[Acute generalized exanthematous pustulosis induced by phloroglucinol]. / Pustulose exanthématique aiguë généralisée induite par le phloroglucinol (Spasfon®).

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a severe drug eruption. We report herein the first case of AGEP induced by phloroglucinol (Spasfon®). PATIENTS AND METHODS: A 27-year-old pregnant woman developed a febrile exanthematous pustulosis eruption three days after treatment with intravenous phloroglucinol and paracetamol for nephritic colic. She had no previous history of psoriasis. The laboratory workup showed hyperleukocytosis with neutrophilia. A cytobacteriological sample of the pustules was negative. Skin biopsy revealed marked neutrophilic and leukocytoclastic vasculitis. Reintroduction of phloroglucinol after delivery resulted in the same clinical symptoms within a few hours of intake. A diagnosis of phloroglucinol-induced AGEP was made on the basis of intrinsic imputability of I4 (S3 C3) using the imputability criteria of Begaud et al. The outcome was favorable after withdrawal of the drug. DISCUSSION: To the best of our knowledge, this is the first case of phloroglucinol-induced AGEP confirmed by reintroduction of the drug.

Cardiovascular risk and lupus disease.

AIM: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The aim of this study was to evaluate subclinical atherosclerosis and to determine the prevalence of risk factors for CVD in SLE patients. METHODS: One hundred fifty-three patients (149 women and 4 men), aged (37±11.6) years with a definite diagnosis of SLE according to the revised criteria of the American College of Rheumatology (ACR), underwent physical examination, carotid and leg arteries B-mode ultrasound with a measure of ankle-brachial pressure index (ABPI); 94 patients had myocardial tomoscintigraphy. The laboratory check-up was: total cholesterol (TC), HDLc, LDLc, homocystein, glycemia, vascular cell adhesion molecules (VCAM-I). All patients had a normal renal function at the time of the study. RESULTS: The mean age is 37 years. Cardiovascular events were noticed in 15 patients (6 angina, 2 myocardial infarction and 7 strokes). Cardiovascular risk factors (CVRF) were: dyslipidemia (62.8%), moderate homocysteinemia (55%), BMI>25 (39%) and hypertension (35%) which is associated with a stroke (P<0.0006). The cumulative prednisone dose per patient was 45.5g. V.C.A.M-I level was high in 86.2 % of cases.95% of our patients had at least two CVRF. Myocardial perfusion stress scanning showed abnormalities in 21 patients (22.3%). Perfusion defects were linked with a stroke (P<0.01) and coronary events (P<0.02). Carotid atheroma was present in 32 patients (20.9%). Carotid plaques were associated with age (P<0.01), total cholesterol (TC)(P<0.05), and steroid dose (P<0.01). Intima-media-thickness was correlated with age (P<0.0003), TC (P<0.0007), LDLc (P<0.002), and homocysteine (P<0.03). 70% patients had a mediacalcinosis in femoral and popliteal arteries. The ABPI was correlated with V.C.A.M-I (P<0.0005). CONCLUSION: In Algeria, as elsewhere, young women with SLE have subclinical atherosclerosis which must be detected and they are at high risk of a vascular event.

Childhood cryptosporidiosis: a case report.

Cryptosporidium has emerged as an important cause of diarrheal illness worldwide, especially amongst young children and patients with infectious or iatrogenic immune deficiencies. The authors describe a case of mild cryptosporidiosis in a well-nourished, immunocompetent, one-year-old child. Rapid clinical and parasitological improvement was observed after a 3-day course of nitazoxanide.

Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma.

BACKGROUND: We explored the addition of rituximab to high-dose cytarabine (ara-C), oxaliplatin (L-OHP), and dexamethasone [R-DHAOx], in resistant and relapsed patients with CD20-positive follicular non-Hodgkin's lymphoma. METHODS: Twenty-two patients were included; they were treated previously with one to five chemotherapy regimens, including 13 patients who had also received rituximab. R-DHAOx consisted of rituximab, 375mg/m(2), day 1; dexamethasone, 40mg/d, days one to four; L-OHP, 130mg/m(2), day 1; and ara-C, 2000mg/m(2) every 12 h, day 2. Courses were repeated every 21 days for eight courses. RESULTS: Twenty-one patients (95%) achieved a complete response and one had a partial response. Responses were obtained in patients with and without resistance to prior treatment, either alone or combined with rituximab. The median follow-up time was 58.3 months (range, 8.7-92.6 months). Progression-free survival reached a plateau at 84% at 38.2 months. Only two of the 21 complete responders have relapsed. Tumor molecular markers disappeared in all 10 complete responders whose markers were found before treatment. Peripheral neuropathy related to the cumulative dose of L-OHP, and myelosuppression were the most prominent toxic effects. CONCLUSIONS: R-DHAOx is highly active for salvage treatment of patients with follicular non-Hodgkin's lymphoma, and it produces long-term antitumor efficacy.

The first founder DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome.

Deoxyguanosine kinase (dGK) deficiency is a frequent cause of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this study, we describe a new splice site mutation in the DGUOK gene and the clinical, radiologic, and genetic features of these DGUOK patients. This new DGUOK homozygous mutation (c.444-62C>A) was identified in three patients from two North-African consanguineous families with combined respiratory chain deficiencies and mitochondrial DNA depletion in the liver. Brain MRIs are normal in DGUOK patients in the literature. Interestingly, we found subtentorial abnormal myelination and moderate hyperintensity in the bilateral pallidi in our patients. This new mutation creates a cryptic splice site in intron 3 (in position -62) and is predicted to result in a larger protein with an in-frame insertion of 20 amino acids. In silico analysis of the putative impact of the insertion shows serious clashes in protein conformation: this insertion disrupts the alpha5 helix of the dGK kinase domain, rendering the protein unable to bind purine deoxyribonucleosides. In addition, a common haplotype that segregated with the disease in both families was detected by haplotype reconstruction with 10 markers (microsatellites and SNPs), which span 4.6 Mb of DNA covering the DGUOK locus. In conclusion, we report a new DGUOK splice site mutation that provide insight into a critical protein domain (dGK kinase domain) and the first founder mutation in a North-African population.

[Pyoderma gangrenosum with aseptic spleen abscess]. / Pyoderma gangrenosum et abcès splénique aseptique.

BACKGROUND: Pyoderma gangrenosum is a neutrophilic dermatosis in which systemic involvement is rare. It may be associated with systemic disease. We report a case of pyoderma gangrenosum in the spleen. CASE REPORT: A 68-year-old man presenting pyoderma gangrenosum with pustules and stage I multiple myeloma was admitted for asthenia and abdominal pain. There were no skin lesions. Laboratory tests showed inflammatory syndrome with polynuclear leucocytes of 25,000/mm(3). CAT scans and abdominal ultrasound revealed a splenic abscess. A spleen biopsy was performed and histological examination showed polynuclear leukocyte infiltration, while cultures were negatives. Diagnosis of pyoderma gangrenosum with splenic involvement was made. Increased systemic corticosteroid therapy produced a successful outcome. Haematological findings remained unchanged. DISCUSSION: Spleen involvement in pyoderma gangrenosum is very rare and can mimic an infectious process. In such cases, routine screening is essential for associated diseases, particularly haematological malignancies.

[Emergence of macrolide resistant Streptococcus pyogenes strains in pediatric patients in France]. / Emergence de la résistance aux macrolides chez Streptococcus pyogenes en pédiatrie.

A total of 206 recent throat isolates of Streptococcus pyogenes collected between 2002 and 2004 from children were tested for their susceptibility to penicillin, amoxycillin, erythromycin, clarythromycin and clindamycin. The erythromycin resistant isolates were further studied for their genetic mechanism of resistance by means of PCR. In all, 14.5% of the strains were erythromycin resistant and 13.5 and 1% expressed the constitutive MLS(B) and M resistance phenotypes and harbored the ermB and mef A genes respectively.

[Current Streptococcus pyogenes sensitivity responsible for acute tonsillopharyngitis in France]. / Sensibilité actuelle en France de Streptococcus pyogenes responsable d'angine aiguë.

OBJECTIVE: Current guidelines recommend that only tonsillopharyngitis due to group A beta-haemolytic streptococcus (GABHS) diagnosed by rapid diagnostic test should be treated with antibiotics. Empirical antibiotic therapy must be based on epidemiological surveillance of resistance of GABHS to antibiotics. The aim of our study was to assess the activity of antimicrobial agents currently recommended for the treatment of GABHS tonsillopharyngitis. Method The activity of penicillin G, amoxicillin, cefaclor, cefpodoxime, cefuroxime, erythromycin, clarithromycin and clindamycin was determined against 93 consecutive GABHS isolates collected in 2002. MIC50 and MIC90 of antibiotics tested were determined by agar dilution method according to CA-SFM guidelines. Macrolide resistance genes (ermA, ermB, mef) were detected by PCR. Genetic diversity of erythromycin-resistant isolates was analysed by pulsotypic method after digestion by SmaI (Finger-printing II, Biorad). RESULTS: The activity of beta-lactam agents tested was similar and no resistant strain was detected (0%). Nevertheless, this study shows an increasing emergence of erythromycin-resistant GABHS strains reaching 14% in 2002 (vs. 6.2% in a previous study carried out in 1996-1999). CONCLUSION: The empirical antibiotic therapy of tonsillopharyngitis must consider, on the one hand, the high risk of GABHS eradication failure associated with in vitro resistance to erythromycin and clarithromycin, and on the other hand, the sustained susceptibility of GABHS to beta-lactam agents. These results reinforce the recommendations to use beta-lactam agents as first line treatment of GABHS tonsillopharyngitis.

Clonal relationship between U.S. and French serotype V group B streptococcus isolates.

We examined the genetic diversity of serotype V group B streptococcus (GBS) isolates in the Paris area and compared them with the predominant American serotype V clone. Pulsed-field gel electrophoresis yielded 11 patterns for 64 French GBS. One pattern was obtained with 60% of the isolates tested and was indistinguishable from that of the predominant American clone.

In vivo selection of a target/efflux double mutant of Pseudomonas aeruginosa by ciprofloxacin therapy.

We report the emergence after 4 days of ciprofloxacin monotherapy of a double mutant of Pseudomonas aeruginosa overexpressing the multidrug efflux system MexAB-OprM and harbouring a mutation in the gyrB gene. Compared with its initial susceptible counterpart, this mutant exhibited a significant increase in resistance to most of the beta-lactam antibiotics tested (16 x MIC of ticarcillin) and to ciprofloxacin (128 x MIC). Combined ceftazidime and amikacin therapy finally eradicated the resistant isolate and cured the patient of his infection. This case illustrates how strains of P. aeruginosa may develop high levels of fluoroquinolone resistance by combining efflux mechanisms and target alterations.

Genotypic characterization of Pseudomonas aeruginosa strains recovered from patients with cystic fibrosis after initial and subsequent colonization.

Chronic infection by Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) is preceded by a period of colonization and acute infection. Early aggressive antibiotic treatment of initial colonisation may prevent or at least delay chronic pulmonary infection. We initiated treatment with a combination of IV beta-lactam tobramycin, followed by nebulized colistin when PA was first isolated from patients with CF. Subsequent serial PA isolates obtained from these colonized CF patients were characterized by means of molecular methods to determine whether they were genetically related to the initial strain. Initial colonization was eradicated in all 19 patients. All patients reacquired PA within 3-25 months during the 3 years of follow-up. Fourteen patients acquired a new PA strain with a distinct genotypic profile, suggesting a new source of contamination. Five patients had two PA isolates with identical genotypes, suggesting either previous undetected respiratory tract colonization or a persistent environmental source of contamination.

Identification and functional characterization of arylamine N-acetyltransferases in eubacteria: evidence for highly selective acetylation of 5-aminosalicylic acid.

Arylamine N-acetyltransferase activity has been described in various bacterial species. Bacterial N-acetyltransferases, including those from bacteria of the gut flora, may be involved in the metabolism of xenobiotics, thereby exerting physiopathological effects. We characterized these enzymes further by steady-state kinetics, time-dependent inhibition, and DNA hybridization in 40 species, mostly from the human intestinal microflora. We report for the first time N-acetyltransferase activity in 11 species of Proteobacteriaceae from seven genera: Citrobacter amalonaticus, Citrobacter farmeri, Citrobacter freundii, Klebsiella ozaenae, Klebsiella oxytoca, Klebsiella rhinoscleromatis, Morganella morganii, Serratia marcescens, Shigella flexneri, Plesiomonas shigelloides, and Vibrio cholerae. We estimated apparent kinetic parameters and found that 5-aminosalicylic acid, a compound efficient in the treatment of inflammatory bowel diseases, was acetylated with a catalytic efficiency 27 to 645 times higher than that for its isomer, 4-aminosalicylic acid. In contrast, para-aminobenzoic acid, a folate precursor in bacteria, was poorly acetylated. Of the wild-type strains studied, Pseudomonas aeruginosa was the best acetylator in terms of both substrate spectrum and catalytic efficiency. DNA hybridization with a Salmonella enterica serovar Typhimurium-derived probe suggested the presence of this enzyme in eight proteobacterial and four gram-positive species. Molecular aspects together with the kinetic data suggest distinct functional features for this class of microbial enzymes.

Breast milk transmission of a Panton-Valentine leukocidin-producing Staphylococcus aureus strain causing infantile pneumonia.

We report on a 38-day-old infant who developed pleuropneumonia due to a Staphylococcus aureus strain responsible for familial furunculosis, which was acquired by maternal breast-feeding. All isolates from the infant and parents were genetically related by randomly amplified polymorphic DNA analysis and produced Panton-Valentine leukocidin.

Mechanisms of macrolide resistance in clinical pneumococcal isolates in France.

The genetic basis of macrolide resistance was investigated in a collection of 48 genotypically unrelated clinical isolates of Streptococcus pneumoniae obtained between 1987 and 1997 in France. All strains were resistant to erythromycin, clindamycin, and streptogramin B, exhibiting a macrolide-lincosamide-streptogramin B resistance phenotype, and harbored the erm(B) gene. None of the strains carried the mef(A) or erm(A) subclass erm(TR) gene.

Resistance to macrolides in Streptococcus pyogenes in France in pediatric patients.

A total of 1,500 recent throat isolates of Streptococcus pyogenes collected between 1996 and 1999 from children throughout France were tested for their susceptibility to erythromycin, azithromycin, josamycin, clindamycin, and streptogramin B. The erythromycin-resistant isolates were further studied for their genetic mechanism of resistance, by means of PCR. The clonality of these strains was also investigated by means of serotyping and ribotyping. In all, 6.2% of the strains were erythromycin resistant, and 3.4 and 2.8% expressed the constitutive MLS(B) and M resistance phenotypes and harbored the ermB and mefA genes, respectively; ermTR was recovered from one isolate which also harbored the ermB gene. Ten serotypes and 8 ribotypes were identified, but we identified 17 strains by combining serotyping with ribotyping. Among the eight ribotypes, the mefA gene was recovered from six clusters, one being predominant, while the ermB gene was recovered from four clusters, of which two were predominant.

Characterization of extended-spectrum beta-lactamase-producing Salmonella typhimurium by phenotypic and genotypic typing methods.

During 1994, 10 isolates of extended-spectrum beta-lactamase-producing Salmonella typhimurium were recovered from children transferred to our hospital from two different centers. Two additional isolates were recovered from two nurses from one of these centers. The aim of this study was to determine if there is any relationship between these isolates. The characterization was done by phenotypic and genotypic methods: biotyping, phage typing, antibiotic susceptibility pattern determination, plasmid analysis, ribotyping (by the four endonucleases EcoRI, SmaI, BglII, and PvuII), pulsed-field gel electrophoresis (PFGE) of genome macrorestriction patterns with XbaI, and randomly amplified polymorphic DNA (RAPD) pattern determination (with the three primers 217 d2, B1, and A3). The same biotype, the same serotype, and an identical antibiotype were found. All isolates were resistant to oxyimino-beta-lactams, gentamicin, tobramycin, and sulfamethoxazole-trimethoprim. All isolates showed an indistinguishable pattern by ribotyping and very similar patterns by PFGE and RAPD. The overall results indicated the spread of a closely related strain of S. typhimurium in children and nurses.

The link between phylogeny and virulence in Escherichia coli extraintestinal infection.

Previous studies suggesting a link between Escherichia coli phylogenetic groups and extraintestinal virulence have been hampered by the difficulty in establishing the intrinsic virulence of a bacterial strain. Indeed, unidentified virulence factors do exist, and the susceptibility of the host to infection is highly variable. To overcome these difficulties, we have developed a mouse model of extraintestinal virulence to test the virulence of the strains under normalized conditions. We then assessed the phylogenetic relationships compared to the E. coli reference (ECOR) collection, the presence of several known virulence determinants, and the lethality to mice of 82 human adult E. coli strains isolated from normal feces and during the course of extraintestinal infections. Commensal strains belong mainly to phylogenetic groups A and B1, are devoid of virulence determinants, and do not kill the mice. Strains exhibiting the same characteristics as the commensal strains can be isolated under pathogenic conditions, thus indicating the role of host-dependent factors, such as susceptibility linked to underlying disease, in the development of infection. Some strains of phylogenetic groups A, B1, and D are able to kill the mice, their virulence being most often correlated with the presence of virulence determinants. Lastly, strains of the B2 phylogenetic group represent a divergent lineage of highly virulent strains which kill the mice at high frequency and possess the highest level of virulence determinants. The observed link between virulence and phylogeny could correspond to the necessity of virulence determinants in a genetic background that is adequate for the emergence of a virulent clone, an expression of the interdependency of pathogenicity and metabolic activities in pathogenic bacteria.

Phylogenetic analysis of Escherichia coli strains causing neonatal meningitis suggests horizontal gene transfer from a predominant pool of highly virulent B2 group strains.

Phylogenetic relationships of 69 neonatal meningitis Escherichia coli strains isolated worldwide were studied. Restriction fragment length polymorphism of rrn operons (rrn RFLP) in these isolates was compared with that of the 72 strains of the ECOR reference collection. Distributions of K1 antigen, of polymerase chain reaction-detected ibe10 gene, pap, afa, sfa/foc, hly, and aer operons, and of a 14.9-kb rrn-containing HindIII fragment previously associated with neonatal meningitis were compared. Oligoclonality was observed for the meningitis strains. Factorial analysis of correspondence on the rrn RFLP data showed a frequency gradient of meningitis strains from the phylogenetic B2 group (68%) to the A group (6%), via the D and B1 groups (26%). The distribution of the virulence determinants argues for their horizontal transfer during the evolution of E. coli. Analysis of the status of some neonates further suggests that neonatal meningitis results from a balance between bacterial genes of virulence and host factors.