Sitafloxacin Hydrate

Sitafloxacin is one of the oral respiratory quinolones for the treatment of community‐acquired pneumonia. The pharmacokinetic (PK) changes of sitafloxacin in critical illness have been previously reported. However, sitafloxacin exposure and target attainment have never been confirmed in this population. To develop a population pharmacokinetic (PK) model of sitafloxacin, plasma and epithelial lining fluid (ELF) concentrations were obtained after sitafloxacin administration as a 200‐mg single dose under fasting condition in 12 subjects. A population pharmacokinetic analysis was performed using a nonlinear mixed‐effects modeling approach. The probability of target attainment (PTA) and cumulative fraction of response (CFR) against the MIC distribution of S. pneumoniae isolated from Thai patients was estimated by Monte Carlo simulations. The pharmacokinetics of sitafloxacin in plasma was best described by a one‐compartment model linking to the ELF compartment. The partition coefficient which relates drug exposure in ELF to drug exposure in plasma was estimated to be 0.77. Age was a significant covariate that impacted the relative bioavailability. Results from Monte Carlo simulations showed that the maximum approved dose of sitafloxacin 100 mg q 12 h provided > 90% PTA and CFR in both plasma and ELF. The current maximal dosing of sitafloxacin provided adequate exposure in plasma and ELF for the treatment of critically ill Thai patients with pneumonia.

Mycobacterium goodii is a rapidly growing non-tuberculosis mycobacterium, which is known to cause skin, bone and soft tissue infections, but there are a few reports of respiratory infections due to M. goodii. A 67-year-old man had suffered from productive cough, shortness of breath and weight loss for 6 months. He had a history of total gastrectomy for gastric ulcer perforation. Computed tomography (CT) showed dense consolidation in the right lower lobe and nodular lesions in both lungs. Transbronchial cryobiopsy was performed on a lesion in the right lower lobe and granulomatous lesions were observed pathologically. Because M. goodii was identified from two sputum samples using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), we made a diagnosis of M. goodii pulmonary disease. To confirm the diagnosis, whole genome sequencing analysis was performed, which showed average nucleotide identity of 99.18 %. The patient was responded well to the initial therapy with amikacin, imipenem/cilastatin, doxycycline, sulfamethoxazole/trimethoprim, and clarithromycin, followed by 18 months of ambulatory treatment with doxycycline, sulfamethoxazole/trimethoprim, clarithromycin, and sitafloxacin. The sputum culture remained negative and CT findings also significantly improved 6 months after the introduction of treatment. In this case, the development of M. goodii pulmonary disease is might be associated with the history of gastrectomy. For identifying the pathogen, MALDI-TOF MS and whole genome sequencing analysis were useful and the intensive initial treatment in accordance with the drug susceptibility testing was successful.