Pharmacological considerations in the emergence of resistance

被引:6
作者
Amsden, GW
机构
[1] Bassett Healthcare, Clin Pharmacol Res Ctr, Cooperstown, NY 13326 USA
[2] Bassett Healthcare, Dept Pharm, Cooperstown, NY 13326 USA
[3] Bassett Healthcare, Dept Med, Cooperstown, NY 13326 USA
关键词
macrolide; pharmacokinetics; resistance; azithromycin; clarithromycin;
D O I
10.1016/S0924-8579(98)00098-3
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Resistance to macrolides in vitro is increasingly being reported. However, there has been no corresponding increase in clinical failures noted. Lack of clinical failures due to resistance is most likely the result of the high intracellular concentrations that these drugs achieve in phagocytes. In the case of clarithromycin, concentrations in both monocytes and granulocytes fluctuate between peaks of approximate to 22-25 mg/l and troughs of approximate to 5 mg/l during a standard dosing interval. In contrast, azithromycin attains concentrations of over 60 mg/l in granulocytes and at least 100 mg/l in monocytes. After 7 days, azithromycin concentrations of > 32 mg/l are still observed. These data also imply that against pathogens with increasing minimum inhibitory concentrations (MICs), macrolides with relatively lower or less sustained intracellular concentrations will become ineffective clinically much sooner than compounds, such as azithromycin, that concentrate to a high degree and are retained in white blood cells for prolonged periods. (C) 1999 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.
引用
收藏
页码:S7 / S14
页数:8
相关论文
共 28 条
[1]  
*ABB, 1997, CLAR PROD INF
[2]   The role of advanced generation macrolides in the prophylaxis and treatment of Mycobacterium avium complex (MAC) infections [J].
Amsden, GW ;
Peloquin, CA ;
Berning, SE .
DRUGS, 1997, 54 (01) :69-80
[3]   Comparison of the plasma, urine and blister fluid pharmacokinetics of clarithromycin and azithromycin in normal subjects [J].
Amsden, GW ;
Ballow, CH ;
Forrest, A .
CLINICAL DRUG INVESTIGATION, 1997, 13 (03) :152-161
[4]   Carriage of antibiotic-resistant Streptococcus pneumoniae by children in Eastern and Central Europe - A multicenter study with use of standardized methods [J].
Appelbaum, PC ;
Gladkova, C ;
Hryniewicz, W ;
Kojouharov, B ;
Kotulova, D ;
Mihalcu, F ;
Schindler, J ;
Setchanova, L ;
Semina, N ;
Trupl, J ;
Tyski, S ;
Urbaskova, P ;
Jacobs, MR .
CLINICAL INFECTIOUS DISEASES, 1996, 23 (04) :712-717
[5]   Comparative in vitro assessment of sparfloxacin activity and spectrum using results from over 14,000 pathogens isolated at 190 medical centers in the USA [J].
Ballow, CH ;
Jones, RN ;
Johnson, DM ;
Deinhart, JA ;
Schentag, JJ ;
Tritsch, M ;
Ellis, S ;
Burger, J ;
Cole, E ;
Venezia, R ;
George, M ;
Wolf, D ;
Slifkin, M ;
DePalma, J ;
Rudrik, J ;
Sullivan, K ;
Lewis, G ;
Dooley, G ;
Sawicki, R ;
Desiderio, D ;
Louma, R ;
Motyl, M ;
Ruffin, L ;
Torresan, J ;
Dunaway, G ;
Keck, G ;
Truitt, L ;
Brecher, S ;
VanEnk, R ;
Whelen, C ;
Fader, R ;
Whisler, G ;
Jenkins, S ;
Thacker, D ;
DAmato, R ;
Buck, R ;
Buescher, S ;
Lambert, K ;
Tristram, D ;
Kehl, S ;
Lawson, C ;
Washington, J ;
Robertson, K ;
Beall, A ;
Padgett, L ;
Rahman, L ;
Riddle, G ;
DellaLatta, P ;
Marcon, M ;
Northern, I .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 1997, 29 (03) :173-186
[7]   ATTENUATION OF SHOCK-INDUCED HEPATIC MICROCIRCULATORY DISTURBANCES BY THE USE OF A STARCH-DEFEROXAMINE CONJUGATE FOR RESUSCITATION [J].
BAUER, M ;
FEUCHT, K ;
ZIEGENFUSS, T ;
MARZI, I .
CRITICAL CARE MEDICINE, 1995, 23 (02) :316-322
[8]   Emergence of Mycobacterium avium populations resistant to macrolides during experimental chemotherapy [J].
Bermudez, LE ;
Petrofsky, M ;
Kolonoski, P ;
Young, LS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1998, 42 (01) :180-183
[9]   SYNTHESIS, INVITRO AND INVIVO ACTIVITY OF NOVEL 9-DEOXO-9A-AZA-9A-HOMOERYTHROMYCIN A DERIVATIVES - A NEW CLASS OF MACROLIDE ANTIBIOTICS, THE AZALIDES [J].
BRIGHT, GM ;
NAGEL, AA ;
BORDNER, J ;
DESAI, KA ;
DIBRINO, JN ;
NOWAKOWSKA, J ;
VINCENT, L ;
WATROUS, RM ;
SCIAVOLINO, FC ;
ENGLISH, AR ;
RETSEMA, JA ;
ANDERSON, MR ;
BRENNAN, LA ;
BOROVOY, RJ ;
CIMOCHOWSKI, CR ;
FAIELLA, JA ;
GIRARD, AE ;
GIRARD, D ;
HERBERT, C ;
MANOUSOS, M ;
MASON, R .
JOURNAL OF ANTIBIOTICS, 1988, 41 (08) :1029-1047
[10]  
CAUCHIE P, 1998, 4 INT C MACR AZ STRE