PMID- 23295931
OWN - NLM
STAT- MEDLINE
DCOM- 20130730
LR  - 20211021
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 57
IP  - 3
DP  - 2013 Mar
TI  - Activities of drug combinations against Mycobacterium tuberculosis grown in 
      aerobic and hypoxic acidic conditions.
PG  - 1428-33
LID - 10.1128/AAC.02154-12 [doi]
AB  - Mycobacterium tuberculosis is exposed to hypoxia and acidity within granulomatous 
      lesions. In this study, an acidic culture model of M. tuberculosis was used to 
      test drug activity against aerobic 5-day-old (A5) and hypoxic 5-, 12-, and 
      19-day-old (H5, H12, and H19, respectively) bacilli after 7, 14, and 21 days of 
      exposure. In A cultures, CFU and pH rapidly increased, while in H cultures growth 
      stopped and pH increased slightly. Ten drugs were tested: rifampin (R), isoniazid 
      (I), pyrazinamide (Z), ethambutol (E), moxifloxacin (MX), amikacin (AK), 
      metronidazole (MZ), nitazoxanide (NZ), niclosamide (NC), and PA-824 (PA). 
      Rifampin was the most active against A5, H5, H12, and H19 bacilli. Moxifloxacin 
      and AK efficiently killed A5 and H5 cells, I was active mostly against A5 cells, 
      Z was most active against H12 and H19 cells, and E showed low activity. Among 
      nitrocompounds, NZ, NC, and PA were effective against A5, H5, H12, and H19 cells, 
      while MZ was active against H12 and H19 cells. To kill all A and H cells, A5- and 
      H5-active agents R, MX, and AK were used in combination with MZ, NZ, NC, or PA, 
      in comparison with R-I-Z-E, currently used for human therapy. Mycobacterial 
      viability was determined by CFU and a sensitive test in broth (day to positivity, 
      MGIT 960 system). As shown by lack of regrowth in MGIT, the most potent 
      combination was R-MX-AK-PA, which killed all A5, H5, H12, and H19 cells in 14 
      days. These observations demonstrate the sterilizing effect of drug combinations 
      against cells of different M. tuberculosis stages grown in aerobic and hypoxic 
      acidic conditions.
FAU - Piccaro, Giovanni
AU  - Piccaro G
AD  - Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto 
      Superiore di Sanita, Rome, Italy.
FAU - Giannoni, Federico
AU  - Giannoni F
FAU - Filippini, Perla
AU  - Filippini P
FAU - Mustazzolu, Alessandro
AU  - Mustazzolu A
FAU - Fattorini, Lanfranco
AU  - Fattorini L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130107
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antitubercular Agents)
RN  - 0 (Culture Media)
RN  - 0 (Drug Combinations)
SB  - IM
MH  - Aerobiosis/*drug effects/physiology
MH  - Anaerobiosis/*drug effects/physiology
MH  - Antitubercular Agents/*pharmacology
MH  - Colony Count, Microbial
MH  - Culture Media
MH  - *Drug Combinations
MH  - Hydrogen-Ion Concentration
MH  - Microbial Sensitivity Tests
MH  - Microbial Viability/drug effects
MH  - Mycobacterium tuberculosis/*drug effects/growth & development
PMC - PMC3591868
EDAT- 2013/01/09 06:00
MHDA- 2013/07/31 06:00
PMCR- 2013/09/01
CRDT- 2013/01/09 06:00
PHST- 2013/01/09 06:00 [entrez]
PHST- 2013/01/09 06:00 [pubmed]
PHST- 2013/07/31 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - AAC.02154-12 [pii]
AID - 02154-12 [pii]
AID - 10.1128/AAC.02154-12 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2013 Mar;57(3):1428-33. doi: 10.1128/AAC.02154-12. 
      Epub 2013 Jan 7.