[Ertapenem administered intravenously or subcutaneously for urinary tract infections caused by ESBL producing enterobacteriacea]. / Ertapénem intraveineux ou sous-cutané pour le traitement des infections urinaires à entérobactérie sécrétrice de BLSE.

INTRODUCTION: Ertapenem could be used to treat urinary tract infections (UTI) caused by ESBL producing enterobacteriacae (ESBL-E) and administered subcutaneously. METHOD: The authors made a retrospective study on adult patients treated with ertapenem administered intravenously or subcutaneously for UTI caused by ESBL-E, between May 2009 and August 2011 at the Chambery hospital, France. RESULTS: Twenty-five patients were treated (13 cases of prostatitis, ten of pyelonephritis, two of cystitis) mostly caused by Escherichia coli (24 cases). Subcutaneous injections were administered to 20 patients and 23 were treated through outpatient parenteral antibiotic therapy (OPAT). All patients were cured at the end of the ertapenem therapy. Urine samples collected during treatment for 12 patients were sterile. Three months after the end of the treatment, five patients had relapsed, and six had developed a UTI caused by another bacteria. CONCLUSION: Ertapenem administered intravenously or subcutaneously could be an effective treatment for UTI caused by ESBL-E, especially using OPAT.

New combinations of mutations in VanD-Type vancomycin-resistant Enterococcus faecium, Enterococcus faecalis, and Enterococcus avium strains.

We studied the clinical isolates Enterococcus faecium NEF1, resistant to high levels of vancomycin (MIC, 512 microg/ml) and teicoplanin (MIC, 64 microg/ml); Enterococcus faecium BM4653 and BM4656 and Enterococcus avium BM4655, resistant to moderate levels of vancomycin (MIC, 32 microg/ml) and to low levels of teicoplanin (MIC, 4 microg/ml); and Enterococcus faecalis BM4654, moderately resistant to vancomycin (MIC, 16 microg/ml) but susceptible to teicoplanin (MIC, 0.5 microg/ml). The strains were distinct, were constitutively resistant via the synthesis of peptidoglycan precursors ending in D-alanyl-D-lactate, and harbored a chromosomal vanD gene cluster that was not transferable. New mutations were found in conserved domains of VanS(D): at T(170)I near the phosphorylation site in NEF1, at V(67)A at the membrane surface in BM4653, at G(340)S in the G2 ATP-binding domain in BM4655, in the F domain in BM4656 (a 6-bp insertion), and in the G1 and G2 domains of BM4654 (three mutations). The mutations resulted in constitutivity, presumably through the loss of the phosphatase activity of the sensor. The chromosomal Ddl D-Ala:D-Ala ligase had an IS19 copy in NEF1, a mutation in the serine (S(185)F) or near the arginine (T(289)P) involved in D-Ala1 binding in BM4653 or BM4655, respectively, and a mutation next to the lysine (P(180)S) involved in D-Ala2 binding in BM4654, leading to the production of an impaired enzyme. In BM4653 vanY(D), a new insertion sequence, ISEfa9, belonging to the IS3 family, resulted in the absence of D,D-carboxypeptidase activity. Strain BM4656 had a functional D-Ala:D-Ala ligase, associated with high levels of both VanX(D) and VanY(D) activities, and is the first example of a VanD-type strain with a functional Ddl enzyme. Study of these five clinical isolates, displaying various assortments of mutations, confirms that all VanD-type strains isolated so far have undergone mutations in the vanS(D) or vanR(D) gene, leading to constitutive resistance, but that the Ddl host ligase is not always impaired. Based on sequence differences, the vanD gene clusters could be assigned to two subtypes: vanD-1 and vanD-4.