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PloS One 2024Current antimicrobial susceptibility testing (AST) requires 16-24 hours, delaying initiation of appropriate antibiotics. Hence, there is a need for rapid AST. This study...
Can flow cytometric measurements of reactive oxygen species levels determine minimal inhibitory concentrations and antibiotic susceptibility testing for Acinetobacter baumannii?
Current antimicrobial susceptibility testing (AST) requires 16-24 hours, delaying initiation of appropriate antibiotics. Hence, there is a need for rapid AST. This study aims to develop and evaluate the feasibility of a rapid flow cytometric AST assay to determine minimum inhibitory concentration (MIC) for carbapenem-resistant Acinetobacter baumannii (CRAB). Antibiotic exposure causes increased intracellular reactive oxygen species (ROS) in bacteria. We hypothesized that ROS can be used as a marker to determine MIC. We assessed three CRAB clinical isolates across fifteen antibiotics at various concentrations in a customized 96-well microtiter plate. The antibiotics assessed include amikacin, beta-lactams (ampicillin/sulbactam, aztreonam, cefepime, ceftolozane/tazobactam, doripenem, imipenem, meropenem, and piperacillin/tazobactam), levofloxacin, polymyxin B, rifampicin, trimethoprim/sulfamethoxazole, and tetracyclines (tigecycline and minocycline). These clinical CRAB isolates were assessed for ROS after antibiotic treatment. Increased ROS levels indicated by increased RedoxSensorTM Green (RSG) fluorescence intensity was assessed using flow cytometry (FCM). MIC was set as the lowest antibiotic concentration that gives a ≥1.5-fold increase in mode RSG fluorescence intensity (MICRSG). Accuracy of MICRSG was determined by comparing against microtiter broth dilution method performed under CLSI guidelines. ROS was deemed accurate in determining the MICs for β-lactams (83.3% accuracy) and trimethoprim/sulfamethoxazole (100% accuracy). In contrast, ROS is less accurate in determining MICs for levofloxacin (33.3% accuracy), rifampicin (0% accuracy), amikacin (33.3% accuracy), and tetracyclines (33.3% accuracy). Collectively, this study described an FCM-AST assay to determine antibiotic susceptibility of CRAB isolates within 5 hours, reducing turnaround time up to 19 hours.
Topics: Acinetobacter baumannii; Flow Cytometry; Microbial Sensitivity Tests; Anti-Bacterial Agents; Reactive Oxygen Species; Humans; Carbapenems; Acinetobacter Infections
PubMed: 38913680
DOI: 10.1371/journal.pone.0305939 -
Heliyon Jun 2024Hyperammonemia syndrome has a high mortality rate in the immunosuppressed population due to its association with mental status changes. Recently studies have shown that...
Hyperammonemia syndrome has a high mortality rate in the immunosuppressed population due to its association with mental status changes. Recently studies have shown that organisms' infection can lead to hyperammonemia in post-transplant patients. Symptoms typically occur within 30 days postoperatively. However, the late-onset hyperammonemia caused by infection after kidney transplantation has never been reported. In this case study, a 64-year-old Chinese male presented with symptoms such as nausea, vomiting, trouble sleeping, and deteriorating mental status 81 days after kidney transplantation. His plasma ammonia level was significantly elevated, and there was no evidence of liver synthetic dysfunction. Although common methods for ammonia clearance, such as haemodialysis and oral lactulose were initiated, his serum ammonia levels remained high. Metagenomic sequencing of serum determined infection. Levofloxacin and minocycline were administered respectively, which resulted in a decrease in ammonia levels, but normalization was not achieved. The computed tomographic scan revealed the presence of cerebral edema. Unfortunately, the patient eventually became brain dead with multiple organ failure. This case highlights that can cause late-onset hyperammonemia in kidney transplant patients. Once the mental status changes are identified, immediate empiric treatments should be initiated without waiting for a confirmed diagnosis of spp. infection.
PubMed: 38912440
DOI: 10.1016/j.heliyon.2024.e32134 -
Regenerative Therapy Jun 2024With over 9 million fatalities per year expected by 2030, infectious diseases will remain a significant burden on the world economy and cause high mortality rates. An...
With over 9 million fatalities per year expected by 2030, infectious diseases will remain a significant burden on the world economy and cause high mortality rates. An excellent method to increase the bioactivity of levofloxacin (LEV) in pediatric abdominal wound repair is the finding of a stimuli-based drug delivery system (DDS). We designed and developed an LEV incorporated with zeolite imidazole framework-8 (ZIF-8) as a promising nanocarrier for wound healing applications. The spectral analysis and morphological analysis confirm the formation of our newly fabricated composites. Mouse embryonic fibroblast NIH3T3 cells, the cytotoxicity, cytocompatibility, and cell proliferation characteristics of LEV@ZIF-8 were evaluated in vitro. LEV@ZIF-8 composite considerably improved the biocompatibility against NIH3T3 cells after 72-h of exposure, according to in vitro experiments. Under acidic circumstances, the pH-responsive drug release studies exhibit superior LEV release, and in physiological circumstances, there is no unintended drug release. The LEV@ZIF-8 composite-treated cells demonstrate the most remarkable cell growth and migration method in a very short time, according to the results of the wound scratch experiment. The composite exposure concentration depended on inhibition against various microorganisms in the antibacterial activity testing. According to the study, LEV@ZIF-8 are appropriate and effective DDS for stimuli-based pediatric abdominal wound repair.
PubMed: 38911026
DOI: 10.1016/j.reth.2024.05.003 -
Journal of Global Antimicrobial... Jun 2024The World Health Organization named Stenotrophomonas maltophilia a critical multi-drug resistant threat, necessitating rapid diagnostic strategies. Traditional culturing...
OBJECTIVES
The World Health Organization named Stenotrophomonas maltophilia a critical multi-drug resistant threat, necessitating rapid diagnostic strategies. Traditional culturing methods require up to 96 hours, including 72 hours for bacterial growth, identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) through protein profile analysis, and 24 hours for antibiotic susceptibility testing. In this study, we aimed at developing an artificial intelligence-clinical decision support system (AI-CDSS) by integrating MALDI-TOF MS and machine learning to quickly identify levofloxacin and trimethoprim/sulfamethoxazole resistance in S. maltophilia, optimizing treatment decisions.
METHODS
We selected 8,662 S. maltophilia from 165,299 MALDI-TOF MS-analyzed bacterial specimens, collected from a major medical center and four secondary hospitals. We exported mass-to-charge values and intensity spectral profiles from MALDI-TOF MS .mzML files to predict antibiotic susceptibility testing results, obtained with the VITEK-2 system using machine learning algorithms. We optimized the models with GridSearchCV and 5-fold cross-validation.
RESULTS
We identified distinct spectral differences between resistant and susceptible S. maltophilia strains, demonstrating crucial resistance features. The machine learning models, including random forest, light-gradient boosting machine, and XGBoost, exhibited high accuracy. We established an AI-CDSS to offer healthcare professionals swift, data-driven advice on antibiotic use.
CONCLUSIONS
MALDI-TOF MS and machine learning integration into an AI-CDSS significantly improved rapid S. maltophilia resistance detection. This system reduced the identification time of resistant strains from 24 hours to minutes after MALDI-TOF MS identification, providing timely and data-driven guidance. Combining MALDI-TOF MS with machine learning could enhance clinical decision-making and improve S. maltophilia infection treatment outcomes.
PubMed: 38909685
DOI: 10.1016/j.jgar.2024.06.004 -
Frontiers in Microbiology 2024has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction...
OBJECTIVE
has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction of multi-drug resistance (MDR) resistance phenotypes of isolates and clinical samples by genotype is helpful for timely antibiotic treatment.
METHODS
In the study, whole genome sequencing (WGS) data of 494 isolates were used to screen key anti-microbial resistance (AMR)-associated genes related to imipenem (IPM), meropenem (MEM), piperacillin/tazobactam (TZP), and levofloxacin (LVFX) resistance in by comparing genes with copy number differences between resistance and sensitive strains. Subsequently, for the direct prediction of the resistance of to four antibiotics by the AMR-associated features screened, we collected 74 positive sputum samples to sequence by metagenomics next-generation sequencing (mNGS), of which 1 sample with low quality was eliminated. Then, we constructed the resistance prediction model.
RESULTS
We identified 93, 88, 80, 140 AMR-associated features for IPM, MEM, TZP, and LVFX resistance in . The relative abundance of AMR-associated genes was obtained by matching mNGS and WGS data. The top 20 features with importance degree for IPM, MEM, TZP, and LVFX resistance were used to model, respectively. Then, we used the random forest algorithm to construct resistance prediction models of , in which the areas under the curves of the IPM, MEM, TZP, and LVFX resistance prediction models were all greater than 0.8, suggesting these resistance prediction models had good performance.
CONCLUSION
In summary, mNGS can predict the resistance of by directly detecting AMR-associated genes, which provides a reference for rapid clinical detection of drug resistance of pathogenic bacteria.
PubMed: 38903781
DOI: 10.3389/fmicb.2024.1413434 -
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 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 -
Antimicrobial Agents and Chemotherapy Jun 2024Inhalation anthrax is the most severe form of infection, often progressing to fatal conditions if left untreated. While recommended antibiotics can effectively treat...
Inhalation anthrax is the most severe form of infection, often progressing to fatal conditions if left untreated. While recommended antibiotics can effectively treat anthrax when promptly administered, strains engineered for antibiotic resistance could render these drugs ineffective. Telavancin, a semisynthetic lipoglycopeptide antibiotic, was evaluated in this study as a novel therapeutic against anthrax disease. Specifically, the aims were to (i) assess potency of telavancin against 17 isolates by minimum inhibitory concentration (MIC) testing and (ii) evaluate protective efficacy in rabbits infected with a lethal dose of aerosolized anthrax spores and treated with human-equivalent intravenous telavancin doses (30 mg/kg every 12 hours) for 5 days post-antigen detection versus a humanized dose of levofloxacin and vehicle control. Blood samples were collected at various times post-infection to assess the level of bacteremia and antibody production, and tissues were collected to determine bacterial load. The animals' body temperatures were also recorded. Telavancin demonstrated potent bactericidal activity against all strains tested (MICs 0.06-0.125 μg/mL). Further, telavancin conveyed 100% survival in this model and cleared from the bloodstream and organ tissues more effectively than a humanized dose of levofloxacin. Collectively, the low MICs against all strains tested and rapid bactericidal activity demonstrate that telavancin has the potential to be an effective alternative for the treatment or prophylaxis of anthrax infection.
PubMed: 38888319
DOI: 10.1128/aac.00112-24 -
Frontiers in Pharmacology 2024() infections typically occur in early childhood. Although the prevalence of in children is lower than that in adults, the eradication rate of this infection in...
() infections typically occur in early childhood. Although the prevalence of in children is lower than that in adults, the eradication rate of this infection in children is relatively low because of resistance. In this study, we analyzed personalized treatment strategies to achieve treatment goals based on resistance characteristics. This retrospective single-center study was conducted between January 2019 and December 2022 and enrolled 1,587 children who presented with upper gastrointestinal symptoms and underwent endoscopy. culturing and antimicrobial susceptibility testing were performed. Culture-positive results for were obtained in 535 children. The resistance rates to clarithromycin (CLA), metronidazole (MET), and levofloxacin (LEV) were 39.8%, 78.1%, and 20.2%, respectively. None of the isolates were resistant to tetracycline (TET), amoxicillin (AMO), or furazolidone (FZD). Double resistance rates to CLA + MET, CLA + LEV, and MET + LEV were 19.1%, 3.0%, and 5.8%, respectively. Notably, triple-resistant to CLA + MET + LEV was 9.7%. Based on susceptibility tests, individualized triple therapy [proton pump inhibitor (PPI) +AMO + CLA/MET] was selected for 380 children with sensitive to MET and/or CLA. In 155 children resistant to CLA and MET, bismuth-based quadruple therapy was recommended; for unable to receive bismuth, concomitant therapy was recommended for 14 children (<8 years of age); triple therapy with TET was recommended for 141 children (>8 years of age), with 43 children (>14 years of age) requiring FZD rather than TET. Resistance to in Chinese children was relatively poor. Personalized therapy regimens should be based on susceptibility tests and avoided factors associated with treatment failure.
PubMed: 38887553
DOI: 10.3389/fphar.2024.1392787 -
GMS Hygiene and Infection Control 2024The aims of this study were to: (i) determine antibiotic susceptibility of clinical isolates, (ii) investigate the presence of different classes of integrons and genes...
AIM
The aims of this study were to: (i) determine antibiotic susceptibility of clinical isolates, (ii) investigate the presence of different classes of integrons and genes responsible for sulphonamide resistance, (iii) assess the molecular epidemiology of the isolates by determining their clonal relatedness, and (iv) investigate the potential sources of infection by collecting environmental samples when necessary.
METHODS
99 isolates from clinical specimens of hospitalized patients were screened by PCR for , , genes, and integron-associated integrase genes: , , and . PFGE was used to determine the clonal relatedness of the isolates.
RESULTS
Susceptibility rates for trimethoprim-sulfamethoxazole, levofloxacin, and ceftazidime were 90.9%, 91.9%, and 53.5% respectively. All trimethoprim-sulfamethoxazole-resistant isolates were positive for and . PFGE analysis revealed that 24 of the isolates were clonally related, clustering in seven different clones. Five of the nine trimethoprim-sulfamethoxazole-resistant isolates were clonally related. The first isolate in this clone was from a wound sample of a patient in the infectious diseases clinic, and the other four were isolated from the bronchoalveolar lavage samples of patients in the thoracic surgery unit. The patient with the first isolate neither underwent bronchoscopy nor stayed in the thoracic surgery unit. Although clustering was observed in bronchoalveolar lavage samples, no growth was detected in environmental samples.
CONCLUSION
The findings demonstrated that the gene carried by class 1 integrons plays an important role in trimethoprim-sulfamethoxazole resistance in isolates. PFGE analysis revealed a high degree of genetic diversity. However, detection of clonally related isolates suggests the acquisition from a common source and/or cross-transmission of this microorganism between the patients.
PubMed: 38883406
DOI: 10.3205/dgkh000481