The role of colonization with resistant Gram-negative bacteria in the treatment of febrile neutropenia after stem cell transplantation.

Background: Febrile neutropenia (FN) is a common complication of stem cell transplantation.

Aim: To evaluate the frequency of sepsis in patients with FN colonized with resistant Gram-negative bacteria (extended-spectrum β-lactamase (ESBL)-positive, multidrug-resistant (MDR) Pseudomonas aeruginosa) and the choice of primary antibiotic in colonized patients.

Methods: This retrospective study analysed data from patients undergoing haematopoietic stem cell transplantation from January 2018 to September 2022.

A hit expansion of 3-benzamidopyrazine-2-carboxamide: Toward inhibitors of prolyl-tRNA synthetase with antimycobacterial activity.

This study presents an exploration of the chemical space around derivatives of 3-benzamidopyrazine-2-carboxamides, previously identified as potent antimycobacterial compounds with predicted binding to mycobacterial prolyl-transfer RNA synthetase. New urea derivatives (Series-1) were generally inactive, probably due to their preference for cis-trans conformation (confirmed by density functional theory calculations and experimentally by nuclear overhauser effect spectroscopy NMR). Series-2 (3-benzamidopyrazine-2-carboxamides with disubstituted benzene ring) demonstrated that substituents larger than fluorine are not tolerated in the ortho position of the benzene ring.

Introduction of continuous glucose monitoring (CGM) is a key factor in decreasing HbA1c in war refugee children with type 1 diabetes.

Aims: Our aim was to describe the changes in therapy and diabetes control in Ukrainian war refugee children with diabetes (CwD) during the first year of their stay in Czechia.

Methods: A total of 124 CwD (62 male, 62 female) were enrolled into this observational study. Anthropometric, laboratory and diabetes management data were acquired at baseline and at 3 months intervals for 12 months.

High-Pressure Inactivation of in Human Breast Milk.

Although Holder pasteurization is the recommended method for processing breast milk, it does affect some of its nutritional and biological properties and is ineffective at inactivating spores. The aim of this study was to find and validate an alternative methodology for processing breast milk to increase its availability for newborn babies and reduce the financial loss associated with discarding milk that has become microbiologically positive. We prepared two series of breast milk samples inoculated with the () strain to verify the effectiveness of two high-pressure treatments: (1) 350 MPa/5 min/38 °C in four cycles and (2) cumulative pressure of 350 MPa/20 min/38 °C.

-Pyrazinylhydroxybenzamides as biologically active compounds: a hit-expansion study and antimicrobial evaluation.

The development of novel antimicrobial drugs is an essential part of combatting the uprising of antimicrobial resistance. Proper hit-to-lead development is crucially needed. We present a hit-expansion study of -pyrazinyl- and -pyridyl-hydroxybenzamides with a comprehensive determination of structure-activity relationships.

Overweight and obesity in children and adolescents with endocrine disorders.

Obesity has become a serious medical condition where many factors can contribute to excess weight gain. The most common type of childhood obesity is simple obesity, which is due to gene-obesogenic environment interaction. Only a minority are due to pathological causes.

Antimycobacterial pyridine carboxamides: From design to in vivo activity.

Tuberculosis is the number one killer of infectious diseases caused by a single microbe, namely Mycobacterium tuberculosis (Mtb). The success rate of curing this infection is decreasing due to emerging antimicrobial resistance. Therefore, novel treatments are urgently needed.

Correction: Juhás et al. Improving Antimicrobial Activity and Physico-Chemical Properties by Isosteric Replacement of 2-Aminothiazole with 2-Aminooxazole. 2022, , 580.

In the original publication [...

Design, Synthesis and Antimicrobial Evaluation of New -(1-Hydroxy-1,3-dihydrobenzo[][1,2]oxaborol-6-yl)(hetero)aryl-2-carboxamides as Potential Inhibitors of Mycobacterial Leucyl-tRNA Synthetase.

Tuberculosis remains a serious killer among infectious diseases due to its incidence, mortality, and occurrence of resistant mycobacterial strains. The challenge to discover new antimycobacterial agents forced us to prepare a series of -(1-hydroxy-1,3-dihydrobenzo[][1,2]oxaborol-6-yl)(hetero)aryl-2-carboxamides 1-19 via the acylation of 6-aminobenzo[][1,2]oxaborol-1(3)-ol with various activated (hetero)arylcarboxylic acids. These novel compounds have been tested in vitro against a panel of clinically important fungi and bacteria, including mycobacteria.

Better Outcome of Off-Label High-Dose Ceftazidime in Hemato-Oncological Patients with Infections Caused by Extensively Drug-Resistant .

Background: sepsis in immunocompromised patients is a serious complication of cancer treatment, especially in the case of an Extensively Drug Resistant (XDR) pathogen. The aim of the study is to evaluate the efficacy of high-dose ceftazidime in the treatment of XDR infection and to compare it with the conventionally treated cohort in hemato-oncological patients.

Methods: We identified 27 patients with XDR infection during the 2008-2018 period, 16 patients served as a conventionally treated cohort with an antipseudomonal beta-lactam antibiotic in standard dose (cohort A), and 11 patients were treated with high-dose ceftazidime (cohort B).

Hybridization Approach Toward Novel Antituberculars: Design, Synthesis, and Biological Evaluation of Compounds Combining Pyrazinamide and 4-Aminosalicylic Acid.

Apart from the SARS-CoV-2 virus, tuberculosis remains the leading cause of death from a single infectious agent according to the World Health Organization. As part of our long-term research, we prepared a series of hybrid compounds combining pyrazinamide, a first-line antitubercular agent, and 4-aminosalicylic acid (PAS), a second-line agent. Compound was found to be the most potent, with a broad spectrum of antimycobacterial activity and selectivity toward mycobacterial strains over other pathogens.

Pediatric Cushing's disease: Case reports and retrospective review.

Background: We report four pediatric subjects with Cushing's disease (CD) diagnosed in the Czech Republic. We focus on initial symptoms of Cushing's syndrome (CS) which can lead to early diagnosis, on typical symptoms of CS in children, their age and sex distribution, the mean length of symptoms prior to diagnosis, indication for examination, post-cure growth, sexual development and pituitary function in our four CD patients after transsphenoidal pituitary surgery (TSS). We describe the diagnostic process leading to confirmation of CD and we emphasize the biochemical and radiological diagnostic difficulties.

Superiority of ceftazidime off-label high-dose regimen in PK/PD target attainment during treatment of extensively drug-resistant Pseudomonas aeruginosa infections in cancer patients.

Aim: The objective of this study was to evaluate off-label high-dose ceftazidime population pharmacokinetics in cancer patients with suspected or proven extensively drug-resistant (XDR) Pseudomonas aeruginosa infections and then to compare the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target after standard and off-label high-dose regimens using population model-based simulations. A further aim was to clinically observe the occurrence of adverse effects during the off-label high-dose ceftazidime treatment.

Methods: In patients treated with off-label high-dose ceftazidime (3 g every 6 h), blood samples were collected and ceftazidime serum levels measured using LC-MS/MS.

Adenosine-Mimicking Derivatives of 3-Aminopyrazine-2-Carboxamide: Towards Inhibitors of Prolyl-tRNA Synthetase with Antimycobacterial Activity.

Multidrug-resistant tuberculosis (MDR-TB) poses a significant threat to mankind and as such earned its place on the WHO list of priority pathogens. New antimycobacterials with a mechanism of action different to currently used agents are highly required. This study presents the design, synthesis, and biological evaluation of 3-acylaminopyrazine-2-carboxamides derived from a previously reported inhibitor of human prolyl-tRNA synthetase.

[Clinical experience with the use of newer antibiotics in internal medicine].

The alarming rise in antibiotic resistance between Gram-positive and Gram-negative bacteria makes maximum use of known and available antibiotics necessary. The aim of this work is to highlight some advantages and disadvantages of antibiotics that have appeared on the market in recent years, and share clinical experience with their use in internal medicine. Flucloxacillin is an antibiotic with a significant antistaphylococcal effect, the most significant indications of the oral form are infections of the skin and soft tissues with the causative agent of Staphylococcus aureus and streptococci.

Improving Antimicrobial Activity and Physico-Chemical Properties by Isosteric Replacement of 2-Aminothiazole with 2-Aminooxazole.

Antimicrobial drug resistance is currently one of the most critical health issues. Pathogens resistant to last-resort antibiotics are increasing, and very few effective antibacterial agents have been introduced in recent years. The promising drug candidates are often discontinued in the primary stages of the drug discovery pipeline due to their unspecific reactivity (PAINS), toxicity, insufficient stability, or low water solubility.

[A cirrhotic patient in an internal medicine ward].

Liver cirrhosis represents a common condition with substantial mortality. Manifestation and progression of ascites, hepatic encephalopathy or gastrointestinal bleeding are among main reasons for hospital admission. Infections represent another specific area in cirrhotic patients.

Quantitative Risk Assessment of Growth during the Warming of Thawed Pasteurized Human Banked Milk Using a Predictive Mathematical Model.

is relatively resistant to pasteurization. We assessed the risk of growth during warming and subsequent storage of pasteurized banked milk (PBM) in the warmed state using a predictive mathematical model. Holder pasteurization followed by storage below -18 °C was used.

Risk Factors for Infections, Antibiotic Therapy, and Its Impact on Cancer Therapy Outcomes for Patients with Solid Tumors.

Infections represent a significant cause of morbidity and mortality in cancer patients. Multiple factors related to the patient, tumor, and cancer therapy can affect the risk of infection in patients with solid tumors. A thorough understanding of such factors can aid in the identification of patients with substantial risk of infection, allowing medical practitioners to tailor therapy and apply prophylactic measures to avoid serious complications.

as a Major Cause of Discarded Pasteurized Human Banked Milk: A Single Human Milk Bank Experience.

A systematic study, performed from 2017-2020 looked at the rate of positive post-pasteurization findings, the quantity of in pasteurized banked human milk (PBM), and the rate of toxicogenic isolates from PBM. During the study period, 6815.71 L (30,943 tested bottles) of PBM were tested, with an average amount per year of 1703.

Design, synthesis and biological evaluation of substituted 3-amino-N-(thiazol-2-yl)pyrazine-2-carboxamides as inhibitors of mycobacterial methionine aminopeptidase 1.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) is the number one cause of deaths due to a single infectious agent worldwide. The treatment of TB is lengthy and often complicated by the increasing drug resistance. New compounds with new mechanisms of action are therefore needed.

Cystic ovarian teratoma as a novel tumor and growth hormone deficiency as a new condition presenting in Multiple Endocrine Neoplasia type 2B: Case reports and review of the literature.

Background: We describe early and typical nonendocrine symptoms of Multiple Endocrine Neoplasia type 2B (MEN2B) presented in our patients with de novo M918T mutation in the RET proto-oncogene in early childhood, however, the diagnosis of MEN2B and medullary thyroid carcinoma (MTC) was confirmed late, in the second decade of life. In this paper, we emphasize the possibility of growth retardation, growth hormone (GH) deficiency and ovarian teratoma as a new symptom of MEN2B.

Case Reports: Advanced MTC with palpable mass on the neck and nonendocrine symptoms such as marfanoid habitus, thickened lips, mucosal neuromas led to the diagnosis in case 1 at the age of 13 years and GH deficiency and nonendocrine symptoms in case 2 at the age of 11 years.

Effect of Restriction of Fluoroquinolone Antibiotics on Infections in the University Hospital Hradec Králové.

is the most common pathogen responsible for hospital-acquired diarrhea. This complication of antibiotic treatment mainly endangers the health of elder patients. Preventing the development of infections (CDI) is still a challenge that needs to be addressed.

5-Alkylamino--phenylpyrazine-2-carboxamides: Design, Preparation, and Antimycobacterial Evaluation.

According to the World Health Organization, tuberculosis is still in the top ten causes of death from a single infectious agent, killing more than 1.7 million people worldwide each year. The rising resistance developed by against currently used antituberculars is an imperative to develop new compounds with potential antimycobacterial activity.