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1.
An Acad Bras Cienc ; 96(1): e20230188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38597489

RESUMO

The growing increase in the fish farming sector has favored the establishment of bacterial outbreaks caused by Aeromonas hydrophila in several species. The hexane extract of Hesperozygis ringens (HEHR) (Lamiaceae) leaves increased the survival rate of silver catfish (Rhamdia quelen) experimentally infected by A. hydrophila. However, it is noteworthy that no reports have been found on the possible mechanisms of action of this extract in infected fish. This study aimed to evaluate the effect of the HEHR, administered through single immersion bath, on lipid peroxidation and antioxidant defenses in muscle and liver tissue of silver catfish challenged with A. hydrophila. The results showed that the oxidative status of silver catfish was altered, although oxidative stress was not triggered during the experiment. HEHR at 30 mg/L (HEHR30) was not characterized as a pro-oxidant agent in the presence of infection, unlike florfenicol and HEHR at 15 mg/L treatments in some cases. In short, HEHR30 provided an important increase in hepatic catalase activity, characterizing one of the possible mechanisms involved in the greater survival of fish experimentally infected by A. hydrophila. Additionally, HEHR30 did not induce lipid peroxidation, nor reduced antioxidant defenses of silver catfish infected or not by A. hydrophila.


Assuntos
Peixes-Gato , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Lamiaceae , Animais , Aeromonas hydrophila , Antioxidantes/farmacologia , Hexanos , Imersão , Oxirredução , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Negativas/microbiologia
2.
Front Public Health ; 12: 1376513, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601497

RESUMO

Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.


Assuntos
Carbapenêmicos , Infecções por Bactérias Gram-Negativas , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Negativas/microbiologia , Unidades de Terapia Intensiva
3.
BMJ Case Rep ; 17(4)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627053

RESUMO

This case of Pleisimonas shigelloides bacteremia resulting after a catfish barb injury highlights an unusual presentation of a common condition that requires alternative therapy for successful treatment. An otherwise healthy male in his early 40s presented to the emergency department with sepsis and rapidly spreading cellulitis shortly after a catfish injury at a freshwater lake. His broad-spectrum antibiotics were narrowed to ciprofloxacin when P. shigelloides grew from his blood culture. The case presents a unique mode of bacteremia, as usually P. shigelloides bacteremia develops in immunocompromised hosts after bowel wall translocation. The venomous nature of catfish barbs also contributed to the severity and rapidity of his presentation secondary to the local tissue effects of envenomation. With proper antibiotics and supportive care, he made a full recovery.


Assuntos
Bacteriemia , Peixes-Gato , Infecções por Bactérias Gram-Negativas , Plesiomonas , Animais , Humanos , Masculino , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/complicações , Bacteriemia/tratamento farmacológico , Bacteriemia/complicações , Antibacterianos/uso terapêutico
4.
BMC Infect Dis ; 24(1): 434, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654148

RESUMO

BACKGROUND: The problem of resistance to beta-lactam antibiotics, which is caused by ESBL and AmpC ß-lactamases, is getting worse globally. Infections caused by bacterial isolates harboring these enzymes are difficult to treat with carbapenems being the sole effective treatment option for such infections. The objective of this study was to determine the frequency of ESBLs and AmpC-producing Gram-negative bacilli isolated from clinical specimens and to evaluate the sensitivity of cefepime-tazobactam combination against them. METHODS: This is an observational cross-sectional study carried out on 100 Gram-negative bacilli at Theodor Bilharz Research Institute Hospital during the period from February 2015 to January 2016. ESBL production was screened by using the disc diffusion test followed by confirmation by the combined disc confirmatory test, the screening for AmpC production was conducted using the cefoxitin disc test, which was subsequently confirmed by the AmpC disc test. Isolates confirmed positive for ESBL and/ or AmpC production were investigated for their susceptibility to antibiotics. RESULTS: Among 100 Gram-negative bacilli, 44 isolates were confirmed as ESBL producers by the combined disc confirmatory test out of 56 isolates that tested positive for ESBL production through the disc diffusion test. The presence of AmpC production was assessed using the cefoxitin disc test, 32 isolates were screened to be AmpC producers, and the AmpC disc test confirmed AmpC production in 9 isolates of them. Using the Mast® D68C set, 32 isolates were ESBL producers, 3 were AmpC producers, and 4 isolates were ESBL/AmpC co-producers. The highest sensitivity was to cefepime-tazobactam (91.48%) followed by the carbapenems. CONCLUSION: Cefepime-tazobactam showed remarkable activity against ESBL and/or AmpC-producing Gram-negative bacilli and may be considered as a therapeutic alternative to carbapenems.


Assuntos
Antibacterianos , Proteínas de Bactérias , Cefepima , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Tazobactam , beta-Lactamases , beta-Lactamases/metabolismo , Cefepima/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Estudos Transversais , Antibacterianos/farmacologia , Tazobactam/farmacologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Cefalosporinas/farmacologia , Masculino , Feminino , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia
5.
BMC Infect Dis ; 24(1): 307, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481174

RESUMO

BACKGROUND: Infections are one of the most common causes of death after lung transplant (LT). However, the benefit of 'targeted' prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear. METHODS: All consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016-2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis ('standard' vs. 'targeted' on the preoperative bacterial isolation). RESULTS: One hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to 'targeted' prophylaxis, while 24 (52%) to 'standard' prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with 'standard' prophylaxis and twelve (75%) with 'targeted' therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the 'standard' and 11 to the 'targeted' prophylaxis (p = 0.027). CONCLUSIONS: The administration of a 'targeted' prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections.


Assuntos
Infecções por Bactérias Gram-Negativas , Transplante de Pulmão , Humanos , Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Estudos Retrospectivos , Bactérias Gram-Negativas , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológico , Transplantados
6.
Infect Dis (Lond) ; 56(5): 335-347, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38436567

RESUMO

BACKGROUND: Stenotrophomonas maltophilia (S. maltophilia) is a nosocomial pathogen causing life-threatening invasive infections with a high mortality rate in some patient populations, especially those who are severely ill or immunocompromised. There is a need for data on mortality in patients with S. maltophilia bacteremia. OBJECTIVE: In this meta-analysis, we aimed to investigate risk factors for mortality in S. maltophilia bacteremia. METHODS: Studies comparing patients who died from S. maltophilia bacteremia with patients who survived were considered for inclusion. Studies were included if they reported one or more risk factors for mortality. Mortality risk factors included clinical predisposing factors, predisposing comorbidities and appropriateness of antibiotic therapy. RESULTS: Nineteen studies with 1248 patients were included in the meta-analysis. Five hundred and six (40.5%) patients died. The following risk factors for mortality were identified: ICU admission, septic shock, need for mechanical ventilation, indwelling central venous catheter, neutropenia, comorbid hematological malignancies, chronic kidney disease, inappropriate antimicrobial therapy and prior antibiotic use. CONCLUSIONS: Appropriate antimicrobial therapy had a protective effect against mortality in S. maltophilia bacteremia. Indwelling central venous catheter, neutropenia, hematological malignancies and chronic kidney disease were also risk factors for mortality.


Assuntos
Bacteriemia , Infecção Hospitalar , Infecções por Bactérias Gram-Negativas , Neoplasias Hematológicas , Neutropenia , Insuficiência Renal Crônica , Stenotrophomonas maltophilia/imunologia , Humanos , Estudos Retrospectivos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Fatores de Risco , Antibacterianos/uso terapêutico , Neoplasias Hematológicas/complicações , Infecção Hospitalar/tratamento farmacológico , Neutropenia/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico
7.
J Infect Public Health ; 17(5): 843-853, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554590

RESUMO

BACKGROUND: Colistin is a viable option for multidrug resistant gram-negative bacteria emerged from inappropriate antibiotic use. Nonetheless, suboptimal colistin concentrations and nephrotoxicity risks hinder its clinical use. Thus, the aim of this study is to investigate clinical outcomes in correlation with pharmacokinetic differences and infection types in critically ill patients on intravenous colistin methanesulfornate sodium (CMS). METHODS: A systematic literature search of Embase, Google Scholars, and PubMed was performed to identify clinical trials evaluating pharmacokinetic parameters along with clinical outcomes of CMS treatment from inception to July 2023. The pooled analyses of clinical impact of CMS on nephrotoxicity, mortality, clinical cure, and colistin concentration at steady state (Css,avg) were performed. This study was registered in the PROSPERO (CRD 42023456120). RESULTS: Total of 695 critically ill patients from 17 studies were included. The mortality was substantially lower in clinically cured patients (OR 0.05; 95% CI 0.02 - 0.14), whereas the mortality rate was statistically insignificant between nephrotoxic and non-nephrotoxic patients. Inter-patient variability of pharmacokinetic parameters of CMS and colistin was observed in critically ill patients. The standard mean differences of Css,avg were statistically insignificant between clinically cure and clinically failure groups (standard mean difference (SMD) -0.25; 95% CI -0.69 - 0.19) and between nephrotoxic and non-nephrotoxic groups (SMD 0.67; 95% CI -0.27-1.61). The clinical cure rate is substantially lower in pneumonia patients (OR 0.09; 95% CI 0.01 - 0.56), and pharmacokinetic parameters pertaining to microbiological cure were different among strains. CONCLUSION: The mortality rate was substantially lower in clinically cured patients with CMS. However, no significant differences in Css,avg of colistin were examined to determine the impact of pharmacokinetic differences on clinical outcomes including mortality rate and nephrotoxicity risk. Nevertheless, the clinical cure rate is substantially lower in patients with respiratory infection than patients with urinary tract infection.


Assuntos
Infecções Bacterianas , Infecções por Bactérias Gram-Negativas , Humanos , Colistina/efeitos adversos , Estado Terminal/terapia , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Bactérias , Mesilatos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia
8.
J Med Case Rep ; 18(1): 180, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38523318

RESUMO

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacteria known for causing opportunistic and nosocomial infections in humans. S. maltophilia is an emerging pathogen of concern due to it's increasing prevalence, diverse disease spectrum, intrinsic multi-drug resistance and high mortality rates in immunocompromised individuals. S. maltophilia is a rare cause of neonatal sepsis associated with significant morbidity and mortality. The bacterium's multi-drug resistance poses a considerable challenge for treatment, with various mechanisms contributing to its resistance. CASE PRESENTATION: We report a case involving a 40-h-old male African neonate who exhibited symptoms of neonatal sepsis. The blood culture revealed Stenotrophomonas maltophilia, which was sensitive to ciprofloxacin and gentamicin but resistant to other antibiotics. Lumbar puncture for CSF could not be done because the father declined. We treated the newborn with the empirical first-line antibiotics as per the national guideline intravenous ampicillin and gentamicin for six days, and the child recovered fully with a repeated negative blood culture. CONCLUSIONS: This report describes a neonatal sepsis case caused by S. maltophilia, a multi-drug resistant bacteria and a rare cause of neonatal sepsis. We report that early detection of the bacterial and antimicrobial management based on local antibiogram data may be essential for successful patient's management.


Assuntos
Infecções por Bactérias Gram-Negativas , Sepse Neonatal , Stenotrophomonas maltophilia , Criança , Recém-Nascido , Masculino , Humanos , Sepse Neonatal/diagnóstico , Sepse Neonatal/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Antibacterianos/uso terapêutico , Gentamicinas/uso terapêutico
9.
Ann Clin Microbiol Antimicrob ; 23(1): 26, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504262

RESUMO

INTRODUCTION: Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge. AIM: The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies. METHOD: A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis. RESULT: Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010. CONCLUSIONS: Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option.


Assuntos
Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Humanos , Combinação Trimetoprima e Sulfametoxazol , Minociclina/uso terapêutico , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , 60607 , Resistência Microbiana a Medicamentos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia
10.
J Med Case Rep ; 18(1): 171, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38504363

RESUMO

BACKGROUND: Aeromonas veronii is a very rare and highly pathogenic microorganism. We investigate the clinical characteristics and significance of endogenous endophthalmitis caused by Aeromonas veronii in our patient. CASE PRESENTATION: A 30-year-old Asian women with systemic lupus erythematosus, uremia, and hypertension developed acute infectious endophthalmitis caused by Aeromonas veronii. After emergency vitrectomy and antibiotic therapy, the clinical condition worsened requiring enucleation. CONCLUSIONS: Aeromonas veronii can cause infection in the human eye, which can manifest as acute endophthalmitis. Early diagnosis and targeted therapy are important for successful treatment.


Assuntos
Aeromonas , Endoftalmite , Infecções por Bactérias Gram-Negativas , Humanos , Feminino , Adulto , Aeromonas veronii , Endoftalmite/diagnóstico , Endoftalmite/tratamento farmacológico , Antibacterianos/uso terapêutico , Vitrectomia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico
11.
Ann Hematol ; 103(5): 1745-1752, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38453704

RESUMO

Stenotrophomonas maltophilia (SM) bloodstream infections (BSIs) contribute to significant mortality in hematologic malignancy (HM) and hematopoietic stem cell transplantation (HSCT) patients. A risk score to predict SM BSI could reduce time to appropriate antimicrobial therapy (TTAT) and improve patient outcomes. A single center cohort study of hospitalized adults with HM/HSCT was conducted. Patients had ≥ 1 blood culture with a Gram-negative (GN) organism. A StenoSCORE was calculated for each patient. The StenoSCORE2 was developed using risk factors for SM BSI identified via logistic regression. Receiver operating characteristic (ROC) curves were plotted. Sensitivity and specificity for the StenoSCORE and StenoSCORE2 were calculated. Thirty-six SM patients and 534 non-SM patients were assessed. A StenoSCORE ≥ 33 points was 80% sensitive, 68% specific, and accurately classified 69% of GN BSIs. StenoSCORE2 variables included acute leukemia, prolonged neutropenia, mucositis, ICU admission, recent meropenem and/or cefepime exposure. The StenoSCORE2 performed better than the StenoSCORE (ROC AUC 0.84 vs. 0.77). A StenoSCORE2 ≥ 4 points was 86% sensitive, 76% specific, and accurately classified 77% of GN BSIs. TTAT was significantly longer for patients with SM BSI compared with non-SM BSI (45.16 h vs. 0.57 h; p < 0.0001). In-hospital and 28-day mortality were significantly higher for patients with SM BSI compared to non-SM BSI (58.3% vs. 18.5% and 66.7% vs. 26.4%; p-value < 0.0001). The StenoSCORE and StenoSCORE2 performed well in predicting SM BSIs in patients with HM/HSCT and GN BSI. Clinical studies evaluating whether StenoSCORE and/or StenoSCORE2 implementation improves TTAT and clinical outcomes are warranted.


Assuntos
Bacteriemia , Infecções por Bactérias Gram-Negativas , Neoplasias Hematológicas , Sepse , Stenotrophomonas maltophilia , Adulto , Humanos , Estudos de Coortes , Bacteriemia/epidemiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Estudos Retrospectivos , Fatores de Risco , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico
12.
BMC Infect Dis ; 24(1): 327, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500029

RESUMO

BACKGROUND: Ralstonia pickettii is a low virulent, gram-negative bacillus that is rarely associated with human infections and may cause bacteremia. Microbacterium species are gram-positive coryneforms that are generally considered as a contaminant in Gram staining of blood cultures, especially when the time to positivity is longer than 48 h. Both these bacterial species are emerging opportunistic pathogens that may occasionally cause serious infections and even life-threatening health conditions. CASE PRESENTATION: Here, we report the case of a patient with bacteremia caused by both R. pickettii and Microbacterium. We advocate for providers to order rapid antibiotic susceptibility testing, since our patient's suffered two kinds of rare pathogens with the opposite of drug sensitivity results to imipenem. CONCLUSIONS: Our case present a patient suffered septic shock caused by R. pickettii and Microbacterium. Improving the antibiotic management based on the result of antimicrobial susceptibility tests is the key of successful treatment.


Assuntos
Bacteriemia , Infecções por Bactérias Gram-Negativas , Ralstonia pickettii , Humanos , Microbacterium , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/etiologia , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/complicações
13.
J Glob Antimicrob Resist ; 36: 393-398, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342378

RESUMO

OBJECTIVES: This study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime-avibactam for carbapenem-resistant Gram-negative bacterial infections. METHODS: This multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime-avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. RESULTS: Of the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.6%) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28-4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24-3.78, P < 0.01). Only one patient developed resistance to ceftazidime-avibactam during treatment. CONCLUSIONS: Treatment with ceftazidime-avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.


Assuntos
Antibacterianos , Compostos Azabicíclicos , Infecções por Bactérias Gram-Negativas , Adulto , Humanos , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Inibidores de beta-Lactamases/efeitos adversos , Ceftazidima/efeitos adversos , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Estudos Prospectivos
14.
Bioorg Chem ; 145: 107203, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38377817

RESUMO

Antimicrobial photodynamic therapy (PDT) is a promising alternative to antibiotics for eradicating pathogenic bacterial infections. It holds advantage of not inducing antimicrobial resistance but is limited for the treatment of gram-negative bacterial infection due to the lack of photosensitizer (PS) capable of targeted permeating the outer membrane (OM) of gram-negative bacteria. To facilitate the targeted permeability of PS, cyclic polymyxin b nonapeptide that can specifically bind to the lipopolysaccharide on OM, is conjugated to an FDA approved PS chlorin e6 via variable linkers. Based on structure to activity study, C6pCe6 with aminohexanoic linker and P2pCe6 with amino-3, 6-dioxaoctanoic linker are identified to preferentially image gram-negative bacteria. These two conjugates also exhibit improved aqueous dispersity and enhanced ROS generation, consequently enabled their selective bactericidal activities against gram-negative bacteria upon 660 nm light irradiation. The effective photobactericidal ability of P2pCe6 is further validated on P. aeruginosa infected G. mellonella. Moreover, it is demonstrated to effectively treat the P. aeruginosa infection and accelerate the healing process at the wound site of mouse. Owing to the light irradiation triggered targeted imaging and enhanced bactericidal capacities, P2pCe6 hold great potential to serve as a potent PS for mediating the phototheranostics of gram-negative bacterial infection.


Assuntos
Anti-Infecciosos , Infecções por Bactérias Gram-Negativas , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Fotoquimioterapia/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Anti-Infecciosos/farmacologia , Bactérias Gram-Negativas
15.
Transpl Infect Dis ; 26(2): e14238, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265107

RESUMO

BACKGROUND: Performance of active screening for multidrug-resistant Gram-negative bacteria (MDR-GNB) and administration of targeted antibiotic prophylaxis (TAP) in colonized patients undergoing liver (LT) and/or kidney transplantation (KT) are controversial issues. METHODS: Self-administered electronic cross-sectional survey disseminated from January to February 2022. Questionnaire consisted of four parts: hospital/transplant program characteristics, standard screening and antibiotic prophylaxis, clinical vignettes asking for TAP in patients undergoing LT and KT with prior infection/colonization with four different MDR-GNB (extended-spectrum cephalosporin-resistant Enterobacterales [ESCR-E], carbapenem-resistant Enterobacterales [CRE], multidrug-resistant Pseudomonas aeruginosa [MDR-Pa], and carbapenem-resistant Acinetobacter baumannii [CRAb]). RESULTS: Fifty-five respondents participated from 14 countries, mostly infectious disease specialists (69%) with active transplant programs (>100 procedures/year for 34.5% KT and 23.6% LT), and heterogeneous local MDR-GNB prevalence from <15% (30.9%), 15%-30% (43.6%) to >30% (16.4%). The frequency of screening for ESCR-E, CRE, MDR-Pa, and CRAb was 22%, 54%, 17%, and 24% for LT, respectively, and 18%, 36%, 16%, and 11% for KT. Screening time-points were mainly at transplantation 100%, only one-third following transplantation. Screening was always based on rectal swab cultures (100%); multi-site sampling was reported in 40% of KT and 35% of LT. In LT clinical cases, 84%, 58%, 84%, and 40% of respondents reported TAP for prior infection/colonization with ESCR-E, CRE, MDR-Pa, and CRAb, respectively. In KT clinical cases, 55%, 39%, 87%, and 42% of respondents reported TAP use for prior infection/colonization with ESCR-E, CRE, MDR-Pa, and CRAb, respectively. CONCLUSION: There is a large heterogeneity in screening and management of MDR-GNB carriage in LT and KT.


Assuntos
Infecções por Bactérias Gram-Negativas , Transplante de Rim , Humanos , Antibioticoprofilaxia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/prevenção & controle , Transplante de Rim/efeitos adversos , Estudos Transversais , Bactérias Gram-Negativas , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Fígado , Carbapenêmicos , Inquéritos e Questionários
18.
ACS Infect Dis ; 10(2): 527-540, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38294409

RESUMO

Gram-negative bacterial infections are difficult to manage as many antibiotics are ineffective owing to the presence of impermeable bacterial membranes. Polymicrobial infections pose a serious threat due to the inadequate efficacy of available antibiotics, thereby necessitating the administration of antibiotics at higher doses. Antibiotic adjuvants have emerged as a boon as they can augment the therapeutic potential of available antibiotics. However, the toxicity profile of antibiotic adjuvants is a major hurdle in clinical translation. Here, we report the design, synthesis, and biological activities of xanthone-derived molecules as potential antibiotic adjuvants. Our SAR studies witnessed that the p-dimethylamino pyridine-derivative of xanthone (X8) enhances the efficacy of neomycin (NEO) against Escherichia coli and Pseudomonas aeruginosa and causes a synergistic antimicrobial effect without any toxicity against mammalian cells. Biochemical studies suggest that the combination of X8 and NEO, apart from inhibiting protein synthesis, enhances the membrane permeability by binding to lipopolysaccharide. Notably, the combination of X8 and NEO can disrupt the monomicrobial and polymicrobial biofilms and show promising therapeutic potential against a murine wound infection model. Collectively, our results unveil the combination of X8 and NEO as a suitable adjuvant therapy for the inhibition of the Gram-negative bacterial infections.


Assuntos
Infecções por Bactérias Gram-Negativas , Xantonas , Animais , Camundongos , Antibacterianos/farmacologia , Biofilmes , Escherichia coli , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Mamíferos , Neomicina/farmacologia , Xantonas/farmacologia
19.
Ann Pharmacother ; 58(1): 21-27, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37125743

RESUMO

BACKGROUND: Stenotrophomonas maltophilia is a multidrug-resistant organism with limited antibiotic treatment options. Minocycline and doxycycline may be appropriate, but clinical data are limited. OBJECTIVE: To compare tetracyclines (minocycline and doxycycline [TCN]) with standard of care, sulfamethoxazole-trimethoprim (TMP-SMZ), in S. maltophilia pneumonia treatment. METHODS: This retrospective, 2-center study evaluated patients treated for S. maltophilia pneumonia with TCN or TMP-SMZ for clinical success, defined as resolution of leukocytosis, fever, and tachypnea. Patients were classified as treatment with TCN or TMP-SMZ based on definitive agent used for ≥50% of the treatment course and ≥4 days. Inclusion criteria were age ≥18 years, S. maltophilia confirmed on respiratory culture from January 2013 to November 2020, and appropriate definitive antibiotic dosing. Pregnancy, incarceration, S. maltophilia-resistant or intermediate to definitive therapy, and combination therapy for treatment of S. maltophilia pneumonia were exclusion criteria. Secondary outcomes were microbiologic success and recurrence or reinfection within 30 days requiring treatment. RESULTS: A total of 80 patients were included (21 TCN [15 minocycline, 6 doxycycline], 59 TMP-SMZ). There was no difference in clinical success (28.6% vs 25.4%; P = 0.994), microbiologic success (n = 28, 55.6% vs 66.4%; P = 0.677), or recurrence or reinfection (n = 24, 66.7% vs 26.7%; P = 0.092) between TCN and TMP-SMZ, respectively. CONCLUSION AND RELEVANCE: Clinical and microbiologic success rates were similar in patients treated with TCN compared with TMP-SMZ for S. maltophilia pneumonia. These data suggest minocycline and doxycycline may be options to treat S. maltophilia pneumonia, but conclusive clinical data continue to be lacking.


Assuntos
Infecções por Bactérias Gram-Negativas , Pneumonia , Stenotrophomonas maltophilia , Humanos , Adolescente , Minociclina/uso terapêutico , Doxiciclina/uso terapêutico , Estudos Retrospectivos , Reinfecção/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Antibacterianos/uso terapêutico , Pneumonia/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Testes de Sensibilidade Microbiana
20.
Microb Pathog ; 186: 106464, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043626

RESUMO

Koumine (KM) has anxiolytic, anti-inflammatory and growth-promoting effects in pigs and sheep. Based on the growth-promoting and immunological effects of koumine, the present study was conducted on Cyprinus carpio (C. carpio) with four KM concentrations: 0 mg/kg, 0.2 mg/kg, 2 mg/kg, and 20 mg/kg for 10 weeks, followed by a 1-week Aeromonas hydrophila (A. hydrophila) infection experiment. The effect of KM on the immunity of A. hydrophila infected carp was analyzed by histopathology, biochemical assay, and qRT-PCR to assess the feasibility of KM in aquaculture. The results showed that the presence of KM alleviated pathogen damage to carp tissues. At 2 mg/kg and 20 mg/kg concentrations of KM successively and significantly elevated (p < 0.05) the SOD activities in the intestinal tract, hepatopancreas and kidney of carp. The expression levels of hepatopancreatic antioxidant genes Nrf2 and IGF-1 were significantly up-regulated in the same group (p < 0.05), while the expression levels of immune genes IL-8 and IL-10 were down-regulated. In summary, KM at concentrations of 2 mg/kg and 20 mg/kg could regulate the expression of antioxidant and immune genes in various tissues in an orderly and rapid manner, and significantly improve the antioxidant and immune abilities of carp, which is conducive to the improvement of the resilience of carp.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Animais , Ovinos , Suínos , Antioxidantes/metabolismo , Imunidade Inata/genética , Carpas/metabolismo , Aeromonas hydrophila/metabolismo , Doenças dos Peixes/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/veterinária , Suplementos Nutricionais/análise
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