Efficacy of omadacycline in the treatment of Legionella pneumonia: a case report.

Legionella, one of the main pathogens that causes community-acquired pneumonia, can lead to Legionella pneumonia, a condition characterized predominantly by severe pneumonia. This disease, caused by the bacterium Legionella pneumophila, can quickly progress to critical pneumonia and is often associated with damage to multiple organs. As a result, it requires close attention in terms of clinical diagnosis and treatment. Omadacycline, a new type of tetracycline derivative belonging to the aminomethylcycline class of antibiotics, is a semi-synthetic compound derived from minocycline. Its key structural feature, the aminomethyl modification, allows omadacycline to overcome bacterial resistance and broadens its range of effectiveness against bacteria. Clinical studies have demonstrated that omadacycline is not metabolized in the body, and patients with hepatic and renal dysfunction do not need to adjust their dosage. This paper reports a case of successful treatment of Legionella pneumonia with omadacycline in a patient who initially did not respond to empirical treatment with moxifloxacin. The patient also experienced electrolyte disturbance, as well as dysfunction in the liver and kidneys, delirium, and other related psychiatric symptoms.

Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound.

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects. The molecule was obtained by removal the dimethylamino substituent at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with α-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of α-Syn preformed fibrils (α-SynPFF) in biophysical assays and in a SH-SY5Y-α-Syn-tRFP cell model. In addition, DDMC rendered α-SynPFF less inflammogenic. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in Parkinson's disease and other synucleinopathies.

Novel Tetracyclines Versus Alternative Antibiotics for Treating Acute Bacterial Infection: A Meta-Analysis of Randomized Controlled Trials.

This meta-analysis assessed the efficacy and safety of novel tetracyclines for treating acute bacterial infections. Data from PubMed, Web of Science, EBSCO, Cochrane databases, Ovid Medline, and Embase databases were accessed until 11 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of novel tetracyclines with that of other antibiotics for treating acute bacterial infections were included. Primary outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of eight RCTs were included, involving 2283 and 2197 patients who received novel tetracyclines and comparators, respectively. Overall, no significant difference was observed in the clinical response rate at test of cure between the experimental and control groups (for modified intent-to-treat [MITT] population, risk ratio [RR]: 1.02, 95% confidence interval [CI]: 0.99-1.05; for clinically evaluable [CE] population, RR: 1.02, 95% CI: 1.00-1.04; and for microbiological evaluable [ME] population, RR: 1.01, 95% CI: 0.99-1.04). No significant difference in the microbiological response at the end of treatment was observed between the experimental and control groups (for ME population, RR: 1.01, 95% CI: 0.99-1.03; for microbiological MITT population, RR: 1.01, 95% CI: 0.96-1.07). No difference was observed concerning the risk of treatment-emergent adverse events (TEAEs), serious adverse events, and discontinuation of treatment due to TEAEs and all-cause mortality between the two groups. In conclusion, clinical efficacy and safety profile for novel tetracyclines in the treatment of acute bacterial infections were found to be similar to those for other available antibiotics.

Omadacycline: A Modernized Tetracycline.

When tetracyclines were introduced in the 1940s, these antibiotics offered a broad spectrum of activity against multiple types of pathogens. However, their utility waned after the selection of tetracycline resistance in the pathogens against which they were effective. Omadacycline is a semisynthetic aminomethylcycline antibacterial derived from the tetracycline class of antibiotics that is unaffected by these resistance mechanisms. It has an appropriate spectrum of activity for community-acquired infections, including those caused by many resistant organisms. Omadacycline offers a well-tolerated treatment for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Omadacycline has minimal known drug-drug interactions, and should be administered in a fasting state, avoiding dairy and cation-containing products for at least 4 hours after dosing. It does not require dose adjustments for sex, age, or hepatic or renal impairment, and has a safety profile similar to that of other oral tetracyclines. Because omadacycline can be administered effectively orally, it can help reduce hospitalization costs associated with intravenous antibiotic administration. This special supplement to Clinical Infectious Diseases offers an in-depth examination of omadacycline development, including discussions of pharmacokinetic and pharmacodynamic trials, spectrum of activity and preclinical data, early clinical trials, phase III clinical trials, and an integrated safety summary.

Bioconversion of Tetracycline Antibiotics to Novel Glucoside Derivatives by Single-Vessel Multienzymatic Glycosylation.

The single-vessel multienzyme UDP-α-D-glucose recycling system was coupled with a forward glucosylation reaction to produce novel glucose moiety-conjugated derivatives of different tetracycline antibiotic analogs. Among five tetracycline analogs used for the reaction, four molecules (chlorotetracycline, doxytetracycline, meclotetracycline, and minotetracycline) were accepted by a glycosyltransferase enzyme, YjiC, from Bacillus licheniformis to produce glucoside derivatives. However, the enzyme was unable to conjugate sugar units to rolitetracycline. All glucosides of tetracycline derivatives were characterized by ultraviolet absorbance maxima, ultra-pressure liquid chromatography coupled with photodiode array, and high-resolution quadruple time-of-flight electrospray mass spectrometry analyses. These synthesized glucosides are novel tetracycline derivatives.