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1.
Euro Surveill ; 29(28)2024 Jul.
Article in English | MEDLINE | ID: mdl-38994602

ABSTRACT

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an important pathogen causing serious nosocomial infections. We describe an outbreak of CRAb in an intensive care unit in the Netherlands in 2021. During an outbreak of non-resistant A. baumannii, while infection control measures were in place, CRAb isolates carrying highly similar bla NDM-1 - and tet(x3)-encoding plasmids were isolated from three patients over a period of several months. The chromosomal and plasmid sequences of the CRAb and non-carbapenemase-carrying A. baumannii isolates cultured from patient materials were analysed using hybrid assemblies of short-read and long-read sequences. The CRAb isolates revealed that the CRAb outbreak consisted of two different strains, carrying similar plasmids. The plasmids contained multiple antibiotic resistance genes including the tetracycline resistance gene tet(x3), and the bla NDM-1 and bla OXA-97 carbapenemase genes. We determined minimal inhibitory concentrations (MICs) for 13 antibiotics, including the newly registered tetracycline antibiotics eravacycline and omadacycline. The CRAb isolates showed high MICs for tetracycline antibiotics including eravacycline and omadacycline, except for minocycline which had a low MIC. In this study we show the value of sequencing multidrug-resistant A. baumannii for outbreak tracking and guiding outbreak mitigation measures.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Anti-Bacterial Agents , Cross Infection , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests , Tetracyclines , beta-Lactamases , Acinetobacter baumannii/genetics , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/isolation & purification , Acinetobacter baumannii/enzymology , Humans , Acinetobacter Infections/microbiology , Acinetobacter Infections/epidemiology , Tetracyclines/pharmacology , Anti-Bacterial Agents/pharmacology , Cross Infection/microbiology , Cross Infection/epidemiology , beta-Lactamases/genetics , Netherlands/epidemiology , Drug Resistance, Multiple, Bacterial/genetics , Plasmids/genetics , Disease Outbreaks , Bacterial Proteins/genetics , Carbapenems/pharmacology , Intensive Care Units
2.
Int J Crit Illn Inj Sci ; 14(2): 94-100, 2024.
Article in English | MEDLINE | ID: mdl-39005973

ABSTRACT

Background: This study aims to determine the prevalence of secondary bacterial infections (SBIs) in hospitalized coronavirus disease 2019 (COVID-19) subjects and evaluate their antibiotic susceptibility. The study also sought to identify risk factors for the outcome of SBIs in COVID-19 subjects. Methods: This single-center cross-sectional retrospective study was carried out at Sohar Hospital in Oman. The study examined hospitalized COVID-19 subjects diagnosed with SBIs during March 2020-December 2022. The relevant subjects' data were extracted from hospital electronic health records and analyzed using STATA version 14. The Chi-square test or Fisher's exact test was employed for analyzing categorical variables, and P < 0.05 was deemed statistically significant. Results: The research encompassed a total of 817 bacteria recovered from various clinical samples of 421 subjects. The older individuals (39.4%) and men (65.6%) experienced bacterial infections more frequently, with bloodstream and respiratory infections being the most common. Gram-negative bacilli (GNB) were responsible for a higher proportion (85.6%) of infections, with Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae being the most common pathogens. Subjects who underwent mechanical ventilation, received corticosteroid therapy, and who had underlying comorbidities, such as diabetes and chronic renal disease, were found to have higher mortality rates. Neutrophilia, elevated C-reactive protein, lymphocytopenia, decreased serum albumin level, sepsis, and pneumonia were found to be independent contributors to mortality. Conclusions: SBI is common among COVID-19-hospitalized subjects. GNB were primarily linked to SBI. The severity and the likelihood of SBI increased in subjects undergoing medical interventions and immunosuppressive therapy.

3.
J Maine Med Cent ; 6(2)2024.
Article in English | MEDLINE | ID: mdl-38994175

ABSTRACT

Introduction: Given the uncertainties related to IV iron therapy and the potential risk of infection, health care providers may hesitate to use this preparation to treat hospitalized patients with bacterial infections, even if clinically indicated. The aim of this study was to examine patterns of prescribing IV iron in patients who were hospitalized and treated for a bacterial infection, and their associated clinical outcomes. Methods: This retrospective chart review evaluated adult patients who received both IV iron sucrose and antibiotics during the same admission at Maine Medical Center in 2019. Data collected included iron studies, practices for prescribing IV iron, and clinical outcomes. Data were summarized using descriptive statistics. Results: A total of 197 patients were evaluated. The median duration of antibiotic therapy was 5(4-9) days. Iron and antibiotic administration overlapped in 153(77.7%) patients, with a mean overlap of 2.7(1-7) days. In the 44 patients without overlap, 20(46%) received IV iron before antibiotics. More than half (57%) of infection types involved urinary tract and respiratory systems. Approximately 2% of patients had antibiotic therapy broadened or duration extended, 7% died, and 16% were readmitted within 30 days of discharge. Discussion: Prior studies evaluating the risk of infection with IV iron published conflicting results. This is the only study that analyzed outcomes in patients receiving IV iron and antibiotics for infection but not undergoing hemodialysis during a hospital admission. Although our findings support that IV iron treatment is safe among patients with concomitant infection and iron deficiency, this finding may not be the case for all clinical subgroups. Conclusions: This study showed that when patients were administered IV iron in the setting of acute bacterial infection in our facility, most patients did not have negative outcomes.

4.
Cureus ; 16(6): e62096, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38989372

ABSTRACT

Streptococcus suis infection in humans occurs due to consuming raw or undercooked pork meat and after contact with pigs. The highest prevalence occurs in Southeast Asian countries, which have the largest pork industry. We report the first case of a 50-year-old healthy male patient from a rural area of São Paulo, Brazil, with septicemia from undercooked pork meat ingestion. The patient was diagnosed at the emergency department with septicemia and multiple organ dysfunctions, including streptococcal toxic shock syndrome. Blood cultures yielded the growth of S. suis. The patient was treated with ceftriaxone and was maintained for two weeks, according to sensitivity tests. The outcome was favorable but developed deafness as a sequela. This report aims to give importance to recognizing this disease regarding typical signs and symptoms and occupational and epidemiological history.

5.
Animals (Basel) ; 14(13)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38998064

ABSTRACT

Intestinal infections caused by Escherichia coli and Salmonella enterica pose a huge economic burden on the swine industry that is exacerbated by the development of antimicrobial resistance in these pathogens, thus raising the need for alternative prevention and treatment methods. Our aim was to test the beneficial effects of the flavonoid luteolin in an in vitro model of porcine intestinal infections. We infected the porcine intestinal epithelial cell line IPEC-J2 with E. coli and S. enterica subsp. enterica serovar Typhimurium (106 CFU/mL) with or without previous, concurrent, or subsequent treatment with luteolin (25 or 50 µg/mL), and measured the changes in the reactive oxygen species and interleukin-6 and -8 levels of cells. We also tested the ability of luteolin to inhibit the adhesion of bacteria to the cell layer, and to counteract the barrier integrity damage caused by the pathogens. Luteolin was able to alleviate oxidative stress, inflammation, and barrier integrity damage, but it could not inhibit the adhesion of bacteria to IPEC-J2 cells. Luteolin is a promising candidate to be used in intestinal infections of pigs, however, further studies are needed to confirm its efficacy. The use of luteolin in the future could ultimately lead to a reduced need for antibiotics in pig production.

6.
J Control Release ; 373: 128-144, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-38977134

ABSTRACT

In recent decades, there has been a burgeoning interest in cell membrane coating strategies as innovative approach for targeted delivery systems in biomedical applications. Platelet membrane-coated nanoparticles (PNPs), in particular, are gaining interest as a new route for targeted therapy due to their advantages over conventional drug therapies. Their stepwise approach blends the capabilities of the natural platelet membrane (PM) with the adaptable nature of manufactured nanomaterials, resulting in a synergistic combination that enhances drug delivery and enables the development of innovative therapeutics. In this context, we present an overview of the latest advancements in designing PNPs with various structures tailored for precise drug delivery. Initially, we describe the types, preparation methods, delivery mechanisms, and specific advantages of PNPs. Next, we focus on three critical applications of PNPs in diseases: vascular disease therapy, cancer treatment, and management of infectious diseases. This review presents our knowledge of PNPs, summarizes their advancements in targeted therapies and discusses the promising potential for clinical translation of PNPs.

7.
Infection ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995551

ABSTRACT

OBJECTIVES: Advancements in Artificial Intelligence(AI) have made platforms like ChatGPT increasingly relevant in medicine. This study assesses ChatGPT's utility in addressing bacterial infection-related questions and antibiogram-based clinical cases. METHODS: This study involved a collaborative effort involving infectious disease (ID) specialists and residents. A group of experts formulated six true/false, six open-ended questions, and six clinical cases with antibiograms for four types of infections (endocarditis, pneumonia, intra-abdominal infections, and bloodstream infection) for a total of 96 questions. The questions were submitted to four senior residents and four specialists in ID and inputted into ChatGPT-4 and a trained version of ChatGPT-4. A total of 720 responses were obtained and reviewed by a blinded panel of experts in antibiotic treatments. They evaluated the responses for accuracy and completeness, the ability to identify correct resistance mechanisms from antibiograms, and the appropriateness of antibiotics prescriptions. RESULTS: No significant difference was noted among the four groups for true/false questions, with approximately 70% correct answers. The trained ChatGPT-4 and ChatGPT-4 offered more accurate and complete answers to the open-ended questions than both the residents and specialists. Regarding the clinical case, we observed a lower accuracy from ChatGPT-4 to recognize the correct resistance mechanism. ChatGPT-4 tended not to prescribe newer antibiotics like cefiderocol or imipenem/cilastatin/relebactam, favoring less recommended options like colistin. Both trained- ChatGPT-4 and ChatGPT-4 recommended longer than necessary treatment periods (p-value = 0.022). CONCLUSIONS: This study highlights ChatGPT's capabilities and limitations in medical decision-making, specifically regarding bacterial infections and antibiogram analysis. While ChatGPT demonstrated proficiency in answering theoretical questions, it did not consistently align with expert decisions in clinical case management. Despite these limitations, the potential of ChatGPT as a supportive tool in ID education and preliminary analysis is evident. However, it should not replace expert consultation, especially in complex clinical decision-making.

8.
JCI Insight ; 9(13)2024 May 28.
Article in English | MEDLINE | ID: mdl-38973612

ABSTRACT

Staphylococcus aureus is a major human pathogen. An effective anti-S. aureus vaccine remains elusive as the correlates of protection are ill-defined. Targeting specific T cell populations is an important strategy for improving anti-S. aureus vaccine efficacy. Potential bottlenecks that remain are S. aureus-induced immunosuppression and the impact this might have on vaccine-induced immunity. S. aureus induces IL-10, which impedes effector T cell responses, facilitating persistence during both colonization and infection. Thus, it was hypothesized that transient targeting of IL-10 might represent an innovative way to improve vaccine efficacy. In this study, IL-10 expression was elevated in the nares of persistent carriers of S. aureus, and this was associated with reduced systemic S. aureus-specific Th1 responses. This suggests that systemic responses are remodeled because of commensal exposure to S. aureus, which negatively implicates vaccine function. To provide proof of concept that targeting immunosuppressive responses during immunization may be a useful approach to improve vaccine efficacy, we immunized mice with T cell-activating vaccines in combination with IL-10-neutralizing antibodies. Blocking IL-10 during vaccination enhanced effector T cell responses and improved bacterial clearance during subsequent systemic and subcutaneous infection. Taken together, these results reveal a potentially novel strategy for improving anti-S. aureus vaccine efficacy.


Subject(s)
Interleukin-10 , Staphylococcal Infections , Staphylococcal Vaccines , Staphylococcus aureus , Interleukin-10/metabolism , Interleukin-10/immunology , Animals , Staphylococcal Infections/prevention & control , Staphylococcal Infections/immunology , Staphylococcal Vaccines/immunology , Mice , Staphylococcus aureus/immunology , Female , Mice, Inbred C57BL , Th1 Cells/immunology , Immunization/methods , Humans , Antibodies, Neutralizing/immunology , Vaccine Efficacy , Vaccination/methods
9.
Article in English | MEDLINE | ID: mdl-38970408

ABSTRACT

Hydroxyurea decreases painful events among children with sickle cell disease but could increase the risk of infections in treated patients through leucopenia. We performed a case-control study, comparing hydroxyurea treatment for sickle cell disease in cases with an invasive bacterial infection and in controls without infection. No difference was found.

10.
Article in English | MEDLINE | ID: mdl-38985990

ABSTRACT

INTRODUCTION: Melioidosis may occasionally be encountered in non-endemic areas and medical imaging is frequently used to identify and characterise sites of disease. The purpose of this study is to describe the spectrum of imaging findings encountered in melioidosis patients treated in the tertiary public hospitals of Perth, Western Australia, between 2002 and 2022. METHODS: A database search and electronic medical record review was used to identify cases. Cases were included if they had Burkholderia pseudomallei isolated on culture and if they had at least one diagnostic imaging study performed at a Perth public tertiary hospital. The relevant imaging studies were reviewed, and imaging findings were recorded. RESULTS: Thirty-six cases were identified. The most common disease manifestation was bacteraemia (72%, 26 cases), followed by pulmonary infection (58%, 21 cases), skin and soft tissue infection (22%, eight cases), prostate abscess (14%, five cases) and septic arthritis (6%, two cases). A previously unreported case of isolated melioid pleural effusion was identified, as was a case of reactivated chronic latent pulmonary melioidosis with an apparent delay of over 20 years between the onset of symptoms and the time of infection. In cases with pulmonary melioidosis, the major lung abnormalities on CT chest could be categorised into one of two distinct patterns: nodular-predominant (78%) or consolidation-predominant (22%). CONCLUSION: Further research is required to assess the utility of the pattern-based categorisation of lung abnormalities on CT chest seen in the pulmonary melioidosis cases of this series.

11.
JMIR Form Res ; 8: e54044, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38986131

ABSTRACT

BACKGROUND: Machine learning has advanced medical event prediction, mostly using private data. The public MIMIC-3 (Medical Information Mart for Intensive Care III) data set, which contains detailed data on over 40,000 intensive care unit patients, stands out as it can help develop better models including structured and textual data. OBJECTIVE: This study aimed to build and test a machine learning model using the MIMIC-3 data set to determine the effectiveness of information extracted from electronic medical record text using a named entity recognition, specifically QuickUMLS, for predicting important medical events. Using the prediction of extended-spectrum ß-lactamase (ESBL)-producing bacterial infections as an example, this study shows how open data sources and simple technology can be useful for making clinically meaningful predictions. METHODS: The MIMIC-3 data set, including demographics, vital signs, laboratory results, and textual data, such as discharge summaries, was used. This study specifically targeted patients diagnosed with Klebsiella pneumoniae or Escherichia coli infection. Predictions were based on ESBL-producing bacterial standards and the minimum inhibitory concentration criteria. Both the structured data and extracted patient histories were used as predictors. In total, 2 models, an L1-regularized logistic regression model and a LightGBM model, were evaluated using the receiver operating characteristic area under the curve (ROC-AUC) and the precision-recall curve area under the curve (PR-AUC). RESULTS: Of 46,520 MIMIC-3 patients, 4046 were identified with bacterial cultures, indicating the presence of K pneumoniae or E coli. After excluding patients who lacked discharge summary text, 3614 patients remained. The L1-penalized model, with variables from only the structured data, displayed a ROC-AUC of 0.646 and a PR-AUC of 0.307. The LightGBM model, combining structured and textual data, achieved a ROC-AUC of 0.707 and a PR-AUC of 0.369. Key contributors to the LightGBM model included patient age, duration since hospital admission, and specific medical history such as diabetes. The structured data-based model showed improved performance compared to the reference models. Performance was further improved when textual medical history was included. Compared to other models predicting drug-resistant bacteria, the results of this study ranked in the middle. Some misidentifications, potentially due to the limitations of QuickUMLS, may have affected the accuracy of the model. CONCLUSIONS: This study successfully developed a predictive model for ESBL-producing bacterial infections using the MIMIC-3 data set, yielding results consistent with existing literature. This model stands out for its transparency and reliance on open data and open-named entity recognition technology. The performance of the model was enhanced using textual information. With advancements in natural language processing tools such as BERT and GPT, the extraction of medical data from text holds substantial potential for future model optimization.

12.
Sex Transm Infect ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902026

ABSTRACT

OBJECTIVE: The reservoir of sexually transmissible bacterial enteric pathogens in asymptomatic men who have sex with men (MSM) may impact future outbreaks, and the evolution of antimicrobial resistance. We aimed to estimate the pooled prevalence and explore any factors associated with Shigella spp, Campylobacter spp, diarrhoeagenic Escherichia coli and Salmonella spp in asymptomatic MSM using the random effects model. METHODS: We searched Embase, MEDLINE, CINAHL and Web of Science Core Collections for manuscripts published up to February 2024. One author screened citations and abstracts; two authors independently conducted a full-text review. We included manuscripts which measured the prevalence of Shigella spp, Campylobacter spp, diarrhoeagenic E. coli and Salmonella spp in asymptomatic MSM. Quality and risk of bias was assessed independently by two authors using the Joanna Briggs Institute critical appraisal tools. We calculated pooled prevalence and CIs using the random effects model. RESULTS: Six manuscripts were included in the final review. The manuscripts were from Australia (n=2), the UK (n=2), the Netherlands (n=1) and the USA (n=1) and included data from 3766 asymptomatic MSM tested for bacterial enteric pathogens. The prevalence of Shigella spp was 1.1% (95% CI 0.7% to 1.7%), Campylobacter spp 1.9% (95% CI 1.5% to 2.5%), diarrhoeagenic E. coli 3.8% (95% CI 2.1% to 6.7%) and Salmonella spp 0.3% (95% CI 0.1% to 0.6%). Two manuscripts demonstrated that the detection of bacterial enteric pathogen was more frequent in asymptomatic MSM using HIV-pre-exposure prophylaxis (PrEP), living with HIV, reporting <5 new sexual partners in the past 3 months, reporting insertive oral-anal sex and group sex compared with MSM testing negative. CONCLUSION: Despite a small number of manuscripts, this review has estimated the pooled prevalence, and highlighted some possible associations with sexually transmissible bacterial enteric pathogens in asymptomatic MSM, which can inform future clinical guidelines, public health control strategies and research to increase our understanding of transmission and the evolution of antimicrobial resistance. PROSPERO REGISTRATION NUMBER: CRD42024518700.

13.
ACS Appl Mater Interfaces ; 16(24): 30915-30928, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38847621

ABSTRACT

Multidrug-resistant (MDR) bacteria pose serious threats to public health due to the lack of effective and biocompatible drugs to kill MDR bacteria. Photodynamic antibacterial therapy has been widely studied due to its low induction of resistance. However, photosensitizers that can efficiently generate reactive oxygen species (ROS) through both type I and type II mechanisms and that have the capability of multiple modes of action are rarely reported. Addressing this issue, we developed a near-infrared-emitting triphenylamine indole iodoethane (TTII) and its silver(I) self-assembled (TTIIS) aggregation-induced emission (AIE) photosensitizer for multimode bacterial infection therapy. TTII can efficiently produce both Type I ROS •OH and Type II ROS 1O2. Interestingly, the Ag(I)-π interaction contributed in TTIIS efficiency promotion of the generation of 1O2. Moreover, by releasing Ag+, TTIIS enabled photodynamic-Ag(I) dual-mode sterilization. As a result, TTIIS achieved an effective enhancement of antibacterial activity, with a 1-2-fold boost against multidrug-resistant Escherichia coli (MDR E. coli). Both TTII and TTIIS at a concentration as low as 0.55 µg mL-1 can kill more than 98% of methicillin resistant Staphylococcus aureus (MRSA) on MRSA-infected full-thickness defect wounds of a mouse, and both TTII and TTIIS were effective in eliminating the bacteria and promoting wound healing.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Escherichia coli , Photosensitizing Agents , Reactive Oxygen Species , Silver , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Silver/chemistry , Silver/pharmacology , Animals , Drug Resistance, Multiple, Bacterial/drug effects , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Reactive Oxygen Species/metabolism , Photochemotherapy , Microbial Sensitivity Tests , Methicillin-Resistant Staphylococcus aureus/drug effects
14.
Neurohospitalist ; 14(3): 301-307, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38895010

ABSTRACT

Lyme disease is a multisystem disorder transmitted through the Ixodes tick and is most commonly diagnosed in northeastern and mid-Atlantic states, Wisconsin, and Minnesota, though its disease borders are expanding in the setting of climate change. Approximately 10%-15% of untreated Lyme disease cases will develop neurologic manifestations of Lyme neuroborreliosis (LNB). Due to varying presentations, LNB presents diagnostic challenges and is associated with a delay to treatment. We discuss three cases of LNB admitted to our referral center in a traditionally low-incidence state to highlight clinical pearls in LNB diagnosis. Three patients from low-incidence areas with prior diagnostic evaluations presented in August with neurologic manifestations of radiculoneuritis, cranial neuropathies, and/or lymphocytic meningitis. MRI findings included cranial nerve, nerve root, and leptomeningeal enhancement leading to broad differential diagnoses. Lumbar puncture demonstrated lymphocytic pleocytosis (range 85-753 cells/uL) and elevated protein (87-318 mg/dL). Each patient tested positive for Lyme on two-tiered serum testing and was diagnosed with LNB. All three cases were associated with a delay to health care presentation (mean 20 days) and a delay to diagnosis and treatment (mean 54 days) due to under-recognition and ongoing evaluation. With the geographic expansion of Lyme disease, increasing awareness of LNB manifestations and acquiring detailed travel histories in low-incidence areas is crucial to prompt delivery of care. Clinicians should be aware of two-tiered serum diagnostic requirements and use adjunctive studies such as lumbar puncture and MRI to eliminate other diagnoses. Treatment with an appropriate course of antibiotics leads to robust improvement in neurological symptoms.

16.
Bioorg Chem ; 150: 107534, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38896935

ABSTRACT

Bacterial infections and the consequent outburst of bactericide-resistance issues are fatal menace to both global health and agricultural produce. Hence, it is crucial to explore candidate bactericides with new mechanisms of action. The filamenting temperature-sensitive mutant Z (FtsZ) protein has been recognized as a new promising and effective target for new bactericide discovery. Hence, using a scaffold-hopping strategy, we designed new 7H-pyrrolo[2,3-d]pyrimidine derivatives, evaluated their antibacterial activities, and investigated their structure-activity relationships. Among them, compound B6 exhibited the optimal in vitro bioactivity (EC50 = 4.65 µg/mL) against Xanthomonas oryzae pv. oryzae (Xoo), which was superior to the references (bismerthiazol [BT], EC50 = 48.67 µg/mL; thiodiazole copper [TC], EC50 = 98.57 µg/mL]. Furthermore, the potency of compound B6 in targeting FtsZ was validated by GTPase activity assay, FtsZ self-assembly observation, fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR) assay, molecular dynamics simulations, and morphological observation. The GTPase activity assay showed that the final IC50 value of compound B6 against XooFtsZ was 235.0 µM. Interestingly, the GTPase activity results indicated that the B6-XooFtsZ complex has an excellent binding constant (KA = 103.24 M-1). Overall, the antibacterial behavior suggests that B6 can interact with XooFtsZ and inhibit its GTPase activity, leading to bacterial cell elongation and even death. In addition, compound B6 showed acceptable anti-Xoo activity in vivo and low toxicity, and also demonstrated a favorable pharmacokinetic profile predicted by ADMET analysis. Our findings provide new chemotypes for the development of FtsZ inhibitors as well as insights into their underlying mechanisms of action.

17.
J Infect Chemother ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38942288

ABSTRACT

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease that presents a formidable challenge due to the absence of established therapeutic strategies that are explicitly tailored to its management. This study aimed to assess the impact of routine antimicrobial therapy on patients diagnosed with SFTS in Japan. We conducted a comprehensive retrospective cohort analysis using extensive data from a national inpatient database. METHODS: This study scrutinized data from adult patients with SFTS and categorized them based on whether they received antimicrobial treatment within the initial 2 days of hospital admission. A meticulous evaluation was carried out on a range of outcomes, such as in-hospital mortality rates, overall costs associated with hospitalization, and length of hospital stay. Overlap weighting was applied along with multivariate regression models to enhance the reliability of the findings through confounder adjustment. The outcomes showed no significant improvement in the prognosis of patients with SFTS who received routine antimicrobial therapy. The use of antimicrobials did not yield statistically significant improvements in in-hospital mortality rates or other secondary outcomes, suggesting that such therapeutic interventions may not be necessary during the early stages of hospital admission. CONCLUSION: In our study, administration of antimicrobials within 2 days of admission for SFTS did not affect prognosis. The standard use of antimicrobial treatments may be an issue that should be reconsidered.

18.
Int J Antimicrob Agents ; : 107262, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945178

ABSTRACT

PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates. RESULTS: In the study involving 96 articles and 9,716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of Polymyxin B doesn't significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

19.
Medicina (Kaunas) ; 60(6)2024 May 29.
Article in English | MEDLINE | ID: mdl-38929518

ABSTRACT

Respiratory tract infections (RTIs) pose a substantial health burden worldwide, especially among immunocompromised groups like cancer patients. The aim of this prospective cohort study was to explore lower respiratory tract infections in cancer patients. We followed 107 cases with clinically or radiologically suspected lower respiratory tract infections until discharge or death, comprising 65 males and 42 females across diverse age groups. Clinical evaluations, including patient history, examination, and malignancy diagnosis, were conducted. Nasopharyngeal swabs (NPSs), sputum samples, and blood samples were collected within 24 h of symptom onset. Multiplex Real-Time PCR allowed for the simultaneous detection of viral, bacterial, and fungal infections, while conventional microbiological culture methods were used for bacterial and fungal analysis. SARS-CoV-2 infection was excluded in all of the enrolled patients using real-time RT-PCR. Hematological and biochemical analyses included hemoglobin, lymphocyte, neutrophil, and platelet counts, along with ALT, AST, creatinine, and CRP levels. Significant differences were noted in clinical presentations, management outcomes, and prognostic markers among patients with different hematological malignancies. Distinct clinical profiles were identified for leukemia, lymphoma, and solid tumors, with variations in age distribution and symptom prevalence. ICU admission rates varied significantly, with solid tumor patients exhibiting higher rates. The hematological and biochemical biomarkers differed across malignancies, with notable associations between lymphopenia, thrombocytopenia, and mortality following respiratory episodes. This study highlights the critical role of rapid pathogen detection and infection control measures in safeguarding vulnerable cancer patients from nosocomial transmission.


Subject(s)
Biomarkers , Neoplasms , Respiratory Tract Infections , Humans , Male , Female , Prospective Studies , Middle Aged , Respiratory Tract Infections/mortality , Respiratory Tract Infections/blood , Respiratory Tract Infections/diagnosis , Aged , Neoplasms/complications , Neoplasms/blood , Neoplasms/mortality , Adult , Biomarkers/blood , Biomarkers/analysis , Cohort Studies , Aged, 80 and over
20.
Antibiotics (Basel) ; 13(6)2024 May 30.
Article in English | MEDLINE | ID: mdl-38927178

ABSTRACT

Introduction: Actions to reduce and optimize antimicrobial use are crucial in the management of infectious diseases to counteract the emergence of short- and long-term resistance. This is particularly important for pediatric patients due to the increasing incidence of serious infections caused by resistant bacteria in this population. The aim of this study was to evaluate the impact of a pediatric antimicrobial stewardship program (PROA-NEN) implemented in a Spanish tertiary hospital by assessing the use of systemic antimicrobials, clinical indicators, antimicrobial resistance, and costs. Methods: In this quasi-experimental, single-center study, we included pediatric patients (0-18 years) admitted to specialized pediatric medical and surgical units, as well as pediatric and neonatal intensive care units, from January 2015 to December 2019. The impact of the PROA-NEN program was assessed using process (consumption trends and prescription quality) and outcome indicators (clinical and microbiological). Antibiotic prescription quality was determined using quarterly point prevalence cross-sectional analyses. Results: Total antimicrobial consumption decreased during the initial three years of the PROA-NEN program, followed by a slight rebound in 2019. This decrease was particularly evident in intensive care and surgical units. Antibiotic use, according to the WHO Access, Watch and Reserve (AWaRe) classification, remained stable during the study period. The overall rate of appropriate prescription was 83.2%, with a significant increase over the study period. Clinical indicators did not substantially change over the study period. Direct antimicrobial expenses decreased by 27.3% from 2015 to 2019. Conclusions: The PROA-NEN program was associated with reduced antimicrobial consumption, improved appropriate use, and decreased costs without compromising clinical and/or microbiological outcomes in patients.

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