Treatment of rosacea during pregnancy.

BACKGROUND: Exacerbation of rosacea may occur during pregnancy and there are multiple associated cases of rosacea fulminans (RF). Treatment during pregnancy poses a significant challenge as many rosacea treatments are contraindicated or have limited evidence regarding potential adverse fetal effects. OBJECTIVE: Review the pregnancy categories of various treatments and develop algorithms for treating pregnant patients with rosacea and RF. METHODS: Rosacea treatments showing efficacy in randomized controlled trials were searched through DailyMed to review pregnancy labelling. Searching the PubMed/MEDLINE database for English articles using keywords "rosacea fulminans AND pregnancy" without publishing-time restrictions yielded 8 articles. We summarized treatments used in cases of RF during pregnancy. RESULTS: Topical ivermectin was more effective than metronidazole, but has a more concerning pregnancy category. Three pregnant women with RF were treated successfully with topical metronidazole in combination with other therapies. Azithromycin is the only oral rosacea therapy that is considered safe for pregnant patients and it has been used to treat RF. CONCLUSIONS: This review highlights the challenging aspects of treating pregnant patients with rosacea, as there is limited pregnancy-related treatment efficacy and safety data. The pregnancy categories of therapeutic options are summarized. Further studies are needed to learn which therapies are effective and safe for use during pregnancy.

Eravacycline for the treatment of complicated intra-abdominal infections.

Introduction: Complicated intra-abdominal infections (cIAIs) are among the most frequent infections, contributing to significant morbidity and healthcare costs. Several medical needs remain unmet, related to the pharmacokinetic capacities of the available drugs and their limited spectrum of activity for targeting multidrug-resistant Gram-negative and Gram-positive bacteria. Eravacycline, a new synthetic fluorocycline, could have useful properties in cIAIs.Areas covered: The antimicrobial activity of eravacycline against the microorganisms most frequently cultured in cIAIs has been confirmed in worldwide panels of clinical isolates, including enterococci, ESBL-producing Enterobacteriaceae, Acinetobacter baumannii and anaerobes. Pharmacokinetic data demonstrate interesting characteristics with good tissue concentrations including biliary tract and digestive tissues. At a conventional dosage of 1 mg/kg q12h, no adjustment is required on the basis of race or gender, or in elderly (≥ 65 years old) patients, patients with renal impairment or patients undergoing hemodialysis. Phase 2 and 3 trials assessing the clinical efficacy and safety of eravacycline demonstrated non-inferiority versus carbapenems and a good safety profile.Expert opinion: Eravacycline may be particularly suitable for the treatment of cIAIs. Results from clinical trials and real-world data are now expected in specific subgroups of patients to confirm the safety profile and efficacy observed in registration trials.

Prevalence of Medication-Dietary Supplement Combined Use and Associated Factors.

INTRODUCTION: The use of medication has increased in recent years in the US while the use of dietary supplements has remained stable but high. Interactions between these two kinds of products may have important consequences, especially in the case of widely used medications such as antihypertensives and antibiotics. The aim of this paper is to estimate the prevalence of potentially serious drug-dietary supplement interactions among tetracyclines, thiazides, and angiotensin II receptor blocker users by means of the NHANES 2013-2014 dataset. METHODS: Data from 2013-2014 NHANES were obtained. Potential interactions analysed were tetracyclines with calcium, magnesium, and zinc, thiazides with vitamin D, and angiotensin II receptors blockers with potassium. Prevalence was calculated for each potential interaction. Logistic regression was used to assess associated factors. RESULTS: 864 prescriptions issued to 820 patients were analysed. Overall prevalence of potential interaction was 49%. Older age and higher educational level were strongly associated with being at risk of a potential interaction. Factors such as age, race, civil status, citizenship, country of birth, BMI, and physical activity did not show notable associations. CONCLUSIONS: Healthcare professionals should be aware of other medical products when they prescribe or dispense a medication or a dietary supplement, especially to the older population and people with a higher educational level.

Omadacycline for Community-Acquired Bacterial Pneumonia.

BACKGROUND: Omadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia. METHODS: In a double-blind trial, we randomly assigned (in a 1:1 ratio) adults with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) to receive omadacycline (100 mg intravenously every 12 hours for two doses, then 100 mg intravenously every 24 hours), or moxifloxacin (400 mg intravenously every 24 hours). A transition to oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours), respectively, was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was early clinical response, defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours, without receipt of rescue antibacterial therapy. A secondary end point was investigator-assessed clinical response at a post-treatment evaluation 5 to 10 days after the last dose, with clinical response defined as resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary. A noninferiority margin of 10 percentage points was used. RESULTS: The intention-to-treat population included 386 patients in the omadacycline group and 388 patients in the moxifloxacin group. Omadacycline was noninferior to moxifloxacin for early clinical response (81.1% and 82.7%, respectively; difference, -1.6 percentage points; 95% confidence interval [CI], -7.1 to 3.8), and the rates of investigator-assessed clinical response at the post-treatment evaluation were 87.6% and 85.1%, respectively (difference, 2.5 percentage points; 95% CI, -2.4 to 7.4). Adverse events that emerged after treatment initiation were reported in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group; the most frequent events were gastrointestinal (10.2% and 18.0%, respectively), and the largest difference was for diarrhea (1.0% and 8.0%). Twelve deaths (8 in the omadacycline group and 4 in the moxifloxacin group) occurred during the trial. CONCLUSIONS: Omadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438 .).

In Vitro and In Vivo Activity of Omadacycline against Two Biothreat Pathogens, Bacillus anthracis and Yersinia pestis.

The in vitro activity and in vivo efficacy of omadacycline (OMC) were evaluated against the causative pathogens of anthrax and plague, Bacillus anthracis and Yersinia pestis, respectively. MICs of OMC were determined by broth microdilution according to CLSI guidelines for 30 isolates each of Y. pestis and B. anthracis The in vivo efficacy of omadacycline was studied at a range of dosages in both a postexposure prophylaxis (PEP) murine model of anthrax and plague as well as in a delayed treatment model of inhalational anthrax. Omadacycline was active in vitro against Y. pestis (MIC90 of 1 µg/ml) and B. anthracis (MIC90 of 0.06 µg/ml). Omadacycline was less active in vitro than ciprofloxacin (CIP) against Y. pestis (CIP MIC90 of 0.03 µg/ml) but was more potent in vitro against B. anthracis (CIP MIC90 of 0.12 µg/ml). In the mouse model of infection, the survival curves for all treatment cohorts differed significantly from the vehicle control (P = 0.004). The median survival for the vehicle-treated controls was 6 days postchallenge, while all antibiotic-treated mice survived the entire study. Omadacycline treatment with 5, 10, or 20 mg/kg of body weight twice daily for 14 days had significant efficacy over the vehicle control in the treatment of aerosolized B. anthracis Additionally, for postexposure prophylaxis treatment of mice infected with Y. pestis, the survival curves for omadacycline (40 mg/kg twice daily), ciprofloxacin, and doxycycline cohorts differed significantly from the vehicle control (P < 0.0001). Omadacycline is potent and demonstrates efficacy against both B. anthracis and Y. pestis The well-characterized oral and intravenous pharmacokinetics, safety, and tolerability warrant further assessment of the potential utility of omadacycline in combating these serious biothreat organisms.

Eravacycline for the treatment of intra-abdominal infections.

INTRODUCTION: There has been a dramatic increase in the incidence of multidrug-resistant pathogens over the past few years, which highlights the need for new anti-infective therapeutics. Eravacycline is a novel, broad-spectrum synthetic tetracycline indicated for the treatment of severe infections caused by Gram-positive and Gram-negative bacteria. AREAS COVERED: In this review, the authors report eravacycline's pharmacokinetic characteristics and its microbiological spectrum of activity. Furthermore, the authors also highlight the safety and efficacy data from the recent studies on urinary and intra-abdominal infections. EXPERT OPINION: The profile of eravacycline offers several advantages. Indeed, eravacycline has a broad-spectrum activity toward pathogens involved in complicated urinary tract (cUTIs) and intra-abdominal infections (cIAIs), including extended-spectrum beta-lactamase and carbapenem-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The availability of an oral formulation supports eravacycline's possible use in sequential therapy. High urinary concentrations favor its use in cUTIs and may reduce the overuse of other antimicrobials that may select resistance, such as carbapenems. Eravacycline efficacy and tolerability have been investigated in a Phase II clinical trial in cIAIs comparing two dosages of eravacycline with ertapenem, showing comparable efficacy among the three arms and a low rate of adverse effects. The results of new Phase III studies are awaited to confirm eravacycline's future applications in severe nosocomial infections.

Slow-acting, disease-modifying osteoarthritis agents.

There is evidence to suggest that tetracyclines have benefit beyond their antimicrobial activity. The ability to inhibit metalloproteinase activity may provide a disease-modifying effect in OA, and available data suggest that further investigation is warranted. Controlled, double-blind, prospective clinical studies have not been completed. The canine cruciate ligament transection model studies are frequently cited as the most convincing in vivo evidence of a benefit of oral tetracycline therapy for the treatment of OA. Until more evidence becomes available, the use of tetracyclines as therapeutic agents for OA should be considered investigational.

Tetracyclines in ophthalmology.

Tetracycline and its congeners demonstrate antimicrobial activity against bacteria, Chlamydiae and Toxoplasma gondii. Ophthalmologists can use these drugs to treat bacterial and chlamydial infections, and also for ocular rosacea and similar disorders. Side effects associated with systemic tetracycline use are most commonly related to the gastrointestinal tract and to signs of yeast superinfection. Minocycline use may be limited by its vestibular toxicity. Temporary growth retardation and staining of erupting teeth may occur with oral use of tetracycline in children under 8 years; these drugs should not be given in pregnancy or to young children. Topical tetracycline application yields good tear and aqueous humor concentrations.

Tetracyclines, chloramphenicol, erythromycin, and clindamycin.

The tetracyclines are active in vitro against many urinary tract pathogens such as Chlamydia, Mycoplasma pneumoniae, Brucella, rickettsiae, and Nocardia. Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and infections due to Salmonella typhi. Erythromycin is active in vitro against M. pneumoniae, Legionella spp., Streptococcus pneumoniae, and group A beta-hemolytic streptococci; it may also be used as prophylactic therapy for subacute bacterial endocarditis and for recurrence of acute rheumatic fever in patients who are allergic to penicillin. Clindamycin should be used primarily for the treatment of anaerobic infections. The tetracyclines may cause gastrointestinal upset; phototoxic dermatitis; hepatitis, especially in pregnant women; discoloration of the teeth and bone dysplasia in the human fetus and in children; and superinfections, especially oral and anogenital candidiasis. The tetracyclines should be used with caution in patients with renal insufficiency. The most important toxic effect of chloramphenicol is bone marrow suppression, which is dose related or idiosyncratic. The incidence of undesirable side effects associated with the use of erythromycin is low; gastrointestinal irritation is the most common, and cholestatic hepatitis may occur with the use of erythromycin estolate. Pseudomembranous colitis is the most important toxic effect associated with the use of clindamycin.