High Intrapulmonary Rifampicin and Isoniazid Concentrations Are Associated With Rapid Sputum Bacillary Clearance in Patients With Pulmonary Tuberculosis.

BACKGROUND: Intrapulmonary pharmacokinetics may better explain response to tuberculosis (TB) treatment than plasma pharmacokinetics. We explored these relationships by modeling bacillary clearance in sputum in adult patients on first-line treatment in Malawi. METHODS: Bacillary elimination rates (BER) were estimated using linear mixed-effects modelling of serial time-to-positivity in mycobacterial growth indicator tubes for sputum collected during the intensive phase of treatment (weeks 0-8) for microbiologically confirmed TB. Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks. Pharmacokinetic-pharmacodynamic relationships were investigated using individual-level measures of drug exposure (area-under-the-concentration-time-curve [AUC] and Cmax) for rifampicin, isoniazid, pyrazinamide, and ethambutol, in plasma, epithelial lining fluid, and alveolar cells as covariates in the bacillary elimination models. RESULTS: Among 157 participants (58% human immunodeficiency virus [HIV] coinfected), drug exposure in plasma or alveolar cells was not associated with sputum bacillary clearance. Higher peak concentrations (Cmax) or exposure (AUC) to rifampicin or isoniazid in epithelial lining fluid was associated with more rapid bacillary elimination and shorter time to sputum negativity. More extensive disease on baseline chest radiograph was associated with slower bacillary elimination. Clinical outcome was captured in 133 participants, with 15 (11%) unfavorable outcomes recorded (recurrent TB, failed treatment, or death). No relationship between BER and late clinical outcome was identified. CONCLUSIONS: Greater intrapulmonary drug exposure to rifampicin or isoniazid in the epithelial lining fluid was associated with more rapid bacillary clearance. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration and better treatment outcomes.

Extensor mechanism tendinopathy in patients with lateral patellar maltracking.

OBJECTIVE: Patellar maltracking is an important subset of patellofemoral pain syndrome. We hypothesize that maltracking patients have an increased incidence of extensor mechanism dysfunction due to repetitive attempts at stabilization of the patella. Our purpose is to delineate imaging features to identify maltracking patients at risk for extensor mechanism tendinopathy. MATERIALS AND METHODS: Retrospective review of knee MRIs performed for anterior knee pain over a year was conducted to identify 218 studies with imaging findings of maltracking. The cases were evaluated for the presence and degree of patellar and quadriceps tendinopathy, tibial tuberosity-trochlear groove distance (TT-TG) and the distribution and grade of patellofemoral chondrosis. Cases were compared to 100 healthy, age-matched control knee MRIs. RESULTS: The mean age of maltracking patients with either patellar or quadriceps tendinosis was 41.2 years versus 48.2 years in the control population (p = 0.037). The TT-TG was significantly higher in maltracking patients with either patellar or quadriceps tendinosis at 16.49 mm versus 14.99 mm (p = 0.006). Maltrackers with isolated lateral patellofemoral chondrosis had a higher mean TT-TG at 17.4 mm versus 15.4 mm (p = 0.007). Extensor mechanism tendinosis was increased in the maltracking population compared to the controls at 57.8% versus 27.3% (p = 0.004). CONCLUSION: Extensor mechanism tendinosis is more common in the maltracking population and occurs at a younger age. TT-TG distance is significantly increased in patients with extensor mechanism dysfunction and in patients with isolated lateral patellofemoral chondrosis. TT-TG measurement can be used independently to identifying maltrackers who may be at risk for future complications.