Manica Mueller-Premru

Synthesis and antibacterial activity of 5-ylidenethiazolidin-4-ones and 5-benzylidene-4,6-pyrimidinediones

5-benzylidenethiazolidin-4-ones and 5-benzylidenepyrimidine-4,6-diones (compounds 1-9), carrying 2,3,4-trifluoro or 3,4,5-trimethoxy groups on the benzylidene moiety, and rhodanine derivatives 10 and 11 were synthesized and assayed in vitro for their antimicrobial activity against four standard bacterial strains (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). Compounds 1-3 and 9 that were active against S. aureus, were also tested against methicillin-resistant S. aureus (MRSA) ATCC 43300, Streptococcus pneumoniae ATCC 49619 and Streptococcus pyogenes ATCC 19615. (Z)-5-(2,3,4-Trifluorobenzylidene)rhodanine (1) inhibited the growth of S. aureus at 0.5 microg/mL and MRSA at 32 microg/mL. Stronger antimicrobial activity against S. aureus was observed for compounds bearing the rhodanine ring than those containing other heterocyclic moieties. Neither of the compounds 1-11 inhibited the growth of Gram-negative bacteria E. coli or P. aeruginosa.

One-year experience with modified BD Geneohm™ MRSA assay for detection of methicillin-resistant Staphylococcus aureus from pooled nasal, skin, and throat samples

We report our 1-year experience with modified GeneOhm MRSA assay (formerly IDI-MRSA) for pooled surveillance specimens in low methicillin-resistant Staphylococcus aureus (MRSA) prevalence clinical setting. We have successfully modified the GeneOhm MRSA assay protocol during the specimen preparation step by adding an extra washing step followed by pooling of up to 3 samples per patient (nose, skin, with or without throat) at the lysis step. The sensitivity of the modified assay compared with conventional cultivation was 94.3%, specificity 99.2%, negative predictive value 99.2%, and positive predictive value 94.3%. The modified test is reliable and performed well compared with conventional culture methods in our clinical setting with low-level prevalence of MRSA colonization. Our findings support the use of pooling of the patients samples as a cost-effective way of screening for MRSA colonization.

Benzoxazine Series of Histidine Kinase Inhibitors as Potential Antimicrobial Agents with Activity against Enterococci

Background: Antibacterial activity of three members of a benzoxazine series of histidine kinase inhibitors (4a, 4b and 6) was studied on standard strains, and with 4b also on clinical isolates of enterococci. Methods: Susceptibility to each compound was tested using a broth macrodilution method with a range of dilutions from 0.016 to 128 μg/ml on four standard strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212) and in the case of 4b also on 52 clinical isolates of enterococci (7 vancomycin-susceptible E. faecalis, 15 vancomycin-susceptible Enterococcus faecium and 30 vancomycin-resistant E. faecium), and on two additional standard strains (S. aureus ATCC 43300 and E. faecalis ATCC 51299). Results: Neither of the compounds inhibited the growth of E. coli ATCC 25922 or P. aeruginosa ATCC 27853. Compound 4b inhibited the growth of S. aureus ATCC 29213 at 8 μg/ml, S. aureus ATCC 43300 at 32 μg/ml, E. faecalis ATCC 29212, and E. faecalis ATCC 51299 at 16 μg/ml, while 4a and 6 did so at higher concentrations. For clinical isolates of enterococci, the minimal inhibitory concentrations of 4b were in the range of 0.5–16 μg/ml. Conclusions: Compound 4b promises to be a potentially useful antimicrobial agent for vancomycin-susceptible and -resistant enterococci.

Prevention of nosocomial lower respiratory tract infections in patients after intracranial artery aneurysm surgery with a short course of antimicrobials

Nosocomial infections at a department of neurosurgery were followed prospectively. In 1999, a high incidence of nosocomial lower respiratory tract infections (NLRTI) was observed in patients after intracranial artery aneurysm surgery (ICAAS). From February to December 2000, a short course of ciprofloxacin and co-trimoxazole was given prophylactically to all patients with ICAAS. The incidence of nosocomial infections in patients after ICAAS fell from 78.4 to 30.9% (P<0.0001). The incidence of NLRTI fell from 43.3 to 13.6% (P<0.0001) and the incidence of urinary tract infections from 12.4 to 2.5% (P=0.015). No significant change in antibiotic sensitivity at the department was observed. Antibiotic use decreased from 100.4 defined daily doses (DDD) to 85.4 DDD per 100 bed-days.