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The first case of septicemia caused by imipenem-susceptible, meropenem-resistant Klebsiella pneumoniae.

Kayama S, Shigemoto N, Kuwahara R, Ishino T, Imon K, Onodera M, Yokozaki M, Ohge H, Sugai M - Ann Lab Med (2013)

View Article: PubMed Central - PubMed

Affiliation: Project Research Center for Nosocomial Infectious Diseases, Hiroshima University, Hiroshima City, Japan.

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Klebsiella pneumoniae is a common nosocomial pathogen causing pneumonia and bacteremia in intensive care units (ICUs)... This phenotype is susceptible to imipenem (IPM) but resistant to other carbapenems (imipenem-susceptible, meropenem-resistant Klebsiella, ISMRK)... On hospital day 31, blood endotoxins were identified, and the patient was treated with both continuous hemodiafiltration and polymyxin B hemoperfusion... After K1 was found to be ESBL-positive, empirical antimicrobial treatment was changed from ampicillin/sulbactam to meropenem (MEM, 1 g i.v. every 8 hr)... On hospital day 32, susceptibility testing revealed that these isolates were resistant to MEM, and treatment with amikacin (400 mg i.v. per day) and IPM/cilastatin (0.5 g i.v. every 8 hr) was started... However, the patient's condition did not improve, and he died of respiratory failure on hospital day 33... Each of the 5 isolates (K1-K5) was positive for cefepime (FEP) and cefpirome (CPR) by DDST, suggesting the production of ESBL... Additionally, on MHT, all 5 isolates were found to be positive for MEM but negative for IPM... After the revision of carbapenem breakpoints for Enterobacteriaceae issued by CLSI in June 2010, ISMRK was confirmed to be susceptible to IPM by the micro-dilution method... However, medical bacteriology laboratories using susceptibility panels with only IPM as a representative of carbapenems may not identify the carbapenemase production of ISMRK and are likely to report the isolate as an ESBL-producing Klebsiella sp... In the case reported here, the patient's treatment was changed from MEM to IPM/cilastatin after susceptibility test results were reported on day 32, but the patient did not recover... Additionally, Mochon et al. reported that empirical MEM therapy was administered to a patient with K. pneumoniae carrying blaNDM-1, and the strain was susceptible to ertapenem, IPM, and MEM; however, this treatment was discontinued because of the increase in the MICs of the isolates to those drugs used during the therapy... These cases show a lack of correlation between in vitro results and treatment efficacy.

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Phenotypic detection of extended spectrum β-lactamase and carbapenemases in the K1 isolate, an imipenem-susceptible meropenem-resistant Klebsiella pneumoniae strain isolated from venous blood. (A) DDST with amoxicillin/clavulanate. K. pneumoniae K1 was inoculated onto the surface of a Muller-Hinton agar plate. Cephalosporin disks were applied at a distance of 20 mm from the clavulanate-containing disk; an enhanced zone of inhibition toward the clavulanate-containing disk was observed. (B) SMA test using IPM and MEM. K. pneumoniae K1 was inoculated onto the surface of a Muller-Hinton agar plate. An SMA disk was placed adjacent to either the IPM or MEM disk; an enhanced zone of inhibition toward the SMA disk was observed. (C) Modified Hodge test using IPM or MEM. E. coli ATCC25922 was inoculated onto the surface of a Muller-Hinton agar plate and organisms (K1, K5, K. pneumoniae ATCC BAA-1705 for positive control and K. pneumoniae ATCC BAA-1706 for negative control) were inoculated as streaks.Abbreviations: A/C, amoxicillin/clavulanate; CTX, cefotaxime; CPR, cefpirome; CAZ, ceftazidime; CFPM, cefepime; DDST, double-disk synergy test; IPM, imipenem; MEM, meropenem; SMA, sodium mercaptoacetic acid.
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Figure 1: Phenotypic detection of extended spectrum β-lactamase and carbapenemases in the K1 isolate, an imipenem-susceptible meropenem-resistant Klebsiella pneumoniae strain isolated from venous blood. (A) DDST with amoxicillin/clavulanate. K. pneumoniae K1 was inoculated onto the surface of a Muller-Hinton agar plate. Cephalosporin disks were applied at a distance of 20 mm from the clavulanate-containing disk; an enhanced zone of inhibition toward the clavulanate-containing disk was observed. (B) SMA test using IPM and MEM. K. pneumoniae K1 was inoculated onto the surface of a Muller-Hinton agar plate. An SMA disk was placed adjacent to either the IPM or MEM disk; an enhanced zone of inhibition toward the SMA disk was observed. (C) Modified Hodge test using IPM or MEM. E. coli ATCC25922 was inoculated onto the surface of a Muller-Hinton agar plate and organisms (K1, K5, K. pneumoniae ATCC BAA-1705 for positive control and K. pneumoniae ATCC BAA-1706 for negative control) were inoculated as streaks.Abbreviations: A/C, amoxicillin/clavulanate; CTX, cefotaxime; CPR, cefpirome; CAZ, ceftazidime; CFPM, cefepime; DDST, double-disk synergy test; IPM, imipenem; MEM, meropenem; SMA, sodium mercaptoacetic acid.

Mentions: Identification of ESBL and metallo-β-lactamase (MBL) activities was performed using a double-disk synergy test (DDST), a sodium mercaptoacetic acid (SMA) test, and a modified Hodge test (MHT) [2] (Fig. 1). Each of the 5 isolates (K1-K5) was positive for cefepime (FEP) and cefpirome (CPR) by DDST, suggesting the production of ESBL. Additionally, on MHT, all 5 isolates were found to be positive for MEM but negative for IPM. Conversely, all 5 isolates were positive by SMA. The presence of genes in the IMP-1 and CTX-M-2 families was confirmed by PCR mapping of the integron [1]. Furthermore, nucleotide sequencing of the PCR products for blaIMP-1-type isolates showed sequences identical to blaIMP-6 (DDBJ AB616660). Multi-locus sequence typing of K1 indicated that the isolate belonged to ST37, the same sequence type of ISMRK that we previously reported [1]. Pulsed-field gel electrophoresis of the 5 isolates showed indistinguishable genomic DNA patterns, suggesting that the isolates are genetically identical (data not shown). Plasmid profiling and Southern hybridization analyses showed the isolates possessed blaIMP-6 and blaCTX-M-2 on a 50-kb plasmid, as previously reported [1].


The first case of septicemia caused by imipenem-susceptible, meropenem-resistant Klebsiella pneumoniae.

Kayama S, Shigemoto N, Kuwahara R, Ishino T, Imon K, Onodera M, Yokozaki M, Ohge H, Sugai M - Ann Lab Med (2013)

Phenotypic detection of extended spectrum β-lactamase and carbapenemases in the K1 isolate, an imipenem-susceptible meropenem-resistant Klebsiella pneumoniae strain isolated from venous blood. (A) DDST with amoxicillin/clavulanate. K. pneumoniae K1 was inoculated onto the surface of a Muller-Hinton agar plate. Cephalosporin disks were applied at a distance of 20 mm from the clavulanate-containing disk; an enhanced zone of inhibition toward the clavulanate-containing disk was observed. (B) SMA test using IPM and MEM. K. pneumoniae K1 was inoculated onto the surface of a Muller-Hinton agar plate. An SMA disk was placed adjacent to either the IPM or MEM disk; an enhanced zone of inhibition toward the SMA disk was observed. (C) Modified Hodge test using IPM or MEM. E. coli ATCC25922 was inoculated onto the surface of a Muller-Hinton agar plate and organisms (K1, K5, K. pneumoniae ATCC BAA-1705 for positive control and K. pneumoniae ATCC BAA-1706 for negative control) were inoculated as streaks.Abbreviations: A/C, amoxicillin/clavulanate; CTX, cefotaxime; CPR, cefpirome; CAZ, ceftazidime; CFPM, cefepime; DDST, double-disk synergy test; IPM, imipenem; MEM, meropenem; SMA, sodium mercaptoacetic acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756248&req=5

Figure 1: Phenotypic detection of extended spectrum β-lactamase and carbapenemases in the K1 isolate, an imipenem-susceptible meropenem-resistant Klebsiella pneumoniae strain isolated from venous blood. (A) DDST with amoxicillin/clavulanate. K. pneumoniae K1 was inoculated onto the surface of a Muller-Hinton agar plate. Cephalosporin disks were applied at a distance of 20 mm from the clavulanate-containing disk; an enhanced zone of inhibition toward the clavulanate-containing disk was observed. (B) SMA test using IPM and MEM. K. pneumoniae K1 was inoculated onto the surface of a Muller-Hinton agar plate. An SMA disk was placed adjacent to either the IPM or MEM disk; an enhanced zone of inhibition toward the SMA disk was observed. (C) Modified Hodge test using IPM or MEM. E. coli ATCC25922 was inoculated onto the surface of a Muller-Hinton agar plate and organisms (K1, K5, K. pneumoniae ATCC BAA-1705 for positive control and K. pneumoniae ATCC BAA-1706 for negative control) were inoculated as streaks.Abbreviations: A/C, amoxicillin/clavulanate; CTX, cefotaxime; CPR, cefpirome; CAZ, ceftazidime; CFPM, cefepime; DDST, double-disk synergy test; IPM, imipenem; MEM, meropenem; SMA, sodium mercaptoacetic acid.
Mentions: Identification of ESBL and metallo-β-lactamase (MBL) activities was performed using a double-disk synergy test (DDST), a sodium mercaptoacetic acid (SMA) test, and a modified Hodge test (MHT) [2] (Fig. 1). Each of the 5 isolates (K1-K5) was positive for cefepime (FEP) and cefpirome (CPR) by DDST, suggesting the production of ESBL. Additionally, on MHT, all 5 isolates were found to be positive for MEM but negative for IPM. Conversely, all 5 isolates were positive by SMA. The presence of genes in the IMP-1 and CTX-M-2 families was confirmed by PCR mapping of the integron [1]. Furthermore, nucleotide sequencing of the PCR products for blaIMP-1-type isolates showed sequences identical to blaIMP-6 (DDBJ AB616660). Multi-locus sequence typing of K1 indicated that the isolate belonged to ST37, the same sequence type of ISMRK that we previously reported [1]. Pulsed-field gel electrophoresis of the 5 isolates showed indistinguishable genomic DNA patterns, suggesting that the isolates are genetically identical (data not shown). Plasmid profiling and Southern hybridization analyses showed the isolates possessed blaIMP-6 and blaCTX-M-2 on a 50-kb plasmid, as previously reported [1].

View Article: PubMed Central - PubMed

Affiliation: Project Research Center for Nosocomial Infectious Diseases, Hiroshima University, Hiroshima City, Japan.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Klebsiella pneumoniae is a common nosocomial pathogen causing pneumonia and bacteremia in intensive care units (ICUs)... This phenotype is susceptible to imipenem (IPM) but resistant to other carbapenems (imipenem-susceptible, meropenem-resistant Klebsiella, ISMRK)... On hospital day 31, blood endotoxins were identified, and the patient was treated with both continuous hemodiafiltration and polymyxin B hemoperfusion... After K1 was found to be ESBL-positive, empirical antimicrobial treatment was changed from ampicillin/sulbactam to meropenem (MEM, 1 g i.v. every 8 hr)... On hospital day 32, susceptibility testing revealed that these isolates were resistant to MEM, and treatment with amikacin (400 mg i.v. per day) and IPM/cilastatin (0.5 g i.v. every 8 hr) was started... However, the patient's condition did not improve, and he died of respiratory failure on hospital day 33... Each of the 5 isolates (K1-K5) was positive for cefepime (FEP) and cefpirome (CPR) by DDST, suggesting the production of ESBL... Additionally, on MHT, all 5 isolates were found to be positive for MEM but negative for IPM... After the revision of carbapenem breakpoints for Enterobacteriaceae issued by CLSI in June 2010, ISMRK was confirmed to be susceptible to IPM by the micro-dilution method... However, medical bacteriology laboratories using susceptibility panels with only IPM as a representative of carbapenems may not identify the carbapenemase production of ISMRK and are likely to report the isolate as an ESBL-producing Klebsiella sp... In the case reported here, the patient's treatment was changed from MEM to IPM/cilastatin after susceptibility test results were reported on day 32, but the patient did not recover... Additionally, Mochon et al. reported that empirical MEM therapy was administered to a patient with K. pneumoniae carrying blaNDM-1, and the strain was susceptible to ertapenem, IPM, and MEM; however, this treatment was discontinued because of the increase in the MICs of the isolates to those drugs used during the therapy... These cases show a lack of correlation between in vitro results and treatment efficacy.

Show MeSH
Related in: MedlinePlus