Se Joong Kim

BACKGROUND: Heated and humidified high-flow nasal cannula (HFNC) oxygen therapy has recently been introduced for hypoxic respiratory failure. However, it has not been well-evaluated for acute respiratory failure with hypercapnia. METHODS: This retrospective study included acute respiratory failure patients with hypercapnia in the medical intensive care unit (MICU) from April 2011 to February 2013, who required HFNC oxygen therapy for hypoxemia. Respiratory parameters were recorded and arterial blood gas analyses conducted before, and at 1 and 24 h after initiation of HFNC oxygen therapy. RESULTS: decreased by 4.2±5.5 and 3.7±10.8 mmHg in 1 and 24 h, respectively, resulting in significant improvement in hypercapnia (P=0.006 and 0.062, respectively). CONCLUSIONS: in acute respiratory failure with hypercapnia.

Therapeutic drug monitoring in tuberculosis remains controversial. We evaluated the relationship between antituberculosis drug levels in blood and clinical outcome. Serum concentrations of first-line antituberculosis drugs were measured in tuberculosis patients between March 2006 and April 2013. Venous blood was drawn 2 h after drug ingestion and was analyzed using high-performance liquid chromatography-tandem mass spectrometry. We retrospectively reviewed the data and determined the association of serum drug levels with clinical outcome. Among 413 patients, the prevalences of low serum concentrations of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA) were 59.9%, 27.8%, 12.8%, and 8.7%, respectively. The low INH group had a greater percentage of patients with a history of tuberculosis treatment (19.2% versus 11.0%; P = 0.026) and was more likely to present with drug-resistant strains (17.6% versus 8.8%; P = 0.049) than the normal INH group; however, low levels of INH, RMP, EMB, and PZA were not related to treatment outcome. Low INH level had a tendency to be associated with 2-month culture positivity, but it was not statistically significant (P = 0.072) in multivariate analysis. Seventeen (4.1%) patients experienced a recurrence. However, the recurrence rate was not statistically different between the low and normal INH groups. Low serum INH may play a role in recurrence and in acquired drug resistance. However, the serum level of INH was not directly related to either treatment response or recurrence rate. The role and usefulness of therapeutic drug monitoring should be evaluated in further prospective studies.

RATIONALE: Levofloxacin (LFX) and moxifloxacin (MXF) are the two most frequently recommended fluoroquinolones for treatment of patients with multidrug-resistant tuberculosis (MDR-TB). However, studies comparing the effectiveness of LFX and MXF among patients with MDR-TB are lacking. OBJECTIVES: To compare the effectiveness of LFX and MXF in terms of culture conversion after 3 months of treatment for MDR-TB. METHODS: In this prospective multicenter randomized open label trial, we randomly assigned 182 patients with MDR-TB (sensitive to LFX and MXF) to receive either LFX (750 mg/day; 90 patients) or MXF (400 mg/day; 92 patients) with a background drug regimen. The primary outcome was the proportion of patients who achieved sputum culture conversion at 3 months of treatment. Secondary outcomes were time to culture conversion and time to smear conversion, with data censored at 3 months, and the proportions of adverse drug reactions. MEASUREMENTS AND MAIN RESULTS: At 3 months of treatment, 68 (88.3%) of the 77 patients in the LFX group and 67 (90.5%) of the 74 in the MXF group showed conversion to negative sputum cultures (odds ratio for LFX compared with MXF, 0.78; 95% confidence interval, 0.27-2.20). Adverse drug reactions were reported in six patients (7.7%) in the LFX group and four (5.2%) in the MXF group (P = 0.75). CONCLUSIONS: The choice of LFX or MXF for treatment of patients with MDR-TB may not affect sputum culture conversion at 3 months of treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 01055145).