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Biomedical subjects

G Scalise

Publications and source records attributed to G Scalise.

At least 37 records · Page 2Linked to original sources

[Vascular graft infection by Staphylococcus epidermidis: efficacy of various perioperative prophylaxis protocols in an animal model].

A rat model was used to investigate the efficacy of levofloxacin, cefazolin and teicoplanin in the prevention of vascular prosthetic graft infection. Graft infections were established in the subcutaneous tissue of 300 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis (10 mg/kg), two contaminated groups with intraperitoneal cefazolin prophylaxis (30 mg/kg), two contaminated groups with intraperitoneal teicoplanin prophylaxis (10 mg/kg) and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or te- icoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture. The efficacy of levofloxacin against the methicillin- susceptible strain did not differ from that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The levofloxacin-rifampin combination proved to be similarly effective to the rifampin-teicoplanin combination and more effective than the rifampin-cefazolin combination against both strains. The rifampin-levofloxacin combination may be useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis because it takes advantage of the good anti-staphylococcal activity of both drugs.

Animals↗

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

Adult↗

Clinical manifestations and molecular epidemiology of late recurrent candidemia, and implications for management.

The aim of this study was to define the epidemiology and clinical manifestations of late recurrent candidemia. For this purpose, late recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by the same Candida sp. A total of five patients with recurrent candidemia were investigated. For all patients, isolates from the initial and recurrent episodes of candidemia were available for in vitro susceptibility testing and genetic characterization by DNA-based techniques. The results revealed the following salient features: prolonged duration between the initial and recurrent episodes (range, 1-8 months); recurrence of candidemia despite anti-fungal therapy; importance of retained intravascular catheters, neutropenia, and corticosteroids as factors predisposing to recurrence; high morbidity and mortality; no emergence of antifungal drug resistance between the initial and recurrent episodes; and relapse of infection due to the original infecting strain, rather than reinfection with a new strain. These findings raise several issues about the management and follow-up of patients with candidemia, which require assessment in future studies.

Aged↗

Combination studies between polycationic peptides and clinically used antibiotics against Gram-positive and Gram-negative bacteria.

The in vitro interaction between five polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, and ranalexin, and several clinically used antimicrobial agents was evaluated against several clinical isolates of Gram-positive and Gram-negative aerobic bacteria, using the microbroth dilution method. The combination studies showed synergy between ranalexin and polymyxin E, doxycycline and clarithromycin. In addition, magainin II was shown to be synergic with betalactam antibiotics.

Amino Acid Sequence↗

In-vitro activity and killing effect of polycationic peptides on methicillin-resistant Staphylococcus aureus and interactions with clinically used antibiotics.

The in-vitro activity of nisin, a 34-residue peptide produced by several Lactococcus lactis strains, and ranalexin, a 20-residue peptide isolated from the skin of the bullfrog Rana catesbeiana, alone and in combination with amoxycillin, amoxycillin-clavulanate, imipenem, clarithromycin, ciprofloxacin, rifampin and vancomycin was investigated against 40 nosocomial isolates of methicillin-resistant Staphylococcus aureus (MRSA). All isolates were inhibited at concentrations of 1 to 32 microg/ml. Synergy was observed when the peptides were combined with other agents, with the exception of the beta-lactams. Finally, the consecutive exposures to each peptide did not result in selection of stable mutants with decreased susceptibility. Our finding show that nisin and ranalexin are active against MRSA, and that their activity is enhanced when they are combined with several antimicrobial agents.

Amoxicillin↗

Environmental and serological evidence for the presence of toxocariasis in the urban area of Ancona, Italy.

To evaluate the Toxocara spp. eggs environmental contamination of the soil of the urban or suburban area Ancona (Italy), 22 public playgrounds were selected and several cores of soil were taken from any selected areas. To study the Toxocara seroprevalence in the inhabitants of Ancona, blood samples were collected from selected groups of individuals. One hundred and sixty-three blood samples were tested using an enzyme linked immunosorbent assay (ELISA) technique (Lofarma Lab, Milan, Italy) for the detection of IgG-specific antibodies to T. canis excretory-secretory antigens. Toxocara spp. eggs were found in the soil samples from 14 (63.6%) playgrounds. Toxocara seroprevalence was detected in blood specimens from six (8.1%) out of 74 symptomatic individuals and from one (1.1%) out of 89 asymptomatic controls. Among symptomatic individuals, the association between Toxocara seroprevalence and eosinophilia resulted statistically significant (p = 0.029). The high environmental contamination frequency found make necessary to prompt preventive public health measures, such as control of stray animals, treatment of infected pets and hygiene education of the population.

Adolescent↗

Efficacy of rifampin-levofloxacin as a prophylactic agent in preventing Staphylococcus epidermidis graft infection.

OBJECTIVES: To investigate the efficacy of levofloxacin in the prevention of vascular prosthetic graft infection in a rat model. METHODS: Graft infections were established in the subcutaneous tissue of 225 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis, two contaminated groups with intraperitoneal cefazolin prophylaxis, two contaminated groups with intraperitoneal teicoplanin prophylaxis and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or teicoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture. RESULTS: The efficacy of levofloxacin against the methicillin-susceptible strain was not different to that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The combination levofloxacin-rifampin demonstrated to be similarly effective to the combination rifampin-teicoplanin and more effective than the combination rifampin-cefazolin against both strains. CONCLUSIONS: Rifampin-levofloxacin combination seems useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis.

Animals↗

Analysis of antibody response to Cryptococcus neoformans in five patients with AIDS and cryptococcosis by immunoblotting.

OBJECTIVES: The serological response of five patients with AIDS and cryptococcosis to non capsular antigens from Cryptococcus neoformans var. neoformans has been investigated. METHODS: Pressates of different isolates of C. neoformans were used as antigenic preparation for immunoblotting of patient samples. RESULTS: Multiple sera and cerebrospinal fluids sequentially collected from five AIDS patients with cryptococcosis showed a wide heterogeneity in antibody response with bands at 48. 43, 38 and 26 kD being present in all clinical samples of all five patients. The variation in banding patterns of the sequential samples from three patients was correlated with a decrease of the antigen titre and with an amelioration of the cryptococcal infection. CONCLUSIONS: We identified antibodies to four immunodominant non-capsular antigens, which might represent major target molecules of the humoral response of patients with cryptococcosis.

AIDS-Related Opportunistic Infections↗

Anticryptosporidial activity of ranalexin, lasalocid and azithromycin alone and in combination in cell lines.

The in vitro anticryptosporidial activities of ranalexin, lasalocid and azithromycin alone and in combination were investigated against four clinical isolates of Cryptosporidium parvum. Susceptibility was tested by inoculating the isolates on to cell monolayers and determining the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of the above-mentioned compounds. Ranalexin showed moderate anticryptosporidial activity: at a concentration of 64 mg/L it reduced parasite counts by 33.8%. Azithromycin at a concentration of 8 mg/L gave inhibition comparable to that observed with the highest concentration of ranalexin. Lasalocid showed the highest activity, with a 70.3% reduction in parasite counts at 2 mg/L. The combination of ranalexin 64 mg/L and lasalocid 2 mg/L completely suppressed parasite growth without harming the monolayer.

Acquired Immunodeficiency Syndrome↗

Activity of nitazoxanide alone and in combination with azithromycin and rifabutin against Cryptosporidium parvum in cell culture.

The in vitro activity of nitazoxanide alone and in combination with azithromycin and rifabutin was investigated against four clinical isolates of Cryptosporidium parvum. The susceptibility tests were performed by inoculation of the isolates on toe cell monolayers and determination of the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of each agent. Antibiotic-free plates were used as controls. Experiments were performed in triplicate. Nitazoxanide showed moderate anticryptosporidial activity: it suppressed the growth of parasites by >50% at 8 mg/L. A parasite reduction of 79.8-83.9% was observed when nitazoxanide 8 mg/L was combined with azithromycin 8 mg/L and rifabutin 8 mg/L. The study suggests that nitazoxanide may be active in inhibiting C. parvum growth in vitro upon combination with azithromycin or rifabutin.

AIDS-Related Opportunistic Infections↗

In vitro anti-cryptosporidial activity of cationic peptides alone and in combination with inhibitors of ion transport systems.

The anti-cryptosporidial activity of four cationic peptides alone and in combination with five ion transport system (ITS) inhibitors was investigated for six clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients. The susceptibility tests were performed by inoculating the protozoa on to cell monolayers and determining the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with serial dilutions of cecropin P1, magainin II, indolicidin and ranalexin alone or in combination with amiloride and its analogues. No agent was able to inhibit parasite growth completely. The peptides had some inhibitory effect on parasite growth: cecropin P1, magainin II, indolicidin and ranalexin at a concentration of 50 microM produced 30.6, 33.2, 38.5 and 42.1% reductions, respectively, in schizont count. Conversely, the ITS inhibitors were scarcely effective. Positive interaction was demonstrated when the peptides were tested in combination with ITS inhibitors.

AIDS-Related Opportunistic Infections↗

Inhibition of growth of Pneumocystis carinii by lactoferrins alone and in combination with pyrimethamine, clarithromycin and minocycline.

The in vitro activity of lactoferrins alone and in combination with clarithromycin, minocycline and pyrimethamine was investigated against three clinical isolates of Pneumocystis carinii. Susceptibility was tested by inoculating isolates on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with serial dilutions of each agent. At 20 mg/L, bovine lactoferrin, the most active agent, suppressed the growth of cystic and trophic forms by >60%. Human lactoferrin, at the same concentration, suppressed the growth of cystic and trophic forms by >50%. Lactoferrins at 20 mg/L combined with clarithromycin 4 mg/L had high anti-P. carinii activity, with a >90% decrease in cystic and trophic form counts. Our study suggests that lactoferrins may inhibit P. carinii growth in vitro and act synergically with other clinically used compounds. These findings lend experimental support to the use of iron-chelating agents in the therapy of pneumocystis infections.

Animals↗

Efficacy of polycationic peptides in preventing vascular graft infection due to Staphylococcus epidermidis.

A rat model was used to investigate the efficacy of two polycationic peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides. The in vitro activity of the peptides was compared with those of vancomycin and teicoplanin by MIC determination and time-kill study. Moreover, the efficacy of collagen-sealed peptide-soaked Dacron was evaluated in a rat model of graft infection. Graft infections were established in the dorsal subcutaneous tissue of 120 adult male Wistar rats. The in vivo study included a control group, one contaminated group that did not receive any antibiotic prophylaxis and four contaminated groups that received an antibiotic-soaked graft. Experiments demonstrated that the activities of buforin II and ranalexin were greater than those of vancomycin and teicoplanin. Particularly, rats with buforin II-coated Dacron grafts showed no evidence of staphylococcal infection while, for the rats with ranalexin-, vancomycin- and teicoplanin-coated Dacron grafts, the quantitative graft cultures demonstrated bacterial growth (1.9 x 10(2) +/- 0.6 x 10(2) cfu/mL, 6. 2 x 103 +/- 1.9 x 10(3) cfu/mL and 5.1 x 10(4) +/- 4.8 x 10(3) cfu/mL, respectively). The study demonstrated that the use of peptide-soaked Dacron graft can result in significant bacterial growth inhibition and indicates that these compounds may be potentially useful in prosthetic surgery.

Animals↗

Comparative activities of polycationic peptides and clinically used antimicrobial agents against multidrug-resistant nosocomial isolates of Acinetobacter baumannii.

The in vitro activity of buforin II, cecropin P1, indolicidin, magainin II and ranalexin, alone and in combination with eight clinically used antimicrobial agents was investigated against 12 multidrug-resistant strains of Acinetobacter baumannii isolated from immunocompromised patients. Antimicrobial activities were measured by MIC, MBC and viable count. The peptides had a varied range of inhibitory values: overall, the organisms were more susceptible to buforin II (MIC range 0.25-16 mg/L), cecropin P1 (0.50-32 mg/L) and magainin II (0.50-16 mg/L). Synergy occurred when magainin II was combined with beta-lactam antibiotics.

Acinetobacter↗

In vitro activities of the new antifungal triazole SCH 56592 against common and emerging yeast pathogens.

A broth microdilution method performed in accordance with the National Committee for Clinical Laboratory Standards guidelines was used to compare the in vitro activity of the new antifungal triazole SCH 56592 (SCH) to that of fluconazole (FLC), itraconazole (ITC), and ketoconazole (KETO) against 257 clinical yeast isolates. They included 220 isolates belonging to 12 different species of Candida, 15 isolates each of Cryptococcus neoformans and Saccharomyces cerevisiae, and seven isolates of Rhodotorula rubra. The MICs of SCH at which 50% (MIC(50)) and 90% (MIC(90)) of the isolates were inhibited were 0.06 and 2.0 microg/ml, respectively. In general, SCH was considerably more active than FLC (MIC(50) and MIC(90) of 1.0 and 64 microg/ml, respectively) and slightly more active than either ITC (MIC(50) and MIC(90) of 0.25 and 2.0 microg/ml, respectively) and KETO (MIC(50) and MIC(90) of 0.125 and 4.0 microg/ml, respectively). Our in vitro data suggest that SCH has significant potential for clinical development.

Antifungal Agents↗

Mupirocin prophylaxis against methicillin-susceptible, methicillin-resistant, or vancomycin-intermediate Staphylococcus epidermidis vascular-graft infection.

A rat model was used to investigate the efficacy of mupirocin in the prevention of vascular prosthetic graft infection due to Staphylococcus epidermidis strains with different susceptibility patterns (methicillin susceptible, methicillin resistant, and with intermediate resistance to vancomycin). The effect of mupirocin-soaked Dacron was compared to that of perioperative intraperitoneal prophylaxis with vancomycin. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses (1 cm(2)) followed by topical inoculation with 5 x 10(7) CFU of one staphylococcal strain. The study included a control group (no graft contamination), three contaminated groups that did not receive any antibiotic prophylaxis, three contaminated groups that received mupirocin-soaked grafts, three contaminated groups in which perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg of body weight) was administered, and three contaminated groups that received mupirocin-soaked grafts and perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Data analysis showed the efficacy of mupirocin against all three strains, with growth of the strains in treated rats significantly different than that in the untreated control. In addition, mupirocin was more effective than vancomycin against the strain with intermediate susceptibility to the glycopeptide. Finally, the combination of mupirocin and vancomycin produced complete suppression of the growth of all of the strains.

Aminoglycosides↗

Polycationic peptides as prophylactic agents against methicillin-susceptible or methicillin-resistant Staphylococcus epidermidis vascular graft infection.

Several polycationic peptides isolated from animals, plants, and bacterial species possess a broad spectrum of antimicrobial activity. A rat model was used to investigate the efficacies of two peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infections. The effect of peptide-soaked collagen-sealed Dacron was compared to that of rifampin-soaked collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible rifampin-susceptible Staphylococcus epidermidis and methicillin-resistant rifampin-susceptible S. epidermidis. Graft infections were established in the back subcutaneous tissue of 240 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses, followed by topical inoculation with 2 x 10(7) CFU of S. epidermidis. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups to which perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg of body weight) was administered, six contaminated groups that received a peptide- or rifampin-soaked graft, and six contaminated groups that received a peptide- or rifampin-soaked graft and perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Overall, the efficacies of the polycationic peptides against the methicillin-susceptible and methicillin-resistant strains were not significantly different from that of rifampin. Nevertheless, the combinations of ranalexin- and buforin II-coated grafts with cefazolin treatment demonstrated efficacies significantly higher than that of the combination of rifampin-coated grafts and cefazolin treatment against the methicillin-resistant strain.

Animals↗