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In vitro technical comment
41
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.
42
found--especially for cefoxitin (43%) and clindamycin (62%). Clearly, part of the problem relates to the fact that anaerobic organisms have MICs that cluster very near to the breakpoint concentration used in these tests. In general, susceptibility tests (and in turn broth-disk elution tests) are best applied to antimicrobial agents demonstrating few resistant strains or that exhibit widely separated populations of MICs--notably chloramphenicol and tetraycline. The problem this poses for laboratories that routinely use this methodology is whether it is better to do a simple test, which is riddled with inaccuracy, rather than doing any test at all. In the ancillary test for evaluating susceptibility--determination of fBlactamase production--laboratories reported results on the anaerobic isolate of B. thetaiotamicron-ovatus
THE ANTIMICROBIC NEWSLETTER, VOLUME 5, NUMBER 6, JUNE 1988
group that was submitted. Of the 474 respondents, the greatest percent positive correct results (94.1%) were received from those laboratories that performed the nitrocefin test. Other test results that were evaluated as correct were: acidometric, 54.5%; iodometric, 60.0%; and other, 79.4%. It is worthwhile to note that a newly constituted group of the NCCLS, "Working Group on Anaerobic Susceptibility Testing" chaired by S. M. Finegold have expressed serious concerns about susceptibility testing of strict anaerobic bacteria. In a soon to be published review and position paper (J. Clinical Microbiology, July 1988) they state, "With regard to guidance for therapy, we conclude that none of the tests now recomm e n d e d by the NCCLS (or any other group) has been established
as reliable for predicting the clinical or bacteriologic outcome."
REFERENCES
1. National Committee for Clinical Laboratory Standards. Approved standard Mll-A: Standard reference agar dilution procedure for antimicrobial susceptibility testing of anaerobic bacteria. NCCLS, Villanova, PA, 1985. 2. Kurzynski TA, Yrios JW, Helstad AG, et ah Aerobically incubated thioglycolate broth disk method for antibiotic susceptibility testing of anaerobes. Antimicrob Agents Chemother 10:727-732, 1976. 3. National Committee for Clinical Laboratory Standards: Proposed guideline M17-P. Alternative methods for antimicrobial susceptibility testing of anaerobic bacteria. NCCLS, Villanova, PA, 1985. D. AMSTERDAM, R. N. JONES
REPORTS FROM THE LITERATURE
IMPROVING THE USE OF ANTIMICROBIAL A G E N T S IN THE HOSPITAL SETTING The Infectious Disease Society of America (IDSA) has undertaken the task of setting guidelines that will deal with issues of antimicrobial therapy. J. Joseph Marr, H. L. Moffet, and C. M. Kunin, as spokesmen for the IDSA, offer these guidelines as a method to evaluate and control the use of antimicrobial agents in the hospital setting.1 The IDSA plans to address other matters related to antimicrobial agents in forthcoming issues of The Journal of Infectious Diseases (JID). These include: "empiric use of antimicrobial agents; differentiation between colonization and infection; monitoring serum levels; and outpatient parenteral therapy." As a focus of in-
terest to the readers of The Antimicrobic Newsletter, we comment on the guidelines in the recent JID and anticipate proferred comments and perspective on other i s s u e s - - s u c h as monitoring serum levels. Several methods are proposed to evaluate the uses of antimicrobics in the hospital setting. These include: the monitoring of formulary practice and usage trends, microbiology laboratory practices and trends in resistance, and patterns of use of antibiotics by the medical staff. The formulary composition of antimicrobial compounds should be reviewed to determine agent similarity (redundancy) and indications as well as their relative cost and frequency of use by the medical staff. Monitoring the trends of antibiotic use (and cost) can be achieved by identifying the annual acquisition costs and consumption of each antimicrobial agent, class
© 1988 BY ELSEVIER SCIENCE PUBLISHING CO., INC.
(e.g., antibacterial, antifungal) and group (e.g., aminoglycoside, cephalosporin) of drugs. This information should incorporate both the total usage in grams and the number of patients treated with each drug. When calculating acquisition costs, separate accounting should be made for initial acquisition, preparation, and administration, as well as surcharges for hospital administrative costs. The report recommends that trends can be usefully analyzed w h e n categorized according to medical service and calculated on the basis of patient days for the entire institution and for each service. Annual review is advisable and corrective action possible w h e n deviations are observed. The report suggests that procedures for performing susceptibility tests be in accord with national standards as indicated by NCCLS or other quality assurance groups. 0738-1751/88/$0.00 + 2.20
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.
42
found--especially for cefoxitin (43%) and clindamycin (62%). Clearly, part of the problem relates to the fact that anaerobic organisms have MICs that cluster very near to the breakpoint concentration used in these tests. In general, susceptibility tests (and in turn broth-disk elution tests) are best applied to antimicrobial agents demonstrating few resistant strains or that exhibit widely separated populations of MICs--notably chloramphenicol and tetraycline. The problem this poses for laboratories that routinely use this methodology is whether it is better to do a simple test, which is riddled with inaccuracy, rather than doing any test at all. In the ancillary test for evaluating susceptibility--determination of fBlactamase production--laboratories reported results on the anaerobic isolate of B. thetaiotamicron-ovatus
THE ANTIMICROBIC NEWSLETTER, VOLUME 5, NUMBER 6, JUNE 1988
group that was submitted. Of the 474 respondents, the greatest percent positive correct results (94.1%) were received from those laboratories that performed the nitrocefin test. Other test results that were evaluated as correct were: acidometric, 54.5%; iodometric, 60.0%; and other, 79.4%. It is worthwhile to note that a newly constituted group of the NCCLS, "Working Group on Anaerobic Susceptibility Testing" chaired by S. M. Finegold have expressed serious concerns about susceptibility testing of strict anaerobic bacteria. In a soon to be published review and position paper (J. Clinical Microbiology, July 1988) they state, "With regard to guidance for therapy, we conclude that none of the tests now recomm e n d e d by the NCCLS (or any other group) has been established
as reliable for predicting the clinical or bacteriologic outcome."
REFERENCES
1. National Committee for Clinical Laboratory Standards. Approved standard Mll-A: Standard reference agar dilution procedure for antimicrobial susceptibility testing of anaerobic bacteria. NCCLS, Villanova, PA, 1985. 2. Kurzynski TA, Yrios JW, Helstad AG, et ah Aerobically incubated thioglycolate broth disk method for antibiotic susceptibility testing of anaerobes. Antimicrob Agents Chemother 10:727-732, 1976. 3. National Committee for Clinical Laboratory Standards: Proposed guideline M17-P. Alternative methods for antimicrobial susceptibility testing of anaerobic bacteria. NCCLS, Villanova, PA, 1985. D. AMSTERDAM, R. N. JONES
REPORTS FROM THE LITERATURE
IMPROVING THE USE OF ANTIMICROBIAL A G E N T S IN THE HOSPITAL SETTING The Infectious Disease Society of America (IDSA) has undertaken the task of setting guidelines that will deal with issues of antimicrobial therapy. J. Joseph Marr, H. L. Moffet, and C. M. Kunin, as spokesmen for the IDSA, offer these guidelines as a method to evaluate and control the use of antimicrobial agents in the hospital setting.1 The IDSA plans to address other matters related to antimicrobial agents in forthcoming issues of The Journal of Infectious Diseases (JID). These include: "empiric use of antimicrobial agents; differentiation between colonization and infection; monitoring serum levels; and outpatient parenteral therapy." As a focus of in-
terest to the readers of The Antimicrobic Newsletter, we comment on the guidelines in the recent JID and anticipate proferred comments and perspective on other i s s u e s - - s u c h as monitoring serum levels. Several methods are proposed to evaluate the uses of antimicrobics in the hospital setting. These include: the monitoring of formulary practice and usage trends, microbiology laboratory practices and trends in resistance, and patterns of use of antibiotics by the medical staff. The formulary composition of antimicrobial compounds should be reviewed to determine agent similarity (redundancy) and indications as well as their relative cost and frequency of use by the medical staff. Monitoring the trends of antibiotic use (and cost) can be achieved by identifying the annual acquisition costs and consumption of each antimicrobial agent, class
© 1988 BY ELSEVIER SCIENCE PUBLISHING CO., INC.
(e.g., antibacterial, antifungal) and group (e.g., aminoglycoside, cephalosporin) of drugs. This information should incorporate both the total usage in grams and the number of patients treated with each drug. When calculating acquisition costs, separate accounting should be made for initial acquisition, preparation, and administration, as well as surcharges for hospital administrative costs. The report recommends that trends can be usefully analyzed w h e n categorized according to medical service and calculated on the basis of patient days for the entire institution and for each service. Annual review is advisable and corrective action possible w h e n deviations are observed. The report suggests that procedures for performing susceptibility tests be in accord with national standards as indicated by NCCLS or other quality assurance groups. 0738-1751/88/$0.00 + 2.20