The first nationwide multicenter study ofAcinetobacter baumanniirecovered in Serbia: emergence of OXA-72, OXA-23 and NDM-1-producing isolates

Background The worldwide emergence and clonal spread of carbapenem-resistantAcinetobacter baumannii(CRAB) is of great concern. The aim of this nationwide study was to investigate the prevalence of CRAB isolates in Serbia and to characterize underlying resistance mechanisms and their genetic relatedness. Methods Non-redundant clinical samples obtained from hospitalized patients throughout Serbia were included in the prospective, observational, multicenter study conducted from January to June 2018. Samples were initially screened for the presence ofAcinetobacter baumannii-calcoaceticus(Acb) complex using conventional bacteriological techniques. Acb complexes recovered from clinical samples obtained from inpatients with confirmed bacterial infections were further evaluated for the presence ofA. baumannii. Identification to the species level was done by the detection of thebla(OXA-51)gene andrpoBgene sequence analysis. Susceptibility testing was done by disk diffusion and broth microdilution method. CRAB isolates were tested for the presence of acquired carbapenemases(bla(OXA-24-like),bla(OXA-23-like,)bla(OXA-58-like),bla(OXA-143-like),bla(IMP),bla(VIM),bla(GIM),bla(SPM),bla(SIM),bla(NDM)) by PCR. Clonal relatedness was assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results Acb complex was isolated in 280 out of 2401 clinical samples (11.6%). Overall,A. baumanniiwas identified in 237 out of 280 Acb complex (84.6%). CRAB prevalence was found to be 93.7% (237/222). The MIC50/MIC(90)for imipenem and meropenem were 8/ gt 32 mu g/mL and 16/ gt 32 mu g/mL, respectively. Although susceptibility was high for colistin (95.7%;n = 227) and tigecycline (75.1%;n = 178), ten isolates (4.3%) were classified as pandrug-resistant. The following carbapenemases-encoding genes were found: 98 (44.2%)bla(OXA-24-like), 76 (34.5%)bla(OXA-23-like), and 7 (3.2%)bla(NDM-1). PFGE analysis revealed six different clusters. MLST analysis identified three STs: ST2 (n = 13), ST492 (n = 14), and ST636 (n = 10). Obtained results evaluated that circulating CRAB clones in Serbia were as follows:bla(OXA66)/bla(OXA23)/ST2 (32.4%),bla(OXA66)/bla(OXA23)/bla(OXA72)/ST2 (2.7%),bla(OXA66)/bla(OXA72)/ST492 (37.8%), andbla(OXA66)/bla(OXA72)/ST636 (27.1%). Conclusion This study revealed extremely high proportions of carbapenem resistance amongA. baumanniiclinical isolates due to the emergence ofbla(OXA-72),bla(OXA-23), andbla(NDM-1)genes among CRAB isolates in Serbia and their clonal propagation

3D printed mucoadhesive gelatin based buccal films

The oral mucoadhesive film is a novel and attractive formulation for local and/or systemic drug delivery through the mucosal membrane of the oral cavity. Certain active pharmaceutical ingredients (API) in conventional formulations (tablets, capsules, syrups) are absorbed in the gastrointestinal tract and undergo first-pass metabolism through the liver, thereby reducing their bioavailability. This problem can be overcome by using intraoral formulations, such as mucoadhesive buccal films that disintegrate and dissolve in the oral cavity where the absorption of API occurs. In this work, the mucoadhesive films were prepared by 3D paste printing and the influence of processing parameters on film properties and the release rate of a drug was investigated. Gelatin (GA) and the blend of gelatin/polyvinylpyrrolidone (GA/PVP) were used because of their biocompatibility. Propranolol hydrochloride (PRH) was used as a model substance because it has high first-pass metabolism and is soluble in water. Film morphology and drug distribution were followed by SEM analysis. Dissolution test in simulated saliva was done to see how PRH was released from films. Mucoadhesion test revealed that the GA/PVP films with PRH have the highest adhesion force. Obtained results introduce GA/PVP as a promising material with good adhesion and rate of drug release