Search Results (17)

Background: Four of the six ESKAPE pathogens are responsible for a majority of antimicrobial resistance (AMR)-related deaths worldwide. Identifying the pathogens that evade antibiotic treatments more efficiently than others can help diagnose pathogens requiring more attention. The study was thus designed to evaluate the biofilm and resistance properties of five ESKAPE pathogens comparatively. A total of 165 clinical isolates of 5 ESKAPE pathogen species (E. faecium, S. aureus, K. pneumoniae, A. baumannii, and P. aerurginosa) were collected from a tertiary hospital in Bangladesh. Methodology: Following secondary identification, antibiotic susceptibility was determined by the disc diffusion method and minimum inhibitory concentration. The biofilm formation was determined by the microtiter plate biofilm formation assay. The biofilm-forming genes were screened by PCR. Detection of carbapenemase and Metallo-β-lactamase was performed by the modified carbapenem inactivation method (mCIM) and the EDTA-modified carbapenem inactivation method (eCIM) test, respectively. Results: Among Gram-positive isolates, E. faecium exhibited higher multi-drug resistance (MDR) rates (90%) compared to S. aureus (10%). In Gram-negative isolates, A. baumannii and K. pneumoniae showed elevated resistance to carbapenems (74.29% and 45.71%, respectively), cephalosporins, and β-lactam inhibitors, while P. aeruginosa demonstrated relatively lower resistance. Colistin resistance was highest in K. pneumoniae (42.86%). Biofilm formation was prevalent, with 88.5% of isolates forming biofilms, including 15.8% strong biofilm producers. Notably, K. pneumoniae and A. baumannii exhibited higher biofilm-forming capabilities compared to P. aeruginosa. A significant correlation was observed between biofilm formation and resistance to carbapenems, cephalosporins, and piperacillin/tazobactam (p < 0.05), suggesting a potential role of biofilms in disseminating resistance to these antibiotics. Carbapenemase production was detected in 23.8% of Gram-negative isolates, with K. pneumoniae showing the highest prevalence (34.3%). Additionally, 45.8% of carbapenemase producers expressed Metallo-β-lactamases (MBLs). Among S. aureus isolates, 46.7% carried the mecA gene, confirming methicillin resistance (MRSA), while 20% of E. faecium isolates exhibited vancomycin resistance, primarily mediated by the vanB gene. Conclusions: These findings can help pinpoint the pathogens of significant threat. Full article

Background/Objectives: Multidrug-resistant (MDR) bacterial colonization poses a significant risk for subsequent infections, especially within hospital environments. Healthcare workers can inadvertently transmit these MDR bacteria to vulnerable patients, exacerbating the problem. This study aimed to determine the colonization rates of MDR bacteria among patients and healthcare workers in a rural Ethiopian hospital with limited resources. Methods: Between 26 May and 6 June 2024, nasal, rectal, vagino-rectal exudate, and stool samples were collected from patients (n = 78) and healthcare workers (n = 11) at Gambo General Hospital (Oromia Region, Ethiopia). Samples were cultured on chromogenic media selective for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), and carbapenemase-producing Enterobacteriaceae (CPE). Bacterial identification was performed using MALDI-TOF mass spectrometry (Bruker), antimicrobial susceptibility testing using the MicroScan WalkAway system (Beckman Coulter), and genotypic characterization with the MDR Direct Flow Chip kit (Vitro). Results: MRSA nasal colonization was detected in 43.3% of patients (13/30; 95% CI: 27.4–60.8%) and 27.3% of healthcare workers (3/11; 95% CI: 6.0–61.0%) (p = 0.73). Rectal (or stool) colonization by MDR bacteria was significantly higher in pediatric patients (85.0%, 17/20; 95% CI: 62.1–96.8%) than in adults (14.3%, 4/28; 95% CI: 5.7–31.5%) (p < 0.001). Notably, a high proportion of pediatric patients harbored Escherichia coli strains co-producing NDM carbapenemase and CTX-M ESBL, and VRE strains were also predominantly isolated in this group. Conclusions: This study reveals a concerningly high prevalence of MRSA and MDR Enterobacteriaceae, especially among children at Gambo Hospital. The VRE prevalence was also substantially elevated compared to other studies. These findings underscore the urgent need for strengthened infection control measures and antimicrobial stewardship programs within the hospital setting. Full article

In this study, we isolated and identified bacteria from the feces of a diarrheal cynomolgus monkey. The results showed that the isolated strain was P. aeruginosa, named PA/CM-101101. Morphological observations indicated that when cultured on Luria–Bertani (LB) nutrient agar at 37 °C for 24 h, the strain formed smooth, slightly elevated colonies with neat and wavy edges. On acetamide agar at the same temperature and duration, the colonies appeared flat with irregular edges and a faint pink periphery, while the medium changed to rose-red; in LB broth at 37 °C for 24 h, the medium became turbid and yellowish-green. Gram staining revealed that it was negative and rod-shaped, without sporulation characteristics. The 16S rRNA gene sequence analysis showed that the sequence identity of the strain shared more than 98.4% similarity with 11 strains of P. aeruginosa from various sources in GenBank. The animal toxicity test showed that it had a strong pathogenic effect on mice. The results of drug sensitivity tests showed that strain PA/CM-101101 was sensitive to amikacin, azithromycin, cefoperazone, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, levofloxacin, meropenem, norfloxacin, ofloxacin, and polymyxin B; however, it displayed resistance to ampicillin, cefadroxil, cefazolin, erythromycin, and vancomycin. The research findings provide valuable insights for diagnosis and treatment strategies for cynomolgus monkeys. It also provides a reference for molecular epidemiological studies. To our knowledge, this is the first time P. aeruginosa isolated from the diarrhea feces of cynomolgus monkey has been reported. Full article

Staphylococcus aureus is a significant bacterial pathogen responsible for a wide range of diseases in both humans and animals. This study aimed to investigate nucleotide sequence variations, gene expression patterns, and serum biomarkers, including acute phase proteins (APPs), hormonal fluctuations, and iron profile parameters in sheep affected by pneumonia. Additionally, the study focused on the isolation and characterization of S. aureus from pneumonic sheep, with particular emphasis on the prevalence of methicillin-resistant S. aureus (MRSA) strains. Blood samples were collected from both healthy and pneumonic sheep for gene expression and biochemical analyses, while nasal swabs from pneumonic sheep were used for bacterial isolation and identification. Out of 100 nasal swabs analyzed, 44% tested positive for Staphylococcus spp., and 61.4% of these were confirmed as S. aureus by PCR. The mecA gene, a key marker of methicillin resistance, was identified in 17 isolates (38.6% of the S. aureus-positive samples). MRSA isolates showed complete resistance to amoxicillin, cloxacillin, and erythromycin, and high resistance to penicillin, amoxicillin, and tetracycline; however, all MRSA strains remained fully susceptible to vancomycin. Gene expression analysis revealed that TLR2, CLEC4E, PTX3, CXCL8, and IL15RA were significantly upregulated (p < 0.05) in pneumonic ewes, while SOCS3 expression was markedly downregulated. Sequence analysis of immune-related genes revealed notable nucleotide differences between healthy and affected animals. Furthermore, the pneumonic group exhibited significantly elevated levels of APPs, cortisol, and growth hormone, along with reduced levels of insulin, T3, and T4. These findings underscore the zoonotic risk posed by MRSA and emphasize the need for robust surveillance and antibiotic stewardship to control its spread. The study also highlights the importance of molecular diagnostics in accurately identifying MRSA and elucidating resistance mechanisms, thereby facilitating targeted treatment and informed management strategies. Full article

Objectives: This study aimed to analyze the antibiotic resistance patterns of microorganisms isolated from intensive care unit (ICU) patients and evaluate their impact on mortality and length of ICU stay. Given the increasing prevalence of multidrug-resistant (MDR) pathogens in critically ill patients, understanding their resistance profiles is crucial for optimizing empirical antibiotic therapy and improving patient outcomes. Methods: This retrospective study included 237 ICU patients admitted between 1 July 2022, and 1 January 2024. The initial culture growth results from blood and urine samples were analyzed. Microorganism identification was performed using VITEK 2 Compact and conventional bacteriological methods, while antibiotic susceptibility testing followed CLSI 2022 and EUCAST 2022 guidelines. Results: A total of 237 ICU patients were included in this study. The most frequently isolated microorganisms were Escherichia coli (E. coli) (44.3%), Klebsiella pneumoniae (K. pneumoniae) (35.0%), and Pseudomonas aeruginosa (P. aeruginosa) (25.3%), with Acinetobacter baumannii (A. baumannii) (31.2%) being the most resistant pathogen. Among Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) (12.2%) and vancomycin-resistant enterococci (VRE) (21.5%) were the most frequently identified multidrug-resistant (MDR) pathogens. Regarding antimicrobial resistance, carbapenem resistance was highest in A. baumannii (55%), followed by P. aeruginosa (40%) and K. pneumoniae (30%). Additionally, ESBL-producing E. coli (43.2%) and K. pneumoniae (38.5%), as well as carbapenemase-producing K. pneumoniae (18.6%) and E. coli (9.2%), were identified as key resistance mechanisms impacting clinical outcomes. Patients with MDR infections had significantly longer ICU stays (p < 0.05) and higher mortality rates. The Kaplan–Meier survival analysis revealed that A. baumannii infections were associated with the highest mortality risk (HR: 4.6, p < 0.001), followed by MRSA (HR: 3.5, p = 0.005) and P. aeruginosa (HR: 2.8, p = 0.01). Among laboratory biomarkers, elevated procalcitonin (≥2 ng/mL, OR: 2.8, p = 0.008) and CRP (≥100 mg/L, OR: 2.2, p = 0.01) were significantly associated with ICU mortality. Additionally, patients who remained in the ICU for more than seven days had a 1.4-fold increased risk of mortality (p = 0.02), further emphasizing the impact of prolonged hospitalization on adverse outcomes. Conclusions: MDR pathogens, particularly A. baumannii, MRSA, P. aeruginosa, and K. pneumoniae, are associated with longer ICU stays and higher mortality rates. Carbapenem, cephalosporin, fluoroquinolone, and aminoglycoside resistance significantly impact clinical outcomes, emphasizing the urgent need for antimicrobial stewardship programs. ESBL, p-AmpC, and carbapenemase-producing Enterobacterales further worsen patient outcomes, highlighting the need for early infection control strategies and optimized empirical antibiotic selection. Biomarkers such as procalcitonin and CRP, alongside clinical severity scores, serve as valuable prognostic tools for ICU mortality. Full article

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) presents a major public health challenge due to its multidrug resistance and high virulence. Developing representative model strains is crucial for systematically assessing pathogenesis and antimicrobial therapies. Methods: The highly virulent MRSA strain T144, isolated from pigs, was characterized through whole-genome sequencing and antimicrobial susceptibility testing. Infection models were successfully established in Galleria mellonella and mice to evaluate virulence. A mouse lung infection model was specifically developed to assess bacterial load dynamics, immune responses, and the efficacy of vancomycin treatment. Results: MRSA T144 demonstrated broad-spectrum antibiotic resistance and high mortality rates in both Galleria mellonella and mouse models. Whole-genome sequencing identified multiple virulence-associated genes, including hemolysins and enterotoxins. The concentration of 7 × 10⁸ CFUs was optimized for establishing the mouse lung infection model. In the mouse lung infection model, MRSA T144 demonstrated rapid bacterial proliferation within the first 24 h, followed by a slower growth rate. Significant changes in immune markers were observed, with elevated levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17a, TNF-α) and decreased IL-10 levels. Vancomycin treatment significantly improved survival rates and reduced bacterial load, confirming the model’s utility for antimicrobial efficacy studies. Conclusions: The successful establishment of MRSA T144 infection models provides a robust platform for investigating bacterial dynamics, immune responses, and antimicrobial efficacy against highly virulent MRSA strains. These findings highlight the potential of MRSA T144 as a valuable model for developing novel therapeutic strategies. Full article

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19. Full article

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections. Full article

Adiponectin is primarily known for its protective role in metabolic diseases, and it also possesses immunoregulatory properties. Elevated levels of adiponectin have been observed in various inflammatory diseases. However, studies investigating adiponectin levels in the serum of COVID-19 patients have yielded conflicting results. This study aimed to assess serum adiponectin levels in 26 healthy controls, as well as in 64 patients with moderate and 60 patients with severe COVID-19, to determine a potential association between serum adiponectin and the severity of COVID-19. Serum adiponectin levels in severe COVID-19 patients were significantly lower than in those with moderate disease and healthy controls, who exhibited similar serum adiponectin levels. Among patients with moderate disease, positive correlations were observed between serum adiponectin and C-reactive protein levels. Of note, serum adiponectin levels of severe COVID-19 cases were comparable between patients with and without dialysis or vasopressor therapy. Superinfection with bacteria did not exert a notable influence on serum adiponectin levels in patients with severe disease. Patients who were diagnosed with severe COVID-19 and vancomycin-resistant enterococci bacteremia showed a significant reduction in their serum adiponectin levels. An analysis conducted on the entire cohort, including both moderate and severe COVID-19 patients, showed that individuals who did not survive had lower serum adiponectin levels when compared to those who survived. In summary, this study highlights a decrease in serum adiponectin levels in severe COVID-19 cases, indicating the potential utility of adiponectin as an additional biomarker for monitoring disease severity in COVID-19 or critical illnesses in general. Full article

Valley surface water is considered a focal public health concern owing to the presence of multi-drug-resistant bacteria. The distribution of antimicrobial resistance (AMR) bacteria in the surface water is affected by the presence of multiple factors, including antibiotics coming from wastewater discharge or other contaminant sources such as pharmaceuticals, biocides, and heavy metals. Furthermore, there is evidence suggesting that high levels of antibiotic resistance genes (ARGs) can be transferred within bacterial communities under the influence of heavy metal stress. Hence, the primary aim of this study is to investigate the presence of heavy metals and bacterial ARGs in upstream as well as downstream locations of Wadi Hanifah Valley in Riyadh, Saudi Arabia. Sample collection was conducted at eighteen surface water sites within the valley in total. The selection of ARGs was associated with the most common antibiotics, including β-lactam, tetracycline, erythromycin, gentamicin, sulphonamide, chloramphenicol, vancomycin, trimethoprim, and colistin antibiotics, which were detected qualitatively using polymerase chain reaction (PCR) technology. The tested antibiotic resistance genes (ARGs) included (bla_NDM-1 (for the antibiotic class Beta-lactamases), mecA (methicillin-resistant Staphylococcus aureus), tet(M) and tet(B) (for the antibiotic class Tetracycline), ampC (for the antibiotic class Beta-lactamases), vanA (for the antibiotic class vancomycin), mcr-1 (for the antibiotic class colistin), erm(B) (for the antibiotic class erythromycin), aac6′-Ie-aph2-Ia (for the antibiotic class Gentamicin), sulII (for the antibiotic class sulphonamide), catII (for the antibiotic class Chlorophincol), and dfrA1 (for the antibiotic class trimethoprim). Moreover, an assessment of the levels of heavy metals such as lithium (Li), beryllium (Be), chromium (Cr), cobalt (Co), arsenic (As), cadmium (Cd), tin (Sn), mercury (Hg), and lead (Pb) was conducted by using inductively coupled plasma mass spectrometry (ICPMS). According to our findings, the concentrations of sulphonamide, erythromycin, and chloramphenicol ARGs (erm(B), sulII, and catII) were observed to be the most elevated. Conversely, two ARGs, namely mecA and mcr-1, were not detected in the samples. Moreover, our data illustrated a significant rise in ARGs in the bacteria of water samples from the upstream sites as compared with the water samples from the downstream sites of Wadi Hanifah Valley. The mean concentration of Li, Be, Cr, Co, As, Cd, Sn, Hg, and Pb in the water samples was estimated to be 37.25 µg/L, 0.02 µg/L, 0.56 µg/L,0.32 µg/L, 0.93 µg/L, 0.01 µg/L, 200.4 µg/L, 0.027 µg/L, and 0.26 µg/L, respectively, for the selected 18 sites. Furthermore, it was revealed that the concentrations of the screened heavy metals in the water samples collected from various sites did not surpass the maximum limits set by the World Health Organization (WHO). In conclusion, this study offers a concise overview of the presence of heavy metals and ARGs in water samples obtained from the Wadi Hanifah Valley in Riyadh, KSA. Such findings will contribute to the ongoing monitoring and future risk assessment of ARGs spread in surface water. Full article

The Gram-negative Elizabethkingia express multiple antibiotic resistance and cause severe opportunistic infections. Vancomycin is commonly used to treat Gram-positive infections and has also been used to treat Elizabethkingia infections, even though Gram-negative organisms possess a vancomycin permeability barrier. Elizabethkingia anophelis appeared relatively vancomycin-susceptible and challenge with this drug led to morphological changes indicating cell lysis. In stark contrast, vancomycin growth challenge revealed that E. anophelis populations refractory to vancomycin emerged. In addition, E. anophelis vancomycin-selected mutants arose at high frequencies and demonstrated elevated vancomycin resistance and reduced susceptibility to other antimicrobials. All mutants possessed a SNP in a gene (vsr1 = vancomycin-susceptibility regulator 1) encoding a PadR family transcriptional regulator located in the putative operon vsr1-ORF551, which is conserved in other Elizabethkingia spp as well. This is the first report linking a padR homologue (vsr1) to antimicrobial resistance in a Gram-negative organism. We provide evidence to support that vsr1 acts as a negative regulator of vsr1-ORF551 and that vsr1-ORF551 upregulation is observed in vancomycin-selected mutants. Vancomycin-selected mutants also demonstrated reduced cell length indicating that cell wall synthesis is affected. ORF551 is a membrane-spanning protein with a small phage shock protein conserved domain. We hypothesize that since vancomycin-resistance is a function of membrane permeability in Gram-negative organisms, it is likely that the antimicrobial resistance mechanism in the vancomycin-selected mutants involves altered drug permeability. Full article

This study focused on the identification of bacterial profiles of semen in normozoospermic men and their possible involvement in changes to the sperm structural integrity and functional activity. Furthermore, we studied possible fluctuations of selected cytokines, oxidative markers, and antibacterial proteins as a result of bacterial presence in the ejaculate. Sperm motility was assessed with computer-assisted sperm analysis, while sperm apoptosis, necrosis and acrosome integrity were examined with fluorescent methods. Reactive oxygen species (ROS) generation was quantified via luminometry, sperm DNA fragmentation was evaluated using the TUNEL protocol and chromatin-dispersion test, while the JC-1 assay was applied to evaluate the mitochondrial membrane potential. Cytokine levels were quantified with the biochip assay, whilst selected antibacterial proteins were quantified using the ELISA method. The predominant species identified by the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were Staphylococcus hominis, Staphylococcus capitis and Micrococcus luteus. The results revealed that the sperm quality decreased proportionally to the increasing bacterial load and occurrence of conditionally pathogenic bacteria, including Enterococcus faecalis, Staphylococcus aureus and Escherichia coli. Antimicrobial susceptibility tests revealed a substantial resistance of randomly selected bacterial strains to ampicillin, vancomycin, tobramycin, and tetracycline. Furthermore, an increased bacterial quantity in semen was accompanied by elevated levels of pro-inflammatory cytokines, including interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor alpha as well as ROS overproduction and lipid peroxidation of the sperm membranes. Our results suggest that semen quality may be notably affected by the bacterial quantity as well as quality. It seems that bacteriospermia may be associated with inflammatory processes, oxidative stress, sperm structural deterioration, and a subsequent risk for the development of subfertility, even in normozoospermic males. Full article

Background: Healthcare-associated infections (HAIs) cause increases in length of stay, mortality, and healthcare costs. A previous study conducted in Taiwan obtained similar results to those reported in Korea and Japan in 2015. Changes in microorganisms have been noted in recent years. Understanding the recent condition of HAIs in intensive care units (ICUs) can enable healthcare providers to develop effective infection control protocols to reduce HAIs. Methods: We used the Taiwan Nosocomial Infection Surveillance System to evaluate the incidence densities of HAIs, the proportions of causative pathogens, and the proportions of antimicrobial resistance (AMR). The Poisson regression model was constructed to incidence density, and the chi-square test was used to assess proportion. Results: The incidence density of HAIs decreased 5.7 to 5.4 per 1000 person-days. However, the proportions of Klebsiella pneumoniae and Enterococcus faecium significantly increased. In addition, the proportions of carbapenem-resistant K. pneumoniae and vancomycin-resistant Enterococcus faecium significantly increased over time. Conclusion: Analysis of the microorganisms involved in HAIs in ICUs showed elevated proportions of K. pneumoniae and E. faecium with AMR. Infection control protocols have been implemented for several years and require improvements regarding environmental cleanliness and medical staff prevention. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Recently, the role of released bacterial-derived membrane vesicles (MVs) in antibiotic resistance has garnered attention. Here we examined the effect of exogenous MRSA-derived MVs on VAN activity against MRSA in vitro, using minimum inhibitory concentration and checkerboard assays, and ex vivo, incorporating components of host innate immunity such as neutrophils and serum complement present in blood. Additionally, the proteome of MVs from VAN-exposed MRSA was characterized to determine if protein expression was altered. The presence of MVs increased the VAN MIC against MRSA to values where clinical failure is commonly observed. Furthermore, the presence of MVs increased survival of MRSA pre-treated with sub-MIC concentrations of VAN in whole blood and upon exposure to human neutrophils but not human serum. Unbiased proteomic analysis also showed an elevated expression of MV proteins associated with antibiotic resistance (e.g., marR) or proteins that are functionally linked to cell membrane/wall metabolism. Together, our findings indicate MRSA-derived MVs are capable of lowering susceptibility of the pathogen to VAN, whole-blood- and neutrophil-mediated killing, a new pharmacodynamic consideration for a drug increasingly linked to clinical treatment failures. Full article

This study aimed to evaluate the reduction in vancomycin through intermittent haemodialysis (IHD) and prolonged haemodialysis (PHD) in acute kidney injury (AKI) patients with sepsis and to identify the variables associated with subtherapeutic concentrations. A prospective study was performed in patients admitted at an intensive care unit (ICU) of a Brazilian hospital. Blood samples were collected at the start of dialytic therapy, after 2 and 4 h of treatment and at the end of therapy to determine the serum concentration of vancomycin and thus perform pharmacokinetic evaluation and PK/PD modelling. Twenty-seven patients treated with IHD, 17 treated with PHD for 6 h and 11 treated with PHD for 10 h were included. The reduction in serum concentrations of vancomycin after 2 h of therapy was 26.65 ± 12.64% and at the end of dialysis was 45.78 ± 12.79%, higher in the 10-h PHD group, 57.70% (40, 48–64, 30%) (p = 0.037). The ratio of the area under the curve to minimal inhibitory concentration (AUC/MIC) at 24 h in the PHD group was significantly smaller than at 10 h (p = 0.047). In the logistic regression, PHD was a risk factor for an AUC/MIC ratio less than 400 (OR = 11.59, p = 0.033), while a higher serum concentration of vancomycin at T0 was a protective factor (OR = 0.791, p = 0.009). In conclusion, subtherapeutic concentrations of vancomycin in acute kidney injury (AKI) patients in dialysis were elevated and may be related to a higher risk of bacterial resistance and mortality, besides pointing out the necessity of additional doses of vancomycin during dialytic therapy, mainly in PHD. Full article