Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial.
Aged; Humans; Male; Adult; Female; Middle Aged; Double-Blind Method; Administration Intravenous; Microbial Sensitivity Tests; pneumonia; Randomized Controlled Trials as Topic; antibiotic; lefamulin; moxifloxacin; pleuromutilin; Anti-Bacterial Agents/administration & dosage/adverse effects/therapeutic use; Diterpenes/administration & dosage/adverse effects/therapeutic use; Linezolid/adverse effects/therapeutic use; Moxifloxacin/administration & dosage/adverse effects/therapeutic use; Pneumonia Bacterial/drug therapy/metabolism; Polycyclic Compounds/administration & dosage/adverse effects/therapeutic use; Thioglycolates/administration & dosage/adverse effects/therapeutic use
BACKGROUND: Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP. METHODS: In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5-10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%). RESULTS: There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference -2.9%, 95% confidence interval [CI] g -8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference -2.6%, 95% CI -8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference -2.5%, 95% CI -8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin. CONCLUSIONS: Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT02559310.
File TM; Goldberg L; Das A; Sweeney C; Saviski J; Gelone SP; Seltzer E; Paukner S; Wicha WW; Talbot GH; Gasink LB
Clinical Infectious Diseases
2019
2019-11-13
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1093/cid/ciz090" target="_blank" rel="noreferrer noopener">10.1093/cid/ciz090</a>
Omadacycline: A novel tetracycline derivative with oral and intravenous formulations.
antimicrobial resistance; pneumonia; antibiotic; ABSSSI; omadacycline
Omadacycline, an aminomethylcycline, is a novel member of the tetracycline class of antibiotics. It has received approval by the U.S. Food and Drug Administration (FDA) for treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSIs) and is available in both oral and intravenous formulations. It is also being evaluated in clinical trials for the treatment of cystitis and pyelonephritis. The omadacycline molecule was designed to overcome tetracycline resistance and has broad spectrum activity that includes gram-positive bacteria, gram-negative bacteria, anaerobes, atypicals, and other drug-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), as well as Yersinia pestis and Bacillus anthracis, organisms of biodefense interest. Omadacycline has minimal drug-drug pharmacokinetic interactions and a favorable safety profile, with the most common adverse events being gastrointestinal symptoms.
Watkins Richard R; Deresinski Stan
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2019
2019-03
<a href="http://doi.org/10.1093/cid/ciz242" target="_blank" rel="noreferrer noopener">10.1093/cid/ciz242</a>
Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects.
antibiotic; discoloration; inflammatory disease; rheumatoid arthritis; tetracycline; wavelength
Minocycline is a tetracycline derivative antibiotic commonly prescribed for acne, rosacea, and other inflammatory skin disorders. Minocycline turns black when oxidized, leading to discoloration of the skin, nails, bulbar conjunctiva, oral mucosa, teeth, bones, and thyroid gland. Hyperpigmentation has been reported after long-term minocycline therapy with at least 100 mg/day. Three types of minocycline-induced cutaneous hyperpigmentation can result. Type I is the most common, and is associated with blue-black discoloration in areas of previous inflammation and scarring. Type II most commonly affects the legs and is characterized by blue-gray pigmentation of previously normal skin. Type III is the least common and is characterized by diffuse muddy-brown discoloration predominantly on sun exposed skin. Minocycline-induced hyperpigmentation may be cosmetically disfiguring and prompt identification is essential. Without treatment, symptoms may take several months, to years to resolve, after discontinuation of the drug. However, the pigmentation may never completely disappear. In fact, there have been few reports of complete resolution associated with any therapeutic intervention. We report a case of a patient on long-term minocycline therapy utilized as an anti-inflammatory agent to control symptoms of rheumatoid arthritis, which led to minocycline-induced hyperpigmentation of the face. To remove the blue-gray cutaneous deposits, 3 Q-switched lasers (Neodymium: yttrium aluminum garnet (Nd:YAG) 1064 nm, Alexandrite 755 nm, and Ruby 694 nm) were used in test areas. The Alexandrite 755 nm laser proved to provide effective clearing of the minocycline hyperpigmentation requiring just 2 treatments, with minimal treatment discomfort and down time.
Nisar Mahrukh S; Iyer Karthik; Brodell Robert T; Lloyd Jenifer R; Shin Thuzar M; Ahmad Asad
Clinical, cosmetic and investigational dermatology
2013
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.2147/CCID.S42166" target="_blank" rel="noreferrer noopener">10.2147/CCID.S42166</a>