5809dcba933e4b9315e96ab83e0ef8f0 286336.pdf 643119151ece266cc054ca64215a0bc030c627a9 286336.pdf b6cd87aba2b0bb0fc15005c6c8de7f49bca19e9225f5a1efcce35d757db0689e 286336.pdf Title: Activity of Antibiotics and Potential Antibiofilm Agents against Biofilm-Producing Mycobacterium avium-intracellulare Complex Causing Chronic Pulmonary Infections Subject: Nontuberculous mycobacteria (NTM) cause lung infections in patients with underlying pulmonary diseases (PD). The Mycobacterium avium-intracellulare complex (MAC) is the most frequently involved NTM. The MAC-PD treatment is based on the administration of several antibiotics for long periods of time. Nonetheless, treatment outcomes remain very poor. Among the factors involved is the ability of MAC isolates to form biofilm. The aim of the study was to assess the in vitro activity of different antibiotics and potential antibiofilm agents (PAAs) against MAC biofilm. Four antibiotics and six PAAs, alone and/or in combination, were tested against planktonic forms of 11 MAC clinical isolates. Biofilm was produced after 4 weeks of incubation and analyzed with the crystal violet assay. The antibiotics and PAAs were tested by measuring the absorbance (minimum biofilm inhibition concentrations, MBICs) and by performing subcultures (minimum biofilm eradication concentrations, MBECs). The clarithromycin/amikacin and clarithromycin/ethambutol combinations were synergistic, decreasing the MBECs values compared to the individual antibiotics. The amikacin/moxifloxacin combination showed indifference. The MBIC values decreased significantly when PAAs were added to the antibiotic combinations. These results suggest that antibiotic combinations should be further studied to establish their antibiofilm activity. Moreover, PAAs could act against the biofilm matrix, facilitating the activity of antibiotics. Keywords: nontuberculous mycobacteria; biofilm; antibiotic combinations; potential antibiofilm agents; minimum biofilm inhibitory concentrations; minimum biofilm eradication concentrations Author: Elena Portell-Buj, Cecibel González-Criollo, Alexandre López-Gavín, Mariana Fernández-Pittol, Maria Antònia Busquets, Joan Estelrich, Montserrat Garrigó, Marc Rubio, Griselda Tudó and Julian Gonzalez-Martin Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue May 24 10:02:10 2022 CEST ModDate: Tue May 24 10:04:50 2022 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 626385 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JGVQYD+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ACKGZT+VnURWPalladioL Type 1 Custom yes yes no 15 0 ZSEHVR+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 URMRKZ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 YFJYVC+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 AHMLQB+URWPalladioL-BoldItal Type 1 Custom yes yes no 32 0 YYFPCJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 51 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 73 0 XIRVNA+EURB10 Type 1 Builtin yes yes no 80 0 RWBCRL+CMSY10 Type 1 Builtin yes yes no 90 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 102 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 106 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 110 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 114 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-03-21 02:36:57 CET RepresentationInformation: 286336.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-03-20 12:58:31 CET Size: 626385 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 253 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Mycobacterium avium-intracellulare Complex Isolates Destination: subsection.4.1 Item: Title: Antibiotics and Potential Antibiofilm Agents Destination: subsection.4.2 Item: Title: Minimum Inhibitory Concentration Destination: subsection.4.3 Item: Title: Fractional Inhibitory Concentration Index Destination: subsection.4.4 Item: Title: Biofilm Formation Destination: subsection.4.5 Item: Title: Minimum Biofilm Eradication Concentrations and Minimum Biofilm Inhibition Concentrations Destination: subsection.4.6 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Activity of Antibiotics and Potential Antibiofilm Agents against Biofilm-Producing Mycobacterium avium-intracellulare Complex Causing Chronic Pulmonary Infections Author: Elena Portell-Buj, Cecibel González-Criollo, Alexandre López-Gavín, Mariana Fernández-Pittol, Maria Antònia Busquets, Joan Estelrich, Montserrat Garrigó, Marc Rubio, Griselda Tudó and Julian Gonzalez-Martin Subject: Nontuberculous mycobacteria (NTM) cause lung infections in patients with underlying pulmonary diseases (PD). The Mycobacterium avium-intracellulare complex (MAC) is the most frequently involved NTM. The MAC-PD treatment is based on the administration of several antibiotics for long periods of time. Nonetheless, treatment outcomes remain very poor. Among the factors involved is the ability of MAC isolates to form biofilm. The aim of the study was to assess the in vitro activity of different antibiotics and potential antibiofilm agents (PAAs) against MAC biofilm. Four antibiotics and six PAAs, alone and/or in combination, were tested against planktonic forms of 11 MAC clinical isolates. Biofilm was produced after 4 weeks of incubation and analyzed with the crystal violet assay. The antibiotics and PAAs were tested by measuring the absorbance (minimum biofilm inhibition concentrations, MBICs) and by performing subcultures (minimum biofilm eradication concentrations, MBECs). The clarithromycin/amikacin and clarithromycin/ethambutol combinations were synergistic, decreasing the MBECs values compared to the individual antibiotics. The amikacin/moxifloxacin combination showed indifference. The MBIC values decreased significantly when PAAs were added to the antibiotic combinations. These results suggest that antibiotic combinations should be further studied to establish their antibiofilm activity. Moreover, PAAs could act against the biofilm matrix, facilitating the activity of antibiotics. 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