SOX10 mutations mimic isolated hearing loss.

Ninety genes have been identified to date that are involved in non-syndromic hearing loss, and more than 300 different forms of syndromic hearing impairment have been described. Mutations in SOX10, one of the genes contributing to syndromic hearing loss, induce a large range of phenotypes, including several subtypes of Waardenburg syndrome and Kallmann syndrome with deafness. In addition, rare mutations have been identified in patients with isolated signs of these diseases. We used the recent characterization of temporal bone imaging aspects in patients with SOX10 mutations to identify possible patients with isolated hearing loss due to SOX10 mutation. We selected 21 patients with isolated deafness and temporal bone morphological defects for mutational screening. We identified two SOX10 mutations and found that both resulted in a non-functional protein in vitro. Re-evaluation of the two affected patients showed that both had previously undiagnosed olfactory defects. Diagnosis of anosmia or hyposmia in young children is challenging, and particularly in the absence of magnetic resonance imaging (MRI), SOX10 mutations can mimic non-syndromic hearing impairment. MRI should complete temporal bones computed tomographic scan in the management of congenital deafness as it can detect brain anomalies, cochlear nerve defects, and olfactory bulb malformation in addition to inner ear malformations.

Pulse-field gel electrophoresis typing of methicillin-resistant Staphylococcus aureus strains susceptible to aminoglycosides isolated from 1993 to 2002.

Methicillin-resistant Staphylococcus aureus (MRSA) susceptible strains to aminoglycosides (AS-MRSA) have been increasingly isolated in the Albert Cheneiver Hospital during the past 10 years. The aim of this study was first, to analyse the genotypes and the profiles of resistance to antibiotics and second to compare the AS-MRSA with the MRSA resistant to gentamicin (GR-MRSA) and with MRSA resistant to kanamycin and tobramycin, but susceptible to gentamicin (GS-MRSA), previously studied in our laboratory. All the AS-MRSA consecutively isolated from clinical samples (carriage isolates excluded) from 01/01/1993 to 31/12/2002 (33 isolates) were typed by DNA macrorestriction. Their susceptibilities to other anti-staphylococcal drugs (erythromycin, lincomycin, tetracycline, rifampicin, fusidic acid and fosfomycin) were studied by the French standard disk method. The 33 strains showed a heterogeneous resistance to oxacillin and fell into five phenotypes. The main phenotype (51.5% of the AS-MRSA strains) was susceptible to the six antibiotics studied. DNA macrorestriction defined 24 genotypes (percentage similarity <80%). Among them 16 genotypes contained only one strain each, and none contained more than three isolates. Conversely the comparison with GR-MRSA and GS-MRSA isolated during the same period showed that the strains were not closely linked. The diversity of our isolates showed that it was not an epidemic phenomenon, in contrast to the results of similar studies. Our findings may be explained by the patients coming mostly from different hospital units. This work indicates the need for further studies on the genome, to determine whether AS-MRSA have derived from strains that occurred before aminoglycosides came into clinical use.

Comparative pulsed-field gel electrophoresis typing of gentamicin-resistant and -susceptible methicillin-resistant Staphylococcus aureus strains isolated in France between 1991 and 1998. Changes in antibiotic susceptibility.

Using macrorestriction of genomic DNA and pulsed-field gel electrophoresis, we examined 504 non-redundant, infection-causing human isolates of methicillin-resistant Staphylococcus aureus susceptible (G(S): 238 isolates) or resistant to gentamicin (G(R): 266 isolates). The strains were isolated at Albert Chenevier Hospital (Créteil, France) between 1 January 1991 and 31 December 1998. Their susceptibility to erythromycin, lincomycin, tetracycline, rifampicin, fusidic acid and fosfomycin was also studied. Seventy-six genotypes were identified (percentage similarity<80). Ten types, each containing at least eight strains, predominated. G(R) strains showed higher genetic polymorphism than G(S) strains: the 266 G(R) isolates belonged to 67 genotypes, five of which predominated (44, 42, 38, 30 and 15 isolates); the 238 G(S) isolates belonged to only 18 types, four of which predominated (112, 83, 11 and 10 isolates). Fifty-six percent of G(R) strains (34 Gt) were resistant to erythromycin, lincomycin, tetracycline and rifampicin, and were isolated at relatively stable frequencies. Resistance to five antibiotics studied (susceptible to fusidic acid) was observed among 16.5% of G(R) strains. The frequency of strains with this profile diminished from 30% in the early 1990s to 10% in 1998. One hundred and twenty-six G(S) isolates were susceptible to all six antibiotics; this profile was only found from 1993 onwards, and was increasingly frequent (60% of G(S) strains in 1996). Resistance to erythromycin and lincomycin only was found in 70 G(S) isolates; this profile accounted for approximately half the isolates in 1992/1993 and only one-third in 1998. These results, obtained over an eight-year period, show an overall increase in antibiotic susceptibility. They confirm the spread of two major clones of MRSA-G(S) and support the hypotheses that G(S) strains derive from G(R) strains that have lost the aac6'-aph2" gene; and that G(S) strains are genetically related to those that were present before the use of gentamicin and persisted at a low frequency until 1992-1993.

A clinical trial of mupirocin in the eradication of methicillin-resistant Staphylococcus aureus nasal carriage in a digestive disease unit.

We assessed the incidence of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) on admission, the rate of acquisition during the hospital stay and the relationship with subsequent infection in a digestive disease unit. The efficacy of a program of nasal carriage eradication with mupirocin was evaluated simultaneously. Over one year 484 patients were studied prospectively on admission for nasal and stool carriage of MRSA, then every week for nasal carriage. Nearly 70% (68.8%) of patients had chronic liver diseases. Nasal carriers were assigned to a five-day course of intranasal mupirocin ointment. One hundred and seventeen (24.2%) patients were MRSA positive, 57 (11.8%) of which were carriers on admission and 60 (12.4%) acquired carriage. Of these, 86 were treated with mupirocin with a success rate of 98.8% and 25.9% of them recolonized. Fourteen patients were retreated, to allow eradication in 71.4% of cases. Seventy percent of these became carriers again. One high-level mupirocin-resistant strain was isolated before treatment and seven during or after treatment. Hospital stay and stool carriage were independently associated with reacquisition (P = 0.0105 and P = 0.0462, respectively). Molecular analysis showed identity between the strains isolated from infection samples and from nasal swabs during the same week. For every patient who became recolonized, nasal strains isolated before and after eradication were the same in 70% of cases. Mortality during hospital stay was independently associated with age (P = 0.0081), MRSA nasal carriage (P = 0.02631), MRSA infection (P < 0.0001) and liver disease (P = 0.0017). This study did not show a change in the prevalence rate of infection in the unit during treatment with mupirocin. This treatment should only be attempted once due to the risk of emergence of high-level resistant strains.

A 5-year epidemiological study of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates in a medium- and long-stay neurological unit.

Thirty-eight different strains of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBL Kp), isolated from urine and pus samples of 38 patients hospitalized in a medium- and long-stay neurology department between 1 January 1992 and 31 December 1996, were analysed by antibiotic resistance phenotyping, DNA macrorestriction by pulsed-field electrophoresis and isoelectric focusing of beta-lactamases. An epidemiological survey was conducted to identify risk factors for infection by ESBL Kp in this setting. The 38 isolates were distributed into 13 antibiotypes, three of which predominated (13, six and six isolates). The DNA macrorestriction pattern identified 15 genotypes, four of which predominated (11, six, four and four isolates). A combination of the two typing methods revealed several epidemic clones that emerged consecutively. Two main types of ESBL (SHV-2 and CTX-1) were identified by isoelectric focusing, the former predominating. The case-control study showed that the length of hospital stay, degree of malnutrition and dependency, and urinary sphincter status were the main factors significantly associated with ESBL Kp isolation.