Piperacillin/tazobactam as an alternative antibiotic therapy to carbapenems in the treatment of urinary tract infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae: an in silico pharmacokinetic study.

Piperacillin/tazobactam (TZP) as an alternative treatment to carbapenems for infections involving extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) remains debated. In this study, the probabilities of pharmacodynamic (PD) target attainment with different TZP regimens in ESBL-producing Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp) were evaluated in the context of pyelonephritis. Minimum inhibitory concentrations (MICs) of 144 ESBL-Ec and 111 ESBL-Kp from pyelonephritis were measured, and two previously published population pharmacokinetic models were used to determine by Monte Carlo simulation the probabilities of reaching two PD targets (50%fT>MIC and 100%fT>MIC) with TZP doses of 4 g three times daily and 4.5 g four times daily given as short (1 h) or prolonged (4 h) infusions or as 12-18 g/day continuous infusions. Only MICs of the 133 ESBL-Ec and 74 ESBL-Kp strains susceptible to TZP according to inhibition zone diameter were considered for the simulations. Results were similar with the two models, and only prolonged and continuous infusions allowed to reach 50%fT>MIC with a probability of >90% irrespective of bacterial species. Continuous infusion and prolonged infusion combined with the maximum dosage were the only condition allowing to achieve 100%fT>MIC with a probability of >70% with this population of ESBL-Ec. A probability of >90% to reach 100%fT>MIC with ESBL-Kp could be obtained only with the 18 g/day continuous-infusion regimen. TZP may be used for treatment for mild pyelonephritis involving susceptible ESBL-Ec provided that administration modalities are optimised. Conversely, for ESBL-Kp the risk of treatment failure may be higher, supporting the use of continuous infusion.

Concomitant presence of Aspergillus fumigatus and Stenotrophomonas maltophilia in the respiratory tract: a new risk for patients with liver disease?

Concomitant lung colonization by Aspergillus fumigatus and Stenotrophomonas maltophilia was reported mainly in patients with cystic fibrosis (CF) and immunocompromised patients. The aim of the study was to assess the frequency of co-culture of A. fumigatus and S. maltophilia in respiratory samples of hospitalized patients, and to determine its associated factors. Between 2007 and 2011, all patients who had A. fumigatus in their respiratory samples were retrospectively enrolled in the study. Their clinical and laboratory data, including the presence of S. maltophilia in a respiratory sample, were collected within the same month. Of the 257 enrolled patients (372 respiratory samples), 71 % were immunocompromised and 32 % had chronic respiratory disease. S. maltophilia was isolated within the same month in 20 patients (7.8 %). In the univariate analysis, factors associated with concomitant culture of A. fumigatus and S. maltophilia were liver disease (P = 0.009), orotracheal intubation (P = 0.001), ventilator-associated pneumonia (P = 0.006), central venous catheter (P = 0.003), parenteral nutrition (P = 0.008) and culture of Pseudomonas aeruginosa in respiratory samples (P = 0.002). In the multivariate analysis, the simultaneous presence of P. aeruginosa in the respiratory tract (odds ratio (OR) = 3.19, 95 % confidence interval (CI) 1.11-9.14, P = 0.031), liver disease (OR = 3.92, 95 % CI 1.32-11.62, P = 0.014) and orotracheal intubation (OR = 3.42, 95 % CI 1.17-9.96, P = 0.024) were independently associated with the co-culture of S. maltophilia and A. fumigatus. Factors independently associated with the concomitant culture of A. fumigatus and S. maltophilia were identified. These results support a future prospective study focusing on liver disease and its complications.

New procedure to reduce the time and cost of broncho-pulmonary specimen management using the Previ Isola® automated inoculation system.

The microbiological diagnosis of respiratory tract infections requires serial manual dilutions of the clinical specimen before agar plate inoculation, disrupting the workflow in bacteriology clinical laboratories. Automated plating instrument systems have been designed to increase the speed, reproducibility and safety of this inoculating step; nevertheless, data concerning respiratory specimens are lacking. We tested a specific procedure that uses the Previ Isola® (bioMérieux, Craponne, France) to inoculate with broncho-pulmonary specimens (BPS). A total of 350 BPS from a university-affiliated hospital were managed in parallel using the manual reference and the automated methods (expectoration: 75; broncho-alveolar lavage: 68; tracheal aspiration: 17; protected distal sample: 190). A specific enumeration reading grid, a pre-liquefaction step and a fluidity test, performed before the inoculation, were designed for the automated method. The qualitative (i.e., the number of specimens yielding a bacterial count greater than the clinical threshold) and quantitative (i.e., the discrepancy within a 0.5 log value) concordances were 100% and 98.2%, respectively. The slimmest subgroup of expectorations could not be managed by the automated method (8%, 6/75). The technical time and cost savings (i.e., number of consumed plates) reached 50%. Additional studies are required for specific populations, such as cystic fibrosis specimens and associated bacterial variants. An automated decapper should be implemented to increase the biosafety of the process. The PREVI Isola® adapted procedure is a time- and cost-saving method for broncho-pulmonary specimen processing.

Emerging severe and fatal infections due to Klebsiella pneumoniae in two university hospitals in France.

Severe infections caused by hypermucoviscous Klebsiella pneumoniae have been reported in Southeast Asian countries over the past several decades. This report shows their emergence in France, with 12 cases observed during a 2-year period in two university hospitals. Two clones (sequence type 86 [ST86] and ST380) of serotype K2 caused five rapidly fatal bacteremia cases, three of which were associated with pneumonia, whereas seven liver abscess cases were caused by K1 strains of ST23.

Impact of peptidoglycan O-acetylation on autolytic activities of the Enterococcus faecalis N-acetylglucosaminidase AtlA and N-acetylmuramidase AtlB.

Autolysins are potentially lethal enzymes that partially hydrolyze peptidoglycan for incorporation of new precursors and septum cleavage after cell division. Here, we explored the impact of peptidoglycan O-acetylation on the enzymatic activities of Enterococcus faecalis major autolysins, the N-acetylglucosaminidase AtlA and the N-acetylmuramidase AtlB. We constructed isogenic strains with various O-acetylation levels and used them as substrates to assay E. faecalis autolysin activities. Peptidoglycan O-acetylation had a marginal inhibitory impact on the activities of these enzymes. In contrast, removal of cell wall glycopolymers increased the AtlB activity (37-fold), suggesting that these polymers negatively control the activity of this enzyme.