scholarly journals Antibiotics in critically ill children—a narrative review on different aspects of a rational approach

2021 ◽  
Author(s):  
Nora Bruns ◽  
Christian Dohna-Schwake
Keyword(s):  
Antibiotic Therapy ◽  
Critically Ill ◽  
Antibiotic Treatment ◽  
Antibiotic Stewardship ◽  
Narrative Review ◽  
Rational Approach ◽  
Critically Ill Children ◽  
Resistant Bacteria ◽  
Therapeutic Drug ◽  
List Type

Abstract Especially critically ill children are exposed to antibiotic overtreatment, mainly caused by the fear of missing out a severe bacterial infection. Potential adverse effects and selection of multi-drug resistant bacteria play minor roles in decision making. This narrative review first describes harm from antibiotics and second focuses on different aspects that could help to reduce antibiotic overtreatment without harming the patient: harm from antibiotic treatment, diagnostic approaches, role of biomarkers, timing of antibiotic therapy, empiric therapy, targeted therapy, and therapeutic drug monitoring. Wherever possible, we linked the described evidence to the current Surviving Sepsis Campaign guidelines. Antibiotic stewardship programs should help guiding antibiotic therapy for critically ill children. Impact Critically ill children can be harmed by inadequate or overuse of antibiotics. Hemodynamically unstable children with a suspicion of infection should be immediately treated with broad-spectrum antibiotics. In contrast, in hemodynamically stable children with sepsis and organ dysfunction, a time frame of 3 h for proper diagnostics may be adequate before starting antibiotics if necessary. Less and more targeted antibiotic treatment can be achieved via antibiotic stewardship programs.

scholarly journals Personalized Antibiotic Therapy for the Critically Ill: Implementation Strategies and Effects on Clinical Outcome of Piperacillin Therapeutic Drug Monitoring—A Descriptive Retrospective Analysis

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1452
Author(s):  
Schrader Nikolas ◽  
Riese Thorsten ◽  
Kurlbaum Max ◽  
Meybohm Patrick ◽  
Kredel Markus ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Antibiotic Therapy ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Implementation Strategy ◽  
Care Staff ◽  
Therapeutic Drug ◽  
Health Care Staff ◽  
Standard Operating

Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians’ alertness.

scholarly journals Duration of antibiotic therapy in critically ill patients: a randomized controlled trial of a C-reactive protein-based protocol versus an evidence-based best practice strategy without biomarkers

2020 ◽  
Author(s):  
Isabela Nascimento Borges ◽  
Rafael Carneiro ◽  
Rafael Bergo ◽  
Larissa Martins ◽  
Enrico Colosimo ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Critically Ill ◽  
Antibiotic Treatment ◽  
Median Duration ◽  
Critically Ill Patients ◽  
Treatment Time ◽  
C Reactive Protein ◽  
Daily Monitoring ◽  
Reactive Protein ◽  
To Receive

Abstract Background: The rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance . We therefore sought to evaluate the effectiveness of a C reactive protein-based protocol in reducing antibiotic treatment time in critically ill patients.Methods: A randomized, open-label, controlled clinical trial conducted in two intensive care units of a university hospital in Brazil. Critically ill infected adult patients were randomly allocated to: i) intervention to receive antibiotics guided by daily monitoring of CRP levels, and ii) control to receive antibiotics according to the best practices for rational use of antibiotics.Results : 130 patients were included in the CRP (n=64) and control (n=66) groups. In the intention to treat analysis, the median duration of antibiotic therapy for the index infectious episode was 7.0 (5.0-8.8) days in the CRP and 7.0 (7.0-11.3) days in the control (p = 0.011) groups. A significant difference in the treatment time between the two groups was identified in the curve of cumulative suspension of antibiotics, with less exposure in the CRP group (p = 0.007). In the per protocol analysis, involving 59 patients in each group, the median duration of antibiotic treatment was 6.0 (5.0-8.0) days for the CRP and 7.0 (7.0- 10.0) days for the control (p = 0.011) groups. Conclusions: Daily monitoring of CRP levels may aid in the reduction of antibiotic treatment time of critically ill patients, even in a scenario of judicious use of antimicrobials. Trial Registry : ClinicalTrials.gov Identifier: NCT02987790. Registered 09 December 2016, https://clinicaltrials.gov/ct2/show/NCT02987790 .

scholarly journals P43 Pharmacokinetics and target attainment of antibiotics in critically ill children – a systematic review of current literature

2019 ◽  
Vol 104 (6) ◽  
pp. e35.1-e35
Author(s):  
S Hartman ◽  
R Brüggemann ◽  
L Orriëns ◽  
N Dia ◽  
M Schreuder ◽  
...  
Keyword(s):  
Critically Ill ◽  
Patient Population ◽  
Current Knowledge ◽  
Volume Of Distribution ◽  
Critically Ill Children ◽  
Therapeutic Drug ◽  
Healthy Children ◽  
Target Attainment ◽  
Critically Ill Adults ◽  
Ill Adults

BackgroundPharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). To what extent this affects the PK of antibiotics in critically children is largely unknown. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.MethodsSystematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, trough concentrations, AUC, probability of target attainment, and elimination half-life.Results45 relevant articles were identified. Studies focusing on vancomycin were most prevalent (15/45). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a larger Vd and higher Cl than healthy children and critically ill adults. Reduced target attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 32/45 articles included information on both Vd and Cl, but a dosing advice was given in only 18 articles.ConclusionThe majority of studies focus on agents where therapeutic drug monitoring is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl that is observed in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.Disclosure(s)Nothing to disclose

scholarly journals Multidrug resistant bacteria in critically ill patients: a step further antibiotic therapy

2018 ◽  
Vol 2 ◽  
pp. 103-103 ◽  
Author(s):  
Martina Tosi ◽  
Erika Roat ◽  
Sara De Biasi ◽  
Elena Munari ◽  
Sophie Venturelli ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria

Red blood cell transfusion in critically ill children: A narrative review*

2011 ◽  
Vol 12 (2) ◽  
pp. 174-183 ◽  
Author(s):  
George K. Istaphanous ◽  
Derek S. Wheeler ◽  
Steven J. Lisco ◽  
Aryeh Shander
Keyword(s):  
Blood Cell ◽  
Critically Ill ◽  
Red Blood Cell ◽  
Narrative Review ◽  
Red Blood Cell Transfusion ◽  
Critically Ill Children

scholarly journals Infections with Carbapenem-Resistant Gram-Negative Bacteria are a Serious Problem Among Critically Ill Children: A Single-Centre Retrospective Study

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 69 ◽  
Author(s):  
Fatih Aygun ◽  
Fatma Deniz Aygun ◽  
Fatih Varol ◽  
Cansu Durak ◽  
Haluk Çokuğraş ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Critically Ill ◽  
Bacterial Infections ◽  
Invasive Mechanical Ventilation ◽  
Critically Ill Children ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Culture Positive

Children in paediatric intensive care units (PICUs) are vulnerable to infections because invasive devices are frequently used during their admission. We aimed to determine the prevalence, associated factors, and prognosis of infections in our PICU. This retrospective study evaluated culture results from 477 paediatric patients who were treated in the PICU between January 2014 and March 2019. Ninety patients (18.9%) had bacterial infections, with gram-negative bacteria being the predominant infectious agents. Culture-positive patients were younger than culture-negative patients, and age was related to mortality and various clinical factors. Culture-positive bacterial infections in the PICU were associated with increased use of invasive mechanical ventilation (odds ratio(OR); 2.254), red blood cell (RBC) transfusions (OR:2.624), and inotropic drugs (OR:2.262). Carbapenem resistance was found in approximately one-third of gram-negative bacteria, and was most common in tracheal aspirate specimens and cases involving Klebsiella spp. Total parenteral nutrition was a significant risk factor (OR:5.870). Positive blood culture results were associated with poorer patient survival than other culture results. These findings indicate that infections, especially those involving carbapenem-resistant bacteria, are an important issue when treating critically ill children.

scholarly journals O33 Towards personalised weaning of sedatives and analgesics using mechanism-based modelling of iatrogenic withdrawal in critically ill children

2019 ◽  
Vol 104 (6) ◽  
pp. e14.3-e15
Author(s):  
S Goulooze ◽  
E Krekels ◽  
M van Dijk ◽  
T Hankemeier ◽  
D Tibboel ◽  
...  
Keyword(s):  
Critically Ill ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Statistical Significance ◽  
Prolonged Treatment ◽  
Morphine Dependence ◽  
Critically Ill Children ◽  
Population Pharmacokinetic ◽  
List Type ◽  
Over Time

BackgroundProlonged treatment with analgesics and sedatives can result in iatrogenic withdrawal syndrome (IWS) in children being weaned from these drugs.1Personalized weaning strategies might lower the incidence of IWS, but this requires a quantitative understanding of withdrawal over time in individual patients.MethodsData from 81 children (aged 1 month to 17 years) collected during an observational clinical study on IWS2 were used, including a total of 1782 withdrawal assessments performed by PICU nurses, on a numerical rating scale (NRSwithdrawal) from 0 (no withdrawal) to 10 (worst withdrawal possible). Population pharmacokinetic models from literature were used to generate concentration-time profiles in each patient of all key analgesics and sedatives: morphine, fentanyl, methadone, midazolam, lorazepam, propofol, esketamine and clonidine. A mechanism-based withdrawal model was developed using NONMEM 7.3 to quantify IWS over time. The final model was used to perform simulations in which different weaning strategies were compared.ResultsA novel mechanism-based withdrawal model structure was developed with a hypothetical compartment, which equilibrates with the central pharmacokinetic compartment, and which characterizes the development and disappearance of drug dependence over time. With this model and available data, withdrawal dynamics could be established with statistical significance for fentanyl (p< 10-6), morphine (p=0.043) and esketamine (p=0.002), and not for any of the other drugs. Compared with fentanyl, development and disappearance of esketamine and morphine dependence is slower.ConclusionsGiven the patient‘s use of fentanyl, morphine and esketamine, the developed model can dynamically predict IWS from these substances under different weaning strategies. The results show that the optimal strategy for weaning of drug dependent children depends on both the type of drug and the drug levels prior to weaning. In this study, there was insufficient information to characterise midazolam withdrawal dynamics, potentially because of slow midazolam weaning with insufficiently high NRSwithdrawal scores.ReferencesBest KM, Boullata JI, Curley MAQ. Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: A Systematic Review and Conceptual Model. Pediatr Crit Care Med ( 2015) 16(2): 175–183.Ista E, de Hoog M, Tibboel D, Duivenvoorden HJ, van Dijk M. Psychometric evaluation of the sophia observation withdrawal symptoms scale in critically ill children. Pediatr Crit Care Med ( 2013).14(8): 761–769.Disclosure(s)Nothing to disclose

Procalcitonin-Guided Antibiotic Therapy Duration in Critically Ill Adults

2015 ◽  
Vol 26 (2) ◽  
pp. 99-106 ◽  
Author(s):  
Caroline Walker
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Antibiotic Therapy ◽  
Critically Ill ◽  
Bacterial Infections ◽  
Unit Length ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Control Group ◽  
Duration Of Treatment

Procalcitonin is a promising biomarker for antibiotic therapy because its levels rise and fall quickly with bacterial infections. A multi-database literature search was reviewed with 3 primary prospective randomized control trials used in further analysis. The results indicated that a procalcitonin-guided antibiotic protocol reduces the number of days a patient has to take antibiotics while having no effect on mortality when compared with control groups. Short-term studies did not show a difference in the intensive care unit length of stay, infection relapse rate, super-infection rate, or multidrug-resistant bacteria rate between the procalcitonin-protocol and control group. Because procalcitonin-guided antibiotic therapy has been shown to reduce the duration of treatment with antibiotics in critically ill patients without worsening the mortality rate or other outcomes, the implementation of a procalcitonin-guided antibiotic therapy should be considered for patients with proven or highly suspected bacterial infections in the intensive care unit.

Dilemmas in Primary Care: Antibiotic Treatment of Acute Otitis Media

1986 ◽  
Vol 20 (9) ◽  
pp. 666-669 ◽  
Author(s):  
Bev Lorraine True ◽  
Dennis K. Helling
Keyword(s):  
Primary Care ◽  
Antibiotic Therapy ◽  
Otitis Media ◽  
Antibiotic Treatment ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Rational Approach ◽  
Recurrence Rates ◽  
Middle Ear Fluid ◽  
Initial Antibiotic Therapy

Antibiotic treatment of acute otitis media (AOM) accounts for a significant number of all antibiotic prescriptions each year. In the primary care setting, initial antibiotic selection is rarely based on direct evidence, such as cultures of middle ear fluid. Initial antibiotic therapy by the primary care practitioner involves the evaluation and application of information related to prevalence of infecting organisms; in vitro antibiotic spectrum and penetration into middle ear fluid; initial cure rate, relapse and recurrence rates; and antibiotic cost, safety, and convenience. The influence of these factors on the initial antibiotic choice for AOM is reviewed. Several therapeutic dilemmas confronting the prescriber are discussed and a rational approach to initial antibiotic therapy is presented.

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