Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae: Results From the INCREMENT Cohort

Palacios‐Baena, Zaira R.; Gutiérrez‐Gutiérrez, Belén; Calbo, Esther; Almirante, Benito; Viale, Pierluigi; Oliver, Antonio; Pintado, Vicente; Gasch, Oriol; Martínez-Martínez, Luis; Pitout, Johann; Akova, Murat; Peña, Carmen; Gil-Bermejo, José Molina; Hernández, Alicia; Venditti, Mario; Prim, Núria; Bou, Germán; Tacconelli, Evelina; Tumbarello, Mario; Hamprecht, Axel; Giamarellou, Helen; Almela, Manel; Pérez, Federico; Schwaber, Mitchell J.; Bermejo, Joaquín; Lowman, Warren; Hsueh, Po-Ren; Paño‐Pardo, José Ramón; Torre‐Cisneros, Julián; Souli, María; Bonomo, Robert A.; Carmeli, Yehuda; Paterson, David L.; Pascual, Álvaro; Rodríguez-Baño, Jesús; Gálvez, Jordi; Falcone, Marco; Russo, Alessandro; Daikos, George L.; Trecarichi, Enrico Maria; Losito, Angela Raffaella; Gómez, Juana Carretero; Iosifidis, Εlias; Roilides, Emmanuel; Karaiskos, Ilias; Doi, Yohei; Tuon, Felipe Francisco; Navarro, Ferrán; Mirelis, Beatriz; Martínez, José Antonio; Calle, C. de la; Morata, Laura; Juan, Rafael San; Fernández‐Ruiz, Mario; Larrosa, Nieves; Puig, Mireia; Molina, José Antonio; Gonzalez, Virginia; Rucci, V.; Gopegui, Enrique Ruíz de; Marinescu, C.; Fariñas, M.C.; Cano, María Eliecer; Gozalo, Mónica; Mora-Rillo, Marta; Gómez-Zorrilla, Sílvia; Tubau, Fé; Pournaras, Spyros; Tsakris, Athanassios; Zarkotou, Olympia; Azap, Özlem Kurt; Antoniadou, Anastasia; Poulakou, Garyfallia; Virmani, Divya; Caño,; Machuca, Isabel; Helvaci,; Şahin, Ahmet; Ruíz-Garbajosa, Patricia; Bartoletti, Michele; Giannella, Maddalena; Peter, Silke; Badía, Cristina; Xercavins, Mariona; Fontanals, Dionísia; Jové, E.

doi:10.1093/cid/cix606

Cited by 51 publications

(37 citation statements)

References 26 publications

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“…Using INCREMENT cohort data, Palacios-Baena et al compared the empirical use of drugs other than carbapenems or BLBLIs (86 patients; 43 received an aminoglycoside) and carbapenems (249 patients) for BSI due to ESBL producers for mortality, clinical cure, and length of hospital stay. No significant differences (or trends) in any outcome were shown (106). Toxicity was not formally evaluated, but significant toxicity would be expected to have some effect on length of stay.…”

Section: Aminoglycosidesmentioning

confidence: 99%

“…According to these data, the current EUCAST susceptibility breakpoint (Յ0.25 mg/liter) seems to be more appropriate than the breakpoint of Յ1 mg/liter recommended by CLSI, at least for ESBL-E. The study by Palacios-Baena et al mentioned above, which examined the outcomes for patients with BSI due to ESBL-E who were treated empirically with active drugs other than BLBLIs or carbapenems, included 19 patients treated with a fluoroquinolone as the only active drug according to CLSI breakpoints, and the mortality rate was 10.5%, similar to that for patients treated with carbapenems (106).…”

Section: Fluoroquinolones and Trimethoprim-sulfamethoxazolementioning

confidence: 99%

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Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

et al. 2018

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Therapy of invasive infections due to multidrug-resistant (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producing (CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.

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Section: Aminoglycosidesmentioning

confidence: 99%

Section: Fluoroquinolones and Trimethoprim-sulfamethoxazolementioning

confidence: 99%

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

et al. 2018

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“…These findings have important implications for the management of the increasingly common problem of ESBL-producing E. coli bacteremia in these vulnerable patients (14). Previous studies conducted in general patient populations have identified an increased risk of treatment failure with cefepime as empiric therapy for ESBL-producing E. coli bacteremia, while retrospective studies evaluating piperacillin-tazobactam as empiric therapy for these infections have shown conflicting results (6,9,11,15,16). A recent international, multicenter study conducted by Gudiol et al comparing BLBLI combination therapy to carbapenems for the treatment of ESBL-producing Enterobacteriaceae bacteremia in neutropenic patients with hematologic malignancy identified a…”

Section: Discussionmentioning

confidence: 99%

Carbapenem versus Cefepime or Piperacillin-Tazobactam for Empiric Treatment of Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Patients with Hematologic Malignancy

Benanti

Brown

Shigle

et al. 2019

Antimicrob Agents Chemother

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Infections with extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli are common in patients with hematologic malignancy. The utility of cefepime and piperacillin-tazobactam as empiric therapy for ESBL-producing E. coli bacteremia in patients with hematologic malignancy is largely unknown. We conducted a single-center, retrospective cohort review of 103 adult inpatients with leukemia and/or hematopoietic stem cell transplant (HCT) recipients with monomicrobial ESBL-producing E. coli bacteremia. No association between increased 14-day mortality and empiric treatment with cefepime (8%) or piperacillin-tazobactam (0%) relative to that with carbapenems (19%) was observed (P = 0.19 and P = 0.04, respectively). This observation was consistent in multivariate Cox proportional hazards models adjusted for confounding and an inverse probability of treatment-weighted (IPTW) Cox proportional hazards model. Both fever and persistent bacteremia were more common in patients treated empirically with cefepime or piperacillin-tazobactam. Empiric treatment with cefepime or piperacillin-tazobactam did not result in increased mortality relative to that with treatment with carbapenems in patients with hematologic malignancy and ESBL-producing E. coli bacteremia, although most patients were changed to carbapenems early in treatment. However, due to prolonged fever and persistent bacteremia, their role may be limited in this patient population.

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“…Nevertheless, evidence is emerging that empiric or definitive treatment with BL/BLIs is probably as effective as carbapenem therapy in the setting of ESBL (E. coli or K. pneumoniae) bacteremia (9-11). Data regarding the usefulness of carbapenem-sparing antibiotics other than BL/BLIs for definitive treatment have also been reported, though also within an IV regimen (12-14). The effectiveness of non-intravenous (oral or intramuscular) antibiotic treatment for the management of ESBL or Amp-C bacteremia has not been widely assessed to date (3, 15).…”

Section: Introductionmentioning

confidence: 99%

Non-intravenous, carbapenem-sparing antibiotics for the treatment of bacteremia due to ESBL or AMP-C β-lactamase: A propensity score study

Meije¹,

Pigrau

Fernández-Hidalgo

et al. 2018

Preprint

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Introduction: Carbapenems are considered the treatment of choice for extended-spectrum β–lactamase (ESBL) or Amp-C β–lactamase-producing Enterobacteriaceae bacteremia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. Objective: To compare the 30 day-mortality and clinical failures associated with the use of carbapenems vs an alternative non-intravenous antibiotic for the definitive treatment of ESBL/Amp-C positive Enterobacteriaceae bacteremia. Methods: This is a 12-year retrospective study (2004 - 2015) including all patients with bacteremia due to ESBL/Amp-C-producing Enterobacteriaceae. Given the lack of randomization of the initial therapies, a propensity score for receiving carbapenems was calculated. Results: There were 1115 patients with a first episode of bacteremia due to E. coli or K. pneumoniae, of which 123 were ESBL/Amp C-positive (11%). There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (cotrimoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared to the carbapenem group, patients treated with the alternative regimen had a shorter hospital stay (median [IQR]: 7 days [5-10] vs 12 days [9-18], p<0,001). The use of an alternative non-IV treatment did not increase mortality (OR 0.27; 95% CI 0.05-1.61; p=.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95; 95% CI (0.94-26.01, p=.059). Conclusion: Alternative non-IV carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/Amp-C-positive Enterobacteriaceae bloodstream infections, allowing a reduction in carbapenem use. The use of cotrimoxazole in this setting has shown favourable results.

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Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae: Results From the INCREMENT Cohort

Abstract: We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E.

Cited by 51 publications

References 26 publications

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

Carbapenem versus Cefepime or Piperacillin-Tazobactam for Empiric Treatment of Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Patients with Hematologic Malignancy

Non-intravenous, carbapenem-sparing antibiotics for the treatment of bacteremia due to ESBL or AMP-C β-lactamase: A propensity score study

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