Journal of Chemotherapy
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Pharmacokinetic Study of Cefaclor in Chronic Maxillary Sinusitis P.D. Goumas, E. Moschovakis, G. Petrikkos & E. Giamarellou To cite this article: P.D. Goumas, E. Moschovakis, G. Petrikkos & E. Giamarellou (1992) Pharmacokinetic Study of Cefaclor in Chronic Maxillary Sinusitis, Journal of Chemotherapy, 4:3, 155-158, DOI: 10.1080/1120009X.1992.11739155 To link to this article: http://dx.doi.org/10.1080/1120009X.1992.11739155
Published online: 15 Jul 2016.
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Date: 09 August 2017, At: 13:11
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Journal of Chemotherapy
Pharmacokinetic Study of Cefaclor in Chronic Maxillary Sinusitis P.D. GOUMAS- E . MOSCHOVAKIS G. PETRIKKOS * - E . GIAMARELLOU *
Summary ---------------------- -------The pharmacokinetics of the maxillary sinus fluid were studied in 42 patients (26 males and 16 females), suffering from chronic maxillary sinusitis, after oral administration of 0.5g or 1g cefaclor. A thin plastic catheter, for sinus secretion sampling, was inserted in the sinus cavity and remained in place throughout the study. Sinus fluid levels of cefaclor (0.5g), measured by agar and well-diffusion microbiological method, ranged between 0.17-0 .19, 0.28-0.42, 0.18-0.22 and 0.12-0.16 Jlg/ml at 2, 4, 6 and 8 hour intervals respectively. Levels ranging between 0.1.5-0.26, 0.37-0.90, 0.23-0.27 and 0.16-0 .19 Jlg/ml were found after the administration of 1g cefaclor at the same time intervals respectively. Higher levels were found in purulent nasal material than in cystic fluid aspirates. Key words: pharmacokinetics, cefaclor, sinusitis, sinus fluid, maxillary sinus.
Ear, Nose and Throat Dept., Medical School, University of Patras, Greece. * 1st Dept. Propedeutic Medicine, Medical School, University of Athens, Greece. © Edizioni Riviste Scientifiche - Firenze
Vol. 4 - n. 3 (155-158) - 1992
INTRODUCTION
Chronic maxillary sinusitis is a common and difficult to be defined infection. Prolonged or repeated infections of the sinuses can lead to irreversible mucosal damage, resulting in ciliate epithelium replacement by stratified squamous epithelium and loss of effective clearance of bacteria 1 • In contrast to acute sinusitis, where pneumococci are the most frequent pathogens, Haemophilus influem:ae and bacteria other than pneumococci, as well as streptococcal organisms and anaerobes are isolated quite frequently in chronic sinusitis 2 • 3 • 4 • An appropriate antibiotic for treating sinusitis should not only cover the spectrum of implicated pathogens but should be concentrated in adequate levels at the site of infection. Cefaclor is an oral cephalosporin substantially more active than cefalexin and cefradine against Gram-positive and Gram-negative bacteria such as staphylococci and streptococci, with the exception of Staphylococcus pyogenes where it is not as active as cefalothin . Cefaclor is also more active than cefalexin against many Gram-negative bacteria such as meningococci, gonococci, H. influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and the Salmonellae and Shigellae s •6 • 7 • Anaerobic Grampositive cocci and most strains of Bacteroides spp other than B. fragilis are also usually cefaclor-sensitive. The Clostridium spp and B. fragilis are usually resistant 8 • As cefaclor is an antimicrobial agent active against most of the pathogens implicated in sinusitis, this study was designed to evaluate the pharmacokinetics of the drug in 42 patients suffering from chronic exacerbated sinusitis. ISSN l120-009X
P.D. GOUMAS - E. MOSCHOVAKIS - G. PETRJKKOS - E. GIAMARELLOU
156
Downloaded by [University of Auckland Library] at 13:11 09 August 2017
PATIENTS AND METHODS
In all patients antral secretions were obtained undiluted by aspiration with a trocar inserted through the inferior nasal meatus. Quantitative aerobic and anaerobic cultures were performed by conventional methods in all specimens. Then a thin plastic catheter was inserted through the trocar to the maxillary sinus and the trocar was removed. The catheter remained in place for all the pharmacokinetic sampling. Purulent nasal secretions were obtained after aspirating the ethmoid sinus with a catheter. Cefaclor (Eli Lilly) was administered orally as a single 0.5g dose in 23 patients and a 1g dose in 19 patients. Sinus and nasal secretion specimens with simultaneous blood specimens were obtained at 2, 4, 6 and 8 hours post dose. Cefaclor levels were measured by the agar-well diffusion method with Antibiotic Medium No. 2 (Oxoid) and Bacillus subtilis spores MB 29 SDR. Forty-two patients, 26 males and 16 females, mean age 33 ± 12 years, entered the study after informed consent was obtained. They were all characterized as suffering from chronic maxillary sinusitis based on clinical definition of > 4 episodes per year for > 2 continuous years. Opaque sinus transillumination at physical examination and maxillary sinus air fluid levels were observed by conventional x-rays in all patients. In 30 patients the infection was unilateral and in 12 bilateral while in 4 patients the frontal sinuses were also involved. RESULTS
Culture results are shown in Table 1. The 3 number of the isolated pathogens were > 10 cfu/ml of purulent material. After culture results 59.5% of the infections were characterized as purely aerobic, 4.8% as purely anaerobic, 21.4% as mixed aerobic-anaerobic while in 14.3% sterile effusions were found. Streptococcus sp, Staphylococcus sp and H. influenzae were the most frequently isolated pathogens among the aerobes and Bacteroides sp among the anaerobes. Pharmacokinetic results are shown in Tables 2 and 3 as in Figures 1 and 2.
TABLE 1 -Culture results in 42 patients with chronic maxi/lary sinusitis. Type of pathogen
Number
A. Aerobes
39
Streptococcus spp (Streptococcus pneumoniae) (Enterococci)
11
Staphylococcus spp (Staph. aureus) (Staph . epidermidis)
10
Enterobacteriaceae (Proteus mirabilis) (Citrobacter diversus) (Escherichia coli)
3
(8) (3)
(20.5) (7.7)
(5) (8)
(12 .8) (20.5)
(1) (1) (1)
(2 .6) (2.6) (2.6)
1
2.6
11
28.2
Pseudomonas non aeruginosa Haemophilus influem:ae
13
B. Anaerobes
Bacteroides sp (Bacteroides fragilis)
%
10 (3)
76 .9 (23 .1)
Propionibacterium acnes
2
15.4
Diphtheroides sp
1
7.7
Two hours after oral administration of 0.5g cefaclor mean levels were 0.18 ± 0.5 ~g/ ml in sinus fluid, 0.15 ~g/ml in cystic fluid and 1.14±0.36 J..Lg/ml in nasal secretions while mean serum levels were 2.04 ± 1.13 ~g/ml. Peak sinus fluid levels were found at 4h (mean level: 0.37±0.11 ~g/ml ). At 6h and 8h mean sinus fluid levels were 0.23±0.06 J..Lg/ml and 0.14 ±0.02 ~g/ml respectively. Mean cystic fluid levels at 4h, 6h and 8h were 0.22, 0.19±0.05 and 0.14±0.02 ~g/ml while mean nasal secretion levels were 0.41, 0.20 and 0 ~g/ml at the same time intervals respectively. Mean serum levels were 0.18 ± 0.11 at 4h and not detectable at 6h and 8h. After oral administration of 1g cefaclor mean sinus fluid levels were 0.24, 0.66 , 0.27 and 0.18 ~g/ml at 2h, 4h, 6h and 8h respectively. Mean cystic fluid levels were 0.19, 0. 37, 0.23 and 0.17 ± 0.01 J..Lg/ml while mean nasal secretion levels were 1.16 ± 0.41, 0. 65 ± 0.4 3, 0.11 and 0 J..L g/ml at 2h, 4h, 6h and 8h respectively. Mean serum levels at 2h and 4h were 2.98 ± 1.01 and 0.38 ±0.41 ~g/ml respectively while they were not detectable at 6h and 8h.
157
PHARMACOKINETIC STUDY OF CEFACLOR IN CHRONIC MAXILLARY SINUSITIS
TABLE 2 - Levels of cefaclor in serum, sinus, cystic and nasal secretions after one dose of 0.5g cefaclor in 23 patients with chronic maxillary sinusitis.
Mean cefaclor levels in J.l.g/ml at indicated time post-dose (number of patients)
Downloaded by [University of Auckland Library] at 13:11 09 August 2017
Time 2h
4h
Serum levels (n) (±sd)
2.04 (6) (1.13)
0.18 (5) (0.11)
0
Sinus secretion levels (n) (±sd)
0.18 (3) (0.05)
0.37 (3) (0.11)
0.23 (4) (0.06)
0.14 (3) (0.02)
Cystic fluid levels (n) (±sd)
0.15 (1)
0.22 (1)
0.19 (3) (0.05)
0.14 (2) (0.01)
Nasal secretion levels (n) (±sd)
1.14 (2) (0.36)
0.41 (1)
0.20 {1)
0
8h
6h (3)
{3)
0
(1)
TABLE 3 - Levels of cefaclor in serum, sinus, cystic and nasal secretions after one dose of lg cefaclor in 19 patients with chronic maxillary sinusitis.
Mean cefaclor levels in J.l.g/ml at indicated time post-dose (number of patients)
Time 2h
4h
Serum levels (n) (±sd)
2.98 (4) (1.01)
0.38 (4) (0.41)
0
Sinus secretion levels (n) (±sd)
0.24 (2) (0.03)
0.66 {4) (0.18)
0.27 (1)
0.18 (2) (0 .01)
Cystic fluid levels (n) (±sd)
0.19 (1)
0.37 (1)
0.23 (1)
0.17 (2) (0.01)
Nasal secretion levels (n) (±sd)
1.16 (2) (0.41)
0.65 (2) (0.43)
0.11 (1)
0
IJQ/ml
6h
8h (1)
0
(1)
(1)
fJQ/ml
2.0,...-- - - - - - - - - - - - - - - -- - 2r-------~-----------------------------
3.6,...-- - - - - - - - - - - - - - - - - - s~---~---------------------2.6~---------------------
1 .or-----:--;:::==~---~ Serum levelaj
6h
2h
6h
Time In hours
Figure 1 - Levels of cefaclor in serum, sinus, cystic and
n~sal secretions after one dose of 0.5g cefaclor in 23 patients
With chronic maxillary sinusitis.
Time In hours
Figure 2 - Levels of cefaclor in serum, sinus, cystic and nasal secretions after one dose of lg cefaclor in 19 patients with chronic maxillary sinusitis.
158
P.D. GOUMAS - E. MOSCHOVAKIS - G. PETRIKKOS - E. GIAMARELLOU
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DISCUSSION
In the treatment of sinusitis the choice among different antibiotics should be based not only on the expected bacteriological findings and antibiotic susceptibility patterns, but also on other factors such as the possibility of side effects, the cost of therapy, the ability of antibiotics to affect normal flora as well as their pharmacokinetic behavior in sinus secretions. It has been found that penicillin, erythromycin and cefradine provide rather low concentrations in sinus secretions in comparison to ampicillin, doxycycline and spiramycin 9 • However, ampicillin is not active against staphylococci and B-lactamase producing H. influenzae while a high percentage of pneumococci are currently resistant to tetracyclines. Bacteriological studies carried out in this series of patients after sinus puncture and aspiration, the only method for obtaining reliable culture results 1 , revealed the following range of pathogens: 5. pneumoniae, H. influenzae, 5. epidermidis and 5. aureus. Since H. influenzae and 5. aureus are mostly involved in sinusitis complications, cefaclor or cefatrizine in the therapy of sinusitis seem appropriate. Data from other previous studies ' · 6 • 7 • 8 show that the minimum inhibitory concentrations (MICs) of cefaclor against streptococci other than enterococci are about 0.25 l!g/ml. The MICs for staphylococci and H. influenzae range between 2-8 11g/ml while the MICs for enterococci are 64 l!g/ml and for Enterobacteriaceae and P. aeruginosa are > 128 l!g/ml. Cefaclor levels in sinus fluid, 2h after oral administration of 0.5 and lg, are much lower than the concomitant serum levels while they are higher than serum levels 4h postdose, and are dose dependent . The concentrations of cefaclor in sinus fluid achieve the MICs for streptococci which are commonly implicated in maxillary sinusitis. On the other hand, the sinus fluid levels of cefaclor obtained are lower
than the MICs for several aerobic pathogens implicated in chronic sinusitis. This phenomenon may be explained by the single dose of cefaclor. It should also be pointed out that in chronic sinusitis, anaerobes are also implicated in almost 50% of the cases 1 • The lower rate of anaerobes in this study may be explained by the fact that most patients were suffering from chronic exacerbated sinusitis. It is concluded that the cefaclor levels obtained in infected sinus fluid after a single oral dose of 0.5g or lg are below the concentrations required for inhibiting the implicated pathogens. Probably higher levels can be expected after multiple dose therapy. However it seems that the highest tolerated dose of cefaclor should be prescribed in cases of chronic maxillary sinusitis. REFERENCES ' Lundberg C, Engquist S. Localization of bacteria and the cause of tissue destruction in maxillary si nusitis. Acta Otolaryngol (Stockh) 1984; Suppl. 407 : 30-32. 'Karma P, Jokipii L, Sipila P, Luotonen J, Jokipii AM. Bacteria in chronic maxillary si nusitis . Arch Otolaryngol 1979; 105 : 386-390. 'Su WY, Chen L, Shnian YH, Wei·Fu T . Bacteriological study in chronic maxillary sinusitis. Laryngoscope 1983; 93: 93 1-934 . • Gwaltney J , Sydnor A, Sande M. Etiology and antimicrobial treatment of acute sinusitis. Ann Otol Rhino! Laryngol 1981; 90 (Suppl 84) 68-71. ' Bill NJ, Washington JA . Comparison of in vitro activity of cephalexin, cephradine and cefaclor. Antimicrob Agents Chemother 1977; 11 : 470-474 . • Scheid WW, Korzenowski OM, Sande MA. In vitro susceptibility studies with cefaclor and cephalexin . Antimicrob Agents Chemother 1977; 12: 290-292. ' Sanders CC . In vitro studies with cefaclor, a new oral cephalosporin. Antimicrob Agents Chemother 197 7; 12: 490497. • Bach VT, Khurau MM, Thadepalli H . In vitro activity of cefaclor against aerobic and anaerobic bacteria. Antimicrob Agents Chemother 1978; 13: 210-213 . ' Axelsson A, Brorson JE . The concentration of antibiotics in sinus secretions - Ampicillin, cephradine and ery thromycines tolate. Ann Otol 1974; 83: 323-330.
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Pharmacokinetic Study of Cefaclor in Chronic Maxillary Sinusitis P.D. Goumas, E. Moschovakis, G. Petrikkos & E. Giamarellou To cite this article: P.D. Goumas, E. Moschovakis, G. Petrikkos & E. Giamarellou (1992) Pharmacokinetic Study of Cefaclor in Chronic Maxillary Sinusitis, Journal of Chemotherapy, 4:3, 155-158, DOI: 10.1080/1120009X.1992.11739155 To link to this article: http://dx.doi.org/10.1080/1120009X.1992.11739155
Published online: 15 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yjoc20 Download by: [University of Auckland Library]
Date: 09 August 2017, At: 13:11
Downloaded by [University of Auckland Library] at 13:11 09 August 2017
Journal of Chemotherapy
Pharmacokinetic Study of Cefaclor in Chronic Maxillary Sinusitis P.D. GOUMAS- E . MOSCHOVAKIS G. PETRIKKOS * - E . GIAMARELLOU *
Summary ---------------------- -------The pharmacokinetics of the maxillary sinus fluid were studied in 42 patients (26 males and 16 females), suffering from chronic maxillary sinusitis, after oral administration of 0.5g or 1g cefaclor. A thin plastic catheter, for sinus secretion sampling, was inserted in the sinus cavity and remained in place throughout the study. Sinus fluid levels of cefaclor (0.5g), measured by agar and well-diffusion microbiological method, ranged between 0.17-0 .19, 0.28-0.42, 0.18-0.22 and 0.12-0.16 Jlg/ml at 2, 4, 6 and 8 hour intervals respectively. Levels ranging between 0.1.5-0.26, 0.37-0.90, 0.23-0.27 and 0.16-0 .19 Jlg/ml were found after the administration of 1g cefaclor at the same time intervals respectively. Higher levels were found in purulent nasal material than in cystic fluid aspirates. Key words: pharmacokinetics, cefaclor, sinusitis, sinus fluid, maxillary sinus.
Ear, Nose and Throat Dept., Medical School, University of Patras, Greece. * 1st Dept. Propedeutic Medicine, Medical School, University of Athens, Greece. © Edizioni Riviste Scientifiche - Firenze
Vol. 4 - n. 3 (155-158) - 1992
INTRODUCTION
Chronic maxillary sinusitis is a common and difficult to be defined infection. Prolonged or repeated infections of the sinuses can lead to irreversible mucosal damage, resulting in ciliate epithelium replacement by stratified squamous epithelium and loss of effective clearance of bacteria 1 • In contrast to acute sinusitis, where pneumococci are the most frequent pathogens, Haemophilus influem:ae and bacteria other than pneumococci, as well as streptococcal organisms and anaerobes are isolated quite frequently in chronic sinusitis 2 • 3 • 4 • An appropriate antibiotic for treating sinusitis should not only cover the spectrum of implicated pathogens but should be concentrated in adequate levels at the site of infection. Cefaclor is an oral cephalosporin substantially more active than cefalexin and cefradine against Gram-positive and Gram-negative bacteria such as staphylococci and streptococci, with the exception of Staphylococcus pyogenes where it is not as active as cefalothin . Cefaclor is also more active than cefalexin against many Gram-negative bacteria such as meningococci, gonococci, H. influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and the Salmonellae and Shigellae s •6 • 7 • Anaerobic Grampositive cocci and most strains of Bacteroides spp other than B. fragilis are also usually cefaclor-sensitive. The Clostridium spp and B. fragilis are usually resistant 8 • As cefaclor is an antimicrobial agent active against most of the pathogens implicated in sinusitis, this study was designed to evaluate the pharmacokinetics of the drug in 42 patients suffering from chronic exacerbated sinusitis. ISSN l120-009X
P.D. GOUMAS - E. MOSCHOVAKIS - G. PETRJKKOS - E. GIAMARELLOU
156
Downloaded by [University of Auckland Library] at 13:11 09 August 2017
PATIENTS AND METHODS
In all patients antral secretions were obtained undiluted by aspiration with a trocar inserted through the inferior nasal meatus. Quantitative aerobic and anaerobic cultures were performed by conventional methods in all specimens. Then a thin plastic catheter was inserted through the trocar to the maxillary sinus and the trocar was removed. The catheter remained in place for all the pharmacokinetic sampling. Purulent nasal secretions were obtained after aspirating the ethmoid sinus with a catheter. Cefaclor (Eli Lilly) was administered orally as a single 0.5g dose in 23 patients and a 1g dose in 19 patients. Sinus and nasal secretion specimens with simultaneous blood specimens were obtained at 2, 4, 6 and 8 hours post dose. Cefaclor levels were measured by the agar-well diffusion method with Antibiotic Medium No. 2 (Oxoid) and Bacillus subtilis spores MB 29 SDR. Forty-two patients, 26 males and 16 females, mean age 33 ± 12 years, entered the study after informed consent was obtained. They were all characterized as suffering from chronic maxillary sinusitis based on clinical definition of > 4 episodes per year for > 2 continuous years. Opaque sinus transillumination at physical examination and maxillary sinus air fluid levels were observed by conventional x-rays in all patients. In 30 patients the infection was unilateral and in 12 bilateral while in 4 patients the frontal sinuses were also involved. RESULTS
Culture results are shown in Table 1. The 3 number of the isolated pathogens were > 10 cfu/ml of purulent material. After culture results 59.5% of the infections were characterized as purely aerobic, 4.8% as purely anaerobic, 21.4% as mixed aerobic-anaerobic while in 14.3% sterile effusions were found. Streptococcus sp, Staphylococcus sp and H. influenzae were the most frequently isolated pathogens among the aerobes and Bacteroides sp among the anaerobes. Pharmacokinetic results are shown in Tables 2 and 3 as in Figures 1 and 2.
TABLE 1 -Culture results in 42 patients with chronic maxi/lary sinusitis. Type of pathogen
Number
A. Aerobes
39
Streptococcus spp (Streptococcus pneumoniae) (Enterococci)
11
Staphylococcus spp (Staph. aureus) (Staph . epidermidis)
10
Enterobacteriaceae (Proteus mirabilis) (Citrobacter diversus) (Escherichia coli)
3
(8) (3)
(20.5) (7.7)
(5) (8)
(12 .8) (20.5)
(1) (1) (1)
(2 .6) (2.6) (2.6)
1
2.6
11
28.2
Pseudomonas non aeruginosa Haemophilus influem:ae
13
B. Anaerobes
Bacteroides sp (Bacteroides fragilis)
%
10 (3)
76 .9 (23 .1)
Propionibacterium acnes
2
15.4
Diphtheroides sp
1
7.7
Two hours after oral administration of 0.5g cefaclor mean levels were 0.18 ± 0.5 ~g/ ml in sinus fluid, 0.15 ~g/ml in cystic fluid and 1.14±0.36 J..Lg/ml in nasal secretions while mean serum levels were 2.04 ± 1.13 ~g/ml. Peak sinus fluid levels were found at 4h (mean level: 0.37±0.11 ~g/ml ). At 6h and 8h mean sinus fluid levels were 0.23±0.06 J..Lg/ml and 0.14 ±0.02 ~g/ml respectively. Mean cystic fluid levels at 4h, 6h and 8h were 0.22, 0.19±0.05 and 0.14±0.02 ~g/ml while mean nasal secretion levels were 0.41, 0.20 and 0 ~g/ml at the same time intervals respectively. Mean serum levels were 0.18 ± 0.11 at 4h and not detectable at 6h and 8h. After oral administration of 1g cefaclor mean sinus fluid levels were 0.24, 0.66 , 0.27 and 0.18 ~g/ml at 2h, 4h, 6h and 8h respectively. Mean cystic fluid levels were 0.19, 0. 37, 0.23 and 0.17 ± 0.01 J..Lg/ml while mean nasal secretion levels were 1.16 ± 0.41, 0. 65 ± 0.4 3, 0.11 and 0 J..L g/ml at 2h, 4h, 6h and 8h respectively. Mean serum levels at 2h and 4h were 2.98 ± 1.01 and 0.38 ±0.41 ~g/ml respectively while they were not detectable at 6h and 8h.
157
PHARMACOKINETIC STUDY OF CEFACLOR IN CHRONIC MAXILLARY SINUSITIS
TABLE 2 - Levels of cefaclor in serum, sinus, cystic and nasal secretions after one dose of 0.5g cefaclor in 23 patients with chronic maxillary sinusitis.
Mean cefaclor levels in J.l.g/ml at indicated time post-dose (number of patients)
Downloaded by [University of Auckland Library] at 13:11 09 August 2017
Time 2h
4h
Serum levels (n) (±sd)
2.04 (6) (1.13)
0.18 (5) (0.11)
0
Sinus secretion levels (n) (±sd)
0.18 (3) (0.05)
0.37 (3) (0.11)
0.23 (4) (0.06)
0.14 (3) (0.02)
Cystic fluid levels (n) (±sd)
0.15 (1)
0.22 (1)
0.19 (3) (0.05)
0.14 (2) (0.01)
Nasal secretion levels (n) (±sd)
1.14 (2) (0.36)
0.41 (1)
0.20 {1)
0
8h
6h (3)
{3)
0
(1)
TABLE 3 - Levels of cefaclor in serum, sinus, cystic and nasal secretions after one dose of lg cefaclor in 19 patients with chronic maxillary sinusitis.
Mean cefaclor levels in J.l.g/ml at indicated time post-dose (number of patients)
Time 2h
4h
Serum levels (n) (±sd)
2.98 (4) (1.01)
0.38 (4) (0.41)
0
Sinus secretion levels (n) (±sd)
0.24 (2) (0.03)
0.66 {4) (0.18)
0.27 (1)
0.18 (2) (0 .01)
Cystic fluid levels (n) (±sd)
0.19 (1)
0.37 (1)
0.23 (1)
0.17 (2) (0.01)
Nasal secretion levels (n) (±sd)
1.16 (2) (0.41)
0.65 (2) (0.43)
0.11 (1)
0
IJQ/ml
6h
8h (1)
0
(1)
(1)
fJQ/ml
2.0,...-- - - - - - - - - - - - - - - -- - 2r-------~-----------------------------
3.6,...-- - - - - - - - - - - - - - - - - - s~---~---------------------2.6~---------------------
1 .or-----:--;:::==~---~ Serum levelaj
6h
2h
6h
Time In hours
Figure 1 - Levels of cefaclor in serum, sinus, cystic and
n~sal secretions after one dose of 0.5g cefaclor in 23 patients
With chronic maxillary sinusitis.
Time In hours
Figure 2 - Levels of cefaclor in serum, sinus, cystic and nasal secretions after one dose of lg cefaclor in 19 patients with chronic maxillary sinusitis.
158
P.D. GOUMAS - E. MOSCHOVAKIS - G. PETRIKKOS - E. GIAMARELLOU
Downloaded by [University of Auckland Library] at 13:11 09 August 2017
DISCUSSION
In the treatment of sinusitis the choice among different antibiotics should be based not only on the expected bacteriological findings and antibiotic susceptibility patterns, but also on other factors such as the possibility of side effects, the cost of therapy, the ability of antibiotics to affect normal flora as well as their pharmacokinetic behavior in sinus secretions. It has been found that penicillin, erythromycin and cefradine provide rather low concentrations in sinus secretions in comparison to ampicillin, doxycycline and spiramycin 9 • However, ampicillin is not active against staphylococci and B-lactamase producing H. influenzae while a high percentage of pneumococci are currently resistant to tetracyclines. Bacteriological studies carried out in this series of patients after sinus puncture and aspiration, the only method for obtaining reliable culture results 1 , revealed the following range of pathogens: 5. pneumoniae, H. influenzae, 5. epidermidis and 5. aureus. Since H. influenzae and 5. aureus are mostly involved in sinusitis complications, cefaclor or cefatrizine in the therapy of sinusitis seem appropriate. Data from other previous studies ' · 6 • 7 • 8 show that the minimum inhibitory concentrations (MICs) of cefaclor against streptococci other than enterococci are about 0.25 l!g/ml. The MICs for staphylococci and H. influenzae range between 2-8 11g/ml while the MICs for enterococci are 64 l!g/ml and for Enterobacteriaceae and P. aeruginosa are > 128 l!g/ml. Cefaclor levels in sinus fluid, 2h after oral administration of 0.5 and lg, are much lower than the concomitant serum levels while they are higher than serum levels 4h postdose, and are dose dependent . The concentrations of cefaclor in sinus fluid achieve the MICs for streptococci which are commonly implicated in maxillary sinusitis. On the other hand, the sinus fluid levels of cefaclor obtained are lower
than the MICs for several aerobic pathogens implicated in chronic sinusitis. This phenomenon may be explained by the single dose of cefaclor. It should also be pointed out that in chronic sinusitis, anaerobes are also implicated in almost 50% of the cases 1 • The lower rate of anaerobes in this study may be explained by the fact that most patients were suffering from chronic exacerbated sinusitis. It is concluded that the cefaclor levels obtained in infected sinus fluid after a single oral dose of 0.5g or lg are below the concentrations required for inhibiting the implicated pathogens. Probably higher levels can be expected after multiple dose therapy. However it seems that the highest tolerated dose of cefaclor should be prescribed in cases of chronic maxillary sinusitis. REFERENCES ' Lundberg C, Engquist S. Localization of bacteria and the cause of tissue destruction in maxillary si nusitis. Acta Otolaryngol (Stockh) 1984; Suppl. 407 : 30-32. 'Karma P, Jokipii L, Sipila P, Luotonen J, Jokipii AM. Bacteria in chronic maxillary si nusitis . Arch Otolaryngol 1979; 105 : 386-390. 'Su WY, Chen L, Shnian YH, Wei·Fu T . Bacteriological study in chronic maxillary sinusitis. Laryngoscope 1983; 93: 93 1-934 . • Gwaltney J , Sydnor A, Sande M. Etiology and antimicrobial treatment of acute sinusitis. Ann Otol Rhino! Laryngol 1981; 90 (Suppl 84) 68-71. ' Bill NJ, Washington JA . Comparison of in vitro activity of cephalexin, cephradine and cefaclor. Antimicrob Agents Chemother 1977; 11 : 470-474 . • Scheid WW, Korzenowski OM, Sande MA. In vitro susceptibility studies with cefaclor and cephalexin . Antimicrob Agents Chemother 1977; 12: 290-292. ' Sanders CC . In vitro studies with cefaclor, a new oral cephalosporin. Antimicrob Agents Chemother 197 7; 12: 490497. • Bach VT, Khurau MM, Thadepalli H . In vitro activity of cefaclor against aerobic and anaerobic bacteria. Antimicrob Agents Chemother 1978; 13: 210-213 . ' Axelsson A, Brorson JE . The concentration of antibiotics in sinus secretions - Ampicillin, cephradine and ery thromycines tolate. Ann Otol 1974; 83: 323-330.
