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Drugs Jun 2024Cefepime/enmetazobactam (EXBLIFEP), an intravenous (IV) antibacterial fixed-dose combination of a 4th generation cephalosporin and an extended-spectrum β-lactamase... (Review)
Review
Cefepime/enmetazobactam (EXBLIFEP), an intravenous (IV) antibacterial fixed-dose combination of a 4th generation cephalosporin and an extended-spectrum β-lactamase (ESBL) inhibitor, is being developed by Allecra Therapeutics and ADVANZ PHARMA for the treatment of infections caused by multi-drug-resistant (MDR) Gram-negative bacteria. In February 2024, cefepime/enmetazobactam was approved in the USA for use in adults with complicated urinary tract infections (cUTI) including pyelonephritis, caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex. In March 2024, cefepime/enmetazobactam was approved in the EU for use in adults for the treatment of cUTI, including pyelonephritis, and hospital-acquired pneumonia, including ventilator associated pneumonia, and the treatment of patients with bacteraemia occurring in association with or suspected to be associated with any of these infections. This article summarizes the milestones in the development of cefepime/enmetazobactam leading to this first approval for the treatment of adults with infections caused by MDR Gram-negative bacteria.
Topics: Humans; Cefepime; Anti-Bacterial Agents; Urinary Tract Infections; Drug Approval; Gram-Negative Bacterial Infections; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Cephalosporins; beta-Lactamase Inhibitors; United States; Drug Combinations; Pyelonephritis
PubMed: 38761353
DOI: 10.1007/s40265-024-02035-2 -
PloS One 2024The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five...
The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five patients diagnosed with diabetic foot ulcers were investigated. A number of these patients (97.33%) had type 2 diabetes, with a significant proportion of them having been diagnosed for 1-5 years (29.33%). Notably, a substantial number of these individuals were on insulin usage (78.66%). Among the patients under examination, 49.33% reported having no use of tobacco products, alcohol, or betel leaf. The ulcers analyzed in this study were classified into grades 1-5 according to the Wagner scale. Wagner grade 2 diabetic foot ulcers had the highest number of culture-positive patients, at 33.33%. Pus samples collected from patients were cultured on selective media, and bacterial identity was confirmed by biochemical tests and polymerase chain reaction. A total of 141 isolates were isolated. Among the isolates, 82.97% gram-negative bacteria and 17.02% gram-positive bacteria were detected. Klebsiella pneumoniae was the most common isolate. Proteus spp., Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also detected. Approximately 61.33% of the ulcers exhibited were polybacterial. In this study, it was observed that all bacterial isolates, except for Proteus spp., were primarily detected in patients classified under Wagner's grade 2. Moreover, antibiotic susceptibility was also tested on these 141 isolates. Among them, Escherichia coli showed the highest multidrug resistance, 81.81%. Most of the gram-negative bacteria were resistant to ampicillin. All of the gram-negative isolates exhibited high levels of susceptibility to piperacillin-tazobactam, and these levels were Klebsiella pneumoniae (97.56%), Pseudomonas aeruginosa (95.24%), Escherichia coli (81.82%), and Proteus spp. (80%). On the other hand, gram-positive Staphylococcus aureus mostly showed sensitivity towards vancomycin and norfloxacin (79.17%).
Topics: Humans; Diabetic Foot; Male; Female; Middle Aged; Anti-Bacterial Agents; Microbial Sensitivity Tests; Bangladesh; Aged; Adult; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Escherichia coli; Diabetes Mellitus, Type 2; Staphylococcus aureus
PubMed: 38758936
DOI: 10.1371/journal.pone.0301767 -
Journal of Materials Chemistry. B Jun 2024The presence of a variety of bacteria is an inevitable/indispensable part of human life. In particular, for patients, the existence and spreading of bacteria lead to...
The presence of a variety of bacteria is an inevitable/indispensable part of human life. In particular, for patients, the existence and spreading of bacteria lead to prolonged treatment period with many more complications. The widespread use of urinary catheters is one of the main causes for the prevalence of infections. The necessity of long-term use of indwelling catheters is unavoidable in terms of the development of bacteriuria and blockage. As is known, since a permanent solution to this problem has not yet been found, research and development activities continue actively. Herein, polyethylene glycol (PEG)-like thin films were synthesized by a custom designed plasma enhanced chemical vapor deposition (PE-CVD) method and the long-term effect of antifouling properties of PEG-like coated catheters was investigated against and . The contact angle measurements have revealed the increase of wettability with the increase of plasma exposure time. The antifouling activity of surface-coated catheters was analyzed against the Gram-negative/positive bacteria over a long-term period (up to 30 days). The results revealed that PE-CVD coated PEG-like thin films are highly capable of eliminating bacterial attachment on surfaces with relatively reduced protein attachment without having any toxic effect. Previous statements were supported with SEM, XPS, FTIR spectroscopy, and contact angle analysis.
Topics: Urinary Catheters; Escherichia coli; Surface Properties; Proteus mirabilis; Polyethylene Glycols; Bacterial Adhesion; Biofouling; Humans; Coated Materials, Biocompatible
PubMed: 38758163
DOI: 10.1039/d4tb00311j -
International Journal of Dermatology May 2024
PubMed: 38757487
DOI: 10.1111/ijd.17119 -
BMC Microbiology May 2024Bullet-related bacterial wound infection can be caused by high-velocity bullets and shrapnel injuries. In Ethiopia, significant injuries were reported that may cause...
Bullet-related bacterial wound infections among injured personnel at emergency site hospitals in Bahir Dar: prevalence, antimicrobial susceptibility and associated factors.
BACKGROUND
Bullet-related bacterial wound infection can be caused by high-velocity bullets and shrapnel injuries. In Ethiopia, significant injuries were reported that may cause severe wound infections, persistent systemic infections and may lead to amputation and mortality. The magnitude, antimicrobial susceptibility profiles, and factors associated with bacterial wound infections among patients with bullet-related injuries are not yet studied particularly at health facilities in Bahir Dar, Northwest Ethiopia. Therefore, this study was aimed to determine the prevalence, bacterial profiles, antimicrobial susceptibility profiles, and factors associated with bacterial infections among patients with bullet-related injuries at referral health facilities in Bahir Dar, Northwest Ethiopia.
METHODS
A Hospital-based cross-sectional study was conducted among patients with bullet-related injuries at three referral health facilities in Bahir Dar from May 25 to July 27, 2022. A total of 384 patients with bullet-related injuries were included in the study. Sociodemographic and clinical data were collected using a structured questionnaire. Wound swabs were collected aseptically and cultured on Blood and MacConkey agar following bacteriological standards. Biochemical tests were performed to differentiate bacteria for positive cultivation and antimicrobial susceptibility profiles of the isolates were done on Muller Hinton agar using the Kirby-Bauer disk diffusion technique according to the 2021 Clinical Laboratory Standard Institute (CLSI) guideline. The data were entered using Epi-Info version 7.3 and analyzed using SPSS version 25. Descriptive data were presented using frequency, percentages, figures, and charts. Logistic regression was carried out to identify factors associated with bacterial wound infections. P-value < 0.05 was considered statistically significant.
RESULTS
The prevalence of bullet-related bacterial wound infection among three referral hospitals in Bahir Dar city was 54.7%. The most commonly isolated Gram-negative organism was Klebsiella spps 49 (23.3%) while among Gram-positive organism, Staphylococcus aureus 58 (27.6%) and coagulase-negative staphylococci (CONS) 18 (8.6%). Contamination, hospitalization and smoking habit were significantly associated with the presence of bullet-related bacterial wound infections. Over 97% multidrug resistant (MDR) bacterial isolates were identified and of theses, E. coli, Proteus species, Citrobactor, and Staphylococcus aureus were highly drug resistant.
CONCLUSION
Increased prevalence of bullet-related bacterial wound infection was noticed in this study. S. aureus followed by Klebsiella species were most commonly isolated bacteria. High frequency of resistance to Ampicillin, Oxacillin, Cefepime, Ceftriaxone, Ceftazidime, Vancomycin, and Norfloxacin was observed. Therefore, proper handling of bullet injuries, prompt investigation of bacterial infections, monitoring of drug sensitivity patterns and antibiotic usage are critical.
Topics: Humans; Ethiopia; Male; Cross-Sectional Studies; Adult; Female; Prevalence; Wound Infection; Anti-Bacterial Agents; Microbial Sensitivity Tests; Young Adult; Wounds, Gunshot; Bacterial Infections; Middle Aged; Bacteria; Emergency Service, Hospital; Adolescent
PubMed: 38755533
DOI: 10.1186/s12866-024-03324-2 -
Frontiers in Microbiology 2024The permanence of HIV patients in healthcare provision centers exposes their weak immunity to various nosocomial microorganisms that migrate into and out of the hospital...
Correlation of CD4+ count and viral load with urinary tract infection and antimicrobial resistance pattern of bacterial uropathogens among HIV patients in Wolaita Sodo, South Ethiopia.
BACKGROUND
The permanence of HIV patients in healthcare provision centers exposes their weak immunity to various nosocomial microorganisms that migrate into and out of the hospital environment. The incidence of bacterial infections, including urinary tract infection, was inversely correlated with CD4+ T cells. Urinary tract infection (UTI) is one of the clinical problems among HIV patients. There was scarcity of published data on the relationship between viral load, CD4+ level, and UTI. This study aimed to assess the relationship between viral load and CD4 with bacterial UTI among HIV patients.
METHODS
The cross-sectional study was conducted in the Wolaita Sodo Town Health Center ART clinic. The socio-demographic data were collected using a pre-designed questionnaire. Patients' charts were reviewed to collect the current CD4 and viral load. Urine specimens were inoculated on blood agar, cysteine lactose electrolyte deficient (CLED) agar, and MacConkey agar, and bacterial species were finally identified using various biochemical methods. Antimicrobial sensitivity testing was conducted using standard microbiological tests. Bivariate and multivariate analyses were employed to describe the association between pairs of variables and to examine the relationship between independent variables and dependent variables.
RESULTS
In this study, the overall prevalence of urinary tract infection (UTI) was 13.7%. , and were bacterial uropathogens detected in this study. (45.7%) was the predominant isolate followed by (14.3%). Positive correlation between CD4+ count and urinary tract infection was detected and found statistically significant ( = 0.288 > 0.01), whereas the viral load and urinary tract infection negatively correlated and showed statistically significant association ( < 0.01). The resistance rate of was 94%, 75%, and 69% to ciprofloxacin, norfloxacin, and cefepime, respectively. This study revealed that exhibited 94% and 75% resistance to amoxicillin-clavulanic acid and tetracycline, respectively. demonstrated complete resistance (100%) to amoxicillin-clavulanic acid, tetracycline, and trimethoprim-sulfamethoxazole, while showing 100% susceptibility to ciprofloxacin and nitrofurantoin. In the present study, the magnitude of the multi-drug resistance (MDR) was found to be 80%. CD4+ count, combination of antiretroviral therapy (ART) drugs, and a history of hospitalization were risk factors for urinary tract infection.
CONCLUSION
In the current study, urinary tract infection emerged as a significant health concern among people living with HIV following their ART. The occurrence of urinary tract infection among HIV patients could be influenced by multifactorial factors that require further study. The CD4+ count was positively correlated with the prevalence of UTI, whereas the viral load was negatively correlated. The CD4+ count, combination of ART, and history of hospitalization were independent risk factors for UTI. The prevalence of MDR bacterial pathogens were notably high. Therefore, the treatment of UTI in HIV patients should be prescribed based on antibacterial susceptibility testing results.
PubMed: 38746741
DOI: 10.3389/fmicb.2024.1363287 -
International Journal of Surgery... May 2024With the antibiotic crisis, the topical antibacterial control including chronic wounds gains increasing importance. However, little is known regarding tolerance...
Antiseptic management of critical wounds: differential bacterial response upon exposure to antiseptics and first insights into antiseptic/phage interactions - experimental studies.
BACKGROUND
With the antibiotic crisis, the topical antibacterial control including chronic wounds gains increasing importance. However, little is known regarding tolerance development when bacteria face repetitive exposure to the identical antiseptics as commonly found in clinical practice.
MATERIALS AND METHODS
We exposed clinical isolates foremost of chronic wounds in vitro to dilutions of two antisepctics used for wound therapy: polyhexanide or octenidine. Adaptive response was determined by growth/kill curves, minimal inhibitory concentration (MIC), and whole genome sequencing. Antiseptic/bacteriophage combinations were studied by liquid-infection assays and bacterial plating.
RESULTS
Polyhexanide acted stronger against Escherichia coli and Proteus mirabilis while octenidine was more potent against Staphylococcus aureus. Otherwise, the antiseptic efficacy varied across isolates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Upon repetitive exposure with constant antiseptic concentrations P. aeruginosa and P. mirabilis adaptation was evident by a reduced lag-phase and a two-fold increased MIC. Under increasing octenidine concentrations, P. aeruginosa adapted to an eightfold higher dosage with mutations in smvA, opgH and kinB affecting an efflux pump, alginate and biofilm formation, respectively. S. aureus adapted to a fourfold increase of polyhexanide with a mutation in the multiple peptide resistance factor MprF, also conferring cross-resistance to daptomycin. Antiseptic/bacteriophage combinations enhanced bacterial inhibition and delayed adaptation.
CONCLUSION
Different bacterial species/strains respond unequally to low-level antiseptic concentrations. Bacterial adaptation potential at phenotypic and genotypic levels may indicate the necessity for a more nuanced selection of antiseptics. Bacteriophages represent a promising yet underexplored strategy for supporting antiseptic treatment which may be particularly beneficial for the management of critical wounds.
PubMed: 38742847
DOI: 10.1097/JS9.0000000000001605 -
Microbiological Research Aug 2024The global dissemination of the multidrug resistance efflux pump gene cluster tmexCD-toprJ has greatly weakened the effects of multiple antibiotics, including...
BACKGROUND
The global dissemination of the multidrug resistance efflux pump gene cluster tmexCD-toprJ has greatly weakened the effects of multiple antibiotics, including tigecycline. However, the potential origin and transmission mechanisms of the gene cluster remain unclear.
METHODS
Here, we concluded a comprehensive bioinformatics analysis on integrated 73,498 bacterial genomes, including Pseudomonas spp., Klebsiella spp., Aeromonas spp., Proteus spp., and Citrobacter spp., along with 1,152 long-read metagenomic datasets to trace the origin and propagation of tmexCD-toprJ.
RESULTS
Our results demonstrated that tmexCD-toprJ was predominantly found in Pseudomonas aeruginosa sourced from human hosts in Asian countries and North American countries. Phylogenetic and genomic feature analyses showed that tmexCD-toprJ was likely evolved from mexCD-oprJ of some special clones of P. aeruginosa. Furthermore, metagenomic analysis confirmed that P. aeruginosa is the only potential ancestral bacterium for tmexCD-toprJ. A putative mobile genetic structure harboring tmexCD-toprJ, int-int-hp-hp-tnfxB-tmexCD-toprJ, was the predominant genetic context of tmexCD-toprJ across various bacterial genera, suggesting that the two integrase genes play a pivotal role in the horizontal transmission of tmexCD-toprJ.
CONCLUSIONS
Based on these findings, it is almost certain that the tmexCD-toprJ gene cluster was derived from P. aeruginosa and further spread to other bacteria.
Topics: Pseudomonas aeruginosa; Multigene Family; Metagenomics; Phylogeny; Tigecycline; Genome, Bacterial; Anti-Bacterial Agents; Humans; Drug Resistance, Multiple, Bacterial; Genomics; Bacterial Proteins; Computational Biology; Microbial Sensitivity Tests; Drug Resistance, Bacterial
PubMed: 38739956
DOI: 10.1016/j.micres.2024.127747 -
Transplantation Proceedings May 2024Donor organ shortages cause increasing demand for mechanical circulatory support in patients with end-stage heart failure not only as a bridge to heart transplantation...
BACKGROUND
Donor organ shortages cause increasing demand for mechanical circulatory support in patients with end-stage heart failure not only as a bridge to heart transplantation but mainly as a destination therapy. Improved results and increased applicability and durability of left ventricular assist devices (LVADs) have established this treatment option as an alternative to heart transplantation in selected patients. One of the most common complications after LVAD implantation is driveline infections (DLIs).
METHODS
This study aimed to expand the understanding of DLI epidemiology and potential changes in implantation techniques regarding optimizing DLI prevention and treatment among all patients undergoing LVAD (Medtronic's Heartware HVAD and HeartMate 3 Abbott LVAD system) implantation with at least 12 months of follow-up time between 2015 and 2022.
RESULTS
There were 120 individuals with LVAD implantation, of whom 90 had 12 months of follow-up (85 men [94%], 5 women [6%]) with a median age of 58 years (50.25-63.75). The median body mass index was 27.12 kg/m (25.27-29.68). Of the 90 patients, 43 had ischemic heart failure (48%), 43 had dilated cardiomyopathy (48%), and the remaining 3 had other etiologies (3%), such as postinflammatory, and the remaining 1 had congenital heart defect (1%). Preoperative echocardiography revealed a mean left ventricle ejection fraction of 13.8% and a median left ventricle dimension of 7.55 cm (6.92-8.2). Imaging confirmed pulmonary hypertension in 61 patients (68%). Thirty-four of the 90 patients had diabetes (38%), and 16 were active smokers (18%). Median follow-up was 30 months (17.25-42), with the longest period being 82 months. More than half of the patients (n = 52; 57%) experienced a DLI. The median time to the first episode of DLI was 13 months (6-25). The most common pathogen revealed in wound swab culture was methicillin-sensitive Staphylococcus aureus (n = 23; 44%), Pseudomonas aeruginosa (n = 9; 17%), Proteus mirabilis (n = 4; 7%), and others. We observed that deeper driveline implantation below the left rectus muscle and just above the posterior rectus sheath resulted in fewer DLIs and longer free-from-DLI follow-up time. There was no statistically significant difference in DLI frequency between patients with or without diabetes mellitus.
CONCLUSIONS
Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of destination therapy. DLI is the most common complication after LVAD implantation. Optimal surgical techniques and early implementation of targeted antibiotics are crucial. Significant challenges remain in optimizing DLI prevention and treatment.
Topics: Humans; Heart-Assist Devices; Female; Male; Middle Aged; Heart Failure; Prosthesis-Related Infections; Retrospective Studies
PubMed: 38734518
DOI: 10.1016/j.transproceed.2024.03.029 -
Ecotoxicology and Environmental Safety Jun 2024Cadmium (Cd) pollution is a serious global environmental problem, which requires a global concern and practical solutions. Microbial remediation has received widespread...
Cadmium (Cd) pollution is a serious global environmental problem, which requires a global concern and practical solutions. Microbial remediation has received widespread attention owing to advantages, such as environmental friendliness and soil amelioration. However, Cd toxicity also severely deteriorates the remediation performance of functional microorganisms. Analyzing the mechanism of bacterial resistance to Cd stress will be beneficial for the application of Cd remediation. In this study, the bacteria strain, up to 1400 mg/L Cd resistance, was employed and identified as Proteus mirabilis Ch8 (Ch8) through whole genome sequence analyses. The results indicated that the multiple pathways of immobilizing and detoxifying Cd maintained the growth of Ch8 under Cd stress, which also possessed high Cd extracellular adsorption. Firstly, the changes in surface morphology and functional groups of Ch8 cells were observed under different Cd conditions through SEM-EDS and FTIR analyses. Under 100 mg/L Cd, Ch8 cells exhibited aggregation and less flagella; the Cd biosorption of Ch8 was predominately by secreting exopolysaccharides (EPS) and no significant change of functional groups. Under 500 mg/L Cd, Ch8 were present irregular polymers on the cell surface, some cells with wrapping around; the Cd biosorption capacity exhibited outstanding effects (38.80 mg/g), which was mainly immobilizing Cd by secreting and interacting with EPS. Then, Ch8 also significantly enhanced the antioxidant enzyme activity and the antioxidant substance content under different Cd conditions. The activities of SOD and CAT, GSH content of Ch8 under 500 mg/L Cd were significantly increased by 245.47%, 179.52%, and 241.81%, compared to normal condition. Additionally, Ch8 significantly induced the expression of Acr A and Tol C (the resistance-nodulation-division (RND) efflux pump), and some antioxidant genes (SodB, SodC, and Tpx) to reduce Cd damage. In particular, the markedly higher expression levels of SodB under Cd stress. The mechanism of Ch8 lays a foundation for its application in solving soil remediation.
Topics: Proteus mirabilis; Cadmium; Soil Pollutants; Biodegradation, Environmental
PubMed: 38728947
DOI: 10.1016/j.ecoenv.2024.116432