Formulary activities: Notes from the P&T committee consideration of the impact of new oral antimicrobial agents

ANNLDO 5(6) 39 AA, 1988

ISSN 0738-1751

EDITORIAL BOARD Editor DANIEL AMSTERDAM, PhD,

Associate Editors STEVEN L. BARRIERE, PharmD,

State University of New York at Buffalo and Erie County Medical Center Buffalo, New York

UCLA Medical Center Los Angeles, California

RONALD N. JONES, MD, Clinical Microbiology Institute Tualatin, Oregon

HAROLD C. NEU, MD, College of Physicians and Surgeons, Columbia University, New York, New York

C()NTI.N

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EDITOR'S NOTE

39

D. AMSTERDAM

Formulary Activities: Notes from the P&T Committee Consideration of the Impact of N e w Oral Antimicrobial Agents

39

S. L. BARRIERE

In Vitro Technical Comment: Broth Disk Elution Method for Anaerobic Susceptibility Testing, A Simple Unreliable Test 41 D. AMSTERDAM, R. N. JONES

Reports From the Literature: Improving the Use of Antimicrobial Agents in the Hospital Setting 42 D. AMSTERDAM

EDITOR'S NOTE Readers of The Newsletter may have noticed that, beginning with the April issue, a fifth Associate Editor has been added to the masthead. Dr. Steven L. Barriere, who is a Clinical Specialist in Infectious Disease at the UCLA Medical Center, was asked to join the Editorial Board because of his recognized expertise in several areas related to the study and evaluation of antimicrobial agents. Dr. Barriere's first article as an Associate Editor apELSEVIER

VOLUME 5, NUMBER 6, JUNE 1988

CLYDE THORNSBERRY, PhD, Center for Infectious Diseases Centers for Disease Control Atlanta, Georgia

LOWELL S. YOUNG, MD, Kuzell Institute for Arthritis and Infectious Diseases Medical Research Institute of San Francisco Pacific Presbyterian Medical Center San Francisco, California

FORMULARY ACTIVITIES: NOTES FROM THE P&T COMMITTEE CONSIDERATION OF THE IMPACT OF NEW ORAL ANTIMICROBIAL AGENTS S t e v e n L. Barriere Cost-containment has become a prominent watch-word over the past five years. With regard to drug therapy, antimicrobials have been a major target for containment strategies because they comprise the largest share of drug product budgets in U.S. hospitals. 1 Moreover, antimicrobials are frequently overused and misused. Recent cost-containment strategies have involved the use of: 1) single broad spectrum antimicrobials rather than combinations, 2) newer antimicropears in this month's issue. But, this is not the first time Dr. Barriere has contributed to The Newsletter. In a provocative presentation (The AMN, Vol. 4, No. 10, October 1987) Dr. Barriere discussed his novel approach in evaluating antimicrobial agents by using the area under the bactericidal curve as an indicator of antimicrobic efficacy. We trust that readers of The Newsletter will appreciate the forthcoming contributions of Dr. Barriere. In another section in this issue,

bials with prolonged half-lives (hence less frequent dosing) over those that require multiple daily doses, and 3) a movement towards home parenteral therapy for patients requiring long term treatment who otherwise need not be hospitalized. Assuming equivalent clinical outcomes, all of these are effective at reducing costs. In m a n y institutions these practices are routine. The expense, inconvenience, and hazards of parenteral therapy are minimized, but not completely avoided. the results of a CAP survey related to performing anaerobic antimicrobic susceptibility is reviewed. Disheartening is the conclusion that there has been little progress made in increasing proficiency in testing the antimicrobial susceptibility of anaerobic organisms and that the methodology that enjoys the most widespread usage is the one that is least capable of producing meaningful results. On a subject that has graced these pages several (continued on page 44) 0738-1751/88/$0.00 + 2.20

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It has been recognized for some time that certain oral antimicrobials are absorbed well enough from the GI tract that serum concentrations approach or even exceed those achieved after parenteral therapy. 2 Examples include chloramphenicol, metronidazole, clindamycin, and trimethoprim-sulfamethoxazole. However, these agents have only limited utility for the treatment of deep-seated bacterial infection and their long term use may be associated with serious adverse effects. Oral ~-lactams are also widely used, but because of either poor absorption or relatively lower potency vs comparable parenteral agents, their use is often limited to upper respiratory, skin/soft tissue, or urinary tract infections. 2 Treatment of more serious or deepseated infections such as pneumonia, osteomyelitis, and endocarditis has generally involved parenteral agents, often for prolonged courses. However, with the introduction of the fluorinated quinolones and more potent oral [3-1actam compounds, this practice is beginning to change. N e w fluoroquinolones such as ciprofloxacin have been shown to be effective in a wide variety of more serious infections because of excellent potency and bactericidal activity. Included in these are lower respiratory tract and bone and joint infections. 3 A few patients with endocarditis and meningitis have also been successfully treated with these orally-administered antimicrobials. N e w oral [3lactams such as those described in a recent issue of The A M N by Jones, hold a good deal of promise in these same infections because they are far more potent against

THE A N T I M I C R O B I C NEWSLETTER, V O L U M E 5, N U M B E R 6, J U N E 1988

gram-negative bacteria than older congeners, and some have prolonged elimination half-lives that permit infrequent dosing. 4 Examples of the more promising cephem compounds in this category are cefetamet, 7432-S, and CS-807. Replacement of parenteral therapy with these potent, well-absorbed oral agents is potentially cost-effective. This, of course, assumes equivalent efficacy. Oral agents tend to be safer and are not associated with the adverse effects which complicate parenteral therapy such as phlebitis and infiltration at the IV site. Parenteral therapy is expensive and, depending upon the type of IV delivery system used, the cost to prepare and administer a dose of an intravenous antibiotic may be greater than the drug acquisition cost. For example, we have estimated that, in our institution, the cost of personnel and supplies to prepare and administer one dose of an antibiotic in a minibag system is nearly $5.00. Most of the older cephalosporins, many penicillins, and some aminoglycosides cost less than this. Therefore, avoidance of these costs and the inconvenience mentioned above is highly desirable in our current era of fixed-rate reimbursement for health care. As an example, we have successfully treated several patients suffering from gram-negative osteomyelitis with oral ciprofloxacin. These patients would normally have received a parenteral third generation cephalosporin or a combination of an aminoglycoside plus a broadspectrum [3-1actam for a period of at least 6 - 8 weeks. The total cost to the institution for the parenteral medications, labor, and supplies

would have been at least $5,000. Instead, our cost for 6 - 8 weeks of oral ciprofloxacin was $250-300. At the present time, there are still many hospitals in the U.S. with patients whose healthcare coverage provides fee-for-service reimbursement. As a result, certain hospital services are revenue, rather than cost, centers. One of the most important is the pharmacy that can produce as much as 10-15% of the total hospital revenue with charges for medications and services. Much of the pharmacy revenue is derived from parenteral medications. In these hospitals, replacement of in-patient parenteral drugs will result in revenue reductions that may be substantial. Some hospitals operate home parenteral therapy programs that produce revenue and reduce the costs of hospital care. 5 These programs may also be largely supplanted by the availability of potent, new oral antimicrobials. The operating revenues lost with these reductions in parenteral therapies must be made up in other areas. It is also important to note, however, that fee-for-service reimbursement is likely to be completely eliminated as more coverage providers switch to flat rate reimbursement or other contractual arrangements. Under these circumstances, less costly therapy is, obviously, highly desirable. Other pitfalls in the use of oral agents include the vagaries of GI absorption, patient noncompliance, and drug interactions. An example is the marked reduction in absorption of the fluoroquinolones from the GI tract when administered with magnesium-or aluminum-containing antacids. 3

The Antimicrobic Newsletter (ISSN 0738-1751) is issued monthly in one indexed volume per year by Elsevier Science Publishing Co., Inc., 52 Vanderbilt Avenue, New York, NY 10017. Printed in USA (at Fame Avenue, Hanover, PA 17331). Subscription price per year: $75.00. Outside of the USA, Canada and Mexico, add $33.00. Second-class postage pending at New York, NY, and at additional mailing offices. Postmaster: Send address changes to The Antimicrobic Newsletter, Elsevier Science Publishing Co., Inc., 52 Vanderbilt Avenue, New York, NY 10017. NOTICE: No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. No suggested test or procedure should be carried out unless, in the reader's judgment, its risk is justified. Because of rapid advances in the medical sciences, we recommend that the independent verification of diagnoses and drug dosages should be made. Discussions, views and recommendations as to medical procedures, choice of drugs and drug dosages are the responsibility of the authors.

© 1988 BY ELSEVIER S C I E N C E P U B L I S H I N G CO., INC.

0738-1751/88/$0.00 + 2.20

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THEANTIMICROBICNEWSLETTER,VOLUME5, NUMBER6, JUNE1988 The use of n e w oral agents for serious infections should be undertaken judiciously. Although they are potentially safer and more "'cost-effective" than parenteral therapy, drug interactions and patient compliance must be monitored very carefully. Clearly, n e w potent ~-lactams and quinolones are significant additions to the therapeutic armamentarium. Their impact on the management of cer-

tain infectious diseases may be very significant. However, their fiscal effects, albeit temporary, must also be monitored very carefully.

1. Barriere SL: Cost containment of antimicrobial therapy. Drug Intell Clin Pharm 19:278-281, 1985. 2. Rehm SJ, McHenry MC: Oral antimicrobial drugs. Med Clin North Am 67:57-98, 1983.

3. Sanders WE: Efficacy, safety, and potential economic benefits of oral ciprofloxacin in the treatment of infections. Rev Infect Dis 10:528-543, 1988. 4. Jones RN: Antimicrobial activity, spectrum, and pharmacokinetics of old and new orally administered cephems. Antimicrob News 5:1-7, 1988. 5. Eisenberg JM, Kitz DS: Savings from outpatient antibiotic therapy of osteomyelitis. JAMA 255:1584-1588, 1986.

IN V I T R O T E C H N I C A L COMMENT Broth-Disk Elution Method for Anaerobic Susceptibility Testing; A Simple Unreliable Test

standard strain ATCC 29742. Laboratories were challenged with identifying the organism, evaluating the presence of a [3-1actamase as normally carried out in their laboratory and assessing susceptibility to eight antimicrobial agents including carbenicillin, cefoxitin, chloramphenicol, clindamycin, erythromycin, metronidazole, penicillin, and tetracycline. Of special interest here are the latter two diagnostic testing capabilities. The results concluded that identification accuracy ran true to previous performance surveys (1984 and 1985) indicating that nearly 70% of participants correctly identified the organism to the species level. When challenged to perform susceptibility tests according to their routine laboratory practice,

participants responded by indicating that 57% (the largest portion) used the broth disk-elufion methodology. Fewer than 1% of the laboratories used the NCCLS reference agar dilution test; 1 and 26% used in-house (3%) or commercial (23%) microdilution systems. The responses indicate that the widespread application of the broth-disk elution method continues; the reasons for its use seem to be based on the ability to use a commonly used medium without the need for special preparations or dependence u p o n cosily commercial reagents. The data in Table 1 confirm the generally accepted knowledge of the poor reliability of the broth disk elution tests as it is currently executed. 2,3 False-resistant and falsesusceptible results were frequently

REFERENCES

A recent College of American Pathologists' survey (Bacteriology D-01, 1988) evaluated participating laboratories for their capability in identifying, testing the susceptibility and detmining the production of ~-lactamase of an anaerobic org a n i s m - - a Bacteroides thetaiotamicron-ovatus group. The bacterium, a pure culture purportedly recovered from a bacteremic 60-year-old febrile male was similar to the NCCLS anaerobic quality control

T A B L E 1. Modal MICs (~g/ml) and interpretive results for several methods used for determining susceptibility of B.

thetaiotaomicron-ovatus group strain (CAP D-01, 1988) Broth microdilution

Broth-disk elution Antimicrobic

Mode MIC

Interp.

Breakpoints reporteda

Carbenicillin 464 S 64 Cefoxitin 416 S 16 Chloramphenicol 48 S 8,16 Clindamycin ~2 S 1,2,4 Erythromycin 42 S 2 Metronidazole ~<16 S 16 Penicillin >2 R 2,16 Tetracycline 44 S 4 • Post-elution breakpoints reported by participants. t, False-resistant and false-susceptibleerror compared to reference method. c Agar dilution method. 0738-1751/88/$0.00+ 2.20

% Major errorsb

Mode MIC

Interp.

Ref. Lab MICs~

10 43 7 62 34 4 8 8

32,64 >16 48 4,8 8 ->4 40.5,1

S R S R R -R S

64 16 8 8 -42 >2,>32 48

© 1988BYELSEVIERSCIENCEPUBLISHINGCO., INC.