In situ management and molecular analysis of candidaemia related to a totally implantable vascular access in a cystic fibrosis patient.

We describe a case of candidaemia in a paediatric cystic fibrosis (CF) patient with a totally implantable vascular access (TIVA). Serial quantitative blood cultures during therapy with amphotericin B delivered via the catheter suggested that the patient was responding to therapy. The TIVA was finally removed because of persistent fever, but its culture remained sterile. Randomly amplified polymorphic DNA (RAPD) analysis of Candida albicans from various anatomical sites showed that the patient's sputum was the most likely source of TIVA contamination. Investigation of TIVA-related candidaemia by molecular analysis could guide rational antifungal chemoprophylaxis of TIVA-related candidaemia.

Failure of oily chloramphenicol depot injection to treat plague in a murine model.

Effective low-cost single-dose therapy would be invaluable in treating human plague. The efficacy of single- or two-dose injections of oily chloramphenicol (OCm) was compared with that of standard multiple injections of reference drugs (streptomycin or chloramphenicol) in a murine plague model. A single injection of OCm was ineffective. Two doses cleared bacteraemia and limited bacterial growth in the mouse spleen but were less effective in reducing mortality than standard therapy. However, because of the marked pharmacokinetic differences between mice and humans, the failure of depot injection of OCm in murine plague treatment is not indicative of its ineffectiveness in human plague.

Assessment of a fluoroquinolone, three beta-lactams, two aminoglycosides, and a cycline in treatment of murine Yersinia pestis infection.

Amoxicillin, cefotaxime, ceftriaxone, gentamicin, doxycycline, and ofloxacin were active in vitro, like the reference drug streptomycin, against the virulent strain Yersinia pestis 6/69M. The comparative efficacies of these drugs in vivo were evaluated in a standardized and reproducible mouse model of systemic infection. Each antibiotic was injected intravenously once, at 24 h postinfection, and then repeatedly during 48 h. In vivo results were measured by counting the viable bacteria recovered from the whole spleens of mice sacrificed at selected times. All the drugs were manifestly successful; ceftriaxone, ofloxacine, and the reference drug were the most effective. Therefore, gentamicin and doxycycline could be used, depending on the clinical forms of the Y. pestis infection. Further investigations on beta-lactams, especially those used in the present study, could be carried out to confirm or not confirm their activities against Y. pestis. Ofloxacin appeared to be as active and to perform as rapidly as streptomycin in the treatment of murine Y. pestis infection, which is in agreement with the previous successes obtained with the use of fluoroquinolones in the treatment of murine infections caused by other pathogenic yersiniae.

In vitro killing activities of antibiotics at clinically achievable concentrations in cerebrospinal fluid against penicillin-resistant Streptococcus pneumoniae isolated from children with meningitis.

We evaluated the in vitro killing activities of ceftriaxone, imipenem, vancomycin, gentamicin, fosfomycin, and rifampin, alone and in combination, against 26 Streptococcus pneumoniae strains (penicillin G MICs, > 0.125 to 2 micrograms/ml) isolated from the cerebrospinal fluid of children with meningitis. The antibiotics were tested at clinically achievable concentrations in cerebrospinal fluid. After 5 h of incubation, imipenem was the most effective drug. None of the combinations had synergistic activity. Killing by beta-lactam antibiotics or vancomycin was enhanced by the addition of gentamicin, reduced by the addition of rifampin, and unaffected by the addition of fosfomycin.

Identification of regions of the Escherichia coli chromosome specific for neonatal meningitis-associated strains.

Specific virulence factors associated with the pathogenesis of Escherichia coli strains causing neonatal meningitis (ECNM), such as the K1 capsular polysaccharide, the S fimbriae, and the Ibe10 protein, have been previously identified. However, some other yet unidentified factors are likely to be involved in the pathogenesis of ECNM. To identify specialized unique DNA regions associated with ECNM virulence, we used the representational difference analysis technique. The genomes of two strains belonging to nonpathogenic phylogenetic group A of the ECOR reference collection were subtracted from E. coli strain C5, isolated from a case of neonatal meningitis. Strain C5 belongs to the phylogenetic group B2 as do the majority of ECNM. We have isolated and mapped 64 DNA fragments which are specific for strain C5 and not found in nonpathogenic strains. Of these clones, 44 were clustered in six distinct regions on the chromosome. The sfa and ibe10 genes were located in regions 2 and 6, respectively. A group of genes (cnf1, hra, hly, and prs) known to be present in a pathogenicity island of the uropathogenic strain E. coli J96 colocalized with region 6. The occurrence of these DNA regions was tested in a set of meningitis-associated strains and in a control group composed of non-meningitis-associated strains belonging to the same B2 group. Regions 1, 3, and 4 were present in 91, 82, and 81%, respectively, of the meningitis strains and in 40, 13, and 47% of the control strains. Together, these data suggest that regions 1, 3, and 4 code for factors associated with the ability of E. coli to invade the meninges of neonates.