Clinical considerations for oral beta-lactams as step-down therapy for Enterobacteriaceae bloodstream infections

Mogle, Bryan T.; Beccari, Mario V.; Steele, Jeffrey; Fazili, Tasaduq; Kufel, Wesley D

doi:10.1080/14656566.2019.1594774

Cited by 24 publications

(30 citation statements)

References 14 publications

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“…46 Even when reported as susceptible, oral β-lactam antibiotics given at traditional doses may result in subtherapeutic serum concentrations when organism minimum inhibitory concentrations are at the upper range of susceptibility. 8 , 15 Therefore, individual patient characteristics associated with oral β-lactam pharmacokinetics, measured or predicted organism minimum inhibitory concentrations, and limitations of alternative treatments should be considered before the selection of an oral β-lactam antibiotic. Involvement of infectious diseases and antimicrobial stewardship programs should be considered to optimize patient selection.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, fluoroquinolones, TMP-SMX, and parenteral antibiotics are considered the mainstays of definitive treatment. 6 , 7 , 8 , 9 , 10 , 11 These mainstays are increasingly limited by antibiotic resistance rates, adverse effects, cost, or decreased patient satisfaction. 12 , 13 , 14 Additional oral antibiotics, if effective, would be a valuable addition to step-down treatment options.…”

Section: Introductionmentioning

confidence: 99%

“…Oral β-lactam antibiotics are not routinely recommended as step-down therapy for Enterobacterales bacteremia owing to concern over subtherapeutic serum concentrations. 8 , 15 Although potential subtherapeutic concentrations may legitimately preclude their routine or empirical use before organism identification and susceptibility determination, their role as step-down therapy on an individual patient basis is understudied, to our knowledge. 11 , 16 Given the limited available data, our objective was to compare rates of mortality and recurrent bacteremia in patients treated with β-lactam antibiotics vs fluoroquinolones or TMP-SMX as oral step-down therapy for Enterobacterales bacteremia from a suspected urinary source.…”

Section: Introductionmentioning

confidence: 99%

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Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source

et al. 2020

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IMPORTANCE Oral β-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there is a lack of outcomes data, specifically after initial treatment with parenteral antibiotics. Given the limited data and increasing limitations of fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), oral β-lactam antibiotics may be a valuable additional treatment option. OBJECTIVE To compare definitive therapy with oral β-lactam antibiotics vs fluoroquinolones or TMP-SMX for Enterobacterales bacteremia from a suspected urine source. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted from January 1, 2007, to September 30, 2015, at 114 Veterans Affairs hospitals among 4089 adults with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia and matching urine culture results. Additional inclusion criteria were receipt of active parenteral antibiotic(s) followed by conversion to an oral antibiotic. Exclusion criteria were previous Enterobacterales bacteremia, urologic abscess, or chronic prostatitis. Data were analyzed from April 15, 2019, to July 26, 2020. EXPOSURES Conversion of therapy to an oral β-lactam antibiotic vs fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics. MAIN OUTCOMES AND MEASURES The main outcome was a composite of either 30-day all-cause mortality or 30-day recurrent bacteremia. Propensity-based overlap weights were used to adjust for differences between groups. Log binomial regression models were used to estimate adjusted relative risks (aRRs) and adjusted risk differences (aRDs). RESULTS Of the 4089 eligible patients (3731 men [91.2%]; median age, 71 years [interquartile range, 63-81 years]), 955 received an oral β-lactam antibiotic, and 3134 received fluoroquinolones or TMP-SMX. The primary outcome occurred for 42 patients (4.4%) who received β-lactam antibiotics and 94 patients (3.0%) who received fluoroquinolones or TMP-SMX (aRD, 0.99% [95% CI, −0.42% to 2.40%]; aRR, 1.31 [95% CI, 0.87-1.95]). Mortality rates were 3.0% (n = 29) for patients receiving β-lactam antibiotics vs 2.6% (n = 82) for those receiving fluoroquinolones or TMP-SMX (aRD, 0.06% [95% CI, −1.13% to 1.26%]; aRR, 1.02 [95% CI, 0.67-1.56]). Recurrent bacteremia rates were 1.5% (n = 14) among those receiving β-lactam antibiotics vs 0.4% (n = 12) among those receiving fluoroquinolones or TMP-SMX (aRD, 1.03% [95% CI, 0.24%-1.82%]; aRR, 3.43 [95% CI, 0.42-27.90]). CONCLUSIONS AND RELEVANCE In this cohort study of adults with E coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, the relative risk of recurrent bacteremia was not significantly higher with β-lactam antibiotics compared with fluoroquinolones or TMP-SMX, and the absolute risk and risk difference were small (ie, <3%). No significant difference in mortality was observed. Oral β-lactam antibiotics may be a reasonable step-down treatment option, primarily (continued) Key Points Question Are mortality and recurren...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source

et al. 2020

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“…Most bacterial species within the Enterobacter genus are commonly found in human and animal intestines. Only a few Enterobacter species have been identified as conditional pathogens and have been described to cause extra‐intestinal and invasive infections in humans (Logan et al, ; Logan, Renschler, Sumanth, Weinstein, & Ramanan, ; Lukac, Bonomo, & Logan, ; Mogle, Beccari, Steele, Fazili, & Kufel, ). In aquaculture, the pathogenicity of Enterobacter has been reported relatively infrequently.…”

Section: Discussionmentioning

confidence: 99%

The composition of the microbial community associated with Macrobrachium rosenbergii zoeae varies throughout larval development

Wang

Yin

et al. 2020

Journal of Fish Diseases

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The giant river prawn, Macrobrachium rosenbergii, is an economically important freshwater prawn. The cultivation of zoea larvae is crucial for the success of the M. rosenbergii industry. In this study, we surveyed the microbial community diversity and structure associated with M. rosenbergii zoeae at different stages of larval development. Samples of zoea larvae from different developmental stages were collected and subjected to high‐throughput DNA sequencing. Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were the dominant phyla in all six sample groups. At the genus level, the relative abundance of Bacillus decreased, and that of Enterobacter increased with the growth of the zoeae. This may have been related to the intestinal development of the zoea larvae. The microbial diversity of M. rosenbergii zoea larvae decreased significantly with development. The beta diversity analysis showed that the closer the developmental stage of M. rosenbergii, the more similar the structure of the associated bacterial communities.

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“…Cunha [17] recommends, for example, that amoxicillin be dosed at 1 g every 8 hours, and cephalexin at 1 g every 6 hours, when treating serious infections—both in contrast to commonly used longer dosing intervals. Based on various dosing regimens and various MICs, Mogle et al calculated the probability of achieving the target f T > MIC for various antibiotic regimens [21]. They similarly concluded that cephalexin dosed at 1 g every 6 hours is most likely to achieve these targets, whereas high-dose amoxicillin and amoxicillin/clavulanate should be used and dosed every 8 hours, and ideally only when MICs are known to be sufficiently low to allow pharmacodynamic target attainment.…”

Section: Discussionmentioning

confidence: 99%

Oral Fluoroquinolone or Trimethoprim-Sulfamethoxazole vs ß-Lactams as Step-Down Therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis

Punjabi

Tien

Meng

et al. 2019

Open Forum Infectious Diseases

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Background Using published data, we sought to compare outcomes in patients transitioned to either oral fluoroquinolones (FQs) or trimethoprim-sulfamethoxazole (TMP-SMX) vs ß-lactams (BLs) after an initial intravenous (IV) course for gram-negative rod (GNR) bacteremia. Methods We conducted a systematic review of PubMed and EMBASE and published IDWeek abstracts. We included studies that reported all-cause mortality and/or infection recurrence in patients transitioned to oral FQ/TMP-SMX and BLs. Results Eight retrospective studies met inclusion criteria with data for 2289 patients, of whom 65% were transitioned to oral FQs, 7.7% to TMP-SMX, and 27.2% to BLs. Follow-up periods ranged from 21 to 90 days. All-cause mortality was not significantly different between patients transitioned to either FQ/TMP-SMX or BLs (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69–1.87). Overall recurrence of infection, either bacteremia or the primary site, occurred more frequently in patients transitioned to oral BLs vs FQs (OR, 2.05; 95% CI, 1.17–3.61). Analysis limited to recurrent bacteremia was similarly suggestive, although limited by small numbers (OR, 2.15; 95% CI, 0.93–4.99). However, based on known pharmacokinetics/pharmacodynamics, prescribed ß-lactam dosing regimens were frequently suboptimal. Conclusions In the step-down IV to oral treatment of GNR bacteremia, we found insufficient data regarding outcomes after oral TMP-SMX; however, selection of an FQ over commonly utilized ß-lactam regimens may reduce chances of infection recurrence. Although this may be a class effect, it may simply be the result of inadequate dosing of ß-lactams. Additional investigations are warranted to determine outcomes with TMP-SMX and optimized oral ß-lactam dosing regimens.

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Clinical considerations for oral beta-lactams as step-down therapy for Enterobacteriaceae bloodstream infections

Cited by 24 publications

References 14 publications

Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source

Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source

The composition of the microbial community associated with Macrobrachium rosenbergii zoeae varies throughout larval development

Oral Fluoroquinolone or Trimethoprim-Sulfamethoxazole vs ß-Lactams as Step-Down Therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis

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