New Microbiologica最新文献

The pillar of treatment success, defined as viral suppression and immune restoration, should be integrated into a modern vision of therapeutic success with pharmacological attributes of ART, such as potency, forgiveness, and genetic barrier of single drugs and regimens, as well as their longterm tolerability and safety. Moreover, the longterm success of lifelong treatment cannot be separated from the opinions and preferences of PLWH. Regimen Optimization in the setting of HIV suppression may reduce pill burden, and/or dosing frequency, enhance tolerability and/or decrease toxicity, prevent or mitigate DDIs, eliminate food/fluid requirements, relieve pill fatigue, decrease stigma or concerns associated with taking oral med, allow pregnancy, reduce costs (DHHS 2023). Regimen Optimization should be tailored by a person-centered perspective, based on the individual therapeutic history, past toxicities and comorbidities. The treatment strategy should be based on the perceived tolerability and quality of life, considering the preferences of people on treatment along with the virological and pharmacological factors. The health care system should facilitate universal and rapid access to personalized, robust, and effective therapies. The BIC/FTC/TAF association ensures all these characteristics and therefore represents a valid strategy for optimizing treatment in PLWH virologically suppressed.

The study's objective was to assess whether the performance of the DIAGNOVITAL SARS-CoV-2 Mutation Detection Assays is affected by Omicron mutations. In silico evaluation of 67,717 Variant of Concern, Variant of Interest sequences and 6,612 sequences of the Omicron variants involving BA1., BA2., BA3 sub-lineages downloaded from the GISAID database by 17 December 2021, were performed. The sequences were aligned according to the reference genome MN908947.3 using MAFFT multiple sequence alignment software version 7. Our findings showed that among 6,612 Omicron, 41 Spike gene mutations with a frequency of ≥70% were identified. Some of the Omicron mutations (R408S, N440K, G446S, Q493S, Q498R) could affect the diagnostic performance of K417N, L452R, and E484K assays against the Omicron sub-lineages. However, L452R and K417N mutation tests allow differentiation of the Delta and Omicron variants mutation profile. The COVID-19 pandemic lasted longer than expected, and the rapid modification of diagnostic kits seems necessary to combat the pandemic.

The aim of the TWODAY Study was to investigate the frequency of early treatment change after rapid start of a tailored ART regimen (a 2-drug regimen - 2DR, when clinically feasible or a 3-drug regimen - 3DR, otherwise). TWODAY was an open-label, prospective, proof-of-concept, single center study. ART-naïve patients started their first-line regimen within a few days from the first laboratory testing with a 2DR of dolutegravir (DTG) and lamivudine (3TC) if CD4+ count >200 cells/mL, HIVRNA <500,000 copies/mL, no transmitted drug resistance to DTG or 3TC and HBsAg undetectable; otherwise, ART was started with a 3DR. The primary endpoint was the proportion of patients who needed to change ART within four week from start, for any reason. Thirty-two patients were enrolled; 19 (59.3%) were deemed eligible for a 2DR. Median time from laboratory testing to ART start was 5 days (5; 5). No regimen modification occurred within one month. In conclusion, no regimen modification was needed within the first month of treatment. Starting a 2DR within a few days after HIV diagnosis was feasible, relying upon complete results of the needed laboratory tests (including resistance testing). A 2DR can be safely proposed provided full laboratory tests are readily available.

Ceftolozane (CTLZ) is a novel cephalosporin antibiotic that exhibits broad-spectrum activity against gram-negative pathogens, including Pseudomonas aeruginosa, especially when combined with tazobactam (TAZ). We examined the minimum inhibitory concentration (MIC) of CTLZ/TAZ for 21 multidrug-resistant P. aeruginosa (MDRP) and eight carbapenem-resistant P. aeruginosa (CRPA) strains isolated at Okayama University Hospital, Japan. Consequently, 81% (17/21) of the MDRP strains and 25% (2/8) of the CRPA strains were resistant to CTLZ/TAZ (MIC >8 μg/mL). All 18 blaIMP-positive strains showed resistance to CTLZ/TAZ, whereas the drug retained in vitro susceptibility in 54.5% (6/11 strains) of blaIMP-negative strains.

Food safety is the primary concern of the food industry. The aim of the current research is to study the antimicrobial effects of cell-free supernatant of Lactobacillus pentosus against Bacillus cereus and Klebsiella pneumoniae. B. cereus and K. pneumoniae were isolated from infant formula milk product and meat sample, respectively. Their identification was performed through morphological characterization and biochemical testing. Molecular identification of K. pneumoniae was based on 16s ribotyping. A previously isolated and reported strain of L. pentosus was used for the isolation of CFS (Cellfree supernatants). Antimicrobial activity was studied through agar well diffusion assay. Inhibitory activity was recorded by measuring the zone of inhibition. CFS activity was evaluated for temperature and pH. The antimicrobial activity of CFS of L. pentosus produced at different temperatures and pH was investigated against B. cereus and K. pneumoniae. A clear zone of inhibition was observed against B. cereus while no ZOI was formed against K. pneumoniae. K. pneumoniae was found resistant to the CFS. Crude bacteriocin exhibited heat stability for a temperature of 121°C for 30 minutes and pH range of 3-7. The current study concluded that bacteriocin produced from L. pentosus can be used for the control of B. cereus. Its heat and pH stability allows its potential therapeutic use in the food industry as a food preservative and to control food poisoning cases due to B. cereus. K. pneumoniaeis was found resistant to the isolated bacteriocin, and therefore L. pentosus cannot be used for control against K. pneumoniae.

Management of heavily treatment experienced (HTE) people with HIV remains a challenge. Tailored antiretroviral therapy (ART) is needed in this fragile population who almost invariably harbor viral quasispecies with resistance-associated mutations (RAMs). The reference method for HIV genotypic resistance testing (GRT) has long been Sanger sequencing (SS), but next-generation sequencing (NGS), following recent progress in workflow and cost-effectiveness, is replacing SS because of higher sensitivity. From the PRESTIGIO Registry, we present a case of a 59-year-old HTE woman who failed darunavir/ritonavir plus raltegravir at low-viremia levels due mainly to high pill burden and poor adherence. NGS-GRT was performed on HIV-RNA at failure and the results were compared to all past SS-GRT data available (historical genotype). In this case, NGS-GRT did not detect any minority drug-resistant variants. After discussing several therapeutic options, the treatment was changed to dolutegravir 50 mg twice daily plus doravirine 100 mg once a day, based on clinical history, adherence issues, and pill burden, as well as the historical SS-GRT and the latest NGS-GRT results. At six months follow-up visit, the patient had HIV-RNA below 30 copies/ml and CD4+ T cell count increased from 673 cells/ mm3 to 688 cells/ mm3. Close follow-up of this patient is ongoing.

The intestinal microbiota plays a fundamental role in physiological homeostasis as well as in pathologic conditions. Hepatitis C virus is the leading cause of chronic liver diseases worldwide. The treatment of this infection has been revolutionized by the availability of direct-acting antiviral agents which guarantee a high rate (about 95%) of viral clearance. Few studies have assessed the change in the gut microbiota of patients treated with direct-acting antiviral agents against HCV, and many aspects still need to be clarified. The aim of the study was to evaluate the effects of antiviral therapy on gut microbiota. We enrolled patients with HCV-related chronic liver disease attending the Infectious Diseases Unit of the A.O.U. Federico II of Naples from January 2017 to March 2018 and treated with DAAs. For each patient, a fecal sample was collected and analyzed for the assessment of microbial diversity before the start of therapy and by SVR12 time. We excluded patients who had received antibiotics in the previous 6 months. Twelve patients were enrolled (6 male, 8 genotype 1 (1 subtype 1a), 4 genotype 2). Fibrosis scores were F0 in 1 patient, F2 in 1 patient, F3 in 4 patients and cirrhosis in the remaining 6 (all in Child-Pugh class A). All were treated with DAAs for 12 weeks (5 with Paritaprevir-Ombitasvir-Ritonavir-Dasabuvir, 3 with Sofosbuvir-Ledipasvir, 1 with Sofosbuvir-Ribavirin, 1 with Sofosbuvir-Daclatasvir, 1 with Sofosbuvir-Velpatasvir) and 100% achieved SVR12. In all patients, we observed a trend in reduction of potentially pathogenic microorganisms (i.e., Enterobacteriaceae). Furthermore, a trend of increase in α-diversity was observed in patients by SVR12 compared to baseline. This trend was markedly more evident in patients without liver cirrhosis than in those with cirrhosis. Our study shows that viral eradication obtained with DAA is associated with a trend in restoring the heterogeneity of α-diversity and in reducing the percentage of potentially pathogenic microbial species, although this benefit is less evident in patients with cirrhosis. Further studies with larger sample size are needed to confirm these data.

Since the outbreak of the 2019 pandemic coronavirus disease (COVID-19), great attention has been given to identifying the main clinical features of the disease. Identification of laboratory parameters able to classify patients based on their risk is mandatory to improve their clinical management. We retrospectively evaluated twenty-six laboratory tests measured in COVID-19 positive patients admitted to the hospital in March and April 2020 to find any correlation between their changes and the risk of death. We divided them into surviving and non-surviving patients. A total of 1587 patients were recruited, 854 males with median age of 71 (IQR 56-81) and 733 females with median age of 77 (IQR 61-87). On admission, death was found to be positively correlated with age (p=0.001), but not with sex (p=0.640) or with hospitalization in days (p=0.827). Brain natriuretic peptide (BNP), creatinine, C-reactive protein (CRP), INR, leukocyte count, lymphocyte count, neutrophil count, and procalcitonin (PCT) demonstrated a statistically significant difference between the two groups (p<0.001), suggesting their role as markers of disease severity; only lymphocyte count resulted as an independent risk factor for death.

Microbial biofilm is of paramount importance in the development of mucositis or peri-implantitis in patients with dental implants. This study was designed to investigate whether an electromagnetic field at high frequency waves directly applied on 33 titanium implants could remove experimentally-induced Enterococcus faecalis bacterial biofilm. A specially designed device (X-IMPLANT) was used to generate the electromagnetic field, with output power of 8 W, supply frequency (action/pause) 3/2s, and an output frequency of 625±5% kHz in plastic devices containing the biofilm-covered implants immersed in sterile saline. The bacterial biofilm on both treated and untreated control implants was quantitatively measured by phenol red-based Bio-Timer-Assay reagent. The kinetic analysis of the curves showed that the electrical treatment generated by the X-IMPLANT device completely removed the bacterial biofilm after 30 minutes of treatment (p<0.01). Elimination of the biofilm was also confirmed by chromatic observation in the macro-method. Our data seem to indicate that the procedure could be considered for clinical application in peri-implantitis to counteract bacterial biofilm on dental implants.

Currently, the infection of hypervirulent Klebsiella pneumoniae (hvKp) is becoming increasingly serious and the virulent mechanisms of hvKp are still not very clear. An effective gene-editing method for genes on hvKp virulence plasmid can help us reveal related virulent mechanisms. There are a few reports focusing on the methods mentioned above, however with certain limitations. In this work, we first constructed the pRE112-basing recombinant suicide plasmid to knock out or replace the genes in the hvKp virulence plasmid based on the principle of homology recombination. Results showed that the target virulent genes iucA, iucB, iroB, and rmpA2 on the hvKp virulence plasmid were scarlessly knocked out or replaced by marker genes, and mutant hvKp strains with the expected phenotypes were obtained. These indicated that we established an efficient gene-editing method for genes on hvKp virulence plasmid, which could help us explore the functions of these genes and reveal the virulent mechanisms of hvKp.