TY  - JOUR
AU  - Božić, Dragana
AU  - Ćirković, Ivana
AU  - Milovanović, Jovica
AU  - Bufan, Biljana
AU  - Folić, Miljan
AU  - Savić Vujović, Katarina
AU  - Pavlović, Bojan
AU  - Jotić, Ana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5341
AB  - Bacterial biofilms play an important role in the pathogenesis of chronic upper respiratory tract infections. In addition to conventional antimicrobial therapy, N-acetyl-L-cysteine (NAC) and propolis are dietary supplements that are often recommended as supportive therapy for upper respiratory tract infections. However, no data on the beneficial effect of their combination against bacterial biofilms can be found in the scientific literature. Therefore, the aim of our study was to investigate the in vitro effect of N-acetyl-L-cysteine (NAC) and dry propolis extract in fixed combinations (NAC/dry propolis extract fixed combination) on biofilm formation by bacterial species isolated from patients with chronic rhinosinusitis, chronic otitis media, and chronic adenoiditis. The prospective study included 48 adults with chronic rhinosinusitis, 29 adults with chronic otitis media, and 33 children with chronic adenoiditis. Bacteria were isolated from tissue samples obtained intraoperatively and identified using the MALDI-TOF Vitek MS System. The antimicrobial activity, synergism, and antibiofilm effect of NAC/dry propolis extract fixed combination were studied in vitro. A total of 116 different strains were isolated from the tissue samples, with staphylococci being the most frequently isolated in all patients (57.8%). MICs of the NAC/dry propolis extract fixed combination ranged from 1.25/0.125 to 20/2 mg NAC/mg propolis. A synergistic effect (FICI ≤ 0.5) was observed in 51.7% of strains. The majority of isolates from patients with chronic otitis media were moderate biofilm producers and in chronic adenoiditis they were weak biofilm producers, while the same number of isolates in patients with chronic rhinosinusitis were weak and moderate biofilm producers. Subinhibitory concentrations of the NAC/propolis combination ranging from 0.625–0.156 mg/mL to 10–2.5 mg/mL of NAC combined with 0.062–0.016 mg/mL to 1–0.25 mg/mL of propolis inhibited biofilm formation in all bacterial strains. Suprainhibitory concentrations ranging from 2.5–10 mg/mL to 40–160 mg/mL of NAC in combination with 0.25–1 mg/mL to 4–16 mg/mL of propolis completely eradicated the biofilm. In conclusion, the fixed combination of NAC and dry propolis extract has a synergistic effect on all stages of biofilm formation and eradication of the formed biofilm in bacteria isolated from upper respiratory tract infections.
PB  - MDPI
T2  - Pharmaceuticals
T1  - In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections
VL  - 16
IS  - 11
DO  - 10.3390/ph16111604
ER  - 

@article{
author = "Božić, Dragana and Ćirković, Ivana and Milovanović, Jovica and Bufan, Biljana and Folić, Miljan and Savić Vujović, Katarina and Pavlović, Bojan and Jotić, Ana",
year = "2023",
abstract = "Bacterial biofilms play an important role in the pathogenesis of chronic upper respiratory tract infections. In addition to conventional antimicrobial therapy, N-acetyl-L-cysteine (NAC) and propolis are dietary supplements that are often recommended as supportive therapy for upper respiratory tract infections. However, no data on the beneficial effect of their combination against bacterial biofilms can be found in the scientific literature. Therefore, the aim of our study was to investigate the in vitro effect of N-acetyl-L-cysteine (NAC) and dry propolis extract in fixed combinations (NAC/dry propolis extract fixed combination) on biofilm formation by bacterial species isolated from patients with chronic rhinosinusitis, chronic otitis media, and chronic adenoiditis. The prospective study included 48 adults with chronic rhinosinusitis, 29 adults with chronic otitis media, and 33 children with chronic adenoiditis. Bacteria were isolated from tissue samples obtained intraoperatively and identified using the MALDI-TOF Vitek MS System. The antimicrobial activity, synergism, and antibiofilm effect of NAC/dry propolis extract fixed combination were studied in vitro. A total of 116 different strains were isolated from the tissue samples, with staphylococci being the most frequently isolated in all patients (57.8%). MICs of the NAC/dry propolis extract fixed combination ranged from 1.25/0.125 to 20/2 mg NAC/mg propolis. A synergistic effect (FICI ≤ 0.5) was observed in 51.7% of strains. The majority of isolates from patients with chronic otitis media were moderate biofilm producers and in chronic adenoiditis they were weak biofilm producers, while the same number of isolates in patients with chronic rhinosinusitis were weak and moderate biofilm producers. Subinhibitory concentrations of the NAC/propolis combination ranging from 0.625–0.156 mg/mL to 10–2.5 mg/mL of NAC combined with 0.062–0.016 mg/mL to 1–0.25 mg/mL of propolis inhibited biofilm formation in all bacterial strains. Suprainhibitory concentrations ranging from 2.5–10 mg/mL to 40–160 mg/mL of NAC in combination with 0.25–1 mg/mL to 4–16 mg/mL of propolis completely eradicated the biofilm. In conclusion, the fixed combination of NAC and dry propolis extract has a synergistic effect on all stages of biofilm formation and eradication of the formed biofilm in bacteria isolated from upper respiratory tract infections.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections",
volume = "16",
number = "11",
doi = "10.3390/ph16111604"
}

Božić, D., Ćirković, I., Milovanović, J., Bufan, B., Folić, M., Savić Vujović, K., Pavlović, B.,& Jotić, A.. (2023). In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections. in Pharmaceuticals
MDPI., 16(11).
https://doi.org/10.3390/ph16111604

Božić D, Ćirković I, Milovanović J, Bufan B, Folić M, Savić Vujović K, Pavlović B, Jotić A. In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections. in Pharmaceuticals. 2023;16(11).
doi:10.3390/ph16111604 .

Božić, Dragana, Ćirković, Ivana, Milovanović, Jovica, Bufan, Biljana, Folić, Miljan, Savić Vujović, Katarina, Pavlović, Bojan, Jotić, Ana, "In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections" in Pharmaceuticals, 16, no. 11 (2023),
https://doi.org/10.3390/ph16111604 . .

TY  - JOUR
AU  - Milojković, Marko
AU  - Nenadović, Željka
AU  - Stanković, Slaviša
AU  - Božić, Dragana
AU  - Stanković-Nedeljković, Nataša
AU  - Ćirković, Ivana
AU  - Petrović, Marija
AU  - Dimkić, Ivica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3716
AB  - Drug resistance of Pseudomonas aeruginosa is a leading problem in hospital infections. The aim of this study was to determine the best molecular genetic discrimination method for Pseudomonas spp. isolates among 94 outpatients and inpatients and see their grouping by phenotype characteristics (biofilm formation, frequency of serotypes, pigmentation, production of different class of beta-lactamases, and susceptibility to different antibiotic classes) and genotype. The most common serotypes were P1, P6, and P11, while co-productions of pyoverdine and pyocyanin were observed in 70 % of isolates. A total of 77.66 % isolates were mostly weak and moderate biofilm producers. Isolates were susceptible to colistin (100 %), aztreonam (97.87 %), imipenem (91.49 %), doripenem (90.43 %), and meropenem (84.04 %). MICs values confirmed susceptibility to ceftazidime and cefepime and singled out meripenem as the most effective inhibitor. Most isolates were resistant to aminoglycosides and fluoroquinolones. Only two isolates produced ESBL, eight were carbapenemase producers, and five isolates produced MBLs. Twenty-nine isolates were multidrug-resistant; 82.8 % of which produced both pigments, 58.3 % were non-typeable, while the P6 and P11 serotypes were equally distributed (16.7 %). Thirteen MDR isolates were strong enzyme producers. RAPD PCR analysis using primer 272 proved the best at discriminatory fingerprinting for Pseudomonas isolates, as it allocated 12 clusters. A correlation between DNA patterns and antibiotic resistance, production of pigments, serotypes distribution, and biofilm formation was not observed, and only confirmed higher genetic heterogeneity among P. aeruginosa isolates, which suggests that other molecular methods are needed to reveal potential relations between genotypic patterns and phenotypic characteristics.
AB  - Antibiotska rezistencija Pseudomonas aeruginosa vodeći je problem u bolničkim infekcijama. Cilj ovoga istraživanja bio je utvrditi najbolju diskriminatorno molekularno-genetičku metodu među 94 ambulantna i bolnička Pseudomonas spp. izolata kako bi se uvidjelo njihovo grupiranje u smislu različitih fenotipskih obilježja (stvaranje biofilma, učestalost serotipova, pigmentacija, proizvodnja različitih klasa beta-laktamaza i osjetljivost na različite skupine antibiotika) u skladu s genotipom. Najčešći serotipovi bili su P1, P6 i P11, a proizvodnja i pioverdina i piocijanina primijećena je kod 70 % izolata. Ukupno 77,66 % izolata uglavnom je iskazalo slabu i umjerenu proizvodnju biofilma. Izolati su bili osjetljivi na kolistin (100 %), aztreonam (97,87 %), imipenem (91,49 %), doripenem (90,43 %) i meropenem (84,04 %). Vrijednosti MIC-ova potvrdile su podložnost izolata ceftazidimu i cefepimu, a izdvojile su meropenem kao najučinkovitiji inhibitor. Većina izolata bila je otporna na aminoglikozid i fluorokinolon. Samo dva izolata proizvela su ESBL, osam izolata sintetiziralo je karbapenemaze, a pet izolata imalo je sposobnost proizvodnje MBL-a. Dvadeset devet izolata bilo je višestruko rezistentno na antibiotike, od kojih je 82,8 % proizvodilo oba pigmenta, 58,3 % bili su netipabilni, a serotipovi P6 i P11 bili su podjednako zastupljeni među njima (16,7 %). Trinaest MDR izolata bili su snažni proizvođači enzima. RAPD PCR analiza korištenjem 272 početnica pokazala se kao najbolja diskriminatorna metoda otiskom prsta (fingerprinting) za Pseudomonas izolate, izdvajajući čak 12 različitih klastera. U ovom istraživanju nije zabilježena povezanost između DNA obrazaca i otpornosti na antibiotike, proizvodnje pigmenata, distribucije serotipova i stvaranja biofilma, što potvrđuje puno veću genetičku heterogenost unutar samih izolata P. aeruginosa, pod čim se podrazumijeva uključivanje drugih molekularnih metoda u otkrivanju potencijalnih odnosa između genetičkih obrazaca i fenotipskih obilježja.
PB  - Sciendo
T2  - Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology
T1  - Phenotypic and genetic properties of susceptible and multidrug-resistant Pseudomonas aeruginosa isolates in Southern Serbia
T1  - Fenotipska i genetička obilježja osjetljivih i višestruko otpornih izolata Pseudomonas aeruginosa u južnoj Srbiji
VL  - 71
IS  - 3
SP  - 231
EP  - 250
DO  - 10.2478/aiht-2020-71-3418
ER  - 

@article{
author = "Milojković, Marko and Nenadović, Željka and Stanković, Slaviša and Božić, Dragana and Stanković-Nedeljković, Nataša and Ćirković, Ivana and Petrović, Marija and Dimkić, Ivica",
year = "2020",
abstract = "Drug resistance of Pseudomonas aeruginosa is a leading problem in hospital infections. The aim of this study was to determine the best molecular genetic discrimination method for Pseudomonas spp. isolates among 94 outpatients and inpatients and see their grouping by phenotype characteristics (biofilm formation, frequency of serotypes, pigmentation, production of different class of beta-lactamases, and susceptibility to different antibiotic classes) and genotype. The most common serotypes were P1, P6, and P11, while co-productions of pyoverdine and pyocyanin were observed in 70 % of isolates. A total of 77.66 % isolates were mostly weak and moderate biofilm producers. Isolates were susceptible to colistin (100 %), aztreonam (97.87 %), imipenem (91.49 %), doripenem (90.43 %), and meropenem (84.04 %). MICs values confirmed susceptibility to ceftazidime and cefepime and singled out meripenem as the most effective inhibitor. Most isolates were resistant to aminoglycosides and fluoroquinolones. Only two isolates produced ESBL, eight were carbapenemase producers, and five isolates produced MBLs. Twenty-nine isolates were multidrug-resistant; 82.8 % of which produced both pigments, 58.3 % were non-typeable, while the P6 and P11 serotypes were equally distributed (16.7 %). Thirteen MDR isolates were strong enzyme producers. RAPD PCR analysis using primer 272 proved the best at discriminatory fingerprinting for Pseudomonas isolates, as it allocated 12 clusters. A correlation between DNA patterns and antibiotic resistance, production of pigments, serotypes distribution, and biofilm formation was not observed, and only confirmed higher genetic heterogeneity among P. aeruginosa isolates, which suggests that other molecular methods are needed to reveal potential relations between genotypic patterns and phenotypic characteristics., Antibiotska rezistencija Pseudomonas aeruginosa vodeći je problem u bolničkim infekcijama. Cilj ovoga istraživanja bio je utvrditi najbolju diskriminatorno molekularno-genetičku metodu među 94 ambulantna i bolnička Pseudomonas spp. izolata kako bi se uvidjelo njihovo grupiranje u smislu različitih fenotipskih obilježja (stvaranje biofilma, učestalost serotipova, pigmentacija, proizvodnja različitih klasa beta-laktamaza i osjetljivost na različite skupine antibiotika) u skladu s genotipom. Najčešći serotipovi bili su P1, P6 i P11, a proizvodnja i pioverdina i piocijanina primijećena je kod 70 % izolata. Ukupno 77,66 % izolata uglavnom je iskazalo slabu i umjerenu proizvodnju biofilma. Izolati su bili osjetljivi na kolistin (100 %), aztreonam (97,87 %), imipenem (91,49 %), doripenem (90,43 %) i meropenem (84,04 %). Vrijednosti MIC-ova potvrdile su podložnost izolata ceftazidimu i cefepimu, a izdvojile su meropenem kao najučinkovitiji inhibitor. Većina izolata bila je otporna na aminoglikozid i fluorokinolon. Samo dva izolata proizvela su ESBL, osam izolata sintetiziralo je karbapenemaze, a pet izolata imalo je sposobnost proizvodnje MBL-a. Dvadeset devet izolata bilo je višestruko rezistentno na antibiotike, od kojih je 82,8 % proizvodilo oba pigmenta, 58,3 % bili su netipabilni, a serotipovi P6 i P11 bili su podjednako zastupljeni među njima (16,7 %). Trinaest MDR izolata bili su snažni proizvođači enzima. RAPD PCR analiza korištenjem 272 početnica pokazala se kao najbolja diskriminatorna metoda otiskom prsta (fingerprinting) za Pseudomonas izolate, izdvajajući čak 12 različitih klastera. U ovom istraživanju nije zabilježena povezanost između DNA obrazaca i otpornosti na antibiotike, proizvodnje pigmenata, distribucije serotipova i stvaranja biofilma, što potvrđuje puno veću genetičku heterogenost unutar samih izolata P. aeruginosa, pod čim se podrazumijeva uključivanje drugih molekularnih metoda u otkrivanju potencijalnih odnosa između genetičkih obrazaca i fenotipskih obilježja.",
publisher = "Sciendo",
journal = "Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology",
title = "Phenotypic and genetic properties of susceptible and multidrug-resistant Pseudomonas aeruginosa isolates in Southern Serbia, Fenotipska i genetička obilježja osjetljivih i višestruko otpornih izolata Pseudomonas aeruginosa u južnoj Srbiji",
volume = "71",
number = "3",
pages = "231-250",
doi = "10.2478/aiht-2020-71-3418"
}

Milojković, M., Nenadović, Ž., Stanković, S., Božić, D., Stanković-Nedeljković, N., Ćirković, I., Petrović, M.,& Dimkić, I.. (2020). Phenotypic and genetic properties of susceptible and multidrug-resistant Pseudomonas aeruginosa isolates in Southern Serbia. in Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology
Sciendo., 71(3), 231-250.
https://doi.org/10.2478/aiht-2020-71-3418

Milojković M, Nenadović Ž, Stanković S, Božić D, Stanković-Nedeljković N, Ćirković I, Petrović M, Dimkić I. Phenotypic and genetic properties of susceptible and multidrug-resistant Pseudomonas aeruginosa isolates in Southern Serbia. in Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology. 2020;71(3):231-250.
doi:10.2478/aiht-2020-71-3418 .

Milojković, Marko, Nenadović, Željka, Stanković, Slaviša, Božić, Dragana, Stanković-Nedeljković, Nataša, Ćirković, Ivana, Petrović, Marija, Dimkić, Ivica, "Phenotypic and genetic properties of susceptible and multidrug-resistant Pseudomonas aeruginosa isolates in Southern Serbia" in Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology, 71, no. 3 (2020):231-250,
https://doi.org/10.2478/aiht-2020-71-3418 . .