Potent Rifamycin-Sparing Regimen Cures Guinea Pig Tuberculosis as Rapidly as the Standard Regimen

Strategies involving new drug combinations, as well as new uses of existing drugs, are urgently needed to reduce the time required to cure patients with drug-sensitive or multidrug-resistant (MDR) tuberculosis (TB). We compared the sterilizing activity of the standard first-line antitubercular regimen, rifampin-isoniazid-pyrazinamide (RHZ), with that of the novel regimen PA-824–moxifloxacin–pyrazinamide (PaMZ), which is currently being studied in clinical trials ({"type":"clinical-trial","attrs":{"text":"NCT01498419","term_id":"NCT01498419"}}NCT01498419), in the guinea pig model of chronic TB infection, in which animals develop necrotic granulomas histologically resembling their human counterparts. Guinea pigs were aerosol infected with ∼2 log₁₀ bacilli of wild-type Mycobacterium tuberculosis H37Rv, and antibiotic treatment was initiated 6 weeks after infection. Separate groups of animals received RHZ, PaMZ, or single or two-drug components of the latter regimen administered at human-equivalent doses 5 days/week for a total of 8 weeks. Relapse rates were assessed 3 months after discontinuation of treatment to determine the sterilizing activity of each combination regimen. PaMZ given at human-equivalent doses was safe and well tolerated for the entire treatment period and rendered guinea pig lungs culture negative more rapidly than RHZ did. After 1 month of treatment, 80% and 50% of animals in the RHZ and PaMZ groups, respectively, had lung culture-positive relapse. Both combination regimens prevented microbiological relapse when administered for a total of 2 months. Our data support the use of PaMZ as a novel isoniazid- and rifamycin-sparing regimen suitable for treatment of both drug-sensitive TB and MDR-TB.     

Long term G‐CSF‐induced remission of ulcerative colitis‐like inflammatory bowel disease in a patient with glycogen storage disease Ib and evaluation of associated neutrophil function

We present a 23‐year‐old female with Glycogen storage disease Ib (GSD Ib) who was diagnosed with ulcerative colitis‐like inflammatory bowel disease (IBD) at 7 years of age. G‐CSF therapy reversed the IBD, was required to maintain IBD remission and was well tolerated. Neutrophil functions at time of diagnosis showed impaired chemotaxis but normal superoxide anion production and bactericidal activity. Ulcerative colitis‐like IBD may also be seen in GSD Ib and is responsive to G‐CSF therapy. Neutrophil dysfunction is variable among patients with GSD Ib. Pediatr Blood Cancer. 2010;55:1410–1413. © 2010 Wiley‐Liss, Inc.