OBJECTIVE: To evaluate the frequency of antimicrobial-resistant bloodstream infections (AMR BSI) in Thailand.
METHODS: We analyzed data from 2022, generated by 111 public hospitals in health regions 1 to 12, using the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), and submitted to the Ministry of Public Health, Thailand. Multilevel Poisson regression models were used.
RESULTS: The most common cause of community-origin AMR BSI was third-generation cephalosporin-resistant Escherichia coli (3GCREC, 65.6%; 5101/7773 patients) and of hospital-origin AMR BSI was carbapenem-resistant Acinetobacter baumannii (CRAB, 51.2%, 4968/9747 patients). The percentage of patients tested for BSI was negatively associated with the frequency of community-origin 3GCREC BSI and hospital-origin CRAB BSI (per 100,000 tested patients). Hospitals in health regions 4 (lower central region) had the highest frequency of community-origin 3GCREC BSI (adjusted incidence rate ratio, 2.06; 95% confidence interval: 1.52-2.97). Health regions were not associated with the frequency of hospital-origin CRAB BSI, and between-hospital variation was high, even adjusting for hospital level and size.
CONCLUSIONS: The high between-hospital variation of hospital-origin CRAB BSI suggests the importance of hospital-specific factors. Our approach and findings highlight health regions and hospitals where actions against AMR infection, including antimicrobial stewardship and infection control, should be prioritized.

Staphylococcus aureus is one of the most common potentially pathogenic bacteria that may asymptomatically colonize many sites of healthy carriers. Non-nasal carriage, especially in the oral cavity, and its role in transmitting antimicrobial-resistant S. aureus strains in the healthcare community, is poorly understood. This study aimed to assess the prevalence and antimicrobial susceptibility of S. aureus in both oral and nasal cavities among preclinical dentistry students. A total of 264 oral and nasal swabs were taken from 132 participants, and all specimens were cultured using standard diagnostic procedures and antimicrobial susceptibility testing (EUCAST). The prevalence of S. aureus exclusively in the nasal (11.4%) or oral (9.1%) cavity was comparable, while concurrent oral and nasal carriage was present in 27.3% of participants. Although antibiotic resistance rates observed in both oral and nasal isolates were similar (ranging from 2.7% to 95.5%), 16.7% of carriers exhibited distinct antibiotic resistance profiles between oral and nasal isolates. Three (2.7%) methicillin-resistant S. aureus (MRSA) were isolated from the mouth and nose but multidrug resistance (27.3%) was more frequent in the oral than in the nasal isolates: 34% and 21.1%, respectively. This study demonstrated that preclinical dentistry students have a similar rate of oral S. aureus carriage as the nasal carriage rate, and that the oral cavity can be colonized by antimicrobial-resistant strains that do not originate from the nose. Consequently, the oral cavity seems to be an unjustly overlooked body site in screening for S. aureus carriage.

The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) has imposed further challenges to the clinical management of MRSA infections. When exposed to β-lactam antibiotics, these strains can easily acquire reduced β-lactam susceptibility through chromosomal mutations, including those in RNA polymerase (RNAP) genes such as rpoBC, which may then lead to treatment failure. Despite the increasing prevalence of such strains and the apparent challenges they pose for diagnosis and treatment, there is limited information available on the actual mechanisms underlying such chromosomal mutation-related transitions to reduced β-lactam susceptibility, as it does not directly associate with the expression of mecA. This study investigated the cellular physiology and metabolism of six missense mutants with reduced oxacillin susceptibility, each carrying respective mutations on RpoBH929P, RpoBQ645H, RpoCG950R, RpoCG498D, RpiAA64E, and FruBA211E, using capillary electrophoresis-mass spectrometry-based metabolomics analysis. Our results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides. These mutations also led to the accumulation of UDP-Glc/Gal and UDP-GlcNAc, which are precursors of UTP-associated peptidoglycan and wall teichoic acid. Excessive amounts of building blocks then contributed to the cell wall thickening of mutant strains, as observed in transmission electron microscopy, and ultimately resulted in decreased susceptibility to β-lactam in OS-MRSA.
OBJECTIVE: The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) strains has created new challenges for treating MRSA infections. These strains can become resistant to β-lactam antibiotics through chromosomal mutations, including those in the RNA polymerase (RNAP) genes such as rpoBC, leading to treatment failure. This study investigated the mechanisms underlying reduced β-lactam susceptibility in four rpoBC mutants of OS-MRSA. The results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides and precursors of peptidoglycan as well as wall teichoic acid. This, in turn, caused thickening of the cell wall and ultimately resulted in decreased susceptibility to β-lactam in OS-MRSA. These findings provide insights into the mechanisms of antibiotic resistance in OS-MRSA and highlight the importance of continued research in developing effective treatments to combat antibiotic resistance.

Antibiotic-resistant bacteria causing nosocomial infections pose a significant global health concern. This study focused on examining the lipid profiles of both non-resistant and clinically resistant strains of Staphylococcus aureus (MRSA 1418), E. coli (ESBL 1384), and Acinetobacter 1379. The main aim was to investigate the relationship between lipid profiles, hydrophobicity, and antibiotic resistance so as to identify the pathogenic potential and resistance factors of strains isolated from patients with sepsis and urinary tract infections (UTIs). The research included various tests, such as antimicrobial susceptibility assays following CLSI guidelines, biochemical tests, biofilm assays, and hydrophobicity assays. Additionally, gas chromatography mass spectrometry (GC-MS) and GC-Flame Ionization Detector (GC-FID) analysis were used for lipid profiling and composition. The clinically isolated resistant strains (MRSA-1418, ESBL-1384, and Acinetobacter 1379) demonstrated resistance phenotypes of 81.80%, 27.6%, and 63.6%, respectively, with a multiple antibiotic resistance index of 0.81, 0.27, and 0.63. Notably, the MRSA-1418 strain, which exhibited resistance, showed significantly higher levels of hemolysin, cell surface hydrophobicity, biofilm index, and a self-aggregative phenotype compared to the non-resistant strains. Gene expression analysis using quantitative real-time PCR (qPCR). Indicated elevated expression levels of intercellular adhesion biofilm-related genes (icaA, icaC, and icaD) in MRSA-1418 (pgaA, pgaC, and pgaB) and Acinetobacter 1379 after 24 h compared to non-resistant strains. Scanning electron microscopy (SEM) was employed for structural investigation. These findings provide valuable insights into the role of biofilms in antibiotic resistance and suggest potential target pathways for combating antibiotic-resistant bacteria.

UNASSIGNED: Racial and ethnic disparities in infectious disease burden have been reported in the USA and globally, most recently for COVID-19. It remains unclear whether such disparities also exist for priority bacterial pathogens that are increasingly antibiotic-resistant. We conducted a scoping review to summarize published studies that report on colonization or community-acquired infection with pathogens among different races and ethnicities.
UNASSIGNED: We conducted an electronic literature search of MEDLINE®, Daily, Global Health, Embase, Cochrane Central, and Web of Science from inception to January 2022 for eligible observational studies. Abstracts and full-text publications were screened in duplicate for studies that reported data for race or ethnicity for at least one of the pathogens of interest.
UNASSIGNED: Fifty-four observational studies in 59 publications met our inclusion criteria. Studies reported results for Enterobacterales, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus, and were conducted in Australia, Brazil, Israel, New Zealand, and USA. USA studies most often examined Black and Hispanic minority groups with studies regularly reporting a higher risk of these pathogens in Black persons and mixed results for Hispanic persons. Ethnic minority groups (e.g. Bedouins in Israel, Aboriginals in Australia) were often reported to be at a higher risk in other countries.
UNASSIGNED: Sufficient evidence was identified in this scoping review justifying future systematic reviews and meta-analyses evaluating the relationship between community-acquired pathogens and race and ethnicity. However, we noted that only a fraction of studies reported data stratified by race and ethnicity, highlighting a substantial gap in the literature.

Hypervirulent Klebsiella pneumoniae (hvKp) is an emerging pathogen and causes endophthalmitis, liver abscess, osteomyelitis, meningitis, and necrotizing soft tissue infections in both immunodeficient and healthy people. The acquisition of the antibiotic resistance genes of hvKp has become an emerging concern throughout the globe. In this study, a total of 74 K. pneumoniae isolates were collected and identified by VITEK2 and blaSHV gene amplification. Out of these, 18.91% (14/74) isolates were identified as hvKp by both phenotypic string test and genotypic iucA PCR amplification. The antibiotic susceptibility revealed that 57.14% (8/14) isolates were multidrug-resistant (MDR) and 35.71% (5/14) isolates were extremely drug-resistant (XDR). All the isolates were resistant to β-lactam, β-lactamase + inhibitor groups of antibiotics, and the least resistance to colistin. Of 14 hvKp isolates, all isolates are positive for iroB (100%), followed by iutA (92.85%), peg344 (85.71%), rmpA (57.14%), and magA (21.42%) genes. Among serotypes, K1 was the most prevalent serotype 21.4% (3/14), followed by K5 14.3% (2/14). The most common carbapenemase gene was blaOXA-48 (78.57%) followed by blaNDM (14.28%) and blaKPC (14.28%) which co-carried multiple resistance genes such as blaSHV (100%), blaCTX-M (92.85%), and blaTEM (78.57%). About 92.85% (13/14) of hvKp isolates were strong biofilm producers, while one isolate (hvKp 10) was the only moderate biofilm producer. The (GTG)5-PCR molecular typing method revealed high diversity among the hvKp isolates in the tertiary care hospital. Our findings suggest that MDR-hvKp is an emerging pathogen and a challenge for clinical practice. In order to avoid hvKp strain outbreaks in hospital settings, robust infection control and effective surveillance should be implemented.

BACKGROUND: Antimicrobial use (AMU) is closely related to the emergence of antimicrobial-resistant (AMR) bacteria. Meanwhile, long-term care hospitals (LTCHs) have been pointed out to be important reservoirs for AMR. However, evidence illustrating the association between AMU and AMR in LTCHs is lacking compared to that of acute care hospitals.
METHODS: We evaluated the impact of an antimicrobial stewardship (AS) program implementation, in a LTCH on AMU and antibiotic susceptibility between three periods: the pre-AS-period (pre-AS); the first period after AS implementation (post-AS 1), in which initiated recommendation the blood culture collection and definitive therapy by AS team; and the second period (post-AS 2), implementation of a balanced use of antibiotics was added.
RESULTS: After the AS implementation, a significant increase in the number of blood cultures collected was observed. Conversely, the AMU of piperacillin-tazobactam (PIPC/TAZ), which has activity against Pseudomonas aeruginosa, was increased and occupied 43.0% of all injectable AMU in post-AS 1 compared with that in pre-AS (35.5%). In the post-AS 2 period, we analyzed the %AUD and recommended hospital-wide PIPC/TAZ sparing; this resulted in the significant reduction in %AUD of PIPC/TAZ, which was associated with improved susceptibility of P. aeruginosa to PIPC/TAZ.
CONCLUSIONS: These results suggest that AS programs aimed at implementing antibiotic sparing may lead to improve AMR, highlighting the necessity of correcting overuse of a single class of antibiotics and usefulness of AMU monitoring in the LTCH setting.

The continuous rise of antimicrobial resistance (AMR) is a serious concern as it endangers the effectiveness of healthcare interventions that rely on antibiotics in the long run. The increasing resistance of Neisseria gonorrhoeae, the bacteria responsible for causing gonorrhea, to commonly used antimicrobial drugs, is a major concern. This has now become a critical global health crisis. In the coming years, there is a risk of a hidden epidemic caused by the emergence of gonococcal AMR. This will worsen the global situation. Infections caused by N. gonorrhoeae were once considered easily treatable. However, over time, they have become increasingly resistant to commonly used therapeutic medications, such as penicillin, ciprofloxacin, and azithromycin. As a result, this pathogen is developing into a true \"superbug,\" which means that ceftriaxone is now the only available option for initial empirical treatment. Effective management strategies are urgently needed to prevent severe consequences, such as infertility and pelvic inflammatory disease, which can result from delayed intervention. This review provides a thorough analysis of the escalating problem of N. gonorrhoeae, including its pathogenesis, current treatment options, the emergence of drug-resistant mechanisms, and the potential for vaccine development. We aim to provide valuable insights for healthcare practitioners, policymakers, and researchers in their efforts to combat N. gonorrhoeae antibiotic resistance by elucidating the multifaceted aspects of this global challenge.

BACKGROUND: Due to high mortality and limited treatment options, the rise in carbapenemase-producing Enterobacterales (CPE) has become a major concern. This study aimed to evaluate the incidence and characteristics of subsequent CPE bacteraemia in rectal CPE carriers and investigate the risk factors for CPE bacteraemia compared with non-carbapenemase-producing (non-CP) Enterobacterales bacteraemia.
METHODS: A retrospective analysis was conducted on adult patients who were confirmed to have CPE colonisation by stool surveillance culture at a tertiary hospital from January 2018 to February 2022. All episodes of Enterobacterales bacteraemia up to 6 months after CPE colonisation were identified.
RESULTS: Of 1174 patients identified as rectal CPE carriers, 69 (5.8%; 95% CI 4.6-7.3%) experienced subsequent CPE bacteraemia during the 6 months after the diagnosis of CPE colonisation. Colonisation by a Klebsiella pneumoniae carbapenemase (KPC) producer (or CP-K. pneumoniae), colonisation by multiple CPE species, chronic kidney disease and haematological malignancy were independently associated with CPE bacteraemia in CPE carriers. When CPE carriers developed Enterobacterales bacteraemia, the causative agent was more frequently non-CP Enterobacterales than CPE (63.6% vs. 36.4%). Among these patients, colonisation with a KPC producer, CPE colonisation at multiple sites, shorter duration from colonisation to bacteraemia (< 30 days) and recent intraabdominal surgery were independent risk factors for CPE bacteraemia rather than non-CP Enterobacterales bacteraemia.
CONCLUSIONS: In CPE carriers, non-CP Enterobacterales were more often responsible for bacteraemia than CPE. Empirical antibiotic therapy for CPE should be considered when sepsis is suspected in a CPE carrier with risk factors for CPE bacteraemia.

The discovery of compounds with antibacterial activity is crucial in the ongoing battle against antibiotic resistance. We developed two QSAR models to design six novel heteroaryl drug candidates and assessed their antibacterial properties against nine ATCC strains, including Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and also Salmonella enterica and Escherichia coli, many of which belong to the ESKAPE group. We combined PB4, a previously tested compound from published studies, with GC-VI-70, a newly discovered compound, with the best cytotoxicity/MIC profile. By testing sub-MIC concentrations of PB4 with five antibiotics (linezolid, gentamycin, ampicillin, erythromycin, rifampin, and imipenem), we evaluated the combination\'s efficacy against the ATCC strains. To assess the compounds\' cytotoxicity, we conducted a 24 h and 48 h 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on colorectal adenocarcinoma (CaCo-2) cells. We tested the antibiotics alone and in combination with PB4. Encouragingly, PB4 reduced the MIC values for GC-VI-70 and for the various clinically used antibiotics. However, it is essential to note that all the compounds studied in this research exhibited cytotoxic activity against cells. These findings highlight the potential of using these compounds in combination with antibiotics to enhance their effectiveness at lower concentrations while minimizing cytotoxic effects.