No abstract

We evaluated treatment with linezolid, dosed at 800 mg once daily for 1 to 4 months as guided by sputum culture status and tolerance and then at 1,200 mg thrice weekly until >1 year after culture conversion, in addition to individually optimized regimens among 10 consecutive patients with extensively drug-resistant tuberculosis or fluoroquinolone-resistant multidrug-resistant tuberculosis. All achieved stable cure, with anemia corrected and neuropathy stabilized, ameliorated, or avoided after switching to intermittent dosing. Serum linezolid profiles appeared better optimized.

Cytochrome P450 2B6 (CYP2B6) is the main metabolizing pathway for efavirenz (EFV), the prescription of which is associated with neurologic side effects. The authors conducted a study on the prevalence of CYP2B6 polymorphism, profile of side effects, and pharmacokinetics of EFV in a group of human immunodeficiency virus (HIV)-infected southern Chinese. Patients with HIV were recruited at the Shenzhen City Third People's Hospital, China. The prevalence of CYP2B6 G516T and plasma EFV concentration were determined. Pharmacokinetics was assessed using blood samples of selected patients at time 0, 1, 2, 4, 8, 12, and 24 hours after the last dose of EFV. Between October 2007 and June 2008, 79 Chinese patients with HIV were recruited. Sequencing of CYP2B6 at position 516 gave 42 GG, 34 GT, and 3 TT genotypes, with corresponding mean spot plasma EFV level of 3.4, 4.1, and 8.1 mg/L, respectively. The allelic frequency of 516 G>T was 0.25. Univariate analysis showed that plasma EFV level correlated with genotype (P = 0.02). Eighteen patients completed the pharmacokinetic study: TT genotype gave the longest half-life (t 1/2), highest plasma EFV concentration, and largest area under the curve. The volume of distribution per surface area (Vd ss), total clearance (Cltot), and elimination rate constant (ke) were the lowest. There was no association between the occurrence of side effects and the EFV concentration (chi2 test, P > 0.05). The EFV pharmacokinetics of TT genotype differed significantly from GG and GT genotypes. Accumulation of EFV may potentially occur over time, causing toxicity in TT and GT genotypes.

No abstract

Serum concentration of seven antifungal agents, amphotericin B, 5-flucytosine, ketoconazole, fluconazole, itraconazole, miconazole and econazole were assayed using a single step sample preparation and an isocratic High Performance Liquid Chromatography (HPLC) procedure based on three mobile phases of similar components. Our method was simple, flexible and rapid, the assays being completed within half an hour. The method showed high reproducibility, good sensitivity with detection limits of 0.078 to 0.625 mg/L except for miconazole and econazole, and high recovery rates of 86-l05%. Out of 24 therapeutic agents tested only aztreonam and trimethoprim were found to interfere with the assay of 5-flucytosine and fluconazole respectively, using this protocol. HPLC assay should be useful in the clinical laboratory for monitoring patients on antifungal therapy.

The biliary excretion of cefoperazone and ceftazidime was studied by endoscopic cannulation of the common bile duct, in patients with complete biliary obstruction and in an unobstructed control group. Patients were given each drug prophylactically for 24 h before endoscopy and as a single dose at the time of cannulation. In unobstructed patients biliary excretion of ceftazidime was passive. At the time of cannulation bile contained 10% of the peak serum concentration, rising to 20% 90 min later. Cefoperazone excretion was active. At cannulation biliary concentrations were 200% of the serum peak, 900% at 60 min and 700% at 90 min. In obstructed patients, bile sampled immediately at decompression contained neither antibiotic. Passive excretion of both drugs occurred rapidly after relief of obstruction and biliary concentrations were 20% of maximum serum levels at 60 min. Twenty-four hours later passive excretion had further improved, but the active excretion mechanism of cefoperazone had still not recovered. We conclude that obstruction impairs active as well as passive biliary excretion of antibiotics, that drainage is essential for the control of sepsis in obstructed cholangitis, and that both cefoperazone and ceftazidime achieve similar and therapeutic concentrations in bile during the 24 h after decompression.

Fibreoptic bronchoscopy was performed on 190 patients with chest radiographic lesions and negative sputum smears for acid-fast bacilli. Aside from obtaining transbronchial biopsies for histological examination, bronchial aspirate specimens were also tested for Mycobacterium tuberculosis complex DNA by a conventional polymerase chain reaction (PCR) technique. Of 177 transbronchial biopsies performed, a diagnosis was found in 64 cases [43 cases of tuberculosis (TB), 17 cases of lung carcinoma and four cases of other infective/inflammatory diseases] giving a diagnostic yield of 36.2%. PCR was positive in 105 of 108 finally diagnosed cases of TB and 22 of 82 non-TB cases. The sensitivity, specificity, positive predictive value and negative predictive value of PCR when applied to bronchial aspirate specimens for diagnosing smear-negative pulmonary TB were 97.2%, 73.2%, 82.7% and 95.2% respectively. Therefore, detection of M. tuberculosis complex DNA in bronchial aspirates by PCR might have an adjunctive place to transbronchial biopsies in the rapid diagnosis of smear-negative pulmonary tuberculosis.

Tuberculostearic acid [(R)-10-methyloctadecanoic acid (TBSA)] is a structural component of mycobacteria, and its detection in appropriate clinical specimens has potential application as a rapid screening method for the presence of Mycobacterium tuberculosis and other mycobacteria. We used the highly sensitive technique of gas chromatography-mass spectrometry (GC-MS) combined with selected ion monitoring (SIM) of m/e 312 and m/e 167 for detecting TBSA in 405 clinical sputum specimens collected in Hong Kong, where tuberculosis is still common. TBSA was detected in 39 M. tuberculosis smear-positive, culture-positive specimens; 63 of 66 smear-negative, culture-positive specimens; and 1 of 300 smear-negative, culture-negative specimens. Thus, for screening of sputa from individuals with suspected pulmonary tuberculosis, the detection of TBSA by GC-MS/SIM is highly specific and more sensitive than conventional microscopy and more rapid but slightly less sensitive than conventional culture methods.