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. 2022 Oct 31;11(11):1519.
doi: 10.3390/antibiotics11111519.

Prompt and Appropriate Antimicrobial Therapy Improves Outcomes of NDM-Producing and KPC-Producing Klebsiella pneumoniae Bloodstream Infections in Patients Hospitalized for COVID-19: A Comparative Retrospective Case-Series

Davide Fiore Bavaro  1 , Alessandra Belati  1 , Lucia Diella  1 , Melita Anna Poli  2 , Angela Calamo  2 , Giovanna De Candia  3 , Maurantonio Altamura  2 , Felicia Anna Spadavecchia  3 , Gaetano Brindicci  1 , Nicolò De Gennaro  1 , Francesco Di Gennaro  1 , Annalisa Saracino  1 , Sergio Carbonara  2
Affiliations

Prompt and Appropriate Antimicrobial Therapy Improves Outcomes of NDM-Producing and KPC-Producing Klebsiella pneumoniae Bloodstream Infections in Patients Hospitalized for COVID-19: A Comparative Retrospective Case-Series

Davide Fiore Bavaro et al. Antibiotics (Basel). .

Abstract

Secondary bloodstream infections (BSIs) caused by KPC- and NDM-producing Klebsiella pneumoniae (K.p.) during the course of COVID-19 infections lead to significant mortality. Herein, a comparative retrospective case series of KPC- or NDM-K.p. BSIs occurring in COVID-19 subjects treated with Ceftazidime/Avibactam (CAZ/AVI) for KPC-K.p., or CAZ/AVI+ Aztreonam (ATM) for NDM-K.p is reported. All patients hospitalized for COVID-19 in two Italian hospitals with a BSI between March and September 2021 were included. The main outcome was 14-day mortality. Overall, 44 patients were included: 23 with KPC-K.p. and 21 with NDM-K.p. BSIs. The median (q1-q3) age was 67 (57-75) years, and 32 (72%) were males. The two groups were similar in terms of baseline comorbidity, or severity of COVID-19. Notably, 14-day mortality of KPC-K.p. BSIs and NDM-K.p. BSIs (26% vs. 38%, p = 0.521) and 28-day mortality (35% vs. 48%, p = 0.541) were similar. A Cox regression model of delayed initiation of an appropriate antibiotic therapy after the onset of symptoms independently predicted mortality: initiation between 24 and 72 h (aHR = 12.03; 95% CI = 1.10-130, p = 0.041); and initiation after 72h (aHR = 36.9, 95% CI = 3.22-424, p = 0.004). Moreover, a trend towards an increased risk of mortality was observed for polymicrobial infections (aHR = 3.73, 95% CI = 0.87-15.8, p = 0.074), while a protective effect was observed for a beta-lactam loading dose at the start of treatment (aHR = 0.16, 95% CI = 0.02-1.10, p = 0.064). The high mortality of KPC and NDM-K.p. BSIs in COVID-19 patients may be reduced by an early and appropriate antibiotic therapy. Further efforts should be made to develop antimicrobial stewardship and infection control programs in COVID-19 wards.

Keywords: COVID-19; KPC-Klebsiella pneumoniae; NDM-Klebsiella pneumoniae; SARS-CoV2; bloodstream infections.

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Conflict of interest statement

No author has any conflict of interest to declare related to the article.

Figures

Figure 1
Figure 1
Patient flow-chart. Legend: BSI = Bloodstream infection; CR-K.p. = Carbapenem-resistant K. pneumoniae; KPC-K.p. = K. pneumoniae producer of K. pneumoniae carbapenemase; NDM-K.p. = K. pneumoniae producer of New Delhi metallo-β-lactamase. * Twenty-nine out of the 44 patients showed a prior colonization with the same pathogen responsible for the BSI.
Figure 2
Figure 2
Kaplan–Meier survival curves for 14-day risk of mortality according to (a) time from symptom onset to targeted therapy; (b) mono- or polymicrobial BSI; (c) use of Beta-lactam loading dose.
Figure 2
Figure 2
Kaplan–Meier survival curves for 14-day risk of mortality according to (a) time from symptom onset to targeted therapy; (b) mono- or polymicrobial BSI; (c) use of Beta-lactam loading dose.
See this image and copyright information in PMC

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