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Clinical outcomes in elderly patients with infections caused by NDM-producing Klebsiella pneumoniae: results from a real-life retrospective single center study in an endemic area

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Abstract

Real-life outcomes data for elderly patients with infections caused by Klebsiella pneumoniae producing New Delhi metallo-beta-lactamase (NDM-Kp) are lacking. We conducted a retrospective cohort study enrolling 33 consecutive adult patients (mean age 77.4 years; 48.5% males; mean Charlson Comorbidity Index—CCI 5.9) hospitalized for NDM-Kp infections during a 24-month period in an Italian highly endemic area. 78.8% were admitted to Internal Medicine ward. 45.4% of patients had bloodstream infections (BSI), 39.4% urinary tract infections (UTI) without BSI, 9.1% respiratory tract infections and 6.1% intra-abdominal infections. 93.9% had rectal colonization.

Adequate definitive antibiotic therapy (mainly represented by aztreonam plus ceftazidime/avibactam) was provided to 36.4% of cases. Mean age and CCI of patients adequately treated were significantly lower than those inadequately treated (71.2 vs 80.9 years, p = 0.041, and 4.6 vs 6.7, p = 0.040, respectively). Patients adequately treated had a mean hospitalization length significantly higher (28 vs 15 days, p = 0.016). The overall 30-day survival rate of patients adequately and inadequately treated was 83.3% and 57.1%, respectively: this difference was not statistically significant. Mean age and CCI of 22 patients who survived at 30 days were lower than those of 11 patients who died (73.7 vs 84.8 years, p = 0.003, and 5.3 vs 7.2, p = 0.049, respectively). Twelve survivors received an inadequate therapy: 8/12 had UTI. Six of nine patients inadequately treated who died within 30 days, died before microbiological diagnosis. Our study provides real-life data on outcomes of elderly and multimorbid patients hospitalized for infections caused by NDM-Kp. Further studies with larger sample size are warranted.

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References

  1. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K et al (2009) Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 53(12):5046–5054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wu W, Feng Y, Tang G, Qiao F, McNally A, Zong Z (2019) NDM metallo-β-lactamases and their bacterial producers in health care settings. Clin Microbiol Rev 32(2):e00115-18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Marshall S, Hujer AM, Rojas LJ, Papp-Wallace KM, Humphries RM, Spellberg B et al (2017) Can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in enterobacteriaceae? Antimicrob Agents Chemother 61(4):e02243-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lohans CT, Brem J, Schofield CJ (2017) New Delhi metallo-β-lactamase 1 catalyzes avibactam and aztreonam hydrolysis. Antimicrob Agents Chemother 61(12):e01224-e1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Karlowsky JA, Kazmierczak KM, de Jonge BLM, Hackel MA, Sahm DF, Bradford PA (2017) In vitro activity of aztreonam-avibactam against enterobacteriaceae and pseudomonas aeruginosa isolated by clinical laboratories in 40 countries from 2012 to 2015. Antimicrob Agents Chemother 61(9):e00472-e517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Farhat N, Khan AU (2020) Evolving trends of New Delhi metallo-betalactamse (NDM) variants: a threat to antimicrobial resistance. Infect Genet Evol 86:104588

    Article  CAS  PubMed  Google Scholar 

  7. Khan AU, Maryam L, Zarrilli R (2017) Structure, genetics and worldwide spread of New Delhi metallo-β-lactamase (NDM): a threat to public health. BMC Microbiol. 17(1):101

    Article  PubMed  PubMed Central  Google Scholar 

  8. Tavoschi L, Forni S, Porretta A, Righi L, Pieralli F, Menichetti F, On Behalf Of The Tuscan Clinical Microbiology Laboratory Network et al (2020) Prolonged outbreak of New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE), Tuscany, Italy, 2018 to 2019. Euro Surveill 25(6):2000085

    Article  PubMed  PubMed Central  Google Scholar 

  9. Seo H, Kim HJ, Kim MJ, Chong YP, Kim SH, Lee SO et al (2021) Comparison of clinical outcomes of patients infected with KPC- and NDM-producing Enterobacterales: a retrospective cohort study. Clin Microbiol Infect 27(8):1167.e1-1167.e8

    Article  PubMed  Google Scholar 

  10. Snyder BM, Montague BT, Anandan S, Madabhushi AG, Pragasam AK, Verghese VP et al (2019) Risk factors and epidemiologic predictors of blood stream infections with New Delhi metallo-b-lactamase (NDM-1) producing Enterobacteriaceae. Epidemiol Infect 147:e137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mauri C, Maraolo AE, Di Bella S, Luzzaro F, Principe L (2021) The Revival of Aztreonam in combination with avibactam against metallo-beta lactamase-producing gram-negatives: a systematic review of in vitro studies and clinical cases. Antibiotics 10:1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gatti M, Viaggi B, Rossolini GM, Pea F, Viale P (2021) An evidence-based multidisciplinary approach focused at creating algorithms for targeted therapy of bsis, cutis, and ciais caused by Enterobacterales in critically ill adult patients. Infect Drug Resist 14:2461–2498

    Article  PubMed  PubMed Central  Google Scholar 

  13. Falcone M, Daikos GL, Tiseo G, Bassoulis D, Giordano C, Galfo V, Leonildi A, Tagliaferri E, Barnini S, Sani S, Farcomeni A, Ghiadoni L, Menichetti F (2021) Efficacy of ceftazidime-avibactam plus aztreonam in patients with bloodstream infections caused by metallo-β-lactamase-producing Enterobacterales. Clin Infect Dis 72(11):1871–1878

    Article  CAS  PubMed  Google Scholar 

  14. Bassetti M, Echols R, Matsunaga Y, Ariyasu M, Doi Y, Ferrer R et al (2021) Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. Lancet Infect Dis 21(2):226–240

    Article  CAS  PubMed  Google Scholar 

  15. Paul M, Carrara E, Retamar P, Tängdén T, Bitterman R, Bonomo RA et al (2022) European society of clinical microbiology and infectious diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine). Clin Microbiol Infect 28(4):521–547

    Article  CAS  PubMed  Google Scholar 

  16. https://www.who.int/. Accessed 6 Apr 2023

  17. R Core Team (2022) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria

    Google Scholar 

  18. Stone NR, Woodford N, Livermore DM, Howard J, Pike R, Mushtaq S et al (2011) Breakthrough bacteraemia due to tigecycline-resistant E. coli with New Delhi metallo-β-lactamase (NDM)-1 successfully treated with colistin in a patient with calciphylaxis. J Antimicrob Chemother 66(11):2677–2678

    Article  CAS  PubMed  Google Scholar 

  19. Petersen-Morfin S, Bocanegra-Ibarias P, Morfin-Otero R et al (2017) New Delhi metallo-beta-lactamase (NDM-1)-Producing Klebsiella pneumoniae isolated from a burned patient. Am J Case Rep 18:805–809

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chien JM, Koh TH, Chan KS, Chuah TH, Tan TT (2012) Successful treatment of NDM-1 Klebsiella pneumoniae bacteraemia in a neutropenic patient. Scand J Infect Dis 44(4):312–314

    Article  CAS  PubMed  Google Scholar 

  21. Seija V, Medina Presentado JC, Bado I, Papa Ezdra R, Batista N, Gutierrez C et al (2015) Sepsis caused by New Delhi metallo-β-lactamase (blaNDM-1) and qnrD-producing Morganella morganii, treated successfully with fosfomycin and meropenem: case report and literature review. Int J Infect Dis 30:20–26

    Article  PubMed  Google Scholar 

  22. Daikos GL, Tsaousi S, Tzouvelekis LS, Anyfantis I, Psichogiou M, Argyropoulou A et al (2014) Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother 58(4):2322–2328

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Paño-Pardo JR et al (2017) Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis 17(7):726–734

    Article  PubMed  Google Scholar 

  24. Meini S, Laureano R, Tascini C, Arena F, Fani L, Frullini A, Passaleva MT, Roberts AT, Mannini D, Sbrana F, Ripoli A, Rossolini GM (2018) Clinical outcomes of elderly patients with bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae in an Italian internal medicine ward. Eur J Intern Med 48:50–56

    Article  PubMed  Google Scholar 

  25. Xu L, Sun X, Ma X (2017) Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob 16(1):18

    Article  PubMed  PubMed Central  Google Scholar 

  26. Tumbarello M, Trecarichi EM, De Rosa FG, Giannella M, Giacobbe DR, Bassetti M, Losito AR, Bartoletti M, Del Bono V, Corcione S, Maiuro G, Tedeschi S, Celani L, Cardellino CS, Spanu T, Marchese A, Ambretti S, Cauda R, Viscoli C, Viale P, ISGRI-SITA (Italian Study Group on Resistant Infections of the SocietàItalianaTerapiaAntinfettiva) (2015) Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother 70(7):2133–43

    Article  CAS  PubMed  Google Scholar 

  27. Hyle EP, Lipworth AD, Zaoutis TE, Nachamkin I, Bilker WB, Lautenbach E (2005) Impact of inadequate initial antimicrobial therapy on mortality in infections due to extended-spectrum beta-lactamase-producing enterobacteriaceae: variability by site of infection. Arch Intern Med 165(12):1375–1380

    Article  PubMed  Google Scholar 

  28. Ammerlaan H, Seifert H, Harbarth S, Brun-Buisson C, Torres A, Antonelli M, European Practices of Infections with Staphylococcus aureus (SEPIA) Study Group et al (2009) Adequacy of antimicrobial treatment and outcome of staphylococcus aureus bacteremia in 9 Western European countries. Clin Infect Dis 49(7):997–1005

    Article  CAS  PubMed  Google Scholar 

  29. Eklöf J, Gliese KM, Ingebrigtsen TS, Bodtger U, Jensen JS (2019) Antibiotic treatment adequacy and death among patients with Pseudomonas aeruginosa airway infection. PLoS ONE 14(12):e0226935

    Article  PubMed  PubMed Central  Google Scholar 

  30. Boattini M, Bianco G, Iannaccone M, Ghibaudo D, Almeida A, Cavallo R, Costa C (2021) Fast-track identification of CTX-M-extended-spectrum-β-lactamase- and carbapenemase-producing Enterobacterales in bloodstream infections: implications on the likelihood of deduction of antibiotic susceptibility in emergency and internal medicine departments. Eur J Clin Microbiol Infect Dis 40(7):1495–1501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Quadri F, Mazer-Amirshahi M, Fox ER, Hawley KL, Pines JM, Zocchi MS, May L (2015) Antibacterial drug shortages from 2001 to 2013: implications for clinical practice. Clin Infect Dis 60(12):1737–1742

    Article  PubMed  Google Scholar 

  32. Simner PJ, Patel R (2020) Cefiderocol antimicrobial susceptibility testing considerations: the achilles’ heel of the trojan horse? J Clin Microbiol 59(1):e00951-e1020

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Internal Medicine Unit, Felice Lotti Hospital of Pontedera, Azienda Unità Sanitaria Locale Toscana Nord-Ovest, Pisa, Italy

    Maddalena Mura, Benedetta Longo, Roberto Andreini & Simone Meini

  2. Fondazione Toscana Gabriele Monasterio, Pisa, Italy

    Francesco Sbrana & Andrea Ripoli

  3. Microbiology Laboratory, Felice Lotti Hospital of Pontedera, Azienda Unità Sanitaria Locale Toscana Nord-Ovest, Pisa, Italy

    Elisabetta Andreoli

  4. Infectious Disease Unit, Hospital of Livorno, Azienda Unità Sanitaria Locale Toscana Nord-Ovest, Pisa, Italy

    Spartaco Sani

  5. Department of Medical Biotechnologies, University of Siena, Siena, Italy

    Mario Tumbarello

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  1. Maddalena Mura
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Correspondence to Maddalena Mura.

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Mura, M., Longo, B., Andreini, R. et al. Clinical outcomes in elderly patients with infections caused by NDM-producing Klebsiella pneumoniae: results from a real-life retrospective single center study in an endemic area. Intern Emerg Med 18, 2261–2269 (2023). https://doi.org/10.1007/s11739-023-03416-3

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