Extended-spectrum β-lactamases (ESBLs) and/or AmpC enzymes combined with deficiency of porins OmpK35 and OmpK36 are important for the development of carbapenem-resistant Klebsiella pneumoniae. We characterized the clinical K. pneumoniae human isolates and investigated the effect of meropenem induction on the ompK35 and ompK36 mutation to develop carbapenem resistance from six carbapenem-susceptible ESBL-producing K. pneumoniae strains. 163 clinical K. pneumoniae isolates were grouped mostly into the ESBL + AmpC (44.2%) and ESBL (42.9%) phenotypes. The resistance rate differed between cephalosporins (52.1% for cefepime - 97.5% for cefotaxime) and carbapenems (16% for meropenem - 28.2% for imipenem) (P < 0.001). The ESBL group showed the lowest resistance to cefoxitin and cefepime and all carbapenems, whereas the AmpC group exhibited the lowest resistance to cefepime and the highest resistance to all carbapenems. PCR amplification identified bla TEM, bla SHV, bla CTX-M-3-like, and bla CTX-M-14-like of AmpA β-lactamase genes and bla DHA and bla CMY of AmpC β-lactamase genes. Compared to all 163 clinical isolates, the 56 carbapenem-resistant isolates carried less frequently of bla TEM, bla CTXM-14-like, and bla CTXM-3-like and more frequently of bla DHA-1 and bla CMY-2. The carbapenem-resistant isolates differed in prevalence against imipenem, ertapenem, and meropenem and lacked OmpK35 more frequently than OmpK36, but abnormal PCR amplicons were detected fewer in the Omp K35-deficient group than in the OmpK36-deficient group (32.5% vs. 68.4%, respectively). The carbapenem-resistant isolate mostly carried bla DHA (91.1%) and three isolates carried bla KPC-2. Following induction with meropenem insertion sequences in ompK36, not ompK36, were identified as IS5 for KP08, IS1 for KP15, and IS903 for KP16 isolates. OmpK36 deficiency increased resistance to ertapenem, but not imipenem and meropenem. Clinical isolates belonged mainly to ESBL + AmpC group and ESBL group with difference in resistance to cephalosporins and carbapenems, the bla genes. Carbapenem resistant isolates lacked OmpK35 expression, than the OmpK36 expression, Meropenem induction developed the carbapenem resistant isolates with insertion of different insertion sequences in ompK36, not ompK35.
The community-associated Klebsiella pneumoniae has gradually increased [
The mechanism of carbapenem resistance involves mutations in penicillin-binding proteins (PBPs) to prevent carbapenem binding [
The aim of this study was to investigate the effect of low-dosage meropenem treatment on the induction of carbapenem resistance in five carbapenem-susceptible K. pneumoniae strains with ESBL production with expression of OmpK35 and OmpK36 and one isolate without Ompk35 expression.
163 K. pneumoniae isolates were collected from the Chiayi Branch of Taichung Veterinary Hospital and identified by biochemical methods using the GDN ID-8 Kit (Bio Star, Taiwan) and PCR identification of 16S rDNA sequences [
Resistance to β-lactam antimicrobials, including ampicillin, cefoxitin (FOX), ceftriaxone (CRO), ceftazidime (CAZ), cefotaxime (CTX), and cefepime (FEP) of cephalosporins, as well as ertapenem (ETP), meropenem (MEM), and imipenem (IMP) of carbapenems, were tested using the disc diffusion method (Becton, Dickinson and Company, USA) and the guidelines of the Clinical and Laboratory Standard Institute [
ESBL isolates were identified by the differences in diameter of the inhibition zones between cefotaxime and cefotaxime/clavulanic acid or between ceftazidime and ceftazidime/clavulanic acid. Active AmpC enzyme was identified using disks with 300 µg of 3-aminophenylboronic acid and carbapenemase production was detected by the Modified Hodge Test (MHT) based on the Centers for Disease Control and Prevention guidelines [
PCR amplification of AmpA blaTEM, blaSHV, blaCTX-M-3, blaCTX-M-14 and blaKPC-1 [
PCR products were purified using a DNA purification kit (ProTECH, Taiwan) and sequenced. DNA sequences were aligned and compared using Lasergene v7.1 software (DNASTAR Inc, USA) and the BLAST program of the National Center for Biotechnology Information.
ESBL-producing isolates KP07, KP08, KP10, KP13, KP15 and KP16 were used. Except that isolate KP15 lacked OMPK15 due to a deletion in the promoter region of ompK35, all isolates carried normal PCR size and protein expression of ompK35 and ompK36. These bacteria were cultured firstly in Muller-Hinton
Target | Primer sequence (5’ to 3’) | TAa (˚C) | Size (bp) | |
---|---|---|---|---|
Multiplex PCR | ||||
blaTEM | F | GAAGATCAGTTGGGTGCACGAGT | 59 | 520 |
R | CAACTTTATCCGCCTCCATCCAGT | |||
blaSHV | F | AACGGAACTGAATGAGGCGCT | 59 | 141 |
R | TCCACCATCCACTGCAGCAGCT | |||
blaCTX-M-3 | F | AATCACTGCGCCAGTTCACGCT | 59 | 479 |
R | GAACGTTTCGTCTCCCAGCTGT | |||
blaCTX-M-14 | F | TACCGCAGATAATACGCAGGTG | 59 | 355 |
R | CAGCGTAGGTTCAGTGCGATCC | |||
blaDHA | F | AACTTTCACAGGTGTGCTGGGT | 59 | 405 |
R | CCGTACGCATACTGGCTTTGC | |||
blaVIM | F | GTTTGGTCGCATATCGCAAC | 57 | 147 |
R | CTTYTCAATCTCCGCGAGAAG | |||
blaIPM-1 | F | GGAATAGAGTGGCTTAATTCTCAATC | 57 | 272 |
R | GCTTCTAAATTTGCGTCACCC | |||
blaIPM-2 | R | GYAACCAAACCACTACGTTATCT | 57 | 193 |
blaSPM | F | ATGAACTCACCTAAATCGAGAGC | 57 | 340 |
R | GTGCCGTCCAAATGAAAGTG | |||
blaSIM | F | GGCTTAGTAGTTCTTGACAATCAC | 57 | 516 |
R | CAATAGTGATGCGTCTCCGA | |||
blaGIM | F | TGTAGCGTTGCCAGCTTTAG | 57 | 431 |
R | CAGCACCTGGATAGTAGAGC | |||
blaKHM | F | CGTTTGGTCTGCTGTTGTTTAC | 57 | 322 |
R | GGAATGGACTTGGAGTTGAGAA | |||
blaNDM | F | ACTTATGCCAATGCGTTGTC | 57 | 225 |
R | TCTGTCCTTGATCAGGCAG | |||
Single PCR | ||||
KP16S | F | AGCACAGAGAGCTTG | 50 | 126 |
R | ACTTTGGTCTTGCGAC | |||
blaCMY-2 | F | CTGACAGCCTCTTTCTCCACA | 56 | 1005 |
R | CTACGTAGCTGCCAAATCCAC | |||
blaKPC | F | TGTCACTGTATCGCCGTC | 54 | 1000 |
R | CTCAGTGCTCTACAGAAAACC | |||
OmpK35 | F | TGATCCCTGCCCTGCTGGT | 56 | 717 |
R | CCGGAGTCATGTTGTAAGTCT |
OmpK36 | F | ACAGAGGGTTAATAACATGAA | 51 | 1112 |
---|---|---|---|---|
R | TAGAACTGGTAAACCAGGC | |||
OmpK35-FL1 | F | GTTACGCACTGTTTCGG | 52 | 1572 |
R | GGTGTACTGCAGATTAGAAC | |||
OmpK36-FL | F | GCAGCACAATGAAATAGCC | 53 | 1265 |
R | GACAAGAGTATACCAGCGAG | |||
OmpK35-Pro | F | GTTACGCACTGTTTCGG | 52 | 502 |
R | CCAGAATATTGCGCTTCATC | |||
OmpK35-Ter | F | CCAGACTTACAACATGACTC | 51 | 349 |
R | GGTGTACTGCAGATTAGAAC | |||
IS1 | F | TGACTCCAACTTATTGATAGTGT | 46 | 997 |
R | CATGAATGGCGTTGGATG | |||
IS5 | F | TATTTCCGGTTTTTACTGAGA | 51 | 529 |
R | CATCATGAGCCATCAACTC | |||
IS903 | F | CTTTTGCTGAGTTGAAGGA | 51 | 987 |
R | TGTGTTTTCAGGCAATACG |
aTA: annealing temperature.
Broth (MHB) containing 0.1 μg/ml meropenem for 16 hours at 100 rpm, followed by subculture in MHB supplemented with 0.5 μg/ml, 1 μg/ml, and 2 μg/ml meropenem, subsequently. The bacterial solution was plated onto Muller-Hinton Agar (MHA), and meropenem discs were plated thereafter. Colonies in the inhibition zone were selected, and outer membrane proteins were analyzed using a previously described method [
Duncan’s multiple range test and SPSS software (version 18, Chicago, IL, USA) were used to analyze differences among groups.
The 163 isolates were separated into four phenotypic groups: the ESBL + AmpC group (44.2%), the ESBL group (42.9%), the AmpC group (7.4%), and neither group (5.5%). The prevalence was 87.1% (142 isolates) for ESBL-producing isolates, and 50.3% (82 isolates) for AmpC isolates, with the different resistance patterns among the ESBL and AmpC phenotypes (
Characters | ESBL and AmpC phenotypes | ||||
---|---|---|---|---|---|
ESBLs + AmpC | ESBLs | AmpC | Neither | Total | |
Number | 72 | 70 | 12 | 9 | 163 |
Resistance to cephalosporins | |||||
cefoxitin | 68 (94.4)a,x | 18 (25.7)c,z | 11 (91.7)a,x | 6 (66.7)b,x | 103 (63.2) |
ceftriaxone | 71 (98.6)a,x | 69 (98.6)a,x | 7 (58.3)b,y | 1 (11.1)c,y | 148 (90.8) |
ceftazidime | 71 (98.6)a,x | 63 (90.0)a,x | 11 (91.7)a,x | 5 (55.6)b,x | 150 (92.0) |
cefotaxime | 71 (98.6)a,x | 69 (98.6)a,x | 12 (100.0)a,x | 7 (77.8)b,x | 159 (97.5) |
cefepime | 41 (56.9)a,y | 41 (58.6)a,y | 2 (16.7)b,z | 1 (11.1)b,y | 85 (52.1) |
Resistance to carbapenem | |||||
Imipenem | 33 (45.8)a,x | 3 (4.3)b | 7 (58.3)a | 3 (33.3)a | 46 (28.2) |
Meropenem | 16 (22.2)b,y | 3 (4.3)b | 6 (50.0)a | 1 (11.1)b | 26 (16.0) |
Ertapenem | 26 (36.1)b,xy | 4 (5.7)c | 8 (66.7)a | 2 (22.2) | 40 (24.5) |
AmpA genes | |||||
blaSHV | 72 (100.0) | 70 (100.0) | 12 (100.0) | 9 (100.0) | 163 (100) |
blaTEM | 60 (83.3) | 53 (75.7) | 9 (75.0) | 1 (11.1) | 123 (75.5) |
blaCTX-M3 | 6 (8.3) | 13 (18.6) | 0 (0.0) | 0 (0.0) | 19 (11.7) |
blaCTX-M14 | 31 (43.1) | 25 (35.7) | 0 (0.0) | 0 (0.0) | 56 (34.4) |
AmpC genes | |||||
blaDHA | 67 (93.1) | 13 (18.6) | 9 (75.0) | 4 (44.4) | 93 (57.1) |
blaCMY2 | 7 (9.7) | 3 (4.3) | 3 (25.0) | 0 (0.0) | 13 (8.0) |
a-dDifferent letters indicate significant difference between different ESBL and AmpC types, and x-zDifferent letters indicate significant difference between antibiotics in each ESBL and AmpC phenotypes, P < 0.05.
and carbapenems (16% for meropenem - 28.2% for imipenem) (P < 0.001). The ESBL + AmpC group with respect to resistance revealed no differences among ceftriaxone, cefotaxime, and cefoxitin as well as lower resistance to cefepime in cephalosporins and the highest resistance for imipenem, followed by ertapenem and r meropenem in carbapenem. The ESBL group showed the lowest resistance to cefoxitin and cefepime and all carbapenems, whereas the AmpC group exhibited the lowest resistance to cefepime and the highest resistance to all carbapenems. Nine isolates of the none group differed in resistance to cephalosporin, but some were resistant to carbapenems.
PCR amplification identified blaTEM, blaSHV, blaCTX-M-3-like, and blaCTX-M-14-like of AmpA β-lactamase genes and blaDHA and blaCMY of AmpC β-lactamase genes (
Of the 56 carbapenem-resistant isolates, 42.9% of the isolates were resistance to all three carbapenems and one carbapenem, respectively, while 14.3% isolates were resistant to two carbapenems (
Characters | Carbapenem resistant patterns | Total [No, (%)] | |||||||
---|---|---|---|---|---|---|---|---|---|
Imipenem | R | R | I | R | R | R | I | I | 46 (82.1) |
Meropenem | R | I | R | I | I | S | I | S | 26 (46.4) |
Ertapenem | R | R | R | I | S | S | R | R | 40 (71.4) |
No. | 24 | 6 | 2 | 16 | 8 | 56 | |||
ESBL and AmpC phenotypes [No, (%)] | |||||||||
ESBL + AmpC | 15 (62.5) | 4 (66.7) | 1 (50.0) | 14 (87.5) | 6 (75.0) | 40 (71.4) | |||
ESBLs | 2 (8.3) | 0 (0.0) | 1 (50.0) | 1 (6.3) | 1 (12.5) | 5 (8.9) | |||
AmpC | 6 (25.0) | 1 (16.6) | 0 (0.0) | 0 (0.0) | 1 (12.5) | 8 (14.3) | |||
Neither | 1 (4.2) | 1 (16.6) | 0 (0.0) | 1 (6.3) | 0 (0.0) | 3 (5.4) | |||
AmpA gnes [No, (%)] | |||||||||
blaTEM | 14 (58.3) | 5 (83.3) | 1 (50.0) | 8 (72.7) | 3 (100.0) | 2 (100.0) | 5 (71.4) | 1 (100.0) | 39 (69.6) |
blaCTX-M3 | 0 (0.0) | 1 (16.7) | 1 (50.0) | 1 (9.1) | 0 (0.0) | 0 (0.0) | 1 (14.3) | 0 (0.0) | 4 (7.1) |
blaCTX-M14 | 6 (25.0) | 2 (33.3) | 0 (0.0) | 4 (36.4) | 0 (0.0) | 0 (0.0) | 3 (42.9) | 1 (100.0) | 16 (28.6) |
AmpC genes [No, (%)] | |||||||||
blaDHA | 20 (83.3) | 6 (100.0) | 1 (50.0) | 11 (100.0) | 3 (100.0) | 2 (100.0) | 7 (100.0) | 1 (100.0) | 51 (91.1) |
blaCMY2 | 5 (20.8) | 1 (16.7) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 4 (57.1) | 0 (0.0) | 10 (17.9) |
ESBL and AmpC phenotype | Outmembrane protein deficiency | ||||||||
OmpK35 | OmpK36 | OmpK35 + OmpK36 | Normal | Total | |||||
ESBL + AmpC | 27 (67.5) | 0 (0.0) | 6 (15.0) | 7 (17.5) | 40 (55.6) | ||||
ESBLs | 3 (60.0) | 0 (0.0) | 2 (40.0) | 0 (0.0) | 5 (7.1) | ||||
AmpC | 4 (50.0) | 0 (0.0) | 4 (50.0) | 0 (0.0) | 8 (66.7) | ||||
No | 2 (66.7) | 0 (0.0) | 0 (0.0) | 1 (33.3) | 3 (33.3) | ||||
Total | 36 (64.3) | 0 (0.0) | 12 (21.4) | 8 (14.3) | 56 (34.4) |
for blaVIM, blaIPM-1-like, blaIPM-2-like, blaSPM, blaSIM, blaGIM, and blaKHM, of the AmpB β-lactamase genes blaKPC were identified in three isolates (Supplementary
Compared to all clinical isolates, the carbapenem-resistant isolates carried less frequently of blaTEM (69.6% vs. 75.5%), blaCTXM-14-like (28.6% vs. 34.4%), and blaCTXM-3-like (7.1% vs. 11.7%) of AmpA genes and more frequently of blaDHA-1 (91.1% vs. 57.1%) and blaCMY-2 (17.9% vs. 8%) of AmpC genes, Eight isolates expressed both OmpK35 and OmpK36, 36 isolates lacked OmpK35 individually and 12 isolates lacked both OmpK35 and OmpK36; however, no isolate with single deficiency in OmpK36 was observed. These results may imply that deficiency in OmpK35 and OmpK36 may partly contribute to carbapenem resistance. PCR detected the abnormal ompK35 and ompK36 that differed among ESBL and/or AmpC phenotypes. Among 56 carbapenem-resistant isolates, abnormal PCR products were found in 29.3% (14/48) and 75.0% (9/12) of isolates with no OmpK35 and OmpK36 expression, respectively (
K. pneumoniae ATCC 13883 was used as a control in NB broth with or without 20% sorbitol to evaluate the expression of OmpA, OmpK35 and OmpK36. Deficiency in OmpK35, OmpK36 and OmpK35/OmpK36 was observed separately in 69.4%, 1.4% and 8.3% of isolates in the ESBL + AmpC group, 60.0%, 5.7% and 2.9% of isolates in the ESBL group, 50.0%, 8.3% and 33.3% of isolates in the AmpC group, and 33.3%, 0% and 11.1% of isolates in the neither group. The analysis of 15 ESBL- and non-ESBL-producing isolates revealed that ESBL-producing I solate 92 with the AmpC phenotype and blaDHA-1 and deficiency in OmpK35 and OmpK36 i exhibited the highest MIC against ertapenem and imipenem, whereas non-ESBL producing isolates 110 and 114 with the AmpC
phenotype and both blaDHA-1 and blaCMY-2 and deficiency in OmpK35 and OmpK36 exhibited the highest MIC against all three carbapenems (
ESBL-producing isolates KP07, KP08, KP10, KP13, KP15 and KP16 exhibited intermediate susceptibility to carbapenem (isolates KP07, KP08, KP10 and KP16 contain blaTEM, and isolates KP10 and KP16 contain blaCTX-M-14 and blaCMY). With the exception of isolate KP15 with a deletion in the promoter region of ompK35 and no OmpK35 expression normal PCR products and expression of ompK35 and ompK36 and were generated from other isolates. In total, 119 isolates were collected from KP07 (9), KP08 (17), KP10 (3), KP13 (36), KP15 (9) and KP16 (45). Only six isolates generated abnormal PCR products: KP08-1, KP08-2, KP08-12 and KP08-15 from KP08; KP15-4 from KP15; and KP16-22 from KP16. Although PCR analysis revealed three insertion sequences IS1, IS5, and IS903 present in all six isolates, only one insertion sequence was found in the ompK36 gene at different locations for each mutant isolate. Sequence analysis of ompK36 PCR products revealed an IS5 insertion at −48 bp in KP08-1 and KP08-12, at
ESBL | Strain | β-lactamase | Carbapenem | Outer membrane | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AmpA | AmpC | ETP | MIC | MEM | MIC | IMP | MIC | ompK35 | ompK36 | ||||||||
+ | 2 | TEM, SHV | DHA | S | 0.19 | S | 0.047 | S | 0.38 | Inserted | |||||||
13 | SHV | - | S | 0.094 | S | 0.064 | S | 0.19 | Inserted | ||||||||
55 | TEM, SHV, CTXM14 | - | S | 0.094 | S | 0.016 | S | 0.19 | Inserted | ||||||||
58 | SHV | - | S | 0.006 | S | 0.032 | S | 0.25 | Inserted | ||||||||
67 | TEM, SHV | - | S | 0.064 | S | 0.016 | S | 0.094 | Inserted | ||||||||
87 | SHV | - | S | 0.023 | S | 0.032 | S | 0.25 | Inserted | ||||||||
92 | SHV | DHA | R | 16 | I | 2 | R | 6 | Inserted | Inserted | |||||||
96 | TEM, SHV, CTXM14 | DHA | R | 16 | I | 2 | R | 4 | Inserted | ||||||||
98 | SHV | - | S | 0.064 | S | 0.023 | S | 0.19 | Inserted | ||||||||
− | 60 | SHV | DHA | S | 0.25 | S | 0.032 | S | 0.75 | Inserted | |||||||
79 | SHV | - | S | 0.012 | S | 0.023 | S | 0.125 | Inserted | ||||||||
100 | TEM, SHV | DHA | S | 0.19 | S | 0.023 | S | 0.25 | Inserted | ||||||||
110 | SHV | CMY-2, DHA | R | >32 | R | 12 | R | >32 | Inserted | Inserted | |||||||
114 | TEM, SHV | CMY-2, DHA | R | >32 | R | 4 | R | 12 | Inserted | Inserted | |||||||
119 | TEM, SHV | CMY-2, DHA | R | 4 | S | 0.5 | I | 2 | Inserted | ||||||||
+433 bp in KP08-2, and at 78 bp in KP08-15. Additionally, an IS1 insertion at −74 bp was discovered in KP15-4, as was an IS903 insertion at +910 bp (
Although no isolates altered antimicrobial resistance genes, the MIC value increased the highest against ertapenem, followed by meropenem and imipenem. Exception of KP08-15 with IS5 insertion in 5’-end ompK36, all KP08 derivatives were resistant to ertapenem and exhibited reduced susceptibility to meropenem and imipenem (
The prevalence of ESBL-producing K. pneumoniae differs among regions and sources in Taiwan: increasing from 3.4% - 10.3% in 1995 to 11.3% in 2000 [
Characters | Item | Strain | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
KP08 | KP08-1 | KP08-2 | KP08-12 | KP08-15 | KP15 | KP15-4 | KP16 | KP16-22 | ||
ompK36 | IS family | − | IS5 | IS5 | IS5 | IS5 | − | IS1 | − | IS903 |
Location | − | −48 bp | 433 bp | −48 bp | 78 bp | − | −74 bp | − | 910 bp | |
Target sequence | TAAG | CTAA | AAAG | ATAA | GCCGACTG | GTAAGGATC | ||||
MIC (μg/ml) | Ertapenem | 0.023 | 2 (R) | 4 (R) | 2 (R) | 1.5 (R) | 0.047 | 2 (R) | 0.094 | 6 (R) |
ratio | 1 | 87.0 | 173.9 | 87.0 | 65.2 | 1 | 42.6 | 1 | 63.8 | |
Meropenem | 0.023 | 0.38 (S) | 1 (S) | 0.5 (S) | 0.38 (S) | 0.023 | 0.5 (S) | 0.047 | 0.75(S) | |
ratio | 1 | 16.5 | 43.5 | 21.7 | 16.5 | 1 | 21.7 | 1 | 16.0 | |
Imipenem | 0.19 | 0.38 (S) | 0.75(S) | 0.38(S) | 0.38 (S) | 0.125 | 0.25 (S) | 0.38 | 2 or 3(I) | |
ratio | 1 | 2 | 3.9 | 2 | 2 | 1 | 2 | 1 | 7.9 | |
Zome (mm) | Ertapenem | 28 | 17 | 13 | 18 | 18 | 26 | 14 | 26 | 14 |
Meropenem | 28 | 22 | 19 | 22 | 21 | 25 | 18 | 25 | 19 | |
Imipenem | 28 | 26 | 25 | 25 | 27 | 26 | 23 | 24 | 20 | |
Cefepime | 25 | 15 | 13 | 16 | 17 | 15 | 9 | 20 | 15 | |
Ceftriazone | 15 | 10 | 9 | 11 | 12 | 10 | 6 | 12 | 10 | |
Ceftazidime | 11 | 8 | 6 | 9 | 9 | 6 | 6 | 8 | 6 | |
Cefotaxime | 18 | 11 | 10 | 12 | 14 | 11 | 6 | 14 | 11 | |
Cefoxitin | 23 | 13 | 12 | 13 | 12 | 14 | 6 | 9 | 6 |
87.1% in the current study (
Carbapenem-resistant ESBL-producing isolates are gradually increasing annually due to the use of meropenem and ertapenem for the treatment of ESBL-producing bacterial infections [
In K. pneumoniae, porins OmpK35 and OmpK36 play multiple roles in the development of antibiotic resistance and virulence. Isolates with deficiency in both OmpK35 and OmpK36 showed a significant decrease in virulence (i.e., a slower growth rate), an increase of susceptibility to neutrophil phagocytosis [
Altered susceptibility to carbapenem is associated with carbapenem type, insertion sequence type, insertion location, and the MIC of the parental strain (
In clinical isolates, ESBL or AmpC-producing isolates associated with carbapenem resistance were more common with deficiency in OmpK35, not OmpK36. The isolate dependent IS1, IS5, and IS903 were able to insert into ompK36 to cause resistance to ertapenem and reduced susceptibility to imipenem and carbapenem.
The authors would like to acknowledge funding of the Chiayi Branch, Taichung Veterans General Hospital (RVHCY101013 and RVHCY102003), Taiwan.
Lee, J.-J., Huang, Y.-C., Hsiao, Y., Lee, C.-H., Liu, C.-S. and Chu, C. (2018) Insertion Sequence-Dependent OmpK36 Mutation Associated Ertapenem Resistance in Clinical Klebsiella pneumoniae. Advances in Microbiology, 8, 253-269. https://doi.org/10.4236/aim.2018.84017