{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:18:09Z","timestamp":1790691489053,"version":"4.1.0"},"reference-count":90,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Microbiol Rev"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:sec>\n                    <jats:title>SUMMARY<\/jats:title>\n                    <jats:p>In certain unique clinical settings, the ability of the antimicrobial agent administered to kill the pathogen outright may be quite important. These situations invariably involve infection of a site not easily accessed by host defenses and\/or of a structure with essential anatomic or physiologic function such as the heart (endocarditis), central nervous system (meningitis), or bone (osteomyelitis). Likewise, infections in immunosuppressed hosts, especially those who are neutropenic, are often thought to require microbicidal therapy. Proof of the cidal nature of an antimicrobial agent in vitro is tedious, complex, and fraught with error. Although several methods for assessing in vitro bactericidal activity have been standardized (NCCLS M26-A and M21-A), the clinical relevance of these determinations is questionable and the tests are performed infrequently in most laboratories. Most of the clinical data supporting the need for microbicidal therapy and testing have focused on bacterial infections. However, given the fact that most serious fungal infections occur in profoundly immunosuppressed individuals, it is generally assumed that a cidal regimen would be preferable in that setting as well. In view of this clinical concern and the perceived need to assess the fungicidal activity of a variety of agents, we considered that it would be useful to review what is known about the issues and problems in assessing bactericidal activity and the clinical utility of such measurements. Following this review, we discuss the issue of how one defines fungicidal activity in vitro and in vivo and how feasible it might be to determine the fungicidal activity of organism-drug combinations for purposes of both drug development and clinical care. Proposed methods for fungal time-kill determinations and minimal fungicidal concentration determinations are also discussed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/cmr.17.2.268-280.2004","type":"journal-article","created":{"date-parts":[[2004,4,14]],"date-time":"2004-04-14T14:17:57Z","timestamp":1081952277000},"page":"268-280","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":293,"title":["Determination of Fungicidal Activities against Yeasts and Molds: Lessons Learned from Bactericidal Testing and the Need for Standardization"],"prefix":"10.1128","volume":"17","author":[{"given":"M. A.","family":"Pfaller","sequence":"first","affiliation":[{"name":"Department of Pathology and Epidemiology, University of Iowa College of Medicine and College of Public Health, Iowa City, Iowa"},{"name":"Pfizer Inc., New York, New York"},{"name":"Astrazeneca, Macclesfield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Epidemiology, University of Iowa College of Medicine and College of Public Health, Iowa City, Iowa"},{"name":"Pfizer Inc., New York, New York"},{"name":"Astrazeneca, Macclesfield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. H.","family":"Rex","sequence":"additional","affiliation":[{"name":"Department of Pathology and Epidemiology, University of Iowa College of Medicine and College of Public Health, Iowa City, Iowa"},{"name":"Pfizer Inc., New York, New York"},{"name":"Astrazeneca, Macclesfield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.18.1.40-42.1983"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1179-1186.2003"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg018"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.26.2.220"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.12.2612"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.9.3001-3012.2002"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.31.5.679"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/23.6.817"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(02)00525-4"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.12.2749"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/45.5.673"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1979.03630460058018"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1589"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.2050"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.88.1.99"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(98)00130-8"},{"key":"e_1_3_1_18_2","first-page":"1008","volume":"44","year":"2000","unstructured":"Ernst, E. J., M. E. Klepser, and M. A. Pfaller. 2000. Post antifungal effects of echinocandins, azole, and polycne antifungal agents against Candida albicans and Cryptococcus neoformans.Antimicrob. Agents Chemother.44:1008-1111.","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.12.3846-3853.2002"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(96)00202-7"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.3.954-958.2001"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.9.3204-3208.2002"},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1093\/infdis\/149.6.904","volume":"149","year":"1984","unstructured":"Fass, R. J. 1984. Laboratory test for defining bactericidal activity as predictors of antibiotics efficacy in the treatment of endocarditis due to Staphylococcus aureus in rabbits. J. Infect. Dis.149:904-912.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.1888"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1093\/jac\/15.6.653","volume":"15","year":"1985","unstructured":"Greenwood, D. 1985. Phenotypic resistance to antimicrobial agents. J. Antimicrob. Chemother.15:653-658.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.10.2845-2855.2001"},{"key":"e_1_3_1_27_2","first-page":"335","volume":"34","year":"1963","unstructured":"Gunnison, J. B., M. A. Fraher, and E. Jawetz. 1963. Persistence of Staphylococcus aureus in penicillin in vitro. J. Gen. Microbiol.34:335-349.","journal-title":"J. Gen. Microbiol."},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.6.1881-1884.1999"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/7.3.368"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1412"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.19.6.1075"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.10.2865-2868.2000"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.8.2564-2568.2002"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/49.2.353"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.6.1392"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.5.1207"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1917-1920.2000"},{"key":"e_1_3_1_38_2","first-page":"29","volume":"5","year":"2001","unstructured":"Klepser, M. E., R. E. Lewis, E. J. Ernst, C. R. Petzold, E. M. Bailey, D. S. Burgess, P. L. Carver, M. K. Lacy, R.-C. Mercier, D. P. Nicolau, G. G. Zhanel, and M. A. Pfaller. 2001. Multi-center evaluation of antifungal time-kill methods. Infect. Dis. Pharmacother.5:29-41.","journal-title":"Infect. Dis. Pharmacother."},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.9.1988"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.9.2178"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.1.124-128.2001"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.83.2.161"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1382"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(99)00125-X"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/49.2.345"},{"key":"e_1_3_1_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1170"},{"key":"e_1_3_1_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.5.1034"},{"key":"e_1_3_1_48_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/jac\/5.5.613","volume":"5","year":"1979","unstructured":"Lorian, V., R. P. Siletti, F. X. Biondo, and C. C. DeFreitas. 1979. Paradoxical effect of amingolycosides on the growth of Gram-negative bacilli. J. Antimicrob. Chemother.5:613-616.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_1_49_2","first-page":"30128","volume":"42","year":"1998","unstructured":"Manavathu, E. K., J. L. Cutright, and P. H. Chandrasekar. 1998. Organism-dependent fungicidal activity of azoles. Antimicrob. Agents Chemother.42:30128-3021.","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_1_50_2","first-page":"547","volume":"123","year":"1972","unstructured":"McCracken, G. H., Jr. 1972. The rate of bacteriologic response to antimicrobial therapy in neonatal meningitis. Am. J. Dis. Child.123:547-554.","journal-title":"Am. J. Dis. Child."},{"key":"e_1_3_1_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.29.3.418"},{"key":"e_1_3_1_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.6.1882-1885.2001"},{"key":"e_1_3_1_53_2","first-page":"796","volume":"93","year":"1982","unstructured":"Musher, D. M., and R. Fletcher. 1982. Tolerant Staphylococcus aureus causing vertebral osteomyelitis. Arch. Intern. Med.93:796-800.","journal-title":"Arch. Intern. Med."},{"key":"e_1_3_1_54_2","unstructured":"National Committee for Clinical Laboratory Standards. 1998. Methodology for the serum bactericidal test. Approved guideline M21-A. National Committee for Clinical Laboratory Standards Wayne Pa."},{"key":"e_1_3_1_55_2","unstructured":"National Committee for Clinical Laboratory Standards. 1998. Methods for determining bactericidal activity of antimicrobial agents. Approved guideline M26-A. National Committee for Clinical Laboratory Standards Wayne Pa."},{"key":"e_1_3_1_56_2","unstructured":"National Committee for Clinical Laboratory Standards. 2002. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A2. National Committee for Clinical Laboratory Standards Wayne Pa."},{"key":"e_1_3_1_57_2","unstructured":"National Committee for Clinical Laboratory Standards. 2002. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi. Approved standard M38-A. National Committee for Clinical Laboratory Standards Wayne Pa."},{"key":"e_1_3_1_58_2","doi-asserted-by":"publisher","DOI":"10.1086\/314042"},{"key":"e_1_3_1_59_2","first-page":"425","volume":"17","year":"1998","unstructured":"Nguyen, M. H., C. J. Clancy, V. L. Yu, A. J. Morris, D. R. Snydman, D. A. Sutton, and M. G. Rinaldi. 1998. Does in vitro susceptibility data predict the microbiologic response to amphotericin B? Results of a prospective study of patients with Candida fungemia. J. Infect. Dis.17:425-430.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_1_60_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200007000-00006"},{"key":"e_1_3_1_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.18.5.699"},{"key":"e_1_3_1_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.26.6.815"},{"key":"e_1_3_1_63_2","first-page":"3039","volume":"6","year":"2002","unstructured":"Perea, S., G. Gonzalez, A. W. Fothergill, W. R. Kirkpatrick, M. G. Rinaldi, and T. F. Patterson. 2002. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob. Agents Chemother.6:3039-3041.","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_1_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.5.4.420"},{"key":"e_1_3_1_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.9.2148"},{"key":"e_1_3_1_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.3.857-869.2001"},{"key":"e_1_3_1_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.1.12-23.2002"},{"key":"e_1_3_1_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1857-1869.2002"},{"key":"e_1_3_1_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5520(05)70192-6"},{"key":"e_1_3_1_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.7.1.113"},{"key":"e_1_3_1_71_2","doi-asserted-by":"crossref","first-page":"796","DOI":"10.7326\/0003-4819-93-6-796","volume":"93","year":"1980","unstructured":"Rajashekaraiah, K. R., T. Rice, V. S. Rao, D. Marsh, B. Ramakrishna, and C. A. Kallick. 1980. Clinical significance of tolerant strains of Staphylococcus aureus in patients with endocarditis. Ann. Intern. Med.93:796-801.","journal-title":"Ann. Intern. Med."},{"key":"e_1_3_1_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/136.2.196"},{"key":"e_1_3_1_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.643-658.2001"},{"key":"e_1_3_1_74_2","doi-asserted-by":"publisher","DOI":"10.1086\/342384"},{"key":"e_1_3_1_75_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.12.3381-3388.2000"},{"key":"e_1_3_1_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.11.3347-3351.1998"},{"key":"e_1_3_1_77_2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/0002-9343(84)90662-4","volume":"76","year":"1984","unstructured":"Sculier, J. P., and J. Klastersky. 1984. Significance of serum bactericidal activity in gram negative bacillary bacteremia in patients with and without granulocytopenia. Am. J. Med.76:429-435.","journal-title":"Am. J. Med."},{"key":"e_1_3_1_78_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.5.633"},{"key":"e_1_3_1_79_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/infdis\/136.2.187","volume":"136","year":"1977","unstructured":"Stratton, C. W., and L. B. Reller. 1977. Serum dilution test for bactericidal activity. 1. Selection of a physiologic diluent. J. Infect. Dis.136:187-195.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_1_80_2","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1093\/infdis\/145.2.160","volume":"145","year":"1982","unstructured":"Stratton, C. W., M. P. Weinstein, and L. B. Reller. 1982. Correlation of serum bactericidal activity with antimicrobial agent level and minimal bactericidal concentration. J. Infect. Dis.145:160-168.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_1_81_2","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1001\/archinte.1981.00340130152036","volume":"141","year":"1981","unstructured":"Streinbrecher, U. P. 1981. Serious infection in an adult due to penicillin-tolerant group B streptococcus. Arch. Intern. Med.141:1714-1715.","journal-title":"Arch. Intern. Med."},{"key":"e_1_3_1_82_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.23.1.142"},{"key":"e_1_3_1_83_2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1179\/joc.2002.14.3.246","volume":"14","year":"2002","unstructured":"Tortorano, A. M., E. Dannaoui, J. Meletiadis, M. Mallie, M. A. Viviani, M. A. Piens, A. L. Rigoni, J. M. Bastide, and R. Grillot. 2002. Effect of medium composition on static and cidal activity of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine against Aspergillus fumigatus: a multicenter study. J. Chemother.14:246-252.","journal-title":"J. Chemother."},{"key":"e_1_3_1_84_2","first-page":"1297","volume":"132","year":"1986","unstructured":"Tuomanen, E., R. Cozens, W. Tosch, O. Zak, and A. Tomasz. 1986. The rate of killing of Escherichia coli is strictly proportional to the rate of bacterial growth. J. Gen. Microbiol.132:1297-1304.","journal-title":"J. Gen. Microbiol."},{"key":"e_1_3_1_85_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.4.521"},{"key":"e_1_3_1_86_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1612"},{"key":"e_1_3_1_87_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1960-1965.2002"},{"key":"e_1_3_1_88_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkf247"},{"key":"e_1_3_1_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(85)90436-X"},{"key":"e_1_3_1_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(87)90688-7"},{"key":"e_1_3_1_91_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.5.792"}],"container-title":["Clinical Microbiology Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CMR.17.2.268-280.2004","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CMR.17.2.268-280.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T05:49:42Z","timestamp":1645595382000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CMR.17.2.268-280.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4]]},"references-count":90,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1128\/CMR.17.2.268-280.2004"],"URL":"https:\/\/doi.org\/10.1128\/cmr.17.2.268-280.2004","relation":{},"ISSN":["0893-8512","1098-6618"],"issn-type":[{"value":"0893-8512","type":"print"},{"value":"1098-6618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4]]},"assertion":[{"value":"2004-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}