The antibiotic arms race: current and emerging therapy for<i>Klebsiella pneumoniae</i>carbapenemase (KPC) - producing bacteria

Plazak, Michael E; Heil, Emily L.

doi:10.1080/14656566.2018.1538354

Cited by 12 publications

(10 citation statements)

References 91 publications

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“…Owing to the widespread clinical use of carbapenems in recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP)-associated bacterial infections have become a major threat to human health 1 and the principal reason for the failure of clinical first-line antibiotic treatment. 2 Klebsiella pneumoniae carbapenemase (KPC), especially KPC-2, production is the primary mechanism of carbapenem resistance in China. 3 Carbapenem-resistant Enterobacterales (CRE) bacteria cause the death of 42.14% of patients with infection and 73% of severely infected patients with septic shock.…”

Section: Introductionmentioning

confidence: 99%

Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Sequence Type 11 Due to a Mutation in Plasmid-Borne blakpc-2 to blakpc-33, in Henan, China

Li¹,

Li²,

Dong³

et al. 2021

IDR

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Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a serious problem worldwide. Herein, we describe the evolution of ceftazidime-avibactam (CZA) resistance by sequencing clinical isolates from a patient with CRKP infection undergoing CZA treatment. Patients and Methods: In this study, six CRKP strains were isolated from sputum and blood samples of a patient with CRKP infection after intracerebral hemorrhage. Two strains were selected for whole-genome analysis. Results: Drug susceptibility testing showed that the MIC of CZA for CRKP strains isolated after 6 days of CZA treatment was 64-fold higher than that for three CRKP strains isolated before CZA treatment (4 vs >256 μg/mL), whereas the MIC of imipenem and meropenem was 128-fold (>32 vs 0.25 μg/mL) and 16-fold (> 32 vs 2 μg/mL) lower relatively, respectively. Multilocus sequence typing showed that all six CRKP strains isolated from the patient were ST11 and pulsed-field gel electrophoresis confirmed that they were of the same clone. Two strains were selected for whole-genome analysis. The aspartic acid residue at position 179 in the Ω loop was replaced by a tyrosine residue in the resistant strain, and the plasmid carried a bla KPC-2 to bla KPC-33 mutation. The results of the modified carbapenem inactivation method and the carbapenemase inhibitor enhancement and colloidal gold enzyme immunochromatographic assays for bla KPC-33 were negative. Conclusion: This is the first report from Henan to show that treatment with CZA for 6 days can cause mutations and change the phenotype from CZA sensitive to resistant. Therefore, routine testing for drug susceptibility and carbapenemase phenotypes should be conducted during treatment with CZA, and genotype determination is essential.

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Section: Introductionmentioning

confidence: 99%

Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Sequence Type 11 Due to a Mutation in Plasmid-Borne blakpc-2 to blakpc-33, in Henan, China

Li¹,

Li²,

Dong³

et al. 2021

IDR

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“…The most relevant mechanism of carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemases (KPCs) are the most common enzymes reported worldwide and capable of deactivating all of the beta-lactams [ 20 ]. Among the metallo-beta-lactamases (MBL), New Delhi MBL (NDM), Verona integron-encoded MBL (VIM) and imipenemase MBL (IMP) are the most common enzymes identified worldwide [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of a Lipidated Temporin L Analogue against Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates

et al. 2021

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Over the years, the increasing acquisition of antibiotic resistance genes has led to the emergence of highly resistant bacterial strains and the loss of standard antibiotics’ efficacy, including β-lactam/β-lactamase inhibitor combinations and the last line carbapenems. Klebsiella pneumoniae is considered one of the major exponents of a group of multidrug-resistant ESKAPE pathogens responsible for serious healthcare-associated infections. In this study, we proved the antimicrobial activity of two analogues of Temporin L against twenty carbapenemase-producing K. pneumoniae clinical isolates. According to the antibiotic susceptibility assay, all the K. pneumoniae strains were resistant to at least one other class of antibiotics, in addition to beta-lactams. Peptides 1B and C showed activity on all test strains, but the lipidated analogue C expressed the greater antimicrobial properties, with MIC values ranging from 6.25 to 25 µM. Furthermore, the peptide C showed bactericidal activity at MIC values. The results clearly highlight the great potential of antimicrobial peptides both as a new treatment option for difficult-to-treat infections and as a new strategy of drug-resistance control.

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“…Actualmente, existe evidencia de que con algunos nuevos antibióticos, como ceftazidima/avibactam, no sería necesario la combinación con otros antibióticos (64,65).…”

Section: ) Evitar El Tratamiento Antibiótico Combinado En Las Infecciones Por Bgnunclassified

12 pasos para reducir la incidencia de carbapenemasas

Clara¹,

Desse²,

Nuccetelli³

et al. 2021

ASEI

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La resistencia a los antimicrobianos es un grave problema para la salud mundial. Es aún más crítico en los hospitales debido a la aparición de bacterias Gram negativas resistentes a múltiples fármacos, asociadas a una alta mortalidad. Las opciones de tratamiento en estos casos son escasas, en general de alto costo. La alta densidad de consumo de antibióticos y la transmisión cruzada en este entorno amplifican este problema. Hay más evidencia del impacto de las medidas de control de infecciones que de las intervenciones de comités de antimicrobianos para mitigarlo. Además, pocos países cuentan con programas sólidos de control de infecciones para enfrentar este problema. En la presente revisión se propone una serie de 12 pasos a adoptar para mitigar la prevalencia de resistencia antimicrobiana y reducir la incidencia de carbapenemasas en las instituciones de salud. Estas recomendaciones deben interpretase como un ¨bundle¨ o paquete de medidas, en el cual todas son importantes. Aquellas que involucran la prevención de infecciones y/o colonizaciones y su diseminación son las de mayor impacto demostrado hasta ahora. Es esencial que los programas de optimización de uso de antimicrobianos cuenten con el empoderamiento de la conducción de las instituciones donde se lleven a cabo, así como también que estén constituidos por un equipo multidisciplinario eficiente, sólidamente entrenado, con metas y métricas objetivas y auditorias periódicas. También es recomendable que se incluyan recomendaciones para los tratamientos en pacientes en cuidados de fin de vida.

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The antibiotic arms race: current and emerging therapy forKlebsiella pneumoniaecarbapenemase (KPC) - producing bacteria

Cited by 12 publications

References 91 publications

Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Sequence Type 11 Due to a Mutation in Plasmid-Borne blakpc-2 to blakpc-33, in Henan, China

Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Sequence Type 11 Due to a Mutation in Plasmid-Borne blakpc-2 to blakpc-33, in Henan, China

Antimicrobial Activity of a Lipidated Temporin L Analogue against Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates

12 pasos para reducir la incidencia de carbapenemasas

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