Characterization of macrolide-resistant non-invasive pneumococci in the pre-vaccine era in Serbia

Numerous reports have confirmed that increased macrolide use in the treatment of respiratory tract infection has contributed to the emergence of antibiotic resistance worldwide. Studies have also shown that pneumococcal vaccine can reduce pneumococcal resistance. The aim of this study was to determine the prevalence of co-resistance to penicillin and other antibiotics in macrolide-resistant (MR) non-invasive pneumococcal isolates and to evaluate serotype distribution in resistant strains in the pre-vaccine era in Serbia. About 80% of MR isolates expressed the MLS phenotype with very high resistance to both erythromycin and clindamycin. A total of 132 (84.1%) MR isolates were multiresistant, i.e., they were resistant to erythromycin, penicillin, tetracycline, and trimethoprim–sulfamethoxazole. Among 157 MR pneumococci, 11 different serotypes were found. Four serotypes, 19F, 14, 6B, and 23F, accounted for 77.7% of all MR pneumococcal isolates. Among isolates with the cMLS phenotype, serotypes 19F and 14 were predominant, whereas serotype 6A was the most common among those with the M phenotype, followed by 14. In conclusion, co-resistance to macrolides and penicillin in our non-invasive pneumococcal isolates is high. The majority of tested strains (∼80%) belonged to the four serotypes (19F, 14, 6B, and 23F) that are included in all conjugate vaccine formulations

Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties

The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.This is the peer-reviewed version of the article: Pajic, N. B., Nikolić, I., Mitsou, E., Papadimitriou, V., Xenakis, A., Randjelović, D., Dobricic, V., Smitran, A., Cekic, N., Calija, B.,& Savić, S. D. (2018). Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. Journal of Molecular LiquidsElsevier Science Bv, Amsterdam., 272, 746-758. [https://doi.org/10.1016/j.molliq.2018.10.002]The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/2360

Trends in molecular characteristics and antimicrobial resistance of group B streptococci: a multicenter study in Serbia, 2015–2020

Abstract Group B Streptococcus (GBS) is a major cause of neonatal morbidity and mortality. Serbia has not fully implemented preventive measures against GBS neonatal diseases. Therefore, we aimed to assess the maternal GBS colonisation and invasive neonatal disease rate, to reveal the trends of antimicrobial resistance and serotype distribution of GBS from various patient groups. Randomly selected non-invasive (n = 991) and all invasive GBS (n = 80) collected throughout Serbia from 2015 to 2020 were tested for antimicrobial susceptibility, capsular typing, and hvgA detection. Overall, 877/5621 (15.6%) pregnant women were colonised with GBS. Invasive GBS infections incidence in infants (0.18/1000 live births) showed a decreasing trend (0.3 to 0.1/1000 live births). Type III was overrepresented in infants with invasive infections (n = 35, 58.3%), whereas type V predominated among colonised adults (n = 224, 25.5%) and those with noninvasive (n = 37, 32.5%) and invasive infections (n = 8, 40%). The hypervirulent clone III/ST17 was highly associated with invasive infections (n = 28, 35%), particularly late-onset disease (n = 9, 47.4%), showing an increase from 12.3 to 14.8%. The GBS resistance to erythromycin and clindamycin was 26.7% and 22.1%, respectively, with an upward trend. The emergence of the hypervirulent clone III/ST17 and the escalation in GBS resistance highlight an urgent need for continuous monitoring of GBS infections

Carbapenem-Resistant <i>Acinetobacter baumannii</i>: Biofilm-Associated Genes, Biofilm-Eradication Potential of Disinfectants, and Biofilm-Inhibitory Effects of Selenium Nanoparticles

This study aimed to investigate the biofilm-production ability of carbapenem-resistant Acinetobacter baumannii (CRAB), the biofilm-eradication potential of 70% ethanol and 0.5% sodium hypochlorite, the effects of selenium nanoparticles (SeNPs) against planktonic and biofilm-embedded CRAB, and the relationship between biofilm production and bacterial genotypes. A total of 111 CRAB isolates were tested for antimicrobial susceptibility, biofilm formation, presence of the genes encoding carbapenemases, and biofilm-associated virulence factors. The antibiofilm effects of disinfectants and SeNPs against CRAB isolates were also tested. The vast majority of the tested isolates were biofilm producers (91.9%). The bap, ompA, and csuE genes were found in 57%, 70%, and 76% of the CRAB isolates, with the csuE being significantly more common among biofilm producers (78.6%) compared to non-biofilm-producing CRAB (25%). The tested disinfectants showed a better antibiofilm effect on moderate and strong biofilm producers than on weak producers (p 1.25 mg/mL) and biofilm-embedded CRAB, with a minimum biofilm inhibitory concentration of less than 0.15 mg/mL for 90% of biofilm producers. In conclusion, SeNPs might be used as promising therapeutic and medical device coating agents, thus serving as an alternative approach for the prevention of biofilm-related infections

Biofilm Production and Antimicrobial Resistance of Clinical and Food Isolates of Pseudomonas spp.

Due to its ubiquity, ability to form biofilms, and acquire resistance mechanisms, Pseudomonas spp. become one of the major challenge for healthcare settings and food industry. The aims of this study were to assess the biofilm production of Pseudomonas spp. recovered from clinical and food specimens and to evaluate their antimicrobial resistance. A total of 108 isolates of Pseudomonas spp. were included in the study, 48 being clinical isolates recovered from patients admitted to four tertiary care hospitals throughout Serbia and 60 were isolated from the bulk tank milk samples and meat carcasses. Biofilm production was analyzed by microtiter plate assay. Antimicrobial susceptibility was evaluated by disk diffusion method according to the CLSI guidelines, while class A and B β-lactamases encoding genes were screened by PCR. A total of 98 (90.7%) strains were biofilm producers (moderate producer: 68, 69.4%; strong producer: 8, 8.2%). Although a slightly higher percentage of clinical isolates were biofilm producers (91.7%) compared to food isolates (90%), statistical significance was not observed (P > 0.05). The proportion of carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates was significantly higher among clinical (42%) isolates compared to food (1.7%) Pseudomonads (P < 0.05). The blaPER and blaNDM genes were found in ESBL (seven isolates) and MBL (two isolates) production, respectively. In the present study, we confirmed that biofilm formation was highly present in both clinical and food Pseudomonas spp. irrespective of the prior existence of resistance genes. Additionally, clinical settings pose a major reservoir of MDR Pseudomonas spp. and especially CRPA isolates.We gratefully acknowledge the following persons for supplying the strains used in this study: Snezana Jovanovic, Bojan Rakonjac, Momir Djuric, Lidija Boskovic, Teodora Vitorovic, Snezana Delic, Branislava Kocic, Dragana Andjelkovic