Synthesis, spectral, and anti-microbial studies of thioiminium iodides and amine hydrochlorides

To avoid the undesired deprotonation during the addition of organolithium and organomagnesium reagents to ketones, the thioiminium salts, easily prepared from lactams and amides are converted into 2,2-disubstituted and 2-monosubstituted amines by reaction with simple nucleophiles such as organocerium and organocopper reagents. The reaction of thioiminium iodides with organocerium reagents derived by transmetalation of corresponding lithium reagents with anhydrous cerium(III) chloride has been investigated. These thioiminium iodides act as good electrophiles and accept alkylceriums towards bisaddition. The newly synthesized amines have been characterized by 1H and 13C NMR, IR and mass spectra. The amines have been converted into their hydrochlorides and characterized by COSY. These hydrochlorides have been subjected to antimicrobial screening with clinically isolated microorganisms, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi and Candida albicans. The hydrochlorides show quite good activity against these bacteria and fungus.

Significant Differences Characterise the Correlation Coefficients between Biocide and Antibiotic Susceptibility Profiles in Staphylococcus aureus.

There is a growing concern by regulatory authorities for the selection of antibiotic resistance caused by the use of biocidal products. We aimed to complete the detailed information on large surveys by investigating the relationship between biocide and antibiotic susceptibility profiles of a large number of Staphylococcus aureus isolates using four biocides and antibiotics commonly used in clinical practice. The minimal inhibitory concentration (MIC) for most clinically-relevant antibiotics was determined according to the standardized methodology for over 1600 clinical S. aureus isolates and compared to susceptibility profiles of benzalkonium chloride, chlorhexidine, triclosan, and sodium hypochlorite. The relationship between antibiotic and biocide susceptibility profiles was evaluated using non-linear correlations. The main outcome evidenced was an absence of any strong or moderate statistically significant correlation when susceptibilities of either triclosan or sodium hypochlorite were compared for any of the tested antibiotics. On the other hand, correlation coefficients for MICs of benzalkonium chloride and chlorhexidine were calculated above 0.4 for susceptibility to quinolones, beta-lactams, and also macrolides. Our data do not support any selective pressure for association between biocides and antibiotics resistance and furthermore do not allow for a defined risk evaluation for some of the compounds. Importantly, our data clearly indicate that there does not involve any risk of selection for antibiotic resistance for the compounds triclosan and sodium hypochlorite. These data hence infer that biocide selection for antibiotic resistance has had so far a less significant impact than feared.

Acute Angioedema Triggered by Daptomycin.

INTRODUCTION Daptomycin is a cyclic lipopeptide antibiotic, frequently administered for Staphylococcus aureus bloodstream infections. Numerous studies have shown that daptomycin is relatively safe and well tolerated. Serious adverse events possibly related to this antimicrobial compound are rare. We report a case of acute angioedema triggered by daptomycin. CASE REPORT A 60-year-old woman with S. aureus bacteremia without identified source was treated intravenously with high-dose beta-lactams at our institution. Because S. aureus bacteremia persisted on day 6, and in parallel, acute kidney injury developed, antimicrobial treatment was switched to a combination therapy with daptomycin and ceftriaxone. Shortly after completion of the first daptomycin administration, the patient developed lip and tongue swelling and dyspnea. Acute angioedema was clinically evident. Antibiotic therapy was switched to vancomycin, and the further clinical course was favorable. An intradermal test showed a significant wheal diameter for daptomycin, but negative results for ceftriaxone. CONCLUSION The association with daptomycin in this case is either probable or certain. Clinicians should be aware that daptomycin can cause immediate-type hypersensitivity reactions, including acute angioedema, even upon first administration.