BACKGROUND In recent years,there has been a significant increase in pyogenic liver abscesses(PLAs)caused by multidrug-resistant(MDR)Gram-negative bacteria(GNB),pre-dominantly Klebsiella pneumoniae and Escherichia coli...BACKGROUND In recent years,there has been a significant increase in pyogenic liver abscesses(PLAs)caused by multidrug-resistant(MDR)Gram-negative bacteria(GNB),pre-dominantly Klebsiella pneumoniae and Escherichia coli.AIM To clarify the clinical characteristics and risk factors associated with MDR-GNB-related PLAs,develop a predictive nomogram for personalized risk assessment,and enhance the timeliness of empirical antibiotic selection.METHODS Based on the antibiotic susceptibility profiles,enrolled patients were divided into two groups:A MDR group com-prising 105 individuals and a non-resistant group comprising 163 individuals.A systematic collection of demo-graphic characteristics,laboratory findings,and prognostic indicators was performed.A predictive nomogram was established using multivariate stepwise regression modeling.Model effectiveness was evaluated by examining its discriminative capability,calibration accuracy,and clinical utility through receiver operating characteristic curves with corresponding area under the curve values,calibration graphs,and decision curve analysis.Continuous data were analyzed using the independent-sample t-test if they met normality criteria;otherwise,the Wilcoxon rank-sum test was adopted.For categorical data,Fisher’s exact test was chosen when the expected count in any cell was below five;in all other instances,theχ2 test was applied.RESULTS This retrospective study analyzed clinical and laboratory data from 268 patients diagnosed with Gram-negative PLA at a major healthcare facility from January 2019 to February 2025.Among these,105 cases(39%)were asso-ciated with MDR-GNB,primarily Klebsiella pneumoniae(43%)and Escherichia coli(42%).Mixed infections were rare,accounting for only 3%of cases.Multivariate regression revealed five independent predictors of MDR-GNB liver abscesses:Age≥60 years,diabetes,presence of a malignant tumor,lower C-reactive protein levels,and prolonged prothrombin time.These variables were integrated into a nomogram to facilitate individualized risk assessment.CONCLUSION The results imply that being aged over 60,diabetes,malignant tumor,lower C-reactive protein levels,and higher prothrombin time levels can accurately forecast MDR-GNB infections in PLAs,highlighting the importance of early screening to enable more targeted antibiotic treatments.However,as this was a single-center study without external validation,the generalizability of our model remains limited.Future multicenter,multi-ethnic prospective studies are needed to validate and extend these findings.展开更多
Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosens...Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosensitizer have recently emerged and provided a promising approach for bacterial discrimination and efficient photodynamic antimicrobial applications.However,they often suffer from the shorter excitation wavelength and lower molar extinction coefficients in the visible region,severely limiting their further applications.Herein,three novel BF_(2)-curcuminoid-based AIE photosensitizers,TBBC,TBC and TBBC-C8,have been rationally designed and successfully developed,in which OCH_(3)-and OC_(8)H_(17)-substituted tetraphenylethene(TPE)groups serve as both electron donor(D)and AIE active moieties,BF_(2)bdk group functions as electron acceptor(A),and styrene(or ethylene)group asπ-bridge in this D-π-A-π-D system,respectively.As expected,these resulting BF_(2)-curcuminoids presented solvent-dependent photophysical properties with large molar extinction coefficients in solutions and excellent AIE properties.Notably,TBBC showed an effective singlet oxygen generation efficiency thanks to the smaller singlet-triplet energy gap(△E_(ST)),and remarkable photostability under green light exposure at 530nm(8.9 mW/cm^(2)).More importantly,TBBC was demonstrated effectiveness in selective staining and photodynamic killing of Escherichia coli(E.coli)in vitro probably due to its optimal molecular size compared with TBC and TBBC-C8.Therefore,TBBC will have great potential as a novel AIE photosensitizer to apply in the discrimination and selective sterilization between Gram-positive and Gram-negative bacteria.展开更多
Introduction: Bacterial skin and soft tissue infections (SSTIs) are a cause of frequent inpatient and outpatient care visits whose causative agents are associated with a high antimicrobial resistance burden. For insig...Introduction: Bacterial skin and soft tissue infections (SSTIs) are a cause of frequent inpatient and outpatient care visits whose causative agents are associated with a high antimicrobial resistance burden. For insights on antimicrobial susceptibilities in a rural setting, we examined specimens from suspected SSTIs from two public health facilities in Kenya. We additionally assessed antibiotic use, appropriateness of empiric therapy and risk factors for SSTI. Methodology: Between 2021 and 2023, 265 patients at Kisii and Nyamira County Referral hospitals were enrolled. Wound swabs/aspirates were collected and processed following standard microbiological procedures. Identification and antimicrobial susceptibility were performed using the VITEK 2 Compact platform. Demographic, clinical, and microbiological data were analyzed with R Statistical software. Results: S. aureus was isolated in 16.2% (43/265) of patients with a methicillin resistance (MRSA) proportion of 14% (6/43). While 13/15 drugs elicited susceptibilities ranging from 84% - 100%, penicillin (16%) and trimethoprim-sulfamethoxazole [TMP-SXT] (23%) yielded the lowest susceptibilities. Escherichia coli (n = 33), Klebsiella pneumoniae (n = 8), Pseudomonas aeruginosa (n = 8), and Citrobacter species (n = 4) were the most commonly isolated gram-negative species. Gram-negative strains showed high susceptibilities to most of the tested drugs (71% - 100%) with the exception of ampicillin (18%), TMP-SXT (33%), and first and second generation cephalosporins. Conclusions: The low MRSA prevalence and generally high antibiotic susceptibilities for S. aureus and gram-negative bacteria present opportunities for antibiotic stewardship in the study setting. Diminished susceptibilities against penicillin/ampicillin and TMP-SXT accord with prevailing local data and add a layer of evidence for their cautious empiric use.展开更多
BACKGROUND Immunosuppression is an important factor in the incidence of infections in transplant recipient.Few studies are available on the management of immunosuppression(IS)treatment in the liver transplant(LT)recip...BACKGROUND Immunosuppression is an important factor in the incidence of infections in transplant recipient.Few studies are available on the management of immunosuppression(IS)treatment in the liver transplant(LT)recipients complicated with infection.The aim of this study is to describe our experience in the management of IS treatment during bacterial bloodstream infection(BSI)in LT recipients and assess the effect of temporary IS withdrawal on 30 d mortality of recipients presenting with severe infection.AIM To assess the effect of temporary IS withdrawal on 30 d mortality of LT recipients presenting with severe infection.METHODS A retrospective study was conducted with patients diagnosed with BSI after LT in the Department of Liver Surgery,Renji Hospital from January 1,2016 through December 31,2017.All recipients diagnosed with BSI after LT were included.Univariate and multivariate Cox regression analysis of risk factors for 30 d mortality was conducted in the LT recipients with Gram-negative bacterial(GNB)infection.RESULTS Seventy-four episodes of BSI were identified in 70 LT recipients,including 45 episodes of Gram-positive bacterial(GPB)infections in 42 patients and 29 episodes of GNB infections in 28 patients.Overall,IS reduction(at least 50%dose reduction or cessation of one or more immunosuppressive agent)was made in 28(41.2%)cases,specifically,in 5(11.9%)cases with GPB infections and 23(82.1%)cases with GNB infections.The 180 d all-cause mortality rate was 18.5%(13/70).The mortality rate in GNB group(39.3%,11/28)was significantly higher than that in GPB group(4.8%,2/42)(P=0.001).All the deaths in GNB group were attributed to worsening infection secondary to IS withdrawal,but the deaths in GPB group were all due to graft-versus-host disease.GNB group was associated with significantly higher incidence of intra-abdominal infection,IS reduction,and complete IS withdrawal than GPB group(P<0.05).Cox regression showed that rejection(adjusted hazard ratio 7.021,P=0.001)and complete IS withdrawal(adjusted hazard ratio 12.65,P=0.019)were independent risk factors for 30 d mortality in patients with GNB infections after LT.CONCLUSION IS reduction is more frequently associated with GNB infection than GPB infection in LT recipients.Complete IS withdrawal should be cautious due to increased risk of mortality in LT recipients complicated with BSI.展开更多
Humanity is facing an enormous and growing worldwide threat from the emergence of multi-drug-resistant(MDR)Gram-negative bacteria such as Escherichia coli,Klebsiella pneumoniae,and Acinetobacter baumannii.Polymyxin B ...Humanity is facing an enormous and growing worldwide threat from the emergence of multi-drug-resistant(MDR)Gram-negative bacteria such as Escherichia coli,Klebsiella pneumoniae,and Acinetobacter baumannii.Polymyxin B and E(colistin)constitute the last-line therapies for treating MDR Gram-negative bacteria.Polymyxin is a cationic antibacterial peptide that can destroy the outer membrane of Gram-negative bacteria.With the increasing clinical application of polymyxin,however,there have been many reports of the occurrence of polymyxin-resistant Gram-negative bacteria.This resistance is mainly mediated by the modification or complete loss of lipopolysaccharide(LPS).LPS is also a virulence factor of Gram-negative bacteria,and alterations of LPS may correlate with virulence.Although it is generally believed that the biological costs associated with drug resistance may enable benign susceptible bacteria to overcome resistant bacteria when antibiotic pressure is reduced,some studies have shown that polymyxin-resistant bacteria are associated with higher virulence and greater fitness compared with their susceptible counterparts.To predict the development of polymyxin resis-tance and evaluate interventions for its mitigation,it is important to understand the relative biological cost of polymyxin resistance compared with susceptibility.The impact of polymyxin resistance mecha-nisms on the virulence and fitness of these three Gram-negative bacteria are summarized in this review.展开更多
PCR and DNA sequencing were used to screen and characterize integrons and resistance genes in Gram-negative bacteria isolated from seafood products in Japan.A total of 215 Gram-negative bacteria were isolated from loc...PCR and DNA sequencing were used to screen and characterize integrons and resistance genes in Gram-negative bacteria isolated from seafood products in Japan.A total of 215 Gram-negative bacteria were isolated from local and imported seafood samples collected from retail markets in Hiroshima Prefecture.Class 1 integrons containing gene cassettes encoding resistance to trimethoprim展开更多
The incidence of gram-negative multidrug-resistant(MDR) bacterial pathogens is increasing in hospitals and particularly in the intensive care unit(ICU) setting. The clinical consequences of infections caused by MDR pa...The incidence of gram-negative multidrug-resistant(MDR) bacterial pathogens is increasing in hospitals and particularly in the intensive care unit(ICU) setting. The clinical consequences of infections caused by MDR pathogens remain controversial. The purpose of this review is to summarize the available data concerning the impact of these infections on mortality in ICU patients. Twenty-four studies, conducted exclusively in ICU patients, were identified through Pub Med search over the years 2000-2015. Bloodstream infection was the only infection examined in eight studies, respiratory infections in four and variable infections in others. Comparative data on the appropriateness of empirical antibiotic treatment were provided by only seven studies. In ten studies the presence of antimicrobial resistance was not associated with increased mortality; on the contrary, in other studies a significant impact of antibiotic resistance on mortality was found, though, sometimes, mediated by inappropriate antimicrobial treatment. Therefore, a direct association between infections due to gram-negative MDR bacteria and mortality in ICU patients cannot be confirmed. Sample size, presence of multiple confounders and other methodological issues may influence the results. These data support the need for further studies to elucidate the real impact of infections caused by resistant bacteria in ICU patients.展开更多
Protein secretion plays an important role in bacterial lifestyles. In Gram-negative bacteria, a wide range of proteins are secreted to modulate the interactions of bacteria with their environments and other bacteria v...Protein secretion plays an important role in bacterial lifestyles. In Gram-negative bacteria, a wide range of proteins are secreted to modulate the interactions of bacteria with their environments and other bacteria via various secretion systems. These proteins are essential for the virulence of bacteria, so it is crucial to study them for the pathogenesis of diseases and the development of drugs. Using amino acid composition (AAC), position-specific scoring matrix (PSSM) and N-terminal signal peptides, two different substitution models are firstly constructed to transform protein sequences into numerical vectors. Then, based on support vector machine (SVM) and the “one to one”?algorithm, a hybrid multi-classifier named SecretP v.2.2 is proposed to rapidly and accurately?distinguish different types of Gram-negative?bacterial secreted proteins. When performed on the same test set for a comparison with other methods, SecretP v.2.2 gets the highest total sensitivity of 93.60%. A public independent dataset is used to further test the power of SecretP v.2.2 for predicting NCSPs, it also yields satisfactory results.展开更多
Objective:To detect and evaluate the various methods for metallo-β-lactamases(MBL) production in Pseudomonas aeruginosa(P.aeruginosa) and Acinetobacter species.Methods:A total of 109 P.aeruginosa and 85 Acinetobacter...Objective:To detect and evaluate the various methods for metallo-β-lactamases(MBL) production in Pseudomonas aeruginosa(P.aeruginosa) and Acinetobacter species.Methods:A total of 109 P.aeruginosa and 85 Acinetobacter species were screened for imipenem resistance by Kirby- Bauer disc diffusion methods.Detection of MBL production was(lone by imipenem-EDTA combined disc test,double disc synerygy test(DDST) and imipenem-EDTA MBL E test.Results: A total of 63(57.8%) strains of P.aeruginosa and 46(54.1%) strains of Acinetobacter spp.were found to be resistant to imipenem.Of the 63 imipenem resistant P.aeruginosa tested for MBL production.44(69.89;) were found to be positive and among 46 imipenem resistant Acinetobacter. 19(41.3%) were shown to be the MBL producers.Conclusions:Imipenem-EDTA combined disc test and MBL E test are equally effective for MBL detection in both P.aeruginosa and Acinetobacter spp.,but given the cost-constraints,combined disc can be used as a convenient screening method in the clinical microbiology laboratory.展开更多
Over the past years, infectious disease has caused enormous economic loss in pig industry. Among the pathogens, gram negative bacteria not only cause inflammation, but also cause different diseases and make the pigs m...Over the past years, infectious disease has caused enormous economic loss in pig industry. Among the pathogens, gram negative bacteria not only cause inflammation, but also cause different diseases and make the pigs more susceptible to virus infection. Vaccination, medication and elimination of sick pigs are major strategies of controlling disease. Genetic methods, such as selection of disease resistance in the pig, have not been widely used. Recently, the completion of the porcine whole genome sequencing has provided powerful tools to identify the genome regions that harboring genes controlling disease or immunity. Immunogenornics, which combines DNA variations, transcriptorne, immune response, and QTL mapping data to illustrate the interactions between pathogen and host immune system, will be an effective genomics tool for identification of disease resistance genes in pigs. These genes will be potential targets for disease resistance in breeding programs. This paper reviewed the progress of disease resistance study in the pig focusing on Gram-negative bacilli. Major porcine Gram-negative bacilli and diseases, suggested candidate genes/pathways against porcine Gram-negative bacilli, and distributions of QTLs for immune capacity on pig chromosomes were summarized. Some tools for immunogenomics research were described. We conclude that integration of sequencing, whole genome associations, functional genomics studies, and immune response information is necessary to illustrate molecular mechanisms and key genes in disease resistance.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
Methylation of 16S rRNA is an important mechanism of aminoglycoside resistance among gram-negative pathogens. In this report, 16S rRNA methylase genes were amplified using PCR among gram-negative bacillus isolates fro...Methylation of 16S rRNA is an important mechanism of aminoglycoside resistance among gram-negative pathogens. In this report, 16S rRNA methylase genes were amplified using PCR among gram-negative bacillus isolates from hospitals in the Changchun area of China and 16S rRNA methylase genotypes (armA, rmtB, rmtA, rmtC, rmtD, and npmA) were identified by direct sequencing. Fifty of the isolates (43.1%) harbored 16S rRNA methylase genes. The common 16S rRNA methylase genes were armA and rmtB (12.1% and 31.0%, respectively), whereas the rmtA, rmtC, rmtD, and npmA genes were absent from the sample. It suggests that the predominant 16S rRNA methylase genes among gramnegative bacilli in the Changchun area are armA and rmtB.展开更多
Antibiotic resistant bacteria pathogens remain the leading cause of shellfish borne diseases and a major health threat to humans worldwide. The objectives of this study were to isolate, identify, and determine the ant...Antibiotic resistant bacteria pathogens remain the leading cause of shellfish borne diseases and a major health threat to humans worldwide. The objectives of this study were to isolate, identify, and determine the antibiotic resistance patterns of Gram-negative bacteria from shellfish. We analyzed a total of 540 shellfish (117 clams, 88 oysters, and 136 periwinkles) samples collected from different vendors at Iko and Douglas Creeks in Akwa Ibom State, South-South Nigeria. Conventional cultural techniques, morphological, biochemical characteristics, and PCR amplification were used to identify the bacterial isolates. Antibiotic susceptibility tests (Kirby-Bauer disk diffusion method) and ESBL phenotype (disk) of the isolates were performed. One hundred and thirty-five (135) Gram-negative bacteria comprising 5 genera and 14 species were detected at a prevalence of: <i>Alcaligenes faecalis</i> <i><b>TRB</b></i>-7 38 (28.2%), <i>Pseudomonas oryzihabitans strain <b>KCB</i>005</b> 16 (11.9%), <i>Paenalcaligenes retgerii strain <b>B</i>5</b> 12 (8.9%) <i>Pseudomonas aeruginosa <b>JB</i>2</b> 10 (7.4%), <i>Providencia stuartii <b>DMC</i>-28b</b> 9 (6.7%), <i>Alcaligenes species <b>TLT</i>151</b> 8 (5.9%), <i>Pseudomonas aeruginosa <b>CIFRI DTSB</i>1</b> 7 (5.2%), <i>Paenalcaligenes species <b>UN</i>24</b> 7 (5.2%), <i>Alcaligenes faecalis <b>BT</i>10</b> 7 (5.2%), <i>Vibrio species strain <b>PrVy</i>108</b> 6 (4.4%), <i>Pseudomonas xiamenensis <b>C</i>10-2</b> 5 (3.7%), <i>Providencia vemicola <b>Bu</i>15_38</b> 4 (2.9%), <i>Pseudomonas anguillisceptica</i> <b>4029</b> 3 (2.2%), and <i>Pseudomonas aeruginosa <b>N</i>15-01092</b> 3 (2.2%). All tested isolates showed various degrees of resistance to the thirteen antimicrobials evaluated. High levels of resistance (100%) to cefepime and imipenem were expressed by all isolates except the <i>Providencia</i> species. For the EBSL indicators, all isolates apart from <i>Alcaligenes</i> species were resistant (100%) to ceftriaxone. All <i>Vibrio</i> species were susceptible to norfloxacin, nalidixic acid, and ceftazidime. The identification of antibiotic resistant Gram-negative bacteria (GNARB) from shellfish in this study highlights the risk of disseminated multi-drug resistance—a serious public health concern.展开更多
<b>Background:</b> The increasing resistance of bacteria to various antibiotics is a worldwide public health issue. Carbapenems that have elicited great hope in treating infections caused by multidrug-resi...<b>Background:</b> The increasing resistance of bacteria to various antibiotics is a worldwide public health issue. Carbapenems that have elicited great hope in treating infections caused by multidrug-resistant germs have seen their efficacy narrowed over time with the emergence of other novel resistance mechanisms, notably the production of Carbapenemases. <b>Methods:</b> A prospective cross-sectional study was conducted from May 2017 to May 2018 in Douala (Cameroon) to detect carbapenemase-producing Gram-negative bacilli. Isolated strains were identified using the Vitek2<sup>TM</sup> system. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method on agar plates with 20 selected commercially available antibiotic discs. The bacterial strains were tested for the production of three Carbapenemases (OXA-48, NDM, KPC), using an immuno-chromatographic technique, with the “RESIST-3 O.K.N. K-SeT” rapid detection kit. <b>Results:</b> During the study period, 1687 strains of Gram-negative bacilli were isolated in selected laboratories with a total of 200 multi-resistant strains identified (11.9%). Among the multi-resistant strains, <i>E. coli</i> was the species most represented in <i>Enterobacteriaceae</i> (27.5%) followed by <i>K. pneumoniae</i> (15.5%) and the non-fermenting Gram-negative bacilli were predominantly <i>P. aeruginosa</i> (20.5%). These strains mainly came from urine and pus, <i>i.e.</i> 41% and 32% respectively. Thirty-two (16%) strains produced one of the Carbapenemases with a higher frequency at the General Hospital (84%). NDM-type carbapenemase was the most frequently identified (8.5%), OXA-48 type 7.5%, and no KPC production was observed. Among the <i>Enterobacteriaceae</i> 22.9% produced Carbapenemases and only 5.1% of the non-fermenting bacilli produced these enzymes. The isolates strains were completely resistant to all antibiotics except Amikacin and Fosfomycin. The strains producing the NDM-type carbapenemase showed higher rates of resistance to almost all of the antibiotics tested. <b>Conclusion:</b> Multidrug-resistant strains are experiencing an increase in evolution. The apparition of strains producing Carbapenemases prominently, the NDM and OXA-48 favor this increase. The activities of antibiotics with high efficacies on these strains are low.展开更多
The purpose of this study was to critically evaluate the impact of an institutional blood culture notification protocol called RAIDS （rapid administration of antimicrobials by an infectious diseases specialist） on t...The purpose of this study was to critically evaluate the impact of an institutional blood culture notification protocol called RAIDS （rapid administration of antimicrobials by an infectious diseases specialist） on time to optimization of antimicrobial therapy in hospitalized patients with gram-negative bacteremia. Time to antibiotic optimization was compared in patients with gram-negative bacilli isolated from blood cultures obtained from March-May 2011 （pre-RAIDS） versus March-May 2013 （post-RAIDS）. The results show that patients in the pre-RAIDS study group had a significantly longer time to antibiotic optimization when compared to the post-RAIDS group （median （IQR）, 27.6 （10.8-75.8） h vs. 3.1 （0.8-34.3） h, p = 0.03）. The RAIDS protocol resulted in quicker time to antibiotic de-escalation （pre- vs. post-RAIDS; median （IQR）, 27.6 （10.8-134.5） h vs. 4.3 （1.4-32.6） h, p = 0.03）. There were no differences in clinical outcomes such as clinical cure, microbiological cure, and 30-day mortality between pre-RAIDS and post-RAIDS study groups. Patients in the post-RAIDS arm were more likely to receive appropriate empiric and definitive treatment. Implementation of the RAIDS protocol, which was an ASP （antimicrobial stewardship program） initiative, resulted in quicker time to antibiotic de-escalation and overall treatment optimization. RAIDS reduced the unnecessary use of broad-spectrum antimicrobial in this study population.展开更多
Objective: To compare the serum contents of inflammatory mediators and oxidative stress mediators between patients with gram-positive bacteria and gram-negative bacteria infection. Methods: Patients who were diagnosed...Objective: To compare the serum contents of inflammatory mediators and oxidative stress mediators between patients with gram-positive bacteria and gram-negative bacteria infection. Methods: Patients who were diagnosed with bloodstream bacterial infection in Zigong Third People's Hospital between March 2015 and April 2017 were selected as the research subjects and divided into gram-positive group and gram-negative group according to the results of blood culture and strain identification, and serum levels of inflammatory mediators PCT, IL-1β, IL-6, sTREM-1, TNF-α, NGAL, SAA, HPT and hs-CRP as well as oxidative stress mediators MDA, AOPP, TAC, CAT and SOD were determined. Results: Serum PCT, IL-1β, IL-6, sTREM-1, TNF-α, NGAL, SAA, HPT, hs-CRP, MDA and AOPP levels of gram-negative group were greatly higher than those of gram-positive group while TAC, CAT and SOD levels were greatly lower than those of gram-positive group. Conclusion: The changes of inflammatory mediators and oxidative stress mediators in the serum of patients with gram-negative bacteria infection are more significant than those of patients with gram-positive bacteria infection.展开更多
Objective: to explore the clinical characteristics and risk factors of blood stream infection in carbapenem-negative bacteria. Methods: in this study, 140 patients with suspected carbapenem-resistant gram-negative bac...Objective: to explore the clinical characteristics and risk factors of blood stream infection in carbapenem-negative bacteria. Methods: in this study, 140 patients with suspected carbapenem-resistant gram-negative bacteria were included in the study, and their clinical characteristics and risk factors were recorded. Results: clinical characteristics: ICU and blood surgery strains. Risk factors: 2 groups had no obvious differences in liver, gallbladder and pancreatic disease, diabetes, malignant hematological system diseases, three basic diseases, impaired immune function, invasive diagnosis and treatment operation, solid tumors, urinary system disease, chronic lung disease, carbapenem exposure history, and CVC catheterization level, not statistically significant;2 groups had significant differences in the ICU admission history, indwelling PICC tubes, and the length of hospitalization before the bloodstream infection patients occurred (p <0.05). Conclusion: the analysis of carbapenem-resistant gram-negative bacteria, its clinical emergence of risk factors is unifactorial to multifactorial, univariate, involving more diseases than multifactorial diseases. By summarizing the clinical characteristics and risk factors of bloodstream infection in carbapenem-resistant gram-negative bacteria, can provide support for infection prevention.展开更多
Dynobactin A is a ribosomally synthesized and posttranslationally modified peptide(RiPP)antibiotic that displays potent activity against Gram-negative bacteria.This compound features a bicyclic scaffold consisting of ...Dynobactin A is a ribosomally synthesized and posttranslationally modified peptide(RiPP)antibiotic that displays potent activity against Gram-negative bacteria.This compound features a bicyclic scaffold consisting of a C–C crosslink between Trp1 and Asn4,and a highly unique N–C crosslink between His6 and Tyr8.In this study,we successfully reconstituted the activity of the radical S-adenosylmethionine(SAM)enzyme DynA both in vivo and in vitro,demonstrating that it catalyzes the formation of both C–C and N–C crosslinks in dynobactin A.Biochemical studies and mutagenesis analysis support that the N–C crosslink is formed via a para-quinone methide intermediate,representing an unprecedented mechanism in RiPP biosynthesis.We also showed DynA catalysis proceeds in a stepwise manner,where the N–C crosslink is formed first,followed by a C–C crosslink.These findings provide new insights into radical SAM enzyme chemistry and open avenues for engineering novel RiPP antibiotics targeting Gram-negative bacteria.展开更多
Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity,expanding antibacterial spectra,and reducing required dosages.Previously,compound 15 was identified as a potential adjuvant for Poly...Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity,expanding antibacterial spectra,and reducing required dosages.Previously,compound 15 was identified as a potential adjuvant for Polymyxin B(PB)against multidrug-resistant(MDR)Pseudomonas aeruginosa DK2;however,its clinical utility was hindered by high cytotoxicity,uncertain in vivo efficacy,and an unclear synergetic mechanism.To address these challenges,we synthesized and evaluated a series of novel benzamide derivatives,with A22 emerging as a particularly promising candidate.A22 demonstrated potent synergistic activity to PB,minimal cytotoxicity,improved water solubility,and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains.In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22.Moreover,A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2.Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production,reducing ATP levels,increasing NOX activity,and inhibiting biofilm formation,leading to bacterial death.These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants,offering a robust approach to combating MDR Gram-negative bacterial infections.展开更多
Multidrug-resistant(MDR)gram-negative bacteria(GNB)are responsible for high mortality and morbidity in health care settings world-wide.They have been declared as priority pathogens by the WHO for their continuously es...Multidrug-resistant(MDR)gram-negative bacteria(GNB)are responsible for high mortality and morbidity in health care settings world-wide.They have been declared as priority pathogens by the WHO for their continuously escalating antimicrobial resistance.Neverthe-less,data associated with MDR GNB in health care–associated infections are insufficient.Surgical site infections(SSIs)are among the most commonly occurring health care–associated infections.Such infections are particularly common when bacteria from a patient’s normal microflora are transferred to the surgical sites during surgical procedures.SSIs affect approximately 0.5%–3%of patients under-going surgery,resulting in prolonged hospital stays compared with patients without SSIs.SSIs result in severe problems and lead to a heavy economic burden.Most SSIs can be avoided if suitable preventive measures are employed.Novel findings support the dedicated usage of oral preoperative surgical antimicrobial prophylaxis for specific surgeries based on sites/organs.Immediate interventions are sought to control the transmission of MDR GNB typically found in hospital settings.The present narrative review aims to describe MDR GNB in SSIs in different sites.Antimicrobial resistance epidemiology and preventive measures for SSIs are also discussed.Differ-ent intrinsic and extrinsic factors and control measures are elaborated for curbing SSIs.展开更多
文摘BACKGROUND In recent years,there has been a significant increase in pyogenic liver abscesses(PLAs)caused by multidrug-resistant(MDR)Gram-negative bacteria(GNB),pre-dominantly Klebsiella pneumoniae and Escherichia coli.AIM To clarify the clinical characteristics and risk factors associated with MDR-GNB-related PLAs,develop a predictive nomogram for personalized risk assessment,and enhance the timeliness of empirical antibiotic selection.METHODS Based on the antibiotic susceptibility profiles,enrolled patients were divided into two groups:A MDR group com-prising 105 individuals and a non-resistant group comprising 163 individuals.A systematic collection of demo-graphic characteristics,laboratory findings,and prognostic indicators was performed.A predictive nomogram was established using multivariate stepwise regression modeling.Model effectiveness was evaluated by examining its discriminative capability,calibration accuracy,and clinical utility through receiver operating characteristic curves with corresponding area under the curve values,calibration graphs,and decision curve analysis.Continuous data were analyzed using the independent-sample t-test if they met normality criteria;otherwise,the Wilcoxon rank-sum test was adopted.For categorical data,Fisher’s exact test was chosen when the expected count in any cell was below five;in all other instances,theχ2 test was applied.RESULTS This retrospective study analyzed clinical and laboratory data from 268 patients diagnosed with Gram-negative PLA at a major healthcare facility from January 2019 to February 2025.Among these,105 cases(39%)were asso-ciated with MDR-GNB,primarily Klebsiella pneumoniae(43%)and Escherichia coli(42%).Mixed infections were rare,accounting for only 3%of cases.Multivariate regression revealed five independent predictors of MDR-GNB liver abscesses:Age≥60 years,diabetes,presence of a malignant tumor,lower C-reactive protein levels,and prolonged prothrombin time.These variables were integrated into a nomogram to facilitate individualized risk assessment.CONCLUSION The results imply that being aged over 60,diabetes,malignant tumor,lower C-reactive protein levels,and higher prothrombin time levels can accurately forecast MDR-GNB infections in PLAs,highlighting the importance of early screening to enable more targeted antibiotic treatments.However,as this was a single-center study without external validation,the generalizability of our model remains limited.Future multicenter,multi-ethnic prospective studies are needed to validate and extend these findings.
基金National Natural Science Foundation of China(No.32101150)Key Scientific Research Project of Higher Education of Henan Province(No.22A430007)+2 种基金Natural Science Foundation of Henan Province(No.222300420501)the Science and Technology Project of Henan Province(No.242102230119)Innovation and Entrepreneurship Training Program for College students in China(No.202310482001).
文摘Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosensitizer have recently emerged and provided a promising approach for bacterial discrimination and efficient photodynamic antimicrobial applications.However,they often suffer from the shorter excitation wavelength and lower molar extinction coefficients in the visible region,severely limiting their further applications.Herein,three novel BF_(2)-curcuminoid-based AIE photosensitizers,TBBC,TBC and TBBC-C8,have been rationally designed and successfully developed,in which OCH_(3)-and OC_(8)H_(17)-substituted tetraphenylethene(TPE)groups serve as both electron donor(D)and AIE active moieties,BF_(2)bdk group functions as electron acceptor(A),and styrene(or ethylene)group asπ-bridge in this D-π-A-π-D system,respectively.As expected,these resulting BF_(2)-curcuminoids presented solvent-dependent photophysical properties with large molar extinction coefficients in solutions and excellent AIE properties.Notably,TBBC showed an effective singlet oxygen generation efficiency thanks to the smaller singlet-triplet energy gap(△E_(ST)),and remarkable photostability under green light exposure at 530nm(8.9 mW/cm^(2)).More importantly,TBBC was demonstrated effectiveness in selective staining and photodynamic killing of Escherichia coli(E.coli)in vitro probably due to its optimal molecular size compared with TBC and TBBC-C8.Therefore,TBBC will have great potential as a novel AIE photosensitizer to apply in the discrimination and selective sterilization between Gram-positive and Gram-negative bacteria.
文摘Introduction: Bacterial skin and soft tissue infections (SSTIs) are a cause of frequent inpatient and outpatient care visits whose causative agents are associated with a high antimicrobial resistance burden. For insights on antimicrobial susceptibilities in a rural setting, we examined specimens from suspected SSTIs from two public health facilities in Kenya. We additionally assessed antibiotic use, appropriateness of empiric therapy and risk factors for SSTI. Methodology: Between 2021 and 2023, 265 patients at Kisii and Nyamira County Referral hospitals were enrolled. Wound swabs/aspirates were collected and processed following standard microbiological procedures. Identification and antimicrobial susceptibility were performed using the VITEK 2 Compact platform. Demographic, clinical, and microbiological data were analyzed with R Statistical software. Results: S. aureus was isolated in 16.2% (43/265) of patients with a methicillin resistance (MRSA) proportion of 14% (6/43). While 13/15 drugs elicited susceptibilities ranging from 84% - 100%, penicillin (16%) and trimethoprim-sulfamethoxazole [TMP-SXT] (23%) yielded the lowest susceptibilities. Escherichia coli (n = 33), Klebsiella pneumoniae (n = 8), Pseudomonas aeruginosa (n = 8), and Citrobacter species (n = 4) were the most commonly isolated gram-negative species. Gram-negative strains showed high susceptibilities to most of the tested drugs (71% - 100%) with the exception of ampicillin (18%), TMP-SXT (33%), and first and second generation cephalosporins. Conclusions: The low MRSA prevalence and generally high antibiotic susceptibilities for S. aureus and gram-negative bacteria present opportunities for antibiotic stewardship in the study setting. Diminished susceptibilities against penicillin/ampicillin and TMP-SXT accord with prevailing local data and add a layer of evidence for their cautious empiric use.
基金Supported by the National Key R&D Precision Medicine Program,No.2017YFC0908100Shanghai Key Clinical Specialty Grant,No.Shslczdzk05801.
文摘BACKGROUND Immunosuppression is an important factor in the incidence of infections in transplant recipient.Few studies are available on the management of immunosuppression(IS)treatment in the liver transplant(LT)recipients complicated with infection.The aim of this study is to describe our experience in the management of IS treatment during bacterial bloodstream infection(BSI)in LT recipients and assess the effect of temporary IS withdrawal on 30 d mortality of recipients presenting with severe infection.AIM To assess the effect of temporary IS withdrawal on 30 d mortality of LT recipients presenting with severe infection.METHODS A retrospective study was conducted with patients diagnosed with BSI after LT in the Department of Liver Surgery,Renji Hospital from January 1,2016 through December 31,2017.All recipients diagnosed with BSI after LT were included.Univariate and multivariate Cox regression analysis of risk factors for 30 d mortality was conducted in the LT recipients with Gram-negative bacterial(GNB)infection.RESULTS Seventy-four episodes of BSI were identified in 70 LT recipients,including 45 episodes of Gram-positive bacterial(GPB)infections in 42 patients and 29 episodes of GNB infections in 28 patients.Overall,IS reduction(at least 50%dose reduction or cessation of one or more immunosuppressive agent)was made in 28(41.2%)cases,specifically,in 5(11.9%)cases with GPB infections and 23(82.1%)cases with GNB infections.The 180 d all-cause mortality rate was 18.5%(13/70).The mortality rate in GNB group(39.3%,11/28)was significantly higher than that in GPB group(4.8%,2/42)(P=0.001).All the deaths in GNB group were attributed to worsening infection secondary to IS withdrawal,but the deaths in GPB group were all due to graft-versus-host disease.GNB group was associated with significantly higher incidence of intra-abdominal infection,IS reduction,and complete IS withdrawal than GPB group(P<0.05).Cox regression showed that rejection(adjusted hazard ratio 7.021,P=0.001)and complete IS withdrawal(adjusted hazard ratio 12.65,P=0.019)were independent risk factors for 30 d mortality in patients with GNB infections after LT.CONCLUSION IS reduction is more frequently associated with GNB infection than GPB infection in LT recipients.Complete IS withdrawal should be cautious due to increased risk of mortality in LT recipients complicated with BSI.
基金supported by the National Key Research and Development Program of China (2017YFC1600100 and2017YFC1200203)the National Natural Science Foundation of China (81702040)the National Science Foundation of Zhejiang Province,China (LY20H190002)
文摘Humanity is facing an enormous and growing worldwide threat from the emergence of multi-drug-resistant(MDR)Gram-negative bacteria such as Escherichia coli,Klebsiella pneumoniae,and Acinetobacter baumannii.Polymyxin B and E(colistin)constitute the last-line therapies for treating MDR Gram-negative bacteria.Polymyxin is a cationic antibacterial peptide that can destroy the outer membrane of Gram-negative bacteria.With the increasing clinical application of polymyxin,however,there have been many reports of the occurrence of polymyxin-resistant Gram-negative bacteria.This resistance is mainly mediated by the modification or complete loss of lipopolysaccharide(LPS).LPS is also a virulence factor of Gram-negative bacteria,and alterations of LPS may correlate with virulence.Although it is generally believed that the biological costs associated with drug resistance may enable benign susceptible bacteria to overcome resistant bacteria when antibiotic pressure is reduced,some studies have shown that polymyxin-resistant bacteria are associated with higher virulence and greater fitness compared with their susceptible counterparts.To predict the development of polymyxin resis-tance and evaluate interventions for its mitigation,it is important to understand the relative biological cost of polymyxin resistance compared with susceptibility.The impact of polymyxin resistance mecha-nisms on the virulence and fitness of these three Gram-negative bacteria are summarized in this review.
基金supported by a Grant-in-Aid for Scientific Research(No.25460532 and 26.04912)to Tadashi S.from the Ministry of Education,Culture,Sports,Science,and Technology of Japan
文摘PCR and DNA sequencing were used to screen and characterize integrons and resistance genes in Gram-negative bacteria isolated from seafood products in Japan.A total of 215 Gram-negative bacteria were isolated from local and imported seafood samples collected from retail markets in Hiroshima Prefecture.Class 1 integrons containing gene cassettes encoding resistance to trimethoprim
文摘The incidence of gram-negative multidrug-resistant(MDR) bacterial pathogens is increasing in hospitals and particularly in the intensive care unit(ICU) setting. The clinical consequences of infections caused by MDR pathogens remain controversial. The purpose of this review is to summarize the available data concerning the impact of these infections on mortality in ICU patients. Twenty-four studies, conducted exclusively in ICU patients, were identified through Pub Med search over the years 2000-2015. Bloodstream infection was the only infection examined in eight studies, respiratory infections in four and variable infections in others. Comparative data on the appropriateness of empirical antibiotic treatment were provided by only seven studies. In ten studies the presence of antimicrobial resistance was not associated with increased mortality; on the contrary, in other studies a significant impact of antibiotic resistance on mortality was found, though, sometimes, mediated by inappropriate antimicrobial treatment. Therefore, a direct association between infections due to gram-negative MDR bacteria and mortality in ICU patients cannot be confirmed. Sample size, presence of multiple confounders and other methodological issues may influence the results. These data support the need for further studies to elucidate the real impact of infections caused by resistant bacteria in ICU patients.
文摘Protein secretion plays an important role in bacterial lifestyles. In Gram-negative bacteria, a wide range of proteins are secreted to modulate the interactions of bacteria with their environments and other bacteria via various secretion systems. These proteins are essential for the virulence of bacteria, so it is crucial to study them for the pathogenesis of diseases and the development of drugs. Using amino acid composition (AAC), position-specific scoring matrix (PSSM) and N-terminal signal peptides, two different substitution models are firstly constructed to transform protein sequences into numerical vectors. Then, based on support vector machine (SVM) and the “one to one”?algorithm, a hybrid multi-classifier named SecretP v.2.2 is proposed to rapidly and accurately?distinguish different types of Gram-negative?bacterial secreted proteins. When performed on the same test set for a comparison with other methods, SecretP v.2.2 gets the highest total sensitivity of 93.60%. A public independent dataset is used to further test the power of SecretP v.2.2 for predicting NCSPs, it also yields satisfactory results.
文摘Objective:To detect and evaluate the various methods for metallo-β-lactamases(MBL) production in Pseudomonas aeruginosa(P.aeruginosa) and Acinetobacter species.Methods:A total of 109 P.aeruginosa and 85 Acinetobacter species were screened for imipenem resistance by Kirby- Bauer disc diffusion methods.Detection of MBL production was(lone by imipenem-EDTA combined disc test,double disc synerygy test(DDST) and imipenem-EDTA MBL E test.Results: A total of 63(57.8%) strains of P.aeruginosa and 46(54.1%) strains of Acinetobacter spp.were found to be resistant to imipenem.Of the 63 imipenem resistant P.aeruginosa tested for MBL production.44(69.89;) were found to be positive and among 46 imipenem resistant Acinetobacter. 19(41.3%) were shown to be the MBL producers.Conclusions:Imipenem-EDTA combined disc test and MBL E test are equally effective for MBL detection in both P.aeruginosa and Acinetobacter spp.,but given the cost-constraints,combined disc can be used as a convenient screening method in the clinical microbiology laboratory.
基金supported by National Natural Science Foundation of China(30901021)863the Key Programs for Science and Technology Development of Hubei Province
文摘Over the past years, infectious disease has caused enormous economic loss in pig industry. Among the pathogens, gram negative bacteria not only cause inflammation, but also cause different diseases and make the pigs more susceptible to virus infection. Vaccination, medication and elimination of sick pigs are major strategies of controlling disease. Genetic methods, such as selection of disease resistance in the pig, have not been widely used. Recently, the completion of the porcine whole genome sequencing has provided powerful tools to identify the genome regions that harboring genes controlling disease or immunity. Immunogenornics, which combines DNA variations, transcriptorne, immune response, and QTL mapping data to illustrate the interactions between pathogen and host immune system, will be an effective genomics tool for identification of disease resistance genes in pigs. These genes will be potential targets for disease resistance in breeding programs. This paper reviewed the progress of disease resistance study in the pig focusing on Gram-negative bacilli. Major porcine Gram-negative bacilli and diseases, suggested candidate genes/pathways against porcine Gram-negative bacilli, and distributions of QTLs for immune capacity on pig chromosomes were summarized. Some tools for immunogenomics research were described. We conclude that integration of sequencing, whole genome associations, functional genomics studies, and immune response information is necessary to illustrate molecular mechanisms and key genes in disease resistance.
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.
文摘Methylation of 16S rRNA is an important mechanism of aminoglycoside resistance among gram-negative pathogens. In this report, 16S rRNA methylase genes were amplified using PCR among gram-negative bacillus isolates from hospitals in the Changchun area of China and 16S rRNA methylase genotypes (armA, rmtB, rmtA, rmtC, rmtD, and npmA) were identified by direct sequencing. Fifty of the isolates (43.1%) harbored 16S rRNA methylase genes. The common 16S rRNA methylase genes were armA and rmtB (12.1% and 31.0%, respectively), whereas the rmtA, rmtC, rmtD, and npmA genes were absent from the sample. It suggests that the predominant 16S rRNA methylase genes among gramnegative bacilli in the Changchun area are armA and rmtB.
文摘Antibiotic resistant bacteria pathogens remain the leading cause of shellfish borne diseases and a major health threat to humans worldwide. The objectives of this study were to isolate, identify, and determine the antibiotic resistance patterns of Gram-negative bacteria from shellfish. We analyzed a total of 540 shellfish (117 clams, 88 oysters, and 136 periwinkles) samples collected from different vendors at Iko and Douglas Creeks in Akwa Ibom State, South-South Nigeria. Conventional cultural techniques, morphological, biochemical characteristics, and PCR amplification were used to identify the bacterial isolates. Antibiotic susceptibility tests (Kirby-Bauer disk diffusion method) and ESBL phenotype (disk) of the isolates were performed. One hundred and thirty-five (135) Gram-negative bacteria comprising 5 genera and 14 species were detected at a prevalence of: <i>Alcaligenes faecalis</i> <i><b>TRB</b></i>-7 38 (28.2%), <i>Pseudomonas oryzihabitans strain <b>KCB</i>005</b> 16 (11.9%), <i>Paenalcaligenes retgerii strain <b>B</i>5</b> 12 (8.9%) <i>Pseudomonas aeruginosa <b>JB</i>2</b> 10 (7.4%), <i>Providencia stuartii <b>DMC</i>-28b</b> 9 (6.7%), <i>Alcaligenes species <b>TLT</i>151</b> 8 (5.9%), <i>Pseudomonas aeruginosa <b>CIFRI DTSB</i>1</b> 7 (5.2%), <i>Paenalcaligenes species <b>UN</i>24</b> 7 (5.2%), <i>Alcaligenes faecalis <b>BT</i>10</b> 7 (5.2%), <i>Vibrio species strain <b>PrVy</i>108</b> 6 (4.4%), <i>Pseudomonas xiamenensis <b>C</i>10-2</b> 5 (3.7%), <i>Providencia vemicola <b>Bu</i>15_38</b> 4 (2.9%), <i>Pseudomonas anguillisceptica</i> <b>4029</b> 3 (2.2%), and <i>Pseudomonas aeruginosa <b>N</i>15-01092</b> 3 (2.2%). All tested isolates showed various degrees of resistance to the thirteen antimicrobials evaluated. High levels of resistance (100%) to cefepime and imipenem were expressed by all isolates except the <i>Providencia</i> species. For the EBSL indicators, all isolates apart from <i>Alcaligenes</i> species were resistant (100%) to ceftriaxone. All <i>Vibrio</i> species were susceptible to norfloxacin, nalidixic acid, and ceftazidime. The identification of antibiotic resistant Gram-negative bacteria (GNARB) from shellfish in this study highlights the risk of disseminated multi-drug resistance—a serious public health concern.
文摘<b>Background:</b> The increasing resistance of bacteria to various antibiotics is a worldwide public health issue. Carbapenems that have elicited great hope in treating infections caused by multidrug-resistant germs have seen their efficacy narrowed over time with the emergence of other novel resistance mechanisms, notably the production of Carbapenemases. <b>Methods:</b> A prospective cross-sectional study was conducted from May 2017 to May 2018 in Douala (Cameroon) to detect carbapenemase-producing Gram-negative bacilli. Isolated strains were identified using the Vitek2<sup>TM</sup> system. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method on agar plates with 20 selected commercially available antibiotic discs. The bacterial strains were tested for the production of three Carbapenemases (OXA-48, NDM, KPC), using an immuno-chromatographic technique, with the “RESIST-3 O.K.N. K-SeT” rapid detection kit. <b>Results:</b> During the study period, 1687 strains of Gram-negative bacilli were isolated in selected laboratories with a total of 200 multi-resistant strains identified (11.9%). Among the multi-resistant strains, <i>E. coli</i> was the species most represented in <i>Enterobacteriaceae</i> (27.5%) followed by <i>K. pneumoniae</i> (15.5%) and the non-fermenting Gram-negative bacilli were predominantly <i>P. aeruginosa</i> (20.5%). These strains mainly came from urine and pus, <i>i.e.</i> 41% and 32% respectively. Thirty-two (16%) strains produced one of the Carbapenemases with a higher frequency at the General Hospital (84%). NDM-type carbapenemase was the most frequently identified (8.5%), OXA-48 type 7.5%, and no KPC production was observed. Among the <i>Enterobacteriaceae</i> 22.9% produced Carbapenemases and only 5.1% of the non-fermenting bacilli produced these enzymes. The isolates strains were completely resistant to all antibiotics except Amikacin and Fosfomycin. The strains producing the NDM-type carbapenemase showed higher rates of resistance to almost all of the antibiotics tested. <b>Conclusion:</b> Multidrug-resistant strains are experiencing an increase in evolution. The apparition of strains producing Carbapenemases prominently, the NDM and OXA-48 favor this increase. The activities of antibiotics with high efficacies on these strains are low.
文摘The purpose of this study was to critically evaluate the impact of an institutional blood culture notification protocol called RAIDS （rapid administration of antimicrobials by an infectious diseases specialist） on time to optimization of antimicrobial therapy in hospitalized patients with gram-negative bacteremia. Time to antibiotic optimization was compared in patients with gram-negative bacilli isolated from blood cultures obtained from March-May 2011 （pre-RAIDS） versus March-May 2013 （post-RAIDS）. The results show that patients in the pre-RAIDS study group had a significantly longer time to antibiotic optimization when compared to the post-RAIDS group （median （IQR）, 27.6 （10.8-75.8） h vs. 3.1 （0.8-34.3） h, p = 0.03）. The RAIDS protocol resulted in quicker time to antibiotic de-escalation （pre- vs. post-RAIDS; median （IQR）, 27.6 （10.8-134.5） h vs. 4.3 （1.4-32.6） h, p = 0.03）. There were no differences in clinical outcomes such as clinical cure, microbiological cure, and 30-day mortality between pre-RAIDS and post-RAIDS study groups. Patients in the post-RAIDS arm were more likely to receive appropriate empiric and definitive treatment. Implementation of the RAIDS protocol, which was an ASP （antimicrobial stewardship program） initiative, resulted in quicker time to antibiotic de-escalation and overall treatment optimization. RAIDS reduced the unnecessary use of broad-spectrum antimicrobial in this study population.
文摘Objective: To compare the serum contents of inflammatory mediators and oxidative stress mediators between patients with gram-positive bacteria and gram-negative bacteria infection. Methods: Patients who were diagnosed with bloodstream bacterial infection in Zigong Third People's Hospital between March 2015 and April 2017 were selected as the research subjects and divided into gram-positive group and gram-negative group according to the results of blood culture and strain identification, and serum levels of inflammatory mediators PCT, IL-1β, IL-6, sTREM-1, TNF-α, NGAL, SAA, HPT and hs-CRP as well as oxidative stress mediators MDA, AOPP, TAC, CAT and SOD were determined. Results: Serum PCT, IL-1β, IL-6, sTREM-1, TNF-α, NGAL, SAA, HPT, hs-CRP, MDA and AOPP levels of gram-negative group were greatly higher than those of gram-positive group while TAC, CAT and SOD levels were greatly lower than those of gram-positive group. Conclusion: The changes of inflammatory mediators and oxidative stress mediators in the serum of patients with gram-negative bacteria infection are more significant than those of patients with gram-positive bacteria infection.
文摘Objective: to explore the clinical characteristics and risk factors of blood stream infection in carbapenem-negative bacteria. Methods: in this study, 140 patients with suspected carbapenem-resistant gram-negative bacteria were included in the study, and their clinical characteristics and risk factors were recorded. Results: clinical characteristics: ICU and blood surgery strains. Risk factors: 2 groups had no obvious differences in liver, gallbladder and pancreatic disease, diabetes, malignant hematological system diseases, three basic diseases, impaired immune function, invasive diagnosis and treatment operation, solid tumors, urinary system disease, chronic lung disease, carbapenem exposure history, and CVC catheterization level, not statistically significant;2 groups had significant differences in the ICU admission history, indwelling PICC tubes, and the length of hospitalization before the bloodstream infection patients occurred (p <0.05). Conclusion: the analysis of carbapenem-resistant gram-negative bacteria, its clinical emergence of risk factors is unifactorial to multifactorial, univariate, involving more diseases than multifactorial diseases. By summarizing the clinical characteristics and risk factors of bloodstream infection in carbapenem-resistant gram-negative bacteria, can provide support for infection prevention.
基金supported by grants from the National Natural Science Foundation of China(grant nos.22477049,21921003,32270070,32070050,and U22A20451)from West Light Foundation of the Chinese Academy of Sciences(grant no.xbzg-zdsys-202105).
文摘Dynobactin A is a ribosomally synthesized and posttranslationally modified peptide(RiPP)antibiotic that displays potent activity against Gram-negative bacteria.This compound features a bicyclic scaffold consisting of a C–C crosslink between Trp1 and Asn4,and a highly unique N–C crosslink between His6 and Tyr8.In this study,we successfully reconstituted the activity of the radical S-adenosylmethionine(SAM)enzyme DynA both in vivo and in vitro,demonstrating that it catalyzes the formation of both C–C and N–C crosslinks in dynobactin A.Biochemical studies and mutagenesis analysis support that the N–C crosslink is formed via a para-quinone methide intermediate,representing an unprecedented mechanism in RiPP biosynthesis.We also showed DynA catalysis proceeds in a stepwise manner,where the N–C crosslink is formed first,followed by a C–C crosslink.These findings provide new insights into radical SAM enzyme chemistry and open avenues for engineering novel RiPP antibiotics targeting Gram-negative bacteria.
基金supported by the National Natural Science Foundation of China(No.22107023 and 32300033)the Natural Science Foundation of Hainan(No.222QN220,China)the Scientific Research Foundation of Hainan University(No.KYQD(ZR)-22010 and KYQD(ZR)-23006,China).
文摘Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity,expanding antibacterial spectra,and reducing required dosages.Previously,compound 15 was identified as a potential adjuvant for Polymyxin B(PB)against multidrug-resistant(MDR)Pseudomonas aeruginosa DK2;however,its clinical utility was hindered by high cytotoxicity,uncertain in vivo efficacy,and an unclear synergetic mechanism.To address these challenges,we synthesized and evaluated a series of novel benzamide derivatives,with A22 emerging as a particularly promising candidate.A22 demonstrated potent synergistic activity to PB,minimal cytotoxicity,improved water solubility,and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains.In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22.Moreover,A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2.Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production,reducing ATP levels,increasing NOX activity,and inhibiting biofilm formation,leading to bacterial death.These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants,offering a robust approach to combating MDR Gram-negative bacterial infections.
文摘Multidrug-resistant(MDR)gram-negative bacteria(GNB)are responsible for high mortality and morbidity in health care settings world-wide.They have been declared as priority pathogens by the WHO for their continuously escalating antimicrobial resistance.Neverthe-less,data associated with MDR GNB in health care–associated infections are insufficient.Surgical site infections(SSIs)are among the most commonly occurring health care–associated infections.Such infections are particularly common when bacteria from a patient’s normal microflora are transferred to the surgical sites during surgical procedures.SSIs affect approximately 0.5%–3%of patients under-going surgery,resulting in prolonged hospital stays compared with patients without SSIs.SSIs result in severe problems and lead to a heavy economic burden.Most SSIs can be avoided if suitable preventive measures are employed.Novel findings support the dedicated usage of oral preoperative surgical antimicrobial prophylaxis for specific surgeries based on sites/organs.Immediate interventions are sought to control the transmission of MDR GNB typically found in hospital settings.The present narrative review aims to describe MDR GNB in SSIs in different sites.Antimicrobial resistance epidemiology and preventive measures for SSIs are also discussed.Differ-ent intrinsic and extrinsic factors and control measures are elaborated for curbing SSIs.
