Dual beta-lactam treatment: Pros and cons.

The battle against microscopic pathogens has always baffled the scientific community. Nowadays, multidrug-resistant microorganisms lead to high in-hospital mortality, increased hospital stays, and high health-related costs. Treating infections due to these high-resistance pathogens with a low number of antibiotic molecules creates the need for new strategies. Although some already think of a "postantibiotic era" with bacteriophages as the main futuristic weapon in antibacterial armament, others rethink the usage of the already existent drugs. Dual beta-lactam therapy has been used for quite some time as an empirical therapy for some severe infections such as endocarditis or meningitis. However, studies regarding the use of a beta-lactam combination stopped being made a long time ago, and it seems the scientific community has no interest in evaluating this as a treatment option. Could this strategy be applied to treat infections due to multidrug-resistant bacteria? Could this be the answer while waiting for the "postantibiotic era"? What kind of pathogens could we fight using dual beta-lactams? What are the downsides of this strategy? These are some of the questions the authors try to answer in this review. In addition, we try to convince our peers to turn once more into researching beta-lactam combinations and exploring its potential benefits.

Is Routine Urinary Screening Indicated Prior To Elective Total Joint Arthroplasty? A Systematic Review and Meta-Analysis.

BACKGROUND: Prosthetic joint infection (PJI) is a serious complication after total joint arthroplasty, and prevention is of great importance. The genitourinary tract is a potential source of bacterial seeding and one that can be easily managed. Despite little supportive evidence, routine urine screening and subsequent treatment before elective surgery in patients without symptoms has found its way into clinical practice in many countries. This systematic review and meta-analysis aims to ascertain whether asymptomatic bacteriuria (ASB) is a risk factor for PJI and if so, whether preoperative antibiotic treatment is effective in reducing its risk. METHODS: PubMed, Ovid Medline, and Cochrane databases were searched using a systematic strategy. Selection of papers was exclusive to include only those which offered information about PJI rate specifically in patients with or without asymptomatic abnormal urinalysis or bacteriuria and/or information on whether ASB patients were preoperatively treated with antibiotics or not to be included in the analysis. RESULTS: Six-hundred sixty-three papers were screened, and 10 papers were ultimately included (28,588 patients). Results show an increased risk of developing PJI among ASB patients (odds ratio = 3.64, 95% confidence interval = 1.40-9.42). However, most PJI microorganisms are unrelated to those previously found in the urine and preoperative antibiotic therapy does not influence PJI risk (odds ratio = 0.98, 95% confidence interval = 0.39-2.44). CONCLUSION: Routine urinary screening prior to elective total joint arthroplasty and treatment of asymptomatic patients is not recommended.

Production of Galacto-oligosaccharides by the ß-Galactosidase from Kluyveromyces lactis : comparative analysis of permeabilized cells versus soluble enzyme.

The transgalactosylation activity of Kluyveromyces lactis cells was studied in detail. Cells were permeabilized with ethanol and further lyophilized to facilitate the transit of substrates and products. The resulting biocatalyst was assayed for the synthesis of galacto-oligosaccharides (GOS) and compared with two soluble ß-galactosidases from K. lactis (Lactozym 3000 L HP G and Maxilact LGX 5000). Using 400 g/L lactose, the maximum GOS yield, measured by HPAEC-PAD analysis, was 177 g/L (44% w/w of total carbohydrates). The major products synthesized were the disaccharides 6-galactobiose [Gal-ß(1→6)-Gal] and allolactose [Gal-ß(1→6)-Glc], as well as the trisaccharide 6-galactosyl-lactose [Gal-ß(1→6)-Gal-ß(1→4)-Glc], which was characterized by MS and 2D NMR. Structural characterization of another synthesized disaccharide, Gal-ß(1→3)-Glc, was carried out. GOS yield obtained with soluble ß-galactosidases was slightly lower (160 g/L for Lactozym 3000 L HP G and 154 g/L for Maxilact LGX 5000); however, the typical profile with a maximum GOS concentration followed by partial hydrolysis of the newly formed oligosaccharides was not observed with the soluble enzymes. Results were correlated with the higher stability of ß-galactosidase when permeabilized whole cells were used.

Screening ß-fructofuranosidases mutant libraries to enhance the transglycosylation rates of ß-(2→6) fructooligosaccharides.

ß-Fructofuranosidases can divert their hydrolytic activity towards transglycosylation for the synthesis of high value-added products, including prebiotic fructooligosaccharides (FOS). A directed evolution strategy has been employed to enhance the transferase rate of the ß-fructofuranosidase (SoINV) from the Schwanniomyces occidentalis yeast for the production of ß-(2→6)-linked FOS. To screen for transferase activity of the SoINV functionally expressed in Saccharomyces cerevisiae, a high-throughput screening protocol based on two colorimetric assays was validated (with coefficient of variance below 11%). Mutagenic libraries were constructed by error-prone PCR and clones showing higher glucose:fructose ratio with respect to the parental type were identified. Further analysis by anion-exchange chromatography coupled with pulsed amperometric detection helped to identify mutants with improved yields for the synthesis of ß-(2→6) fructooligosaccharides. Selected mutants displayed transferase initial rates enhanced ~2-fold over parent type, reaching production levels up to 47 g/L after 48 h of reaction for the formation of 6-kestose.