[Federal Register Volume 64, Number 126 (Thursday, July 1, 1999)]
[Notices]
[Pages 35670-35673]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-16759]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention
[Program Announcement 99149]


Changing Antimicrobial Prescribing To Reduce Antimicrobial 
Resistance in Hospitalized Patients; Availability of Funds

A. Purpose

    The Centers for Disease Control and Prevention (CDC) announces the 
availability of fiscal year (FY) 1999 funds for a cooperative agreement 
program for Changing Antimicrobial Prescribing to Reduce Antimicrobial 
Resistance in Hospitalized Patients. This program addresses the 
``Healthy People 2000'' priority area(s) of Immunization and Infectious 
Diseases.
    The impact of antimicrobial resistant infections on patients is 
considered to be substantial, and the societal cost to the United 
States (U.S.) has been estimated to be as high as $4 Billion each year. 
Hospitalized patients are at greatest risk of acquiring these resistant 
infections. An increasing number of hospitals and other healthcare 
facilities are reporting the presence of antimicrobial resistant 
bacteria each year. The knowledge that a defined program to change 
antimicrobial prescribing activity will reduce the incidence of these 
infections will benefit all U.S. hospitals in their battle against 
antimicrobial resistant infections. The proposed study in this program 
announcement will impart such knowledge to the infection control and 
hospital community.
    The purpose of the program is to assist U.S. healthcare 
institutions and public health agencies in evaluating the impact of 
changes in antimicrobial prescribing on the incidence of antimicrobial 
resistance and other health outcomes among hospitalized patients. 
Recipients of this award will form a collaborative network of 
researchers, using similar methodology to allow aggregation of 
surveillance data from all sites into a multi-site study. The change in 
antimicrobial prescribing would be considered a part of routine medical 
practice for the selected patient population groups. Evaluating the 
impact of routine cycling of available select antimicrobial agents for 
empiric therapy is the top priority for this collaborative network. 
Results of this multi-site study will provide other U.S. hospitals with 
guidance to implement programs to reduce antimicrobial resistance at 
their institutions. The objective of this program is to measure (see 
recipient activities) the change in incidence and prevalence of patient 
colonization and infection with select antimicrobial resistant bacteria 
of epidemiologic concern in the following scenario:
    1. During a time of altered antimicrobial prescription activity 
(specifically the routine cycling of available antimicrobial agents).
    2. In a (1) medical intensive care unit and (2) other target 
patient population group(s) (e.g., trauma intensive care unit, 
transplant patients, diabetic patients, etc.).

B. Eligible Applicants

    Applications may be submitted by public and private nonprofit 
organizations and by governments and their agencies; that is, 
universities, colleges, research institutions, hospitals, other public 
and private nonprofit or for-profit organizations participating in the 
healthcare delivery to patients in hospitals. These hospitals must 
fulfill the following criteria and provide appropriate documentation 
(see application instructions) in the application:
    1. Have >250 licenced beds.
    2. Have a medical intensive care unit in which a limited number 
(i.e., 1-4) of attending physicians have ultimate responsibility for 
patient care in that intensive care unit during a typical month (i.e., 
a closed unit).
    3. Have ongoing surveillance in the medical intensive care unit of 
two types: (1) nosocomial infections and (2) rectal (or stool) 
surveillance cultures, on admission or at some standard period, for 
some antimicrobial resistant bacteria.
    4. Have access to a clinical microbiology laboratory which can 
demonstrate proficiency at:
    a. Identifying extended-spectrum ``-lactamase producing 
enterobactericea.
    b. Maintain viable frozen specimens from surveillance samples.

    Note: Public Law 104-65 states that an organization described in 
section 501(c)(4) of the Internal Revenue Code of 1986 that engages 
in lobbying activities is not eligible to receive Federal funds 
constituting an award, grant, cooperative agreement, contract, loan, 
or any other form.

C. Availability of Funds

    Approximately $200,000 is available in FY 1999 to fund 
approximately 3 awards. It is expected that the average award will be 
$80,000, ranging from $60,000 to $100,000. It is expected that the 
awards will begin on or about September 30, 1999 and will be made for a 
12-month budget period within a project period of up to 3 years. The 
funding estimate may change.
    Continuation awards within an approved project period will be made 
on the basis of satisfactory progress as evidenced by required reports 
and the availability of funds.

Funding Preferences

    To achieve appropriate geographic representation of the study 
network, funding preference may be given to approved applications that 
would enhance the geographic diversity of the network (e.g., network 
ideally comprised of sites from different cities or states).

D. Program Requirements

    In conducting activities to achieve the purpose of this program, 
the recipient will be responsible for the activities under 1. 
(Recipient Activities), and CDC will be responsible for the activities 
listed under 2. (CDC Activities).

1. Recipient Activities

    a. Develop consensus among appropriate patient-care, pharmacy and 
infection control personnel towards

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changing antimicrobial prescribing practices in (1) the medical 
intensive care unit, and (2) a second target patient population group 
(e.g., trauma intensive care unit, respiratory care unit, other). 
Implement this change in antimicrobial prescribing practice, 
specifically a cycling program. Characteristics of the cycling program 
should include cycling between classes of agents with similar spectrum 
of coverage available for empiric treatment of patients at a defined 
interval. This should also include provisions to ensure the safety of 
all patients affected by this change in medical practice, and maintain 
the spirit of a multi-center study as part of a collaborative network.
    b. Prior to and during the periods of changes in antimicrobial 
prescribing,
    1. Enhance existing surveillance activities in the medical 
intensive care unit including routine rectal or stool cultures on all 
patients upon admission to the unit in a manner to minimize laboratory 
burden and maximize ability to detect colonization with target 
organisms upon admission and before discharge from the unit. This may 
include combining data with results of routine clinical cultures of 
eligible patients.
    2. Obtain basic demographic, severity of illness, exposure, and 
outcome data on patients in the intensive care unit.
    c. Monitor antimicrobial use in the medical intensive care unit and 
second target patient population group. Document changes in dispensed 
antimicrobials throughout the study period.
    d. Demonstrate infection control activities remain similar 
throughout the study period (i.e., barrier precautions, hand washing 
frequency) through periodic observational studies of healthcare workers 
in the target patient population group.
    e. Obtain technical assistance, if needed.
    f. Monitor and evaluate scientific and operational accomplishments 
and progress in achieving the purpose of this program.
    g. Participate in the development of a research protocol for IRB 
review by all cooperating institutions participating in the research 
project.
    h. As part of the study network manage, analyze, and interpret 
surveillance and observational data; provide select data for 
aggregation among study network; publish and disseminate important 
information in collaboration with the study network.

2. CDC Activities

    a. Provide consultation, scientific and technical assistance in 
protocol development and in general operation of the study network. The 
CDC IRB will also review and approve the protocol initially and on at 
least an annual basis until the research project is completed.
    b. Participate in analysis and interpretation of aggregate 
surveillance data from study network.
    c. Assist in monitoring and evaluating scientific and operational 
accomplishments of the study network and progress in achieving the 
purpose and overall goals of this program.
    d. As needed, perform laboratory evaluation of specimens or 
isolates (e.g., molecular epidemiologic studies, evaluation of 
diagnostic tools) obtained as part of this program.

E. Application Content

    Use the information in the Program Requirements, Other 
Requirements, and Evaluation Criteria sections to develop the 
application content. Your application will be evaluated on the criteria 
listed, so it is important to follow them in laying out your program 
plan.
    Applications should address the following topics in the order 
presented:
    1. Understanding the objectives of the study network and program.
    2. Description of the target population groups.
    3. Description of existing capacity. There are several things 
applicants could do to document their capacity to perform the recipient 
activities:
    a. Demonstration of capacity to alter physician prescribing 
activity in an intensive care unit may include (in decreasing order of 
strength):
    1. Previous publication (peer-reviewed or abstract) of a trial of 
routine cycling of antimicrobial agents in an intensive care unit (in 
appendix).
    2. Photocopies of memorandum or internal documents which cite the 
successful institution of an antimicrobial control program in the 
intensive care unit (in appendix).
    3. Letters of support from pharmacy, critical care, or infectious 
disease departments which cite that alteration of prescribing activity 
in an intensive care unit has been (or is planned to be) accomplished 
(in appendix).
    b. Provide in an appendix to the application a list of the rates of 
antimicrobial resistance among the bacteria listed in the eligibility 
criteria (from routine clinical cultures or surveillance cultures) 
among patients in the medical intensive unit or the hospital.
    4. Operational plan. This should include a description of the 
change in antimicrobial prescribing (i.e., description of best possible 
cycling practice based on relevant surveillance data and patient 
population)
    5. Evaluation plan.
    6. Budget.
    7. Appendix.
    Applicant's operational plan should clearly address all recipient 
activities. The narrative (excluding budget, budget narrative, 
appendices, and required forms) should be no more than 20 double-spaced 
pages, printed on one side, with one inch margins, and unreduced font 
(10 or 12 point). The following information should be presented in 
appendicies: Letters of support or memorandum (see application content 
above), curricula vitae (CV) of co-investigators, and budget. Also, for 
purposes of meeting the eligibility requirement, there are several 
means in which applicants may provide documentation of eligibility in 
the appendix:
    1. Demonstrate the medical intensive care unit is a closed unit 
(i.e., a unit in which a limited number of physicians are responsible 
for patient care in that unit) by submitting a letter from the 
appropriate department describing which clinicians have primary 
responsibility for patient care in the medical intensive care unit.
    2. Demonstrate ongoing surveillance of nosocomial infections or 
antimicrobial resistance in the medical intensive care unit by 
submitting a letter from the infection control department describing 
the type of surveillance currently performed in the medical intensive 
care unit, including any surveillance cultures done routinely.
    3. Provide letter of support from the microbiology or infection 
control laboratory describing the laboratory capacity to perform the 
necessary functions listed in the eligibility criteria. Including 
capacity to change antimicrobial prescribing activity in the target 
population groups, and capacity to obtain and aggregate surveillance 
data (see application instructions).
    In addition, documentation of relevant accomplishments, such as 
abstracts, manuscripts, or bibliographies may be included in 
appendices. Information that should be included in the narrative will 
not be accepted if placed in the appendices.
    Budget Instructions: For each staff member listed under the 
Personnel line item, indicate their specific responsibilities. All 
other line-items should also be clearly justified.

F. Submission and Deadline

Letter of Intent (LOI)

    All eligible parties intending to submit an application are 
requested to

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inform CDC of their intention to do so by submitting a brief LOI no 
later than July 15, 1999. The purpose of the LOI is to assist CDC in 
timely planning and administration of the evaluation process. The LOI 
should be a brief notice that (1) identifies the applicant 
organization, and (2) provides the name, address, and telephone number 
of a contact person. LOI should be submitted to the technical assistant 
contact identified in ``where to obtain additional information'' 
section of this announcement.

Application

    Submit the original and two copies of PHS 5161-1 (OMB Number 0937-
0189) Forms are in the application kit. On or before August 15, 1999 
submit the application to the Grants Management Specialist identified 
in the ``Where to Obtain Additional Information'' section of this 
announcement.
    Deadline: Applications shall be considered as meeting the deadline 
if they are either:
    (a) Received on or before the deadline date; or
    (b) Sent on or before the deadline date and received by Grants 
Management office in time for scheduled review. (Applicants must 
request a legibly dated U.S. Postal Service postmark or obtain a 
legibly dated receipt from a commercial carrier or U.S. Postal Service. 
Private metered postmarks shall not be acceptable as proof of timely 
mailing.)
    Late Applications: Applications which do not meet the criteria in 
(a) or (b) above are considered late applications, will not be 
considered, and will be returned to the applicant.

G. Evaluation Criteria

    Each application will be evaluated individually against the 
following criteria by an independent review group appointed by CDC.
    1. Understanding the objectives of the program (5 points) a. 
Demonstration of a clear understanding of the background and objectives 
of this cooperative agreement program.
    b. Demonstration of a clear understanding of the requirements, 
responsibilities, and complexities that may be encountered in 
participating in this study network.
    2. Description of target population groups involved in the program 
activities, including a medical intensive care unit and another 
population group. (5 points)
    3. Description of existing capacity to perform enhanced 
surveillance during a period of changing antimicrobial prescribing 
activity in the target patient-populations. (40 points). a. Description 
of applicants past experience and documentation of accomplishments in 
conducting active surveillance, applied epidemiologic research, applied 
laboratory research, and prevention research on the incidence of 
nosocomial infections and/or antimicrobial resistant pathogens. (A list 
of relevant papers and abstracts should be included in the appendix, as 
well as the CV for all key professional personnel). (10 points)
    b. Description of applicant's past experience and documentation of 
accomplishments in changing prescribing activity in an intensive care 
unit (e.g., previous experience with routine cycling or antimicrobial 
agents), and demonstrate the capacity to alter physician prescribing 
activity as a part of this study (see application content for suggested 
documentation criteria). (13 points)
    c. Description of applicants past experience of collecting and 
aggregating surveillance data, including documentation (see application 
content) that susceptibility profiles of clinical isolates from medical 
intensive care unit patients include 2 of the following: (1) 
the proportion of Enterobacter cloacae resistant to ceftazidime or 
cefotaxime or ceftriaxone is >25%, (2) Pseudomonas aeurginosa isolates 
resistant to imipenem is >10%, (3) Klebsiella pneumoniae resistant to 
ceftazidime is >5%, and/or Acinetobacter baumanii resistant to 
ceftazidime is >20%. (10 points)
    d. Demonstration of support from non-applicant participating 
departments, laboratories, individuals, or consultants, indicated in 
applicant's operational plan. Applicant should provide (in an appendix) 
letters of support which clearly indicate collaborators' willingness to 
be participants in the study network. Do not include letters of support 
from CDC personnel. (5 points)
    e. Statements supporting applicant's ability to participate in a 
multi center collaborative network (2 points).
    4. Operational plan (45 points). a. The extent to which the 
applicant's plan for establishing and maintaining the enhanced 
surveillance for antimicrobial resistant bacteria clearly describes the 
(1) proposed organizational and operative structure/procedures, (2) 
clearly identifies the roles and responsibilities of all participating 
departments or individuals, and (3) addresses each of the recipient 
activities. (15 points)
    b. The extent to which the applicant describes plans for 
collaboration with CDC and the other members of this study network in 
the establishment and operation of the multi-center study described in 
this programs objectives, including project design/development, 
management and analysis of data, and synthesis and dissemination of 
findings. (10 points)
    c. Description of consensus building process, which is ongoing or 
planned, to change prescribing practices in the target patient-
population as a part of routine change in medical care (i.e., cycled 
availability of antimicrobial agents), and appropriateness of the 
described cycling program to alter the target pathogens as documented 
in that unit (see attachment I). (15 points)
    d. The degree to which the applicant has met the CDC policy 
requirements regarding the inclusion of women, ethnic, and racial 
groups in the proposed research. This includes (1) The proposed plan 
for the inclusion of both sexes and racial and ethnic minority 
populations for appropriate representation; (2) The proposed 
justification when representation is limited or absent; (3) A statement 
as to whether the design of the study is adequate to measure 
differences when warranted; (4) A statement as to whether the plans for 
recruitment and outreach for study participants include the process of 
establishing partnerships with community(ies) and recognition of mutual 
benefits. (5 points)
    5. Evaluation (5 points). Quality of a plan for monitoring and 
evaluating progress in achieving the purpose and overall objectives of 
this cooperative agreement program.
    6. Budget (not scored). Extent to which the line-item budget is 
detailed, clearly justified, and consistent with the purpose and 
objectives of this program. Extent to which applicant shows federal and 
non-Federal (e.g., State or Private Funding) shares of total cost for 
program.
    7. Human Subjects (not scored). Does the application adequately 
address the requirements of Title 45 CFR Part 46 for the protection of 
human subjects?

H. Other Requirements

Technical Reporting Requirements

    Provide CDC with original plus two copies of:
    1. Semiannual progress reports. The first semiannual report is 
required with each year's continuation application and should cover 
program activities from beginning of the current budget period to the 
date of report/application preparation. The second semiannual report is 
due 90 days after the end of each budget period and should cover 
activities for the entire budget period recently completed. This second 
report

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may simply be a ``cut/paste'' update of the first semiannual report to 
add information from date of first report to the end of the budget 
period.
    2. financial status report, no more than 90 days after the end of 
the budget period; and
    3. final financial and performance reports, no more than 90 days 
after the end of the project period.
    Send all reports to the Grants Management Specialist identified in 
the ``Where to Obtain Additional Information'' section of this 
announcement.
    The following other requirements are also applicable:

AR-1  Human Subjects Requirements
AR-2  Requirements for Inclusion of Women and Racial and Ethnic 
Minorities in Research
AR-9  Paperwork Reduction Act Requirements
AR-10  Smoke-Free Workplace Requirements
AR-11  Healthy People 2000
AR-12  Lobbying Restrictions

I. Authority and Catalog of Federal Domestic Assistance Number

    This program is authorized under Public Health Service Act, Section 
301(a) [42 U.S.C. 241(a)], 317(k)(1) [42 U.S.C. 247b(k)(1)], and 
317(k)(2) [42 U.S.C. section 247b(k)(2)], as amended. The catalog of 
federal domestic number is 93.283.

J. Where To Obtain Additional Information

    To receive additional written information and to request an 
application kit, call 1-888-GRANTS4 (1-888-472-6874). You will be asked 
to leave your name and address and will be instructed to identify the 
Announcement number of interest. See also the CDC home page on the 
Internet for information of programs and grants: http://www.cdc.gov
    If you have questions after reviewing the contents of all the 
documents, business management technical assistance may be obtained 
from: Oppie Byrd, Grants Management Specialist, Grants Management 
Branch, Procurement and Grants Office, Announcement 99149, Centers for 
Disease Control and Prevention (CDC). 2920 Brandywine Road, Room 3000, 
Atlanta, GA 30341-4146, Telephone (770) 488-2748, Email address: 
[email protected].
    For program technical assistance, contact: Scott Fridkin, M.D., 
Hospital Infections Program, National Center for Infectious Diseases, 
Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, MS 
E-55, Atlanta, GA 30333, Telephone number: (404) 639-6417, Email 
address: [email protected].

    Dated: June 25, 1999.
John L. Williams,
Director, Procurement and Grants Office, Centers for Disease Control 
and Prevention (CDC).
[FR Doc. 99-16759 Filed 6-30-99; 8:45 am]
BILLING CODE 4163-18-U