Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological Patient
Novel carbapenem-β-lactamase inhibitor combination, <i>imipenem/relebactam</i> (IMI-REL), has been recently approved for treatment of infections with limited or no alternative treatment options. In this study, we described the emergence of the IMI-REL-resistance in a KPC-producing <i&...
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MDPI AG
2022-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/4/778 |
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| author | Paolo Gaibani Linda Bussini Stefano Amadesi Michele Bartoletti Federica Bovo Tiziana Lazzarotto Pierluigi Viale Simone Ambretti |
| author_facet | Paolo Gaibani Linda Bussini Stefano Amadesi Michele Bartoletti Federica Bovo Tiziana Lazzarotto Pierluigi Viale Simone Ambretti |
| author_sort | Paolo Gaibani |
| collection | DOAJ |
| description | Novel carbapenem-β-lactamase inhibitor combination, <i>imipenem/relebactam</i> (IMI-REL), has been recently approved for treatment of infections with limited or no alternative treatment options. In this study, we described the emergence of the IMI-REL-resistance in a KPC-producing <i>Klebsiella pneumoniae</i> (KPC-Kp) strain collected from a hematological patient with no evidence of prior colonization. Interestingly, IMI-REL-resistance was associated with meropenem/vaborbactam (MER-VAB) cross-resistance but was not associated with cross-resistance to ceftazidime/avibactam (CAZ-AVI). Although treatment with CAZ-AVI and gentamicin completely eradicated the infection due KPC-Kp cross-resistance to IMI-REL and MER-VAB, the patient became colonized subsequently by KPC-Kp strains susceptible to IMI-REL and MER-VAB. Whole-genome sequencing performed by hybrid approach using Illumina and Oxford Nanopore platforms demonstrated that all KPC-Kp strains isolated from hematological patient belonged to the ST512 and were clonally related. Analysis of antimicrobial and porins genes demonstrated that cross-resistance to IMI-REL and MER-VAB was associated with increased <i>bla</i><sub>KPC-3</sub> copy number and truncated OmpK35 and OmpK36 with GD134-135 insertion. Phylogenetic analysis demonstrated that KPC-Kp cross-resistance to IMI-REL and MER-VAB was clonally related to a KPC-Kp resistant to IMI-REL as previously described, demonstrating the spread of this multidrug resistant clone in the hematological unit. In conclusion, the results presented in this study reported the emergence of cross-resistance to MER-VAB and IMI-REL in a KPC-Kp strain isolated from a hematological patient and highlight the potential development and diffusion of new multidrug resistance traits. |
| first_indexed | 2024-03-09T10:31:10Z |
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| id | doaj.art-7574890a19c14cbe9057c11f780144ee |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T10:31:10Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
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| series | Microorganisms |
| spelling | doaj.art-7574890a19c14cbe9057c11f780144ee2023-12-01T21:15:14ZengMDPI AGMicroorganisms2076-26072022-04-0110477810.3390/microorganisms10040778Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological PatientPaolo Gaibani0Linda Bussini1Stefano Amadesi2Michele Bartoletti3Federica Bovo4Tiziana Lazzarotto5Pierluigi Viale6Simone Ambretti7Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyDivision of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyMicrobiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyDivision of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyMicrobiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyMicrobiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyDivision of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyMicrobiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyNovel carbapenem-β-lactamase inhibitor combination, <i>imipenem/relebactam</i> (IMI-REL), has been recently approved for treatment of infections with limited or no alternative treatment options. In this study, we described the emergence of the IMI-REL-resistance in a KPC-producing <i>Klebsiella pneumoniae</i> (KPC-Kp) strain collected from a hematological patient with no evidence of prior colonization. Interestingly, IMI-REL-resistance was associated with meropenem/vaborbactam (MER-VAB) cross-resistance but was not associated with cross-resistance to ceftazidime/avibactam (CAZ-AVI). Although treatment with CAZ-AVI and gentamicin completely eradicated the infection due KPC-Kp cross-resistance to IMI-REL and MER-VAB, the patient became colonized subsequently by KPC-Kp strains susceptible to IMI-REL and MER-VAB. Whole-genome sequencing performed by hybrid approach using Illumina and Oxford Nanopore platforms demonstrated that all KPC-Kp strains isolated from hematological patient belonged to the ST512 and were clonally related. Analysis of antimicrobial and porins genes demonstrated that cross-resistance to IMI-REL and MER-VAB was associated with increased <i>bla</i><sub>KPC-3</sub> copy number and truncated OmpK35 and OmpK36 with GD134-135 insertion. Phylogenetic analysis demonstrated that KPC-Kp cross-resistance to IMI-REL and MER-VAB was clonally related to a KPC-Kp resistant to IMI-REL as previously described, demonstrating the spread of this multidrug resistant clone in the hematological unit. In conclusion, the results presented in this study reported the emergence of cross-resistance to MER-VAB and IMI-REL in a KPC-Kp strain isolated from a hematological patient and highlight the potential development and diffusion of new multidrug resistance traits.https://www.mdpi.com/2076-2607/10/4/778imipenem/relebactammeropenem/vaborbactamcross-resistance<i>bla</i> <sub>KPC</sub> <sub>-3</sub> |
| spellingShingle | Paolo Gaibani Linda Bussini Stefano Amadesi Michele Bartoletti Federica Bovo Tiziana Lazzarotto Pierluigi Viale Simone Ambretti Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological Patient Microorganisms imipenem/relebactam meropenem/vaborbactam cross-resistance <i>bla</i> <sub>KPC</sub> <sub>-3</sub> |
| title | Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological Patient |
| title_full | Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological Patient |
| title_fullStr | Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological Patient |
| title_full_unstemmed | Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological Patient |
| title_short | Successful Treatment of Bloodstream Infection due to a KPC-Producing Klebsiella Pneumoniae Resistant to Imipenem/Relebactam in a Hematological Patient |
| title_sort | successful treatment of bloodstream infection due to a kpc producing klebsiella pneumoniae resistant to imipenem relebactam in a hematological patient |
| topic | imipenem/relebactam meropenem/vaborbactam cross-resistance <i>bla</i> <sub>KPC</sub> <sub>-3</sub> |
| url | https://www.mdpi.com/2076-2607/10/4/778 |
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