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SAGE Open Medical Case Reports 2024Malignant otitis externa (skull base osteomyelitis) can be fatal and long-term antibiotic therapy is recommended. Despite being potentially fatal, this infection causes...
Malignant otitis externa (skull base osteomyelitis) can be fatal and long-term antibiotic therapy is recommended. Despite being potentially fatal, this infection causes minor changes in inflammatory biomarkers (white blood cell count and C-reactive protein levels) upon blood testing. Computed tomography and magnetic resonance imaging changes persist over a long period. Therefore, it is difficult to determine the optimal time for the discontinuation of antibiotics. We present a 77-year-old male whose medical history included type 2 diabetes mellitus who suffered from chronic otitis media with Pseudomonas aeruginosa infection. His condition did not improve with proper treatment, and imaging revealed malignant otitis media. Intravenous cefepime treatment was administered. Antibiotic treatment was de-escalated to oral levofloxacin treatment after Gallium-67 scintigraphy showed less accumulation after 6 weeks of Cefepime administration; accumulation almost disappeared after 1 year. In this report, we describe the usefulness of gallium scintigraphy in the evaluation of malignant otitis externa.
PubMed: 38764912
DOI: 10.1177/2050313X241253462 -
BMC Infectious Diseases May 2024The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal...
BACKGROUND
The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal infections (IAI), urinary tract infections (UTI), respiratory tract infections (RTI), and blood stream infections (BSI) in emergency departments (EDs) in China.
METHODS
From 2016 to 2019, 656 isolates were collected from 18 hospitals across China. Minimum inhibitory concentrations were determined by CLSI broth microdilution and interpreted according to CLSI M100 (2021) guidelines. In addition, organ-specific weighted incidence antibiograms (OSWIAs) were constructed.
RESULTS
Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the most common pathogens isolated from BSI, IAI and UTI, accounting for 80% of the Gram-negative clinical isolates, while Pseudomonas aeruginosa (P. aeruginosa) was mainly isolated from RTI. E. coli showed < 10% resistance rates to amikacin, colistin, ertapenem, imipenem, meropenem and piperacillin/tazobactam. K. pneumoniae exhibited low resistance rates only to colistin (6.4%) and amikacin (17.5%) with resistance rates of 25-29% to carbapenems. P. aeruginosa exhibited low resistance rates only to amikacin (13.4%), colistin (11.6%), and tobramycin (10.8%) with over 30% resistance to all traditional antipseudomonal antimicrobials including ceftazidime, cefepime, carbapenems and levofloxacin. OSWIAs were different at different infection sites. Among them, the susceptibility of RTI to conventional antibiotics was lower than for IAI, UTI or BSI.
CONCLUSIONS
Gram-negative bacteria collected from Chinese EDs exhibited high resistance to commonly used antibiotics. Susceptibilities were organ specific for different infection sites, knowledge which will be useful for guiding empirical therapies in the clinic.
Topics: Humans; China; Anti-Bacterial Agents; Microbial Sensitivity Tests; Gram-Negative Bacteria; Emergency Service, Hospital; Gram-Negative Bacterial Infections; Urinary Tract Infections; Respiratory Tract Infections; Intraabdominal Infections; Drug Resistance, Bacterial; Female; Male
PubMed: 38760687
DOI: 10.1186/s12879-024-09294-0 -
Ecotoxicology and Environmental Safety Jul 2024Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut...
Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×10 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics.
Topics: Humans; Bile Acids and Salts; Homeostasis; Anti-Bacterial Agents; Adult; Male; Female; Cross-Sectional Studies; Middle Aged; China; Environmental Exposure; Young Adult
PubMed: 38759535
DOI: 10.1016/j.ecoenv.2024.116451 -
Frontiers in Cellular and Infection... 2024() belongs to the class , characterized by a very small genome size, reduction of metabolic pathways, including transcription factors, and the absence of a cell wall....
INTRODUCTION
() belongs to the class , characterized by a very small genome size, reduction of metabolic pathways, including transcription factors, and the absence of a cell wall. Despite this, they adapt well not only to specific niches within the host organism but can also spread throughout the body, colonizing various organs and tissues. The adaptation mechanisms of , as well as their regulatory pathways, are poorly understood. It is known that, when adapting to adverse conditions, can undergo phenotypic switches that may persist for several generations.
METHODS
To investigate the adaptive properties of related to survival in the host, we conducted a comparative phenotypic and proteogenomic analysis of eight clinical isolates of obtained from patients with urogenital infections and the laboratory strain H-34.
RESULTS
We have shown that clinical isolates differ in phenotypic features from the laboratory strain, form biofilms more effectively and show resistance to ofloxacin. The comparative proteogenomic analysis revealed that, unlike the laboratory strain, the clinical isolates possess several features related to stress survival: they switch carbon metabolism, activating the energetically least advantageous pathway of nucleoside utilization, which allows slowing down cellular processes and transitioning to a starvation state; they reconfigure the repertoire of membrane proteins; they have integrative conjugative elements in their genomes, which are key mediators of horizontal gene transfer. The upregulation of the methylating subunit of the restriction-modification (RM) system type I and the additional components of RM systems found in clinical isolates suggest that DNA methylation may play a role in regulating the adaptation mechanisms of in the host organism. It has been shown that based on the proteogenomic profile, namely the genome sequence, protein content, composition of the RM systems and additional subunits HsdM, HsdS and HsdR, composition and number of transposable elements, as well as the sequence of the main variable antigen Vaa, we can divide clinical isolates into two phenotypes: typical colonies (TC), which have a high growth rate, and atypical (aTC) mini-colonies, which have a slow growth rate and exhibit properties similar to persisters.
DISCUSSION
We believe that the key mechanism of adaptation of in the host is phenotypic restructuring, leading to a slowing down cellular processes and the formation of small atypical colonies. This is due to a switch in carbon metabolism and activation the pathway of nucleoside utilization. We hypothesize that DNA methylation may play a role in regulating this switch.
Topics: Humans; Mycoplasma hominis; Proteogenomics; Mycoplasma Infections; Adaptation, Physiological; Biofilms; Genome, Bacterial; Phenotype; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial
PubMed: 38756231
DOI: 10.3389/fcimb.2024.1398706 -
Drug Target Insights 2024Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market.... (Review)
Review
Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to conduct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields-cardiovascular, cancer, and diabetes-and to further underscore the potential risks associated with the emergence of antimicrobial resistance (AMR) when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By comprehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.
PubMed: 38751378
DOI: 10.33393/dti.2024.3019 -
Respirology Case Reports May 2024A 70-year-old immunocompetent male with a history of insomnia presented with pneumonia and bacteremia caused by . The patient took benzodiazepines and regularly consumed...
A 70-year-old immunocompetent male with a history of insomnia presented with pneumonia and bacteremia caused by . The patient took benzodiazepines and regularly consumed alcohol and natto (fermented soybeans). Initial antibiotic treatment was not effective, and bronchoalveolar lavage was performed. Bronchoalveolar lavage fluid (BALF) analysis revealed an increased lymphocytes fraction, and was detected in the BALF. Whole-genome sequencing confirmed the congruence of the genetic sequences between the strain in the blood culture of the patient, BALF, and strain isolated from the consumed natto, confirming subsp as the causative pathogen of pneumonia and bacteremia. Vancomycin followed by levofloxacin and systemic corticosteroid were used to treat the condition. This case highlights community-acquired pneumonia and bacteremia caused by subsp, particularly in individuals who consume natto.
PubMed: 38745892
DOI: 10.1002/rcr2.1384 -
BMC Genomics May 2024Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment....
BACKGROUND
Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium.
METHODS
In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool.
RESULTS
We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE_PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE_PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins.
CONCLUSION
This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs.
Topics: Mycobacterium tuberculosis; Polymorphism, Single Nucleotide; Whole Genome Sequencing; Genome, Bacterial; Humans; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Mutation; Antitubercular Agents; Bacterial Proteins
PubMed: 38745294
DOI: 10.1186/s12864-024-10390-3 -
PloS One 2024The study of Klebsiella quasipneumoniae, Klebsiella variicola, and AmpC production in extended-spectrum β-lactamase (ESBL)-producing Klebsiella in Japan is limited, and...
INTRODUCTION
The study of Klebsiella quasipneumoniae, Klebsiella variicola, and AmpC production in extended-spectrum β-lactamase (ESBL)-producing Klebsiella in Japan is limited, and existing data are insufficient. This study aims to characterize Klebsiella species, determine AmpC production rates, and analyze antimicrobial resistance patterns in ESBL-producing Klebsiella isolates in Japan.
METHODS
A total of 139 clinical isolates of ESBL-producing Klebsiella were collected in Japan, along with their corresponding antimicrobial susceptibility profiles. The isolates were identified using a web-based tool. ESBL genes within the isolates were identified using multiplex PCR. Screening for AmpC-producing isolates was performed using cefoxitin disks, followed by multiplex PCR to detect the presence of AmpC genes. Antimicrobial resistance patterns were analyzed across the predominant ESBL genotypes.
RESULTS
The web-based tool identified 135 isolates (97.1%) as Klebsiella pneumoniae and 4 (2.9%) as K. quasipneumoniae subsp. similipneumoniae, with no instances of K. variicola detected. Among K. pneumoniae, the CTX-M-1 group emerged as the predominant genotype (83/135, 61.5%), followed by K. quasipneumoniae subsp. similipneumoniae (3/4, 75.0%). The CTX-M-9 group was the second most prevalent genotype in K. pneumoniae (45/135, 33.3%). The high resistance rates were observed for quinolones (ranging from 46.7% to 63.0%) and trimethoprim/sulfamethoxazole (78.5%). The CTX-M-1 group exhibited higher resistance to ciprofloxacin (66/83, 79.5%) compared to the CTX-M-9 group (18/45, 40.0%), a trend also observed for levofloxacin and trimethoprim/sulfamethoxazole. Among the 16 isolates that tested positive during AmpC screening, only one K. pneumoniae isolates (0.7%) were confirmed to carry the AmpC gene.
CONCLUSION
Klebsiella pneumoniae with the CTX-M-1 group is the most common ESBL-producing Klebsiella in Japan and showed a low proportion of AmpC production. These isolates are resistant to quinolones and trimethoprim/sulfamethoxazole, highlighting the challenge of managing this pathogen. The findings underscore the importance of broader research and continuous monitoring to address the resistance patterns of ESBL-producing Klebsiella.
Topics: beta-Lactamases; Klebsiella pneumoniae; Bacterial Proteins; Klebsiella; Japan; Retrospective Studies; Humans; Microbial Sensitivity Tests; Klebsiella Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Male; Female; East Asian People
PubMed: 38743684
DOI: 10.1371/journal.pone.0303353 -
Journal of Medicine and Life Jan 2024Multi-drug resistant (MDR) remain a major clinical problem. Infections caused by carbapenem-resistant strains are particularly difficult to treat. This study aimed to...
Multi-drug resistant (MDR) remain a major clinical problem. Infections caused by carbapenem-resistant strains are particularly difficult to treat. This study aimed to assess the clinical and epidemiological characteristics of MDR isolates. A total of 154 non-repetitive clinical isolates, including ( = 66), ( = 70), and other ( = 18), were collected from the Diagnostic Microbiology Laboratory at King Fahad Hospital of the University. Most isolates were collected from urine specimens ( = 50, 75.8%) and resistance against the third and fourth-generation cephalosporins (ceftriaxone, ceftazidime, cefixime, and cefepime) and fluoroquinolones (ciprofloxacin and levofloxacin) was assessed. Clonal relatedness analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed two clones ( A and B), each comprising two strains. Most samples were collected from respiratory specimens (27.1%, 20 samples), and the strains showed overall resistance to most of the antimicrobials tested (54%‒100%). Moreover, clonal-relatedness analysis using ERIC-PCR revealed seven major clones of . These findings suggest nosocomial transmission among some identical strains and emphasize the importance of strict compliance with infection prevention and control policies and regulations. Environmental reservoirs could facilitate this indirect transmission, which needs to be investigated.
Topics: Humans; Drug Resistance, Multiple, Bacterial; Saudi Arabia; Anti-Bacterial Agents; Microbial Sensitivity Tests; Male; Female; Enterobacteriaceae; Enterobacteriaceae Infections; Klebsiella pneumoniae; Cross Infection; Adult; Escherichia coli; Middle Aged; Hospitals, University
PubMed: 38737657
DOI: 10.25122/jml-2023-0189 -
Laryngoscope Investigative... Jun 2024In chronic rhinosinusitis (CRS), the congestion and blockage of the nose can cause anaerobic conditions within the sinus cavities which may promote the expression of...
INTRODUCTION
In chronic rhinosinusitis (CRS), the congestion and blockage of the nose can cause anaerobic conditions within the sinus cavities which may promote the expression of virulence and antibiotic resistance genes in invading pathogens. is a facultative anaerobic bacteria and causes severe recalcitrant CRS. In this study, we aimed to evaluate the antimicrobial resistance of isolates of CRS patients in planktonic and biofilm form grown in aerobic and anaerobic conditions.
METHODS
clinical isolates of CRS patients ( = 25) were grown in planktonic and biofilm form in aerobic and anaerobic conditions. Minimum inhibitory concentrations (MIC) of planktonic forms and minimum biofilm eradication concentrations (MBEC) were determined. Additionally, metabolic activity by fluorescein diacetate assay, biofilm biomass by crystal violet assay and eDNA concentration were assessed in both conditions.
RESULTS
planktonic cells grown in anaerobic condition exhibited increased gentamicin resistance ( < .01), whereas biofilms grown in anaerobic condition displayed significantly increased MBEC values for gentamicin ( < .0001) and levofloxacin ( < .001). The metabolic activity of anaerobic biofilms was significantly higher compared with aerobic biofilms ( < .0001). However, the biofilm biomass of isolates grown in aerobic conditions was higher than anaerobic conditions ( < .5).
CONCLUSION
isolates from CRS patients grown in anaerobic conditions showed significantly increased resistance to antibiotics with an increased metabolic activity but decreased biofilm biomass.
LEVEL OF EVIDENCE
NA.
PubMed: 38736943
DOI: 10.1002/lio2.1244