Role of the microbiology laboratory in the cost-effective use of antimicrobics

IIDN1 Volume 5, Number 7, July 1986

Editor Paul D. H o e p r i c h , MD Division of Infectious and Immunologic Diseases University of California, Davis Medical Center

Associate Editors R u t h M. Lawrence, MD

Larry K. Pickering, MD

Charles W. Stratton MD

Division of Infectious Diseases Texas Tech University Health Sciences Center

Program in Infectious Diseases and Clinical Microbiology The University of Texas Medical School at Houston

Department of Pathology Vanderbilt University Medical Center

Role of the Microbiology Laboratory in the Cost-effective Use of Antimicrobics

i ()lilt'Ill

Role of the Microbiology Laboratory in the Costeffective Use o f Antimicrobics

Charles W. Stratton,

Vanderbilt University School of Medicine, Nashville, Tennessee

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Charles W. Stratton

Diabetic Foot Infections 52 Stuart H. Cohen CASE REPORT Richard A. Gould and Crystie C. Halsted

54

COMMENTS ON CURRENT PUBLICATIONS

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Elsevier 0278-2316/86/$0.00 + 2.20

MD

The high cost of antimicrobial therapy has become an important issue for clinicians, pharmacists, and hospital administrators alike, While many different methods for improving the cost-effective use of antimicrobics have been considered, the role of the Clinical Microbiology Laboratory must also be explored,

within that hospital. Recognition of variation in the trends of isolation and resistance within a hospital will influence decision as to empiric therapy, necessitating the availability of specific antimicrobics for certain situations. Intensive care units and burn units, for example, are likely to harbor resistant tnicroorganisms and may require newer

General Guidelines for Usage

agents for empiric therapy of nosocomial infections. Conversely, community-acquired infections seen on the general medical or surgery services are less likely to need newer agents. The trends of both isolation and resistance change over time, and formulary decisions will need to be modified. Unless physicians and pharmacists are aware of the prevalence of pathogens and their resistance patterns on a continuous basis, the selection of antimicrobics for clinical use and stocking in the pharmacy will be neither relevant nor cost-effective.

of Antimierobics The Clinical Microbiology Laboratory can provide general guidelines for the use of antimicrobics by determining the prevalence of pathogens and patterns of resistance in the hospital it serves. Hospitals may vary greatly in both respects. Even within a community, different hospitals may have different pathogens and different resistance problems, Thus, the selection of antimierobies for a formulary may need to be individualized for each hospital and perhaps even for services or units

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50 Infectious Diseases Newsletter 5(7) July 1986 Determination of the Prevalence of Pathogens Much of the use of antimicrobics is empiric. Regimens are often designed to achieve the broadest coverage and the greatest microbiologic activity possible. This kind of "fear-medicine" is related, in part, to the physician's concern for a severly ill patient. It is also related to experience with immunosuppressed patients in whom empiric therapy with broad-spectrum antimicrobics plays a prominent role. It is unlikely that much can be done to overcome the anxiety of the concerned physician for the septic patient. However, if physicians are aware of what the most likely pathogens are in their hospital, their use of empiric therapy is more likely to be relevant, Similarly, the hospital formulary should stock antimicrobics with activity against the most likely pathogens. For example, if "methicillin"-resistant staphylococci are commonly isolated, vancomycin should be on the formulary and should be used whenever staphylococcal sepsis is suspected. Information about the isolation of such pathogens can be provided by the Clinical Microbiology Laboratory. By periodically determining and reporting what the prevalent isolates have been in a particular setting, the laboratory can assist in the selection of antimicrobics. This procedure is quite simple. The pathogens recovered from selected sites of infection (eg, blood cultures), selected settings (eg, the Burn Unit), and selected types of acquisition (community vs. nosocomial) are listed in relation to their frequency of isolation. This can be done quarterly and compared with the previous year's cumulative experience. If Pseudomonas aeruginosa is frequently isolated from the

blood, empiric therapy should include drugs active against this pathogen. On the other hand, if "methicillin"-resistant staphylococci are rarely seen in the Burn Unit, empiric therapy need not include vancomycin. Similar observations can be made for other sites and other units. The prevalence of pathogens depends on hospital factors such as patient mix, and on cornmunity factors such as the occurrence of Legionella spp. By informing the hospital staff of the pathogens most commonly encountered, the laboratory will assist in the selection of antimicrobics, This is cost-effective because it may: (1) allow the use of less expensive agents; (2) permit the deletion of agents aimed at specific pathogens; and (3) result in the selection of specific agents that reduce the chances for treatment failures,

Monitoring for Resistance The susceptibility tests carried out in the Clinical Microbiology Laboratory are a means to monitoring for trends in resistance. Knowledge of trends within a particular hospital (or unit) will allow the selection of those antimicrobics that are most likely to be effective, helping to avoid the selection of the latest and most potent antimicrobics until or unless they are needed. If susceptibility data are correlated with antimicrobial use, some insight may be developed in the epidemiology of hospital-acquired infections, Susceptibility reports are most useful if categorized appropriately, The report should include the predominant strains, the patterns of susceptibility, the site(s) of isolation, and the service or unit of origin. The data for communityacquired and hospital-acquired infections should be compared,

Unfortunately, the appropriate categorization of isolation trends and susceptibility patterns is only relevant if a large number of isolates can be included in each category. Smaller hospitals may not have an adequate volume. A smaller hospital, however, can examine the isolation trends and susceptibility patterns for all isolates from blood. Such data would be relevant to septic patients and provide a data base appropriate for clinical decisions. The monitoring of isolation trends and susceptibility patterns should be done quarterly since both will change over time. Such monitoring is particularly important with the increased understanding of the molecular genetics involved in resistance. Many problems with resistance are associated with specific resistance factors (plasmids and transposons). Some hospitals and communities do not have problems with such resistance factors and can successfully utilize older antimicrobics. The susceptibility trends documented by the Clinical Microbiology Laboratory will encourage a particular hospital to use the appropriate (or avoid the inappropriate) antimicrobic(s). Another aspect of monitoring for resistance is the targeting of specific units with routine surveillance cultures. Resistance within a hospital usually begins in special care units such as intensive care units or burn units. Weekly surveillance cultures of nasal-tracheal secretions or urine may identify the onset of problems of resistance within a unit, enabling timely preventive or corrective action. If a particular antimicrobic is monitored (eg, an aminocyclitol), agar plates containing that drug can be used to screen for resistance. The quantity of data to be reviewed and the number of ways to analyze the data make the monitor-

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51 Infectious Diseases Newsletter 5(7) July 1986 ing of trends of isolation and susceptibility very difficult, unless computers are used. If the information is accumulated in a computer, it can be analyzed very easily. In addition, susceptibility nonconformance patterns can be derived. This technique compares the susceptibility pattern of each isolate with previous patterns. If there is a change, the computer will identify that change, often alerting the laboratory to a new resistance problem,

group of pathogens, the best way to compare the MICs is to calculate the ratio of the MICs to the concentrations achievable in the serum, This ratio will give a more accurate picture of activity than MICs alone, Peak concentrations in the serum that are l0 times the MIC values are said to be desirable although there is no clinical proof--only a suggestion of advantage in obtaining bacteriologic cure of infective endocarditis,

Evaluation of New Antlmicroblal

Clinically Relevant Procedures

Agents Some newer antimicrobics are very similar in both spectrum and activity to older agents. Others offer a distinct advantage. The Clinical Microbiology Laboratory can assist in the evaluation of new antimicrobial agents by including the new agents in routine susceptibility tests, The new agent(s) are run in tandem with older agents of the same class that are already on the formulary. If a distinct advantage is ~seen with a new agent in comparison to an older agent, a substitution on the formulary may be advantageous, A disk diffusion method is best for evaluating the spectrum of a new antimicrobic; a microtiter broth dilution method is best for evaluating the activity. In addition to the concurrent testing of the new agent(s), pathogens which have been isolated over a long period can be tested. This allows the use of larger numbers of specific pathoguns such as gentamicin-resistant members of the Enterobacteriaceae. These kinds of studies should not be undertaken routinely, but can be done when needed to assist the formulary committee in making decisions on antimicrobics that are similar in nature, eg, retention of older (and less expensive) agents, or adoption of the least expensive of a number of new agents, If minimum inhibitory concentrations (MICa) are determined for a

Specimens alleged to be sputum should be evaluated microscopically to determine if the specimen is saliva. If it is reported as saliva and no culture is performed, the clinician can obtain a better specimen and avoid the expense and danger of treating the mouth flora with antimicrobics. Similarly, urine that yields three or more isolates is quite likely contaminated with flora from the perineum; the isolates should not be identified or tested for susceptibility. The Clinical Microbiology Laboratory should be involved in the education of clinicians as to what is clinically relevant from a microbiologic viewpoint using both direct communication and published studies.

Rapid Detection, Identification, and Reporting of Pathogens Rapid detection of pathogens in clinical materials is important for the cost-effective use of antimicrobics. Laboratories that employ direct methods for recognizing pathogens in clinical specimens help clinicians to use antimicrobic therapy specific for particular pathogens instead of resorting to more expensive and potentially dangerous empiric therapy. Table 1 lists some examples of tests for the rapid detection of pathogens. Rapid identification after isolation is also useful. For the clinician ordering antibacterial @ 1986 Elsevier Science Publishing Co., Inc. 0278-2316/86/$0.00 + 2.20

therapy, sepsis caused by Escherichia coil is very different from that caused by P. aeruginosa. The report from the laboratory that multiple blood cultures are growing Gramnegative bacilli is incomplete until the identification is made. The more rapidly this is done, the sooner an appropriate antimicrobic can be used. Finally, all of the rapid methods employed by a Clinical Microbiology Laboratory are useless until the clinician learns the results. Rapid methods of detection and identification must be cornbined with rapid reporting. A telephone call (in addition to the written report) will best achieve this goal for clinically important specimens.

Rapid Susceptibility Testing It is very easy to do rapid susceptibility testing on most isolates from blood cultures just as soon as the cultures have turned positive. A full day may be saved over the practice of waiting until an isolate grows on an agar plate. Susceptibility may be known before identification, without compromising clinical utility.

Selective Reporting of Susceptibility Test Results The antimicrobics selected for susceptibility testing must include the agents available in the hospital formulary. However, selective reporting can be utilized. Thus, if a pathogen is susceptible to an older, less expensive antimicrobic of a particular class, only the results with that drug are reported. Some laboratories will only test newer agents if the isolate is resistant to older agents. This is step-wise selective testingas opposed to selective reporting. The advantage of selective reporting over step-wise selective testing is that the susceptibility results to newer, more expensive agents are available sooner if needed.

52 lntectious Diseases Newsletter 5(7) July 1986 Table 1. Examples of the Rapid Detection of Pathogens Specimen

Direct method(s)

Sputum Spinal fluid Buffy coat from peripheral b l o o d Diarrheal feces Pus from abscess

Gram-stain with quellung test India ink stain, cryptococcal a n t i g e n Acridine-orange stain Dark field examination or Gram-stain Gram-stain

Cerv!cal specimen

Direct fluorescent antibody test for Chlamydia

Information for Therapeutic Reassessment

effective use of antimicrobics will be appreciated,

Pathogen detected Streptococcus pneumonhte' Cr)'ptoc~ccus neofi~rman.~ Bacteria (cocci vs. bacilli) causing sepsis Campylobacter spp. Gram-positive cocci, vs. Gram-negative bacilli vs. fungi Chlamydia trachomatis

Education

Bibliography

The Clinical Microbiology Laboratory must take part in the continu-

Bartlett RC: Making optimum use of the microbiology laboratory, lI1 Aids of antimicrobial therapy. JAMA 247:1868-1871, 1982, Bartlett RC: Cost and usefulness of dinical microbiology services. Eur J Clin Microbiol 4:375-378, 1985. Davies J, Smith DI: Plasmid-

determined resistance to antimicrobial agents. Ann Rev Microhiol 32:469518, 1978. Flick RB, Reynolds HY: Changing spectrum of pneumonia-new media creation or clinical reality? Am J Med 74: I-8, 1983. Kunin CM: Problems in antibiotic usage. Definitions, causes, and proposed solutions. Ann Intern Med 83:802-805,1978. McGowan JE Jr: Antimicrobial resistance in hospital organisms and its relation to antibiotic use. Rev Infect Dis 5:1033-1048, 1983. Murray PR, O'Byrne A: Cost of antibiotic therapy. N Engl J Med 308:226, 1983. Neu HC: The emergence of bacterial resistance and its influence on empiric therapy. Rev Infect Dis 5 (Suppl):9-20, 1983. Neu HC: Antimicrobial activity, bacterial resistance and antimierobial pharmacology: is it possible to use new agents cost effectively? Am J Med 78 (Suppl B): 17-22, 1985. Ratner H: Rapid methods for identification of common clinical isolates. Infect Control 3:367-369, 1982. Stratton CW: Susceptibility testing revisited. In Progress in Clinical Pathology Vol IX. Stafenini M, Gorstein F, Fink LM, eds. New York, Grune & Stratton, 1983. Pages 65-100. Young HK: Recent advances in the evolution of drug resistance. J Antimicrob Chemother 16:679-684, 1985.

Improved therapy for diabetics, eg, insulin, oral hypoglycemies, and antimicrobics, is associated with an increased incidence of chronic probIctus, including foot infections,

Ischemic a n d / o r infectious foot lesions account for an estimated 25% of hospital admissions of diabetics, and more in-hospital days are spent treating foot infections

Therapeutic reassessment--the reevalutation of an antimicrobial regimen by the clinician after several days of t r e a t m e n t - - h a s as its goal the cost-effective modification of the regimen. The Clinical Microbiology L a b o r a t o r y plays an important role in the reassessment by providing specific information on the patient's pathogen. This information is traditionally conveyed to the clinician; it can also be conveyed to the pharmacy. The pharmacy may then participate in the effort of cost-effective use of antimicrobics. Reminders to busy clinicians by the pharmacy about costeffective alternative regimens, based upon data from the Clinical Microbiology Laboratory, are often effecrive in lowering costs,

ing education of clinicians, pharmacists, and hospital administrators. It is only through continuing education that the utility of the Clinical Microbiology L a b o r a t o r y in the cost-

Clinical Significance of Susceptibility Data Although data from the Clinical Microbiology Laboratory are often used to compare antimicrobial agents in order to select drugs for therapy, the data should not be interpreted as ensuring clinical efficacy. Susceptibility data must be viewed in the light of appropriate cfinical studies. However, very few studies have attempted to correlate antimicrobial susceptibility test resuits with either bacteriologic cures or clinical cures. Until sufficient clinical data are available, in vitro susceptibility test data should not be used as the sole criterion for selecting antimicrobics for therapy,

Diabetic Foot Infections Stuart H. Cohen,

MD

Division of Infectious and Immunologic Diseases, Department of Internal Medicine, University of California, Davis, Sacramento, California

© 1986 Elsevier Science Publishing Co., Inc. 0278-2316/86/$0.00 + 2.20