Rapid diagnostics and ceftazidime/avibactam for KPC-producing Klebsiella pneumoniae bloodstream infections: impact on mortality and role of combination therapy

Boattini, Matteo; Bianco, Gabriele; Charrier, Lorena; Comini, Sara; Iannaccone, Marco; Almeida, André; Cavallo, Rossana; Rosa, Francesco Giuseppe De; Costa, Cristina

doi:10.1007/s10096-023-04577-x

Cited by 14 publications

(11 citation statements)

References 29 publications

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“…This study did not find any statistically significant differences in prognosis between monotherapy and combination therapy with CAZ/AVI for pulmonary CRKP infections, which may be due to the favorable tissue distribution of CAZ/AVI in airway epithelial cells [ 19 ], consistent with the results of Tumbarello et al The use of CAZ/AVI in bloodstream infections was found to be associated with better prognosis [ 20 ]. This study did not find any statistically significant differences in prognosis between monotherapy and combination therapy with CAZ/AVI for bloodstream CRKP infections, and recent studies have not found any significant effects of CAZ/AVI combination therapy on the prognosis of bloodstream CRKP infections [ 21 ]. Recent small-sample case studies have suggested that CAZ/AVI combination therapy is an effective treatment for central nervous system CRKP infections [ 22 ].…”

Section: Discussionmentioning

confidence: 52%

Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study

Lin,

Zhang,

Zhou

et al. 2023

Infect Dis Ther

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Introduction This study aimed to evaluate the different efficacies between monotherapy and combination therapy with ceftazidime/avibactam (CAZ/AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection. Methods We retrospectively analyzed observational multicenter data from 38 hospitals in China. Multivariate regression analysis was used to explore the association between combination therapy with CAZ/AVI and in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to validate our findings. Results A total of 132 eligible patients were divided into CAZ/AVI combination therapy ( n = 43) and monotherapy ( n = 89) cohorts. Multivariate logistic regression showed that there was no statistically significant relationship between combination therapy and a lower risk of in-hospital mortality [odds ratio (OR) 0.907, 95% confidence interval (CI) 0.329–2.498, p = 0.850]. In the subgroup of critical patients who were in the intensive care unit (ICU) (OR 0.943, 95% CI 0.221–4.033, p = 0.937) or with sequential organ failure assessment (SOFA) ≥ 3 (OR 0.733, 95% CI 0.191–2.808, p = 0.650), CAZ/AVI combination therapy was not a lower risk factor for in-hospital mortality. Moreover, in the subgroup of patients using CAZ/AVI plus tigecycline (accounting for 46.5% in the combination therapy) compared with CAZ/AVI monotherapy, there was no statistical difference between the two groups in in-hospital mortality, nor in the subgroup of patients with CRKP-associated pneumonia. Conclusion Combination therapy (or CAZ/AVI combined with tigecycline) and monotherapy with CAZ/AVI had similar prognoses in patients with only CRKP infection (or CRKP-associated pneumonia), as well as in critically ill patients. Larger randomized controlled trials are warranted to confirm these findings. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00852-8.

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Section: Discussionmentioning

confidence: 52%

Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study

Lin,

Zhang,

Zhou

et al. 2023

Infect Dis Ther

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“…First, in the first wave of the pandemic, due to the severity of the SARS-CoV-2 infection, a higher proportion of deaths within the study occurred in the early stages of hospitalization; therefore, these patients had less time to develop superinfections and to obtain microbiological investigation results. In addition, the successful implementation of rapid diagnostics coupled with infectious counselling intervention for the timely and appropriate use of new drugs such as ceftazidime/avibactam and cefiderocol may suffice to counteract the putative positive influence of such infections on mortality [ 34 , 42 , 43 ].…”

Section: Discussionmentioning

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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“…In the light of the excellent clinical results obtained [ 3 – 9 ], the judicious prescription of ceftazidime/avibactam and the implementation of a surveillance system dedicated to resistance emergence detection should be aimed at. For the time being, KPC-Kp resistance to ceftazidime/avibactam is not perceived as a problem at scale, being deemed a rather uncommon phenomenon [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…The alert issued in Italy based on data from 2014–2017 highlighted the endemic burden of KPC-Kp often characterized by a relevant number of bloodstream infections (BSIs) and endangering patient safety [ 2 ]. In 2018, the novel β-lactam/β-lactamase inhibitor combination ceftazidime/avibactam was introduced into clinical practice having shown excellent clinical activity against KPC-Kp [ 3 – 9 ]. More recently, it has been reported as the only independent survival predictor among KPC-Kp BSI patients [ 6 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…In 2018, the novel β-lactam/β-lactamase inhibitor combination ceftazidime/avibactam was introduced into clinical practice having shown excellent clinical activity against KPC-Kp [ 3 – 9 ]. More recently, it has been reported as the only independent survival predictor among KPC-Kp BSI patients [ 6 , 9 ]. However, 5 years following the onset of clinical use, in vivo selection events of ceftazidime/avibactam-resistant strains [ 10 , 11 ] and nosocomial outbreaks of ceftazidime/avibactam-resistant KPC-Kp have been reported [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Prevalence and mortality of ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae bloodstream infections (2018–2022)

Boattini,

Bianco,

Bastos

et al. 2023

Eur J Clin Microbiol Infect Dis

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Introduction Ceftazidime/avibactam-resistance in Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is a topic of great interest for epidemiological, diagnostic, and therapeutical reasons. However, data on its prevalence and burden on mortality in patients with bloodstream infection (BSI) are lacking. This study was aimed at identifying risk factors for mortality in patients suffering from ceftazidime/avibactam-resistant KPC-Kp BSI. Methods An observational retrospective study (January 2018–December 2022) was conducted at a tertiary hospital including all consecutive hospitalized adult patients with a ceftazidime/avibactam-resistant KPC-Kp BSI. Data on baseline clinical features, management, and admission outcomes were analyzed. Results Over the study period, among all the KPC-Kp BSI events recorded, 38 (10.5%) were caused by ceftazidime/avibactam-resistant KPC-Kp strains, 37 events being finally included. The ceftazidime/avibactam-resistant KPC-Kp strains revealed susceptibility restoration to at least one carbapenem in more than 60% of cases. In-hospital and 30-day all-cause mortality rates were 22% and 16.2%, respectively. Non-survivors suffered from more baseline comorbidities and experienced a more severe ceftazidime/avibactam-resistant KPC-Kp BSI presentation (i.e., both the Pitt Bacteremia and INCREMENT-CPE scores were significantly higher). Presenting with a higher Charlson Comorbidity Index, chronic kidney disease—KDIGO stage 3A or worse—having recently gone through renal replacement therapy, having suffered from an acute kidney injury following the ceftazidime/avibactam-resistant KPC-Kp BSI, and being admitted for cardiac surgery were the strongest predictors of mortality. Conclusion Ceftazidime/avibactam resistance in KPC-Kp BSI easily emerged in our highly KPC-Kp endemic area with remarkable mortality rates. Our findings might provide physicians possibly actionable information when managing patients with a ceftazidime/avibactam-resistant KPC-Kp BSI.

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Rapid diagnostics and ceftazidime/avibactam for KPC-producing Klebsiella pneumoniae bloodstream infections: impact on mortality and role of combination therapy

Cited by 14 publications

References 29 publications

Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study

Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study

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

Prevalence and mortality of ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae bloodstream infections (2018–2022)

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