AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, labor...AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm<sup>3</sup>. In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.展开更多
Objective:To establish extensively drug-resistant Pseudomonas aeruginosa(XDR-PA)infection-induced pneumonia model in rats.Methods:Twenty-four male SD rats were randomly divided into blank group,low bacterial group,med...Objective:To establish extensively drug-resistant Pseudomonas aeruginosa(XDR-PA)infection-induced pneumonia model in rats.Methods:Twenty-four male SD rats were randomly divided into blank group,low bacterial group,medium bacterial group,and high bacterial group.The low,medium and high bacterial groups were given intratracheal instillation of 0.1 mL of bacterial suspension(bacterial concentration in turn is 7.5×10^(9),3×10^(10),6×10^(10)CFU/mL),while the blank group were given the same volume of sterile normal saline.After modeling,the general conditions of rats in each group were observed,including mental state,hair,respiration,activity,eating,weight,and the survival curve was drawn.The pathological characteristics of lung tissue and the infiltration of inflammatory cells were observed.Pathogenic identification of each group was carried out by bacterial culture of lung tissue homogenate.Results:The general state of the blank group was normal,and the rats in other groups showed signs of mental depression,bristling,shortness of breath,even oral and nasal bleeding,decreased food intake and activity,and significant weight loss,and different degrees of death within 48 hours,the difference was statistically significant(P<0.05).Pathological results showed that the alveolar structure of rats in the blank group was complete,and the alveolar space was clear without exudation.The lung tissue of the low and medium bacterial groups showed obvious inflammatory cell infiltration,alveolar structure destruction,alveolar septum thickening,interstitial edema,but the pathological damage of the medium group was more severe,with a mortality rate of up to 50%,and the mortality rate of the low bacterial group was 17%.In the high bacterial group,red blood cells,inflammatory cells and a large amount of fibrin-like exudation can be seen in the alveolar space,which has the pathological characteristics of acute respiratory failure,and the mortality rate is as high as 67%.The results of bacterial culture of lung tissue homogenate showed that the blank group had no bacterial colonies,while PA colony growth can be seen in low,medium and high bacterial groups.Conclusion:9 Intratracheal instillation of low bacterial count(0.1 mL of 7.5×10^(9) CFU/mL)XDR-PA bacterial suspension can successfully construct a rat pneumonia model of XDR-PA infection.展开更多
BACKGROUND Bedaquiline is among the prioritized drugs recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis(XDRTB).Many patients have not achieved better clinical im...BACKGROUND Bedaquiline is among the prioritized drugs recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis(XDRTB).Many patients have not achieved better clinical improvement after bedaquiline is stopped at 24 wk.However,there is no recommendation or guideline on bedaquiline administration beyond 24 wk,which is an important consideration when balancing the benefit of prognosis for XDR-TB against the uncertain safety concerning the newer antibiotics.CASE SUMMARY This paper reported 2 patients with XDR-TB(a female of 58 years of age and a female of 18 years of age)who received bedaquiline for 36 wk,as local experience to be shared.The 2 cases had negative cultures after 24 wk of treatment,but lung imaging was still positive.After discussion among experts,the consensus was made to bedaquiline prolongation by another 12 wk.The 36-wk prolonged use of bedaquiline in both cases achieved a favorable response without increasing the risk of cardiac events or new safety signals.CONCLUSION Longer regimen,including 36-wk bedaquiline treatment,might be an option for patients with XDR-TB.More studies are needed to explore the effectiveness and safety of prolonged use of bedaquiline for 36 wk vs standard 24 wk in the treatment of multidrug-resistant/XDR-TB or to investigate further the biomarkers and criteria indicative for extension of bedaquline to facilitate clinical use of thisnovel drug.展开更多
BACKGROUND Pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii(A.baumannii)is one of the most severe complications associated with craniotomy.However,limited therapeutic options exist f...BACKGROUND Pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii(A.baumannii)is one of the most severe complications associated with craniotomy.However,limited therapeutic options exist for the treatment of A.baumannii ventriculitis due to the poor penetration rate of most antibiotics through the blood-brain barrier.CASE SUMMARY A 68-year-old male patient with severe traumatic brain injury developed pyogenic ventriculitis on postoperative day 24 caused by extensively drug-resistant A.baumannii susceptible to tigecycline only.Successful treatment was accomplished through multi-route administration of tigecycline,including intravenous combined with continuous ventricular irrigation plus intraventricular administration.The pus was cleared on the 3rd day post-irrigation,and cerebrospinal fluid cultures were negative after 12 d.CONCLUSION Our findings suggest that multi-route administration of tigecycline can be a therapeutic option against pyogenic ventriculitis caused by extensively drugresistant A.baumannii.展开更多
BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate i...BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.展开更多
Background:Many herbal essential oils are potential antimicrobials but their pharmaceutical utility is restricted due to a lack of suitable excipients to mollify their dermatotoxicity and irritant property,and outcome...Background:Many herbal essential oils are potential antimicrobials but their pharmaceutical utility is restricted due to a lack of suitable excipients to mollify their dermatotoxicity and irritant property,and outcome of their therapeutic use may vary with different diluents used.Methods:Effect of 16 diluents(dimethyl sulfoxide,liquid paraffin,glycerine,oils of mustard,sunflower,rice bran,palm,groundnut,olive,coconut,sesame,avocado,jojoba,castor,linseed and soybean)was assessed on antimicrobial activity of 2%cinnamon(Cinnamomum zelylanicum album),thyme(Thymus vulgaris)and ajowan(Trachyspermum ammi)oils using agar well diffusion assay.The effect of excipients was evaluated on six Candida albicans,five Escherichia coli,four Acinetobacter lwoffii,two strains each of Staphylococcus aureus,Enterobacter agglomerans,and Enterococcus faecium and one strain each of Acinetobacter calcoaceticus,Escherichia fergusonii,Klebsiella oxytoca,K.pneumoniae ssp.pneumoniae,Leclercia adecarboxylata,Paenibacillus amylolyticus,Proteus mirabilis,P.vulgaris,Pseudomonas aeruginosa,Raoultella terrigena,Staphylococcus capitis ssp.capitis,S.chromogenes,S.epidermidis,S.warneri and Streptococcus pyogenes.Results:Thyme oil(2%)maintained it antimicrobial activity on dilution in dimethyl sulfoxide and glycerine,and ajowan oil(2%)completely lost its antibacterial activity in all diluents except dimethyl sulfoxide.However,cinnamon oil partially lost its antimicrobial activity upon dilution in glycerine,vegetable,and mineral oils in comparison to dimethyl sulfoxide.Olive oil was the best vegetable oil,almost comparable to dimethyl sulfoxide and castor oil was the worst diluent for maintaining antimicrobial activity of cinnamon oil.Conclusion:The study indicated the non-suitability of vegetable oils for pharmaceutical formulations of essential oils except olive oil for dilution of cinnamon oil and glycerol for thyme oil to replace dimethyl sulfoxide as diluent.展开更多
Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis (MDR-TB) remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patien...Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis (MDR-TB) remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. Methods We used 12-locus mycobactedal interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects' medical records. Results All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR (DTM-PCR) identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit (MIRU) pattern (232225172531) and the same MIRU pattern (3677235). Strains from family-2 had the same MIRU pattern (2212261553323) and the same MIRU pattern (3685134). Strains from family-3 did not have the same MIRU pattern and they differed at only one locus (223326173533, 223325173533), and did not have the same VNTR pattern with two locus differed (3667233, 3677234). Conclusions Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a familv. Household tuberculosis transmission could be prevented with adequate treatment of source Patients.展开更多
Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resi...Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resistance ability. The study investigates carbapenemase producing A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, isolated from ICU patients in Khartoum. Methods: A total of 100 nonduplicate Gram-negative coccobacilli strains were obtained from microbiology laboratory of ICU patients’ clinical isolates. Molecular identification of A. baumannii was performed by targeting 16S rRNA gene using specifically designed primers. Then, XDR strains were determined by susceptibility testing (disc diffusion). For detection of carbapenemase genes Polymerase chain reaction (PCR) was carried out. Result: Of 100 ICU clinical isolates, 38 (38.0%) was confirmed A. baumannii strains, those strains showed 100% carbapenem resistance and 60.5% extensive drug resistance to the antibiotics tested. The frequency of carbapenemase producer was 57.9% (22/38) of carbapenem resistance A. baumannii (CRAB). The most common carbapenemase associated with resistance was blaOXA gene followed by blaNDM and blaGES A. baumannii isolates. The co-occurrence of blaOXA-48-like and blaNDM, blaOXA-23-like and blaOXA-51, and blaNDM-1 and blaOXA-51 was detected in 22.7%, 18.2% strains and 4.5% respectively. A unique characteristic of our findings was the coharbouring of the genes blaNDM-1, blaOXA-23-like, blaOXA-51 and blaOXA-143 in 9.1% strains (2/22), and this was the first report in the Khartoum city, Sudan. Conclusion: We have demonstrated for the first time a high prevalence of XDR-carbapenemase producing A. baumannii clinical isolates from ICU patients in Khartoum. Also an emergent blaOXA-143 was reported as High-Risk Clones. This highlights the routine mentoring of XDR-carbapenemase producing A. baumannii to avoid clone dissemination in our region hospitals.展开更多
Our aim was to determine the epidemiological characteristics, the resistance patterns and the spread of Gram negative bacteria related to colonization of patients in adult Intensive Care Units. Methods: A prospective ...Our aim was to determine the epidemiological characteristics, the resistance patterns and the spread of Gram negative bacteria related to colonization of patients in adult Intensive Care Units. Methods: A prospective cohort of patients colonized and/or infected with Gram negative bacteria was conducted at two adult ICUs from hospitals in Brazil (April 2012 to February 2013). Nasal, groin and perineum swabs were performed. Samples were incubated on MacConkey and cetrimide agar (48 h at 37℃) and identification tests (Vitek-BioMérieux), antibiogram (Bauer-Kirby method), Carba NP test, Polymerase Chain Reaction (PCR) and sequencing were performed. The patterns of resistant microorganisms were compared by rep-PCR (Diversilab). Results: There were 53 cases of colonization. In these cases, we identified imipenem-resistant Acinetobacter baumannii (51%), Pseudomonas aeruginosa (32%), Klebsiella pneumoniae ESBL (38%) or imipenem resistant (5.6%). The use of antimicrobials and medical devices were related to colonization (p The resistance patterns expressed by Klebsiella pneumoniae were ESBL (CTX-M, SHV e TEM) and KPC2. A verified profile of Acinetobacter baumannii was related to OXA-23 and OXA-253 (OXA-143 variant). The profiles ESBL and KPC2 expressed by Klebsiella pneumoniae were distributed between the both ICUs. The distribution of OXA-23 and OXA-253 was verified only in one ICU. The similarity of strains ranged from 80% to 95%, highlighting the horizontal transference of these microorganisms.展开更多
The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorat...The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes constructed via a N-[3-(trimethoxysiltyl)propyl]ethylene diamine(TSD)-mediated method(SWCNTs@mSiO2-TSD@Ag).In this system,the outer mesoporous silica shells are able to improve the dispersibility of SWCNTs,which will increase their contact area with bacteria cell walls.Meanwhile,the large number of mesopores in silica layers act as microreactors for in situ synthesis of Ag NPs with controlled small size and uniform distribution,which induces an enhanced antibacterial activity.Compared with TSD modified mesoporous silica coated single-walled carbon nanotubes(SWCNTs@mSiO2-TSD)and commercialAg NPs,this combination nanosystem of SWCNTs@mSiO2-TSD@Ag exhibits much stronger antibacterial performance against multi-drug-resistant bacteria Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)in vitro through damaging the bacterial cell membranes and a fast release of silver ions.Furthermore,the in vivo rat skin infection model verifies that SWCNTS@mSiO2-TSD@Ag have remarkably improved abilities of bacterial clearance,wound healing promoting as well as outstanding biocompatibility.Therefore,this novel nanoplatform indicates promising potentials as a safe and powerful tool for the treatment of clinical drug-resistant infections.展开更多
The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here...The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here,a series of flexible electrostatic hydrogels with excellent antibacterial ability were constructed using a mixture of nitric oxide(NO)-releasing nitrated chitosan(CSNO)and mesotetra(4-carboxyphenyl)porphine(TCPP)with salmon sperm DNA(ssDNA)solution.When cultured with gram-negative bacteria under solar simulator irradiation,TCPP-CSNO_(m)ssDNA_(n) hydrogels released reactive oxygen species(ROS)and NO to produce peroxynitrite ions(ONOO^(−)).ONOO−is efficient at killing bacteria,thereby improving the antimicrobial ability of photodynamic therapy against gram-negative bacteria.The hydrogels exhibited powerful antibacterial activity in vivo when used to treat skin infections caused by drugresistant bacteria,making them a promising candidate for clinical applications.A string of antibacterial hydrogels that release ROS and NO synergistically can bring new possibilities for effectively killing drug-resistant bacteria and be of great value in anti-infection wound dressings and other applications.展开更多
Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse eff...Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.展开更多
This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA comple...This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA complex exhibited a 12-fold enhancement of the molar extinction coefficient in the nearinfrared(NIR)region relative to aqueous cupric acetate.Inspired by this interesting finding,we formulated these photothermal materials into colloidally dispersed nanoparticles via a technique that combined nanoprecipitation and in situ surface polymerization for antibacterial studies.The resultant nanoparticles exhibited rapid and stable photothermal responses to NIR irradiation,with a 4-fold enhanced photothermal conversion efficiency relative to aqueous cupric acetate.Since a positively charged monomer was incorporated during in situ surface polymerization,these positively charged nanoparticles were ingested efficiently and subsequently digested by drug-resistant bacteria.By combining the LA-mediated membrane-damaging effect,copper-mediated Fenton-like reaction,as well as the photothermal effect of the copper–LA complex,a broad-spectrum,multimodal,and synergistic antibacterial effect was achieved both in vitro and in vivo,with the killing efficiency up to 99.99%for ampicillin-resistant Escherichia coli(Ampr E.coli)and 99.9999%for methicillinresistant Staphylococcus aureus(MRSA).Our newly developed nanobiocide represents a class of exceptional broad-spectrum antibacterial materials,holding great potential for treating drug-resistant infections in clinical settings.展开更多
文摘AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm<sup>3</sup>. In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.
基金Science and Technology Projects in Key Fields of Traditional Chinese Medicine in Tianjin(No.2021010)Discipline Development Fund of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine(No.XKJJ201734)。
文摘Objective:To establish extensively drug-resistant Pseudomonas aeruginosa(XDR-PA)infection-induced pneumonia model in rats.Methods:Twenty-four male SD rats were randomly divided into blank group,low bacterial group,medium bacterial group,and high bacterial group.The low,medium and high bacterial groups were given intratracheal instillation of 0.1 mL of bacterial suspension(bacterial concentration in turn is 7.5×10^(9),3×10^(10),6×10^(10)CFU/mL),while the blank group were given the same volume of sterile normal saline.After modeling,the general conditions of rats in each group were observed,including mental state,hair,respiration,activity,eating,weight,and the survival curve was drawn.The pathological characteristics of lung tissue and the infiltration of inflammatory cells were observed.Pathogenic identification of each group was carried out by bacterial culture of lung tissue homogenate.Results:The general state of the blank group was normal,and the rats in other groups showed signs of mental depression,bristling,shortness of breath,even oral and nasal bleeding,decreased food intake and activity,and significant weight loss,and different degrees of death within 48 hours,the difference was statistically significant(P<0.05).Pathological results showed that the alveolar structure of rats in the blank group was complete,and the alveolar space was clear without exudation.The lung tissue of the low and medium bacterial groups showed obvious inflammatory cell infiltration,alveolar structure destruction,alveolar septum thickening,interstitial edema,but the pathological damage of the medium group was more severe,with a mortality rate of up to 50%,and the mortality rate of the low bacterial group was 17%.In the high bacterial group,red blood cells,inflammatory cells and a large amount of fibrin-like exudation can be seen in the alveolar space,which has the pathological characteristics of acute respiratory failure,and the mortality rate is as high as 67%.The results of bacterial culture of lung tissue homogenate showed that the blank group had no bacterial colonies,while PA colony growth can be seen in low,medium and high bacterial groups.Conclusion:9 Intratracheal instillation of low bacterial count(0.1 mL of 7.5×10^(9) CFU/mL)XDR-PA bacterial suspension can successfully construct a rat pneumonia model of XDR-PA infection.
文摘BACKGROUND Bedaquiline is among the prioritized drugs recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis(XDRTB).Many patients have not achieved better clinical improvement after bedaquiline is stopped at 24 wk.However,there is no recommendation or guideline on bedaquiline administration beyond 24 wk,which is an important consideration when balancing the benefit of prognosis for XDR-TB against the uncertain safety concerning the newer antibiotics.CASE SUMMARY This paper reported 2 patients with XDR-TB(a female of 58 years of age and a female of 18 years of age)who received bedaquiline for 36 wk,as local experience to be shared.The 2 cases had negative cultures after 24 wk of treatment,but lung imaging was still positive.After discussion among experts,the consensus was made to bedaquiline prolongation by another 12 wk.The 36-wk prolonged use of bedaquiline in both cases achieved a favorable response without increasing the risk of cardiac events or new safety signals.CONCLUSION Longer regimen,including 36-wk bedaquiline treatment,might be an option for patients with XDR-TB.More studies are needed to explore the effectiveness and safety of prolonged use of bedaquiline for 36 wk vs standard 24 wk in the treatment of multidrug-resistant/XDR-TB or to investigate further the biomarkers and criteria indicative for extension of bedaquline to facilitate clinical use of thisnovel drug.
文摘BACKGROUND Pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii(A.baumannii)is one of the most severe complications associated with craniotomy.However,limited therapeutic options exist for the treatment of A.baumannii ventriculitis due to the poor penetration rate of most antibiotics through the blood-brain barrier.CASE SUMMARY A 68-year-old male patient with severe traumatic brain injury developed pyogenic ventriculitis on postoperative day 24 caused by extensively drug-resistant A.baumannii susceptible to tigecycline only.Successful treatment was accomplished through multi-route administration of tigecycline,including intravenous combined with continuous ventricular irrigation plus intraventricular administration.The pus was cleared on the 3rd day post-irrigation,and cerebrospinal fluid cultures were negative after 12 d.CONCLUSION Our findings suggest that multi-route administration of tigecycline can be a therapeutic option against pyogenic ventriculitis caused by extensively drugresistant A.baumannii.
文摘BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.
基金supported by grants received from CAAST-ACLH(NAHEP/CAAST/2018-19)of ICAR-World Bank-funded National Agricultural Higher Education Project(NAHEP).
文摘Background:Many herbal essential oils are potential antimicrobials but their pharmaceutical utility is restricted due to a lack of suitable excipients to mollify their dermatotoxicity and irritant property,and outcome of their therapeutic use may vary with different diluents used.Methods:Effect of 16 diluents(dimethyl sulfoxide,liquid paraffin,glycerine,oils of mustard,sunflower,rice bran,palm,groundnut,olive,coconut,sesame,avocado,jojoba,castor,linseed and soybean)was assessed on antimicrobial activity of 2%cinnamon(Cinnamomum zelylanicum album),thyme(Thymus vulgaris)and ajowan(Trachyspermum ammi)oils using agar well diffusion assay.The effect of excipients was evaluated on six Candida albicans,five Escherichia coli,four Acinetobacter lwoffii,two strains each of Staphylococcus aureus,Enterobacter agglomerans,and Enterococcus faecium and one strain each of Acinetobacter calcoaceticus,Escherichia fergusonii,Klebsiella oxytoca,K.pneumoniae ssp.pneumoniae,Leclercia adecarboxylata,Paenibacillus amylolyticus,Proteus mirabilis,P.vulgaris,Pseudomonas aeruginosa,Raoultella terrigena,Staphylococcus capitis ssp.capitis,S.chromogenes,S.epidermidis,S.warneri and Streptococcus pyogenes.Results:Thyme oil(2%)maintained it antimicrobial activity on dilution in dimethyl sulfoxide and glycerine,and ajowan oil(2%)completely lost its antibacterial activity in all diluents except dimethyl sulfoxide.However,cinnamon oil partially lost its antimicrobial activity upon dilution in glycerine,vegetable,and mineral oils in comparison to dimethyl sulfoxide.Olive oil was the best vegetable oil,almost comparable to dimethyl sulfoxide and castor oil was the worst diluent for maintaining antimicrobial activity of cinnamon oil.Conclusion:The study indicated the non-suitability of vegetable oils for pharmaceutical formulations of essential oils except olive oil for dilution of cinnamon oil and glycerol for thyme oil to replace dimethyl sulfoxide as diluent.
文摘Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis (MDR-TB) remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. Methods We used 12-locus mycobactedal interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects' medical records. Results All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR (DTM-PCR) identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit (MIRU) pattern (232225172531) and the same MIRU pattern (3677235). Strains from family-2 had the same MIRU pattern (2212261553323) and the same MIRU pattern (3685134). Strains from family-3 did not have the same MIRU pattern and they differed at only one locus (223326173533, 223325173533), and did not have the same VNTR pattern with two locus differed (3667233, 3677234). Conclusions Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a familv. Household tuberculosis transmission could be prevented with adequate treatment of source Patients.
文摘Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resistance ability. The study investigates carbapenemase producing A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, isolated from ICU patients in Khartoum. Methods: A total of 100 nonduplicate Gram-negative coccobacilli strains were obtained from microbiology laboratory of ICU patients’ clinical isolates. Molecular identification of A. baumannii was performed by targeting 16S rRNA gene using specifically designed primers. Then, XDR strains were determined by susceptibility testing (disc diffusion). For detection of carbapenemase genes Polymerase chain reaction (PCR) was carried out. Result: Of 100 ICU clinical isolates, 38 (38.0%) was confirmed A. baumannii strains, those strains showed 100% carbapenem resistance and 60.5% extensive drug resistance to the antibiotics tested. The frequency of carbapenemase producer was 57.9% (22/38) of carbapenem resistance A. baumannii (CRAB). The most common carbapenemase associated with resistance was blaOXA gene followed by blaNDM and blaGES A. baumannii isolates. The co-occurrence of blaOXA-48-like and blaNDM, blaOXA-23-like and blaOXA-51, and blaNDM-1 and blaOXA-51 was detected in 22.7%, 18.2% strains and 4.5% respectively. A unique characteristic of our findings was the coharbouring of the genes blaNDM-1, blaOXA-23-like, blaOXA-51 and blaOXA-143 in 9.1% strains (2/22), and this was the first report in the Khartoum city, Sudan. Conclusion: We have demonstrated for the first time a high prevalence of XDR-carbapenemase producing A. baumannii clinical isolates from ICU patients in Khartoum. Also an emergent blaOXA-143 was reported as High-Risk Clones. This highlights the routine mentoring of XDR-carbapenemase producing A. baumannii to avoid clone dissemination in our region hospitals.
文摘Our aim was to determine the epidemiological characteristics, the resistance patterns and the spread of Gram negative bacteria related to colonization of patients in adult Intensive Care Units. Methods: A prospective cohort of patients colonized and/or infected with Gram negative bacteria was conducted at two adult ICUs from hospitals in Brazil (April 2012 to February 2013). Nasal, groin and perineum swabs were performed. Samples were incubated on MacConkey and cetrimide agar (48 h at 37℃) and identification tests (Vitek-BioMérieux), antibiogram (Bauer-Kirby method), Carba NP test, Polymerase Chain Reaction (PCR) and sequencing were performed. The patterns of resistant microorganisms were compared by rep-PCR (Diversilab). Results: There were 53 cases of colonization. In these cases, we identified imipenem-resistant Acinetobacter baumannii (51%), Pseudomonas aeruginosa (32%), Klebsiella pneumoniae ESBL (38%) or imipenem resistant (5.6%). The use of antimicrobials and medical devices were related to colonization (p The resistance patterns expressed by Klebsiella pneumoniae were ESBL (CTX-M, SHV e TEM) and KPC2. A verified profile of Acinetobacter baumannii was related to OXA-23 and OXA-253 (OXA-143 variant). The profiles ESBL and KPC2 expressed by Klebsiella pneumoniae were distributed between the both ICUs. The distribution of OXA-23 and OXA-253 was verified only in one ICU. The similarity of strains ranged from 80% to 95%, highlighting the horizontal transference of these microorganisms.
基金This work is supported by the National Natural Science Foundation of China(Nos.51802192,81802156,and 81772338)the Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2017ZD05)+2 种基金Natural Science Foundation of Shanghai(No.19ZR1474800)Shanghai Sailing Program(No.18YF1410700)Innovation Research Plan supported by Shanghai Municipal Education Commission(No.ZXWF082101).
文摘The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes constructed via a N-[3-(trimethoxysiltyl)propyl]ethylene diamine(TSD)-mediated method(SWCNTs@mSiO2-TSD@Ag).In this system,the outer mesoporous silica shells are able to improve the dispersibility of SWCNTs,which will increase their contact area with bacteria cell walls.Meanwhile,the large number of mesopores in silica layers act as microreactors for in situ synthesis of Ag NPs with controlled small size and uniform distribution,which induces an enhanced antibacterial activity.Compared with TSD modified mesoporous silica coated single-walled carbon nanotubes(SWCNTs@mSiO2-TSD)and commercialAg NPs,this combination nanosystem of SWCNTs@mSiO2-TSD@Ag exhibits much stronger antibacterial performance against multi-drug-resistant bacteria Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)in vitro through damaging the bacterial cell membranes and a fast release of silver ions.Furthermore,the in vivo rat skin infection model verifies that SWCNTS@mSiO2-TSD@Ag have remarkably improved abilities of bacterial clearance,wound healing promoting as well as outstanding biocompatibility.Therefore,this novel nanoplatform indicates promising potentials as a safe and powerful tool for the treatment of clinical drug-resistant infections.
基金supported by the National Key R&D Program of China(2021YFB3800900)the National Natural Science Foundation of China(22122501,21875014 and 52073013)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910010024)。
文摘The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here,a series of flexible electrostatic hydrogels with excellent antibacterial ability were constructed using a mixture of nitric oxide(NO)-releasing nitrated chitosan(CSNO)and mesotetra(4-carboxyphenyl)porphine(TCPP)with salmon sperm DNA(ssDNA)solution.When cultured with gram-negative bacteria under solar simulator irradiation,TCPP-CSNO_(m)ssDNA_(n) hydrogels released reactive oxygen species(ROS)and NO to produce peroxynitrite ions(ONOO^(−)).ONOO−is efficient at killing bacteria,thereby improving the antimicrobial ability of photodynamic therapy against gram-negative bacteria.The hydrogels exhibited powerful antibacterial activity in vivo when used to treat skin infections caused by drugresistant bacteria,making them a promising candidate for clinical applications.A string of antibacterial hydrogels that release ROS and NO synergistically can bring new possibilities for effectively killing drug-resistant bacteria and be of great value in anti-infection wound dressings and other applications.
文摘Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.
基金supported by the start-up funding from Nankai University(to C.Z.)the National Natural Science Foundation of China(nos.52003123,21620102005,and 81722026)the CAMS Innovation Fund for Medical Sciences(no.2016-I2M-3-022).
文摘This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA complex exhibited a 12-fold enhancement of the molar extinction coefficient in the nearinfrared(NIR)region relative to aqueous cupric acetate.Inspired by this interesting finding,we formulated these photothermal materials into colloidally dispersed nanoparticles via a technique that combined nanoprecipitation and in situ surface polymerization for antibacterial studies.The resultant nanoparticles exhibited rapid and stable photothermal responses to NIR irradiation,with a 4-fold enhanced photothermal conversion efficiency relative to aqueous cupric acetate.Since a positively charged monomer was incorporated during in situ surface polymerization,these positively charged nanoparticles were ingested efficiently and subsequently digested by drug-resistant bacteria.By combining the LA-mediated membrane-damaging effect,copper-mediated Fenton-like reaction,as well as the photothermal effect of the copper–LA complex,a broad-spectrum,multimodal,and synergistic antibacterial effect was achieved both in vitro and in vivo,with the killing efficiency up to 99.99%for ampicillin-resistant Escherichia coli(Ampr E.coli)and 99.9999%for methicillinresistant Staphylococcus aureus(MRSA).Our newly developed nanobiocide represents a class of exceptional broad-spectrum antibacterial materials,holding great potential for treating drug-resistant infections in clinical settings.