-
The Journal of Antimicrobial... Jun 2024Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring...
BACKGROUND
Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring antimicrobial combinations for coverage. However, possible antagonistic interactions between antibiotics have not been thoroughly explored. This study aimed to evaluate the effectiveness of antimicrobial combinations against Elizabethkingia infections, focusing on their impact on pathogenicity, including biofilm production and cell adhesion.
METHODS
Double-disc diffusion, time-kill, and chequerboard assays were used for evaluating the combination effects of antibiotics against Elizabethkingia spp. We further examined the antagonistic effects of antibiotic combinations on biofilm formation and adherence to A549 human respiratory epithelial cells. Further validation of the antibiotic interactions and their implications was performed using ex vivo hamster precision-cut lung sections (PCLSs) to mimic in vivo conditions.
RESULTS
Antagonistic effects were observed between cefoxitin, imipenem and amoxicillin/clavulanic acid in combination with vancomycin. The antagonism of imipenem toward vancomycin was specific to its effects on the genus Elizabethkingia. Imipenem further hampered the bactericidal effect of vancomycin and impaired its inhibition of biofilm formation and the adhesion of Elizabethkingia meningoseptica ATCC 13253 to human cells. In the ex vivo PCLS model, vancomycin exhibited dose-dependent bactericidal effects; however, the addition of imipenem also reduced the effect of vancomycin.
CONCLUSIONS
Imipenem reduced the bactericidal efficacy of vancomycin against Elizabethkingia spp. and compromised its capacity to inhibit biofilm formation, thereby enhancing bacterial adhesion. Clinicians should be aware of the potential issues with the use of these antibiotic combinations when treating Elizabethkingia infections.
PubMed: 38906827
DOI: 10.1093/jac/dkae210 -
Journal of Microbiology (Seoul, Korea) Jun 2024Alcaligenes faecalis is one of the most important and clinically significant environmental pathogens, increasing in importance due to its isolation from soil and...
Alcaligenes faecalis is one of the most important and clinically significant environmental pathogens, increasing in importance due to its isolation from soil and nosocomial environments. The Gram-negative soil bacterium is associated with skin endocarditis, bacteremia, dysentery, meningitis, endophthalmitis, urinary tract infections, and pneumonia in patients. With emerging antibiotic resistance in A. faecalis, it has become crucial to understand the origin of such resistance genes within this clinically significant environmental and gut bacterium. In this research, we studied the impact of antibiotic overuse in poultry and its effect on developing resistance in A. faecalis. We sampled soil and faecal materials from five poultry farms, performed whole genome sequencing & analysis and identified four strains of A. faecalis. Furthermore, we characterized the genes in the genomic islands of A. faecalis isolates. We found four multidrug-resistant A. faecalis strains that showed resistance against vancomycin (MIC >1000 μg/ml), ceftazidime (50 μg/ml), colistin (50 μg/ml) and ciprofloxacin (50 μg/ml). From whole genome comparative analysis, we found more than 180 resistance genes compared to the reference sequence. Parts of our assembled contigs were found to be similar to different bacteria which included pbp1A and pbp2 imparting resistance to amoxicillin originally a part of Helicobacter and Bordetella pertussis. We also found the Mycobacterial insertion element IS6110 in the genomic islands of all four genomes. This prominent insertion element can be transferred and induce resistance to other bacterial genomes. The results thus are crucial in understanding the transfer of resistance genes in the environment and can help in developing regimes for antibiotic use in the food and poultry industry.
PubMed: 38904697
DOI: 10.1007/s12275-024-00129-w -
Journal of Burn Care & Research :... Jun 2024Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse...
A Multicenter, Retrospective Outcome Analysis of Vancomycin Area Under the Curve versus Trough-Based Dosing Strategies in Patients with Burn OR Inhalational Injuries (MONITOR).
Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse effects such as nephrotoxicity. However, sub-therapeutic concentrations may lead to bacterial resistance and clinical failure or death. The most recent Infectious Diseases Society of America (IDSA) publication regarding therapeutic monitoring of vancomycin recommends utilizing area under the curve (AUC)-based monitoring to maximize clinical success. Despite the guideline recommendation for AUC-guided dosing, many institutions still use trough-only monitoring in their practices, including those caring for patients with acute burn injuries. Following burn injury, patients are at a higher risk for infections, multi-organ failure, and pharmacokinetic alterations. The primary objective of this multi-center retrospective study is to determine optimal therapeutic monitoring of vancomycin by comparing clinical success between AUC vs. trough-based monitoring in burn patients. MONITOR was a multicenter, retrospective study of patients with thermal or inhalation injury admitted to one of 13 burn centers from 1/1/17 to 8/31/22 who received vancomycin. Demographic and clinical course data, including acute kidney injury (AKI) incidence and clinical success were obtained. Patients were evaluated for clinical success and grouped according to method of monitoring and adjusting doses: AUC vs. trough-based monitoring. Clinical success was a composite definition and lack of meeting any 1 of 5 criteria: 1) persistent infection, 2) relapse, 3) antibiotic failure (clinical worsening), 4) AKI, 5) death. Five-hundred seventeen vancomycin courses were assessed from 485 patients. There was no difference in the rate of clinical success between AUC monitored and the trough-only monitored groups. Incidence of AKI was higher in the trough-only group; however, was not statistically significant after controlling for renal function on admission, past medical history of chronic kidney disease (CKD), and concomitant nephrotoxins.
PubMed: 38900835
DOI: 10.1093/jbcr/irae109 -
Nanoscale Jun 2024Supramolecular hydrogels serve as an excellent platform to enable reactive oxygen species (ROS) generation while maintaining controlled localized conditions, thereby...
Supramolecular hydrogels serve as an excellent platform to enable reactive oxygen species (ROS) generation while maintaining controlled localized conditions, thereby mitigating cytotoxicity. Herein, we demonstrate hydrogel formation using guanosine-5'-monophosphate (GMP) with tetra(4-carboxylphenyl) ethylene (1) to exhibit aggregation-induced emission (AIE) and tunable mechanical strength in the presence of divalent metal ions such as Ca, Mg, and Fe. The addition of divalent metal ions leads to structural transformation in the metallogels (M-1GMP). Furthermore, the incorporation of Fe ions into the hydrogel (Fe-1GMP) promotes the Fenton reaction that could be upregulated upon adding ascorbic acid (AA), demonstrating antibacterial efficacy ROS generation. studies on AA-loaded Fe-1GMP demonstrate excellent bacterial killing efficacy against , and vancomycin-resistant enterococci (VRE) strains. Finally, studies involving topical administration of Fe-1GMP to Balb/c mice with skin infections further suggest the potential antibacterial efficacy of the hydrogel. Taken together, the hydrogel with its unique combination of mechanical tunability, ROS generation capability and antibacterial efficacy can be used for biomedical applications, particularly in wound healing and infection control.
PubMed: 38899974
DOI: 10.1039/d4nr01011f -
Antimicrobial Agents and Chemotherapy Jun 2024is a pathogenic bacterium responsible for a broad spectrum of infections, including cutaneous, respiratory, osteoarticular, and systemic infections. It poses a...
is a pathogenic bacterium responsible for a broad spectrum of infections, including cutaneous, respiratory, osteoarticular, and systemic infections. It poses a significant clinical challenge due to its ability to develop antibiotic resistance. This resistance limits therapeutic options, increases the risk of severe complications, and underscores the urgent need for new strategies to address this threat, including the investigation of treatments complementary to antibiotics. The evaluation of novel antimicrobial agents often employs animal models, with the zebrafish embryo model being particularly interesting for studying host-pathogen interactions, establishing itself as a crucial tool in this field. For the first time, this study presents a zebrafish embryo model for the assessment of bacteriophage efficacy against infection. A localized infection was induced by microinjecting either methicillin-resistant (MRSA) or methicillin-susceptible (MSSA). Subsequent treatments involved administering either bacteriophage, vancomycin (the reference antibiotic for MRSA), or a combination of both via the same route to explore potential synergistic effects. Our findings indicate that the bacteriophage was as effective as vancomycin in enhancing survival rates, whether used alone or in combination. Moreover, bacteriophage treatment appears to be even more effective in reducing the bacterial load in -infected embryos post-treatment than the antibiotic. Our study validates the use of the zebrafish embryo model and highlights its potential as a valuable tool in assessing bacteriophage efficacy treatments .
PubMed: 38899926
DOI: 10.1128/aac.00561-24 -
World Journal of Clinical Cases Jun 2024This case series investigated the clinical manifestations, diagnoses, and treatment of cerebral abscesses caused by . We retrospectively analyzed the clinical...
BACKGROUND
This case series investigated the clinical manifestations, diagnoses, and treatment of cerebral abscesses caused by . We retrospectively analyzed the clinical characteristics and outcomes of three cases of cerebral abscesses caused by and conducted a comprehensive review of relevant literature.
CASE SUMMARY
Case 1 presented with a history of left otitis media and exhibited high fever, confusion, and vomiting as primary symptoms. Postoperative pus culture indicated a brain abscess caused by infection. Case 2 experienced dizziness for two days as the primary symptom. Postoperative pus culture suggested an intermediate streptococcal brain abscess. Case 3: Enhanced head magnetic resonance imaging (MRI) and diffusion-weighted imaging revealed occupancy of the left temporal lobe, initially suspected to be a metastatic tumor. However, a postoperative pus culture confirmed the presence of a brain abscess caused by infection. The three cases presented in this case series were all patients with community-acquired brain abscesses resulting from angina caused by Streptococcus group infection. All three patients demonstrated sensitivity to penicillin, ceftriaxone, vancomycin, linezolid, chloramphenicol, and levofloxacin. Successful treatment was achieved through stereotaxic puncture, drainage, and ceftriaxone administration with a six -week course of antibiotics.
CONCLUSION
Preoperative enhanced head MRI plays a critical role in distinguishing brain tumors from abscesses. Selecting the correct early diagnostic methods for brain abscesses and providing timely intervention are very important. This case series was in accordance with the CARE guidelines.
PubMed: 38898852
DOI: 10.12998/wjcc.v12.i17.3243 -
BMC Infectious Diseases Jun 2024BACKGROUND PAECILOMYCES: and Penicillium are considered as rare opportunistic pathogens in immunocompromised hosts, and pneumonia caused by Paecilomyces and Penicillium...
BACKGROUND PAECILOMYCES: and Penicillium are considered as rare opportunistic pathogens in immunocompromised hosts, and pneumonia caused by Paecilomyces and Penicillium is rare. In this study, we present first case of severe pneumonia with pleural effusion caused by co-infection of Paecilomyces variotii (P. variotii) and Penicillium oxalicum (P. oxalicum) in a 66-year-old female with poorly controlled type 2 diabetes. CASE PRESENTATION: A 56-year-old woman patient presented to hospital for nausea, poor appetite, and vomiting for one day. On the second day of admission, blood culture and renal puncture fluid culture grew multidrug-resistant Escherichia coli (imipenem/cilastatin sensitive), and she received combination therapy with imipenem/cilastatin (1 g, every 8 h) and vancomycin (0.5 g, every 12 h). On the fourth day, she developed symptoms of respiratory failure. Pulmonary computed tomography (CT) showed an increase in pneumonia compared to before, with minor pleural effusion on both sides. Two fungi were isolated repeatedly from BALF culture, which were confirmed as P. variotii and P. oxalicum by Internal transcribed spacer (ITS) sequencing. Her pleural effusion was completely absorbed, pneumonia symptoms have significantly improved and discharged with receiving liposomal amphotericin B treatment for four weeks. CONCLUSIONS: It is worth noting that clinicians and laboratory personnel should not simply consider Paecilomyces and Penicillium species as contaminants, especially in immunocompromised patients. Early fungal identification and antifungal drug sensitivity are crucial for clinical drug selection and patient prognosis.
Topics: Humans; Female; Penicillium; Pleural Effusion; Middle Aged; Aged; Diabetes Mellitus, Type 2; Coinfection; Paecilomyces; Pneumonia; Mycoses; Immunocompromised Host; Anti-Bacterial Agents; Antifungal Agents
PubMed: 38898444
DOI: 10.1186/s12879-024-09496-6 -
BMC Infectious Diseases Jun 2024Invasive pneumococcal disease (IPD) is a significant health concern in children worldwide. In this study, we aimed to analyze the clinical features, antibiotic...
BACKGROUND
Invasive pneumococcal disease (IPD) is a significant health concern in children worldwide. In this study, we aimed to analyze the clinical features, antibiotic resistance, and risk variables for poor outcomes in patients with IPD in Hangzhou.
METHODS
A retrospective single-centre study was performed using the pediatric intensive care (PIC) database from 2010 to 2018. The clinical characteristics, laboratory data, antimicrobial resistance, and risk factors for in-hospital mortality and sepsis in patients with IPD in intensive care units (ICUs) were analyzed systematically.
RESULTS
A total of 178 IPD patients were included in the study. The majority of the IPD children were 2-10 years old. Antimicrobial resistance tests of S. pneumoniae isolates revealed high resistance to erythromycin, tetracycline and compound sulfamethoxazole (SMZ-Co). All the isolates were sensitive to vancomycin, linezolid, moxifloxacin, telithromycin, ofloxacin, and levofloxacin. IPD patients may experience poor outcomes, including death and sepsis. The in-hospital mortality was 3.93%, and 34.27% of patients suffered from sepsis. Temperature (OR 3.80, 95% CI 1.62-8.87; P = 0.0021), Partial Pressure of Oxygen in Arterial Blood (PaO) (OR 0.99, 95% CI 0.98-1.00; P = 0.0266), and albumin (OR 0.89, 95% CI 0.80-0.99; P = 0.0329) were found to be independent risk factors for sepsis in children with IPD.
CONCLUSION
Pediatric IPD deserves attention in China. Appropriate surveillance and antibiotic selection are crucial in managing resistant strains. Early identification of high-risk individuals with risk factors contributes to the development of appropriate treatment strategies.
Topics: Humans; China; Pneumococcal Infections; Child; Male; Risk Factors; Retrospective Studies; Female; Child, Preschool; Streptococcus pneumoniae; Anti-Bacterial Agents; Infant; Hospital Mortality; Microbial Sensitivity Tests; Sepsis; Adolescent; Intensive Care Units, Pediatric; Drug Resistance, Bacterial
PubMed: 38898407
DOI: 10.1186/s12879-024-09493-9 -
Digestive Diseases and Sciences Jun 2024Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and... (Review)
Review
Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized 'adaptive treatment strategy' is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time.
PubMed: 38896361
DOI: 10.1007/s10620-024-08497-4 -
Brazilian Journal of Microbiology :... Jun 2024Staphylococcus aureus are extremely important microorganisms, either from an epidemiological point of view or as a pathogen, responsible for causing a series of...
Phenotypic and genotypic characteristics of mecA - positive oxacillin-sensitive Staphylococcus aureus isolated from patients with bloodstream infection in a tertiary hospital in Southern Brazil.
Staphylococcus aureus are extremely important microorganisms, either from an epidemiological point of view or as a pathogen, responsible for causing a series of infectious processes, whether simple, restricted to the skin, or invasive infections such as bacteremia. The emergence of Oxacillin Sensitive-Methicillin Resistant S.aureus (OS-MRSA) isolates has imposed difficulties in the treatment of patients with staphylococcal infection, as such isolates can be mistakenly classified as sensitive and lead to failure of the therapy used. Thus, the objective of this study is to evaluate the prevalence, and genotypic and phenotypic characteristics, of OS-MRSA isolates, from bloodstream infections, collected from patients admitted to a hospital in southern Brazil, as well as to evaluate the treatment used. For this, 801 unique isolates of S. aureus, collected from blood cultures, between January 2011 and December 2020 were evaluated. Of these, 96 isolates were classified as sensitive to oxacillin. The isolates were identified and had their sensitivity profile performed by manual and automated methods. The minimum inhibitory concentration for vancomycin, daptomycin, oxacillin, linezolid and teicoplanine was performed by e-test. The mecA, vanA genes, typing of the SCCmec elements, as well as the search for the icaA, tst-1 and pvl virulence genes were performed by PCR. Biofilm formation was performed using the crystal violet technique. The Sequence Type (ST), as well as the Clonal Complex (CC) of the isolates was evaluated by the RTq -PCR. The clinical characteristics of the patients were evaluated through an active search in medical records. After investigating the mecA gene, 27.1% (26/96) of the isolates were considered OS-MRSA, with SCCmec type I being the most prevalent, 46.1% (12/26). Among the evaluated isolates, 41% (9/22) were included in CC5 and ST9. As for virulence, all isolates were positive for the icaA gene and characterized as strong biofilm formers. The pvl gene was found in 92.3% (24/26) of the isolates and the toxic shock syndrome toxin was present in 61.5% of the isolates (16/26). All isolates were negative for the presence of the van A gene. As for the clinical outcome, 73% (19/26) of the patients were discharged from the hospital and 27% (7/26) died. It was possible to observe a high frequency of OS-MRSA isolates causing bloodstream infections. Furthermore, such isolates contain several virulence genes, which may contribute to a worse clinical outcome.
PubMed: 38896343
DOI: 10.1007/s42770-024-01420-z