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Antimicrobial Agents and Chemotherapy Jul 2024In contrast to the epidemiology 10 years earlier at our hospital when the epidemic restriction endonuclease analysis (REA) group strain BI accounted for 72% of isolates...
Epidemiology of infection at one hospital 10 years after an outbreak of the epidemic strain BI/027: changing strain prevalence, antimicrobial susceptibilities, and patient antibiotic exposures.
In contrast to the epidemiology 10 years earlier at our hospital when the epidemic restriction endonuclease analysis (REA) group strain BI accounted for 72% of isolates recovered from first-episode infection (CDI) cases, BI represented 19% of first-episode CDI isolates in 2013-2015. Two additional REA group strains accounted for 31% of isolates (Y, 16%; DH, 12%). High-level resistance to fluoroquinolones and azithromycin was more common among BI isolates than among DH, Y, and non-BI/DH/Y isolates. Multivariable analysis revealed that BI cases were 2.47 times more likely to be associated with fluoroquinolone exposure compared to non-BI cases (95% confidence interval [CI]: 1.12-5.46). In addition, the odds of developing a CDI after third- or fourth-generation cephalosporin exposure was 2.83 times for DH cases than for non-DH cases (95% CI: 1.06-7.54). Fluoroquinolone use in the hospital decreased from 2005 to 2015 from a peak of 113 to a low of 56 antimicrobial days/1,000 patient days. In contrast, cephalosporin use increased from 42 to 81 antimicrobial days/1,000 patient days. These changes correlated with a decrease in geometric mean MIC for ciprofloxacin (61.03 to 42.65 mg/L, = 0.02) and an increase in geometric mean MIC for ceftriaxone (40.87 to 86.14 mg/L, < 0.01) among BI isolates. The BI strain remained resistant to fluoroquinolones, but an overall decrease in fluoroquinolone use and increase in cephalosporin use were associated with a decrease in the prevalence of BI, an increased diversity of strain types, and the emergence of strains DH and Y.
PubMed: 38953622
DOI: 10.1128/aac.00698-24 -
Langmuir : the ACS Journal of Surfaces... Jul 2024The issue of bacterial infectious diseases remains a significant concern worldwide, particularly due to the misuse of antibiotics, which has caused the emergence of...
The issue of bacterial infectious diseases remains a significant concern worldwide, particularly due to the misuse of antibiotics, which has caused the emergence of antibiotic-resistant strains. Fortunately, the rapid development of nanomaterials has propelled significant progress in antimicrobial therapy, offering promising solutions. Among them, the utilization of nanoenzyme-based chemodynamic therapy (CDT) has become a highly hopeful approach to combating bacterial infectious diseases. Nevertheless, the application of CDT appears to be facing certain constraints for its low efficiency in the Fenton reaction at the infected site. In this study, we have successfully synthesized a versatile nanozyme, which was a composite of molybdenum sulfide (MoS) and iron sulfide (FeS), through the hydrothermal method. The results showed that iron/molybdenum sulfide nanozymes (Fe/Mo SNZs) with desirable peroxidase (POD) mimic activity can generate cytotoxic reactive oxygen species (ROS) by successfully triggering the Fenton reaction. The presence of MoS significantly accelerates the conversion of Fe/Fe through a cocatalytic reaction that involves the participation of redox pairs of Mo/Mo, thereby enhancing the efficiency of CDT. Additionally, based on the excellent photothermal performance of Fe/Mo SNZs, a near-infrared (NIR) laser was used to induce localized temperature elevation for photothermal therapy (PTT) and enhance the POD-like nanoenzymatic activity. Notably, both and results demonstrated that Fe/Mo SNZs with good broad-spectrum antibacterial properties can help eradicate Gram-negative bacteria like and Gram-positive bacteria like . The most exciting thing is that the synergistic PTT/CDT exhibited astonishing antibacterial ability and can achieve complete elimination of bacteria, which promoted wound healing after infection. Overall, this study presents a synergistic PTT/CDT strategy to address antibiotic resistance, providing avenues and directions for enhancing the efficacy of wound healing treatments and offering promising prospects for further clinical use in the near future.
PubMed: 38953474
DOI: 10.1021/acs.langmuir.4c00922 -
Spine Jul 2024Retrospective cohort.
STUDY DESIGN
Retrospective cohort.
OBJECTIVE
The purpose of this study was to compare the efficacy of cefazolin versus vancomycin for perioperative infection prophylaxis.
SUMMARY OF BACKGROUND DATA
The relative efficacy of cefazolin alternatives for perioperative infection prophylaxis is poorly understood.
METHODS
This study was a single-center multi-surgeon retrospective review of all patients undergoing primary spine surgery from an institutional registry. Postoperative infection was defined by the combination of three criteria: irrigation and debridement within 3 months of the index procedure, clinical suspicion for infection, and positive intraoperative cultures. Microbiology records for all infections were reviewed to assess the infectious organism and organism susceptibilities. Univariate and multivariate analyses were performed.
RESULTS
A total of 10,122 patients met inclusion criteria. The overall incidence of infection was 0.78%, with an incidence of 0.73% in patients who received cefazolin and 2.03% in patients who received vancomycin (OR 2.83, 95% CI 1.35-5.91, P-0.004). Use of IV vancomycin (OR 2.83, 95% CI 1.35-5.91, P=0.006), BMI (MD 1.56, 95% CI 0.32-2.79, P=0.014), presence of a fusion (OR 1.62, 95% CI 1.04-2.52, P=0.033), and operative time (MD 42.04, 95% CI 16.88-67.21, P=0.001) were significant risk factors in the univariate analysis. In the multivariate analysis, only non-cefazolin antibiotics (OR 2.48, 95% CI 1.18-5.22, P=0.017) and BMI (MD 1.56, 95% CI 0.32-2.79, P=0.026) remained significant independent risk factors. Neither IV antibiotic regimen nor topical vancomycin significantly impacted Gram type, organism type, or antibiotic resistance (P>0.05). The most common reason for antibiosis with vancomycin was a penicillin allergy (75.0%).
CONCLUSIONS
Prophylactic antibiosis with IV vancomycin leads to a 2.5-times higher risk of infection compared to IV cefazolin in primary spine surgery. We recommend the routine use of IV cefazolin for infection prophylaxis, and caution against the elective use of alternative regimens like IV vancomycin unless clinically warranted.
PubMed: 38953398
DOI: 10.1097/BRS.0000000000005081 -
Microbiology Spectrum Jul 2024Delayed time to antimicrobial susceptibility results can impact patients' outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate...
Delayed time to antimicrobial susceptibility results can impact patients' outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate empiric antibacterial therapy (IET) in patients with bloodstream infections (BSI) caused by (ENT) species on in-hospital mortality and length of stay (LOS). This retrospective, multicenter investigation which included 29,570 blood ENT-positive admissions across 161 US healthcare facilities evaluated the association between antimicrobial susceptibility testing (AST) TAT, carbapenem susceptibility, and empiric therapy on post-BSI in-hospital mortality and LOS following an ENT BSI event in adult patients. After adjusting for outcomes covariates, post-BSI in-hospital mortality was significantly higher for patients in the IET vs adequate empiric therapy (AET) group [odds ratio (OR): 1.61 (95% CI: 1.32, 1.98); < 0.0001], and when AST TAT was >63 h [OR:1.48 (95% CI: 1.16, 1.90); = 0.0017]. Patients with carbapenem non-susceptible (carb-NS) ENT BSI had significantly higher LOS (16.6 days, 95% CI: 15.6, 17.8) compared to carbapenem susceptible (carb-S, 12.2 days, 95% CI: 11.8, 12.6), ( < 0.0001). Extended AST TAT was significantly associated with longer LOS for TAT of 57-65 h and >65 h ( = 0.005 and < 0.0001, respectively) compared to TAT ≤42 h (reference). Inadequate empiric therapy (IET), carb-NS, and delayed AST TAT are significantly associated with adverse hospital outcomes in ENT BSI. Workflows that accelerate AST TAT for ENT BSIs and facilitate timely and adequate therapy may reduce post-BSI in-hospital mortality rate and LOS.IMPORTANCEFor patients diagnosed with bloodstream infections (BSI) caused by (ENT), delayed time to antimicrobial susceptibility (AST) results can significantly impact in-hospital mortality and hospital length of stay. However, this relationship between time elapsed from blood culture collection to AST results has only been assessed, to date, in a limited number of publications. Our study focuses on this important gap using retrospective data from 29,570 blood ENT-positive admissions across 161 healthcare facilities in the US as we believe that a thorough understanding of the dynamic between AST turnaround time, adequacy of empiric therapy, post-BSI event mortality, and hospital length of stay will help guide effective clinical management and optimize outcomes of patients with ENT infections.
PubMed: 38953323
DOI: 10.1128/spectrum.00402-24 -
MSystems Jul 2024The erythromycin resistance RNA methyltransferase () confers cross-resistance to all therapeutically important macrolides, lincosamides, and streptogramins (MLS...
UNLABELLED
The erythromycin resistance RNA methyltransferase () confers cross-resistance to all therapeutically important macrolides, lincosamides, and streptogramins (MLS phenotype). The expression of is often induced by the macrolide-mediated ribosome stalling in the upstream co-transcribed leader sequence, thereby triggering a conformational switch of the intergenic RNA hairpins to allow the translational initiation of . We investigated the evolutionary emergence of the upstream regulatory elements and the impact of allelic variation on erm expression and the MLS phenotype. Through systematic profiling of the upstream regulatory sequences across all known operons, we observed that specific subfamilies, such as and , have independently evolved distinct configurations of small upstream ORFs and palindromic repeats. A population-wide genomic analysis of the upstream regions revealed substantial non-random allelic variation at numerous positions. Utilizing machine learning-based classification coupled with RNA structure modeling, we found that many alleles cooperatively influence the stability of alternative RNA hairpin structures formed by the palindromic repeats, which, in turn, affects the inducibility of expression and MLS phenotypes. Subsequent experimental validation of 11 randomly selected variants demonstrated an impressive 91% accuracy in predicting MLS phenotypes. Furthermore, we uncovered a mixed distribution of MLS-sensitive and MLS-resistant loci within the evolutionary tree, indicating repeated and independent evolution of MLS resistance. Taken together, this study not only elucidates the evolutionary processes driving the emergence and development of MLS resistance but also highlights the potential of using non-coding genomic allele data to predict antibiotic resistance phenotypes.
IMPORTANCE
Antibiotic resistance (AR) poses a global health threat as the efficacy of available antibiotics has rapidly eroded due to the widespread transmission of AR genes. Using Erm-dependent MLS resistance as a model, this study highlights the significance of non-coding genomic allelic variations. Through a comprehensive analysis of upstream regulatory elements within the family, we elucidated the evolutionary emergence and development of AR mechanisms. Leveraging population-wide machine learning (ML)-based genomic analysis, we transformed substantial non-random allelic variations into discernible clusters of elements, enabling precise prediction of MLS phenotypes from non-coding regions. These findings offer deeper insight into AR evolution and demonstrate the potential of harnessing non-coding genomic allele data for accurately predicting AR phenotypes.
PubMed: 38953319
DOI: 10.1128/msystems.00430-24 -
Cureus May 2024Introduction Pulmonary tuberculosis (TB) remains a global health concern, exacerbated by the emergence of extensively drug-resistant (XDR) strains of . This study...
Introduction Pulmonary tuberculosis (TB) remains a global health concern, exacerbated by the emergence of extensively drug-resistant (XDR) strains of . This study employs advanced molecular techniques, specifically polymerase chain reaction (PCR) profiling, to comprehensively characterize the genetic landscape of XDR pathogenic bacteria in patients diagnosed with pulmonary TB. The objective of the study is to elucidate the genes that are associated with drug resistance in pulmonary TB strains through the application of PCR and analyze specific genetic loci that contribute to the development of resistance against multiple drugs. Materials and methods A total of 116 clinical samples suspected of TB were collected from the tertiary healthcare setting of Saveetha Medical College and Hospitals for the identification of MTB, which includes sputum (n = 35), nasal swabs (n = 17), blood (n = 44), and bronchoalveolar lavage (BAL) (n = 20). The collected specimens were processed and subjected to DNA extraction. As per the protocol, reconstitution of the DNA pellet was carried out. The reconstituted DNA was stored at -20 °C for the PCR assay. From the obtained positive sample specimens, XDR pulmonary TB specimens were focused on the targeted genes, specifically the gene for rifampicin resistance, , and gene for thepromoter region for isoniazid resistance. Results Out of a total of 116 samples obtained, 53 tested positive for pulmonary TB, indicative of a mycobacterial infection. Among these positive cases, 43 patients underwent treatment at a tertiary healthcare facility. Subsequently, a PCR assay was performed with the extracted DNA for the target genes , , and . Specifically, 22 sputum samples exhibited gene expression for , , and , while nine nasal swabs showed expression of the and genes. Additionally, gene expression was detected in seven blood specimens, and both and genes were expressed in five BAL samples. Conclusion The swift diagnosis and efficient treatment of XDR-TB can be facilitated by employing advanced and rapid molecular tests and oral medication regimens. Utilizing both newly developed and repurposed anti-TB drugs like pretomanid, bedaquiline, linezolid, and ethionamide. Adhering to these current recommendations holds promise for managing XDR-TB effectively. Nevertheless, it is significant to conduct well-designed clinical trials and studies to further evaluate the efficacy of new agents and shorter treatment regimens, thus ensuring continuous improvement in the management of this challenging condition.
PubMed: 38953074
DOI: 10.7759/cureus.61424 -
Frontiers in Cellular and Infection... 2024
Topics: Humans; Anti-Bacterial Agents; Bacteriophages; Drug Resistance, Multiple, Bacterial; Endopeptidases; Methicillin-Resistant Staphylococcus aureus; Phage Therapy; Staphylococcal Infections; Staphylococcus aureus
PubMed: 38953006
DOI: 10.3389/fcimb.2024.1397935 -
PeerJ 2024Agricultural soils contaminated with heavy metals poison crops and disturb the normal functioning of rhizosphere microbial communities. Different crops and rhizosphere...
Agricultural soils contaminated with heavy metals poison crops and disturb the normal functioning of rhizosphere microbial communities. Different crops and rhizosphere microbial communities exhibit different heavy metal resistance mechanisms. Here, indoor pot studies were used to assess the mechanisms of grain and soil rhizosphere microbial communities on chromium (Cr) stress. Millet grain variety 'Jingu 21' () and soil samples were collected prior to control (CK), 6 hours after (Cr_6h), and 6 days following (Cr_6d) Cr stress. Transcriptomic analysis, high-throughput sequencing and quantitative polymerase chain reaction (qPCR) were used for sample determination and data analysis. Cr stress inhibited the expression of genes related to cell division, and photosynthesis in grain plants while stimulating the expression of genes related to DNA replication and repair, in addition to plant defense systems resist Cr stress. In response to chromium stress, rhizosphere soil bacterial and fungal community compositions and diversity changed significantly ( < 0.05). Both bacterial and fungal co-occurrence networks primarily comprised positively correlated edges that would serve to increase community stability. However, bacterial community networks were larger than fungal community networks and were more tightly connected and less modular than fungal networks. The abundances of C/N functional genes exhibited increasing trends with increased Cr exposure. Overall, these results suggest that Cr stress primarily prevented cereal seedlings from completing photosynthesis, cell division, and proliferation while simultaneously triggering plant defense mechanisms to resist the toxic effects of Cr. Soil bacterial and fungal populations exhibited diverse response traits, community-assembly mechanisms, and increased expression of functional genes related to carbon and nitrogen cycling, all of which are likely related to microbial survival during Cr stress. This study provides new insights into resistance mechanisms, microbial community structures, and mechanisms of C/N functional genes responses in cereal plants to heavy metal contaminated agricultural soils. Portions of this text were previously published as part of a preprint (https://www.researchsquare.com/article/rs-2891904/v1).
Topics: Soil Microbiology; Chromium; Rhizosphere; Soil Pollutants; Edible Grain; Stress, Physiological; Fungi; Microbiota; Bacteria
PubMed: 38952992
DOI: 10.7717/peerj.17461 -
BioRxiv : the Preprint Server For... May 2024The microbiota can promote host health by inhibiting pathogen colonization, yet how host-resident fungi, or the mycobiota, contribute to this process remains unclear....
UNLABELLED
The microbiota can promote host health by inhibiting pathogen colonization, yet how host-resident fungi, or the mycobiota, contribute to this process remains unclear. The human skin mycobiota is uniquely stable compared to other body sites and dominated by yeasts of the genus . We observe that colonization of human skin by significantly reduces subsequent colonization by the prominent bacterial pathogen . secreted products possess potent bactericidal activity against and are sufficient to impair skin colonization. This bactericidal activity requires an acidic environment and is exacerbated by free fatty acids, demonstrating a unique synergy with host-derived epidermal defenses. Leveraging experimental evolution to pinpoint mechanisms of adaptation in response to the skin mycobiota, we identified multiple mutations in the stringent response regulator Rel that promote survival against . Similar Rel alleles have been reported in clinical isolates, and natural Rel variants are sufficient for tolerance to antagonism. Partial stringent response activation underlies tolerance to clinical antibiotics, with both laboratory-evolved and natural Rel variants conferring multidrug tolerance. These findings demonstrate the ability of the mycobiota to mediate pathogen colonization resistance, identify new mechanisms of bacterial adaptation in response to fungal antagonism, and reveal the potential for microbiota-driven evolution to shape pathogen antibiotic susceptibility.
HIGHLIGHTS
- reduces colonization of human skin by - Bactericidal activity of is exacerbated by features of the skin niche - Rel variants are sufficient for tolerance to antagonism - Evolved tolerance to yeast antagonism coincides with multidrug tolerance.
PubMed: 38952794
DOI: 10.1101/2024.05.03.592489 -
Iranian Journal of Medical Sciences Jun 2024Spontaneous bacterial peritonitis (SBP) is a fatal complication of ascites fluid infection. The causes of SBP in children differ from those in adults, and these bacteria...
Clinical Findings, Bacterial Agents, and Antibiotic Resistance in Children with Spontaneous Peritonitis in Southern Iran: An Academic Tertiary Referral Center's Experience.
BACKGROUND
Spontaneous bacterial peritonitis (SBP) is a fatal complication of ascites fluid infection. The causes of SBP in children differ from those in adults, and these bacteria are frequently resistant to antibiotics. Therefore, this study investigated the clinical findings, bacterial etiology, and antimicrobial resistance in children with SBP.
METHODS
This study was conducted on all new pediatric ascites patients, who were admitted to the Department of Pediatric Gastroenterology, Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from 2021 to 2022. Required data such as demographic information, and clinical information such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Gram staining, blood culture by Automated Blood Culture System (BACTEC), and antibiogram of ascites fluids by disc diffusion method were all collected. Finally, the data were statistically analyzed using SPSS Software (version 26). Besides, the test, Fisher's exact, Mann-Whitney, and Chi square tests were used for data analysis. In all tests, P≤0.05 was considered statistically significant.
RESULTS
The present study examined 62 children with ascites of which 18 (29%) had SBP. The median (IQR) age was 2.5 (8.1) years. Thirty-four (54.8%) of the participants were girls. Abdominal pain was the most common clinical manifestation in patients (54%), and there was a significant association between abdominal pain and SBP (P=0.02). In 12 positive ascites fluid cultures, coagulase-negative staphylococci had the highest frequency (25%), followed by (16.7%). Third-generation cephalosporins had a 25% sensitivity in the total positive cultures. This sensitivity was 33.3% for Gram-negative cultures and 16.6% for Gram-positive cultures.
CONCLUSION
Although third-generation cephalosporins are recommended as the primary antibiotic for the empirical treatment of SBP, the present study found high bacterial resistance. Finally, empirical therapy should be tailored to each region's bacterial resistance features.
Topics: Humans; Peritonitis; Child; Female; Male; Iran; Child, Preschool; Anti-Bacterial Agents; Tertiary Care Centers; Infant; Adolescent; Drug Resistance, Bacterial; Ascites; Bacterial Infections; Microbial Sensitivity Tests
PubMed: 38952643
DOI: 10.30476/ijms.2023.98747.3082