Isolation of multidrug-resistant Haemophilus influenzae harbouring multiple exogenous genes from a patient diagnosed with acute sinusitis.

In paediatric patients, ß-lactams and macrolides are widely used to treat acute otitis media and sinusitis, which are often caused by either Streptococcus pneumoniae or Haemophilus influenzae. However, resistant isolates have emerged and are becoming more prevalent. H. influenzae generally acquires antimicrobial resistance by mutation or by expression of ß-lactamase. In this study, we isolated H. influenzae from a paediatric patient diagnosed with acute sinusitis. This strain harboured multiple exogenous resistance genes: blaTEM-1, mef(A) and tet(M). DNA sequencing suggested that both mef(A) and tet(M) had been transferred from S. pneumoniae or another Streptococcus. This typical outpatient had not been exposed to excessive levels of antibiotics and had no underlying diseases, strongly suggesting that this type of resistant isolate could become more prevalent.

[Investigation and Improvement of Techniques That Affect the Amount of Dispersal during Preparation of Anticancer Drugs].

Many healthcare workers who handle anticancer drugs are at risk for occupational exposure. However, there are no established permissible limits for occupational exposure to anticancer drugs; thus, in this study, we aimed to search for and improve procedures that have a greater impact on the amount of spatter for handling anticancer drugs in vials, which are frequently used, based on the quantitative evaluation of the amount of exposure. We used sodium riboflavin phosphate (FMN) as a simulated anticancer drug and measured the amount of FMN dispersed to the handling area by the wiping method and the amount of FMN dispersed in both gloves using high-performance liquid chromatography with fluorescence detection (HPLC-FL). In this study, it was suggested that the overall amount of dispersal in the preparation process was affected by the different methods of injecting the drug solution into the infusion bottles and whether recapping. It was also found that the variation in the amount of dispersal differed depending on the selected preparation technique. It was suggested that the amount of dispersal could be reduced by selecting an appropriate dissolution method for multiple vials, recapping, an appropriate method for injecting the drug into the infusion bottle, and properly preparing the internal pressure of the infusion bottle. The results of this study suggest that there are some techniques and procedures in the preparation process of vials that have a significant effect on the amount of dispersal, and that proper implementation of these techniques can contribute to the reduction of dispersal.

Quantitative comparison of anticancer drug dispersal before and after introducing appropriate preparation procedures during anticancer drug preparation.

BACKGROUND: In Japan, engineering controls for preparing injectable anticancer drugs are inadequate and compliance with appropriate preparation procedures is vital. In this study, we evaluated the effects of adherence to appropriate anticancer drug formulation and packaging procedures on reducing anticancer drug dispersal in clinical practice, especially in Japan. METHODS: We quantitatively evaluated the effectiveness of implementing procedures that were experimentally verified to help reduce the amount of anticancer drug dispersed during preparation based on procedures described in the "Anticancer Drug Preparation Manual." The target facilities were four regional hub hospitals in the Kanto area. Contamination of sheets and gloves with 5-fluorouracil (5-FU) and gemcitabine (GEM) in a safety cabinet during formulation was evaluated using wipe tests. Subsequently, the proper preparation procedure was shown on a video, training was provided, and the wipe tests were repeated. RESULTS: Forty-one and 39 pharmacists were engaged in drug preparation before and after intervention, respectively. 5-FU had the highest dispersal per prepared vial on the sheet before intervention. The dispersal amount per prepared vial decreased significantly (P = 0.01) after intervention. The amount of GEM dispersed before and after intervention did not differ significantly. However, the percentage of sheets below the detection limit after intervention was 62%, increasing from 46% before intervention. The amount dispersed on gloves was not significantly reduced by proper preparation technique. Although not explicitly noticeable and quantifiable, pharmacists must consider that a significant amount of anticancer drug is dispersed on gloves despite following appropriate preparation procedures. CONCLUSIONS: Quantitative amounts of anticancer drugs dispersed in the preparations of 5-FU and GEM were found in our study. The difference in the amount of contamination before and after intervention was significantly reduced only for the contamination of sheets with 5-FU. There was no decrease in the amount of glove contamination. There was also no difference between medical facilities. Despite following appropriate preparation procedures, dispersed amounts cannot be maintained below the detection limit, indicating the need for a combination of education and engineering controls.

Emergence of Haemophilus influenzae with low susceptibility to quinolones and persistence in tosufloxacin treatment.

BACKGROUND: The use of non-ß-lactam agents has increased in Japan due to the prevalence of ß-lactam-resistant pathogens. This study aimed to clarify the recent trend of antimicrobial susceptibility and molecular epidemiological features in Haemophilus influenzae. METHODS: Fifty-seven Haemophilus influenzae isolated from a Japanese teaching hospital in 2017 were characterised, and the data were compared with those of a previous study. The MICs were determined using the broth dilution method. Genetic backgrounds were compared by multilocus sequence typing. The bactericidal activity of tosufloxacin at, or near, the therapeutic Cmax was determined in vitro, with susceptible isolates and quinolone low-susceptible isolates by time-kill assay. RESULTS: The results of the susceptibility tests showed that >90% of isolates were susceptible to cephalosporins and carbapenems, whereas ampicillin-susceptible and clarithromycin-susceptible isolates decreased. Regarding quinolones, low-susceptible isolates were noted in 2017, although all isolates were judged as susceptible. All low-susceptible isolates had an amino acid substitution in GyrA, and two isolates had an additional substitution in ParC. These isolates had different genetic backgrounds. Furthermore, the time-kill kinetic assay using the Cmax of tosufloxacin indicated that the low-susceptible isolates could persist for at least 8hours. CONCLUSIONS: This study revealed that Haemophilus influenzae has demonstrated multidrug low-susceptibility in recent years. The low-susceptible isolates had genetic diversity, meaning that resistance occurred independently.