Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of <i>Pseudomonas aeruginosa,</i> and the Impact of Exposure to Cigarette Smoke Condensate

<b>Background/Objectives:</b> <i>Pseudomonas aeruginosa</i> (<i>Psa</i>) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmen...

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Main Authors: Moloko C. Cholo, Charles Feldman, Ronald Anderson, Lebogang Sekalo, Naledi Moloko, Guy A. Richards
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/3/325
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author Moloko C. Cholo
Charles Feldman
Ronald Anderson
Lebogang Sekalo
Naledi Moloko
Guy A. Richards
author_facet Moloko C. Cholo
Charles Feldman
Ronald Anderson
Lebogang Sekalo
Naledi Moloko
Guy A. Richards
author_sort Moloko C. Cholo
collection DOAJ
description <b>Background/Objectives:</b> <i>Pseudomonas aeruginosa</i> (<i>Psa</i>) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmentation by a macrolide, in the absence or presence of cigarette smoke condensate (CSC). <b>Methods:</b> Two susceptible (WT: wild-type and DS: drug-sensitive) and one multidrug-resistant (MDR) strains of <i>Psa</i> were treated with amikacin, cefepime, and ciprofloxacin, individually and in combination, and with and without clarithromycin, followed by the measurement of planktonic growth and biofilm formation by spectrophotometry. Antibiotic interactions were determined using the fractional inhibitory concentration index (FICI) method. Effects on preformed biofilm density were measured following the addition of antibiotics: all procedures were performed in the absence and presence of CSC. <b>Results:</b> The minimal inhibitory concentrations (MICs) of the three agents ranged from 0.125 mg/L to 1 mg/L (WT and DS strains) and 16 mg/L to 64 mg/L (MDR strain), with all resistant to clarithromycin (125 mg/L). MIC values closely correlated with the antibiotic concentrations required to inhibit biofilm formation. FICI revealed synergism between most combinations, with augmentation by clarithromycin. Amikacin had the greatest effect on biofilm density, which was potentiated by combination with the other antibiotics, particularly clarithromycin. Exposure to CSC had variable, albeit modest, effects on bacterial growth and biofilm formation, but low concentrations increased biofilm mass and attenuated synergistic antimicrobial interactions and effects on biofilm density. <b>Conclusions:</b> Amikacin, cefepime, and ciprofloxacin, especially with clarithromycin, exhibit synergistic anti-pseudomonal activity and decrease preformed biofilm density. CSC attenuated these effects, illustrating the pro-infective potential of CS.
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spelling doaj-art-c19055ca9e90436293b37dbdfbed47c42025-08-20T02:11:17ZengMDPI AGAntibiotics2079-63822025-03-0114332510.3390/antibiotics14030325Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of <i>Pseudomonas aeruginosa,</i> and the Impact of Exposure to Cigarette Smoke CondensateMoloko C. Cholo0Charles Feldman1Ronald Anderson2Lebogang Sekalo3Naledi Moloko4Guy A. Richards5Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaDepartment of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South AfricaDepartment of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaDepartment of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaDepartment of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaDepartment of Surgery, Division of Critical Care, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa<b>Background/Objectives:</b> <i>Pseudomonas aeruginosa</i> (<i>Psa</i>) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmentation by a macrolide, in the absence or presence of cigarette smoke condensate (CSC). <b>Methods:</b> Two susceptible (WT: wild-type and DS: drug-sensitive) and one multidrug-resistant (MDR) strains of <i>Psa</i> were treated with amikacin, cefepime, and ciprofloxacin, individually and in combination, and with and without clarithromycin, followed by the measurement of planktonic growth and biofilm formation by spectrophotometry. Antibiotic interactions were determined using the fractional inhibitory concentration index (FICI) method. Effects on preformed biofilm density were measured following the addition of antibiotics: all procedures were performed in the absence and presence of CSC. <b>Results:</b> The minimal inhibitory concentrations (MICs) of the three agents ranged from 0.125 mg/L to 1 mg/L (WT and DS strains) and 16 mg/L to 64 mg/L (MDR strain), with all resistant to clarithromycin (125 mg/L). MIC values closely correlated with the antibiotic concentrations required to inhibit biofilm formation. FICI revealed synergism between most combinations, with augmentation by clarithromycin. Amikacin had the greatest effect on biofilm density, which was potentiated by combination with the other antibiotics, particularly clarithromycin. Exposure to CSC had variable, albeit modest, effects on bacterial growth and biofilm formation, but low concentrations increased biofilm mass and attenuated synergistic antimicrobial interactions and effects on biofilm density. <b>Conclusions:</b> Amikacin, cefepime, and ciprofloxacin, especially with clarithromycin, exhibit synergistic anti-pseudomonal activity and decrease preformed biofilm density. CSC attenuated these effects, illustrating the pro-infective potential of CS.https://www.mdpi.com/2079-6382/14/3/325amikacincefepimeciprofloxacinclarithromycinbiofilmcigarette smoke
spellingShingle Moloko C. Cholo
Charles Feldman
Ronald Anderson
Lebogang Sekalo
Naledi Moloko
Guy A. Richards
Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of <i>Pseudomonas aeruginosa,</i> and the Impact of Exposure to Cigarette Smoke Condensate
Antibiotics
amikacin
cefepime
ciprofloxacin
clarithromycin
biofilm
cigarette smoke
title Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of <i>Pseudomonas aeruginosa,</i> and the Impact of Exposure to Cigarette Smoke Condensate
title_full Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of <i>Pseudomonas aeruginosa,</i> and the Impact of Exposure to Cigarette Smoke Condensate
title_fullStr Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of <i>Pseudomonas aeruginosa,</i> and the Impact of Exposure to Cigarette Smoke Condensate
title_full_unstemmed Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of <i>Pseudomonas aeruginosa,</i> and the Impact of Exposure to Cigarette Smoke Condensate
title_short Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of <i>Pseudomonas aeruginosa,</i> and the Impact of Exposure to Cigarette Smoke Condensate
title_sort effects of anti pseudomonal agents individually and in combination with or without clarithromycin on growth and biofilm formation by antibiotic susceptible and resistant strains of i pseudomonas aeruginosa i and the impact of exposure to cigarette smoke condensate
topic amikacin
cefepime
ciprofloxacin
clarithromycin
biofilm
cigarette smoke
url https://www.mdpi.com/2079-6382/14/3/325
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