Infections caused by KPC-producing Klebsiella pneumoniae: Differences in therapy and mortality in a multicentre study

Mario Tumbarello, Enrico Maria Trecarichi, Francesco Giuseppe De Rosa, Maddalena Giannella, Daniele Roberto Giacobbe, Matteo Bassetti, Angela Raffaella Losito, Michele Bartoletti, Valerio Del Bono, Silvia Corcione, Giuseppe Maiuro, Sara Tedeschi, Luigi Celani, Chiara Simona Cardellino, Teresa Spanu, Anna Marchese, Simone Ambretti, Roberto Cauda, Claudio Viscoli, Pierluigi Viale

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

Objectives: Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals. Methods: The cohort included 661 adults with bloodstream infections (BSIs; n=447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible. Results: Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤ 8 mg/L. Conclusions: KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.

Original languageEnglish
Article numberdkv086
Pages (from-to)2133-2143
Number of pages11
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number7
DOIs
Publication statusPublished - Dec 6 2014

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Klebsiella pneumoniae
Multicenter Studies
meropenem
Mortality
Infection
APACHE
Septic Shock
Klebsiella Infections
Pharmaceutical Preparations
Colistin
Therapeutics
Urinary Tract
Critical Illness
Teaching Hospitals
Respiratory Tract Infections
Chronic Kidney Failure
Cohort Studies
Survival Rate
Retrospective Studies
Logistic Models

Keywords

  • Carbapenem resistance
  • Carbapenemases
  • Colistin resistance
  • Combination therapy
  • Inadequate empirical therapy
  • Meropenem MICs
  • Treatment

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Tumbarello, M., Trecarichi, E. M., De Rosa, F. G., Giannella, M., Giacobbe, D. R., Bassetti, M., ... Viale, P. (2014). Infections caused by KPC-producing Klebsiella pneumoniae: Differences in therapy and mortality in a multicentre study. Journal of Antimicrobial Chemotherapy, 70(7), 2133-2143. [dkv086]. https://doi.org/10.1093/jac/dkv086

Infections caused by KPC-producing Klebsiella pneumoniae : Differences in therapy and mortality in a multicentre study. / Tumbarello, Mario; Trecarichi, Enrico Maria; De Rosa, Francesco Giuseppe; Giannella, Maddalena; Giacobbe, Daniele Roberto; Bassetti, Matteo; Losito, Angela Raffaella; Bartoletti, Michele; Del Bono, Valerio; Corcione, Silvia; Maiuro, Giuseppe; Tedeschi, Sara; Celani, Luigi; Cardellino, Chiara Simona; Spanu, Teresa; Marchese, Anna; Ambretti, Simone; Cauda, Roberto; Viscoli, Claudio; Viale, Pierluigi.

In: Journal of Antimicrobial Chemotherapy, Vol. 70, No. 7, dkv086, 06.12.2014, p. 2133-2143.

Research output: Contribution to journalArticle

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 2014, 'Infections caused by KPC-producing Klebsiella pneumoniae: Differences in therapy and mortality in a multicentre study', Journal of Antimicrobial Chemotherapy, vol. 70, no. 7, dkv086, pp. 2133-2143. https://doi.org/10.1093/jac/dkv086
Tumbarello, Mario ; Trecarichi, Enrico Maria ; De Rosa, Francesco Giuseppe ; Giannella, Maddalena ; Giacobbe, Daniele Roberto ; Bassetti, Matteo ; Losito, Angela Raffaella ; Bartoletti, Michele ; Del Bono, Valerio ; Corcione, Silvia ; Maiuro, Giuseppe ; Tedeschi, Sara ; Celani, Luigi ; Cardellino, Chiara Simona ; Spanu, Teresa ; Marchese, Anna ; Ambretti, Simone ; Cauda, Roberto ; Viscoli, Claudio ; Viale, Pierluigi. / Infections caused by KPC-producing Klebsiella pneumoniae : Differences in therapy and mortality in a multicentre study. In: Journal of Antimicrobial Chemotherapy. 2014 ; Vol. 70, No. 7. pp. 2133-2143.
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title = "Infections caused by KPC-producing Klebsiella pneumoniae: Differences in therapy and mortality in a multicentre study",
abstract = "Objectives: Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals. Methods: The cohort included 661 adults with bloodstream infections (BSIs; n=447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible. Results: Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1{\%}). Logistic regression analysis identified BSI (OR, 2.09; 95{\%} CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95{\%} CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95{\%} CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95{\%} CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95{\%} CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95{\%} CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95{\%} CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤ 8 mg/L. Conclusions: KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.",
keywords = "Carbapenem resistance, Carbapenemases, Colistin resistance, Combination therapy, Inadequate empirical therapy, Meropenem MICs, Treatment",
author = "Mario Tumbarello and Trecarichi, {Enrico Maria} and {De Rosa}, {Francesco Giuseppe} and Maddalena Giannella and Giacobbe, {Daniele Roberto} and Matteo Bassetti and Losito, {Angela Raffaella} and Michele Bartoletti and {Del Bono}, Valerio and Silvia Corcione and Giuseppe Maiuro and Sara Tedeschi and Luigi Celani and Cardellino, {Chiara Simona} and Teresa Spanu and Anna Marchese and Simone Ambretti and Roberto Cauda and Claudio Viscoli and Pierluigi Viale",
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month = "12",
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TY - JOUR

T1 - Infections caused by KPC-producing Klebsiella pneumoniae

T2 - Differences in therapy and mortality in a multicentre study

AU - Tumbarello, Mario

AU - Trecarichi, Enrico Maria

AU - De Rosa, Francesco Giuseppe

AU - Giannella, Maddalena

AU - Giacobbe, Daniele Roberto

AU - Bassetti, Matteo

AU - Losito, Angela Raffaella

AU - Bartoletti, Michele

AU - Del Bono, Valerio

AU - Corcione, Silvia

AU - Maiuro, Giuseppe

AU - Tedeschi, Sara

AU - Celani, Luigi

AU - Cardellino, Chiara Simona

AU - Spanu, Teresa

AU - Marchese, Anna

AU - Ambretti, Simone

AU - Cauda, Roberto

AU - Viscoli, Claudio

AU - Viale, Pierluigi

PY - 2014/12/6

Y1 - 2014/12/6

N2 - Objectives: Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals. Methods: The cohort included 661 adults with bloodstream infections (BSIs; n=447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible. Results: Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤ 8 mg/L. Conclusions: KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.

AB - Objectives: Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals. Methods: The cohort included 661 adults with bloodstream infections (BSIs; n=447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible. Results: Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤ 8 mg/L. Conclusions: KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.

KW - Carbapenem resistance

KW - Carbapenemases

KW - Colistin resistance

KW - Combination therapy

KW - Inadequate empirical therapy

KW - Meropenem MICs

KW - Treatment

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