Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: A report from the OPTAMA Program

  title={Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: A report from the OPTAMA Program},
  author={Heather K. Sun and Joseph L. Kuti and David P. Nicolau},
  journal={Critical Care Medicine},
Objective:To compare the probability of achieving specific pharmacodynamic exposures of commonly used intravenous antibiotics for the empirical treatment of nosocomial pneumonia against those pathogens most commonly implicated in the disease. Design:Ten thousand-subject Monte Carlo simulation. Setting:Research center. Subjects:None. Interventions:Pharmacodynamic analysis was conducted for the following antimicrobials at standard doses: meropenem, imipenem-cilastatin, ceftazidime, cefepime… 

Empiric Pharmacodynamic Performance of 9 Antimicrobials Against Pathogens Implicated in the Cause of Complicated Skin and Soft Tissue Infections: A Report From the OPTAMA Program

Third-generation cephalosporins, fluoroquinolones, and ertapenem should be avoided for the empiric treatment of cSSTIs in place of more broad-spectrum therapy, due to increasing resistance rates among commonly encountered pathogens.

Evaluation of dosing designs of carbapenems for severe respiratory infection using Monte Carlo simulation

Application of Monte Carlo simulation to MIC distributions allows determination of appropriate empiric therapy even if drug susceptibility of a causative organism in individual patients is unknown.

A Pharmacodynamic Simulation to Assess Tigecycline Efficacy for Hospital-Acquired Pneumonia Compared with Other Common Intravenous Antibiotics

Based on contemporary resistance data, tigecycline plus ceftazidime is predicted to achieve its pharmacodynamic targets similarly to combination therapy with imipenem plus vancomycin for the treatment of patients with HAP.

Making the most of surveillance studies: summary of the OPTAMA Program.

  • J. KutiD. Nicolau
  • Biology, Medicine
    Diagnostic microbiology and infectious disease
  • 2005

Support for higher ciprofloxacin AUC 24/MIC targets in treating Enterobacteriaceae bloodstream infection.

This study confirms the pharmacodynamic parameters of ciprofloxacin that are important for optimizing the treatment of serious infections, particularly the benefits of achieving an AUC(24)/MIC >or-250, rather than the conventional target of >or=125.

A pharmacodynamic strategy to optimize empirical antibiotic therapy for gram-negative bacteria in a Brazilian Intensive Care Unit.

  • C. KifferJ. Kuti D. Nicolau
  • Medicine, Biology
    The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases
  • 2007
It is recommended that in the presence of identified resistance problems among Gram-negative bacteria in a unit or hospital, MIC testing of formulary agents should be conducted along with pharmacodynamic simulation to assist in choosing an optimal antibiotic and dosage regimen for empirical use of severe infections until cultures and susceptibilities become available.

Update on the efficacy and tolerability of meropenem in the treatment of serious bacterial infections.

  • J. Mohr
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2008
Compared with clindamycin/tobramycin, meropenem is associated with a reduced length of hospital stay and a shorter duration of therapy among patients with complicated intra-abdominal infections and has an acceptable safety profile.

Meropenem: Focus on its Use in Serious Bacterial Infections

Meropenem is an effective broad-spectrum carbapenem antibiotic frequently prescribed for treatment of severe bacterial infections and has a favourable pharmacokinetic profile enabling distribution into many tissue sites whilst maintaining a good safety and tolerability profile in adult and paediatric patients.



Optimizing Pharmacodynamic Target Attainment Using the MYSTIC Antibiogram: Data Collected in North America in 2002

Given the lack of agreement between percent susceptibility and probability of target attainment for certain antimicrobial regimens, a methodology employing stochastic pharmacodynamic analyses may be a more useful tool for differentiating the most-optimal compounds and dosing regimens in the clinical setting of initial empirical therapy.

Optimizing antimicrobial pharmacodynamics: dosage strategies for meropenem.

Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia.

It is demonstrated that only the age of the patient and the achievement of an area under the curve: minimum inhibitory concentration ratio of > or =87 had a significant effect on eradication of the pathogen (P<.001).

Pharmacodynamics of Fluoroquinolones againstStreptococcus pneumoniae in Patients with Community-Acquired Respiratory Tract Infections

Findings may provide a minimum target free-drug AUC24/MIC ratio for the treatment of infections involving S. pneumoniae with fluoroquinolone antibiotics and provide a paradigm for the selection of fluoroquolones to be brought forward from drug discovery into clinical development and dose selection for clinical trials.

Application of fluoroquinolone pharmacodynamics.

Additional prospective clinical research is needed to characterize quinolone pharmacodynamic parameters and answer unresolved questions regarding optimal pharmacodynamic outcome predictors for Gram-positive bacteria, anaerobes and atypical respiratory pathogens.

Nosocomial pneumonia: the importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU.

The best approach for reducing infection-related mortality seems to be the initial institution of an adequate and broad-spectrum antibiotic regimen in severely ill patients, which should be modified in a de-escalating strategy when the results from microbiologic testing become available.

Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients.

  • M. Kollef
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2000
Clinicians can improve antimicrobial treatment by using empirical combination antibiotic therapy based on individual patient characteristics and the predominant bacterial flora and their antibiotic susceptibility profiles, and this broad-spectrum therapy can be narrowed when initial culture results are received.

Use of Monte Carlo Simulations To Select Therapeutic Doses and Provisional Breakpoints of BAL9141

Pharmacokinetic data obtained in a previous multiple ascending dose study were used to fit a population PK model to using the NPEM2 program, yielding PK parameter estimates and its covariance matrix for BAL9141, and unbiased target attainment rates (TARs) for various time periods during which the concentration remains above the MIC.

Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients

The rationale and tools needed for targeting the dosage of intravenous ciprofloxacin to individual patients' pharmacokinetics and their bacterial pathogens' susceptibilities are provided and shown to be more precise than current guidelines.