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Annals of Medicine Dec 2024complex () is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic... (Review)
Review
complex () is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic fibrosis (CF), can cause severe lung infections that lead to accelerated lung damage, which can be complicated by necrotizing pneumonia accompanied by high fevers, leucocytosis, and bacteraemia, which commonly causes fatal outcomes. Specifically, infection by is considered an exclusion criterion for lung transplantation. The species of exhibit both genetic and phenotypic hypervariability that complicate their accurate microbiological identification. Automated methods such as MALDI-TOF can err in the determination of species. Their slow growth even in selective agars and the absence of international consensuses on the optimal conditions for their isolation make early diagnosis a difficult challenge to overcome. The absence of correlations between antibiograms and clinical results has resulted in the absence of standardized cut-off values of antimicrobial susceptibility, a fact that brings a latent risk since incorrect antibiotic therapy can induce the selection of more aggressive variants that worsen the clinical picture of the host, added to the absence of a clear therapeutic guide for the eradication of pulmonary infections by in patients with CF, resulting in frequently ineffective treatments. There is an urgent need to standardize methods and diagnostic tools that would allow an early and accurate diagnosis, as well as to perform clinical studies of the effectiveness of available antibiotics to eradicate infections, which would allow us to establish standardized therapeutic schemes for -infected patients.
Topics: Humans; Cystic Fibrosis; Burkholderia cepacia complex; Lung Transplantation; Anti-Bacterial Agents; Bacteremia
PubMed: 38261606
DOI: 10.1080/07853890.2024.2307503 -
Journal of Clinical Medicine Sep 2023Chronic granulomatous disease (CGD) is an inborn error of immunity due to defects in the transport or function of subunits of nicotinamide adenine dinucleotide phosphate... (Review)
Review
Chronic granulomatous disease (CGD) is an inborn error of immunity due to defects in the transport or function of subunits of nicotinamide adenine dinucleotide phosphate oxidase, the enzyme that generates the phagocyte respiratory burst responsible for intracellular killing of engulfed micro-organisms. Patients present with infectious or inflammatory complications. Common bacterial pathogens include and complex. Fungal pathogens include species, particularly . Inflammatory complications most commonly manifest as inflammatory bowel disease or lung disease. Granulomata are the distinguishing histological feature. Haematopoietic stem cell transplantation (HSCT) was first considered for CGD in the early 1970's. Since then, refinements in transplant technique, donor selection, conditioning regimens, and graft engineering have widened the option of HSCT to most patients with CGD. This review charts the progress made in HSCT for CGD.
PubMed: 37763024
DOI: 10.3390/jcm12186083 -
and activity of cefiderocol against spp. and complex, including carbapenem-non-susceptible isolates.Antimicrobial Agents and Chemotherapy Dec 2023spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the...
spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the antibacterial activity of the siderophore antibiotic cefiderocol against spp. and Bcc isolates with that of other approved antibacterial drugs, including ceftazidime-avibactam, ciprofloxacin, colistin, imipenem-relebactam, and meropenem-vaborbactam. Isolates were collected in the SIDERO multinational surveillance program. Among 334 spp. isolates [76.6% from respiratory tract infections (RTIs)], cefiderocol had minimum inhibitory concentration (MIC) of 0.06/0.5 µg/mL overall and 0.5/4 µg/mL against 52 (15.6%) carbapenem-non-susceptible (Carb-NS) isolates. Eleven (3.3%) spp. isolates overall and 6 (11.5%) Carb-NS isolates were not susceptible to cefiderocol. Among 425 Bcc isolates (73.4% from RTIs), cefiderocol had MIC of ≤0.03/0.5 µg/mL overall and ≤0.03/1 µg/mL against 184 (43.3%) Carb-NS isolates. Twenty-two (5.2%) Bcc isolates overall and 13 (7.1%) Carb-NS isolates were not susceptible to cefiderocol. Cumulative MIC distributions showed cefiderocol to be the most active of the agents tested against both spp. and Bcc. In a neutropenic murine lung infection model and a humanized pharmacokinetic immunocompetent rat lung infection model, cefiderocol showed significant bactericidal activity against two meropenem-resistant strains compared with untreated controls ( < 0.05) and vehicle-treated controls ( < 0.05), respectively. Meropenem, piperacillin-tazobactam, ceftazidime, and ciprofloxacin comparators showed no significant activity in these models. The results suggest that cefiderocol could be a possible treatment option for RTIs caused by spp. and Bcc.
Topics: Rats; Animals; Mice; Cefiderocol; Meropenem; Carbapenems; Cephalosporins; Burkholderia cepacia complex; Achromobacter; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Ceftazidime; Respiratory Tract Infections; Ciprofloxacin; Microbial Sensitivity Tests
PubMed: 37971240
DOI: 10.1128/aac.00346-23 -
Microorganisms Dec 2023This review was conducted to assess the global incidence of transfusion-transmitted infections (TTIs) caused by contamination of blood components with the complex... (Review)
Review
This review was conducted to assess the global incidence of transfusion-transmitted infections (TTIs) caused by contamination of blood components with the complex (Bcc). Our search encompassed various specialized databases such as Medline/PubMed, Web of Science, Scopus, Scielo, ScienceDirect, and ClinicalKey. An analysis of the literature revealed a total of eleven reported cases where blood components contaminated with Bcc had been transfused, resulting in sepsis among the affected patients. Of these cases, eight were documented in the literature, while the remaining three occurred within the institution involving the authors of this review. A comparative examination was conducted, considering factors such as primary diagnosis, transfused blood component, time elapsed between transfusion and manifestation of symptoms, administration of antibiotics, and final outcome. Interestingly, regardless of the storage temperature, all blood components were found to be susceptible to Bcc contamination. Furthermore, the cases investigated revealed diverse sources of contamination, and it was observed that all the affected patients had compromised immune systems due to underlying illnesses. Based on these findings, a series of preventive strategies were derived to mitigate and decrease the occurrence of similar cases.
PubMed: 38257866
DOI: 10.3390/microorganisms12010040 -
Research Square Jul 2023To report the clinical characteristics, antibiotic susceptibilities, and review the literature of complex () associated endophthalmitis.
PURPOSE
To report the clinical characteristics, antibiotic susceptibilities, and review the literature of complex () associated endophthalmitis.
STUDY DESIGN
Retrospective, observational case series.
METHODS
Clinical and microbiology records were reviewed for patients evaluated at the Bascom Palmer Eye Institute and diagnosed with culture-confirmed endophthalmitis due to . Antibiotic susceptibility profiles were generated using standard microbiologic protocols via an automated VITEK system.
RESULTS
Endophthalmitis associated with BCC was diagnosed in three patients. Infection occurred in the setting of post-penetrating keratoplasty (PKP), glaucoma filtering surgery, and suspected trauma. All isolates demonstrated susceptibility to ceftazidime and meropenem. Presenting visual acuity (VA) ranged from hand motion to light perception. Initial treatment strategies included intravitreal ceftazidime (2.25 mg/0.1 mL) and vancomycin (1.0 mg/0.1mL) injections with fortified topical antibiotics in 2 patients, and surgical debridement of a corneoscleral melt with patch graft along with both topical fortified antibiotics oral antibiotics in the third patient. In all 3 patients, there was no VA improvement at last follow-up, as 2 eyes ultimately underwent enucleation and 1 eye exhibited phthisis bulbi at last follow-up. BCC related endophthalmitis was reviewed among 13 reports. Treatment outcomes were generally poor and antibiotic resistance was common. These BCC isolates cases demonstrated broad resistance patterns, with susceptibilities to ceftazidime (58%), ciprofloxacin (53%), and gentamicin (33%).
CONCLUSIONS
Endophthalmitis caused by is a rare clinical entity with generally poor visual outcomes despite prompt treatment with appropriate antibiotics.
PubMed: 37503162
DOI: 10.21203/rs.3.rs-3181158/v1 -
The Journal of Organic Chemistry Aug 2023We report on novel chemoenzymatic routes toward tenofovir using low-cost starting materials and commercial or homemade enzyme preparations as biocatalysts. The...
We report on novel chemoenzymatic routes toward tenofovir using low-cost starting materials and commercial or homemade enzyme preparations as biocatalysts. The biocatalytic key step was accomplished either via stereoselective reduction using an alcohol dehydrogenase or via kinetic resolution using a lipase. By employing a suspension of immobilized lipase from (Amano PS-IM) in a mixture of vinyl acetate and toluene, the desired ()-ester (99% ee) was obtained on a 500 mg scale (60 mM) in 47% yield. Alternatively, stereoselective reduction of 1-(6-chloro-9-purin-9-yl) propan-2-one (84 mg, 100 mM) catalyzed by lyophilized cells harboring recombinant alcohol dehydrogenase (ADH) from (/Lk-ADH Prince) allowed one to reach quantitative conversion, 86% yield and excellent optical purity (>99% ee) of the corresponding ()-alcohol. The key ()-intermediate was transformed into tenofovir through "one-pot" aminolysis-hydrolysis of ()-acetate in NH-saturated methanol, alkylation of the resulting ()-alcohol with tosylated diethyl(hydroxymethyl) phosphonate, and bromotrimethylsilane (TMSBr)-mediated cleavage of the formed phosphonate ester into the free phosphonic acid. The elaborated enzymatic strategy could be applicable in the asymmetric synthesis of tenofovir prodrug derivatives, including 5'-disoproxil fumarate (TDF, Viread) and 5'-alafenamide (TAF, Vemlidy). The molecular basis of the stereoselectivity of the employed ADHs was revealed by molecular docking studies.
Topics: Tenofovir; Alcohol Dehydrogenase; Escherichia coli; Molecular Docking Simulation; Alanine; Organophosphonates; Lipase; Anti-HIV Agents
PubMed: 37467462
DOI: 10.1021/acs.joc.3c01005 -
Nature Communications Sep 2023The rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol...
The rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol (Fetroja®) is a clinically-used sideromycin, that is utilized for the treatment of severe drug-resistant infections, caused by Gram-negative bacteria; there is evidence of cefiderocol-resistance occurring in bacterial strains however. To increase the efficacy and extend the life-span of sideromycins, we demonstrate strong synergisms between cefiderocol and metallodrugs (e.g., colloidal bismuth citrate (CBS)), against Pseudomonas aeruginosa and Burkholderia cepacia. Moreover, CBS enhances cefiderocol efficacy against biofilm formation, suppresses the resistance development in P. aeruginosa and resensitizes clinically isolated resistant P. aeruginosa to cefiderocol. Notably, the co-therapy of CBS and cefiderocol significantly increases the survival rate of mice and decreases bacterial loads in the lung in a murine acute pneumonia model. The observed phenomena are partially attributable to the competitive binding of Bi to cefiderocol with Fe, leading to enhanced uptake of Bi and reduced levels of Fe in cells. Our studies provide insight into the antimicrobial potential of metallo-sideromycins.
Topics: Mice; Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Bacterial Load; Pseudomonas aeruginosa; Cefiderocol
PubMed: 37658047
DOI: 10.1038/s41467-023-40828-3 -
Journal of Ophthalmic Inflammation and... Nov 2023To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex (BCC) associated endophthalmitis.
PURPOSE
To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex (BCC) associated endophthalmitis.
STUDY DESIGN
Retrospective, observational case series.
METHODS
Clinical and microbiology records were reviewed for patients evaluated at the Bascom Palmer Eye Institute and diagnosed wisth culture-confirmed endophthalmitis due to BCC. Antibiotic susceptibility profiles were generated using standard microbiologic protocols via an automated VITEK system.
RESULTS
Endophthalmitis associated with BCC was diagnosed in three patients. Infection occurred in the setting of post-penetrating keratoplasty (PKP), glaucoma filtering surgery, and suspected trauma. All isolates demonstrated in vitro susceptibility to ceftazidime and meropenem. Presenting visual acuity (VA) ranged from hand motion to light perception. Initial treatment strategies included intravitreal ceftazidime (2.25 mg/0.1 mL) and vancomycin (1.0 mg/0.1 mL) injections with fortified topical antibiotics in 2 patients, and surgical debridement of a corneoscleral melt with patch graft along with both topical fortified antibiotics oral antibiotics in the third patient. In all 3 patients, there was no VA improvement at last follow-up, as 2 eyes ultimately underwent enucleation and 1 eye exhibited phthisis bulbi at last follow-up. BCC related endophthalmitis was reviewed among 13 reports. Treatment outcomes were generally poor and antibiotic resistance was common. These BCC isolates cases demonstrated broad resistance patterns, with susceptibilities to ceftazidime (58%), ciprofloxacin (53%), and gentamicin (33%).
CONCLUSIONS
Endophthalmitis caused by B. cepacia is a rare clinical entity with generally poor visual outcomes despite prompt treatment with appropriate antibiotics.
PubMed: 37922028
DOI: 10.1186/s12348-023-00370-1 -
Frontiers in Microbiology 2023To mine specific proteins and their protein-coding genes as suitable molecular biomarkers for the Complex (BCC) bacteria detection based on mega analysis of microbial...
OBJECTIVE
To mine specific proteins and their protein-coding genes as suitable molecular biomarkers for the Complex (BCC) bacteria detection based on mega analysis of microbial proteomic and genomic data comparisons and to develop a real-time recombinase polymerase amplification (rt-RPA) assay for rapid isothermal screening for pharmaceutical and personal care products.
METHODS
We constructed an automatic screening framework based on Python to compare the microbial proteomes of 78 BCC strains and 263 non-BCC strains to identify BCC-specific protein sequences. In addition, the specific protein-coding gene and its core DNA sequence were validated with a self-built genome database containing 158 thousand bacteria. The appropriate methodology for BCC detection using rt-RPA was evaluated by 58 strains in pure culture and 33 batches of artificially contaminated pharmaceutical and personal care products.
RESULTS
We identified the protein SecY and its protein-coding gene through the automatic comparison framework. The virtual evaluation of the conserved region of gene showed more than 99.8% specificity from the genome database, and it can distinguish all known BCC species from other bacteria by phylogenetic analysis. Furthermore, the detection limit of the rt-RPA assay targeting the gene was 5.6 × 10 CFU of BCC bacteria in pure culture or 1.2 pg of BCC bacteria genomic DNA within 30 min. It was validated to detect <1 CFU/portion of BCC bacteria from artificially contaminated samples after a pre-enrichment process. The relative trueness and sensitivity of the rt-RPA assay were 100% in practice compared to the reference methods.
CONCLUSION
The automatic comparison framework for molecular biomarker mining is straightforward, universal, applicable, and efficient. Based on recognizing the BCC-specific protein SecY and its gene, we successfully established the rt-RPA assay for rapid detection in pharmaceutical and personal care products.
PubMed: 37779692
DOI: 10.3389/fmicb.2023.1270760