In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia
Jin Zhao,1,* Yan Huang,1,* Jian Li,1,* Bo Zhang,1 Zhiwei Dong,2 Dong Wang1 1Department of Pulmonary and Critical Care Medicine, Air Force Medical Center, PLA, Beijing, 100142, People’s Republic of China; 2Department of General Surgery, Air Force Medical Center, PLA, Beijing,...
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| Format: | Article |
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Dove Medical Press
2022-06-01
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| Series: | Infection and Drug Resistance |
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| Online Access: | https://www.dovepress.com/in-vitro-antibacterial-activity-and-resistance-prevention-of-antimicro-peer-reviewed-fulltext-article-IDR |
| _version_ | 1818468385920385024 |
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| author | Zhao J Huang Y Li J Zhang B Dong Z Wang D |
| author_facet | Zhao J Huang Y Li J Zhang B Dong Z Wang D |
| author_sort | Zhao J |
| collection | DOAJ |
| description | Jin Zhao,1,* Yan Huang,1,* Jian Li,1,* Bo Zhang,1 Zhiwei Dong,2 Dong Wang1 1Department of Pulmonary and Critical Care Medicine, Air Force Medical Center, PLA, Beijing, 100142, People’s Republic of China; 2Department of General Surgery, Air Force Medical Center, PLA, Beijing, 100142, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong Wang, Department of Pulmonary and Critical Care Medicine, Air Force Medical Center, PLA, No. 30 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of China, Tel +8613661256489, Fax +86 10-84671291-6202, Email Dongairforce@163.com Zhiwei Dong, Department of General Surgery, Air Force Medical Center, PLA, No. 30 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of China, Tel +8618618261596, Fax +86 10-84671291-3106, Email 598852689@qq.comBackground: Stenotrophomonas maltophilia (S. maltophilia) is a multidrug-resistant gram-negative bacillus that is known to be an opportunistic pathogen, particularly in a hospital environment. The infection has a high morbidity and mortality. Sulfamethoxazole-trimethoprim (SXT) is the first-line agent recommended for its treatment. The global spread of dihydropteroate synthase (sul) genes has resulted in an increased resistance rate. However, the appropriate therapy for infections caused by sul-carrying S. maltophilia has not yet been established.Objective: Our study aimed to identify the optimal antibiotic combinations that could both show high antibacterial activity against sul-carrying S. maltophilia and the ability to prevent the emergence of resistance at clinical dosage regimens.Methods: Time-killing experiments and mutant prevention concentration (MPC) experiments were conducted to evaluate the antibacterial effect and ability to prevent resistance to minocycline, tigecycline, moxifloxacin, and ticarcillin/clavulanic acid (T/K), both alone and in combination, at clinically relevant antimicrobial concentrations.Results: Minocycline, tigecycline, and T/K all exhibited bacteriostatic activity to sul-carrying S. maltophilia. The combination of minocycline plus T/K and tigecycline plus T/K neither enhanced the bactericidal ability nor prevented drug-resistant mutations. Moxifloxacin, at 2 mg/L, showed good bactericidal activity to most S. maltophilia, but bacterial regrowth at 24 h was observed in two strains. When combined with T/K, moxifloxacin showed good bactericidal activity in all moxifloxacin-sensitive strains. The concentrations of moxifloxacin alone were lower than most MPCs of the tested sul-carrying strains. When combined with T/K, the mean steady-state concentrations (MSC) of moxifloxacin could prevent 70% of resistance, and the peak concentration (Cmax) prevented 95% of resistance.Conclusion: The combination of moxifloxacin and T/K can achieve a good in vitro bactericidal effect and prevent the emergence of resistance at clinical dosage regimens, and may be an optimal therapeutic strategy for S. maltophilia infections, especially for vulnerable immunocompromised and critically ill patients.Keywords: sulfamethoxazole-trimethoprim, dihydropteroate synthase, moxifloxacin, mutant prevention concentration, pharmacokinetic, Cmax |
| first_indexed | 2024-04-13T21:11:35Z |
| format | Article |
| id | doaj.art-c1259ccb2bf4464cb7cdd2e4ba5db2c6 |
| institution | Directory Open Access Journal |
| issn | 1178-6973 |
| language | English |
| last_indexed | 2024-04-13T21:11:35Z |
| publishDate | 2022-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj.art-c1259ccb2bf4464cb7cdd2e4ba5db2c62022-12-22T02:29:48ZengDove Medical PressInfection and Drug Resistance1178-69732022-06-01Volume 153039304675917In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophiliaZhao JHuang YLi JZhang BDong ZWang DJin Zhao,1,* Yan Huang,1,* Jian Li,1,* Bo Zhang,1 Zhiwei Dong,2 Dong Wang1 1Department of Pulmonary and Critical Care Medicine, Air Force Medical Center, PLA, Beijing, 100142, People’s Republic of China; 2Department of General Surgery, Air Force Medical Center, PLA, Beijing, 100142, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong Wang, Department of Pulmonary and Critical Care Medicine, Air Force Medical Center, PLA, No. 30 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of China, Tel +8613661256489, Fax +86 10-84671291-6202, Email Dongairforce@163.com Zhiwei Dong, Department of General Surgery, Air Force Medical Center, PLA, No. 30 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of China, Tel +8618618261596, Fax +86 10-84671291-3106, Email 598852689@qq.comBackground: Stenotrophomonas maltophilia (S. maltophilia) is a multidrug-resistant gram-negative bacillus that is known to be an opportunistic pathogen, particularly in a hospital environment. The infection has a high morbidity and mortality. Sulfamethoxazole-trimethoprim (SXT) is the first-line agent recommended for its treatment. The global spread of dihydropteroate synthase (sul) genes has resulted in an increased resistance rate. However, the appropriate therapy for infections caused by sul-carrying S. maltophilia has not yet been established.Objective: Our study aimed to identify the optimal antibiotic combinations that could both show high antibacterial activity against sul-carrying S. maltophilia and the ability to prevent the emergence of resistance at clinical dosage regimens.Methods: Time-killing experiments and mutant prevention concentration (MPC) experiments were conducted to evaluate the antibacterial effect and ability to prevent resistance to minocycline, tigecycline, moxifloxacin, and ticarcillin/clavulanic acid (T/K), both alone and in combination, at clinically relevant antimicrobial concentrations.Results: Minocycline, tigecycline, and T/K all exhibited bacteriostatic activity to sul-carrying S. maltophilia. The combination of minocycline plus T/K and tigecycline plus T/K neither enhanced the bactericidal ability nor prevented drug-resistant mutations. Moxifloxacin, at 2 mg/L, showed good bactericidal activity to most S. maltophilia, but bacterial regrowth at 24 h was observed in two strains. When combined with T/K, moxifloxacin showed good bactericidal activity in all moxifloxacin-sensitive strains. The concentrations of moxifloxacin alone were lower than most MPCs of the tested sul-carrying strains. When combined with T/K, the mean steady-state concentrations (MSC) of moxifloxacin could prevent 70% of resistance, and the peak concentration (Cmax) prevented 95% of resistance.Conclusion: The combination of moxifloxacin and T/K can achieve a good in vitro bactericidal effect and prevent the emergence of resistance at clinical dosage regimens, and may be an optimal therapeutic strategy for S. maltophilia infections, especially for vulnerable immunocompromised and critically ill patients.Keywords: sulfamethoxazole-trimethoprim, dihydropteroate synthase, moxifloxacin, mutant prevention concentration, pharmacokinetic, Cmaxhttps://www.dovepress.com/in-vitro-antibacterial-activity-and-resistance-prevention-of-antimicro-peer-reviewed-fulltext-article-IDRsulfamethoxazole-trimethoprimdihydropteroate synthasemoxifloxacinmutant prevention concentrationpharmacokineticcmax |
| spellingShingle | Zhao J Huang Y Li J Zhang B Dong Z Wang D In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia Infection and Drug Resistance sulfamethoxazole-trimethoprim dihydropteroate synthase moxifloxacin mutant prevention concentration pharmacokinetic cmax |
| title | In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia |
| title_full | In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia |
| title_fullStr | In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia |
| title_full_unstemmed | In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia |
| title_short | In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia |
| title_sort | in vitro antibacterial activity and resistance prevention of antimicrobial combinations for dihydropteroate synthase carrying stenotrophomonas maltophilia |
| topic | sulfamethoxazole-trimethoprim dihydropteroate synthase moxifloxacin mutant prevention concentration pharmacokinetic cmax |
| url | https://www.dovepress.com/in-vitro-antibacterial-activity-and-resistance-prevention-of-antimicro-peer-reviewed-fulltext-article-IDR |
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