RESUMO
Mucormycosis is a rare life-threatening opportunistic infection, with rhinocerebral mucormycosis (ROCM) being the most common presentation. Trichosporon asahii is an emerging pathogen that often causes fatal infections in patients with underlying hematologic malignancies due to its high drug resistance. We report a rare case of concomitant rhinocerebral mucormycosis and T. asahii fungemia secondary to Pseudomonas aeruginosa sepsis in a patient with neutropenia and acute lymphoblastic leukemia. A boy aged one year and two months was diagnosed with B-cell acute lymphoblastic leukemia on January 10 and underwent three courses of regular chemotherapy. He experienced neutropenia for 154 days and was hospitalized for vomiting, diarrhea and fever for 3 days. The day after hospitalization, Pseudomonas aeruginosa was isolated by blood culture and ceftazidime/avibactam was administered. Extracorporeal Membrane Oxygenation (ECMO) was used to provide continuous extracorporeal respiration and circulation for the patient. On day 8, the patient developed T. asahii fungemia. On day 10, he presented with necrotizing skin caused by Rhizopus delemar. He was treated with liposomal amphotericin B for Rhizopus delemar and voriconazole for T. asahii infection. Unfortunately, his health deteriorated and he died on day 11 due to the rapid progression of the infection and multiple organ failure. The management and treatment of such a complex infection requires a multidisciplinary approach and close monitoring of the patient's condition. Therefore, it is imperative to continue to research and report rare cases such as this to further understand the complexities of mucormycosis and trichosporidiosis coinfection and improve patient outcomes.
Assuntos
Coinfecção , Fungemia , Mucormicose , Leucemia-Linfoma Linfoblástico de Células Precursoras , Tricosporonose , Humanos , Masculino , Mucormicose/complicações , Mucormicose/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Fungemia/microbiologia , Fungemia/tratamento farmacológico , Evolução Fatal , Coinfecção/microbiologia , Tricosporonose/microbiologia , Tricosporonose/diagnóstico , Tricosporonose/tratamento farmacológico , Lactente , Infecções Oportunistas/microbiologia , Infecções Oportunistas/complicações , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/complicações , Antifúngicos/uso terapêutico , BasidiomycotaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The Yucatan Peninsula has a privileged wealth of vascular plants with which various Mayan herbal formulations have been developed. However, studies on their antipathogenic and antivirulence properties are scarce. AIM OF THE STUDY: Identify antivirulence properties in Mayan herbal remedies and determine their antipathogenic capacity in burn wounds infected with Pseudomonas aeruginosa. MATERIALS AND METHODS: An ethnobotanical study was conducted in Mayan communities in central and southern Quintana Roo, Mexico. Furthermore, the antipathogenic capacity of three Mayan herbal remedies was analyzed using an animal model of thermal damage and P. aeruginosa infection. Antivirulence properties were determined by inhibiting phenotypes regulated by quorum sensing (pyocyanin, biofilm, and swarming) and by the secretion of the ExoU toxin. The chemical composition of the most active herbal remedy was analyzed using molecular network analysis. RESULTS: It was found that topical administration of the remedy called "herbal soap" (HS) for eleven days maintained 100% survival of the animals, reduced establishment of the bacteria in the burn and prevented its systemic dispersion. Although no curative effect was recorded on tissue damaged by HS treatment, its herbal composition strongly reduced swarming and ExoU secretion. Through analysis of Molecular Networks, it was possible to carry out a global study of its chemical components, and identify the family of oxindole monoterpenoid alkaloids and carboline and tetrahydropyrididole alkaloids. In addition, flavonols, flavan-3-ols, and quinic acid derivatives were detected. CONCLUSIONS: The antipathogenic and antivirulence capacity of ancient Mayan remedies makes them a potential resource for developing new antibacterial therapies to treat burns infected by P. aeruginosa.
Assuntos
Antibacterianos , Queimaduras , Infecções por Pseudomonas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , México , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , Masculino , Percepção de Quorum/efeitos dos fármacos , Virulência/efeitos dos fármacos , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Biofilmes/efeitos dos fármacos , Camundongos , Plantas Medicinais/química , FitoterapiaRESUMO
Aim: To evaluate the action of promethazine, fluoxetine and carbonyl cyanide 3-chlorophenylhydrazone as efflux pump inhibitors (EPIs) against multidrug-resistant Pseudomonas aeruginosa. Methods: The effect of the compounds was evaluated in planktonic cells and bacterial biofilms. Accumulation tests were performed with ethidium bromide to prove their action as EPIs. Then, they were associated with antimicrobials. Results: Effect on planktonic cells and biofilms was found. Assays with ethidium bromide indicate their action as EPIs. Significant reductions in the metabolic activity of biofilms were observed after the association with the antimicrobials, especially for meropenem. Conclusion: It is possible to prove the action of these compounds as EPIs for P. aeruginosa and demonstrate the relevance of efflux pumps in antimicrobial resistance.
[Box: see text].
Assuntos
Antibacterianos , Biofilmes , Reposicionamento de Medicamentos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Prometazina/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Humanos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , HidrazonasRESUMO
INTRODUCTION: Studies may underestimate the impact of antibiotics on bacterial resistance when correlating hospital antibiotic use with resistance rates (RRs) that exclude duplicate cultures as duplicates usually include more resistant isolates. Comparing correlations between antibiotic consumption and RRs resulting from different strategies for excluding duplicates could help explore how their exclusion affects such correlations. METHODS: We obtained antibiotics consumption and Pseudomonas aeruginosa susceptibility data from 2017 to 2021 for seven antibiotics and for carbapenems as a group in a university hospital. We calculated RRs using seven different time criteria for excluding duplicates. We assessed the correlations of antibiotic consumption to the same-year and next-year RR rates for the three most distinct rates. RESULTS: Duplicate cultures represented 53.45% of total cultures. RRs were higher when duplicates were included. We compared RRs resulting from excluding all duplicates, excluding duplicates monthly or admitting one culture per day. All antibiotics except meropenem showed a correlation with same-year RRs, either positive or negative, whereas all antibiotics showed a positive correlation with next-year RRs. For same-year and next-year correlations, the criteria with fewer duplicates (and therefore fewer resistant strains) found more correlations. However, the inclusion of duplicates taken at least 1 month apart found the most correlations. Admitting one culture per day found the fewest correlations. CONCLUSIONS: Excluding duplicates from RRs affects the correlation of antibiotics consumption with RRs in P. aeruginosa. Including at least some duplicate cultures in correlation analyses, such as those taken 1 month apart, should be considered.
Assuntos
Antibacterianos , Infecções por Pseudomonas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Meropeném/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Hospitais , Pseudomonas aeruginosaRESUMO
This study aimed to compare the efficacy of fosfomycin, colistin, tobramycin and their dual combinations in an experimental sepsis model. After sepsis was established with a Pseudomonas aeruginosa isolate (P1), antibiotic-administered rats were divided into six groups: Fosfomycin, tobramycin, colistin and their dual combinations were administered by the intravenous or intraperitoneal route to the groups. The brain, heart, lung, liver, spleen and kidney tissues of rats were cultured to investigate bacterial translocation caused by P1. Given the antibiotics and their combinations, bacterial colony counts in liver tissues were decreased in colistin alone and colistin plus tobramycin groups compared with control group, but there were no significant differences. In addition, a non-statistical decrease was found in the spleen tissues of rats in the colistin plus tobramycin group. There was a > 2 log10 CFU/ml decrease in the number of bacterial colonies in the kidney tissues of the rats in the fosfomycin group alone, but the decrease was not statistically significant. However, there was an increase in the number of bacterial colonies in the spleen and kidney samples in the group treated with colistin as monotherapy compared to the control group. The number of bacterial colonies in the spleen samples in fosfomycin plus tobramycin groups increased compared to the control group. Bacterial colony numbers in all tissue samples in the fosfomycin plus colistin group were found to be close to those in the control group. Colistin plus tobramycin combinations are effective against P. aeruginosa in experimental sepsis, and clinical success may be achieved. New in vivo studies demonstrating the ability of P. aeruginosa to biofilm formation in tissues other than the lung are warranted in future.
Assuntos
Fosfomicina , Infecções por Pseudomonas , Sepse , Animais , Ratos , Pseudomonas aeruginosa , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , Colistina/farmacologia , Colistina/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Tobramicina/farmacologia , Tobramicina/uso terapêutico , Sepse/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Pseudomonas aeruginosa is a Gram-negative bacillus that causes superficial and deep infections, which can be minor to life-threatening. Recently, P. aeruginosa has gained significant relevance due to the increased incidence of multidrug-resistant (MDR) strains that complicate antibiotic treatment. Due to MDR strains, alternative therapies, such as antimicrobial photodynamic therapy (PDT), are presented as a good option to treat nonsystemic infections. PDT combines a photosensitizer agent (PS), light, and oxygen to generate free radicals that destroy bacterial structures such as the envelope, matrix, and genetic material. This work aimed to identify the development stage of the PDT applied to P. aeruginosa to conclude which research stage should be emphasized more. METHODS: Systematic bibliographic search in various public databases was performed. Related articles were identified using keywords, and relevant ones were selected using inclusion and exclusion criteria according to the PRISMA protocol. RESULTS: We found 29 articles that meet the criteria, constituting a good body of evidence associated with using PDT against P. aeruginosa in vitro and less developed for in vivo research. CONCLUSIONS: We conclude that PDT could become an effective adjunct to antimicrobial therapy against P. aeruginosa. This effectiveness depends on the PS used and the location of the infection. Many PS already demonstrated efficacy in PDT, but the evidence is supported significantly by in vitro and very few in vivo studies. Therefore, we conclude that further research efforts should focus on demonstrating the safety and efficacy of these PSs in vivo in animal infection models.
Assuntos
Fotoquimioterapia , Infecções por Pseudomonas , Animais , Infecções por Pseudomonas/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fotoquimioterapia/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas , Pseudomonas aeruginosaRESUMO
We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0-24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection.
Assuntos
Ciprofloxacina , Infecções por Pseudomonas , Humanos , Ratos , Animais , Antibacterianos , Pseudomonas aeruginosa , Infecção Persistente , Ratos Wistar , Infecções por Pseudomonas/tratamento farmacológico , Pulmão , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
INTRODUCTION: Pseudomonas aeruginosa respiratory infections are challenging, and the risk of recurrence is a frequent problem. The aim of this study was to investigate the risk factors associated with the presence of P. aeruginosa, and the risk factors related to the recurrence and death of lower airway infections in inpatients in a Brazilian hospital. METHODS: Retrospective cohort with inpatients that had a sample of airways culture (tracheal aspirate or bronchoalveolar lavage) with the detection of P. aeruginosa. The patients with clinical criteria of infection were classified as ventilator-associated, hospital-acquired, or community-acquired pneumonia. P. aeruginosa in respiratory samples without symptoms was considered colonization. The antimicrobial treatment adequacy and the clinical data were evaluated. Outcome variables included mortality and recurrence. RESULTS: One hundred and fifty-four patients were included in the study, most of them were men, and the majority (102) were considered infected. The average length of stay was superior to 30 days. Previous pulmonary disease was associated with the occurrence of colonization. Aminoglycosides were the most active drug according to susceptibility tests and were successfully used as monotherapy. Septic shock was a risk factor for death in the infected patients. The use of adequate antimicrobial therapy was associated with major survival, independent of the infection classification. CONCLUSION: It is possible to evaluate clinical data associated with recurrence and mortality in patients with different lung infections by P. aeruginosa. Aminoglycoside monotherapy is safe and effective in P. aeruginosa respiratory infections.
Assuntos
Pneumonia Associada à Ventilação Mecânica , Infecções por Pseudomonas , Masculino , Humanos , Feminino , Pseudomonas aeruginosa , Estudos Retrospectivos , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Antibacterianos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologiaRESUMO
BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health.
Assuntos
Antibacterianos , Infecções por Pseudomonas , Estados Unidos , Humanos , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa/genética , Estudos Prospectivos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Carbapenêmicos/uso terapêuticoRESUMO
Pseudomonas aeruginosa has a high adaptive capacity, favoring the selection of antibiotic-resistant strains, which are currently considered a global health problem. The purpose of this work was to investigate the rate and distribution of extensively drug-resistant (XDR) P. aeruginosa in pediatric patients with cystic fibrosis (CF) with recurrent infections and to distinguish the current efficacy of antibiotics commonly used in eradication therapy at a Mexican institute focused on children. A total of 118 P. aeruginosa isolates from 25 children with CF (2015-2019) underwent molecular identification, antimicrobial sensitivity tests, and Random Amplified Polymorphic DNA genotyping (RAPD-PCR). The bacterial isolates were grouped in 84 RAPD profiles, revealing a cross-infection between two sisters, whose resistance profile remained unchanged for more than 2 years. Furthermore, 77.1% (91/118) and 51.7% (61/118) of isolates showed in vitro susceptibility to ceftazidime and amikacin, respectively, antibiotics often used in eradication therapy at our institution. As well, 42.4% (50/118) were categorized as multi-drug resistant (MDR) and 12.7% (15/118) were XDR. Of these resistant isolates, 84.6% (55/65) were identified from patients with recurrent infections. The high frequency of XDR strains in children with CF should be considered a caution mark, as such resistance patterns are more commonly found in adult patients. Additionally, amikacin may soon prove ineffective. Careful use of available antibiotics is crucial before therapeutic possibilities are reduced and "antibiotic resistance crisis" worsens.