PMID- 25345982
OWN - NLM
STAT- MEDLINE
DCOM- 20150701
LR  - 20201209
IS  - 1708-8305 (Electronic)
IS  - 1195-1982 (Linking)
VI  - 21
IP  - 6
DP  - 2014 Nov-Dec
TI  - Targeting of rifamycin SV to the colon for treatment of travelers' diarrhea: a 
      randomized, double-blind, placebo-controlled phase 3 study.
PG  - 369-76
LID - 10.1111/jtm.12168 [doi]
AB  - BACKGROUND: Rifamycin SV is under development for treatment of travelers' 
      diarrhea (TD) in a new oral formulation, Rifamycin SV MMX (RIF-MMX; Santarus 
      Inc., San Diego, CA, USA), which targets its delivery to the colon, making it a 
      unique rifamycin drug. METHODS: This was a randomized, double-blind, phase 3 
      study of adult travelers to Mexico or Guatemala experiencing acute diarrhea. A 
      total of 264 patients received RIF-MMX (2 x 200 mg twice daily for 3 days, 
      n = 199) or placebo (n = 65) in a 3 : 1 ratio. The primary endpoint was the 
      length of time between the administration of first dose of study drug and passage 
      of the last unformed stool (TLUS; after which clinical cure was declared). Other 
      endpoints included eradication of pathogens from the stools, pathogen minimum 
      inhibitory concentration (MIC), and adverse events (AEs). RESULTS: TLUS was 
      significantly shorter in the RIF-MMX group (median: 46.0 hours) compared with 
      placebo (median: 68.0 hours; p = 0.0008) and a larger percentage of RIF-MMX 
      treated patients (81.4%) achieved clinical cure compared with placebo patients 
      (56.9%). TLUS was significantly shorter in the subgroups of patients with 
      enteroaggregative, enterotoxigenic, or diffusely adherent Escherichia coli 
      infections (p = 0.0035) with nonsignificant activity against invasive bacteria 
      (p = 0.3804). Overall pathogen eradication rates were numerically higher in the 
      RIF-MMX group (67.0%) compared with placebo (54.8%) but the difference did not 
      reach significance (p = 0.0836). In vitro resistance to rifamycin SV was observed 
      in some bacteria remaining after treatment of patients with RIF-MMX but was not 
      associated with lower efficacy in them. AEs appeared to be more frequent with 
      placebo (38.5%) than with RIF-MMX (29.6%). CONCLUSIONS: RIF-MMX shortened the 
      duration of TD in patients with a broad range of pathogens and was well 
      tolerated. The unique pharmacokinetic properties of the drug offer evidence that 
      TD pathogens work at the level of the colon.
CI  - (c) 2014 International Society of Travel Medicine.
FAU - DuPont, Herbert L
AU  - DuPont HL
AD  - Center for Infectious Diseases, University of Texas School of Public Health, 
      Houston, TX, USA.
FAU - Petersen, AnnKatrin
AU  - Petersen A
FAU - Zhao, Jeff
AU  - Zhao J
FAU - Mundt, Arley
AU  - Mundt A
FAU - Jiang, Zhi-Dong
AU  - Jiang ZD
FAU - Miller, Stephan
AU  - Miller S
FAU - Flores, Jose
AU  - Flores J
FAU - Shringarpure, Reshma
AU  - Shringarpure R
FAU - Moro, Luigi
AU  - Moro L
FAU - Bagin, Robert G
AU  - Bagin RG
FAU - Ballard, E David
AU  - Ballard ED
FAU - Totoritis, Mark C
AU  - Totoritis MC
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Travel Med
JT  - Journal of travel medicine
JID - 9434456
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Rifamycins)
RN  - L36O5T016N (Rifaximin)
SB  - IM
CIN - J Travel Med. 2014 Nov-Dec;21(6):365-8. PMID: 25345981
MH  - Administration, Oral
MH  - Adult
MH  - Diarrhea/*drug therapy/microbiology/prevention & control
MH  - Double-Blind Method
MH  - Escherichia coli/isolation & purification
MH  - Escherichia coli Infections/*drug therapy/prevention & control
MH  - Female
MH  - Gastrointestinal Agents/*administration & dosage
MH  - Guatemala
MH  - Humans
MH  - Male
MH  - Mexico
MH  - Rifamycins/*administration & dosage
MH  - Rifaximin
MH  - *Travel
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2014/10/28 06:00
MHDA- 2015/07/02 06:00
CRDT- 2014/10/28 06:00
PHST- 2014/02/28 00:00 [received]
PHST- 2014/08/25 00:00 [revised]
PHST- 2014/08/26 00:00 [accepted]
PHST- 2014/10/28 06:00 [entrez]
PHST- 2014/10/28 06:00 [pubmed]
PHST- 2015/07/02 06:00 [medline]
AID - 10.1111/jtm.12168 [doi]
PST - ppublish
SO  - J Travel Med. 2014 Nov-Dec;21(6):369-76. doi: 10.1111/jtm.12168.