Characterization of Drug-Resistant Lipid-Dependent Differentially Detectable Mycobacterium tuberculosis

An estimated 15–20% of patients who are treated for pulmonary tuberculosis (TB) are culture-negative at the time of diagnosis. Recent work has focused on the existence of differentially detectable Mycobacterium tuberculosis (Mtb) bacilli that do not grow under routine solid culture conditions without the addition of supplementary stimuli. We identified a cohort of TB patients in Lima, Peru, in whom acid-fast bacilli could be detected by sputum smear microscopy, but from whom Mtb could not be grown in standard solid culture media. When we attempted to re-grow Mtb from the frozen sputum samples of these patients, we found that 10 out of 15 could be grown in a glycerol-poor/lipid-rich medium. These fell into the following two groups: a subset that could be regrown in glycerol after “lipid-resuscitation”, and a group that displayed a heritable glycerol-sensitive phenotype that were unable to grow in the presence of this carbon source. Notably, all of the glycerol-sensitive strains were found to be multidrug resistant. Although whole-genome sequencing of the lipid-resuscitated strains identified 20 unique mutations compared to closely related strains, no single genetic lesion could be associated with this phenotype. In summary, we found that lipid-based media effectively fostered the growth of Mtb from a series of sputum smear-positive samples that were not culturable in glycerol-based Lowenstein–Jensen or 7H9 media, which is consistent with Mtb’s known preference for non-glycolytic sources during infection. Analysis of the recovered strains demonstrated that both genetic and non-genetic mechanisms contribute to the observed differential capturability, and suggested that this phenotype may be associated with drug resistance.

Disputed issues of systemic toxicity of local anesthetics

Objective: assessment of the "systemic toxicity of local anesthetics,” term validity, and a legal appraisal of the term “lipid resuscitation.” Regulatory documents and specialized literature devoted to the terminology of toxicity of local anesthetics were reviewed and analyzed. The article presents the classification of the adverse events proposed by World Health Organization experts. The legal issues related to the so-called “lipid resuscitation” are discussed. It seems appropriate to replace the term “systemic toxicity” of local anesthetics in all official documents with the term “side effect of the drug” or “side effects.” The use of the “lipid resuscitation” term in clinical practice is not supported by regulatory documents.

Accidental intravenous administration of levobupivacaine in the postoperative period

Levobupivacin was introduced into clinical practice as a drug with a low risk of complications from the cardiovascular and central nervous system. The purpose of the report is to present a case of unintentional intravenous administration of levobupivacaine with epidural analgesia. After vertebral surgery, the patient was mistakenly injected with 10 ml of a 0.5% solution of levobupivacaine. Clinically, systemic toxicity was manifested only in mild euphoria. After lipid resuscitation, the patients condition improved. Despite the successful outcome of the clinical case, the anesthesiologist must always have the means to carry out lipid resuscitation. Education of nurses on epidural drug administration is required. The issue of transporting patients with an epidural catheter to a specialist ward needs further discussion.