P&T News: Jan/Feb 2000
Dena M. Behm-Dillon, Pharm.D.
Peer Review Status: Internally Peer Reviewed by
Antibiotic Advisory Subcommittee
The Antibiotic Advisory Subcommittee (AAS)
The AAS is composed of members drawn from a variety of
disciplines. The co-chairs are from the Infectious Diseases service,
and other members are from Pediatrics, Medical I.C.U., Surgical
I.C.U., Obstetrics/Gynecology, Surgery, Microbiology, Pharmacy, and
Epidemiology. The AAS is an advisory subcommittee to the Pharmacy and
Therapeutics (P&T) Subcommittee. The P&T Subcommittee, in
turn, reports directly to the Hospital Advisory Committee.
The AAS has three primary functions:
1. To analyze anti-infective use and microbial sensitivity patterns within the UIHC and provide recommendations as appropriate to the Pharmacy and Therapeutics Subcommittee.2. To advise the Pharmacy and Therapeutics Subcommittee regarding the anti-infectives that should be stocked at UIHC.
3. To advise the Pharmacy and Therapeutics Subcommittee on whether a medication use evaluation should be conducted on the use of an anti-infective and to assist in criteria development.
There are four steps which implement the primary functions of the AAS, each completed in collaboration with Pharmacy and Medical staffs. These include
1. Targeting specific drugs for appropriate dosing, susceptibility patterns, and safety issues, e.g. protocol antibiotics;
2. Development of criteria for antibiotic utilization proposals;3. Implementation and monitoring the program; and
4. Review of results through data analysis and quarterly report review.
Protocol Antibiotic Program
Many of the objectives of the AAS are met through the Protocol
Antibiotic Program. The program was implemented in 1992 as a
collaborative effort of the AAS, the Pharmacy and Therapeutics
Subcommittee, the Medication Use Evaluation Subcommittee, and the
Medical Staff. The "protocol" classification includes those
anti-infectives which have been approved for stock with the
restriction they be used only according to specific criteria. The
criteria can be obtained from the protocol forms which are in file
boxes on each inpatient care unit.
The purposes of this program are to: prevent development of drug-resistant organisms through appropriate anti-infective selection and monitoring; pinpoint primary drug uses; and finally, monitor the success of strategies to control costs. This last step is conducted through prospective therapeutic drug monitoring by clinical pharmacists and a series of computer-generated reports. The reports describe purchasing, inventory, and drug utilization for inpatients, clinic patients, and the UIHC Ambulatory Care Pharmacies. They permit ongoing review by the AAS, Pharmacy and Therapeutics Subcommittee, and respective departments of drug products and quantities dispensed by pharmacy, drug expenses and susceptibility data for specific patient care units/clinical services, and changes in utilization over time. Feedback is provided through data analysis and quarterly report review. Quarterly reports are then distributed to all clinical departments for review and follow-up, as needed. The Protocol Antibiotic Program facilitates optimal patient care through promotion of appropriate prescribing, and it serves as a means of addressing concerns regarding microbial resistance.
Susceptibility Data
The "Guide to Choice of Antibiotic Therapy", published twice yearly by the UIHC, includes information provided by the Departments of Pathology (Medical Microbiology) and Pharmaceutical Care. It provides hospital-wide, pathogen-specific sensitivity patterns for major antibiotics at UIHC, cost and dosing information, parenteral to oral conversion information, and dosing with decreased renal function. It provides the clinician with readily available clinical data that allow for initial antibiotic selection based on hospital-wide sensitivity trends.
Due to the efforts of the Antibiotic Advisory Subcommittee and the Protocol Antibiotic Program, the susceptibility patterns at UIHC compare favorably with those of other major teaching hospitals. Only 17% of Staphylococcus aureus are resistant to methicillin - a level considerably lower than the community rate of 25%. Just 26% of Pseudomonas aeruginosa are resistant to gentamicin. Many other teaching hospitals no longer consider the use of gentamicin for Pseudomonas aeruginosa because their resistance rates are much higher. This is a significant achievement which is due to the ongoing efforts of UIHC staff to ensure the use of clinically appropriate therapy for the treatment of specific infections.
Appropriate Use of Drug Levels
Vancomycin
Vancomycin levels are frequently ordered inappropriately with
uninterpretable results. Therefore, the AAS developed guidelines for
the appropriate monitoring of levels. The guidelines were
subsequently reviewed by the medical service chiefs and then approved
by the P&T Subcommittee. The following guidelines were approved
in October 1995, but improved adherence is still needed as many
unnecessary levels are still being drawn. Following the guidelines
more closely could lead to more appropriate dosing adjustments, as
well as substantial laboratory savings.
WHO
WHO NOT
WHEN
HOW
Aminoglycosides
The results of serum aminoglycoside levels are often unusable
because the levels are drawn incorrectly or at inappropriate times.
This can result in suboptimal dosage adjustments. Uninterpretable
levels can result in large amounts of wasted laboratory resources.
There are two different methods of dosing aminoglycosides, and each
has its own specific method for monitoring levels.
Multiple-Daily Dosed Aminoglycosides
HOW
WHEN
Extended Interval Dosing (EID) Aminoglycosides
Extended interval dosing of aminoglycosides can be useful in
select patient populations. Traditional multiple daily dosing was
designed to keep serum aminoglycoside concentrations above the
minimum inhibitory concentration for most of the dosage interval,
with the intent to prevent regrowth of organisms. High peaks were
thought to correlate with toxicity, not improved antibacterial
activity. Currently available data support the concept of
administering larger doses less frequently. The rationale is based on
the concentration-dependent bactericidal activity of aminoglycosides,
the extended post-antibiotic effect, the possibility for reduced
nephrotoxicity, and equivalent or reduced ototoxicity.
In vitro, the aminoglycosides eradicate bacteria at a rate proportional to the peak concentration attained. Therefore, high peak levels result in a more rapid and efficient bactericidal effect against susceptible organisms. In fact, peak aminoglycoside serum concentrations of 8 to12 times the minimum inhibitory concentration of the bacteria have been associated with a positive clinical outcome. The post-antibiotic effect (PAE) is defined as the time period that surviving bacteria, following exposure to an antibiotic, cannot metabolize or multiply even though extracellular antibiotic is no longer present. The duration of the PAE for aminoglycosides with gram negative bacteria has been reported to be from 3 to 24 hours in vivo, depending on the peak concentration and the organism. The prolonged post-antibiotic effect is another reason that extended interval dosing is a rational alternative.
Since the uptake of aminoglycosides into renal tubular cells is a saturable process, larger doses would not be expected to be any more nephrotoxic than smaller doses. Both animal and human studies have shown that the concentration in the renal cortex is significantly lower when administered as a single daily dose than when divided and administered more frequently. Animal data support an accumulation threshold in the organ of Corti as well, so there is a potential for less ototoxicity. Clinical trials consistently show that EID has equivalent or less toxicity than multiple daily dosing. Other advantages include a reduction in costs incurred by the institution for preparing, administering and monitoring therapy, and equal therapeutic effectiveness when compared with traditional dosing.
The Pharmacy and Therapeutics Subcommittee has authorized clinical pharmacy staff to determine the proper aminoglycoside dose and dosing interval and to coordinate serum level sampling to refine EID for aminoglycosides, upon request by a UIHC prescriber. If this service is desired, the prescriber should write "Extended-Interval Dosing for Gentamicin via Pharmacy" on a routine A-1a Doctors' Order form.
The following are guidelines for serum sampling when EID is used.
Summary
The Antibiotic Advisory Subcommittee is a multi-disciplinary
group that looks at a number of issues regarding the appropriate use
of antibiotics. Due to its efforts and the cooperation of the Medical
and Pharmacy staff, UIHC has been successful at protecting the
bacterial ecology. The appropriate use of antibiotic levels is
another method by which medicine can be practiced more
cost-effectively to make optimal use of limited resources.
Additional Information
Vancomycin Levels
Gentamicin Levels
Aminoglycoside Extended-Interval Dosing
DRUGS ADDED TO STOCK
FENTANYL
Transmucosal Lozenge: 200 mcg, 400 mcg, 600 mcg
The transmucosal lozenge form of fentanyl (Actiq - Abbott) is
indicated only for the management of breakthrough cancer pain in
patients with malignancies who are already receiving and who are
tolerant to opioid therapy for their underlying persistent cancer
pain. Extensive patient/caregiver education is necessary to ensure
proper storage and disposal of this product.
NOTE: Prescribing is restricted to attending staff physicians from Anesthesia and the Adult Hematology/Oncology Division.
ADDITIONAL ACTIONS
DELAVIRDINE (RESCRIPTOR") TABLETS
A 200 mg tablet was added to stock.
DIDANOSINE (VIDEX") CHEWABLE TABLET
A 200 mg chewable tablet was added to stock.
HYDROXYZINE TABLETS
A 50 mg tablet has been added to stock.
_______________________
Note: The cost following each brief monograph is the UIHC acquisition cost.
DRUGS DELETED FROM STOCK
ALUMINUM HYDROXIDE 600 MG (AMPHOGEL(R)) TABLETS Discontinued by the manufacturer. Aluminum hydroxide oral suspension and 400 mg oral capsules (Alu-Caps(R)) are available.
ALUMINUM HYDROXIDE WITH MAGNESIUM HYDROXIDE WITH SIMETHICONE (MAALOX(R) PLUS EXTRA STRENGTH) TABLETS Discontinued by the manufacturer. A suspension formulation is still available.
ATROPINE 0.5% OPHTHALMIC SOLUTION Discontinued by the manufacturer. Atropine 1% ophthalmic solution is available.
DANAZOL 50 MG TABLETS Deleted due to low use. A 200 mg tablet is available.
ISOSORBIDE (ISMOTIC(R)) ORAL SOLUTION Discontinued by the manufacturer. Glycerin oral solution is available.
NITROGLYCERIN 2% OINTMENT, 60 GRAM TUBE Deleted due to low use. A 30 gram size is still available.
PLASMA PROTEIN FRACTION (PPF) INJECTION Unavailable from any manufacturer. Albumin injection is available.