Objectives:To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. Design:Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose.Setting:Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans.Participants:126 healthy adults 21–45 years of age.Interventions:10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13.Outcome Measures:Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation.Results:No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ.Conclusions:These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics.

NCT00520234.

We conducted a retrospective study to further elucidate the clinical presentations and prognosis of disease due to Mycobacterium kansasii in patients infected with human immunodeficiency virus (HIV). Forty-nine HIV-infected patients first had M. kansasii isolated at a mean CD4 cell count of 62/mm3 and at a mean interval of 17 months after the diagnosis of AIDS. Seventeen of the 49 patients had disseminated disease caused by M. kansasii. Twenty-nine patients had a positive acid-fast smear of sputum, and 35 were known to be cigarette smokers. At the time of initial isolation of M. kansasii, 13 patients had other concurrent pulmonary isolates and 15 had another mycobacterial species concurrently isolated (the Mycobacterium avium complex in 13 instances). Patients who received antimycobacterial treatment survived longer than those who did not. Only one of the 49 patients was definitively determined to be colonized with M. kansasii without disease; therefore, it appears that pulmonary isolates of M. kansasii in HIV-infected patients are almost always associated with disease. The increase in rates of M. kansasii disease among HIV-infected patients has paralleled the rise of AIDS in Louisiana. So far, this state has recorded more coinfections with M. kansasii and HIV than any other.

In April 2008, the Infectious Diseases Society of America (IDSA) entered into an agreement with Connecticut Attorney General Richard Blumenthal to voluntarily undertake a special review of its 2006 Lyme disease guidelines. This agreement ended the Attorney General's investigation into the process by which the guidelines were developed. The IDSA agreed to convene an independent panel to conduct a one-time review of the guidelines. The Review Panel members, vetted by an ombudsman for potential conflicts of interest, reviewed the entirety of the 2006 guidelines, with particular attention to the recommendations devoted to post-Lyme disease syndromes. After multiple meetings, a public hearing, and extensive review of research and other information, the Review Panel concluded that the recommendations contained in the 2006 guidelines were medically and scientifically justified on the basis of all of the available evidence and that no changes to the guidelines were necessary.

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