Comparison of drug susceptibility between Escherichia coli detected in stool cultures of patients undergoing transrectal prostate needle biopsy and Escherichia coli in hospital-wide urine antibiograms

A prostate biopsy is essential for prostate cancer diagnosis. However, infections are one of the biopsy-associated complications, and post-biopsy fever is estimated to occur in approximately 1% of all cases. It may thus be beneficial to perform a rectal swab culture before a transrectal prostate biopsy to confirm the presence of resistant bacteria and select preventive antibacterial agents according to the drug susceptibility results. This study aimed to determine whether there is a difference between the drug susceptibility of bacteria detected in the stool of patients who were scheduled to undergo prostate biopsy and the hospital-wide urine antibiogram. Patients suspected of having prostate cancer who underwent transrectal prostate biopsy via transrectal ultrasonography between August 1, 2016, and June 30, 2020, were included in this study. Stool samples were collected and cultured before biopsy. Overall, 99 patients underwent prostate biopsy, and of these, culture results were available for 81 patients (81.8%). Escherichia coli was detected in 74.0% (60 samples) of the stool culture samples, of which 4 samples were extended-spectrum β-lactamase-producing types. We found greater susceptibility of Escherichia coli to ampicillin, fluoroquinolones, sulfamethoxazole/trimethoprim, and cefixime in the stool culture antibiogram than in the hospital-wide urine antibiogram. We also found a significantly low incidence of ESBL-positive Escherichia coli in the stool culture antibiogram with p-values of 0.009, 0.007, and 0.03 compared to the hospital-wide urine antibiograms for 2017, 2018, and 2019, respectively. Stool culture of prostate cancer patients undergoing biopsy may provide useful information for selecting prophylactic antimicrobial agents.     

Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines

Abstract:  Kynuramines represent their own class of biogenic amines. They are formed either by decarboxylation of kynurenines or pyrrole ring cleavage of indoleamines. N ²-formylated compounds formed in this last reaction can be deformylated either enzymatically by arylamine formamidases or hemoperoxidases, or photochemically. The earlier literature mainly focussed on cardiovascular effects of kynuramine, 5-hydroxykynuramine and their N ¹, N ¹-dimethylated analogs, including indirect effects via release of catecholamines or acetylcholine and interference with serotonin receptors. After the discovery of N ¹-acetyl- N ²-formyl-5-methoxykynuramine (AFMK) and N ¹-acetyl-5-methoxykynuramine (AMK) as major brain metabolites of melatonin, these compounds became of particular interest. They were shown to be produced enzymatically, pseudoenzymatically, by various free radical-mediated and via photochemical processes. In recent years, AFMK and AMK were shown to scavenge reactive oxygen and nitrogen species, thereby forming several newly discovered 3-indolinone, cinnolinone and quinazoline compounds, and to protect tissues from damage by reactive intermediates in various models. AMK is of special interest due to its properties as a potent cyclooxygenase inhibitor, NO scavenger forming a stable nitrosation product, inhibitor and/or downregulator of neuronal and inducible NO synthases, and a mitochondrial metabolism modulator. AMK easily interacts with aromates, forms adducts with tyrosyl and tryptophanyl residues, and may modify proteins.     

Atractylodes macrocephala Koidz promotes intestinal epithelial restitution via the polyamine—Voltage-gated K channel pathway

Ethnopharmacological relevance

Atractylodes macrocephala Koidz (AMK) has been used widely as a digestive and tonic in traditional Chinese medicine. AMK has shown noteworthy promoting effect on intestinal epithelial cell migration, which might represent a promising candidate for the treatment of intestinal mucosa injury. The aim of this study was to investigate the efficacy of AMK on intestinal mucosal restitution and the underlying mechanisms via IEC-6 cell migration model.

Materials and methods

A wounding model of IEC-6 cells was induced by a single-edge razor blade along the diameter of six-well polystyrene plates. The cells were grown in control cultures and in cultures containing spermidine (5 μmol/L, SPD, reference drug), alpha-difluoromethylornithine (2.5 mmol/L, DFMO, polyamine inhibitor), AMK (50, 100, and 200 μg/mL), DFMO plus SPD and DFMO plus AMK for 24 h. The membrane potential (MP) and cytosolic free Ca²⁺ concentration ([Ca²⁺]_cyt) were detected by flow cytometry, and polyamines content was determined via high-performance liquid chromatography (HPLC). The expression of Kv1.1 mRNA and protein levels were assessed by RT-qPCR and Western blot analysis, respectively. Cell migration assay was carried out using the Image-Pro Plus software. All of these indexes were used to evaluate the effectiveness of AMK.

Results

(1) Treatment with AMK caused significant increases in cellular polyamines content, membrane hyperpolarization, an elevation of [Ca²⁺]_cyt and an acceleration of cell migration in IEC-6 cells, as compared to control group. (2) AMK not only reversed the inhibitory effects of DFMO on the polyamines content, MP, and [Ca²⁺]_cyt but also restored IEC-6 cell migration to control levels. (3) The Kv1.1 mRNA and protein expression were significantly increased by AMK treatment in control and polyamine-deficient IEC-6 cells.

Conclusions

The results of our current studies revealed that treatment with AMK significantly stimulates the migration of intestinal epithelial cells through polyamine-Kv1.1 channel signaling pathway, which could promote the healing of intestinal injury. These results suggest the potential usefulness of AMK to cure intestinal disorders characterized by injury and ineffective repair of the intestinal mucosa.     

Relationship between amikacin blood concentration and ototoxicity in low birth weight infants

Amikacin (AMK) is used as empiric therapy for severe infections such as sepsis in low birth weight (LBW) infants. AMK administered once daily (OD) in adults is reported to be therapeutically effective and prevent side effects, however, evidence on AMK administration in LBW infants is limited, with no clear indications of effectiveness. We performed therapeutic drug monitoring analysis of 20 infants treated with AMK OD for severe infections such as bacteremia. Treatment effectiveness was admitted by the patients’ medical records, and side effects of renal dysfunction and ototoxicity were investigated. The mean gestational age was 30.4 ± 5 weeks and mean body weight (Bw) was 1280.2 ± 809.8 g. The mean AMK dose was 14.1 ± 2.6 mg/kg and mean administration period was 10.1 ± 4.1 days. Blood concentration was measured 6.3 ± 2.3 days after AMK administration; mean peak and trough concentrations were 29.1 ± 7.5 μg/mL and 7.6 ± 6.9 μg/mL, respectively. Additionally, therapeutic effect was observed in all patients, and no significant change in serum creatinine (CRE) concentration (a marker of renal dysfunction) was observed, suggesting no renal dysfunction. Ototoxicity was observed in 4 patients, 3 of whom had trough concentrations ≥10 μg/mL. When we categorized patients into two groups using a trough cut-off value of 10 μg/mL, no difference in AMK dose was observed. However, there were significant differences in peak concentration, Bw, volume of distribution and CRE. Our findings suggest AMK trough concentration ≥10 μg/mL significantly affects ototoxicity in neonates.     

The melatonin metabolite N1-acetyl-5-methoxykynuramine is a potent singlet oxygen scavenger

Abstract:  Singlet oxygen was generated by means of rose bengal under irradiation by visible light. N ¹-acetyl-5-methoxykynuramine (AMK) was rapidly destroyed by this reactive oxygen species, whereas its formylated precursor, N ¹-acetyl- N ²-formyl-5-methoxykynuramine (AFMK), was remarkably inert. At photon fluence rates of 1400  μ mol photons/m²s, and using 20  μ m rose bengal, most of initially 0.2 m m AMK was destroyed within 2 min, whereas AFMK remained practically unchanged for much longer periods of time. Competition experiments with other scavengers revealed the following order of reactivity towards singlet oxygen: diazabicyclo-[2,2,2]-octane (DABCO) << imidazole < 4-ethylphenol <  N _α-acetylhistidine < histidine < melatonin < AMK, the last one being about 150 times more effective than DABCO. Contrary to the oxidation in free radical-generating systems, AMK did not form adducts with the tyrosine side chain fragment, 4-ethylphenol, under the influence of singlet oxygen. In UV-exposed cells (keratinocytes, plant cells) it is likely to be more rapidly destroyed by singlet oxygen than formed from AFMK.     

茶多酚对关木通所致小鼠肾脏损伤及锌、铜、镁含量的影响

目的探讨关木通染毒对小鼠肾脏锌、铜、镁含量的影响及茶多酚的拮抗作用. 方法将60只昆明小鼠随机分为:正常对照组、关木通染毒组、茶多酚(TP)处理TP1、TP2、TP3剂量组.用关木通给小鼠连续灌胃染毒, 同时用茶多酚进行干预.合计给药25 d后,称体重,取肾脏称重,并测定微量元素锌、铜、镁含量. 结果小鼠体重、肾重:关木通组与对照组比较显著下降(P<0.01);TP1、TP2组与对照组比较下降(P＜0.05);TP3组与对照组比较无差异.肾脏锌、镁含量:关木通组与对照组比较显著上升(P＜0.01),TP1、TP2组与对照组比较上升(P＜0.05),TP3组与对照组比较无差异,TP3组与TP1、TP2组比较下降(P＜0.05).铜含量:关木通组与对照组比较显著下降(P＜0.01),TP1 、TP2组与对照组比较下降(P＜0.05),TP3组与对照组比较无差异;TP3组与TP1、TP2组比较上升(P＜0.05). 结论茶多酚可调节关木通对肾脏造成的微量元素失衡并对关木通所致肾损伤有一定的保护作用,且存在剂量效应关系.     

白术对小鼠免疫功能影响的实验研究

目的：从免疫功能方面探讨中药白术的强身健体作用。方法：用100％白术水浸出液定给小鼠灌胃,然后测定其外周血白细胞（WBC）、脾脏及胸腺重量、抗体产生能力、淋巴细胞转化率、巨噬细胞吞噬率。结果：与对照组比,用药组小鼠胸腺和WBC有显著性差异（P＜0．05）。其它指标有非常显著性差异（P＜0．001）,未见有副作用。结论：口服白术可明显增强机体的免疫功能。     

In vivo study assessed meropenem and amikacin combination therapy against carbapenem-resistant and carbapenemase-producing Enterobacteriaceae strains

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE), especially for carbapenemase-producing Enterobacteriaceae (CPE), is an emerging cause that pose a significant threat to public health. However, efficient therapy has not been established. We assessed the antimicrobial efficacy of meropenem (MEPM) and amikacin (AMK) combination therapy.Material and methodsTotal eight isolates of Escherichia coli or Klebsiella pneumoniae, including CRE and/or CPE have carbapenemase genes were used. The relationship between phenotype and in vivo efficacy was assessed in neutropenic murine thigh infection model. Efficacy was determined using the change in bacterial density and survival rate.ResultsThe combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-K. pneumoniae isolates than MEPM monotherapy (0.63 ± 0.04 vs. 2.56 ± 0.24 ⊿log₁₀ cfu/mL, p < 0.05; −1.05 ± 0.15 vs. −0.48 ± 0.30 ⊿log₁₀ cfu/mL, p < 0.05). Likewise, the combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-E. coli isolates than MEPM monotherapy (0.90 ± 0.68 vs. 1.86 ± 0.23 ⊿log₁₀ cfu/mL, p < 0.05; −1.81 ± 0.06 vs. −0.88 ± 0.23 ⊿log₁₀ cfu/mL, p < 0.05). Also, combination therapy group showed similar to higher survival rates in CRE + E. coli infection mice, compared to MEPM monotherapy group.ConclusionOur results are the first supportive data to threat CRE infections with combination therapy of MEPM and AMK with in vivo model. The current results verify the promising utility of the combination therapy with MEPM and AMK against CRE isolates with a wide range of MEPM MICs.     

Treatment strategies with alternative treatment options for patients with Mycobacterium avium complex pulmonary disease

Diseases caused by Mycobacterium avium complex (MAC) infection in the lungs are increasing worldwide. The recurrence rate of MAC-pulmonary disease (PD) has been reported to be as high as 25–45%. A significant percentage of recurrences occurs because of reinfection with a new genotype from the environment. A focus on reducing exposure to MAC organisms from the environment is therefore an essential component of the management of this disease as well as standard MAC-PD treatment. A macrolide-containing three-drug regimen is recommended over a two-drug regimen as a standard treatment, and azithromycin is recommended rather than clarithromycin. Both the 2007 and 2020 guidelines recommend a treatment duration of MAC-PD of at least one year after the culture conversion. Previous clinical studies have reported that ethambutol could prevent macrolide resistance. Furthermore, the concomitant use of aminoglycoside, amikacin liposomal inhalation, clofazimine, linezolid, bedaquiline, and fluoroquinolone with modification of guideline-based therapy has been studied.Long-term management of MAC-PD remains challenging because of the discontinuation of multi-drug regimens and the acquisition of macrolide resistance. Moreover, the poor compliance of guideline-based therapy for MAC-PD treatment worldwide is concerning since it causes macrolide resistance.Therefore, in this review, we focus on MAC-PD treatment and summarize various treatment options when standard treatment cannot be maintained, with reference to the latest ATS/ERS/ESCMID/IDSA clinical practice guidelines revised in 2020.