Publications by authors named "Binghua Hao"
Article Synopsis
- Within-patient diversity in bloodstream infections (BSIs) was investigated by sequencing strains from blood cultures of 4 patients, revealing mixed populations in 3 of them with significant genetic variations.
- One strain variant with chromosome 7 trisomy (Tri7) from patient MN showed different growth behaviors and competitiveness compared to its euploid counterpart during infections and antifungal treatments.
- The study suggests that diverse strain populations exist in BSIs, which could impact treatment outcomes and highlight the need for further research into their clinical significance and antifungal resistance.
Article Synopsis
- Traditional belief held that bloodstream infections (BSIs) were primarily caused by a single organism, but this study reveals mixed populations of genetically diverse strains of Candida glabrata in patients.
- Whole genome sequencing showed distinct genetic differences among these strains, impacting their susceptibility to antifungal treatments and their ability to evade the immune system.
- Findings indicate that the persistence and relapse of infections may be linked to a diversity of drug-resistant strains, highlighting the need for a population-based understanding of C. glabrata during BSIs.
Article Synopsis
- * Whole genome sequencing of strains from blood cultures of ten patients revealed that these mixed populations can have significant differences in their susceptibility to antifungal treatments.
- * The study indicates that this genetic diversity can lead to the recovery of both susceptible and resistant strains during infections, suggesting a need for a new understanding of how these infections behave and progress.
Article Synopsis
- Bacterial bloodstream infections (BSIs) may involve a mix of different organisms rather than just single pathogens, specifically investigating the behavior of carbapenem-resistant Klebsiella pneumoniae (CRKP).
- Researchers analyzed 10 strains of CRKP from 6 patients, revealing genetic and phenotypic diversity among strains within individual patients, indicating significant variations in antibiotic resistance and virulence factors.
- The findings challenge traditional beliefs about BSIs being caused by a single organism, suggesting that understanding within-host microbial diversity could change infection management and treatment strategies.
Background: Multidrug-resistant Enterobacterales (MDR-E), including carbapenem-resistant and third-generation cephalosporin-resistant Enterobacterales (CRE, CefR-E), are major pathogens following solid organ transplantation (SOT).
Methods: We prospectively studied patients who underwent lung, liver, and small bowel transplant from February 2015 through March 2017. Weekly perirectal swabs (up to 100 days post-transplant) were cultured for MDR-E.
Article Synopsis
- A study involving 20 patients with infections from carbapenem-resistant Enterobacteriaceae treated with meropenem-vaborbactam showed a 65% clinical success rate and 90% survival rate within 30 days.
- However, 35% of patients experienced microbiologic failures within 90 days post-treatment.
- Notably, one patient faced a recurring infection caused by a resistant mutant strain of Klebsiella pneumoniae.
Article Synopsis
- A study was conducted on 24 carbapenem-resistant (CRE) isolates using ceftazidime-avibactam and colistin to evaluate their effectiveness through time-kill tests.
- Ceftazidime-avibactam showed increased effectiveness at higher concentrations, being bactericidal against 88% of isolates at 4× MIC, while colistin was effective against 83% within 12 hours.
- The two drugs had mixed results when used together, with some synergy and antagonism observed, but overall, the combination did not outperform ceftazidime-avibactam alone against most isolates.
Article Synopsis
- Ceftazidime-avibactam and ceftolozane-tazobactam are new antibiotics used against multidrug-resistant Gram-negative bacteria, but resistance to them has been reported.
- A study compared different testing methods for these antibiotics and found that Etest provided more accurate results than disk diffusion, with higher agreement with standard broth microdilution methods.
- Disk diffusion tests overestimated resistance to ceftazidime-avibactam, indicating a need for better interpretation guidelines before routine clinical use.
Article Synopsis
- A retrospective study was conducted on 21 patients treated with ceftolozane-tazobactam for infections caused by multidrug-resistant Pseudomonas aeruginosa, focusing on treatment outcomes and resistance development.
- The study found that 71% of patients responded well to the treatment, but a concerning 14% developed resistance, primarily linked to genetic mutations rather than external sources.
- Further research is called for to better understand the effectiveness and resistance mechanisms of ceftolozane-tazobactam in various MDR-P. aeruginosa infections.
Article Synopsis
- * By using site-directed mutagenesis and transforming vectors, we showed that these mutations produced enzymes that acted as extended-spectrum β-lactamases, increasing resistance.
- * The D179Y mutation had the most significant impact, leading to higher minimum inhibitory concentrations (MICs) for ceftazidime-avibactam and lower MICs for carbapenems and other β-lactams, indicating the critical role of the KPC Ω-loop in resistance.
Thirty-seven carbapenem-resistant Enterobacteriaceae (CRE)-infected patients were treated with ceftazidime-avibactam. Clinical success and survival rates at 30 days were 59% (22/37) and 76% (28/37), respectively. In 23% (5/22) of clinical successes, CRE infections recurred within 90 days.
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- The study analyzed the effectiveness of several antibiotics against 38 isolates of meropenem-resistant Pseudomonas aeruginosa, focusing on ceftazidime-avibactam, ceftolozane-tazobactam, and others.
- None of the isolates produced carbapenemases, with 74% showing mutations in the oprD gene.
- Both ceftazidime-avibactam and ceftolozane-tazobactam were effective against 92% of isolates, suggesting they are viable treatment options, but should be used carefully to maintain their efficacy.
Article Synopsis
- Avibactam is a new β-lactamase inhibitor that works well with ceftazidime against Klebsiella pneumoniae strains producing carbapenemases (KPCs), which are known for their genetic diversity and resistance mechanisms.
- In tests on 72 KPC-Kp strains, the presence of avibactam significantly reduced the minimum inhibitory concentrations (MICs) of ceftazidime, making it effective against most strains, though some still showed concerning resistance levels.
- Higher drug MICs were noted in strains with specific mutations; therefore, careful use of ceftazidime-avibactam is essential to avoid further resistance development.
Article Synopsis
- - We conducted a study to evaluate how effective plazomicin, a new type of antibiotic, and other aminoglycosides are against 50 strains of carbapenem-resistant Klebsiella pneumoniae, mainly focusing on the role of aminoglycoside-modifying enzymes (AMEs) present in these bacteria.
- - The majority of the strains (94%) were from a specific genetic group (ST258) and showed high levels of resistance, with 98% having AMEs that decreased the effectiveness of other aminoglycosides like gentamicin and tobramycin, while plazomicin showed some potential effectiveness.
- - Our findings indicate that different combinations and types of AMEs enhance resistance levels, and thus
Article Synopsis
- The study investigated C. glabrata infections in a mouse model of intra-abdominal candidiasis (IAC), revealing a high mortality rate with certain strains while others caused varying levels of disease severity.
- A mutated strain lacking phospholipase B genes was found to kill mice similarly to a virulent strain, but resulted in quicker abscess resolution and lower pathogen loads during sublethal infections.
- Compared to C. albicans, C. glabrata was generally less lethal and triggered a milder immune response, leading to more persistent abdominal infections and abscesses.
Article Synopsis
- * A treatment combination of doripenem and colistin was less effective than gentamicin alone, or other combinations involving gentamicin against certain resistant strains.
- * An algorithm that uses ompK36 genotypes and drug susceptibility may help predict the effectiveness of treatments against KPC-producing K. pneumoniae.
Article Synopsis
- The study investigates the poorly understood pathogenesis of intra-abdominal candidiasis using a mouse model infected with Candida albicans.
- Mice developed symptoms like peritonitis and abscesses shortly after infection, with notable changes in biological responses, especially involving the gene RIM101.
- RIM101 plays a crucial role in C. albicans persistence and gene expression during infection, suggesting that it influences the survival of the fungus in abscesses through the activation of other genes like SAP5.
Article Synopsis
- The study investigates the effectiveness of the drug combination doripenem and colistin against various strains of Klebsiella pneumoniae that produce carbapenemase, specifically KPC-2.
- It found that certain genetic mutations in the ompK36 porin gene influenced how well these bacteria responded to the treatment, with the presence of specific mutations linked to higher levels of drug resistance.
- The results indicate that strains with wild-type or other mutations typically had better responses to the drug combination, suggesting that genetic profiling could help predict treatment outcomes for infections caused by these bacteria.
Caspofungin kills Candida albicans by causing both cellular apoptosis and necrosis.
Antimicrob Agents Chemother
January 2013
Article Synopsis
- - Caspofungin kills Candida albicans by blocking the synthesis of (1,3)-β-d-glucan in the cell wall, leading to cell death through both apoptosis and necrosis at specific concentrations (0.125 and 0.5 μg/ml).
- - Approximately 20-25% of C. albicans cells showed early signs of apoptosis, while 5-7% showed late apoptosis/necrosis, with higher concentrations of caspofungin significantly increasing necrosis rates.
- - Various staining techniques revealed that apoptosis is triggered even at low concentrations of caspofungin, with cell imaging confirming characteristics such as chromatin changes and metacaspase activation, highlighting the drug's impact on
Article Synopsis
- The study investigates how the signaling of a lipid called phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and septin proteins help Candida albicans maintain its cell wall integrity when exposed to the antifungal drug caspofungin.
- Researchers found that specific mutants of C. albicans, which have increased levels of PI(4,5)P2 due to a lack of certain enzymes, display abnormal distribution of PI(4,5)P2 and septins across their cell surfaces.
- The findings suggest that the Irs4-Inp51 complex and the Gin4 protein play key roles in this distribution and are crucial for the yeast's natural response to
Article Synopsis
- * PCR testing from plasma or sera outperformed whole blood and BDG in sensitivity for diagnosing IC, particularly for deep-seated candidiasis.
- * Combining blood cultures with PCR or BDG greatly improved diagnosis sensitivity for IC, making these tests valuable in clinical settings.
Article Synopsis
- * The drug caused significant fungal kills, achieving fungicidal effects (>3 log) at various concentrations, and demonstrated post-antifungal effects (PAFEs) that prolonged its activity even after short exposure.
- * Additionally, PAFE experiments revealed that micafungin induced cell wall damage, decreased the fungi's ability to adhere to cells, and made them more susceptible to being attacked by immune cells (mac
Article Synopsis
- Anidulafungin is an antifungal drug that targets the cell walls of Candida species by blocking beta-1,3-glucan synthase, leading to cell death and lasting effects even after the drug is removed.
- In experiments, anidulafungin showed significant fungicidal activity against various Candida isolates, with impressive results at high concentrations (MICs) resulting in effective cell kill and prolonged inhibition of regrowth for over 12 hours.
- The drug also caused changes in cell wall structure and reduced the ability of Candida to adhere to human cells, suggesting that its effectiveness comes not only from killing the fungi directly but also by making it harder for the pathogens to infect and survive in hosts.
Article Synopsis
- Researchers studied a protein called RFX2 from Candida albicans, which shows similarities to a protein in yeasts and is recognized by the immune system in people with candidiasis.
- The study found that the absence of RFX2 made C. albicans more resilient to UV radiation and other stressors, while also increasing its invasive properties and adherence to human cells.
- Mice infected with a C. albicans strain lacking RFX2 showed serious differences in disease progression, including delayed mortality and reduced infection severity, suggesting RFX2 impacts DNA damage responses, growth forms, and overall virulence of the fungus.
Article Synopsis
- * While strain P5 had a similar DNA profile to SC5314, it had a higher concentration of mitochondria and displayed alterations in its respiratory functions, indicating changes in its energy production.
- * This mutant was less harmful to mice, showing reduced damage in kidneys and avoiding death in the host; it also exhibited resistance to immune response and could withstand oxidative stress better than the original strain, suggesting an adaptive survival strategy in hostile environments.