Antimicrobial Stewardship on Patients with Neutropenia: A Narrative Review Commissioned by Microorganisms
Abstract
:Highlights
- “Right first time” and achieving source control is crucial to optimize antibiotic management in neutropenic patients.
- The fear of missed pathogens and the risk of emergent resistant organisms require detailed knowledge of local patterns of susceptibility and a multidisciplinary team.
- A consistent pattern of safety requires shortening duration of therapy.
- Rapid diagnostic tools contribute to improve overall empiric antibiotic use, which should be a priority in neutropenic patients.
- A 5D approach is a core strategy to ensure improving antibiotic use
- Emphasis to a personalized prescription of antibiotics is required.
Abstract
1. Introduction
2. The Epidemiologic Change
Reference | Country | Years | Study Type | Population | Pathogens | Resistance Type | 30-Day Mortality |
---|---|---|---|---|---|---|---|
Cattaneo C et al., 2016 [15] | Italy | 2012–2014 | Prospective, multicentric | ALL and AML (n = 239, 433 BSI episodes) | GPB 44.8%: CoNS 25.4%, S. aureus 4.4%, Enterococcus spp. 2.6% | Methicillin-resistance: CoNS 77.6%, MRSA 80% | 8.5%; higher for CRE + MDR-Pa: 29.6 vs. 6.1% (p < 0.01) |
GNB 38.4%: Enterobacterales 28.1%, P. aeruginosa 10.5%, Polymicrobial 15.7%, fungi 1.1% | ESBL-E 23.2% | ||||||
During Induction phase: GBP 50.9%, GNB 31.9%, polymicrobial 13.8%, fungi 3.4% | CRE 9% | ||||||
During consolidation phase: GPB 38.9%, GNB 46.8%, polymicrobial 14.3%, fungi 0% | MDR-Pa 27% | ||||||
Stoma I et al., 2016 [19] | Belarus | 2013–2015 | Prospective, single center | HSCT (n = 360, 135 BSI episodes) | GPB 34.9%: S. aureus 17%, CoNS 5.2%, Enterococci 3% | Methicillin-resistance: CoNS 27.8%, MRSA 65.2% | 31.1%; higher for carbapenem-resistant nonfermenters (OR 5.46 (95% CI 1.33–20.7), p = 0.0126) |
GNB 64.4%: Enterobacterales 43.7%, Nonfermenters 21.5% | ESBL-E 40.7%, CRE 11.9%, Carbapenem-resistant nonfermenters 79.3% | ||||||
Scheich S et al., 2018 [16] | Germany | 2008–2016 | Retrospective, single center | HM w/GNB BSI (n = 109) | Only Gram-negative episodes evaluated: Enterobacterales 73.4%; Nonfermenters 26.6% | MDR pathogens * 19.4%: P. aeruginosa 37.5%, E. coli 34.4%, K. pneumoniae 25% | 23.2%; higher for MDR vs. non-MDR GNB: 44.1% vs. 14.4% (p < 0.001) |
Ali R et al., 2020 [17] | Turkey | 2006–2016 | Retrospective, single center | HM (n = 552, 950 BSI episodes) | GPB 48.3%: CoNS 37.8%, S. aureus 2.5%, Enterococcus spp. 5% | Methicillin-resistance: CoNS 84.6%, MRSA 19.2% | 17.7%; higher for MDR-GNB infections: ESBL: 27.5% vs. 11.7% (p < 0.01), carbapenem-resistance: 65.4% vs. 14.8% (p < 0.01), MDR: 68.2% vs. 20.4% (p < 0.01) |
VRE 21.6% | |||||||
GNB 42.4%: E. coli 19.4%, Klebsiella spp. 11.8%, Pseudomonas spp. 5.5%, Acinetobacter baumanii 3.5% | ESBL-E 39.4% CRE 9.8% | ||||||
Carbapenem-resistant nonfermenters 32.6% | |||||||
Weber S et al., 2021 [24] | Germany | 2006–2019 | Retrospective, single center | HM, other hematological disorders, SOT (n = 391, 637 BSI episodes) | Common skin contaminants (coagulase-negative Staphylococcus spp., Bacillus spp., Corynebacterium spp., Cutibacterium spp., and Micrococcus spp.) 24.8%; Escherichia spp. 19%; Enterococcus spp. 13% | VRE 10% | Higher for carbapenem-resistant GNB infections: 62.5% vs. 4.7–18.7% |
MDR GNB 6.8% | |||||||
Carbapenem-resistant GNB 2.5% |
3. Antimicrobial Stewardship Programs in Patients with Neutropenia
4. AMS Strategies to Optimize Antibiotic Therapy
4.1. Diagnosis
4.1.1. Risk Assessment
4.1.2. Diagnostic Tools
4.2. Conventional Microbiology
4.3. Biomarkers
4.4. Rapid Diagnostic Testing and Rapid Antimicrobial Susceptibility Testing
4.5. Molecular Biology
4.6. Drug
4.7. Dose
4.8. Duration/Early Discontinuation
4.9. De-Escalation
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Antimicrobial Stewardship Strategy | Rationale | Evidence Gaps |
---|---|---|
1. Diagnosis | The initiation of empirical antibiotic treatment should be prompted by fever and clinical signs, and not by C-reactive protein or other biomarkers. | |
Risk Assessment:
| Appropriate screening methodology is unknown and dependent on local epidemiology. | |
Early and specific microbiology diagnosis is essential to directed therapy and minimizing the use of broad-spectrum antibiotics. | Does not substitute conventional culture-based methods. | |
Cascade or selective antimicrobial susceptibility reports promote available narrow-spectrum antibiotics. | No guidelines available. | |
Rapid antimicrobial susceptibility testing improves management of antibiotic therapy in patients with Gram-negative sepsis. | Gram-positive infections. | |
2. Drug | Appropriate empirical antibiotic is associated with better patient outcomes. | |
Facility-specific treatment guidelines standardize prescribing practices based on local epidemiology. | ||
Monotherapy versus combination therapy has equivalent efficacy. | ||
Therapeutic reconciliation is an effective strategy in preventing adverse drug reactions. | ||
3. Dose | Underdosing of antibiotics is associated with treatment failures and worse outcomes. | |
Administer loading dose when indicated. | ||
Prolonged infusion of beta-lactams is associated with better outcomes. | ||
TDM achieves the efficacy dose and avoids overdosing and adverse effects. | Further studies are needed to demonstrate the benefit of beta-lactam TDM. | |
4. Duration (and early discontinuation) | Shorter antibiotic administration seems safe, does not have a detrimental impact on outcomes, and reduces the use of broad-spectrum antibiotics. | Further studies are needed to reinforce the evidence and to evaluate the impact on resistance. |
5. De-escalation | De-escalation based on microbiology diagnosis is safe, does not have a detrimental impact on outcomes, and reduces the use of broad-spectrum antibiotics. | Further studies are needed to reinforce the evidence and to evaluate the impact on resistance. |
Local Epidemiology | Preferred Antibiotic Treatment | Alternative Antibiotic Treatment |
---|---|---|
Without risk for E-ESBL, CRE, MDR Pseudomonas aeruginosa, or MRSA | Cefepime or Piperacillin/tazobactam or Meropenem or Imipenem/cilastatin | Ceftazidime–avibactam or Aztreonam (consider addition of vancomycin for Gram-positive coverage) or Aminoglycoside (uncomplicated bloodstream infections with complete source control) |
Presumed or confirmed extended-spectrum β-Lactamase-producing Enterobacterales | Meropenem or Imipenem/cilastatin | Ceftazidime–avibactam or Aztreonam (consider addition of vancomycin for Gram-positive coverage) or Aminoglycoside (uncomplicated bloodstream infections with complete source control) |
Presumed or confirmed carbapenem-resistant Enterobacterales | Ceftazidime–avibactam or Meropenem–vaborbactam or Imipenem/cilastatin–relebactam | Cefiderocol or Aminoglycoside (uncomplicated bloodstream infections with complete source control) |
Presumed or confirmed difficult-to-treat Pseudomonas aeruginosa | Ceftolozane–tazobactam or Ceftazidime–avibactam or Imipenem/cilastatin–relebactam | Cefiderocol or Aminoglycoside (uncomplicated bloodstream infections with complete source control) |
Presumed or confirmed MRSA | Add vancomycin | Add Daptomycin or Linezolide |
Antibiotic | Adult Dosage, Assuming Normal Renal and Liver Function |
---|---|
Amikacin | 20 mg/kg/dose IV (subsequent doses and dosing interval based on pharmacokinetic evaluation) |
Aztreonam | 2 g IV every 8 h, infused over 3 h |
Cefepime | 2 g IV every 8 h, infused over 3 h |
Ceftazidime–avibactam | 2.5 g IV every 8 h, infused over 3 h |
Ceftolozane–tazobactam | 3 g IV every 8 h, infused over 3 h |
Gentamicin | 7 mg/kg/dose IV (subsequent doses and dosing interval based on pharmacokinetic evaluation) |
Imipenem/cilastatin | 500 mg IV every 6 h, infused over 3 h |
Imipenem/cilastatin–relebactam | 1.25 g IV every 6 h, infused over 30 min |
Meropenem | 2 g IV every 8 h, infused over 3 h |
Meropenem–vaborbactam | 4 g IV every 8 h, infused over 3 h |
Piperacillin-tazobactam | 4.5 g IV every 6 h, infused over 3 h |
Plazomicin | 15 mg/kg/dose IV (subsequent doses and dosing interval based on pharmacokinetic evaluation) |
Vancomycin | Loading dose up to 35 mg/kg IV (maximum 3 g) and maintenance dose 15–20 mg/kg 8–12 h, adjusted to achieve target AUC24 of 400–600 (subsequent doses based on pharmacokinetic evaluation) |
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Alves, J.; Abreu, B.; Palma, P.; Alp, E.; Vieceli, T.; Rello, J. Antimicrobial Stewardship on Patients with Neutropenia: A Narrative Review Commissioned by Microorganisms. Microorganisms 2023, 11, 1127. https://doi.org/10.3390/microorganisms11051127
Alves J, Abreu B, Palma P, Alp E, Vieceli T, Rello J. Antimicrobial Stewardship on Patients with Neutropenia: A Narrative Review Commissioned by Microorganisms. Microorganisms. 2023; 11(5):1127. https://doi.org/10.3390/microorganisms11051127
Chicago/Turabian StyleAlves, Joana, Betânia Abreu, Pedro Palma, Emine Alp, Tarsila Vieceli, and Jordi Rello. 2023. "Antimicrobial Stewardship on Patients with Neutropenia: A Narrative Review Commissioned by Microorganisms" Microorganisms 11, no. 5: 1127. https://doi.org/10.3390/microorganisms11051127