Originalia
H. M. Theopold, Ch. Matthias, D. Adam
Cefpodoxime Proxetil Concentrations in Head and Neck Tissues Cefpodoxirne proxeW
Summary: Three to six hours prior to surgery in the head and neck a single dose of 200 mg cefpodoxime proxetil was administered orally to 30 patients. During surgery serum and tissue samples (concha, mocosa, cartilage, bone, parotis and tonsil) were taken and the concentrations of cefpodoxime were determined by bioassay. The serum concentrations ranged from 0.72 mg/1 (determined after 6 h 22 min) to 3.34 mg/1 (3 h 15 min). The tissue concentrations were between 0.15 mg/l (determined in bone after 5 h 18 rain) and 1.94 mg/1 (concha 4 h 13 min). Analogously to recent in vitro data the concentrations reached in head and neck tissue were higher thanthe MIC90 values for most pathogens of upper respiratory tract infections. Zusammenfassung: Cefpodoxim Proxetil- Konzentrationen in Geweben des Kopf-Hals-Bereiches. 30 Patienten erhielten drei bis sechs Stunden vor einer Operation im Kopf-Hals-Bereich eine einmalige Dosis von 200 mg Cefpodoxim Proxetil oral. W~ihrend der Operation wurden sowohl Serumals auch verschiedene Gewebeproben (Concha, Mucosa, Knorpel, Knochen, Parotis, Tonsille) entnommen und anschliegend die Konzentrationen von Cefpodoxim im Serum und in den Gewebeproben mittels Bioassay bestimmt. Die ermittelten Serumspiegel lagen zwischen 0,71mg/1 (nach 6 h 22 min) und 3,34 mg/1 (nach 3 h 15 min); die Gewebespiegel lagen zwischen 0,15 mg/kg (Knochen: nach 5 h 18 min) und 1,94 mg/kg (Concha: nach 4 h 13 min). Analog zu den bisher bekannt gewordenen In-vitroWerten (90 MHK) von Cefpodoximlagen die Gewebekonzentrationen im Empfindlichkeitsbereich der meisten isolierten Erreger, die im oberen Respirationstrakt von Bedeutung sind.
Introduction Cefpodoxime proxetil is a recent oral cephalosporinester of the "third generation". The substance is well absorbed in its active form from the intestinal lumen after being hydrolized by esterases in the intestinal wall. Serum protein-binding is about 40% in man. The addition of the aminothiazole group in position 7 results in a higher activity and extension of the antibacterial spectrum compared to older cephalosporins. The methoximino group causes higher stability against b-lactamases [1]. Pharmacokinetic investigations showed that the half life (t 1/2) after a single oral dose of 200 mg is 2 h ( + / - 0.1 h) with maximum concentrations (C max) of 2.96 + / - 0.1 mg/1. Within 24 h about 45% of cefpodoxime is excreted with the urine [1]. Cefpodoxime has a wide range of antibacterial activity
CH~ O-CH-O-~-O-CIH-CH3
o; /OCH~ HN ~N
C
NH~----Jj~._,,,,,J
R-3763, Cefpodoxirne Oc°"
1:1-3746, Na Sa/t of Cefpodoxime
~c,, ON"
N/OCH30~t~N~/CH~O-CHa
/OCHa 0
,J-4., J H H S
HN N C NHA--~ 2..~jy~c / I' "-J' ~I,~",~_s,.~P
H~N~vO~ /NH
~_~
oc.~
0~.N ~~- ~ CH~"O-CH3
~
kSJ
~
~
/CH-O-CH
H H
Figure 1: Chemical Structure: Cephalosporins.
against gram-positive as well as gram-negative microorganisms, especially Neisseria gonorrhoeae (penicillin-resistan0, Streptococcus pneumoniae (penicillin-sensitive), haemolytic streptococci (groups A, B, C and G), Proteus mirabilis, Proteus vulgaris, Haemophilus influenzae (ampicillin-resistant), Klebsiella subspecies and Moraxella catarrhalis (MICgo = 1 mg/1) [2-5]. Lower activity has been shown against different Staphylococcus spp. (MIC90 = 1-8 rag/l) [2, 3] and penicillin-resistant S. pneumoniae (MICg0 = 4 mg/1) [5]. Cefpodoxime is not active against methicillinresistant staphylococci, Pseudomonas spp., Enterococcus spp., and Bacteroides spp. [2, 3, 6]. Materials and Methods 30 patients (15 m/15 f) between the age of 18-54 years (mean 33.1 years), weight 47.90 kg (mean 72 kg) received a single oral dose of 200 mg cefpodoxime proxetil (Sankyo) for prophylactic purposes 3-6 h before undergoing head and neck surgery. Written consent of the patients was obtained. Before drug administration a serum sample was taken to exclude any other antibiotic activity. After 3-6 h tissue samples were taken from the mouth, nasal cartilage, mucosa or middle ear mucosa and/or from the bone during surgery. These samples were immediately rinsed with 0.9% NaC1 solution and cleaned of blood with a dry swab. At the same time serum was withdrawn. All samples were immediately frozen at -20. Cefpodoxime concentrations were examined by bioassay: The tissue and serum concentrations of cefpodoxime were deter-
Received: 21 December 1989/Revisionaccepted: 9 October 1990 Prof. Dr. H. M. Theopold, Med. Fakult/it der LMU Mtinchen, Brienner Str. 12, W-8000Mfinchen2; C. Matthias, Cand. med. der LMU Mfinchen, AgnesstraBe 31, W-8000 Mfinchen40; Prof. Dr. med. Dr. rer. nat. D. Adam, LMU Mfinchen, Haunersches Kinderspital, Lindwurmstrage4, W-8000 Mfinchen2, Germany.
Infection 19 (1991) No. 1 © MMV MedizinVerlag GmbH Miinchen, MiJnchen 1991
41 / 45
H. M. Theopold et al.: Cefpodoxime Proxetil Concentrations in ENT Table 1: Serum and tissue concentrations of cefpodoxime 3roxetil.
Tissue Conc, in I~g/ml 1,5 1,25 -
iiiii!iiiiiiii!ilii, li!,ii;ii!;i ii iiiiiiiiiiiiiii:iiiiiiii illilIlilliiiiii @
N i iii !Niiiiii:!iii!ili
iiiiii [ iiil iiiii:ii] 1 iilli!!/iiiiiiii:!ii!iiiiiiii?iiiiiiiiiiiii:i;!!ililil! N;!iiiii!:iiiiii i iiilt 0,75 -
Concha (7 samples) Max. Min. Mean
1.94 0.3 0.72
3.1 0.72
Mucosa (3 samples) Max. Min. Mean
1.60 0.58 0.76
3.1 2.98
4h 13 5h 11
Cartilage (16 samples) Max. 1.24 Min. 0.19 Mean 0.39
3.1 1.01
4h 05 5h 16
Bone (6 samples) Max. Min. Mean
0.72 0.15 0.35
3.I 1.01
4h 09 5h 18
Parotis (2 samples) Max. Min. Mean
0.48 0.24 0.36
3.34 1.19
3h 15 5h 30
Tonsil (2 samples) Max. Min. Mean
0.23 0.2 0.22
3.23 1.36
4h 01 4h 29
Total (36 samples) Mean
0.47
1.97
4h 13 6h 22
0,50,25 : 0
i 0
-"'-
i
i
2o0 3oo Timeinmin
100 others
concha
4oo
500
- . e . - ca~ilage
Figure 3: Tissue concentrations of cefpodoxime in relation to time (x = cartilage, o = concha, a = other samples).
A standard graph of inhibition zones with known antibiotic concentrations was used. According to this standard curve the antibiotic concentrations of the serum and tissue samples could be determined by measuring the diameters of inhibition zones with a computer technique. The serum concentrations were also determined by a new HPLC-method to compare the results of this method and the bioassay-method. Generally the results of the multi-centre study showed conformity of both methods. Before administering the antibiotic to patients blood for laboratory testing of liver and kidney parameters was taken. After administration of cefpodoxime proxetil the patients were observed and interviewed for possible side effects. Two weeks after surgery this procedure was repeated and laboratory findings were compared to the first data obtained.
Results
mined by an agar diffusion method using Base Agar Antibiotic Medium No. 1 (Oxoid). A fixed amount of test organisms (Morganella morganii IFO 3848 for serum, Proteus rettgeri UC 1.2186 for tissue) was introduced into the agar. Serum Conc, in ~ g / m l 4
3
Serum concentrations 3 h ( + / - 15 min) after dosing ranged between 4.19 mg/l and 1.26 mg/1, and after 6 h ( + / - 15 min) between 2.27 mg/1 and 0.67 rag/1 (Figure 2). This tissue concentrations were between 1.94 mg/kg (concha: after 4 h 14 min) and 0.15 mg/kg (bone: after 5 h 18 min). The data for the different tissues and their relation to serum concentrations are shown in Table 1. The maximum cefopodoxime proxetil tissue concentrations were reached 4 h to 4 h 30 min after administration (Figure 3). The drug was tolerated without any side effects by any of the 30 patients. No toxic or allergic reactions were seen.
Discussion
2
1
0
100
200
300
400
500
Time in min Figure 2: Serum concentration of cefpodoxime in relation to time after a single oral dose of 200 mg.
46 / 42
Cefpodoxime concentrations found in nasal mucosa, concha, cartilage and bone during surgery were higher than the MIC90values for most of the organisms responsible for upper respiratory tract infections. Cefpodoxime MIC90 values for respiratory tract pathogens are lower than those of other oral cephalosporins such as cefaclor and cefadroxil. The MIC90 of cefpodoxime for ampicillin-sensitive H. influenzae (Amp.-S) is 0.25 mg/1 and 0.5 mg/1 forH. influenzae ampicillin-resistant [2-6]. Comparable in vitro findings for cefadroxil are 16 rag/1 for ampicillin-sensitiveand-resistant H. influ-
Infection 19 (1991) No. 1 © MMV Medizin Verlag GmbH Mtinchen, Mtinchen 1991
H. M. Theopold et al.: Cefpodoxime Proxetil Concentrations in ENT
0.25 mg/1 compared to 8 mg/l for cefaclor and 16 mg/1 for cefadroxil [2]. The MIC90 of cefpodoxime against S. p n e u m o niae is 0.06 mg/l compared to 2 mg/1 for cefaclor and 16 mg/1 for cefadroxil, and even for penicillin-resistant S. p n e u m o n i a e t h e M I C 9 o o f c e f p o d o x i m e i s 4 mg/lwhereas cefaclor and cefadroxil are inactive against these strains with MIC90 > 64 mg/l [2]. MICg0 values for streptococci (groups A, B, C and G) are mg/l for all three antibiotics [2--4, 6]. In most cases the tissue concentrations of cefpodoxime were below MIC90 values against staphylococci. This is especially true for methicillin resistant Staphylococcus aureus. The Cmax of cefpodoxime of 2.96 mg/l after a single oral dose of 200 mg of the ester compound is somewhat lower than concentrations found after therapeutic (1 g) doses of cefalexin (C max = 24.7 mg/1), 0.5 g of cefaclor
(C max = 17.8 mg/1) or 1 g ofcefadroxil (C max = 28 mg/1) [7]. With a half-life of 2.1 h, cefpodoxime has longer lasting therapeutically effective serum concentrations [7] than cefalexin (half-life 60 min), cefaclor (half-life 60 min) or cefadroxil (half-life 90 min). The tissue from tonsils which was taken 4 h 01 min and 4 h 29 min, respectively, after the oral application of cefpodoxime proxetil showed concentrations of up to 0.23 mg/1. Additional examinations should be performed on tonsils since concentrations should be comparable to those in the mucosa or conchal tissue (concha 1.94 mg/1 with serum concentration 3.1 mg/kg after 4 h 13 min). Even the concentrations in the cartilage of the septum of up to 1.24 mg/kg with a corresponding serum concentration of 3.1 rag/1 after 4 h 5 min is sufficient for the therapy of infections with sensitive microorganisms.
References
4. Knapp, C.C., Sierra-Madero, J., Washington, J.A.: Antibacterial
enzae. The MIC90 of cefpodoxime against K. p n e u m o n i a e is
activitiesof cefpodoxim,cef~ime and ceftriaxone.Antimicrob.Agents Chemother. 32 (1988) 1896-1898. 1. Sankyo:InvestigatorsManual 1988, SankyoEurope GmbH. 2. Bauernfeind, A., Schweighart, S.: 1989 Cefpodoximein vitro activity. Poster. 16th International Congress of Chemotherapy Jerusalem, Israel, June 11-16, 1989. 3. Fass, R. J., Heisel, V. L.: In vitro activity of U 76, 252 a new oral cephalosporin. Antimicrob.Agents Chemother. 32 (1988) 1085.
5. Sarubbi, F. A., Verghese, A., Caggina, C., Holtsclaw-Berk, S. L.: In vitro activityof cefpodoximproxetil against clinical isolates of Branhamella catarrhalis.Antimicrob.AgentsChemother.33 (1989) 113-114. 6. Chin, N. X., Neu, H. C.: In vitro activity of an oral iminomethoxy
aminothiazolylcephalosporin, R - 3746. Antimicrob.Agents Chemother. 32 (1988) 671-677.
Information Stipendium Klinische Infektiologie
DM 30 000,- werden f/Jr 1991 erneut bereitgestellt for eine halbj~ihrige Weiterbildung in klinischer Infektiologie for eine/n j0ngere/n Mediziner/in aus dem deutschsprachigen Raum. Die Weiterbildung kann erfolgen an einem Institut for Medizinische Mikrobiologie oder einer infektiologisch ausgerichteten Abteilung eines Klinikums innerhalb Europas. Es wird gebeten, Plan, Ziel und Ort der angestrebten Weiterbildung sowie die Zusage der Gastinstitution mitzuteilen. Der/Die Bewerber/in sollte durch Promotion oder einige Publikationen wissenschaftlich ausgewiesen sein. Bewerbungen mit tabellarischem Lebenslauf unter Beiftigung der
Dissertationsschrift oder von Publikationen werden erbeten innerhalb von acht Wochen nach Erscheinen dieser Ausschreibung an: a) Prof. Dr. med. P. M. Shah oder b) Prof. Dr. med. U. Ullmann Zentrumd. Inneren Medizin Direktor d. d. J. W. Goethe-Universit~it Abteilung Med. Theodor-Stern-Kai 7 Mikrobiologie d. 6000 Frankfurt/M. 70 Univ. Kiel Brunswiker Str. 4 2300 Kiel 1 Das Stipendium wird vonder Firma MSD Sharp & Dohme GmbH, Miinchen, bereitgestellt.
Infection 19 (1991) No. 1 © MMV Medizin Verlag GmbH M0nchen, Miinchen 1991
43 / 47
H. M. Theopold, Ch. Matthias, D. Adam
Cefpodoxime Proxetil Concentrations in Head and Neck Tissues Cefpodoxirne proxeW
Summary: Three to six hours prior to surgery in the head and neck a single dose of 200 mg cefpodoxime proxetil was administered orally to 30 patients. During surgery serum and tissue samples (concha, mocosa, cartilage, bone, parotis and tonsil) were taken and the concentrations of cefpodoxime were determined by bioassay. The serum concentrations ranged from 0.72 mg/1 (determined after 6 h 22 min) to 3.34 mg/1 (3 h 15 min). The tissue concentrations were between 0.15 mg/l (determined in bone after 5 h 18 rain) and 1.94 mg/1 (concha 4 h 13 min). Analogously to recent in vitro data the concentrations reached in head and neck tissue were higher thanthe MIC90 values for most pathogens of upper respiratory tract infections. Zusammenfassung: Cefpodoxim Proxetil- Konzentrationen in Geweben des Kopf-Hals-Bereiches. 30 Patienten erhielten drei bis sechs Stunden vor einer Operation im Kopf-Hals-Bereich eine einmalige Dosis von 200 mg Cefpodoxim Proxetil oral. W~ihrend der Operation wurden sowohl Serumals auch verschiedene Gewebeproben (Concha, Mucosa, Knorpel, Knochen, Parotis, Tonsille) entnommen und anschliegend die Konzentrationen von Cefpodoxim im Serum und in den Gewebeproben mittels Bioassay bestimmt. Die ermittelten Serumspiegel lagen zwischen 0,71mg/1 (nach 6 h 22 min) und 3,34 mg/1 (nach 3 h 15 min); die Gewebespiegel lagen zwischen 0,15 mg/kg (Knochen: nach 5 h 18 min) und 1,94 mg/kg (Concha: nach 4 h 13 min). Analog zu den bisher bekannt gewordenen In-vitroWerten (90 MHK) von Cefpodoximlagen die Gewebekonzentrationen im Empfindlichkeitsbereich der meisten isolierten Erreger, die im oberen Respirationstrakt von Bedeutung sind.
Introduction Cefpodoxime proxetil is a recent oral cephalosporinester of the "third generation". The substance is well absorbed in its active form from the intestinal lumen after being hydrolized by esterases in the intestinal wall. Serum protein-binding is about 40% in man. The addition of the aminothiazole group in position 7 results in a higher activity and extension of the antibacterial spectrum compared to older cephalosporins. The methoximino group causes higher stability against b-lactamases [1]. Pharmacokinetic investigations showed that the half life (t 1/2) after a single oral dose of 200 mg is 2 h ( + / - 0.1 h) with maximum concentrations (C max) of 2.96 + / - 0.1 mg/1. Within 24 h about 45% of cefpodoxime is excreted with the urine [1]. Cefpodoxime has a wide range of antibacterial activity
CH~ O-CH-O-~-O-CIH-CH3
o; /OCH~ HN ~N
C
NH~----Jj~._,,,,,J
R-3763, Cefpodoxirne Oc°"
1:1-3746, Na Sa/t of Cefpodoxime
~c,, ON"
N/OCH30~t~N~/CH~O-CHa
/OCHa 0
,J-4., J H H S
HN N C NHA--~ 2..~jy~c / I' "-J' ~I,~",~_s,.~P
H~N~vO~ /NH
~_~
oc.~
0~.N ~~- ~ CH~"O-CH3
~
kSJ
~
~
/CH-O-CH
H H
Figure 1: Chemical Structure: Cephalosporins.
against gram-positive as well as gram-negative microorganisms, especially Neisseria gonorrhoeae (penicillin-resistan0, Streptococcus pneumoniae (penicillin-sensitive), haemolytic streptococci (groups A, B, C and G), Proteus mirabilis, Proteus vulgaris, Haemophilus influenzae (ampicillin-resistant), Klebsiella subspecies and Moraxella catarrhalis (MICgo = 1 mg/1) [2-5]. Lower activity has been shown against different Staphylococcus spp. (MIC90 = 1-8 rag/l) [2, 3] and penicillin-resistant S. pneumoniae (MICg0 = 4 mg/1) [5]. Cefpodoxime is not active against methicillinresistant staphylococci, Pseudomonas spp., Enterococcus spp., and Bacteroides spp. [2, 3, 6]. Materials and Methods 30 patients (15 m/15 f) between the age of 18-54 years (mean 33.1 years), weight 47.90 kg (mean 72 kg) received a single oral dose of 200 mg cefpodoxime proxetil (Sankyo) for prophylactic purposes 3-6 h before undergoing head and neck surgery. Written consent of the patients was obtained. Before drug administration a serum sample was taken to exclude any other antibiotic activity. After 3-6 h tissue samples were taken from the mouth, nasal cartilage, mucosa or middle ear mucosa and/or from the bone during surgery. These samples were immediately rinsed with 0.9% NaC1 solution and cleaned of blood with a dry swab. At the same time serum was withdrawn. All samples were immediately frozen at -20. Cefpodoxime concentrations were examined by bioassay: The tissue and serum concentrations of cefpodoxime were deter-
Received: 21 December 1989/Revisionaccepted: 9 October 1990 Prof. Dr. H. M. Theopold, Med. Fakult/it der LMU Mtinchen, Brienner Str. 12, W-8000Mfinchen2; C. Matthias, Cand. med. der LMU Mfinchen, AgnesstraBe 31, W-8000 Mfinchen40; Prof. Dr. med. Dr. rer. nat. D. Adam, LMU Mfinchen, Haunersches Kinderspital, Lindwurmstrage4, W-8000 Mfinchen2, Germany.
Infection 19 (1991) No. 1 © MMV MedizinVerlag GmbH Miinchen, MiJnchen 1991
41 / 45
H. M. Theopold et al.: Cefpodoxime Proxetil Concentrations in ENT Table 1: Serum and tissue concentrations of cefpodoxime 3roxetil.
Tissue Conc, in I~g/ml 1,5 1,25 -
iiiii!iiiiiiii!ilii, li!,ii;ii!;i ii iiiiiiiiiiiiiii:iiiiiiii illilIlilliiiiii @
N i iii !Niiiiii:!iii!ili
iiiiii [ iiil iiiii:ii] 1 iilli!!/iiiiiiii:!ii!iiiiiiii?iiiiiiiiiiiii:i;!!ililil! N;!iiiii!:iiiiii i iiilt 0,75 -
Concha (7 samples) Max. Min. Mean
1.94 0.3 0.72
3.1 0.72
Mucosa (3 samples) Max. Min. Mean
1.60 0.58 0.76
3.1 2.98
4h 13 5h 11
Cartilage (16 samples) Max. 1.24 Min. 0.19 Mean 0.39
3.1 1.01
4h 05 5h 16
Bone (6 samples) Max. Min. Mean
0.72 0.15 0.35
3.I 1.01
4h 09 5h 18
Parotis (2 samples) Max. Min. Mean
0.48 0.24 0.36
3.34 1.19
3h 15 5h 30
Tonsil (2 samples) Max. Min. Mean
0.23 0.2 0.22
3.23 1.36
4h 01 4h 29
Total (36 samples) Mean
0.47
1.97
4h 13 6h 22
0,50,25 : 0
i 0
-"'-
i
i
2o0 3oo Timeinmin
100 others
concha
4oo
500
- . e . - ca~ilage
Figure 3: Tissue concentrations of cefpodoxime in relation to time (x = cartilage, o = concha, a = other samples).
A standard graph of inhibition zones with known antibiotic concentrations was used. According to this standard curve the antibiotic concentrations of the serum and tissue samples could be determined by measuring the diameters of inhibition zones with a computer technique. The serum concentrations were also determined by a new HPLC-method to compare the results of this method and the bioassay-method. Generally the results of the multi-centre study showed conformity of both methods. Before administering the antibiotic to patients blood for laboratory testing of liver and kidney parameters was taken. After administration of cefpodoxime proxetil the patients were observed and interviewed for possible side effects. Two weeks after surgery this procedure was repeated and laboratory findings were compared to the first data obtained.
Results
mined by an agar diffusion method using Base Agar Antibiotic Medium No. 1 (Oxoid). A fixed amount of test organisms (Morganella morganii IFO 3848 for serum, Proteus rettgeri UC 1.2186 for tissue) was introduced into the agar. Serum Conc, in ~ g / m l 4
3
Serum concentrations 3 h ( + / - 15 min) after dosing ranged between 4.19 mg/l and 1.26 mg/1, and after 6 h ( + / - 15 min) between 2.27 mg/1 and 0.67 rag/1 (Figure 2). This tissue concentrations were between 1.94 mg/kg (concha: after 4 h 14 min) and 0.15 mg/kg (bone: after 5 h 18 min). The data for the different tissues and their relation to serum concentrations are shown in Table 1. The maximum cefopodoxime proxetil tissue concentrations were reached 4 h to 4 h 30 min after administration (Figure 3). The drug was tolerated without any side effects by any of the 30 patients. No toxic or allergic reactions were seen.
Discussion
2
1
0
100
200
300
400
500
Time in min Figure 2: Serum concentration of cefpodoxime in relation to time after a single oral dose of 200 mg.
46 / 42
Cefpodoxime concentrations found in nasal mucosa, concha, cartilage and bone during surgery were higher than the MIC90values for most of the organisms responsible for upper respiratory tract infections. Cefpodoxime MIC90 values for respiratory tract pathogens are lower than those of other oral cephalosporins such as cefaclor and cefadroxil. The MIC90 of cefpodoxime for ampicillin-sensitive H. influenzae (Amp.-S) is 0.25 mg/1 and 0.5 mg/1 forH. influenzae ampicillin-resistant [2-6]. Comparable in vitro findings for cefadroxil are 16 rag/1 for ampicillin-sensitiveand-resistant H. influ-
Infection 19 (1991) No. 1 © MMV Medizin Verlag GmbH Mtinchen, Mtinchen 1991
H. M. Theopold et al.: Cefpodoxime Proxetil Concentrations in ENT
0.25 mg/1 compared to 8 mg/l for cefaclor and 16 mg/1 for cefadroxil [2]. The MIC90 of cefpodoxime against S. p n e u m o niae is 0.06 mg/l compared to 2 mg/1 for cefaclor and 16 mg/1 for cefadroxil, and even for penicillin-resistant S. p n e u m o n i a e t h e M I C 9 o o f c e f p o d o x i m e i s 4 mg/lwhereas cefaclor and cefadroxil are inactive against these strains with MIC90 > 64 mg/l [2]. MICg0 values for streptococci (groups A, B, C and G) are mg/l for all three antibiotics [2--4, 6]. In most cases the tissue concentrations of cefpodoxime were below MIC90 values against staphylococci. This is especially true for methicillin resistant Staphylococcus aureus. The Cmax of cefpodoxime of 2.96 mg/l after a single oral dose of 200 mg of the ester compound is somewhat lower than concentrations found after therapeutic (1 g) doses of cefalexin (C max = 24.7 mg/1), 0.5 g of cefaclor
(C max = 17.8 mg/1) or 1 g ofcefadroxil (C max = 28 mg/1) [7]. With a half-life of 2.1 h, cefpodoxime has longer lasting therapeutically effective serum concentrations [7] than cefalexin (half-life 60 min), cefaclor (half-life 60 min) or cefadroxil (half-life 90 min). The tissue from tonsils which was taken 4 h 01 min and 4 h 29 min, respectively, after the oral application of cefpodoxime proxetil showed concentrations of up to 0.23 mg/1. Additional examinations should be performed on tonsils since concentrations should be comparable to those in the mucosa or conchal tissue (concha 1.94 mg/1 with serum concentration 3.1 mg/kg after 4 h 13 min). Even the concentrations in the cartilage of the septum of up to 1.24 mg/kg with a corresponding serum concentration of 3.1 rag/1 after 4 h 5 min is sufficient for the therapy of infections with sensitive microorganisms.
References
4. Knapp, C.C., Sierra-Madero, J., Washington, J.A.: Antibacterial
enzae. The MIC90 of cefpodoxime against K. p n e u m o n i a e is
activitiesof cefpodoxim,cef~ime and ceftriaxone.Antimicrob.Agents Chemother. 32 (1988) 1896-1898. 1. Sankyo:InvestigatorsManual 1988, SankyoEurope GmbH. 2. Bauernfeind, A., Schweighart, S.: 1989 Cefpodoximein vitro activity. Poster. 16th International Congress of Chemotherapy Jerusalem, Israel, June 11-16, 1989. 3. Fass, R. J., Heisel, V. L.: In vitro activity of U 76, 252 a new oral cephalosporin. Antimicrob.Agents Chemother. 32 (1988) 1085.
5. Sarubbi, F. A., Verghese, A., Caggina, C., Holtsclaw-Berk, S. L.: In vitro activityof cefpodoximproxetil against clinical isolates of Branhamella catarrhalis.Antimicrob.AgentsChemother.33 (1989) 113-114. 6. Chin, N. X., Neu, H. C.: In vitro activity of an oral iminomethoxy
aminothiazolylcephalosporin, R - 3746. Antimicrob.Agents Chemother. 32 (1988) 671-677.
Information Stipendium Klinische Infektiologie
DM 30 000,- werden f/Jr 1991 erneut bereitgestellt for eine halbj~ihrige Weiterbildung in klinischer Infektiologie for eine/n j0ngere/n Mediziner/in aus dem deutschsprachigen Raum. Die Weiterbildung kann erfolgen an einem Institut for Medizinische Mikrobiologie oder einer infektiologisch ausgerichteten Abteilung eines Klinikums innerhalb Europas. Es wird gebeten, Plan, Ziel und Ort der angestrebten Weiterbildung sowie die Zusage der Gastinstitution mitzuteilen. Der/Die Bewerber/in sollte durch Promotion oder einige Publikationen wissenschaftlich ausgewiesen sein. Bewerbungen mit tabellarischem Lebenslauf unter Beiftigung der
Dissertationsschrift oder von Publikationen werden erbeten innerhalb von acht Wochen nach Erscheinen dieser Ausschreibung an: a) Prof. Dr. med. P. M. Shah oder b) Prof. Dr. med. U. Ullmann Zentrumd. Inneren Medizin Direktor d. d. J. W. Goethe-Universit~it Abteilung Med. Theodor-Stern-Kai 7 Mikrobiologie d. 6000 Frankfurt/M. 70 Univ. Kiel Brunswiker Str. 4 2300 Kiel 1 Das Stipendium wird vonder Firma MSD Sharp & Dohme GmbH, Miinchen, bereitgestellt.
Infection 19 (1991) No. 1 © MMV Medizin Verlag GmbH M0nchen, Miinchen 1991
43 / 47
