Tag Archives: Anti-Bacterial Agents

Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. (Betters)

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Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis*. Crit Care Med. 2014 Nov; 42(11):2409-17.

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OBJECTIVES: Delayed antimicrobials are associated with poor outcomes in adult
sepsis, but data relating antimicrobial timing to mortality and organ dysfunction
in pediatric sepsis are limited. We sought to determine the impact of
antimicrobial timing on mortality and organ dysfunction in pediatric patients
with severe sepsis or septic shock.

DESIGN: Retrospective observational study.

SETTING: PICU at an academic medical center.

PATIENTS: One hundred thirty patients treated for severe sepsis or septic shock.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We determined if hourly delays from sepsis
recognition to initial and first appropriate antimicrobial administration were
associated with PICU mortality (primary outcome); ventilator-free,
vasoactive-free, and organ failure-free days; and length of stay. Median time
from sepsis recognition to initial antimicrobial administration was 140 minutes
(interquartile range, 74-277 min) and to first appropriate antimicrobial was 177
minutes (90-550 min). An escalating risk of mortality was observed with each hour
delay from sepsis recognition to antimicrobial administration, although this did
not achieve significance until 3 hours. For patients with more than 3-hour delay
to initial and first appropriate antimicrobials, the odds ratio for PICU
mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76),
respectively. These associations persisted after adjustment for individual
confounders and a propensity score analysis. After controlling for severity of
illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2)
and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first
appropriate antimicrobials, respectively. Initial antimicrobial administration
more than 3 hours was also associated with fewer organ failure-free days (16
[interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04).

CONCLUSIONS: Delayed antimicrobial therapy was an independent risk factor for
mortality and prolonged organ dysfunction in pediatric sepsis.

 

Procalcitonin to predict bacterial coinfection in infants with acute bronchiolitis: a preliminary analysis. (Petrillo)

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Laham JL, Breheny PJ, Gardner BM, Bada H. Procalcitonin to predict bacterial coinfection in infants with acute bronchiolitis: a preliminary analysis. Pediatr Emerg Care. 2014 Jan;30(1):11-5.

OBJECTIVE: The aim of this study was to conduct a preliminary analysis of serum procalcitonin (PCT) to predict bacterial coinfection in infants with acute bronchiolitis.

METHODS: Retrospective cohort chart review of 40 infants admitted with acute bronchiolitis to the pediatric intensive care unit. Logistic regression models were used to determine the association of PCT and white blood count with presence of bacterial coinfection defined by either positive culture or chest radiograph result.

RESULTS: Fifteen (38%) of 40 patients had a diagnosis of bacterial coinfection by positive culture (9/15) or chest radiograph (6/15). Procalcitonin (P < 0.0001) was significantly associated with bacterial coinfection. A cutoff value of 1.5 ng/mL had sensitivity of 0.80, specificity of 1.00, and area under the operating curve of 0.88. White blood count (P = 0.06) was borderline significant with sensitivity of 0.33, specificity of 0.96, and area under the operating curve of 0.67. Three of 15 patients were later found to have bacterial coinfection with initial PCT of less than 1.5 ng/mL. None had follow-up PCT measurements taken. Thirty-five of 40 were prescribed empiric antibiotic therapy, including 20 of 25 patients without evidence of bacterial coinfection. None had a PCT of greater than 1.5 ng/mL. If a PCT cutoff of greater than 1.5 ng/mL had been used, 57% fewer patients would have received antibiotics with a 45% reduction in antimicrobial charges.

CONCLUSIONS: An elevated PCT may assist clinicians in determining presence of bacterial coinfection at admission in infants with acute bronchiolitis. Implementation of a PCT cutoff of 1.5 ng/mL at admission may prevent unnecessary antibiotic use with associated cost savings. Serial PCT levels may increase sensitivity. Further validation is warranted.

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Less is more: combination antibiotic therapy for the treatment of gram-negative bacteremia in pediatric patients. (Hebbar)

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Tamma PD, Turnbull AE, Harris AD, Milstone AM, Hsu AJ, Cosgrove SE. Less is more: combination antibiotic therapy for the treatment of gram-negative bacteremia in pediatric patients. JAMA Pediatr. 2013 Oct 1;167(10):903-910.

IMPORTANCE Definitive combination antibiotic therapy with a β-lactam and an aminoglycoside for the treatment of gram-negative bacteremia is commonly prescribed in pediatric patients; however, its efficacy and toxicity relative to β-lactam monotherapy are unknown.

OBJECTIVE To determine whether definitive combination antibiotic therapy affects mortality and nephrotoxicity in pediatric patients with gram-negative bacteremia.

DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study including pediatric patients (aged ≤18 years) with gram-negative bacteremia hospitalized at the Johns Hopkins Children’s Center between 2002 and 2011.

MAIN OUTCOMES AND MEASURES Outcomes included 30-day mortality and nephrotoxicity classified according to the pediatric RIFLE (risk for renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage renal disease) criteria. To account for nonrandom assignment of combination therapy, propensity score weighting was combined with multivariable logistic regression to estimate the effect of combination therapy on mortality and nephrotoxicity.

RESULTS Of the 879 eligible pediatric patients with bacteremia, 537 (61.1%) received combination therapy. After propensity score adjustment, baseline demographic and clinical characteristics between the groups were well balanced. There was no association between combination therapy and 30-day mortality (odds ratio, 0.98; 95% CI, 0.93-1.02; P = .27). There were 170 patients (19.3%) with evidence of acute kidney injury, including 135 (25.1%) and 35 (10.2%) in the combination therapy and monotherapy arms, respectively. Patients receiving combination therapy had approximately twice the odds of nephrotoxicity compared with those receiving monotherapy (odds ratio, 2.15; 95% CI, 2.09-2.21).

CONCLUSIONS AND RELEVANCE The use of β-lactam monotherapy for gram-negative bacteremia in pediatric patients reduces subsequent nephrotoxicity without compromising survival.

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Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. (Grunwell)

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Oliveira CF, Botoni FA, Oliveira CR, Silva CB, Pereira HA, Serufo JC, Nobre V. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med. 2013 Oct;41(10):2336-43.

OBJECTIVE: We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis.

DESIGN: Randomized open clinical trial.

SETTING: Two university hospitals in Brazil.

PATIENTS: Patients with severe sepsis or septic shock.

INTERVENTIONS: Patients were randomized in two groups: the procalcitonin group and the C-reactive protein group. Antibiotic therapy was discontinued following a protocol based on serum levels of these markers, according to the allocation group. The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25% shorter than in the C-reactive protein group. For both groups, at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and/or bacteremia at inclusion, and patients with evident resolution of the infectious process had antibiotics stopped after 7 days, despite biomarkers levels.

MEASUREMENTS AND MAIN RESULTS: Ninety-four patients were randomized: 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group. The mean age was 59.8 (SD, 16.8) years. The median duration of antibiotic therapy for the first episode of infection was 7.0 (Q1-Q3, 6.0-8.5) days in the procalcitonin group and 6.0 (Q1-Q3, 5.0-7.0) days in the C-reactive protein group (p = 0.13), with a hazard ratio of 1.206 (95% CI, 0.774-1.3; p = 0.13). Overall, protocol overruling occurred in only 13 (13.8%) patients. Twenty-one patients died in each group (p = 0.836).

CONCLUSIONS: C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients, causing no apparent harm.

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