Daptomycin induced acute eosinophilic pneumonia is a rare and potentially life threatening condition characterized by rapid respiratory failure, pulmonary infiltrates and eosinophilia. Risk factors for acute eosinophi...Daptomycin induced acute eosinophilic pneumonia is a rare and potentially life threatening condition characterized by rapid respiratory failure, pulmonary infiltrates and eosinophilia. Risk factors for acute eosinophilic pneumonia include smoking, environmental irritants or inhalants and certain medications such as Daptomycin [1]. In this review of literature, we aim to explore the potential triggers for developing acute eosinophilic pneumonia in patients exposed to Daptomycin. The exact immune mechanism for daptomycin induced AEP is unknown, however the current proposed mechanism describes a T helper 2 lymphocyte response to inactivated daptomycin in the pulmonary surfactant, which leads to eosinophilia. Disordered T regulatory cell function is seen in patients with certain cancers, allergies and autoimmune conditions. We propose that patients with these underlying risk factors may be at increased risk of developing AEP after becoming exposed to Daptomycin. Understanding potential risk factors is crucial for health care workers as it allows them to identify susceptible populations, explore preventative measures and treat accordingly.展开更多
BACKGROUND Vancomycin remains a first-line treatment drug as per the treatment guidelines for methicillin-resistant Staphylococcus aureus(MRSA)bacteremia.However,a number of gram-positive cocci have developed resistan...BACKGROUND Vancomycin remains a first-line treatment drug as per the treatment guidelines for methicillin-resistant Staphylococcus aureus(MRSA)bacteremia.However,a number of gram-positive cocci have developed resistance to several drugs,including glycopeptides.Therefore,there is an urgent need for effective and innovative antibacterial drugs to treat patients with infections caused by drugresistant bacteria.CASE SUMMARY A 24-year-old male was admitted to hospital owing to lumbago,fever,and hematuria.Computed tomography(CT)results showed an abscess in the psoas major muscle of the patient.Repeated abscess drainage and blood culture suggested MRSA,and vancomycin was initiated.However,after day 10,CT scans showed abscesses in the lungs and legs of the patient.Therefore,treatment was switched to daptomycin.Linezolid was also added considering inflammation in the lungs.After 10 d of the dual-drug anti-MRSA treatment,culture of the abscess drainage turned negative for MRSA.On day 28,the patient was discharged without any complications.CONCLUSION This case indicates that daptomycin combined with linezolid is an effective remedy for bacteremia caused by MRSA with pulmonary complications.展开更多
Antibiotic-loaded poly (methyl methacrylate) bone cements (ALPBCs) are widely used as an agent to decrease the occurrence of periprosthetic joint infection (PJI). Most often, the antibiotic used in an ALPBC is gentami...Antibiotic-loaded poly (methyl methacrylate) bone cements (ALPBCs) are widely used as an agent to decrease the occurrence of periprosthetic joint infection (PJI). Most often, the antibiotic used in an ALPBC is gentamicin, tobramycin, or vancomycin. In many recent clinical studies, it has been reported that the pathogens that commonly present in PIJ are becoming resistant to these antibiotics. As such, a new generation of antibiotics is emerging, among which is daptomycin. Literature reports with a clinically relevant medium-dose daptomycin-loaded cement show that the daptomycin release rate from cylindrical specimens is low. Incorporation of a poragen, such as dextrose, glycine, or particulate xylitol, into the cement powder has been shown to be an effective way to increase daptomycin release rate. There are, however, no studies on modeling of daptomycin release from specimens of either a daptomycin-loaded cement or a daptomycin-poragen-loaded cement. In the present work, we determine the profiles of daptomycin release from cylindrical medium-dose daptomycin-xylitol-loaded cement specimens, as a function of the particulate xylitol loading. We used these results and relationships that have been shown to model antibiotic release from ALPBC specimens to obtain the best-fit relationship for the present cements. Through this approach, we demonstrated that, regardless of the xylitol loading, the daptomycin release profile is a mixture of initial burst followed by a slow Fickian diffusion.展开更多
The emergence of daptomycin non-susceptible enterococci(DNSE) poses both treatment and infection control challenges.Clinicians should be vigilant that DNSE may be isolated from patients with or without(de novo DNSE) p...The emergence of daptomycin non-susceptible enterococci(DNSE) poses both treatment and infection control challenges.Clinicians should be vigilant that DNSE may be isolated from patients with or without(de novo DNSE) prior use of daptomycin.Recent epidemiological data suggest the presence of a community reservoir for DNSE which may be associated with environmental,foodborne and agricultural exposures.The mechanisms of nonsusceptibility to daptomycin have not been well characterized and may not parallel those for Staphylococcus aureus.The identification of daptomycin resistance genes in anaerobes,in farm animals and in an ecosystem that has been isolated for million years,suggest that the environmental reservoir for de novo DNSE may be larger than previously thought.Herein,the limited available scientific evidence regarding the possible origin of de novo DNSE is discussed.The current existing evidence is not sufficient to draw firm conclusions on the origin of DNSE.Further studies to determine the mechanisms of de novo daptomycin nonsusceptibility among enterococci are needed.展开更多
We report a case of a haemodialysis patient that presented a catheter-related bacteraemia caused by a Coagulase negative Staphylococcus. With the utilization of molecular biology techniques the bacterial isolate recov...We report a case of a haemodialysis patient that presented a catheter-related bacteraemia caused by a Coagulase negative Staphylococcus. With the utilization of molecular biology techniques the bacterial isolate recovered from catheter was surprisingly identified as S. hominis by sequencing of the 16S ribosomal gene. The S. hominis isolate, which is not often associated with infections in dialysis patients, was resistant to methicillin, being mecA positive, and to daptomycin. The patient was successfully treated with vancomycin together with the catheter retirement.展开更多
Considering that some antibacterial agents can identify the outer structure of pathogens like cell wall and/or cell membrane, we explored a self-enhanced targeted delivery strategy by which a small amount of the antib...Considering that some antibacterial agents can identify the outer structure of pathogens like cell wall and/or cell membrane, we explored a self-enhanced targeted delivery strategy by which a small amount of the antibiotic molecules were modified on the surface of carriers as targeting ligands of certain bacteria while more antibiotic molecules were loaded inside the carriers, and thus has the potential to improve the drug concentration at the infection site, enhance efficacy and reduce potential toxicity. In this study, a novel targeted delivery system against methicillin-resistant Staphylococcus aureus(MRSA)pneumonia was constructed with daptomycin, a lipopeptide antibiotic, which can bind to the cell wall of S.aureus via its hydrophobic tail. Daptomycin was conjugated with N-hydroxysuccinimidyl–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine to synthesize a targeting compound(Dapt–PEG–DSPE) which could be anchored on the surface of liposomes, while additional daptomycin molecules were encapsulated inside the liposomes. These daptomycin-modified, daptomycin-loaded liposomes(DPD-L[D]) showed specific binding to MRSA as detected by flow cytometry and good targeting capabilities in vivo to MRSA-infected lungs in a pneumonia model. DPD-L[D] exhibited more favorable antibacterial efficacy against MRSA than conventional PEGylated liposomal daptomycin both in vitro and in vivo. Our study demonstrates that daptomycin-modified liposomes can enhance MRSAtargeted delivery of encapsulated antibiotic, suggesting a novel drug delivery approach for existing antimicrobial agents.展开更多
Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant...Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.展开更多
文摘Daptomycin induced acute eosinophilic pneumonia is a rare and potentially life threatening condition characterized by rapid respiratory failure, pulmonary infiltrates and eosinophilia. Risk factors for acute eosinophilic pneumonia include smoking, environmental irritants or inhalants and certain medications such as Daptomycin [1]. In this review of literature, we aim to explore the potential triggers for developing acute eosinophilic pneumonia in patients exposed to Daptomycin. The exact immune mechanism for daptomycin induced AEP is unknown, however the current proposed mechanism describes a T helper 2 lymphocyte response to inactivated daptomycin in the pulmonary surfactant, which leads to eosinophilia. Disordered T regulatory cell function is seen in patients with certain cancers, allergies and autoimmune conditions. We propose that patients with these underlying risk factors may be at increased risk of developing AEP after becoming exposed to Daptomycin. Understanding potential risk factors is crucial for health care workers as it allows them to identify susceptible populations, explore preventative measures and treat accordingly.
基金Supported by Shantou Medical and Health Science and Technology ProgramNo. SFK [2020] 66-23
文摘BACKGROUND Vancomycin remains a first-line treatment drug as per the treatment guidelines for methicillin-resistant Staphylococcus aureus(MRSA)bacteremia.However,a number of gram-positive cocci have developed resistance to several drugs,including glycopeptides.Therefore,there is an urgent need for effective and innovative antibacterial drugs to treat patients with infections caused by drugresistant bacteria.CASE SUMMARY A 24-year-old male was admitted to hospital owing to lumbago,fever,and hematuria.Computed tomography(CT)results showed an abscess in the psoas major muscle of the patient.Repeated abscess drainage and blood culture suggested MRSA,and vancomycin was initiated.However,after day 10,CT scans showed abscesses in the lungs and legs of the patient.Therefore,treatment was switched to daptomycin.Linezolid was also added considering inflammation in the lungs.After 10 d of the dual-drug anti-MRSA treatment,culture of the abscess drainage turned negative for MRSA.On day 28,the patient was discharged without any complications.CONCLUSION This case indicates that daptomycin combined with linezolid is an effective remedy for bacteremia caused by MRSA with pulmonary complications.
文摘Antibiotic-loaded poly (methyl methacrylate) bone cements (ALPBCs) are widely used as an agent to decrease the occurrence of periprosthetic joint infection (PJI). Most often, the antibiotic used in an ALPBC is gentamicin, tobramycin, or vancomycin. In many recent clinical studies, it has been reported that the pathogens that commonly present in PIJ are becoming resistant to these antibiotics. As such, a new generation of antibiotics is emerging, among which is daptomycin. Literature reports with a clinically relevant medium-dose daptomycin-loaded cement show that the daptomycin release rate from cylindrical specimens is low. Incorporation of a poragen, such as dextrose, glycine, or particulate xylitol, into the cement powder has been shown to be an effective way to increase daptomycin release rate. There are, however, no studies on modeling of daptomycin release from specimens of either a daptomycin-loaded cement or a daptomycin-poragen-loaded cement. In the present work, we determine the profiles of daptomycin release from cylindrical medium-dose daptomycin-xylitol-loaded cement specimens, as a function of the particulate xylitol loading. We used these results and relationships that have been shown to model antibiotic release from ALPBC specimens to obtain the best-fit relationship for the present cements. Through this approach, we demonstrated that, regardless of the xylitol loading, the daptomycin release profile is a mixture of initial burst followed by a slow Fickian diffusion.
文摘The emergence of daptomycin non-susceptible enterococci(DNSE) poses both treatment and infection control challenges.Clinicians should be vigilant that DNSE may be isolated from patients with or without(de novo DNSE) prior use of daptomycin.Recent epidemiological data suggest the presence of a community reservoir for DNSE which may be associated with environmental,foodborne and agricultural exposures.The mechanisms of nonsusceptibility to daptomycin have not been well characterized and may not parallel those for Staphylococcus aureus.The identification of daptomycin resistance genes in anaerobes,in farm animals and in an ecosystem that has been isolated for million years,suggest that the environmental reservoir for de novo DNSE may be larger than previously thought.Herein,the limited available scientific evidence regarding the possible origin of de novo DNSE is discussed.The current existing evidence is not sufficient to draw firm conclusions on the origin of DNSE.Further studies to determine the mechanisms of de novo daptomycin nonsusceptibility among enterococci are needed.
基金partially supported by grant FIS10/00125 from INSTITUTO DE SALUD CARLOSIII(Spanish Health Ministry)to S.M.-A.
文摘We report a case of a haemodialysis patient that presented a catheter-related bacteraemia caused by a Coagulase negative Staphylococcus. With the utilization of molecular biology techniques the bacterial isolate recovered from catheter was surprisingly identified as S. hominis by sequencing of the 16S ribosomal gene. The S. hominis isolate, which is not often associated with infections in dialysis patients, was resistant to methicillin, being mecA positive, and to daptomycin. The patient was successfully treated with vancomycin together with the catheter retirement.
基金supported by the National Natural Science Foundation of China(No.81102404)the Fundamental Research Funds for the Central Universities(Nos.XDJK2015A012 and XDJK2013A015)the Program for Innovative Research Team in University of Chongqing
文摘Considering that some antibacterial agents can identify the outer structure of pathogens like cell wall and/or cell membrane, we explored a self-enhanced targeted delivery strategy by which a small amount of the antibiotic molecules were modified on the surface of carriers as targeting ligands of certain bacteria while more antibiotic molecules were loaded inside the carriers, and thus has the potential to improve the drug concentration at the infection site, enhance efficacy and reduce potential toxicity. In this study, a novel targeted delivery system against methicillin-resistant Staphylococcus aureus(MRSA)pneumonia was constructed with daptomycin, a lipopeptide antibiotic, which can bind to the cell wall of S.aureus via its hydrophobic tail. Daptomycin was conjugated with N-hydroxysuccinimidyl–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine to synthesize a targeting compound(Dapt–PEG–DSPE) which could be anchored on the surface of liposomes, while additional daptomycin molecules were encapsulated inside the liposomes. These daptomycin-modified, daptomycin-loaded liposomes(DPD-L[D]) showed specific binding to MRSA as detected by flow cytometry and good targeting capabilities in vivo to MRSA-infected lungs in a pneumonia model. DPD-L[D] exhibited more favorable antibacterial efficacy against MRSA than conventional PEGylated liposomal daptomycin both in vitro and in vivo. Our study demonstrates that daptomycin-modified liposomes can enhance MRSAtargeted delivery of encapsulated antibiotic, suggesting a novel drug delivery approach for existing antimicrobial agents.
基金This work was supported by National Natural Science Foundation of China(grant number 31730002,2170057)the National Key R&D Program of China(grant number 2019YFA09005400)。
文摘Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.
