The treatment at the WWTP led to the relative enrichment of ESBLEC. We estimated that >600 billion of ESBLEC are released into the river Doubs daily and the sludge produced by the WWTP, used as fertilizer, contains 2.6 × 10(5) ESBLEC per gram.

In the course of an annual 3-month bloodstream infections (BSI) survey conducted during a four-year period in 31 healthcare institutions located in three noncontiguous French regions, we report 18 ST398 Staphylococcus aureus BSI. ST398 BSI incidence showed a seven-fold increase during the study period (0.002 per 1,000 patient days in 2007 vs. 0.014 in 2010). ST398 BSI isolates differed from the pig-borne multiresistant clone: 17/18 BSI isolates were methicillin susceptible and none was of t011, t034 or t108 pig-borne spa-types. ST398 BSI isolates had homogenous resistance patterns (15/18 with only Eryr) and prophagic content (all harboured the hlb-converting Sau3int phage). The clustering of BSI and pig-borne isolates by spa-typing and MLVA, the occurrence of Sau3int phage in BSI isolates and the lack of this phage in pig-borne isolates suggest that the emergence of BSI isolates could have arisen from horizontal transfer, at least of the Sau3int phage, in genetically diverse MSSA ST398 isolates. The acquisition of the phage likely plays a role in the increasing ability of the lysogenic ST398 isolates to colonize human. The mode of acquisition of the non pig-borne ST398 isolates by our 18 patients remains unclear. ST398 BSI were diagnosed in patients lacking livestock exposure and were significantly associated with digestive portals of entry (3/18 [16.7%] for ST398 vs. 19/767 [2.5%] for non ST398 BSI; p = .012). This raises the question of possible foodborne human infections. We suggest the need for active surveillance to study and control the spread of this human-adapted subclone increasingly isolated in the hospital setting.

Cross-colonisation seems to play an important role in the general spread of P. aeruginosa in ICUs.

Although constitutively overproduced in these bacteria, the MexXY efflux system did not appear to contribute significantly to aminoglycoside resistance. ␤-Lactam resistance was associated with derepression of intrinsic AmpC ␤-lactamase (with isolate-to-isolate variations of up to 58-fold) and sporadic deficiency in a 46-kDa protein identified as the carbapenem-selective porin OprD. Of the 18 isolates, 14 were also found to overproduce the efflux system MexAB-OprM as a result of alteration of the repressor protein MexR (His1073Pro). However, complementation experiments with the cloned mexR gene demonstrated that MexAB-OprM contributed only marginally to ␤-lactam and fluoroquinolone resistance. Of the four isolates exhibiting wild-type MexAB-OprM expression despite the MexR alteration, two appeared to harbor secondary mutations in the mexA-mexR intergenic region and one harbored secondary mutations in the putative ribosome binding site located upstream of the mexAB oprM operon. In conclusion, this study shows that many mechanisms were involved in the multiresistance phenotype of this highly epidemic strain of P. aeruginosa. Our results also demonstrate that the clone sporadically underwent substantial genetic and phenotypic variations during the course of the outbreak, perhaps in relation to local or individual selective drug pressures.

AimsThe defined daily doses (DDD) defined by the WHO are widely used as an indicator to measure antibiotic use in the hospital setting. However, discrepancies exist between countries in terms of antibiotic dosage. The aim of the present study was to compare, for each antibacterial agent available at our university hospital, the prescribed daily doses (PDD) with the DDD. MethodsData were extracted from the pharmacy computer system. Antibiotic use was expressed in DDD per 1000 patient days. We also calculated the ratio of number of DDD : number of treatment-days and estimated the average PDD for each antibiotic and route of administration. ResultsThe average PDD did not correspond to the DDD for many classes of antibiotics. If fluoroquinolones and cephalosporins were prescribed at a dosage close to the DDD, other antimicrobial classes such as penicillins, aminoglycosides or macrolides were not. Overall, the number of DDD overestimated the number of treatment days by 40%. For the most consumed antibiotic at our hospital, i.e. oral amoxicillin-clavulanic acid, the PDD was three times the DDD. ConclusionsOur study shows that, except for the fluoroquinolones and the cephalosporins, the number of DDD did not correctly reflect the number of antibiotic treatment days at our hospital. This does not invalidate the systematic approach of the WHO and hospitals should use the DDDs to make national and international comparisons of their antibiotic use. However, each hospital should define and validate its own indicators to describe the local exposures to antibiotics and to study the relationship with resistance.