications and source records attributed to F Baldelli.

At least 19 recordsLinked to original sources
PubMed2006

Penetration of moxifloxacin into bone in patients undergoing total knee arthroplasty.

OBJECTIVES: To investigate plasma and bone moxifloxacin concentrations following oral administration of a single or double dose of the drug, in order to consider its potential role in the treatment of osteomyelitis. PATIENTS AND METHODS: Thirty consecutive patients undergoing total knee arthroplasty were recruited. Three groups, of ten patients each, were formed: group A received moxifloxacin 400 mg orally 2 h (range 1.5-2.5) preoperatively, group B received moxifloxacin 400 mg orally 4 h (range 3.5-4.5) preoperatively and group C received moxifloxacin 400 mg orally 14 h preoperatively, followed by a second dose 2 h (range 1.5-2.5) preoperatively. During surgery, at the time of bone removal, a blood sample and aliquots of cortical and cancellous bone were collected and moxifloxacin concentrations were measured by HPLC. RESULTS: Mean plasma, cancellous bone and cortical bone concentrations were, respectively: 3.45, 1.89 and 1.43 mg/L for group A; 3.73, 1.81 and 1.56 mg/L for group B; and 6.26, 2.97 and 2.54 mg/L for group C. CONCLUSIONS: These data show a good penetration of moxifloxacin into both cancellous and cortical bone, with concentrations, after double dosing, exceeding the MIC90 for most pathogens involved in osteomyelitis and the clinic susceptibility breakpoint for Mycobacterium tuberculosis.

Administration, Oral↗
PubMed2006

Treatment of post-traumatic hand Staphylococcus aureus osteomyelitis with oral linezolid.

The Authors report on the use of linezolid for the treatment of three patients with osteomyelitis. All three patients had post-traumatic multisensitive hand bone methicillin-susceptible Staphylococcus aureus osteomyelitis, which did not respond to antimicrobial regimens including drugs in vitro active against the isolated strains. Clinical cure and microbiologic eradication was obtained with oral linezolid in all three patients. Linezolid was well tolerated. Mild thrombocytopenia was observed in one patient at the end of the third week of treatment and it was promptly resolved after the discontinuation of linezolid. Linezolid minimum inhibitory concentrations (MICs) consisted of 2 mg/l for all three S. aureus isolates while the bactericidal activity in vitro was not present up to the linezolid concentration of 32 mg/l. In spite of a lack of in vitro bactericidal activity, linezolid was effective in curing the patients and eradicating the infection. Trough and peak plasma concentrations of linezolid were above the MICs of the isolates. These values ranged from 3.93 to 14.95 mg/l at trough and 5.03 to 25.91 mg/l at peak. The oral bioavailability, pharmacokinetic profile and antibacterial spectrum of linezolid make this oxazolidonone antimicrobial an attractive drug for the treatment of chronic osteomyelitis. Prolonged administration requires careful surveillance for side effects, until these complications are better understood.

Acetamides↗
PubMed2006

Clinical efficacy and tolerability of caspofungin in a renal transplant patient with Aspergillus flavus lung infection: case report.

Organ transplant recipients are at increased risk for severe invasive aspergillosis, and amphotericin deoxycholate has been the standard treatment for many years. Currently, however, lipid formulations are preferred due to their few side effects. Also, a number of new antifungal drugs have been developed including new azoles and echinocandins. Caspofungin is the first of the echinocandin derivatives patented to treat patients with invasive aspergillosis who are refractory or intolerant to other therapies. A renal transplant patient on immunosuppressive treatment with chronic hepatitis B virus infection was admitted with fever, hemophthisis and lung consolidation, diagnosed to be probably caused by Aspergillus flavus. The patient developed cholestatic hepatitis most likely related to itraconazole. Clinical failure and in vitro itraconazole resistance of the isolate was also documented while the patient was receiving itraconazole at a reduced dosage. Caspofungin was administered once a day as ambulatory treatment and was well tolerated. Clinical improvement was observed after 6 weeks of treatment and no hepatic toxicity was documented. Caspofungin seems to be a potentially useful antifungal agent in renal transplant patients with invasive aspergillosis. Further evaluation of the efficacy of caspofungin is needed.

Antifungal Agents↗
PubMed2005

A case of rhombencephalitis caused by Listeria monocytogenes successfully treated with linezolid.

Infection of the central nervous system due to Listeria monocytogenes is uncommon. The treatment of choice is ampicillin. We describe in this report a case of rhombencephalitis caused by Listeria monocytogenes successfully treated with linezolid. To the best of our knowledge, this is the first case in which linezolid was used to treat infection of the central nervous system caused by this organism.

Acetamides↗
PubMed2003

Evidence of Toscana virus circulation in Umbria: first report.

To evaluate, for the first time, circulation and clinical expression of Toscana virus (ToSv) in Umbria region we studied: (1) 93 cases of aseptic meningitis and meningoencephalitis admitted to our Department from 1989 to 2001 with negative results for common neurotropic virus; (2) 50 healthy subjects. Specific antibodies (IgM and IgG) anti-TOSv were found in 36.6% of aseptic meningitis, in 6.06% of meningoencephalitis and (IgG) in 16% of healthy subjects.

Adolescent↗
PubMed2003

Humoral response against Cryptococcus neoformans mannoprotein antigens in HIV-infected patients.

Twenty-four sera from healthy donors, 18 from HIV-positive patients (< 200 CD4+/mm3) and 18 sera collected before and during cryptococcosis from HIV-positive patients were analysed for the presence of humoral response to C. neoformans mannoproteins. Our results show that samples from healthy subjects and from HIV-positive patients had one of three antibody response profiles: (i) presence of reactive antibodies against both 105 and 80 kilodalton mannoproteins; (ii) presence of reactive antibodies against one of the two mannoproteins; or (iii) absence of reactive antibodies. Importantly the percentage of unreactive sera increased 6-fold in HIV-positive patients and more than 10-fold in patients with cryptococcosis. In addition, in the latter patients no variation of humoral response before and during cryptococcosis was observed. These results suggest that HIV-positive patients show a marked difficulty in mounting or maintaining antibody response to mannoprotein and this could contribute to predisposition to cryptococcosis.

Antibodies, Bacterial↗
PubMed2002

Expression of endocrine autoantibodies in chronic hepatitis C, before and after interferon-alpha therapy.

Interferon-alpha (IFN-alpha) treatment for chronic hepatitis C (CHC) has been associated with thyroid autoimmunity and/or dysfunction. Only a few data concerning the prevalence of islet-cell or adrenal cortex autoantibodies in IFN-alpha-treated subjects are currently available. The aims of our study were to evaluate in CHC, 1) the prevalence and association of thyroid, islet-cell and adrenal autoantibodies, and 2) the appearance of endocrine dysfunction, before and after a 6 month IFN-alpha treatment. We analyzed serum samples from 203 adult patients at the time of clinical diagnosis of CHC and showed that the prevalence of thyroperoxidase (TPOAb), thyroglobulin (TGAb), TSH-receptor (TRAb), glutamic acid decarboxylase (GAD65Ab), IA-2/ICA512 (IA-2/ICA512Ab) and 21-hydroxylase (21OHAb) autoantibodies was similar to that observed among healthy control subjects of similar age and sex distribution. Among 99 patients with follow-up serum samples, 83 accepted and 16 refused IFN-alpha treatment. The IFN-alpha treatment was associated with increase of TPOAb levels in 3 subjects already positive at baseline, with progression to overt hypothyroidism in 2 of them. The de novo appearance of autoantibodies was observed in 5/80 (6%) cases for TPOAb, 1/81 (1.2%) for GAD65Ab and 2/81 (2.5%) for IA-2/ICA512Ab. Clinical or subclinical signs of either hyperthyroidism or hypothyroidism were demonstrated in 3/5 cases with de novo appearance of TPOAb. Four subjects, initially positive for either GAD65Ab or IA2/ICA512Ab, were all found negative after IFN-alpha-treatment. No subjects showed positivity for 21OHAb either at baseline or after the follow-up period. Our study suggests that, in CHC untreated patients, the prevalence of endocrine autoantibodies is similar to that observed in the general population. Furthermore, we demonstrate that IFN-alpha treatment is associated with the induction or enhancement of thyroid, but not of islet-cell or adrenal cortex autoimmunity.

Adult↗
PubMed2001

Evidence of microevolution in a clinical case of recurrent Cryptococcus neoformans meningoencephalitis.

The aim of this study was to examine three serial isolates of Cryptococcus neoformans from a patient with AIDS for genotypical and phenotypical characteristics. The isolates were obtained during a first episode of cryptococcosis (simultaneous sampling of blood and cerebrospinal fluid) and after a relapse 3 years later (sampling of cerebrospinal fluid). Pulsed-field gel electrophoresis and random amplification of polymorphic DNA revealed that the blood isolate 1525 (first episode) was different from the two cerebrospinal fluid isolates (1526, first episode; 1782, relapse), yet the cerebrospinal fluid isolates were indistinguishable from each other regardless of the analysis performed. Phenotypical studies showed that isolate 1782 had significantly improved resistance to phagocytosis and killing by monocytes and polymorphonuclear cells and an altered efficacy in evoking cytokine response (augmentation of tumour necrosis factor-alpha, interleukin [IL]-1beta, IL-10, and interferon-gamma, decrease of IL-12). Interestingly, capsule size and antifungal drug resistance remained unchanged, while production of phospholipase and protease was consistently enhanced in the 1782 isolate with respect to the 1525 and 1526 isolates. In conclusion, in serial Cryptococcus neoformans isolates from a patient with AIDS, phenotypical changes but not molecular changes were documented, thus supporting the role of microevolution as a pathogenetic mechanism(s) for persistence/reactivation of fungal organisms.

AIDS-Related Opportunistic Infections↗
PubMed2001

Rapid methods to extract DNA and RNA from Cryptococcus neoformans.

Extraction of nucleic acids from the pathogenic yeast Cryptococcus neoformans is normally hampered by a thick and resistant capsule, accounting for at least 70% of the whole cellular volume. This paper presents procedures based on mechanical cell breakage to extract DNA and RNA from C. neoformans and other capsulated species. The proposed system for DNA extraction involves capsule relaxation by means of a short urea treatment and bead beating. These two steps allow a consistent extraction even from strains resistant to other procedures. Yield and quality of DNA obtained with the proposed method were higher than those obtained with two earlier described methods. This protocol can be extended to every yeast species and particularly to those difficult to handle for the presence of a capsule. RNA purification is accomplished using an original lysing matrix and the FastPrep System (Bio101) after a preliminary bead beating treatment. Yields range around 1 mg RNA from 15 ml overnight culture (10(9) cells), RNA appears undegraded, making it suitable for molecular manipulations.

Centrifugation↗
PubMed2000

Normalization of anti-cryptococcal activity and interleukin-12 production after highly active antiretroviral therapy.

OBJECTIVE: To investigate the effect of highly active antiretroviral treatment (HAART) on antifungal and secretory functions of polymorphonuclear leukocytes (PMNL) from HIV-infected patients with high viral load. DESIGN: Antifungal activity, oxygen-dependent mechanisms and interleukin (IL)-12 secretion were evaluated in PMNL from HIV-infected patients before and 3 months after commencing HAART. METHODS: PMNL antifungal activity was evaluated by effects on fungal colony-forming units. Superoxide anion (O2-) production was determined by superoxide dismutase reduction and IL-12 was determined by enzyme-linked immunosorbent assay in supernatant fluids of PMNL cultured for 18 h. RESULTS: PMNL from HIV-infected patients showed dysregulation of antimicrobial and secretory functions. A selective defect in antimicrobial activity against encapsulated Cryptococcus neoformans correlated with baseline O2- overproduction, which drastically decreased upon microbial stimulation. Similarly, constitutive secretion of IL-12 was blocked by exposure to microbial products. PMNL analysed after 3 months of HAART showed restoration of antimicrobial activity against encapsulated C. neoformans, reduction in O2- formation by unstimulated cells and restoration of oxidative burst after appropriate stimulation, and reduction of IL-12 hypersecretion. CONCLUSIONS: PMNL from HIV-infected patients with high viral load have impaired function; HAART normalizes antimicrobial and secretory activities. The effects of HAART on innate immunity provide new prospects for reduction of HAART-mediated opportunistic infections.

Adult↗
PubMed1999

Antibody to capsular polysaccharide enhances the function of neutrophils from patients with AIDS against Cryptococcus neoformans.

OBJECTIVE: To determine the contribution of anti-glucuronoxylomannan monoclonal antibody (MAb18B7) to the fungicidal capacity of polymorphonuclear leukocytes (PMNL) from HIV-infected patients towards Cryptococcus neoformans. DESIGN: Killing activity and superoxide anion generation were evaluated in the presence or absence of MAb18B7 in an in vitro system. METHODS: Killing activity was determined by colony forming unit inhibition assay. Superoxide generation was measured in the presence or absence of zymosan, C. neoformans, or Candida albicans. CD16, CD32, and CD64 molecules on PMNL were evaluated by cytofluorometric analysis. RESULTS: MAb18B7 strongly influenced the phagocytic and killing activities against encapsulated C. neoformans and consistently enhanced superoxide anion generation. Expression of CD16, and to a lesser extent CD64, on PMNL was required for MAb18B7-induced superoxide generation. By blocking CD16 and CD64 molecules with anti-CD16 and anti-CD64 MAb, a significant down-regulation of MAb18B7-induced fungicidal activity was observed. CONCLUSIONS: Our results demonstrate that MAb18B7 selectively enhances the killing mechanisms of PMNL from HIV-infected patients against encapsulated C. neoformans. The availability of CD16 and CD64 molecules on PMNL plays a critical role.

Adult↗
PubMed1999

Granulocyte-macrophage colony-stimulating factor and fluconazole enhance anti-cryptococcal activity of monocytes from AIDS patients.

OBJECTIVE: To investigate the effect of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) and fluconazole on anti-cryptococcal activity of monocytes from AIDS patients and normal subjects. DESIGN: The effect of GM-CSF and fluconazole on fungistatic and fungicidal activity of monocytes was studied in an in vitro system. METHODS: Monocytes were treated in vitro with hrGM-CSF and fluconazole or either agent alone for 24 or 48 h, and fungistatic and fungicidal activity was evaluated in a colony-forming unit inhibition assay. CD11b/CD18 expression in monocytes was measured by flow cytometry analysis. Superoxide anion generation by peripheral blood monocytes was measured in the presence of pre-opsonized zymosan. RESULTS: Defective antifungal capacity of monocytes from AIDS patients was observed. GM-CSF treatment of monocytes from AIDS patients increased fungistatic activity, and the combination of hrGM-CSF and fluconazole resulted in fungicidal activity. The mechanisms involved in the GM-CSF-mediated effect appeared to be mediated by (i) enhancement of phagocytic activity, (ii) increase of superoxide anion generation, and (iii) upregulation of CD11b/CD18 expression on the monocyte surface. CONCLUSIONS: Our data highlight the effect of GM-CSF on anti-cryptococcal activity of human monocytes and show a synergistic effect of GM-CSF with fluconazole, suggesting a new therapeutic strategy in the treatment of cryptococcosis.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Monocyte dysfunction in patients with acquired immunodeficiency syndrome (AIDS) versus Cryptococcus neoformans.

In the present study we investigated the response of monocytes from AIDS patients, susceptible to cryptococcosis (<200 CD4 cells/microl), against Cryptococcus neoformans. Different patterns of response were observed in these cells compared to cells from healthy donors. In particular, fungicidal activity versus this fungus was impaired; this phenomenon could be due to the difficulty of monocytes to internalize C. neoformans in the presence of an intact complement system. Impairment of complement receptor type 3 and direct involvement of this receptor in phagocytosis of C. neoformans were found in monocytes from AIDS patients, which may account for the difficulty in phagocytosis of the fungus. Also, superoxide anion production was dramatically reduced in monocytes from AIDS patients. An increase of spontaneous tumor necrosis factor (TNF) production was evidenced after in vitro addition of C. neoformans. However, this did not activate the antifungal capacity of monocytes from AIDS patients. Moreover, cryptococcus-laden monocytes from AIDS patients were able to induce only a weak response of autologous T-lymphocytes. Hence, monocyte dysfunction could play a part in the progression of cryptococcosis in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Immunogenicity of influenza vaccine (1993-94 winter season) in HIV-seropositive and -seronegative ex-intravenous drug users.

The humoral response (haemagglutination inhibiting antibodies) to trivalent split influenza vaccine for the 1993-94 winter season (A/Beijing/32/92 (H3N2), A/Singapore/6/86 (H1N1) and B/Panama/45/90) was evaluated in a group of young HIV-seropositive ex-intravenous heroin users and compared with responses measured in HIV-seronegative individuals with a similar history. HIV-negative volunteers showed an overall positive response suggesting that previous heroin use did not influence their humoral response to influenza vaccine. Comparable results were obtained in HIV-positive subjects with CD4+ lymphocyte counts > 500 microliters-1, whereas impaired reactivity was found in HIV-positive volunteers with CD4+ counts < 500 microliters-1. Booster vaccination did not increase antibody levels in any of the groups studied, although the data did not exclude a positive influence of a second vaccine dose on persistence of antibody at 120 days after the first dose. No significant changes were observed in p24 antigenemia levels in HIV-positive individuals after vaccination.

Adult↗
PubMed1997

The pp65 antigenaemia test as a predictor of cytomegalovirus-induced end-organ disease in patients with AIDS.

OBJECTIVE: To evaluate the predictive value of pp65 antigenaemia quantitative test for cytomegalovirus (CMV) end-organ disease in patients with advanced HIV infection. DESIGN AND PATIENTS: A prospective study in AIDS patients or HIV-infected subjects with CD4 count < 150 x 10(6)/l or CD4 percentage < 10% was carried out. Patients with a history of CMV disease or positive viraemia or antigenaemia tests and subjects under anti-herpes suppressive therapy were excluded. Clinical, ophthalmoscopic, biochemical and virological (antigenaemia test) evaluations were performed at baseline and every 1-3 months until the onset of CMV end-organ disease. SETTING: Institutional tertiary care centre. RESULTS: Forty-nine patients were evaluable for this study. End-organ disease was observed in 13 patients, 11 with at least one positive test, two with persistently negative assays. Thirteen patients without CMV disease had at least one positive test, whereas 23 always had negative tests. The 12-month Kaplan-Meier estimate of the incidence of CMV disease in our population was 30.9% and was 75% in antigenaemia-positive subjects. The negative predictive value (NPV) of the test was 92%, and the positive predictive value (PPV) was 45.8%. However, the NPV of quantitative (> 20 cells) antigenaemia assay was 92.1% and the PPV was 90.9%. CONCLUSIONS: The antigenaemia test is a quick, simple and easy to perform assay for diagnosing CMV infection. The NPV is fairly good, as is the PPV when the quantitative method (> 20 positive cells) is used. This test could be used as an alternative to polymerase chain reaction in order to select patients at higher risk of CMV disease who can be treated with pre-emptive anti-CMV therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Susceptibility of P. aeruginosa and enterobacteriaceae isolated from 1986 to 1994 in the Microbiology laboratory of the Infectious Diseases Institute of Perugia University].

From 1986 to 1994, 812 P. aeruginosa, 1997 E. coli, 437 P. mirabilis, 400 Klebsiella spp., 238 Enterobacter spp., 130 Serratia spp. strains were isolated from clinical materials in the Microbiology laboratory of the Infectious Diseases Institute of Policlinico Monteluce, Perugia University. During the study period the Authors observed the following variations in the susceptibility patterns: increased resistance of P. aeruginosa to piperacillin from 20.8% to 27.2% (P<0.05), amikacin from 11.9% to 17.5% (P<0.05), netilmicin from 11.8% to 28.6% (P<0.01), pefloxacin from 74.4% to 87.8% (P<0.01); E. coli to norfloxacin, ciprofloxacin and pefloxacin, respectively from 1.3% to 3.6% (P<0.001), from 1.5% to 3.6% (P<0.05) and from 3.2% to 9% (P<0.001); Serratia spp. to ceftazidime from 14% to 33.3% (P<0.05); Enterobacter spp. to norfloxacin from 5.1% to 13.6% (P<0.05), cotrimoxazole from 12.8% to 23.5% (P<0.05) and chloramphenicol from 19.4% to 31.8% (P<0.05). Moreover cephalotin resistant strains of E. coli decreased from 29.3% to 21.3% in the last 4 years (P<0.001).

English Abstract↗