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Drug resistance is rising to alarming levels, constituting one of the major threats to global health. The overexpression of efflux pumps and the formation of biofilms constitute two of the most common resistance mechanisms, favoring the virulence of bacteria. Therefore, the research and development of effective antimicrobial agents that can also counteract resistance mechanisms are extremely important. Pyrazino[2,1-b]quinazoline-3,6-diones, from marine and terrestrial organisms and simpler synthetic analogues, were recently disclosed by us as having relevant antimicrobial properties. In this study, using a multi-step approach, it was possible to synthesize new pyrazino[2,1-b]quinazoline-3,6-diones focusing on compounds with fluorine substituents since, to the best of our knowledge, the synthesis of fluorinated fumiquinazoline derivatives had not been attempted before. The new synthesized derivatives were screened for antibacterial activity and, along with previously synthetized pyrazino[2,1-b]quinazoline-3,6-diones, were characterized for their antibiofilm and efflux-pump-inhibiting effects against representative bacterial species and relevant resistant clinical strains. Several compounds showed relevant antibacterial activity against the tested Gram-positive bacterial species with MIC values in the range of 12.5–77 μM. Furthermore, some derivatives showed promising results as antibiofilm agents in a crystal violet assay. The results of the ethidium bromide accumulation assay suggested that some compounds could potentially inhibit bacterial efflux pumps. [ABSTRACT FROM AUTHOR]

Omadacycline (Nuzyra®) is a new aminomethylcycline, approved by the U. S. Food and Drug Administration in 2018, as a tetracycline antibacterial. It can be used in community-acquired pneumonia and in acute bacterial skin and skin-structure infections. It was developed and is commercialized by Paratek Pharmaceuticals. It is a semisynthetic compound, derived from minocycline, capable of evading widely distributed efflux and target protection antibacterial resistance mechanisms and has demonstrated activity in a broad spectrum of bacteria. [ABSTRACT FROM AUTHOR]

Introduction: Spondylodiscitis in childhood is rare and has non-specific clinical features, requiring a high index of suspicion., Clinical Case: The authors describe a nine month-old female infant, who presented at the emergency room (ER) with a torticollis for four days, without fever or trauma. Cervical X-rays were normal, and she received symptomatic treatment. Six days after, she returned to the ER with the same torticollis and also irritability, anorexia, and cervical hyper-extension. The CT scan showed cervical spondylodiscitis (C6-C7) with pre-vertebral abscess. The laboratory results only revealed a slightly elevated Sedimentation Rate. Treatment was systemic vancomycin, gentamicin and metronidazol for six weeks, followed by two weeks of oral flucloxacillin. The causative organism was not identified. The symptoms and the abscess resolved during the first week of treatment. Five days after finishing the antibiotics the magnetic resonance showed partial C6-C7 fusion, without neurologic compression or functional disability., Comments: Cervical spondylodiscitis with abscess is rare, especially in this age group. This case also emphasizes the importance of investigating an acquired persistent torticollis.

The term neutropenia concerns the reduction of the amount of circulating neutrophils in peripheric blood. The Chronic Benign Neutropenia of Childhood (CBNC) is characterized by the presence of a circulating neutrophils total number (absolute count) below 1,5 x 10(9)L, for over a six-month period. The diagnosis is established when the laboratorial changes occur during the first two years of life, without previous history of serious infections, nor neutrophils morphological changes, nor hypocellular bone marrow examination. The cellularity is normal or increased and a neutrophil maturation arrest at some phase can be observed. Generally, the whole process is solved by the age of four. Because this is a very rare clinical situation, it justifies a bibliographic revision about the theme. We present the clinical case of a 15 month-old-child, admitted with fever and diarrhea associated with neutropenia. Bone marrow aspiration, other laboratorial exams carried out during hospital internment and presented clinical evolution were consistent with CBNC diagnosis.