Combined Porin Loss and Extended Spectrum β-Lactamase Production is Associated with an Increasing Imipenem Minimal Inhibitory Concentration in Clinical Klebsiella pneumoniae Strains

Abstract

For this study, 150 clinical isolates of Klebsiella pneumoniae were collected from one hospital in Beijing, China, and assayed for minimal inhibitory concentration (MIC) of imipenem. To elucidate the mechanisms responsible for imipenem MIC variation among extended-spectrum beta-lactamase (ESBL)-positive and -negative K. pneumoniae strains, a variety of beta-lactamase genes (bla(TEM), bla(CTX-M), bla(SHV), and bla(OXA)) were screened by polymerase chain reaction (PCR). The outer membrane profile and expression of related genes (ompK35 and ompK36) then were analyzed and evaluated, respectively. None of the tested isolates were clinically resistant to imipenem, but the range of MICs among ESBL-positive and -negative strains was significantly different. Deficiency in the expression of outer membrane proteins (OmpK35,36) was observed in some of both ESBL-positive(17.6%) and -negative strains (10.9%), but only the ESBL-positive strains depressed by the expression of ompK35/36 had an increased MIC of imipenem (>or=0.5 mg/l). These results confirmed that the combination of SHV-1, CTX-M-3, CTX-M-14, TEM-1, or OXA-11 production and reduced expression of ompK35/36 may not result in clinical resistance to imipenem but does correlate with increasing imipenem MIC.

Prevalence of carbapenem resistance encoding genes and corresponding MIC90 in enterobacteriaceae at a tertiary medical care center in Lebanon

“…Similarly, it has been shown that carbapenem resistance levels intensify when resistance encoding genes such as bla OXA-48 are combined with permeability defects [13].Yang et al demonstrated similar results, whereby they confirmed that the combination of SHV-1, CTXM-3, CTXM-14, TEM-1 or OXA-11 production reduced the expression of OMPK-35/36 resulting in increased MIC, which may or may not lead to increased resistance clinically [23].…”

In Vitro Susceptibility to Ceftazidime-Avibactam of Carbapenem-Nonsusceptible Enterobacteriaceae Isolates Collected during the INFORM Global Surveillance Study (2012 to 2014)

“…The majority (94%) of the carbapenem-nonsusceptible Enterobacteriaceae that did not contain a carbapenemase harbored ESBLs and/or Ambler class C ␤-lactamases that were encoded by chromosomally located or plasmidcarried genes. The presence of these ␤-lactamases, coupled with reduced expression or loss of function of one or more outer membrane pore-forming proteins, is most likely the reason for the reduced susceptibility to carbapenems observed among these isolates (6)(7)(8). Whereas susceptibility to carbapenems was lost in these isolates, this resistance mechanism did not impact the activity of ceftazidime-avibactam, with 94.7% of the isolates remaining susceptible to this combination.…”

“…Two clinically important mechanisms of resistance to carbapenems among Enterobacteriaceae have been identified. One is the production of carbapenemases, such as serine carbapenemases (KPC and OXA) and metallo-␤-lactamases (VIM, IMP, and NDM) (5), and the other is the production of ESBLs or Ambler class C ␤-lactamases coupled with reduced expression or loss of function of one or more outer membrane pore-forming proteins (6)(7)(8).…”

Molecular characterization of resistance mechanisms in Pseudomonas aeruginosa isolates resistant to carbapenems

“…The transport of carbapenems across the lipid bilayer membranes occurs through protein channels, porins, especially OprD [11]. Lack of OprD participates in the resistance of P. aeruginosa isolates to carbapenems [12][13].…”