Azithromycin possesses biofilm–inhibitory activity and potentiates non-bactericidal colistin methanesulfonate (CMS) and polymyxin B against Klebsiella pneumonia

Abstract

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays.

Case report: Azithromycin-meropenem combination therapy as a low-cost approach to combat PDR gram-negative infections of war wounds in Ukraine

“…Until transportation to Kyiv City Clinical Hospital No 6 and within the first 8 days, only MDR gram-negative isolates were detected. It is important to emphasize that all these four isolates were sensitive to tigecycline, and they hypothetically may be still sensitive to colistin, as colistin-resistance is still not so often encountered in Ukrainian hospital isolates, as demonstrated before ( 16 ) or as demonstrated by other authors ( 17 ). However, despite this rational combined antimicrobial therapy with colistin and tigecycline, the condition of the patient decreased: he had hypothermia, anemia, underwent two blood transfusions, his bilirubin level was increased and PCT varied from 3.247 to 1.698 ng/mL ( Figure 3 ).…”

“…The newly suggested therapy was focused on anti-biofilm therapy and included azithromycin which was effective against gram-negative XDR/PDR Ukrainian Hospital Isolates as shown before ( 16 , 18 ). The combination therapy with azithromycin and meropenem was suggested based on own previous experimental and clinical data which confirmed that both antibiotics demonstrated a strong synergistic effect in vivo against diverse gram-negative hospital isolates.…”

Extracellular host DNA contributes to pathogenic biofilm formation during periodontitis

“…Escherichia coli K12, Klebsiella penumoniae ATCC 10031, Pseudomonas aeruginosa PA01, P. fluorescens SBW25, and Staphylococcus aureus ATCC 29423, were obtained from laboratory stock collections ( Moshynets et al., 2020 ; Chernii et al., 2021 ; Moshynets et al., 2022b ; Volynets et al., 2022 ). The Ukrainian hospital isolates K. pneumoniae UHI 489 and UHI 117 were from previous work ( Moshynets et al., 2022a ) and three oral streptococcal opportunistic pathogenic isolates, Streptococcus gordonii UHI1, S. sanguinis UHI1 and S. mitis UHI1, were isolated from samples collected from patients of the Maxillofacial Surgery Department of the Kyiv Regional clinical hospital with purulent-inflammatory processes and identified using a Bacteriological Analyzer Vitek 2 Compact v9 (bioMérieux, France). Bacteria were incubated aerobically at 37°C except for P. fluorescens SBW25 which was cultured at 28°C.…”

Femtosecond laser modified metal surfaces alter biofilm architecture and reduce bacterial biofilm formation

“…[24][25][26][27] Bacteria forming biolms become adapted to detergents, biocides and antibiotics, gradually reducing their effectiveness. 28,29 A faster and safer solution might therefore lie in a physical surface modication rather than an addition of chemicals. Such a physical modication implies alteration of surface topography, forming nano-or microscale features of different shapes.…”

“…24–27 Bacteria forming biofilms become adapted to detergents, biocides and antibiotics, gradually reducing their effectiveness. 28,29…”