Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative patho...Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative pathogens.Previous studies reported that BAC-adapted Pseudomonas aeruginosa increased the tolerance to PB.Herein,we present the novel finding that the combination of BAC and PB exhibited synergistic antibacterial effects against P.aeruginosa.Time-killing assay demonstrated a significant reduction in bacterial cell viability.Scanning electron microscopy,zeta potential analysis,hydrophobicity measurements,and fluorescence probe analyses collectively revealed severe disruption of the cell envelope and membrane potential induced by the combination of BAC and PB.Transcriptomic analysis revealed that the BAC-PB combination notably downreg-ulated the expression of genes involved in lipid A modification and cell envelope production,including phoPQ,pmrAB,bamABCDE,lptABCDEG,lolB,yidC,and murJ.Additionally,the combination group exhibited augmented production of reactive oxygen species and diminished ATP synthesis.The expression of the genes associated with substance metabolism and energy generation was significantly impeded.This study provides significant implica-tions for the interactions of biocides and antibiotics on Gram-negative pathogens,while also addressing antibiotic resistance and developing the external treatment strategy for Pseudomonas-infected wounds and burns.展开更多
To address the pressing issue of bacterial resistance,antibiotics with new mechanisms were urgently needed;yet,the majority of efforts centered on discovering novel structural compounds,often plagued by lengthy resear...To address the pressing issue of bacterial resistance,antibiotics with new mechanisms were urgently needed;yet,the majority of efforts centered on discovering novel structural compounds,often plagued by lengthy research timelines and unpredictability.In this study,we introduce an alternative strategy that rejuvenates outdated antibiotics through a unique delivery system.Specifically,we leveraged polymyxin B(PMB)and created a liposomal carrier encapsulating PMB and Fe2þ,designated P/Fe@L-P.When administered to PMB-resistant Acinetobacter baumannii,P/Fe@L-P triggered a downregulation of Nrf2 and GPX4 proteins,accompanied by a significant surge in reactive oxygen species and malondialdehyde levels,signifying the induction of ferroptosis.This mechanism imparted potent antibacterial activity,with P/Fe@L-P achieving minimal inhibitory and bactericidal concentrations of 54 and 192 mM,respectively,outperforming free PMB(72 and 768 mM).In vivo evaluations in mice models further validated the superior efficacy of P/Fe@L-P over PMB in treating PMB-resistant Acinetobacter baumannii pneumonia.This work establishes a highly effective and practical“old drug,new trick”paradigm,potentially expediting the fight against the escalating threat of bacterial resistance.展开更多
The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative ba...The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative bacterial infections,serves as a crucial final recourse against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Nevertheless,the clinical usage of PMB is impeded by its pronounced nephrotoxicity and poor infection site targeting.This investigation is geared to construct a nanoparticle formulation(named HA-PMB@H)comprising hyaluronic acid(HA)and PMB via a simple Schiff base reaction and further coating HA by electrostatic action.HA-PMB@H shows an average size of(153.8±24.3)nm,and a mean zeta potential of(−25.6±5.2)mV.Additionally,PMB can be released from HA-PMB@H more thoroughly and efficiently at pH 5.5 compared to pH 7.4,which demonstrates the Schiff base modification of PMB paves the way for its release at focus of infection.The uptake ratio of HA-PMB@H by alveolar epithelial cells(RLE-6TN)surpassed that of free PMB devoid of HA,which facilitates to the intracellular sterilization of PMB.Furthermore,the employment of HA-PMB@H ameliorated the toxicity of PMB towards human embryonic kidney cells(HEK 293)and pulmonary microvascular endothelial cells(HULEC-5a).What is more,HA-PMB@H effectively managed severe pneumonia induced by CRKP samples from clinical patients diagnosed with CRKP infection in vivo,substantially enhancing the survival rate of mice.Consequently,this nano-delivery system holds promising clinical significance in the combat against drug-resistant bacterial infections.展开更多
Background:Intracranial infection after craniotomy is one of the most serious postoperative complications,especially multidrug-resistant(MDR)or extensively drug-resistant(XDR)bacterial meningitis,and strongly affects ...Background:Intracranial infection after craniotomy is one of the most serious postoperative complications,especially multidrug-resistant(MDR)or extensively drug-resistant(XDR)bacterial meningitis,and strongly affects the prognosis of patients.Current treatment experience regarding these infections is scarce.Case presentation:We report a case of severe intracranial infection of XDR Acinetobacter baumannii(A.baumannii)that was treated by intravenous(IV)injection,sequential intraventricular(IVT)injection of tigecycline and polymyxin B,and other anti-infective drugs.Good results were obtained,and the patient was eventually discharged from the hospital.This case is characterized by intracranial infection.Conclusions:The polymyxin B IV+IVT pathway is an ideal treatment strategy for XDR A.baumannii.The tigecycline IVT pathway is also a safe treatment option.展开更多
Polymyxin B,which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections,became available in China in Dec.2017.As dose adjustments are based solely on clinical experience of risk t...Polymyxin B,which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections,became available in China in Dec.2017.As dose adjustments are based solely on clinical experience of risk toxicity,treatment failure,and emergence of resistance,there is an urgent clinical need to perform therapeutic drug monitoring(TDM)to optimize the use of polymyxin B.It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use.We report a consensus on TDM guidelines for polymyxin B,as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society.The consensus panel was composed of clinicians,pharmacists,and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations,sample collection,reporting,and explanation of TDM results.The guidelines provide the first-ever consensus on conducting TDM of polymyxin B,and are intended to guide optimal clinical use.展开更多
Aim To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis （P. gingivalis）, exhibits towards the cationic antimicrobial peptide, polymyxin B. Methodology A gene...Aim To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis （P. gingivalis）, exhibits towards the cationic antimicrobial peptide, polymyxin B. Methodology A genetic screen of P. gingivalis clones generated by a Tn4400-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B （PMB, 50μg·mL^-1）. Results P. gingivalis （ATCC 33277） is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations （200μg·mL^-1）. Approximately 2,700 independent Tn4400 ＇-derived mutants ofP. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose （50 μg·mL^-1）. A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400＇ transposon was integrated into the gene encoding the lipid A 4＇-phosphatase, PGN 0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400＇, was highly sensitive to PMB killing relative to wild-type P. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural （MALDI-TOF MS） analyses revealed that lipid A isolates from 0524-Tn4400＂ and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wildtype P gingivalis lipid A spectrum. Finally, intact 0524- Tn4400＇ and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 （TLR4）-dependent E-selectin expression in human endothelial cells relative to intact wild-type P.. gingivalis or its corresponding LPS isolate. Conclusion The combined molecular evidence provided in this report suggests that PGN 0524, a lipid A 4＇-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, P. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as PMB. These data strongly implicate PGN_0524 as a critical virulence factor for the ability of P.. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and TLR 4 sensing.展开更多
Polymyxin B(PB),as the last-line of defense against multidrug-resistant Gram-negative bacteria,has caused resistance to P.aeruginosa recently.Fortunately,synergistic treatment could preserve the last class of antibiot...Polymyxin B(PB),as the last-line of defense against multidrug-resistant Gram-negative bacteria,has caused resistance to P.aeruginosa recently.Fortunately,synergistic treatment could preserve the last class of antibiotics and reduce the emergency of drug resistance.Here,we performed a screen of 970 approved drugs synergized with PB against the P.aeruginosa DK2,which is severely resistant to PB,MIC=512μg/mL.Encouragingly,we found fluoroquinolones could synergy with PB and achieved an obvious reduction in MIC of PB below the clinical susceptible breakpoint(2 μg/mL).Especially,gemifloxacin achieved the highest synergistic effect with PB,leading to a 4096-fold MIC reduction(reduced from512 μg/mL to 0.125 μg/mL).Furthermore,synergistic effect was also observed in the combination of gemifloxacin and colistin.Finally,outer membrane permeabilization assay showed that gemifloxacin could increase the permeability of bacterial cell membranes for P.aeruginosa which partly explained the synergy mechanism.These results indicate that fluoroquinolones represent attractive synergists to address the emerging threat of polymyxin-resistant infections.展开更多
Polymyxin B(PMB)is considered as the last line of antibiotic defense available to humans.The environmental effects of the combined pollution with PMB and heavy metals and their interaction mechanisms are unclear.We ex...Polymyxin B(PMB)is considered as the last line of antibiotic defense available to humans.The environmental effects of the combined pollution with PMB and heavy metals and their interaction mechanisms are unclear.We explored the effects of the combined pollution with PMB and arsenic(As)on the microbial composition of the soil and in the earthworm gut,as well as the spread and transmission of antibiotic resistance genes(ARGs).The results showed that,compared with As alone,the combined addition of PMB and As could significantly increase the bioaccumulation factor and toxicity of As in earthworm tissues by 12.1%and 16.0%,respectively.PMB treatment could significantly increase the abundance of Actinobacteria in the earthworm gut(from 35.6%to 45.2%),and As stress could significantly increase the abundance of Proteobacteria(from 19.8%to 56.9%).PMB and As stress both could significantly increase the abundance of ARGs and mobile genetic elements(MGEs),which were positively correlated,indicating that ARGs might be horizontally transferred.The inactivation of antibiotics was the main resistance mechanism that microbes use to resist PMB and As stress.Network analysis showed that PMB and As might have antagonistic effects through competition with multi-drug resistant ARGs.The combined pollution by PMB and As significantly promoted the relative abundance of microbes carrying multi-drug resistant ARGs and MGEs,thereby increasing the risk of transmission of ARGs.This research advances the understanding of the interaction mechanism between antibiotics and heavy metals and provides new theoretical guidance for the environmental risk assessment and combined pollution management.展开更多
BACKGROUND Polymyxin B hemoperfusion(PMX-HP)has been used as a treatment for intraabdominal septic shock by absorbing and removing endotoxins of gram-negative bacilli.AIM To investigate the clinical efficacy of PMX-HP...BACKGROUND Polymyxin B hemoperfusion(PMX-HP)has been used as a treatment for intraabdominal septic shock by absorbing and removing endotoxins of gram-negative bacilli.AIM To investigate the clinical efficacy of PMX-HP in patients with gram-negative septic shock who underwent abdominal surgery.METHODS From January 2012 to December 2018,patients who had septic shock secondary to peritonitis were enrolled.They were classified into PMX-HP treated and control groups based on postopreative intervention using PMX-HP.The clinical outcomes were compared using 1:1 propensity score matching methods to balance the overall distribution between the two groups.RESULTS After propensity score matching,40 patients were analyzed(20 patients in the PMX group and 20 patients in the control group).The scores of total Sequential Organ Failure Assessment(SOFA)score,renal SOFA and coagulation SOFA were significantly improved in the PMX group but not in the control group.(from 11.2±5.8 to 4.7±3.5 in PMX group vs 10.0±4.0 to 8.7±7.3 in control group,P=0.047 from 2.6±1.0 to 0.7±1.0 in PMX group vs 2.6±1.5 to 2.8±1.6 in control group,P=0.000,from 1.6±1.5 to 1.3±1.3 in PMX group vs 1.2±1.2 to 2.8±1.8 in control group,P=0.014,respectively).Further,the length of intensive care unit(ICU)stay was significantly shorter in PMX group.However,no statistically significant difference was found in ICU mortality(50%in PMX group vs 50%in control group).CONCLUSION PMX-HP is a feasible adjunct treatment for peritonitis in ICU patients with peritonitis for improved organ impairment and to stabilize hemodynamics.It would be helpful to enhance clinical outcomes especially in patients with complete elimination of the source of gram-negative bacilli infection by surgical procedure accompanied with conventional treatment of sepsis.展开更多
基金supported by the National Natural Science Foundation of China(No.32170121).
文摘Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative pathogens.Previous studies reported that BAC-adapted Pseudomonas aeruginosa increased the tolerance to PB.Herein,we present the novel finding that the combination of BAC and PB exhibited synergistic antibacterial effects against P.aeruginosa.Time-killing assay demonstrated a significant reduction in bacterial cell viability.Scanning electron microscopy,zeta potential analysis,hydrophobicity measurements,and fluorescence probe analyses collectively revealed severe disruption of the cell envelope and membrane potential induced by the combination of BAC and PB.Transcriptomic analysis revealed that the BAC-PB combination notably downreg-ulated the expression of genes involved in lipid A modification and cell envelope production,including phoPQ,pmrAB,bamABCDE,lptABCDEG,lolB,yidC,and murJ.Additionally,the combination group exhibited augmented production of reactive oxygen species and diminished ATP synthesis.The expression of the genes associated with substance metabolism and energy generation was significantly impeded.This study provides significant implica-tions for the interactions of biocides and antibiotics on Gram-negative pathogens,while also addressing antibiotic resistance and developing the external treatment strategy for Pseudomonas-infected wounds and burns.
基金supported by the National Natural Science Foundation of China(Grant No.:81502995)China Postdoctoral Science foundation(Grant No.:2020T130048ZX)Jiangsu Pharmaceutical Association Jin Peiying Fund Project(Grant No.:J2023008).
文摘To address the pressing issue of bacterial resistance,antibiotics with new mechanisms were urgently needed;yet,the majority of efforts centered on discovering novel structural compounds,often plagued by lengthy research timelines and unpredictability.In this study,we introduce an alternative strategy that rejuvenates outdated antibiotics through a unique delivery system.Specifically,we leveraged polymyxin B(PMB)and created a liposomal carrier encapsulating PMB and Fe2þ,designated P/Fe@L-P.When administered to PMB-resistant Acinetobacter baumannii,P/Fe@L-P triggered a downregulation of Nrf2 and GPX4 proteins,accompanied by a significant surge in reactive oxygen species and malondialdehyde levels,signifying the induction of ferroptosis.This mechanism imparted potent antibacterial activity,with P/Fe@L-P achieving minimal inhibitory and bactericidal concentrations of 54 and 192 mM,respectively,outperforming free PMB(72 and 768 mM).In vivo evaluations in mice models further validated the superior efficacy of P/Fe@L-P over PMB in treating PMB-resistant Acinetobacter baumannii pneumonia.This work establishes a highly effective and practical“old drug,new trick”paradigm,potentially expediting the fight against the escalating threat of bacterial resistance.
基金supported by the National Natural Science Foundation of China(Nos.81860543,32360237)Guizhou Provincial Science and Technology Projects(Nos.ZK[2024]235,ZK[2023]Key Project 041).
文摘The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative bacterial infections,serves as a crucial final recourse against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Nevertheless,the clinical usage of PMB is impeded by its pronounced nephrotoxicity and poor infection site targeting.This investigation is geared to construct a nanoparticle formulation(named HA-PMB@H)comprising hyaluronic acid(HA)and PMB via a simple Schiff base reaction and further coating HA by electrostatic action.HA-PMB@H shows an average size of(153.8±24.3)nm,and a mean zeta potential of(−25.6±5.2)mV.Additionally,PMB can be released from HA-PMB@H more thoroughly and efficiently at pH 5.5 compared to pH 7.4,which demonstrates the Schiff base modification of PMB paves the way for its release at focus of infection.The uptake ratio of HA-PMB@H by alveolar epithelial cells(RLE-6TN)surpassed that of free PMB devoid of HA,which facilitates to the intracellular sterilization of PMB.Furthermore,the employment of HA-PMB@H ameliorated the toxicity of PMB towards human embryonic kidney cells(HEK 293)and pulmonary microvascular endothelial cells(HULEC-5a).What is more,HA-PMB@H effectively managed severe pneumonia induced by CRKP samples from clinical patients diagnosed with CRKP infection in vivo,substantially enhancing the survival rate of mice.Consequently,this nano-delivery system holds promising clinical significance in the combat against drug-resistant bacterial infections.
基金supported by grants from the National Natural Science Foundation of China(81571940,81741125)the Guangzhou Science and Technology Planning Project of China(201504281714528)PLA Logistics Research Project of China(CWH17L020,17CXZ008,18CXZ030)
文摘Background:Intracranial infection after craniotomy is one of the most serious postoperative complications,especially multidrug-resistant(MDR)or extensively drug-resistant(XDR)bacterial meningitis,and strongly affects the prognosis of patients.Current treatment experience regarding these infections is scarce.Case presentation:We report a case of severe intracranial infection of XDR Acinetobacter baumannii(A.baumannii)that was treated by intravenous(IV)injection,sequential intraventricular(IVT)injection of tigecycline and polymyxin B,and other anti-infective drugs.Good results were obtained,and the patient was eventually discharged from the hospital.This case is characterized by intracranial infection.Conclusions:The polymyxin B IV+IVT pathway is an ideal treatment strategy for XDR A.baumannii.The tigecycline IVT pathway is also a safe treatment option.
基金the Shanghai Leading Talents Award,Shanghai Municipal Health Commission(No.LJ2016-01)the Clinical Research Plan of Shanghai Hospital Development Center(No.SHDC2022CRW004)。
文摘Polymyxin B,which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections,became available in China in Dec.2017.As dose adjustments are based solely on clinical experience of risk toxicity,treatment failure,and emergence of resistance,there is an urgent clinical need to perform therapeutic drug monitoring(TDM)to optimize the use of polymyxin B.It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use.We report a consensus on TDM guidelines for polymyxin B,as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society.The consensus panel was composed of clinicians,pharmacists,and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations,sample collection,reporting,and explanation of TDM results.The guidelines provide the first-ever consensus on conducting TDM of polymyxin B,and are intended to guide optimal clinical use.
文摘Aim To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis （P. gingivalis）, exhibits towards the cationic antimicrobial peptide, polymyxin B. Methodology A genetic screen of P. gingivalis clones generated by a Tn4400-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B （PMB, 50μg·mL^-1）. Results P. gingivalis （ATCC 33277） is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations （200μg·mL^-1）. Approximately 2,700 independent Tn4400 ＇-derived mutants ofP. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose （50 μg·mL^-1）. A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400＇ transposon was integrated into the gene encoding the lipid A 4＇-phosphatase, PGN 0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400＇, was highly sensitive to PMB killing relative to wild-type P. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural （MALDI-TOF MS） analyses revealed that lipid A isolates from 0524-Tn4400＂ and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wildtype P gingivalis lipid A spectrum. Finally, intact 0524- Tn4400＇ and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 （TLR4）-dependent E-selectin expression in human endothelial cells relative to intact wild-type P.. gingivalis or its corresponding LPS isolate. Conclusion The combined molecular evidence provided in this report suggests that PGN 0524, a lipid A 4＇-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, P. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as PMB. These data strongly implicate PGN_0524 as a critical virulence factor for the ability of P.. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and TLR 4 sensing.
基金supported by the National Key R&D Program of China(No.2017YFB0202600)the National Natural Science Foundation of China(Nos.21672064,21702061,81861138047)+3 种基金the Innovative Research Team of High-level Local Universities in Shanghaithe National Special Fund for State Key Laboratory of Bioreactor Engineering(No.2060204)"Shu Guang"project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation(No.14SG28)the Shanghai Sailing Program(No.17YF1403600)。
文摘Polymyxin B(PB),as the last-line of defense against multidrug-resistant Gram-negative bacteria,has caused resistance to P.aeruginosa recently.Fortunately,synergistic treatment could preserve the last class of antibiotics and reduce the emergency of drug resistance.Here,we performed a screen of 970 approved drugs synergized with PB against the P.aeruginosa DK2,which is severely resistant to PB,MIC=512μg/mL.Encouragingly,we found fluoroquinolones could synergy with PB and achieved an obvious reduction in MIC of PB below the clinical susceptible breakpoint(2 μg/mL).Especially,gemifloxacin achieved the highest synergistic effect with PB,leading to a 4096-fold MIC reduction(reduced from512 μg/mL to 0.125 μg/mL).Furthermore,synergistic effect was also observed in the combination of gemifloxacin and colistin.Finally,outer membrane permeabilization assay showed that gemifloxacin could increase the permeability of bacterial cell membranes for P.aeruginosa which partly explained the synergy mechanism.These results indicate that fluoroquinolones represent attractive synergists to address the emerging threat of polymyxin-resistant infections.
基金supported by the National Natural Science Foundation of China(Nos.41991332 and 41977323).
文摘Polymyxin B(PMB)is considered as the last line of antibiotic defense available to humans.The environmental effects of the combined pollution with PMB and heavy metals and their interaction mechanisms are unclear.We explored the effects of the combined pollution with PMB and arsenic(As)on the microbial composition of the soil and in the earthworm gut,as well as the spread and transmission of antibiotic resistance genes(ARGs).The results showed that,compared with As alone,the combined addition of PMB and As could significantly increase the bioaccumulation factor and toxicity of As in earthworm tissues by 12.1%and 16.0%,respectively.PMB treatment could significantly increase the abundance of Actinobacteria in the earthworm gut(from 35.6%to 45.2%),and As stress could significantly increase the abundance of Proteobacteria(from 19.8%to 56.9%).PMB and As stress both could significantly increase the abundance of ARGs and mobile genetic elements(MGEs),which were positively correlated,indicating that ARGs might be horizontally transferred.The inactivation of antibiotics was the main resistance mechanism that microbes use to resist PMB and As stress.Network analysis showed that PMB and As might have antagonistic effects through competition with multi-drug resistant ARGs.The combined pollution by PMB and As significantly promoted the relative abundance of microbes carrying multi-drug resistant ARGs and MGEs,thereby increasing the risk of transmission of ARGs.This research advances the understanding of the interaction mechanism between antibiotics and heavy metals and provides new theoretical guidance for the environmental risk assessment and combined pollution management.
文摘BACKGROUND Polymyxin B hemoperfusion(PMX-HP)has been used as a treatment for intraabdominal septic shock by absorbing and removing endotoxins of gram-negative bacilli.AIM To investigate the clinical efficacy of PMX-HP in patients with gram-negative septic shock who underwent abdominal surgery.METHODS From January 2012 to December 2018,patients who had septic shock secondary to peritonitis were enrolled.They were classified into PMX-HP treated and control groups based on postopreative intervention using PMX-HP.The clinical outcomes were compared using 1:1 propensity score matching methods to balance the overall distribution between the two groups.RESULTS After propensity score matching,40 patients were analyzed(20 patients in the PMX group and 20 patients in the control group).The scores of total Sequential Organ Failure Assessment(SOFA)score,renal SOFA and coagulation SOFA were significantly improved in the PMX group but not in the control group.(from 11.2±5.8 to 4.7±3.5 in PMX group vs 10.0±4.0 to 8.7±7.3 in control group,P=0.047 from 2.6±1.0 to 0.7±1.0 in PMX group vs 2.6±1.5 to 2.8±1.6 in control group,P=0.000,from 1.6±1.5 to 1.3±1.3 in PMX group vs 1.2±1.2 to 2.8±1.8 in control group,P=0.014,respectively).Further,the length of intensive care unit(ICU)stay was significantly shorter in PMX group.However,no statistically significant difference was found in ICU mortality(50%in PMX group vs 50%in control group).CONCLUSION PMX-HP is a feasible adjunct treatment for peritonitis in ICU patients with peritonitis for improved organ impairment and to stabilize hemodynamics.It would be helpful to enhance clinical outcomes especially in patients with complete elimination of the source of gram-negative bacilli infection by surgical procedure accompanied with conventional treatment of sepsis.
