First detection of TEM-116 extended-spectrum ß-lactamase in a Providencia stuartii isolate from a Tunisian hospital.

PURPOSE: To study the resistance to third-generation cephalosporins in Providencia stuartii strain isolated from hospitalized patient in Tunisia and to identify the responsible genes MATERIALS AND METHODS: This strain was analysed by PCR and sequencing to identify the genes responsible for the ß-lactamase resistance phenotypes. The transferability of the phenotypes was tested by conjugation to Escherichia coli J53. The isoelectric point was determinate by isoelectrofocalisation. RESULTS: This resistance was carried by a 60 kb plasmid that encoded a ß-lactamase with a pI of 5.4. This ß-lactamase revealed identity with the blaTEM-1 gene encoding the TEM-1 ß-lactamase, except for a replacement of the Val residue at position 84 by Ile, and the Ala residue at position 184 by Val. These two mutations were encountered in TEM-116 ß-lactamase. CONCLUSION: This study demonstrates the first description of TEM-116 in the P. stuartii species in the world and the first one in a Tunisian hospital.

Nosocomial dissemination of extended-spectrum ß-lactamase VEB-1a-producing Providencia stuartii isolates in a Tunisian hospital.

A collection of 20 multidrug-resistant Providencia stuartii isolates recovered from 2005 to 2009 at the Military Hospital of Tunis, Tunisia, was analysed. They all expressed the extended-spectrum ß-lactamase (ESBL) VEB-1a. The bla (VEB-1a) gene was plasmid-located and it was associated with complex genetic structures, including Re elements. Pulsed-field gel electrophoresis (PFGE) revealed a clonal relationship between all of these isolates. This study identified a nosocomial dissemination of an ESBL-producing P. stuartii clone in a Tunisian hospital over a long period of time.

[In situ hybridization in undifferentiated nasopharynx carcinoma in Tunisia. Report of 3 cases]. / Hybridation in situ dans les carcinomes indifférenciés du nasopharynx en Tunisie. A propos de 3 observations.

The undifferentiated carcinoma of nasopharyngeal type (UCNT) is highly prevalent in South East Asia countries and has intermediate incidence in Tunisia, where Epstein-Barr virus constitutes one of the key factors of oncogenesis. Our preliminary results, in 3 patients with UCNT, show an elevated rate of EBV antibodies and a latent infection (type II) (expression of LMP and absence of ZEBRA by immunohistochemical reaction) and a positive staining with EBERs probe by in situ hybridation (ISH) in all cases. These results confirm a close association between EBV and tunisian UCNT. Moreover, the use of HIS technique for detection of EBERs constitutes an additional and formal argument of this association.

Comparative pharmacokinetics of oxaliplatin (L-OHP) and carboplatin (CBDCA) in mice with reference to circadian dosing time.

Carboplatin (CBDCA) and oxaliplatin (I-OHP) are non-nephrotoxic platinum (Pt) compounds, which exert their main respective toxicities on the bone marrow and on the intestinal mucosa in mice. Plasma and red blood cell (RBC) drug dispositions were investigated in 324 male B6D2F1 mice after a single IV injection of CBDCA (72 mg kg-1) or I-OHP (17 mg kg-1). Since the toxicities of either drug largely depended upon circadian dosing time, such a pharmacokinetic study was performed following injection of either Pt complex at a time of low (16 h after light onset-HALO), intermediate (0 HALO) or high (8 HALO) toxicity. Pt concentrations in plasma ultrafiltrate (PUF) and in total plasma declined in parallel and became barely detectable by 2 h following CBDCA injection. Conversely, free Pt became undetectable 1 h after I-OHP injection, whereas sustained levels of total Pt were found 24 h post dosing. This suggested that I-OHP had a high binding affinity for plasma proteins. Mean values of t1/2 alpha and mean residence time (MRT) of free Pt for I-OHP (6.7 min and 9.7 min respectively) were half those of CBDCA (12.5 min and 18.1 min respectively). The two drugs had a similar initial volume of distribution (Vdi) of free Pt (10.5 mL) in mice. However, plasma clearance of I-OHP was twice as high (1.06 mL min-1) as that of CBDCA (0.58 mL min-1). Free Pt AUCs were eight to ten times lower for I-OHP than for CBDCA. In contrast, erythrocyte Pt AUCs were three to four times as high for I-OHP as for CBDCA. Circadian changes in pharmacokinetic parameters were large, yet limited to the initial distribution phase (C0, t1/2 alpha, Vdi) as well as mean residence time. The smallest Vdi and the fastest plasma elimination occurred when either drug was injected at 0 HALO. The largest Vdi and the longest elimination were however observed at 8 HALO for CBDCA and 16 HALO for I-OHP. No consistent relationship was found for both Pt complexes with regard to circadian changes in blood pharmacokinetics and in target organ toxicities. The major pharmacokinetics differences between CBDCA and I-OHP were related to both protein binding and RBC handling.