Abstract Polymyxin B (PMB) and colistin, administered as the prodrug colistin methanesulfonate sodium (CMS), are increasingly used to treat carbapenem-resistant Gram-negative bacteria. Nephrotoxicity ...is the major dose-limiting adverse effect of both polymyxins. A retrospective cohort study of 132 patients was conducted to evaluate risk factors for acute kidney injury (AKI), classified according to Acute Kidney Injury Network criteria, in patients treated with ≥48 h of intravenous PMB or CMS, with particular focus on potential differences between each polymyxin. The overall incidence of AKI was 25.8% (34/132) 20.8% (20/96) and 38.9% (14/36) in patients treated with PMB and CMS, respectively; P = 0.06. In the Cox regression model, doses ≥2 million International Units (MIU) of PMB or >9 MIU of CMS were the only variable independently associated with AKI adjusted hazard ratio (aHR) = 2.11, 95% confidence interval (CI) 1.01–4.41; P = 0.04. Vancomycin co-administration was strongly associated with AKI, although this was not statistically significant (aHR = 2.22, 95% CI 0.98–5.04; P = 0.058). There was no statistically significant difference in the incidence of AKI between patients treated with PMB or CMS in the multivariate model (aHR = 1.74, 95% CI 0.82–3.69; P = 0.15). High dose was the main risk factor for AKI regardless of the polymyxin administered. Vancomycin co-administration likely increases the risk of AKI. Although there was a higher overall incidence of AKI in patients treated with CMS compared with PMB, CMS was not significantly associated with this outcome after adjusting for the above variables.
Summary
Background
Schizophyllum commune is one of the causative agents of basidiomycosis including disorders such as allergic bronchopulmonary mycosis, allergic fungal sinusitis, and mucoid ...impaction of bronchi, the incidence of those of which has been increasing. These mycoses are difficult to diagnose because only a limited number of diagnostic tools are currently available. The biggest problem is that no specific antigens of S. commune have been identified to enable serodiagnosis of the disease.
Objective
In this study, we attempted to identify a major antigen of S. commune to establish a reliable serodiagnostic method.
Methods
We used mass spectrometry to identify an antigen that reacted with the serum of a patient with allergic bronchopulmonary mycosis caused by S. commune. The protein was expressed in Escherichia coli, highly purified, and the patient sera IgG and IgE titres against the protein were determined by enzyme‐linked immunosorbent assay.
Results
The protein identified as a major antigen of S. commune was named Sch c 1; it was a homolog of glucoamylase. The IgG and IgE titres against Sch c 1 in patient sera were significantly higher than those in healthy volunteer sera (P < 0.01).
Conclusions and Clinical Relevance
Sch c 1 is recognized by the host immune system of patients as an antigen/allergen. The purified glucoamylase Sch c 1 is a promising candidate antigen for the serodiagnosis of S. commune‐induced mycosis.
Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration, poor efficacy and side effects. Once-daily fixed-combination ...timolol-netarsudil-latanoprost ophthalmic solution (FC-TNL) has the ability to treat glaucoma by lowering the intraocular pressure (IOP) with great efficacy and improving patient compliance. However, the commercialized netarsudil dimesylate precipitated when the pH of the solution was above 5.4, or when maleic acid, the salt of commercial timolol maleate, was mixed with netarsudil dimesylate. Consequently, the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in pH 4.8–5.2 solution by synthesizing timolol mesylate. Next, the morphology of timolol mesylate was observed by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and powder X-ray diffraction. The prepared FC-TNL showed good stability during refrigeration storage. Additionally, FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study. Importantly, once-daily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells. The FC-TNL was stable, safe and effective, being a promising glaucoma therapeutic.
Synthesis of timolol mesylate and preparation of fixed-combination timolol-netarsudil-latanoprost ophthalmic solution with good stability to control and reduce intraocular pressure in rabbit ocular hypertension model. Display omitted
The safety and efficacy profile of caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospective, randomized, double-blind study. The proportion of ...patients who developed significant drug-related adverse event(s) (defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation) was compared in 120 patients caspofungin 50 mg, or 50 mg following a 70-mg loading dose on Day 1 (hereinafter, 70/50 mg) group: 60 patients; micafungin 150 mg: 60 patients. The overall response rate was primarily evaluated in the per-protocol set (PPS) population. The proportion of patients who developed significant drug-related adverse events was 5.0 % (3/60) in the caspofungin group and 10.0 % (6/60) in the micafungin group 95 % confidence interval (CI) for the difference: −15.9 %, 5.2 %. The favorable overall response in the PPS population for patients with esophageal candidiasis, invasive candidiasis, and chronic pulmonary aspergillosis including aspergilloma was 100.0 % (6/6), 100.0 % (3/3), and 46.7 % (14/30) in the caspofungin group, and 83.3 % (5/6), 100.0 % (1/1), and 42.4 % (14/33) in the micafungin group, respectively. In Japanese patients with
Candida
or
Aspergillus
infections, there was no statistical difference in the safety between caspofungin and micafungin. Consistent with other data on these two agents, the efficacy of caspofungin and micafungin was similar.
Invasive fusariosis (IF) is a frequently fatal disease as there are few antifungals to treat it, making the prevention of IF crucial. However, fusarium infections have not been as thoroughly studied ...as other common pathogenic fungi such as Aspergillus or Candida.
To investigate the epidemiology of IF in patients with haematological diseases in Japan and to elucidate the infectious route of fusarium infection.
We retrospectively analysed 29 IF cases in patients with haematological diseases from 2009 to 2019 in Japan. To discover the infectious source of IF, we performed an indoor environment survey targeted at indoor air and drain outlets in medical institutions and residences using culture-based and metagenomic methods. Finally, we performed aerosol- and droplet-mediated dispersion studies.
The epidemiological study showed that the primary pathogen of IF was Fusarium solani species complex (FSSC), and the most common species was Fusarium petroliphilum. Most patients were likely to develop IF during hospitalization. A fusarium culture was positive in 26 of 72 drain samples. Few fusarium were detected from air samples; by contrast, 29 of 108 isolates from the drain outlets were identified as fusarium. Furthermore, similar results were obtained in the metagenomic analysis. Interestingly, species belonging to FSSC were isolated from indoor drain outlets, which was similar to those of the IF patients. In the droplet-mediated dispersion study, eight to 17 colonies of fusarium were isolated.
Our study indicates that causative Fusarium spp. could inhabit drain outlets in hospitals or residences, and droplet-mediated fusarium dispersion is a potential cause of IF.
Gliotoxin is an important virulence factor of Aspergillus fumigatus. Although GliA putatively belongs to the major facilitator superfamily in the gliotoxin biosynthesis cluster, its roles remain ...unclear. To determine the function of GliA, we disrupted gliA in A. fumigatus. gliA disruption increased the susceptibility of A. fumigatus to gliotoxin. The gliT and gliA double-disrupted mutant had even higher susceptibility to gliotoxin than each individual disruptant. The extracellular release of gliotoxin was greatly decreased in the gliA disruptant. Mice infected with the gliA disruptant of A. fumigatus showed higher survival rates than those infected with the parent strain. These results strongly indicate that GliA, in addition to GliT, plays a significant role in the tolerance to gliotoxin and protection from extracellular gliotoxin in A. fumigatus by exporting the toxin. This also allows the fungus to evade the harmful effect of its own gliotoxin production. Moreover, GliA contributes to the virulence of A. fumigatus through gliotoxin secretion.
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