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Bruno Fantin

Publications and source records attributed to Bruno Fantin.

At least 19 recordsLinked to original sources
PubMed2006

Amoxicillin is effective against penicillin-resistant Streptococcus pneumoniae strains in a mouse pneumonia model simulating human pharmacokinetics.

High-dose oral amoxicillin (3 g/day) is the recommended empirical outpatient treatment of community-acquired pneumonia (CAP) in many European guidelines. To investigate the clinical efficacy of this treatment in CAP caused by Streptococcus pneumoniae strains with MICs of amoxicillin > or =2 microg/ml, we used a lethal bacteremic pneumonia model in leukopenic female Swiss mice with induced renal failure to replicate amoxicillin kinetics in humans given 1 g/8 h orally. Amoxicillin (15 mg/kg of body weight/8 h subcutaneously) was given for 3 days. We used four S. pneumoniae strains with differing amoxicillin susceptibility and tolerance profiles. Rapid bacterial killing occurred with an amoxicillin-susceptible nontolerant strain: after 4 h, blood cultures were negative and lung homogenate counts under the 2 log(10) CFU/ml detection threshold (6.5 log(10) CFU/ml in controls, P < 0.01). With an amoxicillin-intermediate nontolerant strain, significant pulmonary bacterial clearance was observed after 24 h (4.3 versus 7.9 log(10) CFU/ml, P < 0.01), and counts were undetectable 12 h after treatment completion. With an amoxicillin-intermediate tolerant strain, 24-h bacterial clearance was similar (5.4 versus 8.3 log(10) CFU/ml, P < 0.05), but 12 h after treatment completion, lung homogenates contained 3.3 log(10) CFU/ml. Similar results were obtained with an amoxicillin-resistant and -tolerant strain. Day 10 survival rates were usually similar across strains. Amoxicillin with pharmacokinetics simulating 1 g/8 h orally in humans is bactericidal in mice with pneumonia due to S. pneumoniae for which MICs were 2 to 4 microg/ml. The killing rate depends not only on resistance but also on tolerance of the S. pneumoniae strains.

Amoxicillin↗
PubMed2006

Spinal tuberculosis: a longitudinal study with clinical, laboratory, and imaging outcomes.

OBJECTIVES: To study imaging changes associated with spinal tuberculosis (ST) over time and evaluate their association with clinical and laboratory data. METHODS: Between 1997 and 2004, patients with proven ST in our institution were prospectively enrolled and treated for 1 year. Clinical and laboratory data were collected at baseline and every 3 months. Computed tomography (CT) and magnetic resonance imaging (MRI) were performed at baseline. MRI was performed at least twice during treatment and at the end of treatment. RESULTS: Nineteen patients were enrolled; neurological signs were present at baseline in 14 patients (74%). Initial MRI/CT findings comprised (in percentages of patients) the following: paravertebral abscesses (100/100); intradiscal abscesses (47/0); and epidural abscesses (82/24) with spinal cord compression (64/18) or radicular compression (36/0). Edema of the vertebral body was observed on initial MRI in all the patients. Full follow-up data were available for 15 patients: all were cured with a mean follow-up of 25 months after the end of treatment. Weight gain was nearly maximal at 6 months, and pain relief was achieved within 9 months. C-reactive protein returned to normal after 3 months. On MRI, all epidural abscesses disappeared within 9 months; paravertebral abscesses disappeared after 3, 6, and 12 months in 45, 50, and 85% of patients, respectively. Vertebral body signal converted to a fatty signal in 75% of cases at 12 months. CONCLUSIONS: Significant imaging abnormalities can persist after successful treatment of ST. These findings suggest that MRI need not be repeated in patients with clinical and laboratory improvement.

Abscess↗
PubMed2006

Acquired gentamicin resistance by permeability impairment in Enterococcus faecalis.

Enterococci are intrinsically resistant to low levels of aminoglycosides. We previously selected in vitro and in vivo Enterococcus faecalis with intermediate-level resistance to gentamicin that did not abolish synergism with a cell-wall-active agent (E. Aslangul et al., Antimicrob. Agents Chemother. 49:4144-4148, 2005). The aim of this study was to investigate the mechanism of resistance to gentamicin in the 1688-G3 third-step mutant (MIC, 512 microg/ml) of E. faecalis JH2-2. No mutations were found in the genes for L6 ribosomal protein and the four copies of 16S rRNA. Production of a known aminoglycoside-modifying enzyme was unlikely due to the distinct resistance phenotype and absence of the corresponding genes. Efflux was also unlikely since ethidium bromide MICs were similar for JH2-2 and 1688-G3 and since the pump inhibitors reserpine and verapamil had no effect on gentamicin resistance in both strains. To study gentamicin accumulation, we developed a nonisotopic method based on a fluorescent polarization immunoassay. Impaired gentamicin accumulation was observed in 1688-G3 compared to JH2-2 and was only partially reversible by the N,N'-dicyclohexylcarbodiimide (DCCD) uncoupler agent. The lower sensitivity of 1688-G3 to DCCD suggested alteration of the FoF1-ATPase. However, no mutations were detected in the structural genes (atp) for the Fo channel and no difference in transcript levels of atpB and atpE was found between 1688-G3 and JH2-2. Our data are compatible with acquisition of intermediate-level gentamicin resistance by uptake impairment in E. faecalis.

Adenosine Triphosphate↗
PubMed2006

Bone involvement in generalized crystal-storing histiocytosis.

The abnormal secretion of monoclonal immunoglobulins observed with monoclonal gammopathies and other clonal B cell dyscrasias can be responsible for a spectrum of deposition disorders. Crystal-storing histiocytosis (CSH) is a rare disease affecting patients with B cell dyscrasias and monoclonal gammopathies, characterized by the accumulation of histiocytes that have phagocytosed an abnormal crystalline immunoglobulin. We describe 2 cases of this rare disorder with multiorgan involvement and prominent bone involvement. Magnetic resonance imaging showed bone marrow infiltration and images of avascular necrosis. Bone specimen analysis gave histological proof of diffuse bone infiltration by the abnormal histiocytes. Bone involvement, which appears to be a specific feature of CSH, links this entity to other storage disorders, such as Gaucher disease. Because the accumulation of abnormal immunoglobulin-loaded histiocytes is clearly pivotal, CSH should be considered not only as an immunoglobulin deposition disease but also as a storage histiocytic disorder.

Aged↗
PubMed2005

Mutator phenotype confers advantage in Escherichia coli chronic urinary tract infection pathogenesis.

It has been suggested that mutator phenotype could be associated with an increase in virulence, but to date experimental evidences are lacking. Epidemiological studies have revealed that urinary tract infection isolates encompass the highest proportion of mutator strains within the Escherichia coli species. Using the uropathogenic strain CFT073 and its mutS- mutator mutant, we show that the mutator strain is selected in vitro in urine and in the late stages of infection in a mouse model having urinary tract infection. Thus, we report that, under specific conditions, i.e., urinary tract infection, the mutator phenotype may confer an advantage in pathogenesis.

Animals↗
PubMed2005

Risk factors for Staphylococcus aureus infection in liver transplant recipients.

Staphylococcus aureus is the leading cause of bacterial infection in liver transplant recipients. Preoperative nasal carriage of methicillin-resistant S. aureus (MRSA) is associated with a high risk of infection. We conducted a retrospective cohort study in order to identify independent risk factors for early-onset S. aureus infection after liver transplantation. Patients were screened preoperatively for methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage. Risk factor analysis was performed by univariate analysis followed by stepwise logistic regression. Of the 323 patients included, 63 (19.5%) patients developed S. aureus infection (36 MRSA, 27 MSSA) within 1 month of surgery. Variables significantly associated with infection in the univariate analysis were MRSA and MSSA nasal carriage, alcoholic cirrhosis, absence of hepatocellular carcinoma, decreased prothrombin ratio, and presence of ascites. In the multivariate analysis, MRSA carriage (odds ratio [OR]: 20.9, P < 0.0001), MSSA carriage (OR: 3.4, P = 0.0004), alcoholic cirrhosis (OR: 2.4, P = 0.01) and decreased prothrombin ratio (OR: 1.2, P = 0.01) were independent predictors of infection. Molecular typing showed that the infecting isolate was identical to the isolate from the nose in most patients. In conclusion, preoperative nasal carriage of MRSA and MSSA is an independent risk factor for S. aureus infection in liver transplant recipients. The infection is most often of endogenous origin. Alcoholic cirrhosis and the severity of liver failure are also associated with a high risk of infection.

Adolescent↗
PubMed2005

Comparative study of postoperative and spontaneous pyogenic spondylodiscitis.

OBJECTIVES: Postoperative spondylodiscitis (POS) is poorly characterized, partly owing to its rarity. The aim of this prospective study was to compare the clinical, biological, bacteriological, and imaging features of postoperative and spontaneous spondylodiscitis (SS). METHODS: A multidisciplinary spondylodiscitis cohort follow-up study was conducted between February 1999 and June 2003 in a 500-bed teaching hospital. All patients hospitalized in internal medicine, orthopedic, and neurosurgery wards with a culture-proven diagnosis of pyogenic spondylodiscitis were included. Clinical and bacteriological data were collected. All patients underwent computed tomography and/or magnetic resonance imaging of the spine. RESULTS: Sixteen patients had SS and 7 patients had POS. Patients with POS tended to be younger (52 versus 69 years), with less frequent underlying diseases (29 versus 75%) and a more prolonged interval between symptom onset and diagnosis (16 versus 3.4 weeks) than patients with SS. Blood cultures were positive in 14 and 81% of cases in the POS and SS groups, respectively, and invasive diagnostic procedures were necessary in 86% of patients with POS and 19% of patients with SS ( P = 0.005). Staphylococci were the more frequent isolates in both groups but were more frequently coagulase-negative in POS patients than in patients with SS ( P = 0.01). Vertebral edema tended to be more frequent in POS and was located more posteriorly than in SS ( P = 0.023). CONCLUSIONS: POS is associated with specific clinical, microbiological, and imaging features possibly related to pathophysiologic characteristics. Knowledge of these characteristics should help reduce the current delay in the diagnosis of POS.

Adult↗
PubMed2005

Relationship between the level of acquired resistance to gentamicin and synergism with amoxicillin in Enterococcus faecalis.

In enterococci, intrinsic low-level resistance to gentamicin does not abolish synergism with a cell wall-active antibiotic while high-level resistance due to acquired aminoglycoside-modifying enzymes does. To study the impact of intermediate levels of resistance to gentamicin (64 < MIC < 500 microg/ml), we selected in vitro three consecutive generations of mutants of Enterococcus faecalis JH2-2 with MICs of gentamicin at 128 microg/ml for G1-1477, 256 microg/ml for G2-1573, and 512 microg/ml for G3-1688. E. faecalis 102, which is highly resistant to gentamicin by enzymatic inactivation was used as control. In in vitro killing curves experiments, gentamicin concentrations allowing bactericidal activity and synergism in combination with amoxicillin increased from 4 microg/ml (1/16th the MIC), 16 microg/ml (one-eighth the MIC), 64 microg/ml (one-quarter the MIC), and 256 microg/ml (one-half the MIC) for strains JH2-2, G1-1477, G2-1573 and G3-1688, respectively. As expected, no bactericidal effect of the combination or synergism could be obtained with strain 102. In rabbits with aortic endocarditis caused by strain G1-1477 or G2-1573, combination therapy with amoxicillin and gentamicin was significantly more active than amoxicillin alone (P < 0.05) but not in those infected with the strains G3-1688 and 102. Thus, intermediate levels of resistance to gentamicin was not associated with a loss of a beneficial effect of the gentamicin-amoxicillin combination in vivo even though higher concentrations of gentamicin were necessary to achieve in vitro synergism. Therefore, the use of an MIC of 500 microg/ml as a clinical cutoff limit to predict in vivo benefit of the combination remains a simple and effective tool.

Amoxicillin↗
PubMed2004

Acute pulmonary embolism: a rare complication of a large non-parasitic hepatic cyst.

A 56-year-old patient with a non-parasitic hepatic cyst developed acute dyspnoea. Pulmonary embolism was diagnosed. Bleeding into the hepatic cyst, leading to its enlargement and compression of the inferior vena cava, was the only likely cause of the pulmonary embolism. This complication of a non-parasitic liver cyst has not been reported previously. The patient was treated with heparin. Surgical evacuation of the cyst using the 'fenestration' technique was also performed. There was no recurrent pulmonary embolism or hepatic cyst during a 1-year follow-up period.

Acute Disease↗
PubMed2004

Activities of dalbavancin in vitro and in a rabbit model of experimental endocarditis due to Staphylococcus aureus with or without reduced susceptibility to vancomycin and teicoplanin.

For the treatment of rabbit endocarditis, dalbavancin given once daily (10 mg/kg of body weight for 4 days) or as a single 40-mg/kg dose was active against Staphylococcus aureus with or without reduced susceptibility to glycopeptides, as expected from its good in vitro activity, even in broth supplemented with 90% serum and given its prolonged elimination half-life.

Animals↗
PubMed2003

Expression of glycopeptide-resistance gene in response to vancomycin and teicoplanin in the cardiac vegetations of rabbits infected with VanB-type Enterococcus faecalis.

VanB-type resistance in enterococci corresponds to resistance to vancomycin but not to resistance to the related glycopeptide teicoplanin, because the vanB gene cluster is activated by the VanR(B)-VanS(B) 2-component regulatory system in response to vancomycin but not to teicoplanin. Mutations in the vanS(B) gene allow for constitutive or teicoplanin-inducible expression of the resistance genes. To analyze in vivo expression of the van genes in rabbits with experimental endocarditis, a VanB-type Enterococcus faecalis with a transcriptional fusion between the P(YB) promoter of resistance genes and the gfpmut1 gene for the green-fluorescent protein in the chromosome was constructed. Rounded heaps containing fluorescent bacteria were detected in vegetation slides from rabbits treated with vancomycin but not in those from control rabbits, revealing induction of a tightly regulated vanB gene cluster. Teicoplanin-resistant mutants were detected as fluorescent bacteria in rabbits treated with teicoplanin. Thus, the reporter system monitored expression of a glycopeptide-resistance gene in vivo at a single-cell level.

Animals↗
PubMed2003

Recurrent valvular replacement due to exacerbation of Behcet's disease by Streptococcus agalactiae infection.

Valvular heart complications in Behcet's disease are rarely reported. Moreover, the risk of dehiscence in postoperative valvular replacement is high in Behcet's disease. We report a case of recurrent aortic prosthetic dehiscence revealing Behcet's disease in a young woman. Each disease exacerbation was concomitant to a Streptococcus agalactiae infection. This infection appears to act as a trigger for Behcet's disease exacerbation. The patient was successfully treated with immunosuppression plus antibiotic therapy.

Journal Article↗
PubMed2003

Hypoparathyroidism preceding Riedel's thyroiditis.

We report the case of a woman who presented with primary hypoparathyroidism and who subsequently developed extensive Riedel's thyroiditis. To our knowledge, this is the first reported case of primary hypoparathyroidism preceding Riedel's thyroiditis. This observation suggests that Riedel's thyroiditis is part of a diffuse fibrotic process that may involve other organs, such as the parathyroid glands.

Journal Article↗
PubMed2003

Activity and diffusion of tigecycline (GAR-936) in experimental enterococcal endocarditis.

The activity of tigecycline (GAR-936), a novel glycylcycline, was investigated in vitro and in experimental endocarditis due to the susceptible Enterococcus faecalis JH2-2 strain, its VanA type transconjugant BM4316, and a clinical VanA type strain, E. faecium HB217 resistant to tetracycline. MICs of GAR-936 were 0.06 micro g/ml for the three strains. In vitro pharmacodynamic studies demonstrated a bacteriostatic effect of GAR-936 that was not enhanced by increasing concentrations to more than 1 micro g/ml and a postantibiotic effect ranging from 1 to 4.5 h for concentrations of 1- to 20-fold the MIC. Intravenous injection of [(14)C]GAR-936 to five rabbits with enterococcal endocarditis sacrificed 30 min, 4 h, or 12 h after the end of the infusion evidenced a lower clearance of GAR-936 from aortic vegetations than from serum and a homogeneous diffusion of GAR-936 into the vegetations. In rabbits with endocarditis, GAR-936 (14 mg/kg of body weight twice a day [b.i.d.]) given intravenously for 5 days was bacteriostatic against both strains of E. faecalis. Against E. faecium HB217, bacterial counts in vegetations significantly decreased during therapy (P < 0.01), and the effect was similar with GAR-936 at 14 mg/kg b.i.d., 14 mg/kg once a day (o.d.), and 7 mg/kg o.d., which provided concentrations in serum constantly above the MIC. Mean serum elimination half-life ranged from 3.3 to 3.6 h. No GAR-936-resistant mutants were selected in vivo with any regimen. We concluded that the combination of prolonged half-life, significant postantibiotic effect, and good and homogeneous diffusion into the vegetations may account for the in vivo activity of GAR-936 against enterococci susceptible or resistant to glycopeptides and tetracyclines, even when using a o.d. regimen in rabbits.

Animals↗
PubMed2003

Influence of VanD type resistance on activities of glycopeptides in vitro and in experimental endocarditis due to Enterococcus faecium.

The consequences of VanD type glycopeptide resistance on the activity of vancomycin and teicoplanin were evaluated in vitro and in a rabbit model of aortic endocarditis with VanD type clinical isolate Enterococcus faecium BM4339 (MICs: vancomycin, 64 microg/ml; teicoplanin, 4 microg/ml) and its susceptible derivative BM4459 (MICs: vancomycin, 1 microg/ml; teicoplanin, 1 microg/ml). The two antibiotics were inactive against BM4339 in vivo, in terms both of reduction of bacterial counts and of prevention of emergence of glycopeptide-resistant subpopulations, despite using teicoplanin at concentrations greater than the MIC for VanD strains. This could be due to the high inoculum effect also observed in vitro with BM4339 and two other VanD type isolates against both antibiotics. These results suggest that detection of VanD type resistance is of major importance because it abolishes in vivo glycopeptide activity and allows the emergence of mutants highly resistant to glycopeptides.

Animals↗
PubMed2003

Influence of reduced susceptibility to glycopeptides on activities of vancomycin and teicoplanin against Staphylococcus aureus in experimental endocarditis.

The influence of reduced susceptibilities to glycopeptides on the activities of vancomycin and teicoplanin against an isogenic pair of clinical Staphylococcus aureus strains in experimental endocarditis was investigated. While vancomycin was similarly active against both strains, teicoplanin was approximately 100-fold less active against the resistant strain and selected for the emergence of more resistant subpopulations.

Animals↗
PubMed2002

Acute respiratory failure due to diaphragmatic weakness revealing a polymyositis.

Of the different respiratory disorders that complicate the course of polymyositis, diaphragmatic weakness is one that is seldom described and most often suspected rather than confirmed. We report a case of severe diaphragmatic weakness as a cause of acute respiratory failure revealing a polymyositis. The diaphragmatic involvement was proven by a very low esophageal pressure in response to cervical magnetic stimulation of the phrenic nerve. Corticosteroids and intravenous gammaglobulin, combined with mechanical ventilation, achieved a progressive recovery of diaphragmatic weakness.

Journal Article↗