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Characterizing Multidrug Efflux Systems in Acinetobacter baumannii Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
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Published on: January 5, 2024

Management of meningitis due to antibiotic-resistant Acinetobacter species

Baek-Nam Kim1, Anton Y Peleg, Thomas P Lodise

  • 1University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, Australia.

The Lancet. Infectious Diseases
|March 28, 2009
PubMed

Insights

Acinetobacter meningitis treatment guidelines are inadequate. Current recommendations fail to achieve therapeutic targets against Acinetobacter isolates, necessitating novel treatment strategies for this serious infection.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Neurosurgery

Background:

  • Acinetobacter meningitis is a growing concern, particularly post-neurosurgery, with high mortality rates.
  • Current Infectious Diseases Society of America guidelines recommend ceftazidime or cefepime for empirical Gram-negative coverage.
  • Pharmacodynamic assessments reveal these cephalosporins are ineffective against most contemporary Acinetobacter isolates in cerebrospinal fluid.

Purpose of the Study:

  • Evaluate the efficacy of current and alternative antibiotic regimens for Acinetobacter meningitis.
  • Identify optimal therapeutic strategies for both carbapenem-susceptible and carbapenem-resistant Acinetobacter meningitis.
  • Address the challenges posed by multidrug-resistant Acinetobacter in neurosurgical patients.

Main Methods:

  • In vitro and pharmacodynamic analyses of antibiotic activity in cerebrospinal fluid.
  • Review of clinical experience with various antibiotic agents, including cephalosporins, meropenem, aminoglycosides, tigecycline, and polymyxins.
  • Consideration of combination therapy and adjunctive measures like hardware removal.

Main Results:

  • Recommended doses of ceftazidime and cefepime achieve pharmacodynamic targets in less than 10% of Acinetobacter isolates.
  • Intravenous meropenem combined with intraventricular aminoglycosides may offer a superior, though imperfect, treatment option.
  • Tigecycline is not recommended for carbapenem-resistant Acinetobacter meningitis due to poor pharmacodynamics.
  • Intravenous polymyxins alone are insufficient; combination therapy with intraventricular antibiotics and hardware removal is most promising.

Conclusions:

  • Current empirical antibiotic therapy for Acinetobacter meningitis is suboptimal.
  • Meropenem plus intraventricular aminoglycosides represents a potential alternative for susceptible strains.
  • Combination therapy, including polymyxins and intraventricular agents with hardware removal, is crucial for resistant cases.
  • Limited new antibiotic development and rising antimicrobial resistance pose future challenges for Acinetobacter meningitis treatment.

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