PMID- 29782237
OWN - NLM
STAT- MEDLINE
DCOM- 20181214
LR  - 20191210
IS  - 1931-8448 (Electronic)
IS  - 1076-6294 (Linking)
VI  - 24
IP  - 7
DP  - 2018 Sep
TI  - Effect of Porins and bla(KPC) Expression on Activity of Imipenem with Relebactam 
      in Klebsiella pneumoniae: Can Antibiotic Combinations Overcome Resistance?
PG  - 877-881
LID - 10.1089/mdr.2018.0065 [doi]
AB  - Imipenem with relebactam is a novel beta-lactam-beta-lactamase inhibitor that has 
      activity against most KPC-producing Enterobacteriaceae. Using 10 isolates of 
      KPC-possessing Klebsiella pneumoniae, we assessed the relationship between 
      imipenem-relebactam minimum inhibitory concentrations (MICs) and mechanisms known 
      to contribute to antimicrobial resistance. The effect of adding a second agent 
      was assessed by time-kill experiments. Mutations affecting the genes encoding 
      porins ompK35 and ompK36 and identification of beta-lactamases were assessed by PCR. 
      Expression of bla(KPC) and acrB was assessed by real-time reverse-transcriptase 
      (RT)-PCR, and production of OmpK36 by SDS-PAGE. Time-kill studies were performed 
      using combinations of imipenem-relebactam with polymyxin B, amikacin, or 
      tigecycline. Seven isolates having a disruption in a single porin, or in neither 
      porin, remained susceptible to imipenem-relebactam. The addition of a second 
      agent did not improve the activity of imipenem-relebactam for these isolates, 
      although the addition of tigecycline was antagonistic for three isolates. Three 
      isolates had major disruptions in both ompK35 and ompK36 that correlated with 
      reduced activity of imipenem-relebactam (MICs 2/4, 8/4, and 512/4 mug/mL). Two of 
      these isolates also had overexpression of bla(KPC), including the isolate with 
      the highest MIC. These isolates were also resistant to polymyxin B and amikacin. 
      The addition of amikacin provided both synergistic and bactericidal activity for 
      the two more resistant isolates. The activity of imipenem-relebactam against K. 
      pneumoniae is affected by major disruptions of both ompK35 and ompK36 and by 
      expression of the KPC gene. Combining imipenem-relebactam with an aminoglycoside 
      may be a promising approach for isolates with reduced susceptibility to 
      imipenem-relebactam.
FAU - Balabanian, Gregory
AU  - Balabanian G
AD  - Department of Medicine and Division of Infectious Diseases, SUNY Downstate 
      Medical Center , Brooklyn, New York.
FAU - Rose, Michael
AU  - Rose M
AD  - Department of Medicine and Division of Infectious Diseases, SUNY Downstate 
      Medical Center , Brooklyn, New York.
FAU - Manning, Nyla
AU  - Manning N
AD  - Department of Medicine and Division of Infectious Diseases, SUNY Downstate 
      Medical Center , Brooklyn, New York.
FAU - Landman, David
AU  - Landman D
AD  - Department of Medicine and Division of Infectious Diseases, SUNY Downstate 
      Medical Center , Brooklyn, New York.
FAU - Quale, John
AU  - Quale J
AD  - Department of Medicine and Division of Infectious Diseases, SUNY Downstate 
      Medical Center , Brooklyn, New York.
LA  - eng
PT  - Journal Article
DEP - 20180521
PL  - United States
TA  - Microb Drug Resist
JT  - Microbial drug resistance (Larchmont, N.Y.)
JID - 9508567
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Azabicyclo Compounds)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Drug Combinations)
RN  - 0 (Porins)
RN  - 71OTZ9ZE0A (Imipenem)
RN  - EC 3.5.2.6 (beta-Lactamases)
RN  - Y1MYA2UHFL (relebactam)
SB  - IM
MH  - Anti-Bacterial Agents/pharmacology
MH  - Azabicyclo Compounds/*pharmacology
MH  - Bacterial Proteins/*genetics
MH  - Drug Combinations
MH  - Drug Resistance, Bacterial/*drug effects/genetics
MH  - Gene Expression Regulation, Bacterial/drug effects/genetics
MH  - Humans
MH  - Imipenem/*pharmacology
MH  - Klebsiella Infections/*drug therapy
MH  - Klebsiella pneumoniae/*drug effects/genetics
MH  - Microbial Sensitivity Tests/methods
MH  - Porins/*genetics
MH  - beta-Lactamases
OTO - NOTNLM
OT  - Klebsiella pneumoniae
OT  - carbapenemase
OT  - relebactam
EDAT- 2018/05/22 06:00
MHDA- 2018/12/15 06:00
CRDT- 2018/05/22 06:00
PHST- 2018/05/22 06:00 [pubmed]
PHST- 2018/12/15 06:00 [medline]
PHST- 2018/05/22 06:00 [entrez]
AID - 10.1089/mdr.2018.0065 [doi]
PST - ppublish
SO  - Microb Drug Resist. 2018 Sep;24(7):877-881. doi: 10.1089/mdr.2018.0065. Epub 2018 
      May 21.