PMID- 23295932
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  - Inoculum effects of ceftobiprole, daptomycin, linezolid, and vancomycin with 
      Staphylococcus aureus and Streptococcus pneumoniae at inocula of 10(5) and 10(7) 
      CFU injected into opposite thighs of neutropenic mice.
PG  - 1434-41
LID - 10.1128/AAC.00362-12 [doi]
AB  - Reduced bactericidal efficacy at a high inoculum is known as the inoculum effect 
      (IE). We used neutropenic mice to compare the IEs of ceftobiprole (CFB), 
      daptomycin (DAP), linezolid (LZD), and vancomycin (VAN) against 6 to 9 strains of 
      Staphylococcus aureus and 4 strains of Streptococcus pneumoniae at 2 inocula in 
      opposite thighs of the same mice. Neutropenic mice had 10(4.5) to 10(5.7) 
      CFU/thigh (low inoculum [LI]) in one thigh and 10(6.4) to 10(7.2) CFU/thigh (high 
      inoculum [HI]) in the opposite thigh when treated for 24 h with subcutaneous 
      (s.c.) doses every 12 h of DAP at 0.024 to 100 mg/kg of body weight and LZD at 
      0.313 to 320 mg/kg and s.c. doses every 6 h of CFB at 0.003 to 160 mg/kg and VAN 
      at 0.049 to 800 mg/kg. Dose-response data were analyzed by a maximum effect 
      (E(max)) model using nonlinear regression. Static doses for each drug and at each 
      inoculum were calculated, and the difference between HI and LI (IE index) gave 
      the magnitude of IE for each drug-organism combination. Mean (range) IE indexes 
      of S. aureus were 2.9 (1.7 to 4.6) for CFB, 4.1 (2.6 to 9.3) for DAP, 4.6 (1.7 to 
      7.1) for LZD, and 10.1 (6.3 to 20.3) for VAN. In S. pneumoniae, the IE indexes 
      were 2.5 (1.3 to 3.3) for CFB, 2.0 (1.6 to 2.8) for DAP, 1.9 (1.7 to 2.2) for 
      LZD, and 1.5 (0.8 to 3.2) for VAN; these values were similar for all drugs. In S. 
      aureus, the IE was much larger with VAN than with CFB, DAM, and LZD (P < 0.05). 
      An in vivo time course of vancomycin activity showed initiation of killing at 4- 
      to 16-fold-higher doses at HI than at LI despite similar initial growth of 
      controls.
FAU - Lee, Dong-Gun
AU  - Lee DG
AD  - Department of Medicine, University of Wisconsin School of Medicine and Public 
      Health, Madison, WI, USA.
FAU - Murakami, Yoichi
AU  - Murakami Y
FAU - Andes, David R
AU  - Andes DR
FAU - Craig, William A
AU  - Craig WA
LA  - eng
PT  - Journal Article
DEP - 20130107
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Acetamides)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cephalosporins)
RN  - 0 (Oxazolidinones)
RN  - 5T97333YZK (ceftobiprole)
RN  - 6Q205EH1VU (Vancomycin)
RN  - ISQ9I6J12J (Linezolid)
RN  - NWQ5N31VKK (Daptomycin)
SB  - IM
MH  - Acetamides/*pharmacology
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Cephalosporins/*pharmacology
MH  - Colony Count, Microbial
MH  - Daptomycin/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Injections, Subcutaneous
MH  - Linezolid
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Microbial Sensitivity Tests
MH  - Neutropenia/complications/microbiology
MH  - Oxazolidinones/*pharmacology
MH  - Pneumococcal Infections/complications/drug therapy/microbiology
MH  - Staphylococcal Infections/complications/drug therapy/microbiology
MH  - Staphylococcus aureus/*drug effects/growth & development
MH  - Streptococcus pneumoniae/*drug effects/growth & development
MH  - Thigh/microbiology
MH  - Vancomycin/*pharmacology
PMC - PMC3591865
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.00362-12 [pii]
AID - 00362-12 [pii]
AID - 10.1128/AAC.00362-12 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2013 Mar;57(3):1434-41. doi: 10.1128/AAC.00362-12. 
      Epub 2013 Jan 7.