Ventilator-associated pneumonia caused by carbapenemase KPC3-producing Klebsiella pneumoniae

Las Enterobacterales productoras de carbapenemasas y específicamente la Klebsiella pneumoniae productora de KPC (KPC-Kp) se siguen extendiendo rápidamente por todo el mundo. A pesar de esta gran y rápida extensión no se han realizado estudios que permitan conocer adecuadamente el pronóstico de la infección por KPC-Kp en las neumonas asociadas a ventilación mecánica (NAVM). El objetivo de nuestro estudio es evaluar si la neumonía asociada a ventilación mecánica por KPC-Kp está asociada con una mayor mortalidad que la causada por cepas de Klebsiella pneumoniae no productoras de KPC (No KPC-Kp) y susceptibles por tanto a carbapenemasas. Se trata de un estudio observacional de cohortes retrospectivo de pacientes con NAVM por Klebsiella pneumoniae realizado en una Unidad de Cuidados Intensivos polivalentes de 35 camas de un Hospital Universitario con más de 40000 ingresos anuales (Hospital Universitario Reina Sofia, Córdoba, España). El periodo de estudio fue de 4 años, desde enero de 2012 hasta diciembre de 2016. Se realizaron diferentes modelos multivariantes ajustados para estudiar la asociación entre la presencia de KPC-Kp y la mortalidad por todas las causas a los 30 días del inicio de la infección. Fueron analizados 69 casos de NAVM por K. pneumoniae de los cuales 39 fueron cepas productoras de KPC con un alto nivel de resistencia a meropenem (CMI >16 mg/ml). Las 30 restantes se dividían en 10 productoras de betalactamasas de espectro extendido y 20 sin mecanismos de resistencia a antibióticos. La mortalidad a los 30 días del grupo KPC-Kp fue del 41% (16/39) y en el grupo susceptible a carbapenemasas fue del 33.3% (10/30). La etiología de la infección KPCKp no se asoció con mayor mortalidad en el análisis controlado por factores de confusión mediante regresión de cox (Hazard ratio [HR] ajustado 1.25; 95% intervalo de confianza [IC] 95%: 0.46-3.41). En el análisis se identificó el uso de una adecuada terapia antibiótica como asociada a una menor mortalidad (HR 0.03; IC 95%: 40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression). We analyze 69 cases of K. pneumoniae VAP of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/mL). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [HR] 1.25; 95% CI: 0.46–3.41). Adequate targeted therapy (HR 0.03; 95% CI: <0.01–0.23) was associated with all-cause mortality. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used

External validation of the INCREMENT-CPE mortality score in a carbapenem-resistant Klebsiella pneumoniae bacteraemia cohort: the prognostic significance of colistin resistance

External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68–0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69–3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55–3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73–4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality.This study was supported by Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001; RD16/0016/0008], co-financed by the European Regional Development Fund ‘A way to achieve Europe’, Operative Program Intelligent Growth 2014–2020

Mortality Associated with Bacteremia Due to Colistin-Resistant Klebsiella pneumoniae with High-Level Meropenem Resistance: Importance of Combination Therapy without Colistin and Carbapenems

Combination therapy including colistin and a carbapenem has been found to be associated with lower mortality in the treatment of bloodstream infections (BSI) due to KPC-producing Klebsiella pneumoniae when the isolates show a meropenem or imipenem MIC of <16 mg/liter. However, the optimal treatment of BSI caused by colistin- and high-level carbapenem-resistant KPC-producing K. pneumoniae is unknown. A prospective cohort study including episodes of bacteremia caused by colistin-resistant and high-level meropenem-resistant (MIC ≥ 64 mg/liter) KPC-producing K. pneumoniae diagnosed from July 2012 to February 2016 was performed. The impact of combination therapy on crude 30-day mortality was analyzed by Cox regression using a propensity score as a covariate to control for indication bias and in an inverse probability of treatment weighting (IPTW) cohort. The study sample comprised 104 patients, of which 32 (30.8%) received targeted monotherapy and 72 (69.2%) received targeted combination therapy; none of them received either colistin or a carbapenem. The 30-day crude mortality rate was 30.8% (43.8% in patients treated with monotherapy and 25% in patients receiving combination therapy). In the Cox regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (hazard ratio [HR], 6.03; 95% confidence interval [CI], 1.65 to 21.9; P = 0.006) and admission to the critical care unit (HR, 2.87; 95% CI, 0.99 to 8.27; P = 0.05). Targeted combination therapy was associated with lower mortality only in patients with septic shock (HR, 0.14; 95% CI, 0.03 to 0.67; P = 0.01). These results were confirmed in the Cox regression analysis of the IPTW cohort. Combination therapy is associated with reduced mortality in patients with bacteremia due to colistin-resistant KPC-producing K. pneumoniae with high-level carbapenem resistance in patients with septic shock.This study was funded by Planes Nacionales de I+D+i 2008-2011 and 2013-2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015/0010 and REIPI RD16/0016/0001; RD16/0016/0001; RD16/00167008) and cofinanced by European Development Regional Fund “A way to achieve Europe” and operative program Intelligent Growth 2014-2020.Peer reviewe

Prognosis of urinary tract infection caused by KPC-producing Klebsiella pneumoniae: The impact of inappropriate empirical treatment

[Introduction] There is scarce information on the prognosis of urinary tract infections (UTI) caused by KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp).[Objetive] To investigate the association between KPC-Kp aetiology and clinical failure and all cause mortality and to explore the impact of inappropriate empirical treatment.[Material and methods] This is a retrospective observational study of hospitalized patients with UTI due to K. pneumoniae. We explored clinical failure at day 21 and 30-day all-cause mortality using different models of adjusted analysis.[Results] We analyzed 142 episodes of UTI; 46 episodes (32.4%) were due to KPC-Kp and 96 episodes (67.6%) were due to non-KPC-Kp strains (62 wild type and 34 EBSL producer). Clinical failure was more frequent in the KPC-Kp group (41.3% vs. 15.6%, p = 0.001). KPC-Kp aetiology and inappropriate empirical therapy were associated in the non-adjusted analysis with clinical failure. When analysed in separate adjusted models, both were found to be associated; inappropriate empirical treatment (OR 2.51; 95% CI, 1.03–6.12; p = 0.04) and KPC-Kp (OR 2.73; 95% CI, 1.03–7.22; p = 0.04) were associated with increased risk of failure. All-cause 30-day mortality was higher in patients with KPC-Kp UTI (39.1% vs. 15.6%, p = 0.002). Bacteraemia was more frequent in patients with KPC-Kp etiology (23.9% vs. 10.4%; p = 0.034). In both cases, the association was not confirmed in the adjusted analysis.[Conclusion] KPC-Kp UTI is associated with higher clinical failure and may be due to an increase in inappropriate empirical treatment.Supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001; RD16/0016/0008)‐ co‐ financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014‐2020. BGG has received a Río Hortega grant from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III.Peer reviewe

Impact of KPC Production and High-Level Meropenem Resistance on All-Cause Mortality of Ventilator-Associated Pneumonia in Association with Klebsiella pneumoniae

Carbapenemase-producing Enterobacterales and specifically Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) are rapidly spreading worldwide. The prognosis of ventilator-associated pneumonia (VAP) caused by KPC-Kp is not well known. Our study tries to assess whether ventilator-associated pneumonia caused by a KPC-Kp strain is associated with higher all-cause mortality than that caused by carbapenem-susceptible isolates. This is a retrospective cohort study of patients with VAP due to K. pneumoniae from a 35-bed polyvalent intensive care unit in a university hospital (>40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression). We analyze 69 cases of K. pneumoniae VAP, of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/ml). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.46 to 3.41). Adequate targeted therapy (HR, 0.03; 95% CI, <0.01 to 0.23) was associated with all-cause mortality. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used.Supported by Plan Nacional de I+D+i 2013 to 2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001; RD16/0016/0008). Cofinanced by the European Regional Development Regional Fund “A way to achieve Europe,” Operational Programme Smart Growth 2014 to 2020. B.G.-G. is a recipient of the “Río Hortega” grant by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

External validation of the INCREMENT-CPE mortality score in a carbapenem-resistant Klebsiella pneumoniae bacteraemia cohort: the prognostic significance of colistin resistance

External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68–0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69–3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55–3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73–4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality

External validation of the INCREMENT-CPE mortality score in a carbapenem-resistant Klebsiella pneumoniae bacteraemia cohort: the prognostic significance of colistin resistance

External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68-0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69-3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55-3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73-4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved