Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

Gutiérrez‐Gutiérrez, Belén; Salamanca, Elena; Cueto, Marina de; Hsueh, Po-Ren; Viale, Pierluigi; Paño‐Pardo, José Ramón; Venditti, Mario; Tumbarello, Mario; Daikos, George L.; Cantón, Rafael; Doi, Yohei; Tuon, Felipe Francisco; Karaiskos, Ilias; Pérez‐Nadales, Elena; Schwaber, Mitchell J.; Azap, Özlem Kurt; Souli, María; Roilides, Emmanuel; Pournaras, Spyros; Akova, Murat; Pérez, Federico; Bermejo, Joaquín; Oliver, Antonio; Almela, Manel; Lowman, Warren; Almirante, Benito; Bonomo, Robert A.; Carmeli, Yehuda; Paterson, David L.; Pascual, Álvaro; Rodríguez-Baño, Jesús; Toro, María Dolores del; Gálvez, Jordi; Falcone, Marco; Russo, Alessandro; Giamarellou, Helen; Trecarichi, Enrico Maria; Losito, Angela Raffaella; García-Vázquez, Elisa; Hernández, Alicia; Gómez, Juana Carretero; Bou, Germán; Iosifidis, Εlias; Prim, Núria; Navarro, Ferrán Martínez; Mirelis, Beatriz; Skiada, Anna; Origüen, Julia; Juan, Rafael San; Fernández‐Ruiz, Mario; Larrosa, Nieves; Puig-Asensio, Mireia; Cisneros, José Miguel; Molina, José Antonio; Gonzalez, Virginia; Rucci, V.; Gopegui, Enrique Ruíz de; Marinescu, C.; Martı́nez-Martı́nez, Luis; Fariñas, M.C.; Cano, María Eliecer; Gozalo, Mónica; Mora-Rillo, Marta; Francisco, Carolina Navarro-San; Peña, Carmen; Gómez-Zorrilla, Sílvia; Tubau, Fé; Tsakris, Athanassios; Zarkotou, Olympia; Antoniadou, Anastasia; Poulakou, Garyfallia; Pitout, Johann; Virmani, Divya; Torre-Cisneros, J; Guzmán-Puche, Julia; Helvacı, Özant; Şahin, Ahmet; Pintado, Vicente; Ruiz, P. Ramos; Bartoletti, Michele; Giannella, Maddalena; Tacconelli, E.; Riemenschneider, F; Calbo, Esther; Badía, Cristina; Xercavins, Mariona; Gasch, Oriol; Fontanals, Dionísia; Jové, E.

doi:10.1016/s1473-3099(17)30228-1

Cited by 395 publications

(328 citation statements)

References 22 publications

Supporting

Mentioning

299

Contrasting

Unclassified

Order By: Relevance

“…Of note, these two cohort studies pointed to a potential advantage of colistin‐meropenem combination therapy when the meropenem MIC was 8 mg/L or less . Interestingly, recent results from the INCREMENT trial that included 437 patients with BSI due to CRE suggest that the true benefit of combination therapy might be limited to patients with a greater severity of illness. In this analysis, combination therapy was associated with lower mortality compared with monotherapy in the high‐mortality‐score stratum (30 [48%] of 63 vs 64 [62%] of 103; aHR 0.56, 95% CI 0.34–0.91) but not in the low‐mortality‐score stratum (17 [24%] of 72 vs 21 [20%] of 105; aOR 1.21, 95% CI 0.56–2.56, p=0.62).…”

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti‐infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP)

et al. 2019

Self Cite

View full text Add to dashboard Cite

The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram‐negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti‐Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin‐based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.

show abstract

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti‐infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP)

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…For bacteremic infections, combination treatment regimens that include meropenem (at least when the MIC is Յ8 mg/liter) are recommended (6,10); however, recent data suggest that combination therapy is needed only in patients at high risk of death (11). In recent years, outbreaks of colistin-resistant KPC-producing K. pneumoniae infections with high-level meropenem resistance (MIC Ն 64 mg/liter) have been reported.…”

mentioning

confidence: 99%

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

Machuca

Gutiérrez‐Gutiérrez

Gracia-Ahufinger

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

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 Ͻ16 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 Ն 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 ϭ 0.006) and admission to the critical care unit (HR, 2.87; 95% CI, 0.99 to 8.27; P ϭ 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 ϭ 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.

show abstract

“…Furthermore, in the absence of published prospective randomized controlled trials, recommended therapy for the treatment of serious infections caused by carbapenemase-producing Enterobacteriaceae is based primarily on observational studies. Data are available to support the use of combination therapy for the treatment of serious infections (10,11); however, these benefits may primarily be limited to those patients with severe underlying conditions (12). Collectively, inclusion of a carbapenem in the treatment of carbapenemaseproducing Enterobacteriaceae appears to be associated with lower mortality rates compared to carbapenem-sparing treatment regimens, but this has not been borne out in all observational studies (13).…”

mentioning

confidence: 99%

Is This the Carbapenemase Test We've Been Waiting for? A Multicenter Evaluation of the Modified Carbapenem Inactivation Method

Butler-Wu

Abbott

2017

J Clin Microbiol

View full text Add to dashboard Cite

A plethora of phenotypic methods exist for the detection of carbapenemases; however, clinical laboratories have struggled for years with accurate, objective phenotypic detection of carbapenemase activity in Enterobacteriaceae. In this issue of the Journal of Clinical Microbiology, V. M. Pierce et al. (J Clin Microbiol 55: 2321-2333, https://doi.org/10.1128/JCM.00193-17) report on a multicenter evaluation of the modified carbapenem inactivation method (mCIM). The high sensitivity, specificity, reproducibility, and ease of interpretation associated with the mCIM for Enterobacteriaceae will likely lead to its adoption by clinical laboratories.

show abstract

Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

Cited by 395 publications

References 22 publications

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

Is This the Carbapenemase Test We've Been Waiting for? A Multicenter Evaluation of the Modified Carbapenem Inactivation Method

Contact Info

Product

Resources

About