{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:13:34Z","timestamp":1792088014589,"version":"4.4.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2003,2,1]],"date-time":"2003-02-01T00:00:00Z","timestamp":1044057600000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Optimizing pharmacokinetic\/pharmacodynamic indices of antibiotics to obtain clinical and microbiological efficacy is essential, but dosing regimens must also be tailored to minimize the risk for emergence of resistance. The aim of the present study was to investigate whether certain concentrations of benzylpenicillin are critical for the selection of resistant subpopulations. A mixed culture of\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            containing ca. 90% susceptible (MIC = 0.031 mg\/liter), 9% intermediate (MIC = 0.25 mg\/liter), and 1% resistant (MIC = 8 mg\/liter) was studied in an in vitro kinetic model. The time that concentrations exceeded the MIC (T&gt;MIC) for the three strains in the culture was varied by different initial concentrations of benzylpenicillin. Samples for viable counts were withdrawn at different times during 24 h and seeded on blood agar plates and on selective antibiotic-containing plates. The T&gt;MIC varied from 46 to 100% for the susceptible strain, from 6 to 100% for the intermediate strain, and from 0 to 48% for the resistant strain. Our study, which may mimic the clinical situation with carriage of a mixed population of\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            with different antibiotic susceptibilities, has shown that selection of resistant bacteria may easily occur if dosing regimens are only targeted toward fully susceptible strains.\n          <\/jats:p>","DOI":"10.1128\/aac.47.2.518-523.2003","type":"journal-article","created":{"date-parts":[[2003,1,23]],"date-time":"2003-01-23T21:05:59Z","timestamp":1043355959000},"page":"518-523","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Suboptimal Antibiotic Dosage as a Risk Factor for Selection of Penicillin-Resistant\n            <i>Streptococcus pneumoniae<\/i>\n            : In Vitro Kinetic Model"],"prefix":"10.1128","volume":"47","author":[{"given":"Inga","family":"Odenholt","sequence":"first","affiliation":[{"name":"Antibiotic Research Unit, Department of Infectious Diseases and Clinical Bacteriology, University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingegerd","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Antibiotic Research Unit, Department of Infectious Diseases and Clinical Bacteriology, University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Lo\u0308wdin","sequence":"additional","affiliation":[{"name":"Antibiotic Research Unit, Department of Infectious Diseases and Clinical Bacteriology, University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Cars","sequence":"additional","affiliation":[{"name":"Antibiotic Research Unit, Department of Infectious Diseases and Clinical Bacteriology, University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1097\/00001432-199612000-00003","volume":"9","year":"1996","unstructured":"Baquero, F. 1996. Epidemiology and management of penicillin-resistant pneumococci. Curr. Opin. Infect. Dis.9:372-379.","journal-title":"Curr. Opin. Infect. Dis."},{"key":"e_1_3_2_3_2","first-page":"29","volume":"9","year":"1997","unstructured":"Baquero, F., and M. C. Negri. 1997. Strategies to minimize the development of antibiotic resistance. J. Chemother.9(Suppl. 3):29-37.","journal-title":"J. Chemother."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/516284"},{"key":"e_1_3_2_5_2","first-page":"7","volume":"77","year":"1998","unstructured":"Craig, W. A. 1998. Choosing an antibiotic on the basis of pharmacodynamics. Ear Nose Throat J.77:7-12.","journal-title":"Ear Nose Throat J."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/321854"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199611000-00010"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1086\/514120","volume":"176","year":"1997","unstructured":"Dagan, R., O. Abramson, E. Leibovitz, D. Greenberg, R. Lang, S. Goshen, P. Yagupsky, A. Leiberman, and D. M. Fliss. 1997. Bacteriologic response to oral cephalosporins: are established susceptibility breakpoints appropriate in the case of acute otitis media? J. Infect. Dis.176:1253-1259.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1097\/00006454-200004000-00033","volume":"19","year":"2000","unstructured":"Dagan, R. 2000. Clinical significance of resistant organisms in otitis media. Pediatr. Infect. Dis. J.19:378-382.","journal-title":"Pediatr. Infect. Dis. J."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"S57","DOI":"10.1097\/00006454-200005001-00009","volume":"19","year":"2000","unstructured":"Dagan, R., E. Leibovitz, A. Leiberman, and P. Yagupsky. 2000. Clinical significance of antibiotic resistance in acute otitis media and implication of antibiotic treatment on carriage and spread of resistant organisms. Pediatr. Infect. Dis. J.19:S57-S65.","journal-title":"Pediatr. Infect. Dis. J."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.2.129"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1086\/319250","volume":"183","year":"2001","unstructured":"Dagan, R., E. Leibovitz, G. Cheletz, A. Leiberman, and N. Porat. 2001. Antibiotic treatment in acute otitis media promotes superinfection with resistant Streptococcus pneumoniae carried before initiation of treatment. J. Infect. Dis.183:880-886.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1253"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1179\/joc.1997.9.1.38"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.4.1078-1085.2001"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)90087-J"},{"key":"e_1_3_2_17_2","first-page":"920","volume":"146","year":"1992","unstructured":"Friedland, I. R., and K. P. Klugman. 1992. Antibiotic-resistant pneumococcal disease in South African children. Am. J. Dis. Child.146:920-923.","journal-title":"Am. J. Dis. Child."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1097\/00006454-199510000-00013","volume":"14","year":"1995","unstructured":"Friedland, I. R. 1995. Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease. Pediatr. Infect. Dis. J.14:885-890.","journal-title":"Pediatr. Infect. Dis. J."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/jac\/38.suppl_A.71","volume":"38","year":"1996","unstructured":"Goldstein, F. W., J. F. Acar, et al. 1996. Antimicrobial resistance among respiratory tract isolates of Streptococcus pneumoniae: results of a 1992-93 Western Europe and USA collaborative study. J. Antimicrob. Chemother.38(Suppl. A):71-84.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.279.5.365"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.9.2436-2440.2001"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-200010000-00019"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.11.2478"},{"key":"e_1_3_2_24_2","unstructured":"Mufson M. A . 1990. Streptococcus pneumoniae p. 1539-1551. In G. L. Mandell R. G. Douglas and J. E. Bennet (ed.) Principles and practice of infectious diseases 3rd ed. Churchill Livingstone Inc. New York N.Y."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.1.122"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508243330802"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.4.588"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.1086\/321848","volume":"33","year":"2001","unstructured":"Steinke, D., and P. Davey. 2001. Association between antibiotic resistance and community prescribing: a critical review of bias and confounding in published studies. Clin. Infect. Dis.33(Suppl. 3):S193-S205.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/clinids\/24.1.85","volume":"24","year":"1997","unstructured":"Tomasz, A. 1997. Antibiotic resistance in Streptococcus pneumoniae. Clin. Infect. Dis.24(Suppl. 1):85-88.","journal-title":"Clin. Infect. Dis."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.47.2.518-523.2003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.47.2.518-523.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T17:55:00Z","timestamp":1645466100000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.47.2.518-523.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,2]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,2]]}},"alternative-id":["10.1128\/AAC.47.2.518-523.2003"],"URL":"https:\/\/doi.org\/10.1128\/aac.47.2.518-523.2003","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,2]]},"assertion":[{"value":"2002-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-10-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}