Tigecycline Pharmacokinetic and Pharmacodynamic Profile in Patients with Chronic Obstructive Pulmonary Disease Exacerbation.

BACKGROUND: We aimed to evaluate the pharmacokinetic profile of tigecycline in plasma and its penetration to sputum in moderately ill patients with an infectious acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: Eleven patients hospitalized with acute respiratory failure due to an acute COPD exacerbation with clinical evidence of an infectious cause received tigecycline 50 mg twice daily after an initial loading dose of 100 mg. Blood and sputum samples were collected at steady state after dose seven. RESULTS: In plasma, mean Cmax pl was 975.95 ± 490.36 ng/mL and mean Cmin pl was 214.48 ±140.62 ng/mL. In sputum, mean Cmax sp was 641.91 ± 253.07 ng/mL and mean Cmin sp was 308.06 ± 61.7 ng/mL. In plasma, mean AUC 0-12 pl was 3765.89 ± 1862.23 ng*h/mL, while in sputum mean AUC 0-12 sp was 4023.27 ± 793.37 ng*h/mL. The mean penetration ratio for the 10/11 patients was 1.65 ± 1.35. The mean Free AUC0-24 pl/MIC ratio for Streptococcus pneumoniae and Haemophilus influenzae was 25.10 ± 12.42 and 6.02 ± 2.97, respectively. CONCLUSIONS: Our findings support the clinical effectiveness of tigecycline against commonly causative bacteria in COPD exacerbations and highlight its sufficient lung penetration in pulmonary infections of moderate severity.

Pearls for the diagnosis and possible pathophysiological mechanisms of valproic acid-induced lupus erythematosus: A literature review.

Background: Drug-induced lupus erythematosus (DILE) accounts for 10-15% of systemic lupus erythematosus (SLE) cases, with more than 100 pharmaceutical agents implicated in its development. Depending on the offending drug, clinical and serological manifestations present great variability and, thus, DILE may be overlooked in clinical practice. Valproic acid (VPA) - induced lupus erythematosus has not been analytically reported in the literature, rendering the recognition of such cases even more difficult.Objective: The aim of this study was to analyze VPA - induced lupus features and to discuss possible pathophysiological mechanisms.Materials and Methods: This literature review was conducted in PubMed and Embase databases in June 2021, in search of DILE cases induced by VPA. We found 164 manuscripts, out of which 140 articles regarding other adverse effects or drugs were discarded. Finally, 15 cases fulfilled the eligibility criteria to be included in this review.Results: Although SLE is more common in females, VPA-induced lupus presented a male predilection. Patients developed DILE within the first three months of treatment with VPA at a percentage of 50%, whereas four patients from one to five years after VPA initiation. DILE frequently presented with mild symptoms. In most patients, serositis manifested with polyarthritis, pleural effusion or pericarditis. Notably, one patient presented with Rowell's syndrome, a rare subtype of lupus erythematosus with erythema multiforme and speckled pattern of antinuclear antibodies (ANAs). Central nervous system, renal and skin involvement was scarcely observed. Cytopenia was noted in 7 patients. Immunological findings included positive ANAs in the vast majority of the patients (86.7%), positive anti-histone antibodies in five, positive anti-dsDNA antibodies in three and hypocomplementemia in two patients. Despite the prompt resolution of clinical symptoms after VPA discontinuation, serological abnormalities persisted up to 18 months. Apart from the discontinuation of VPA administration for the resolution of DILE, treatment included corticosteroids in 8 cases.Conclusion: Valproic acid has been implicated in several cases of DILE. Clinicians should be aware of this entity and recognize it promptly to ensure a favorable outcome. Possible pathophysiologic associations may be extrapolated, but a clearer understanding of this syndrome is to be gained by further studies.

Pharmacokinetics of Linezolid and Ertapenem in experimental parapneumonic pleural effusion.

OBJECTIVE: To determine the extent of linezolid and ertapenem penetration into the empyemic fluid using a rabbit model of empyema. METHODS: An empyema was created via the intrapleural injection of Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracocentesis, 24 hours post inoculation, linezolid (10 mg/kg) and ertapenem (60 mg/kg) were administered intravenously into 10 and 8 infected empyemic rabbits, respectively. Antibiotic levels were determined in samples of pleural fluid and blood serum, collected serially at 1, 2, 4, 6 and 8 hours, after administration each of the two antibiotics. RESULTS: Linezolid as well as ertapenem penetrate well into the empyemic pleural fluid, exhibiting a slower onset and decline compared to the corresponding blood serum levels. Equilibration between blood serum and pleural fluid compartments seems to occur at 1.5 hours for both linezolid and ertapenem, with peak pleural fluid levels (Cmaxpf of 2.02 +/- 0.73 <>g/ml and Cmaxpf of 3.74 +/- 1.39 <>g/ml, correspondingly) occurring 2 hours post antibiotics administration and decreasing very slowly thereafter. The serum concentrations for both antibiotics were significantly lower from the corresponding pleural fluid ones during the 8 hours collecting data, with the exception of samples collected at the 1st hour (Cmaxserum of 2.1 +/- 1.2 <>g/ml for linezolid and Cmaxserum of 6.26 +/- 2.98 <>g/ml for ertapenem). CONCLUSION: Pleural fluid levels of both antibiotics are inhibitory for common specified pathogens causing empyema.