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Leonard Leibovici - One of the best experts on this subject based on the ideXlab platform.

  • Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis
    Cochrane Database of Systematic Reviews, 2014
    Co-Authors: Adi Lador, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    BACKGROUND: Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy.\nOBJECTIVES: Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics.\nSEARCH METHODS: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004.\nSELECTION CRITERIA: We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis.\nDATA COLLECTION AND ANALYSIS: The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible.\nMAIN RESULTS: We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons.We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies.\nAUTHORS' CONCLUSIONS: The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.

  • The Cochrane Library - Beta-Lactam versus Beta-Lactam-aminoglycoside combination therapy in cancer patients with neutropenia.
    The Cochrane database of systematic reviews, 2013
    Co-Authors: M Paul, Agata Schlesinger, Yaakov Dickstein, Karla Soares-weiser, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    Background Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum Beta-Lactams have been introduced as single treatment, and classically, a combination of a Beta-Lactam with an aminoglycoside has been used. Objectives To compare Beta-Lactam monotherapy versus Beta-Lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies. Selection criteria Randomised controlled trials (RCTs) comparing any Beta-Lactam antibiotic monotherapy with any combination of a Beta-Lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed. Data collection and analysis Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors. Main results Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same Beta-Lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different Beta-Lactams－usually a broad-spectrum Beta-Lactam compared with a narrower-spectrum Beta-Lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same Beta-Lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different Beta-Lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials. Authors' conclusions Beta-Lactam monotherapy is advantageous compared with Beta-Lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.

  • Beta-Lactam versus Beta-Lactam-aminoglycoside combination therapy in cancer patients with neutropenia
    Cochrane Database of Systematic Reviews, 2013
    Co-Authors: Yaakov Dickstein, Agata Schlesinger, Karla Soares-weiser, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    BACKGROUND: Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum Beta-Lactams have been introduced as single treatment, and classically, a combination of a Beta-Lactam with an aminoglycoside has been used.\n\nOBJECTIVES: To compare Beta-Lactam monotherapy versus Beta-Lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia.\n\nSEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies.\n\nSELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any Beta-Lactam antibiotic monotherapy with any combination of a Beta-Lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed.\n\nDATA COLLECTION AND ANALYSIS: Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors.\n\nMAIN RESULTS: Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same Beta-Lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different Beta-Lactams－usually a broad-spectrum Beta-Lactam compared with a narrower-spectrum Beta-Lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same Beta-Lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different Beta-Lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials.\n\nAUTHORS' CONCLUSIONS: Beta-Lactam monotherapy is advantageous compared with Beta-Lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.

  • The Cochrane Library - Beta lactam antibiotic monotherapy versus beta lactam‐aminoglycoside antibiotic combination therapy for sepsis
    The Cochrane database of systematic reviews, 2006
    Co-Authors: M Paul, Adi Lador, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    Background Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy. Objectives Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics. Search methods In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004. Selection criteria We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis. Data collection and analysis The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible. Main results We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons. We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies. Authors' conclusions The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.

Simona Grozinsky-glasberg - One of the best experts on this subject based on the ideXlab platform.

  • Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis
    Cochrane Database of Systematic Reviews, 2014
    Co-Authors: Adi Lador, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    BACKGROUND: Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy.\nOBJECTIVES: Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics.\nSEARCH METHODS: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004.\nSELECTION CRITERIA: We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis.\nDATA COLLECTION AND ANALYSIS: The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible.\nMAIN RESULTS: We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons.We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies.\nAUTHORS' CONCLUSIONS: The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.

  • The Cochrane Library - Beta-Lactam versus Beta-Lactam-aminoglycoside combination therapy in cancer patients with neutropenia.
    The Cochrane database of systematic reviews, 2013
    Co-Authors: M Paul, Agata Schlesinger, Yaakov Dickstein, Karla Soares-weiser, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    Background Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum Beta-Lactams have been introduced as single treatment, and classically, a combination of a Beta-Lactam with an aminoglycoside has been used. Objectives To compare Beta-Lactam monotherapy versus Beta-Lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies. Selection criteria Randomised controlled trials (RCTs) comparing any Beta-Lactam antibiotic monotherapy with any combination of a Beta-Lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed. Data collection and analysis Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors. Main results Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same Beta-Lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different Beta-Lactams－usually a broad-spectrum Beta-Lactam compared with a narrower-spectrum Beta-Lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same Beta-Lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different Beta-Lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials. Authors' conclusions Beta-Lactam monotherapy is advantageous compared with Beta-Lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.

  • Beta-Lactam versus Beta-Lactam-aminoglycoside combination therapy in cancer patients with neutropenia
    Cochrane Database of Systematic Reviews, 2013
    Co-Authors: Yaakov Dickstein, Agata Schlesinger, Karla Soares-weiser, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    BACKGROUND: Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum Beta-Lactams have been introduced as single treatment, and classically, a combination of a Beta-Lactam with an aminoglycoside has been used.\n\nOBJECTIVES: To compare Beta-Lactam monotherapy versus Beta-Lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia.\n\nSEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies.\n\nSELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any Beta-Lactam antibiotic monotherapy with any combination of a Beta-Lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed.\n\nDATA COLLECTION AND ANALYSIS: Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors.\n\nMAIN RESULTS: Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same Beta-Lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different Beta-Lactams－usually a broad-spectrum Beta-Lactam compared with a narrower-spectrum Beta-Lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same Beta-Lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different Beta-Lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials.\n\nAUTHORS' CONCLUSIONS: Beta-Lactam monotherapy is advantageous compared with Beta-Lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.

  • The Cochrane Library - Beta lactam antibiotic monotherapy versus beta lactam‐aminoglycoside antibiotic combination therapy for sepsis
    The Cochrane database of systematic reviews, 2006
    Co-Authors: M Paul, Adi Lador, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    Background Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy. Objectives Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics. Search methods In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004. Selection criteria We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis. Data collection and analysis The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible. Main results We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons. We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies. Authors' conclusions The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.

M Paul - One of the best experts on this subject based on the ideXlab platform.

  • The Cochrane Library - Beta-Lactam versus Beta-Lactam-aminoglycoside combination therapy in cancer patients with neutropenia.
    The Cochrane database of systematic reviews, 2013
    Co-Authors: M Paul, Agata Schlesinger, Yaakov Dickstein, Karla Soares-weiser, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    Background Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum Beta-Lactams have been introduced as single treatment, and classically, a combination of a Beta-Lactam with an aminoglycoside has been used. Objectives To compare Beta-Lactam monotherapy versus Beta-Lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies. Selection criteria Randomised controlled trials (RCTs) comparing any Beta-Lactam antibiotic monotherapy with any combination of a Beta-Lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed. Data collection and analysis Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors. Main results Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same Beta-Lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different Beta-Lactams－usually a broad-spectrum Beta-Lactam compared with a narrower-spectrum Beta-Lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same Beta-Lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different Beta-Lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials. Authors' conclusions Beta-Lactam monotherapy is advantageous compared with Beta-Lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.

  • The Cochrane Library - Beta lactam antibiotic monotherapy versus beta lactam‐aminoglycoside antibiotic combination therapy for sepsis
    The Cochrane database of systematic reviews, 2006
    Co-Authors: M Paul, Adi Lador, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    Background Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy. Objectives Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics. Search methods In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004. Selection criteria We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis. Data collection and analysis The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible. Main results We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons. We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies. Authors' conclusions The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.

Adi Lador - One of the best experts on this subject based on the ideXlab platform.

  • Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis
    Cochrane Database of Systematic Reviews, 2014
    Co-Authors: Adi Lador, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    BACKGROUND: Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy.\nOBJECTIVES: Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics.\nSEARCH METHODS: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004.\nSELECTION CRITERIA: We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis.\nDATA COLLECTION AND ANALYSIS: The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible.\nMAIN RESULTS: We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons.We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies.\nAUTHORS' CONCLUSIONS: The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.

  • The Cochrane Library - Beta lactam antibiotic monotherapy versus beta lactam‐aminoglycoside antibiotic combination therapy for sepsis
    The Cochrane database of systematic reviews, 2006
    Co-Authors: M Paul, Adi Lador, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    Background Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy. Objectives Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics. Search methods In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004. Selection criteria We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis. Data collection and analysis The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible. Main results We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons. We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies. Authors' conclusions The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.

Yaakov Dickstein - One of the best experts on this subject based on the ideXlab platform.

  • The Cochrane Library - Beta-Lactam versus Beta-Lactam-aminoglycoside combination therapy in cancer patients with neutropenia.
    The Cochrane database of systematic reviews, 2013
    Co-Authors: M Paul, Agata Schlesinger, Yaakov Dickstein, Karla Soares-weiser, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    Background Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum Beta-Lactams have been introduced as single treatment, and classically, a combination of a Beta-Lactam with an aminoglycoside has been used. Objectives To compare Beta-Lactam monotherapy versus Beta-Lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies. Selection criteria Randomised controlled trials (RCTs) comparing any Beta-Lactam antibiotic monotherapy with any combination of a Beta-Lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed. Data collection and analysis Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors. Main results Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same Beta-Lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different Beta-Lactams－usually a broad-spectrum Beta-Lactam compared with a narrower-spectrum Beta-Lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same Beta-Lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different Beta-Lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials. Authors' conclusions Beta-Lactam monotherapy is advantageous compared with Beta-Lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.

  • Beta-Lactam versus Beta-Lactam-aminoglycoside combination therapy in cancer patients with neutropenia
    Cochrane Database of Systematic Reviews, 2013
    Co-Authors: Yaakov Dickstein, Agata Schlesinger, Karla Soares-weiser, Simona Grozinsky-glasberg, Leonard Leibovici
    Abstract:

    BACKGROUND: Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum Beta-Lactams have been introduced as single treatment, and classically, a combination of a Beta-Lactam with an aminoglycoside has been used.\n\nOBJECTIVES: To compare Beta-Lactam monotherapy versus Beta-Lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia.\n\nSEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies.\n\nSELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any Beta-Lactam antibiotic monotherapy with any combination of a Beta-Lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed.\n\nDATA COLLECTION AND ANALYSIS: Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors.\n\nMAIN RESULTS: Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same Beta-Lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different Beta-Lactams－usually a broad-spectrum Beta-Lactam compared with a narrower-spectrum Beta-Lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same Beta-Lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different Beta-Lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials.\n\nAUTHORS' CONCLUSIONS: Beta-Lactam monotherapy is advantageous compared with Beta-Lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.