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Comparable outcomes for β-lactam/β-lactamase inhibitor combinations and carbapenems in definitive treatment of bloodstream infections caused by cefotaxime-resistant Escherichia coli or Klebsiella pneumoniae.

Harris PN, Yin M, Jureen R, Chew J, Ali J, Paynter S, Paterson DL, Tambyah PA - Antimicrob Resist Infect Control (2015)

Bottom Line: We compared outcomes between patients who had definitive monotherapy with a carbapenem to those who had definitive monotherapy with a BLBLI.The time to resolution of systemic inflammatory response syndrome (SIRS) criteria did not vary between the treatment groups (adjusted HR 0.91, 95% CI 0.32 to 2.59; p = 0.97).The length of hospital admission post-positive blood culture was slightly longer in patients treated with BLBLIs (median duration 15 vs. 11 days), although this was not significant (adjusted HR 0.62; 95% CI 0.27 to 1.42; p = 0.26).

View Article: PubMed Central - PubMed

Affiliation: University of Queensland Centre for Clinical Research, Brisbane, Queensland Australia ; Department of Infectious Diseases, National University Hospital, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

ABSTRACT

Background: Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae.

Methods: All adult patients with a BSI caused by cefotaxime non-susceptible E. coli or K. pneumoniae were included from May 2012-May 2013. We compared outcomes between patients who had definitive monotherapy with a carbapenem to those who had definitive monotherapy with a BLBLI.

Results: There were 92 BSIs that fulfilled the microbiological inclusion criteria. 79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. Four out of 23 (17.4%) patients treated with carbapenem monotherapy and 2 out of 24 (8.3%) patients treated with BLBLI monotherapy died (adjusted HR for survival 0.91, 95% CI 0.13 to 6.28; p = 0.92). The time to resolution of systemic inflammatory response syndrome (SIRS) criteria did not vary between the treatment groups (adjusted HR 0.91, 95% CI 0.32 to 2.59; p = 0.97). The length of hospital admission post-positive blood culture was slightly longer in patients treated with BLBLIs (median duration 15 vs. 11 days), although this was not significant (adjusted HR 0.62; 95% CI 0.27 to 1.42; p = 0.26). There were no significant differences in subsequent isolation of carbapenem resistant organisms (4.3% vs. 4.2%, p = 1.0), C. difficile infection (13.0% vs. 8.3%, p = 0.67) or relapsed BSI (0% vs. 2%, p = 0.23).

Conclusions: BLBLIs appear to have a similar efficacy to carbapenems in the treatment of cefotaxime-resistant E. coli and K. pneumoniae bloodstream infections. Directed therapy with a BLBLI, when susceptibility is proven, may represent an appropriate carbapenem-sparing option.

No MeSH data available.


Related in: MedlinePlus

30-day mortality for patients treated with BLBLI or carbapenem as definitive monotherapy.
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Fig2: 30-day mortality for patients treated with BLBLI or carbapenem as definitive monotherapy.

Mentions: During the period from May 2012 to May 2013 there were there were 476 E. coli and 328 K. pneumoniae bloodstream infections in patients > =21 years old. Out of the total 804 bloodstream infection events, there were 92 (11.4%) that fulfilled the microbiological inclusion criteria, of which 79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. Susceptibility patterns are summarized in Table 1 and MIC distributions for amoxicillin-clavulanate, piperacillin-tazobactam and cefoxitin are shown in Table 2. One patient was excluded as they were discharged without any antibiotic treatment. The median age was 75 years (range 23–100 years; IQR 21) and 53.8% were female. Of the 91 patients given treatment, 44 received definitive treatment that did not include a BLBLI or a carbapenem or were given combination definitive therapy, leaving 47 patients eligible for inclusion in the analysis for definitive therapy (24 receiving a BLBLI and 23 a carbapenem) (see Figure 1). Definitive carbapenem monotherapy included 60.9% given meropenem, 34.8% imipenem and 4.3% ertapenem; for definitive monotherapy with a BLBLI, 95.8% were given piperacillin-tazobactam and 4.2% amoxicillin-clavulanate. In the carbapenem treated group, 17.4% received ‘step-down’ once daily therapy with ertapenem following initial therapy with imipenem or meropenem. In the BLBLI treated group, 8.3% were given ‘step-down’ therapy with amoxicillin-clavualante following piperacillin-tazobactam. Other antibiotic choices, along with the baseline characteristics are reported in Table 3. Mortality was relatively infrequent: four out of 23 (17.4%) patients treated with carbapenem monotherapy and 2 out of 24 (8.3%) patients treated with BLBLI monotherapy (Figure 2). On univariate analysis of mortality, a non-significant result favouring BLBLIs was seen, but this was diminished after adjustment for confounders (see Table 4). The HR for survival at 30 days was 0.91 (95% CI 0.13 to 6.28; p = 0.92) after adjustment for ICU admission, infecting organism, and Pitt score. There was no difference in the time to resolution of SIRS between the two definitive treatment groups (HR 0.91, 95% CI 0.32 to 2.59; p = 0.97) (Figure 3 and Table 4). For the analysis of the length of hospital stay post positive blood culture, four patients were excluded because they had prolonged hospital admission (>40 days) due to unrelated factors. The length of hospital stay post positive blood culture was slightly longer in patients treated with BLBLI compared to carbapenem. For those treated with a BLBLI, the median length of stay was 15 days [IQR 10 to 19 days] while for those given a carbapenem, the median length of stay was 11 days [IQR 8 to 20 days]. In the Cox regression analysis, this difference was not statistically significant (HR 0.62, 95% CI 0.27 to 1.42; p =0.26) (Figure 4 and Table 4). There were no significant differences in subsequent isolation of a carbapenem resistant organism (4.3% vs. 4.2%, p = 1.0), C. difficile infection (13.0% vs. 8.3%, p = 0.67) or relapsed bloodstream infection (0% vs. 2%, p = 0.23).Table 1


Comparable outcomes for β-lactam/β-lactamase inhibitor combinations and carbapenems in definitive treatment of bloodstream infections caused by cefotaxime-resistant Escherichia coli or Klebsiella pneumoniae.

Harris PN, Yin M, Jureen R, Chew J, Ali J, Paynter S, Paterson DL, Tambyah PA - Antimicrob Resist Infect Control (2015)

30-day mortality for patients treated with BLBLI or carbapenem as definitive monotherapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4414382&req=5

Fig2: 30-day mortality for patients treated with BLBLI or carbapenem as definitive monotherapy.
Mentions: During the period from May 2012 to May 2013 there were there were 476 E. coli and 328 K. pneumoniae bloodstream infections in patients > =21 years old. Out of the total 804 bloodstream infection events, there were 92 (11.4%) that fulfilled the microbiological inclusion criteria, of which 79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. Susceptibility patterns are summarized in Table 1 and MIC distributions for amoxicillin-clavulanate, piperacillin-tazobactam and cefoxitin are shown in Table 2. One patient was excluded as they were discharged without any antibiotic treatment. The median age was 75 years (range 23–100 years; IQR 21) and 53.8% were female. Of the 91 patients given treatment, 44 received definitive treatment that did not include a BLBLI or a carbapenem or were given combination definitive therapy, leaving 47 patients eligible for inclusion in the analysis for definitive therapy (24 receiving a BLBLI and 23 a carbapenem) (see Figure 1). Definitive carbapenem monotherapy included 60.9% given meropenem, 34.8% imipenem and 4.3% ertapenem; for definitive monotherapy with a BLBLI, 95.8% were given piperacillin-tazobactam and 4.2% amoxicillin-clavulanate. In the carbapenem treated group, 17.4% received ‘step-down’ once daily therapy with ertapenem following initial therapy with imipenem or meropenem. In the BLBLI treated group, 8.3% were given ‘step-down’ therapy with amoxicillin-clavualante following piperacillin-tazobactam. Other antibiotic choices, along with the baseline characteristics are reported in Table 3. Mortality was relatively infrequent: four out of 23 (17.4%) patients treated with carbapenem monotherapy and 2 out of 24 (8.3%) patients treated with BLBLI monotherapy (Figure 2). On univariate analysis of mortality, a non-significant result favouring BLBLIs was seen, but this was diminished after adjustment for confounders (see Table 4). The HR for survival at 30 days was 0.91 (95% CI 0.13 to 6.28; p = 0.92) after adjustment for ICU admission, infecting organism, and Pitt score. There was no difference in the time to resolution of SIRS between the two definitive treatment groups (HR 0.91, 95% CI 0.32 to 2.59; p = 0.97) (Figure 3 and Table 4). For the analysis of the length of hospital stay post positive blood culture, four patients were excluded because they had prolonged hospital admission (>40 days) due to unrelated factors. The length of hospital stay post positive blood culture was slightly longer in patients treated with BLBLI compared to carbapenem. For those treated with a BLBLI, the median length of stay was 15 days [IQR 10 to 19 days] while for those given a carbapenem, the median length of stay was 11 days [IQR 8 to 20 days]. In the Cox regression analysis, this difference was not statistically significant (HR 0.62, 95% CI 0.27 to 1.42; p =0.26) (Figure 4 and Table 4). There were no significant differences in subsequent isolation of a carbapenem resistant organism (4.3% vs. 4.2%, p = 1.0), C. difficile infection (13.0% vs. 8.3%, p = 0.67) or relapsed bloodstream infection (0% vs. 2%, p = 0.23).Table 1

Bottom Line: We compared outcomes between patients who had definitive monotherapy with a carbapenem to those who had definitive monotherapy with a BLBLI.The time to resolution of systemic inflammatory response syndrome (SIRS) criteria did not vary between the treatment groups (adjusted HR 0.91, 95% CI 0.32 to 2.59; p = 0.97).The length of hospital admission post-positive blood culture was slightly longer in patients treated with BLBLIs (median duration 15 vs. 11 days), although this was not significant (adjusted HR 0.62; 95% CI 0.27 to 1.42; p = 0.26).

View Article: PubMed Central - PubMed

Affiliation: University of Queensland Centre for Clinical Research, Brisbane, Queensland Australia ; Department of Infectious Diseases, National University Hospital, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

ABSTRACT

Background: Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae.

Methods: All adult patients with a BSI caused by cefotaxime non-susceptible E. coli or K. pneumoniae were included from May 2012-May 2013. We compared outcomes between patients who had definitive monotherapy with a carbapenem to those who had definitive monotherapy with a BLBLI.

Results: There were 92 BSIs that fulfilled the microbiological inclusion criteria. 79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. Four out of 23 (17.4%) patients treated with carbapenem monotherapy and 2 out of 24 (8.3%) patients treated with BLBLI monotherapy died (adjusted HR for survival 0.91, 95% CI 0.13 to 6.28; p = 0.92). The time to resolution of systemic inflammatory response syndrome (SIRS) criteria did not vary between the treatment groups (adjusted HR 0.91, 95% CI 0.32 to 2.59; p = 0.97). The length of hospital admission post-positive blood culture was slightly longer in patients treated with BLBLIs (median duration 15 vs. 11 days), although this was not significant (adjusted HR 0.62; 95% CI 0.27 to 1.42; p = 0.26). There were no significant differences in subsequent isolation of carbapenem resistant organisms (4.3% vs. 4.2%, p = 1.0), C. difficile infection (13.0% vs. 8.3%, p = 0.67) or relapsed BSI (0% vs. 2%, p = 0.23).

Conclusions: BLBLIs appear to have a similar efficacy to carbapenems in the treatment of cefotaxime-resistant E. coli and K. pneumoniae bloodstream infections. Directed therapy with a BLBLI, when susceptibility is proven, may represent an appropriate carbapenem-sparing option.

No MeSH data available.


Related in: MedlinePlus