Pseudomonas aeruginosa is the leading cause of nosocomial infections with high mortality rates owing to the limited therapeutic options for multidrug-resistant Pseudomonas aeruginosa (MDRPA) and metallo-beta-lactamase (MBL)-producing strains. Herein, we present a meta-analysis exploring the association between MDRPA and São Paulo MBL-1 (SPM-1)-producing strains vs. mortality. Online databases were screened to identify studies published between 2006 and 2016. A total of 15 studies, comprising 3,201 cases of P. aeruginosa infection, were included. Our results demonstrated a higher mortality rate among patients infected with MDRPA (44.6%, 363/813) than those with non-MDRPA infection (24.8%, 593/2,388) [odds ratio (OR) 2.39, 95% confidence interval (CI) 1.70-3.36, p <0.00001]. The risk of mortality in patients with non-SPM-1 strains was four times higher than that observed in the patients of the SPM-1 group; however, no statistically significant difference was observed (p = 0.43). In conclusion, the results of our study demonstrated that patients infected with MDRPA had a significantly higher mortality rate than that of patients infected with non-MDRPA strains, especially patients with bloodstream infection (BSI), immunosuppression, and inadequate antimicrobial therapy. The absence of studies on the molecular aspects of blaSPM-1 and its association with mortality limited the analysis; therefore, our results should be interpreted with caution. Our findings also highlight the need for more studies on the molecular aspects of resistance and the peculiarities of different nosocomial settings.
Purpose:Pseudomonas aeruginosa appears as the main pathogen in cystic fibrosis (CF) involved in recurrent pneumonia and pulmonary exacerbations. The type III secretion system (T3SS) is one of its main determinants of virulence and is associated with poor clinical progression and increased mortality. This study determined the relationship of clinical features of patients with CF and P. aeruginosa T3SS virulotypes. Materials and Methods: From January 2018 to March 2019, P. aeruginosa were isolated from sputum and/or oropharyngeal swabs. T3SS markers (exoS, exoU, exoT and exoY) were detected by PCR. Clinical severity according to Shwachman-Kulckycki score and spirometry data were associated with T3SS virulotypes. Results: A total of 49 patients had positive cultures for P. aeruginosa. T3SS virulence-related markers were detected as follows: exoS 97.9% (n=48), exoU 63.2% (n=31), exoT 95.9% (n=47) and exoY 97.9% (n=48). The prevalence of exoS+/exoU+ virulotype was higher than previously reported in CF settings, being detected in 61.2% of the evaluated isolates, present in 70% of intermittent infections and with a significantly higher frequency in cases of exacerbations. The presence of exoU in chronic infection was not associated with poor clinical results. In chronic infections, the exoS+/exoU− virulotype prevailed (77.8%) and was associated to worse clinical results according to the Shwachman-Kulckycki score and spirometric. Conclusion: Our findings revealed a high prevalence of the atypical exoS+/exoU+ virulotype among P. aeruginosa isolates from patients with CF, which was associated with intermittent infection and early clinical alterations, while the exoS+/exoU− virulotype was associated with chronic infection and worse clinical results. Finally, the presented data highlight the relevance of T3SS virulence markers in the clinical progression and disease severity in CF patients.
Pseudomonas aeruginosa is an opportunistic pathogen causing different types of infections, particularly in intensive care unit patients. Characteristics that favor its persistence artificial environments are related to its high adaptability, wide arsenal of virulence factors and resistance to several antimicrobial classes. Among the several virulence determinants, T3SS stands as the most important due to the clinical impact of exoS and exoU genes in patient’s outcome. The molecular characterization of P. aeruginosa isolates helps in the comprehension of transmission dynamics and enhance knowledge of virulence and resistance roles in infection process. In the present study, we investigated virulence and resistance properties and the genetic background of P. aeruginosa isolated from ICUs patients at a referral hospital in Brazilian Amazon. A total of 54 P. aeruginosa isolates were characterized by detecting 19 virulence-related genes, antimicrobial susceptibility testing, molecular detection of β-lactamase-encoding genes and genotyping by MLST and rep-PCR. Our findings showed high prevalence of virulence-related markers, where 53.7% of the isolates presented at least 17 genes among the 19 investigated (P = 0.01). The rare exoS+/exoU+ cytotoxic virulotype was detected in 55.6% of isolates. Antimicrobial susceptibility testing revealed percentages of antibiotic resistance above 50% to carbapenems, cephalosporins and fluoroquinolones associated to MDR/XDR isolates. Isolates harboring both blaSPM-1 and blaOXA genes were also detected. Genotyping methods demonstrated a wide genetic diversity of strains spread among the different intensive care units, circulation of international MDR/XDR high-risk clones (ST111, ST235, ST244 and ST277) and emergence of seven novel MLST lineages. Finally, our findings highlight the circulation of strains with high virulence potential and resistance to antimicrobials and may be useful on comprehension of pathogenicity process, treatment guidance and establishment of strategies to control the spread of epidemic P. aeruginosa strains.
Carbapenem resistance among Klebsiella pneumoniae isolates is often related to carbapenemase genes, located in genetic transmissible elements, particularly the blaKPC gene, which variants are spread in several countries. Recently, reports of K. pneumoniae isolates harboring the blaNDM gene have increased dramatically along with the dissemination of epidemic high-risk clones (HRCs). In the present study, we report the multiclonal spread of New Delhi metallo-beta-lactamase (NDM)-producing K. pneumoniae in different healthcare institutions in the state of Pará, Northern Brazil. A total of 23 NDM-producing isolates were tested regarding antimicrobial susceptibility testing features, screening of carbapenemase genes, and genotyping by multilocus sequencing typing (MLST). All K. pneumoniae isolates were determined as multidrug-resistant (MDR), being mainly resistant to carbapenems, cephalosporins, and fluoroquinolones. The blaNDM-7 (60.9%—14/23) and blaNDM-1 (34.8%—8/23) variants were detected. MLST genotyping revealed the predomination of HRCs, including ST11/CC258, ST340/CC258, ST15/CC15, ST392/CC147, among others. To conclude, the present study reveals the contribution of HRCs and non-HRCs in the spread of NDM-1 and NDM-7-producing K. pneumoniae isolates in Northern (Amazon region) Brazil, along with the first detection of NDM-7 variant in Latin America and Brazil, highlighting the need for surveillance and control of strains that may negatively impact healthcare and antimicrobial resistance.
Chronic HIV-1 infection can cause neurological illness, also known as HIV-associated neurocognitive disorders (HAND). The elevated level of pro-inflammatory cytokines and chemokines, such as C-C Chemokine Ligand 5 (CCL5/RANTES), is one of the ways of causing HIV-1-mediated neuroinflammation. C-C Chemokine Receptor 5 (CCR5) is the main coreceptor for viral entry into host cells and for mediating induction of CCL5/RANTES. CCR5 and CCL5 are part of a correlated axis of immune pathways used for effective protection against the HIV-1 virus. The purpose of this paper was to review the literary knowledge about the immunopathological relationship between this immune complex and neuroAIDS. A systematic review of the literature was conducted based on the selection and search of articles, available in English, Spanish, or Portuguese in the time frame of 1990–2022, of primary and secondary types in the PUBMED, Science Direct, SciELO, and LILACS databases through descriptors (MeSH) together with “AND”: “CCR5”; “CCL5”; “neurological manifestations”; or “HIV”. The methodological quality of the articles was assessed using the JBI Checklists and the PRISMA 2020 writing guidelines were followed. A total of 36 articles were included in the final composition of the review. The main cells of the CNS affected by neuroAIDS are: neurons; microglia; astrocytes; and oligodendrocytes. Molecular devices and their associations with cellular injuries have been described from the entry of the virus into the host’s CNS cell to the generation of mental disorders. Furthermore, divergent results were found about the levels of CCL5/RANTES secretion and the generation of immunopathogenesis, while all condensed research for CCR5 indicated that elevation of this receptor causes more neurodegenerative manifestations. Therefore, new therapeutic and interventional strategies can be conditioned on the immunological direction proposed in this review for the disease.
The purpose of the current study is to describe the prevalence of Pseudomonas aeruginosa (PA)-producing MβL among Brazilian isolates and the frequency of blaSPM-1 in MβL-PA-producing isolates. From January 2009 to August 2023, we carried out an investigation on this subject in the internet databases SciELO, PubMed, Science Direct, and LILACS. A total of 20 papers that met the eligibility requirements were chosen by comprehensive meta-analysis software v2.2 for data retrieval and analysis by one meta-analysis using a fixed-effects model for the two investigations. The prevalence of MβL-producing P. aeruginosa was 35.8% or 0.358 (95% CI = 0.324–0.393). The studies’ differences were significantly different from one another (x2 = 243.15; p < 0.001; I2 = 92.18%), so they were divided into subgroups based on Brazilian regions. There was indication of asymmetry in the meta-analyses’ publishing bias funnel plot; so, a meta-regression was conducted by the study’s publication year. According to the findings of Begg’s test, no discernible publishing bias was found. blaSPM-1 prevalence was estimated at 66.9% or 0.669 in MβL-PA isolates (95% CI = 0.593–0.738). The analysis of this one showed an average heterogeneity (x2 = 90.93; p < 0.001; I2 = 80.20%). According to the results of Begg’s test and a funnel plot, no discernible publishing bias was found. The research showed that MβL-P. aeruginosa and SPM-1 isolates were relatively common among individuals in Brazil. P. aeruginosa and other opportunistic bacteria are spreading quickly and causing severe infections, so efforts are needed to pinpoint risk factors, reservoirs, transmission pathways, and the origin of infection.