Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

For persons with nosocomial pneumonia (HAP, VAP, or HCAP) does optimization of antibiotic pharmacokinetic/pharmacodynamic parameters improve outcomes?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

Comparative studies or observational studies that permit calculation of an odds ratio for clinical outcome using an FDA-approved antibiotic for the treatment of nosocomial pneumonia

• Comparing patients with high PK/PD values to patients with low PK/PD values

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

Patients with VAP Patients in the ICU Patients in shock and with sepsis

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

Important subpopulations would include the immunocompromised, as well as populations infected with specific pathogens (e.g., Pseudomonas or other drug-resistant Gram-negatives).

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

Clinical response Length of hospital stay

Reduced 30-day all-cause mortality, in-hospital mortality

Describe any health-related risks, side effects, or harms that you are concerned about.

Adverse effects (e.g., nephrotoxicity) Drug resistance

Relapse of pneumonia within 30 days after antibiotic discontinuation

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Infectious diseases, including HIV/AIDS

AHRQ Priority Populations

• Low income groups
• Minority groups
• Women
• Children
• Elderly
• Individuals with special health care needs, including individuals with disabilities or who need chronic care or end-of-life health care

Federal Health Care Program

• Medicaid
• Medicare
• State Children's Health Insurance Program (SCHIP)

Importance

Describe why this topic is important.

8. Describe why this topic is important.

Nosocomial pneumonia (HCAP, HAP or VAP) is the leading cause of death from nosocomial infection in the United States. The prevalence of antibiotic-resistant bacteria continues to increase, particularly among patients in the intensive care unit with nosocomial pneumonia. The optimal therapeutic regimen is essential to minimizing the risk of drug resistance and treatment failure. It involves choosing the right drug, the right dose and the right duration de-escalated to pathogen-directed therapy that will ensure adequate penetration of the antibiotic at the site of infection.

The pharmacokinetic (PK) (i.e., how the body affects a specific drug after administration) and pharmacodynamic (PD) (i.e., how the biochemical and physiological properties of the drug affect the body) features of antibiotics are used to help achieve optimal antibiotic regimens for nosocomial pneumonia, but not without controversy. Most studies correlating PK/PD measures and clinical response in humans have been conducted in persons with community-acquired pneumonia (CAP) weighted toward treatment of either methicillin sensitive or methicillin resistant S. Aureus (MSSA or MRSA). It is unclear if these findings translate to the treatment of HAP, particularly in patients with late onset VAP or who were previously exposed to antibiotics, because the causative pathogen(s) is/are more likely to be multi-drug resistant. Data are emerging that suggest patients with sepsis are being under-dosed, adding to mortality.

IDSA guidelines for MRSA (2011) and HAP (2005) acknowledge that the evidence supporting recommendations for use of PK/PD measures for dosing and monitoring in adults with nosocomial pneumonia is limited, and even more so in children; the relevance of PK/PD measures to patient outcome involving HAP has not been defined. A systematic review is needed at this time to identify new literature that may clarify the role of PK/PD measures in

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

This topic was given a high priority by a multi-disciplinary stakeholder panel (including patient and employer perspectives) convened to identify and select important research questions on RTIs amenable for systematic review.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

The stakeholder panel noted the uncertainty in the role of PK/PD for dosing and monitoring of antibiotics for persons with HAP and HCAP and resultant variations in practice.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

A report would inform clinical decision-making for patients, payers and providers.

Describe the timeframe in which an answer to your question is needed.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

This would apply to any person with HAP, HCAP or VAP, but particularly to those with serious underlying conditions, the immunocompromised, children and the critically ill, who would be susceptible to multidrug resistant pathogens. Current dosing and monitoring practices are based on PK/PD features of antibiotics for treatment of CAP, but it is unclear if this information can or should be applied to hospitalized patients, particularly the critically ill with VAP, shock or sepsis. We need robust evidence on which to base antibiotic administration decisions in these populations to reduce the risk of drug resistance and clinical failure.

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

A report would inform clinical decision-making for patients, payers and providers.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program

The Blue Cross and Blue Shield Association Technology Evaluation Center is an Evidence-based Practice Center of AHRQ.