Deciphering variable resistance to novel carbapenem-based β-lactamase inhibitor combinations in a multi-clonal outbreak caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae resistant to ceftazidime/avibactam

Pilato, Vincenzo Di; Principe, Luigi; Andriani, Lilia; Aiezza, Noemi; Coppi, Marco; Ricci, Silvia; Giani, Tommaso; Luzzaro, Francesco; Rossolini, Gian María

doi:10.1016/j.cmi.2022.11.011

Cited by 26 publications

(18 citation statements)

References 27 publications

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“…However, it should be considered that KPC-producing Klebsiella pneumonia with specific mechanisms conferring resistance to CAZ-AVI (such as D179Y variants) has been reported worldwide. In these cases, alternative regimens including meropenem/vaborbactam or imipenem/relebactam should be considered [ 63 , 64 ]. Again, the knowledge of local epidemiology is crucial, and an individualized approach is needed for the management of OLT recipients with MDRO infections after transplantation.…”

Section: Resultsmentioning

confidence: 99%

Early Intra-Abdominal Bacterial Infections after Orthotopic Liver Transplantation: A Narrative Review for Clinicians

et al. 2023

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Despite recent advances in the transplant field, infectious complications after orthotopic liver transplantation (OLT) are major causes of morbidity and mortality. Bacterial intra-abdominal infections (IAIs) are predominant during the first month post-transplantation and affect patient and graft survival. Recently, the emergence of multidrug resistant bacteria has generated great concern in OLT patients. We performed this narrative review of the literature in order to propose a “ready-to-use” flowchart for reasoned empirical antibiotic therapy in the case of suspected post-OLT IAIs. The review was ultimately organized into four sections: “Epidemiology and predisposing factors for IAI”; “Surgical-site infections and perioperative prophylaxis”; “MDRO colonization and infections”; and “Reasoned-empirical antibiotic therapy in early intra-abdominal infections post OLT and source control”. Multidisciplinary teamwork is warranted to individualize strategies for the prevention and treatment of IAIs in OLT recipients, taking into account each patient’s risk factors, the surgical characteristics, and the local bacterial epidemiology.

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Section: Resultsmentioning

confidence: 99%

Early Intra-Abdominal Bacterial Infections after Orthotopic Liver Transplantation: A Narrative Review for Clinicians

et al. 2023

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“…Tiri et al reported that the incidence of KPC-producing Klebsiella pneumoniae in COVID-19 ICU patients increased significantly from 6.7% in 2019 to 50% in 2020 [ 29 ]. Likewise, several carbapenemase-producing Enterobacterales outbreaks (including KPC-producing Klebsiella pneumoniae , ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae and NDM-producers) have been reported worldwide [ 16 , 17 , 18 , 30 , 31 ]. A review of studies on carbapenem-resistant Klebsiella pneumoniae in COVID-19 patients from six countries (Italy, China, Egypt, United States, Spain, and Peru) showed that 84% of infected patients were male, with a mean age of 61 years, and the predominant carbapenemases were KPC and NDM.…”

Section: Discussionmentioning

confidence: 99%

“…The antibiotic resistance pattern of these pathogens is very diverse and dependent, among other factors, on local epidemiology and intensive care practices [ 7 , 11 , 12 , 13 , 14 , 15 ]. The data on carbapenem resistance for Acinetobacter baumannii have attracted particular attention given its independent association with 14-day mortality [ 11 ] and the risk of developing superinfections [ 14 ], and several outbreaks of ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae have also been reported [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Impact on Mortality of Colonization and Super-Infection by Carbapenem-Resistant Gram-Negative Organisms in COVID-19 Hospitalized Patients

Casale,

Bianco,

Bastos

et al. 2023

Viruses

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Background: The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients. Methods: Herein, a retrospective study was carried out using data from adult patients hospitalized for COVID-19. The interaction between in-hospital mortality and rectal carriage and superinfection by carbapenemase-producing Enterobacterales and/or carbapenem-resistant Acinetobacter baumannii was assessed. Results: The incidence of KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage was 30%. Bloodstream infection and/or pneumonia due to KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii occurred in 20% of patients. A higher Charlson comorbidity index (OR 1.41, 95% CI 1.24–1.59), being submitted to invasive mechanical ventilation/ECMO ≥ 96 h (OR 6.34, 95% CI 3.18–12.62), being treated with systemic corticosteroids (OR 4.67, 95% CI 2.43–9.05) and having lymphopenia at the time of admission (OR 0.54, 95% CI 0.40–0.72) were the features most strongly associated with in-hospital mortality. Conclusions: Although KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage, and/or bloodstream infection/pneumonia were diagnosed in a remarkable percentage of COVID-19 patients, their impact on in-hospital mortality was not significant. Further studies are needed to assess the burden of antimicrobial resistance as a legacy of COVID-19 in order to identify future prevention opportunities.

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“…This could suggest a different level of expression of the KPC enzyme that cannot be revealed by WGS analysis. In a previous paper, Di Pilato et al found increased KPC production as the most common resistance mechanism in their collection of KP isolates resistant to CAZ-AVI [ 30 ]. These isolates harbored bla KPC-3, lacked functional OmpK35 and carried mutated OmpK36 and were associated with resistance to MVB, pointing out the possible step-wise development of resistance against novel BLICs, depending on the magnitude of the bla KPC gene dosage in a similar genetic background [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing and Molecular Analysis of Ceftazidime–Avibactam-Resistant KPC-Producing Klebsiella pneumoniae from Intestinal Colonization in Elderly Patients

et al. 2023

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Ceftazidime–avibactam (CAZ-AVI) is an active antibiotic combination of a β-lactam–β-lactamase inhibitor against carbapenemase-producing Enterobacterales. Reports of resistance to CAZ-AVI other than metallo-β-lactamases have increased in recent years. The aim of this study was to analyze KPC-Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI from the intestinal carriage of hospitalized elderly patients in Italy, in February 2018–January 2020. Characterization of CAZ-AVI-resistant KP isolates, including MLST, resistome, virulome and plasmid content, was performed by WGS analysis. Out of six CAZ-AVI-resistant KP isolates, three belonged to ST101 and three to ST512; two isolates produced KPC-3 (both ST512), four had mutated KPC-3 (KPC-31, in ST101 and ST512, and KPC-46, both ST101). All CAZ-AVI-resistant KP isolates were multidrug-resistant and carried several resistance genes. The yersiniabactin ybt9 gene cluster was present in all ST101 isolates, while, in ST512 isolates, no virulence genes were detected. Several plasmids were detected: IncF was present in all isolates, as well as IncR and Col440 in ST101 and IncX3 in ST512 isolates. In conclusion, it is important to monitor the circulation of K. pneumoniae resistant to CAZ-AVI to prevent the spread of clones causing difficult-to-treat infections. The presence of mutated KPC-3 in high-risk K. pneumoniae clones resistant to CAZ-AVI in hospitalized patients deserves attention.

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Deciphering variable resistance to novel carbapenem-based β-lactamase inhibitor combinations in a multi-clonal outbreak caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae resistant to ceftazidime/avibactam

Cited by 26 publications

References 27 publications

Early Intra-Abdominal Bacterial Infections after Orthotopic Liver Transplantation: A Narrative Review for Clinicians

Early Intra-Abdominal Bacterial Infections after Orthotopic Liver Transplantation: A Narrative Review for Clinicians

Prevalence and Impact on Mortality of Colonization and Super-Infection by Carbapenem-Resistant Gram-Negative Organisms in COVID-19 Hospitalized Patients

Whole-Genome Sequencing and Molecular Analysis of Ceftazidime–Avibactam-Resistant KPC-Producing Klebsiella pneumoniae from Intestinal Colonization in Elderly Patients

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