PubMed Health⌕ Search

Biomedical subjects

M Venditti

Publications and source records attributed to M Venditti.

At least 19 recordsLinked to original sources

IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features.

Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in the homeostasis and function of the immune system. Recent studies indicate a direct involvement of some members of the family in the development of different subsets of dendritic cells (DC). Here, we report that IRF-1 is a potent modulator of the development and functional maturation of DC. IRF-1-deficient mice (IRF-1(-/-)) exhibited a predominance of plasmacytoid DC and a selective reduction of conventional DC, especially the CD8alpha(+) subset. IRF-1(-/-) splenic DC were markedly impaired in their ability to produce proinflammatory cytokines such as IL-12. By contrast, they expressed high levels of IL-10, TGF-beta, and the tolerogenic enzyme indoleamine 2,3 dioxygenase. As a consequence, IRF-1(-/-) DC were unable to undergo full maturation and retained plasmacytoid and tolerogenic characteristics following virus infection ex vivo and in vivo. Accordingly, DC from IRF-1(-/-) mice were less efficient in stimulating the proliferation of allogeneic T cells and instead, induced an IL-10-mediated, suppressive activity in allogeneic CD4(+)CD25(+) regulatory T cells. Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells.

Animals↗

Hospital-acquired infection surveillance in a neurosurgical intensive care unit.

A prospective study on hospital-acquired infection (HAI) was undertaken in the eight-bed neurosurgical intensive care unit (NSICU) of a teaching hospital in Rome, Italy. All patients admitted for >48 h between January 2002 and December 2004 were included. The infection control team collected the following data from all patients: demographic characteristics, patient origin, diagnosis, severity score, underlying diseases, invasive procedures, HAI, isolated micro-organisms and antibiotic susceptibilities. Overall, 323 patients were included in the study. Mean age was 55.5 years (range 17-91), and mean American Society of Anesthesiologists' score was 2.88. Seventy (21.7%) patients developed 132 NSICU HAIs: 43 pneumonias, 40 bloodstream infections (BSIs), 30 urinary tract infections (UTIs), 10 cases of meningitis associated with an external ventricular drain (EVD) and nine surgical site infections (SSIs). The SSI rate was high (5.6%), but a reduction was achieved during the three-year period. There were 7.2 bloodstream infection episodes per 1000 days of device exposure; 11.00 pneumonias per 1000 days of mechanical ventilation and 4.5 UTIs per 1,000 days of urinary catheterisation. Among patients with an EVD, the SSI relative risk was 11.3 [95% confidence intervals (CI) 4.2-30.6; P<0.01]. Sixty-one (18.9%) patients died. Logistic regression analysis showed that mortality was significantly associated with infection [odds ratio (OR)=2.28; 95%CI 1.11-4.71; P=0.02] and age (OR=1.04; 95%CI 1.01-1.06; P=0.002). Candida spp. were the leading cause of UTIs (40.0%) and the third most common cause of BSIs (12.7%). Antibiotic-resistant pathogens included meticillin-resistant staphylococci (77.5%), carbapenem-resistant Pseudomonas aeruginosa (36.4%), and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (75.0%). Although the overall incidence of infection (21.7%) was within the range of published data, the associated mortality, the increasing severity of illness of patients, and the emergence of multi-drug-resistant organisms shows the need to improve infection control measures.

Adolescent↗

Pulmonary mycobacteriosis in a patient affected by mycosis fungoides: a diagnostic and therapeutic challenge.

Among patients with cutaneous T-cell lymphoma (CTCL), sepsis and pulmonary infections are the first cause of death. We report on a patient with CTCL who, after more than 10 years of aggressive antineoplastic treatments, showed extensive pulmonary infiltrations on staging CT scan. Repeated CT scans were inconclusive for an infectious process, and the patient was still asymptomatic. The diagnosis of mycobacteriosis was made on the microbiologic exam of bronchoalveolar lavage. Specific treatment was started with contemporary dosage reduction of chemotherapy. After six months of antibiotic treatment the pulmonary lesions improved, whereas CTCL progressed. Therefore, a new antineoplastic regimen was started obtaining control of CTCL, without aggravation of the pulmonary lesions. We highlight the diagnostic and therapeutic pitfalls encountered when pulmonary mycobacteriosis complicates the course and treatment of CTCL.

Adult↗

Antibody response in patients with endocarditis caused by Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus expresses a variety of adhesins involved in the colonization of host tissues. This study aimed to evaluate the role of staphylococcal surface proteins in the aetiology of infective endocarditis (IE) and the host immune response to infection. MATERIALS AND METHOD: The ELISA assays were used to assess the adherence of S. aureus isolates recovered from the blood cultures of 19 patients with IE (16 were drug abusers) to subendothelial matrix proteins. Anti-adhesin antibody titre was measured incubating surface-coated bacterial antigens with patients' IgG. S. aureus effects on platelet aggregation were evaluated with an aggregometer. RESULTS: Staphylococcus aureus isolates, from the patients with IE, exhibited a high expression of several surface components recognizing extracellular matrix proteins: clumping factors A and B (ClfA and ClfB) and fibronectin-binding proteins (FnbpA and FnbpB), whereas only four strains expressed the collagen-binding protein CNA. Bacteria also interacted with platelets both in the absence or presence of fibronectin or fibrinogen and some strongly supported platelet aggregation. Almost all patients presented significantly higher antibody reactivity to ClfA, ClfB, FnbpA, CNA and MAP (MHC class II analogous protein) than in sera from healthy individuals. On the contrary, the reactivity to CNA was remarkable only in three patients. The IgG preparations weakly inhibited the binding of bacteria to fibronectin, whereas they exhibited considerable blocking activity on staphylococcal attachment to fibrinogen or collagen. CONCLUSION: Adhesins ClfA, ClfB and FnbpA are produced in vivo and appear important factors both in valve colonization and in promoting host immune responses.

Adhesins, Bacterial↗

Clonality among Enterococcus faecium clinical isolates.

In the course of a survey to determine the epidemiology of enterococcal infections in Italy, a sudden increment, in a 1-year time, was noted in the number of glycopeptide resistant Enterococcus faecium isolated from different wards of the University Hospital in Rome, Italy. The isolates were characterized for clonal relatedness by comparing SmaI gel electropherotypes, presence of vancomycin-resistance genes, and expression of virulence factors. PFGE identified in a single pulsed type all the glycopeptide-resistant isolates but one. Resistance to high levels of aminoglycosides was expressed by these same isolates, which also included a majority of non biofilm-forming strains. Two esp gene-carrying strains were also identified in different PFGE types. Data indicates that a specific clone acquired, in the clinical setting, the genetic determinant for glycopeptide resistance, thus improving environmental adaptation and favoring its persistence and spread.

Drug Resistance, Multiple, Bacterial↗

Extended Spectrum Beta-Lactamase-producing Klebsiella pneumoniae outbreaks during a third generation cephalosporin restriction policy.

In spite of the adoption of third generation cephalosporin restriction policies, two independent outbreaks by Extended Spectrum Beta-Lactamase (ESBL)-producing Klebsiella pneumoniae occurred in two different wards (Neonatal Intensive Care Unit, NICU and Neurosurgery) of a teaching hospital in Rome, Italy. In the former 19 infected neonates were reported, whereas in the latter there were 10 infected patients. In both wards no differences were observed in the mortality rates in periods of outbreak and those with no outbreak. Molecular typing on a total of 19 isolated strains was carried out and restriction patterns were compared. The PFGE showed that nine isolates responsible for infection in the NICU were all included in three closely related clusters. In Neurosurgery nine strains out of ten were strictly related and part of an outbreak occurring between August-December 2003, while one isolate was temporarily (February 2003) and genetically (seven band differences) unrelated to the outbreak strains. When ESBL producing K. pneumoniae clusters from the two wards (NICU vs Neurosurgery) were compared, they appeared to be completely different both for their genotype pattern and plasmid type or presence, thus demonstrating cross transmission by two different genotypes.

Cephalosporins↗

Antimicrobial susceptibility, biochemical and genetic profiles of Staphylococcus haemolyticus strains isolated from the bloodstream of patients hospitalized in critical care units.

Staphylococcus haemolyticus strains (n=20), responsible of blood stream infections, were consecutively isolated from patients hospitalized in two different wards at high risk of infection. Strains displayed high rate of resistance to oxacillin (90%). All strains but two with decreased susceptibility (MIC = 4 microg/mL), were sensitive to vancomycin. Ten strains were resistant to teicoplanin. Among the strains susceptible to glycopeptides, three displayed heteroresistance to vancomycin and seven to teicoplanin, when tested by Etest technique with 2 x McFarland inoculum. Biochemical reactions allowed to assign strains to eight biotypes, with 11 strains clustering under two main biotype A and biotype B. Pulsed-field-gel-electrophoresis (PFGE) identified 11 different PFGE-types. Seven strains grouping under the major PFGE-type 1 and three strains clustering in PFGE-type 2, closely correlated to biotype A and biotype B respectively. Seven teicoplanin-resistant isolates clustered in the PFGE-type 1, two in the PFGE-type 2 and one in PFGE-type 5. Therefore, teicoplanin-resistant strains were biochemically and genetically related and clonally distributed, despite different clones of S. haemolyticus circulated in the units during the study period.

Adult↗

Antimicrobial activity of polyurethanes coated with antibiotics: a new approach to the realization of medical devices exempt from microbial colonization.

Intravascular devices are widely used for vascular access but are associated with substantial risk of development of devices-related bloodstream infection (DR-BSI), which causes a considerable increase of morbidity and mortality, prolonged hospitalisation and growing medical costs. Since conventional treatment of DR-BSI fails in a significant number of cases, resulting in removal of the device, new approaches are needed to prevent bacterial colonization. In this paper, two antibiotics, rifampin and amoxicillin, have been adsorbed on polyurethanes exhibiting acidic or basic properties. The influence of the type of antibiotic-polymer interaction on the amount of adsorbed antibiotic and on the release kinetics was studied. It was seen that the antibiotic-polymer affinity increases both with the introduction in the polymer side-chain of functional groups and with the matrix hydrophilicity. The antimicrobial activity of the treated polymers, evaluated in vitro by the Kirby-Bauer test, depends on the amount of antibiotic adsorbed, on the strength of drug-matrix interaction and on the water swelling of the polymers. The inhibition zone of bacterial growth lasts only a few hours for the amoxi-coated polymers while remains at least for five months for the rifampin-coated ones. The presence of serum proteins decreases by about 30% the inhibition zone diameter of these latest matrices after two months.

Adsorption↗

Impaired myelopoiesis in mice devoid of interferon regulatory factor 1.

Interferon regulatory factor (IRF)-1 is a transcription factor controlling the expression of several genes, which are differentially induced depending on the cell type and signal. IRF-1 modulates multiple functions, including regulation of immune responses and host defence, cell growth, cytokine signalling and hematopoietic development. Here, we investigated the role of IRF-1 in granulocytic differentiation in mice with a null mutation in the IRF-1 gene. We show that IRF-1(-/-) bone marrow cells exhibit an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements as compared to normal mice, suggestive of a defective maturation process. Clonogenetic analyses revealed a reduced number of CFU-G, CFU-M and CFU-GM colonies in IRF-1(-/-) mice, while the number of BFU-E/CFU-E colonies was unchanged. At the molecular level, the expression of CAAT-enhancer-binding protein (C/EBP)-epsilon, -alpha and PU.1 was substantially lower in the CD11b(+) cells from the bone marrow of IRF-1(-/-) mice as compared to cells from wild-type mice. These results, together with the fact that IRF-1 is markedly induced early during granulo-monocytic differentiation of CD34+ cells, highlight the pivotal role of IRF-1 in the early phases of myelopoiesis.

Animals↗

Successful treatment of disseminated cerebritis complicating methicillin-resistant Staphylococcus aureus Endocarditis unresponsive to vancomycin therapy with linezolid.

A unique case of community acquired methicillin resistant Staphylococcus aureus (MRSA) sepsis, with endocardial and cerebral metastatic seeding, caused by a strain representative of the Italian clone, is described. The patient was a 47-y-old man without apparent risk factors for endocarditis and for MRSA infection who developed coma with multiple cerebritis lesions under vancomycin plus amikacin therapy. He was eventually cured with the addition of linezolid to the initial antimicrobial regimen. This observation seems to confirm previous reports of the efficacy of linezolid for the treatment of central nervous system infections caused by multidrug resistant Gram-positive bacteria. To our knowledge, this is the first report of MRSA disseminated cerebritis, a nearly always fatal disease, cured with this oxazolidinone drug. The increase in community acquired MRSA may have some impact on empirical treatment of serious infections caused by this organism.

Acetamides↗

Conservative medical therapy of prosthetic joint infections: retrospective analysis of an 8-year experience.

Successful treatment of prosthetic joint infections often requires multiple surgical interventions and prolonged antimicrobial therapy. However, in certain situations, a surgical approach may not be in the best interest of the patient. A conservative approach was used to treat 34 patients with prosthetic joint infection between 1995 and 2003. Diagnosis of infection was based on clinical-microbiological evidence, confirmed by (99)Tc-labelled leukocyte scintigraphy, and involved 12 Staphylococcus aureus infections, nine Staphylococcus epidermidis infections, two Enterococcus faecalis infections, two mixed infections (S. aureus plus Pseudomonas aeruginosa; S. epidermidis plus E. faecalis), with the infecting pathogen being unidentified for nine patients. Most infections were treated initially with intravenous or intramuscular teicoplanin +/- ciprofloxacin or rifampicin, followed by oral ciprofloxacin or minocycline plus rifampicin. The mean duration of antimicrobial therapy was 41.2 weeks. Overall, only three patients did not respond to therapy, and infection was controlled in the remaining 31 patients. Among these, no relapse was observed in 17 patients during follow-up for 9-57 months; improvement with early (within 6 months of antibiotic discontinuation) or late relapse was observed in seven and three patients, respectively; two patients improved clinically, but continued to receive antibiotic therapy; and two patients whose condition improved initially were lost after a 6-month follow-up following discontinuation of antibiotics. No patient complained of side effects requiring discontinuation of antibiotic therapy. The study confirmed that suppression of infection, with salvage of the infected device in an acceptably functional state, can be achieved in selected cases.

Adult↗

Analysis of virulence factors in cases of enterococcal endocarditis.

Eleven isolates of Enterococcus faecalis causing endocarditis were screened for possible virulence factors with PCR and phenotypic assays. The gene coding for the enterococcal surface protein (esp) was detected in one isolate only, and haemolysin was produced by two isolates. Aggregation substance, biofilm formation and gelatinase were present in seven, nine and eight isolates, respectively. Predisposing factors, particularly hospitalisation and multiple antibiotic therapy, appeared to be more relevant to the development of enterococcal endocarditis following bloodstream infections than the pattern of virulence factors.

Adult↗

Methicillin-resistant staphylococcal bacteremia in patients with hematologic malignancies: clinical and microbiological retrospective comparative analysis of S. haemolyticus, S. epidermidis and S. aureus.

Although Staphylococcus haemolyticus (SH) represents an emerging etiology of methicillin-resistant (MR) coagulase-negative staphylococcal nosocomial bacteremia, little is known of clinical significance of this infection. Thus, we performed case-control retrospective comparative analysis of MRSH bacteremias (MRSHB), methicillin-resistant S. epidermidis bacteremias (MRSEB), and methicillin-resistant S. aureus bacteremias (MRSAB) in patients with hematologic malignancies. Most patients in the three groups were neutropenic and had a central venous catheter (CVC) in place at the onset of bacteremia. However, MRSHB patients had a CVC in place prior to bacteremia for a time significantly more prolonged than MRSEB and MRSAB ones (p<0.05). Severe sepsis or septic shock were more common in patients with MRSAB as compared with MRSHB (p=0.02). Nosocomial attributable mortality rate was very low in the 3 study groups (0 to 5.4%) and only two patients developed metastatic infections. Overall, reduced susceptibility to teicoplanin was observed in 19 (47.5%) MRSH and in 4 (10%) MRSE isolates. Resistance to teicoplanin was observed in 6 isolates, all MRSH. Reduced susceptibility or resistance to vancomycin was observed in 2 isolates, both MRSH. All MRSA isolates were susceptible to the glycopeptides. Comparison between cases of bacteremia in patients with MRSH isolates with reduced susceptibility to teicoplanin and those with susceptible MRSH did not reveal significant differences in the clinical-microbiological response to teicoplanin therapy and outcome. Our results seem to suggest that MRSHB in hematologic patients is associated with low morbidity and mortality rates. MRSH frequently shows a reduced susceptibility to teicoplanin; however these in vitro data do not seem associated with an unfavorable clinical response to teicoplanin therapy for MRSHB in patients with hematologic malignancies.

Adolescent↗

[Systemic Salmonella Arizona infection: description of a rare surgical case].

Salmonella arizona enteritis has been described in patients resident in the southern states of the USA and in Mexico, whereas in Europe it is rarer. The virulence of this bacillus is, however, still little known and we have few descriptions of severe systemic infections, which are all present in patients with immune system impairment. Only two cases have been reported in Italy where the infection has occurred as severe sepsis with the pathogenic agent being isolated in the blood. Here we report what is, on the basis of our knowledge, the third case in Italy of a systemic Salmonella arizona infection.

Aged↗

Actinomycosis of submandibular gland: an unusual presentation.

An unusual presentation of oro-facial actinomycosis, mimicking the clinical appearance of a malignant lesion is reported. The patient, a 74-year-old female, presented with a right submandibular mass, which slowly grew in size over a period of about 2 months, and a modest dysphagia. A painless cervical mass was palpable over the submandibular region. The rhino-pharyngo-laryngeal region, explored by flexible fiberoptic examination, was normal. At ultrasonography, a 2x2 cm infiltrating dyshomogeneous mass, involving the right submandibular gland, was visible. No connection with adjacent organs was found. There was no associated cervical lymphoadenopathy. Ultrasound-guided fine-needle aspiration cytology, performed on lesion, revealed no evidence of malignancy. The presence of characteristic colonies of actinomyces infection was found. The patient was treated initially with tetracycline chloridrate 100 mg: 1 tablet every 12 hours for 7 weeks, but a repeat ultrasonography showed no resolution. A further fine-needle aspiration cytology showed no actinomyces infection in the specimen. The patient was treated with methylprednisolone, 20 mg every 24 hours, for 5 days. After steroid treatment, the patient has been well and, upon repeat ultrasonography, total resolution of the submandibular lesion was confirmed. In conclusion, the clinical presentation of cervicofacial actinomycosis is variable and may mimic a malignant lesion or chronic granulomatous infections. Diagnostic and therapeutic findings are discussed.

Actinomycosis↗

Activity of moxifloxacin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy.

We tested the in vitro bactericidal activity of moxifloxacin, a new 8-methoxyquinolone, alone and in combination with vancomycin or teicoplanin at different multiples of minimum inhibitory concentration (MIC) against 8 methicillin-ciprofloxacin-resistant Staphylococcus aureus (M-C-RSA) and 1 methicillin-ciprofloxacin susceptible S. aureus (M-C-SSA) recently isolated from device-associated infections unresponsive to or relapsing after glycopeptide therapy, despite device removal. MICs of vancomycin ranged from 1 to 4 microg/ml, MICs of teicoplanin ranged from 2 to 8 microg/ml; MICs of moxifloxacin were always 2 microg/ml against M-C-RSA isolates and 0.125 microg/ml against the M-C-SSA isolate. The 9 strains resulted tolerant when tested for vancomycin, teicoplanin, and moxifloxacin used alone at 2 x MIC. In all cases the combination of moxifloxacin and teicoplanin or vancomycin appeared to be bactericidal already at MIC concentration for glycopeptides plus 0.5 x MIC concentration for moxifloxacin. If these results are confirmed in vivo in animal experiments, the combination of moxifloxacin with glycopeptides might be useful for treating device-associated infections, and in preventing the frightening phenomenon of increasing MICs for glycopeptides.

Anti-Infective Agents↗