Journal of Antimicrobial Chemotherapy (1977), 3, 411-416
Studies on cinoxacin
P.-A. Mardh Institute of Medical Microbiology, University of Lund, S-223 62 Lund, Sweden S. Colleen Department of Urology, University Hospital, S-221 85 Lund, Sweden and K.-E. Andersson Department of Clinical Pharmacology, Institute of Pharmacology, University of Arhus, Dk-8000 Arhus C, Denmark
Bacteria were isolated from urine specimens obtained from patients with chronic urinary tract diseases treated with various antibiotics and chemotherapeutics for long periods of time because of recurrent or relapsing urinary tract infections. The micro-organisms were studied for their in vitro susceptibility to cinoxacin and nalidixic acid. The Gram-negative bacteria investigated were usually more susceptible to cinoxacin than to nalidixic acid. Ninety-eight of 108 strains of Escherichia coli were inhibited by 32 ng/ml of cinoxacin and 61 by 32 ng/ml of nalidixic acid. The corresponding numbers for 27 strains of Klebsiella pneumoniae were 22 and 12, and for 25 strains of Proteus mirabilis 20 and 10, respectively. None of 16 strains of Pseudomonas aeruginosa were inhibited by cinoxacin in this concentration, nor were 24 strains of staphylococci and streptococci. Introduction Cinoxacin [l-ethyl-l,4-dihydro-4,oxo-(l,3)dioxolo (4,5-g)cinnoline-3-carboxylic acid] is a synthetic organic acid with a cinnoline (1,2-benzodiazine) as the basic ring structure. The substance (compound 6471, Eli Lilly & Co.) is chemically related to nalidixic acid and oxolinic acid (Wick, Preston, White & Gordee, 1973). It has been shown to exhibit antimicrobial activity in vitro against Gram-negative bacteria encountered in urinary tract infections (Kurtz & Turck, 1975; Lumish & Norden, 1975; Jones & Fuchs, 1976), and also to be clinically effective (Panwalker, Giamarellou & Jackson, 1976). In the present study, bacteria isolated from urine specimens of patients with urinary tract infections attending a renal or a urological clinic were tested for their in vitro susceptibility to cinoxacin and nalidixic acid by determination of the minimal inhibitory concentrations (MIC) of the drugs; the susceptibility to cinoxacin was also tested in disc diffusion tests. 411
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
1. In vitro activity of ciooxadn, as compared to nalidixic acid, against urinary tract pathogens
412
P.-A. Mardh, S. Colleen and K.-E. Andersson Materials and methods
Clinical material and organisms studied
Table I. The minimum inhibitory concentrations (MIC) of cinoxacin ( Q and nalidixic acid (N) for 199 strains of Gram-negative bacilli isolated from urine specimens
Species
]VIIC (ng/ml)
No. of strains
studied 1
E. coli
108
Citrobacter
C N C N C N C N C N C N C N C N
1
Enterobacter spp.
16
K. pneumoniae
27
P. mirabilis
25
Proteus spp.
4
Acinetobacter
2
Ps. aeruginosa
16
Cumulative number of strains inhibited by: 2 4 8 16 32 64 128 256 512 >512
3 17 63 86 97 98 101 107 1 10 53 59 61 97 98 1
100
108 108 1
3
7 11 12 13 3 9 10 4 9 18 22 5 10 12 8 13 20 3 10 4 2 4 1 1
15 14 18 22 10
16 15 25 21 18
1
22 23 19
16 27 24 20
2 2 4 2
9
27 25 25
16 16
Table II. The minimum inhibitory concentrations (MIC) of cinoxacin for 25 strains of Grampositive cocci isolated from urine specimens Species
S. aitreus S. epidermidis •S". saprophyticus Group B streptococci S. faecalis
No. of strains tested 4 6 6 3 6
MIC (ug/ml) Cumulative number of strains inhibited by: 64 128 256 512 >512 4 3 1
6 6 3 6
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One hundred and ninety-nine strains of Gram-negative rods and 25 strains of Grampositive cocci were studied. The strains tested were isolated from consecutive urine specimens containing more than 105 bacteria/ml, as determined by the calibrated loop technique. All specimens were obtained from patients attending the Renal or Urological Departments of the University Hospital, Lund. Most of them had chronic urinary tract diseases and had been treated with various antibiotics and chemotherapeutics for long periods of time because of recurrent or relapsing urinary tract infections. The susceptibility of the Gram-negative bacilli to cinoxacin and nalidixic acid was tested, while the cocci were tested only against cinoxacin. The numbers of strains of the different species studied are shown in Tables I and II.
In vitro activity of cinoxacin
413
Antimicrobial agents
Cinoxacin was obtained from the Lilly Research Laboratories, Indianapolis, Indiana, and nalidixic acid from Winthrop AB, Stockholm, Sweden. Stock solutions of the drugs (containing 1000 ug/ml) were prepared in 0-1 M-phosphate buffered saline, pH 7-2, and stored at — 20°C. Test solutions were prepared fresh at each test occasion. In the disc diffusion tests, paper filter discs containing 30 ug of cinoxacin (BBL) and 30 ug of nalidixic acid (AB Biodisk, Stockholm) were used.
Susceptibility tests To determine the minimum inhibitory concentrations of cinoxacin and nalidixic acid, the 224 strains studied were harvested from blood agar plates, which had been incubated at 37°C for 18 h. The bacteria were suspended in saline to give a density of 105 bacteria/ ml. The test medium containing cinoxacin or nalidixic acid in various concentrations was spot-inoculated with a replicating device. The bacteria were tested against the antimicrobial agents in concentrations varying between 1 and 512 ug/ml. Non-antibiotic containing plates were used as controls. The plates were incubated at 37°C overnight after being left to dry for 40 min at room temperature. MIC was defined as the lowest concentrations of the antimicrobial agents that completely inhibited growth or allowed formation of single colonies at the most. Sixty-five of the Gram-negative strains (E. coli, K. pneumoniae, P. mirabilis) were studied in disc diffusion tests with cinoxacin and nalidixic acid. Petri dishes, 9 cm in diameter, to which 20 ml of the test medium had been added, which gave a 3 mm thick agar layer were used. The saline suspension of the bacteria to be tested was spread over the plates with a cotton-tipped swab to obtain an even film. The plates were stored in room temperature for 30 min before incubated at 37°C. They were read after overnight incubation. The inhibitory zones were measured by the aid of a sliding calliper.
Results Susceptibility tests The MIC's of cinoxacin and nalidixic acid for the 199 strains of Gram-negative bacteria tested are given in Table I. Gram-negative baccilli were usually more susceptible to cinoxacin than to nalidixic acid. For 139 of the strains, the MIC of cinoxacin was more than 2-fold lower than that for nalidixic acid. For two strains only, the reverse was found. Figure 1 gives the cumulative percentage of the 3 most frequently isolated species (E. coli, K. pneumoniae, P. mirabilis) inhibited by increasing concentrations of the two antibiotics studied. Cinoxacin in a concentration of 32 ug/ml inhibited 98 of the 108 strains of E. coli (91 %). Nalidixic acid in the same concentration inhibited 61 of the strains (56%). Corresponding numbers for 27 strains of K. pneumoniae were 22 and 12, and for 25 strains of P. mirabilis 20 and 10, respectively. None of 16 strains of Ps.
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Media The strains were isolated and maintained on blood agar plates consisting of Blood Agar Base No. 2 (Oxoid) with 4 % defibrinated horse blood. The susceptibility tests were all made on Mueller-Hinton medium (Difco), pH 7 4.
414
P.-A. Mardh, S. Colleen and K.-E. Andersson
24 8
16
32
64 128 256 512 »5I2
16 32 64 128 256 512*512 Antibiotic conctntrotion (/ig/ml)
Figure 1. Cumulative percentages of 108 strains of Escherichia coli, 25 strains of Klebsiella pneumoniae, and 25 strains of Proteus mirabilis inhibited by increasing concentrations of cinoxacin ( • • ) and nalidixic acid ( • •).
aeruginosa was inhibited by cinoxacin and nalidixic acid in the concentrations indicated above. Nine of the 16 strains were inhibited by cinoxacin 512 ug/ml, while only 2 were inhibited by nalidixic acid in the same concentration. The MIC's of cinoxacin for the staphylococcal and streptococcal strains studied are shown in Table II. Gram-positive cocci were generally less susceptible to cinoxacin than the Gram-negative rods studied (except for Ps. aeruginosa). Among the staphylococcal and streptoccocal strains tested, S. aureus was more susceptible than the others. The distribution of the inhibitory zones obtained in disc diffusion test with 75 of the Gram-negative strains when testing cinoxacin and nalidixic acid are shown in Figure 2.
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
24 8
415
In vitro activity of cinoxacin
T
e.coli
T
1
0
5
0
10
.. . . nJlli Infli i 15
20
25
30
35
40
10
15
20
25
30
35
40
35
40
i i
n
i
P. mirabilis
5 -
n
I
10
lll.l.
mi I III 15 20 25 Inhibitory zone
• i 30
I
Figure 2. Inhibitory zones in disc diffusion tests with cinoxacin (unfilled bars) and nalidixic acid (filled bars) produced by 41 strains of Escherichia coli, 13 strains of Klebsiella pneumoniae and 11 strains of Proteus mirabilis using discs containing 30 ng of the substances. Tests performed on Mueller-Hinton medium.
Discussion In previous studies, the in vitro susceptibility of bacteria to cinoxacin has been tested (Wick, Preston, White & Gordee, 1973; Giamarellou & Jackson, 1975; Kurtz & Turck, 1975; Jones & Fuchs, 1976). All bacterial strains tested in the present investigation were isolated from urine specimens of patients treated for long periods of time with various antibiotics and chemotherapeutics. Thus, the strains of bacteria were obtained from a group of patients in whom the treatment of urinary tract infections often offers therapeutic problems. The antibacterial spectrum of cinoxacin was, as also others have found, similar to that known for nalidixic acid (Goss & Cook, 1975). However, the in vitro activity of cinoxacin was, per unit of weight, generally higher than that of nalidixic acid. Thus, approximately 70% of the strains of Enterobacteriaceae were more susceptible to cinoxacin. In agreement with previous studies (Wick et ah, 1973; Kurtz & Turck, 1975; Jones & Fuchs, 1976), Pseudomonas aeruginosa was found to be more susceptible to cinoxacin than to nalidixic acid. It should be noted, however, that 9 out of 16 strains were inhibited by cinoxacin 512 ug/ml, whereas only 2 of these 16 strains were inhibited by nalidixic acid in the same concentration. Peak concentrations in urine exceeding 500 ug/ml can be obtained during cinoxacin treatment (Colleen, Andersson & Mardh, 1976). Cinoxacin showed a poor activity against group B and D streptococci (MIO512 Ug/ml). S. saprophyticus is a common cause of acute cystourethritis in women of fertile age (Maskell, 1974). It has recently been described that this bacterium also can engage the upper urinary tract and cause recurrent and relapsing urinary tract infections
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
1
i
416
P.-A. Mardh, S. Colleen and K.-E. Andersson
Acknowledgements This study was supported by grant no. 16X-4509 from the Swedish Medical Research Council. We wish to acknowledge the supply of cinoxacin from Eli Lilly & Co. and also for their support. References Colleen, S., Andersson, K.-E. & M&rdh, P.-A. Studies on cinoxacin. 3. Concentrations of cinoxacin in serum, urine, and tissues of urological patients. Journal of Antimicrobial Chemotherapy. In press. Giamarellou, H. & Jackson, G. G. Antibacterial activity of cinoxacin in vitro. Antimicrobial Agents and Chemotherapy 7: 688-92 (1975). Goss, W. A., Deitz, W. H. & Cook, T. M. Mechanism of action of nalidixic acid on Escherichia coli. Journal of Bacteriology 88: 1112-8 (1964). Goss, W. A. & Cook, T. M. Nalidixic acid—mode of action. In Antibiotics. Mechanisms of Action of Antimicrobial and Antitumour agents. (Corcoran, J. W. & Hahn, E. F., Eds). Springer Verlag New York (1975). Vol. 3. pp. 174-96. Hovelius, B., Bygren, P., Colleen, S. & Mardh, P.-A. Urinvagsinfektioner orsakade av Staphylococcus saprophyticus, biotyp 3—bakteriologi, epidemiologi och klinik. Hygiea 85: 46 (1976). Jones, R. N. & Fuchs, P. C. In vitro antimicrobial activity of cinoxacin against 2,968 clinical bacterial isolates. Antimicrobial Agents and Chemotherapy 10: 146-9 (1976). Kurtz, S. & Turck, M. In vitro activity of cinoxacin, an organic acid antibacterial. Antimicrobial Agents and Chemotherapy 7: 370-3 (1975). Lumish, R. M. & Norden, C. W. Cinoxacin: in vitro antibacterial studies of a new synthetic organic acid. Antimicrobial Agents and Chemotherapy 4: 415-20 (1975). Mardh, P.-A., Arhammer, M., Colleen, S. & Andersson, K.-E. Studies on cinoxacin. 4. Microcalorimetric investigation of the action of cinoxacin against Escherichia coli. Journal of Antimicrobial Chemotherapy. In press. Maskell, R. Importance of coagulase-negative staphylococci as pathogens in the urinary tract. Lancet, ii: 1155-8 (1974). Pannwalker, A. P., Giamarellou, H. & Jackson, G. G. Efficacy of cinoxacin in urinary tract infections. Antimicrobial Agents and Chemotherapy 9: 502-5 (1975). Washington II, I. A. & Barry, A. L. Dilution test procedures. In Manual of Clinical Microbiology (Lennette, E. H., Spaulding, E. H. & Truant, I. P., Eds). 2nd ed. American Society for Microbiology. Washington, D. S. (1974), pp. 410-7. Wick, W. E., Preston, D. A., White, W. A. & Gordee, R. S. Compound 64716, a new synthetic antibacterial
Studies on cinoxacin
P.-A. Mardh Institute of Medical Microbiology, University of Lund, S-223 62 Lund, Sweden S. Colleen Department of Urology, University Hospital, S-221 85 Lund, Sweden and K.-E. Andersson Department of Clinical Pharmacology, Institute of Pharmacology, University of Arhus, Dk-8000 Arhus C, Denmark
Bacteria were isolated from urine specimens obtained from patients with chronic urinary tract diseases treated with various antibiotics and chemotherapeutics for long periods of time because of recurrent or relapsing urinary tract infections. The micro-organisms were studied for their in vitro susceptibility to cinoxacin and nalidixic acid. The Gram-negative bacteria investigated were usually more susceptible to cinoxacin than to nalidixic acid. Ninety-eight of 108 strains of Escherichia coli were inhibited by 32 ng/ml of cinoxacin and 61 by 32 ng/ml of nalidixic acid. The corresponding numbers for 27 strains of Klebsiella pneumoniae were 22 and 12, and for 25 strains of Proteus mirabilis 20 and 10, respectively. None of 16 strains of Pseudomonas aeruginosa were inhibited by cinoxacin in this concentration, nor were 24 strains of staphylococci and streptococci. Introduction Cinoxacin [l-ethyl-l,4-dihydro-4,oxo-(l,3)dioxolo (4,5-g)cinnoline-3-carboxylic acid] is a synthetic organic acid with a cinnoline (1,2-benzodiazine) as the basic ring structure. The substance (compound 6471, Eli Lilly & Co.) is chemically related to nalidixic acid and oxolinic acid (Wick, Preston, White & Gordee, 1973). It has been shown to exhibit antimicrobial activity in vitro against Gram-negative bacteria encountered in urinary tract infections (Kurtz & Turck, 1975; Lumish & Norden, 1975; Jones & Fuchs, 1976), and also to be clinically effective (Panwalker, Giamarellou & Jackson, 1976). In the present study, bacteria isolated from urine specimens of patients with urinary tract infections attending a renal or a urological clinic were tested for their in vitro susceptibility to cinoxacin and nalidixic acid by determination of the minimal inhibitory concentrations (MIC) of the drugs; the susceptibility to cinoxacin was also tested in disc diffusion tests. 411
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
1. In vitro activity of ciooxadn, as compared to nalidixic acid, against urinary tract pathogens
412
P.-A. Mardh, S. Colleen and K.-E. Andersson Materials and methods
Clinical material and organisms studied
Table I. The minimum inhibitory concentrations (MIC) of cinoxacin ( Q and nalidixic acid (N) for 199 strains of Gram-negative bacilli isolated from urine specimens
Species
]VIIC (ng/ml)
No. of strains
studied 1
E. coli
108
Citrobacter
C N C N C N C N C N C N C N C N
1
Enterobacter spp.
16
K. pneumoniae
27
P. mirabilis
25
Proteus spp.
4
Acinetobacter
2
Ps. aeruginosa
16
Cumulative number of strains inhibited by: 2 4 8 16 32 64 128 256 512 >512
3 17 63 86 97 98 101 107 1 10 53 59 61 97 98 1
100
108 108 1
3
7 11 12 13 3 9 10 4 9 18 22 5 10 12 8 13 20 3 10 4 2 4 1 1
15 14 18 22 10
16 15 25 21 18
1
22 23 19
16 27 24 20
2 2 4 2
9
27 25 25
16 16
Table II. The minimum inhibitory concentrations (MIC) of cinoxacin for 25 strains of Grampositive cocci isolated from urine specimens Species
S. aitreus S. epidermidis •S". saprophyticus Group B streptococci S. faecalis
No. of strains tested 4 6 6 3 6
MIC (ug/ml) Cumulative number of strains inhibited by: 64 128 256 512 >512 4 3 1
6 6 3 6
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
One hundred and ninety-nine strains of Gram-negative rods and 25 strains of Grampositive cocci were studied. The strains tested were isolated from consecutive urine specimens containing more than 105 bacteria/ml, as determined by the calibrated loop technique. All specimens were obtained from patients attending the Renal or Urological Departments of the University Hospital, Lund. Most of them had chronic urinary tract diseases and had been treated with various antibiotics and chemotherapeutics for long periods of time because of recurrent or relapsing urinary tract infections. The susceptibility of the Gram-negative bacilli to cinoxacin and nalidixic acid was tested, while the cocci were tested only against cinoxacin. The numbers of strains of the different species studied are shown in Tables I and II.
In vitro activity of cinoxacin
413
Antimicrobial agents
Cinoxacin was obtained from the Lilly Research Laboratories, Indianapolis, Indiana, and nalidixic acid from Winthrop AB, Stockholm, Sweden. Stock solutions of the drugs (containing 1000 ug/ml) were prepared in 0-1 M-phosphate buffered saline, pH 7-2, and stored at — 20°C. Test solutions were prepared fresh at each test occasion. In the disc diffusion tests, paper filter discs containing 30 ug of cinoxacin (BBL) and 30 ug of nalidixic acid (AB Biodisk, Stockholm) were used.
Susceptibility tests To determine the minimum inhibitory concentrations of cinoxacin and nalidixic acid, the 224 strains studied were harvested from blood agar plates, which had been incubated at 37°C for 18 h. The bacteria were suspended in saline to give a density of 105 bacteria/ ml. The test medium containing cinoxacin or nalidixic acid in various concentrations was spot-inoculated with a replicating device. The bacteria were tested against the antimicrobial agents in concentrations varying between 1 and 512 ug/ml. Non-antibiotic containing plates were used as controls. The plates were incubated at 37°C overnight after being left to dry for 40 min at room temperature. MIC was defined as the lowest concentrations of the antimicrobial agents that completely inhibited growth or allowed formation of single colonies at the most. Sixty-five of the Gram-negative strains (E. coli, K. pneumoniae, P. mirabilis) were studied in disc diffusion tests with cinoxacin and nalidixic acid. Petri dishes, 9 cm in diameter, to which 20 ml of the test medium had been added, which gave a 3 mm thick agar layer were used. The saline suspension of the bacteria to be tested was spread over the plates with a cotton-tipped swab to obtain an even film. The plates were stored in room temperature for 30 min before incubated at 37°C. They were read after overnight incubation. The inhibitory zones were measured by the aid of a sliding calliper.
Results Susceptibility tests The MIC's of cinoxacin and nalidixic acid for the 199 strains of Gram-negative bacteria tested are given in Table I. Gram-negative baccilli were usually more susceptible to cinoxacin than to nalidixic acid. For 139 of the strains, the MIC of cinoxacin was more than 2-fold lower than that for nalidixic acid. For two strains only, the reverse was found. Figure 1 gives the cumulative percentage of the 3 most frequently isolated species (E. coli, K. pneumoniae, P. mirabilis) inhibited by increasing concentrations of the two antibiotics studied. Cinoxacin in a concentration of 32 ug/ml inhibited 98 of the 108 strains of E. coli (91 %). Nalidixic acid in the same concentration inhibited 61 of the strains (56%). Corresponding numbers for 27 strains of K. pneumoniae were 22 and 12, and for 25 strains of P. mirabilis 20 and 10, respectively. None of 16 strains of Ps.
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Media The strains were isolated and maintained on blood agar plates consisting of Blood Agar Base No. 2 (Oxoid) with 4 % defibrinated horse blood. The susceptibility tests were all made on Mueller-Hinton medium (Difco), pH 7 4.
414
P.-A. Mardh, S. Colleen and K.-E. Andersson
24 8
16
32
64 128 256 512 »5I2
16 32 64 128 256 512*512 Antibiotic conctntrotion (/ig/ml)
Figure 1. Cumulative percentages of 108 strains of Escherichia coli, 25 strains of Klebsiella pneumoniae, and 25 strains of Proteus mirabilis inhibited by increasing concentrations of cinoxacin ( • • ) and nalidixic acid ( • •).
aeruginosa was inhibited by cinoxacin and nalidixic acid in the concentrations indicated above. Nine of the 16 strains were inhibited by cinoxacin 512 ug/ml, while only 2 were inhibited by nalidixic acid in the same concentration. The MIC's of cinoxacin for the staphylococcal and streptococcal strains studied are shown in Table II. Gram-positive cocci were generally less susceptible to cinoxacin than the Gram-negative rods studied (except for Ps. aeruginosa). Among the staphylococcal and streptoccocal strains tested, S. aureus was more susceptible than the others. The distribution of the inhibitory zones obtained in disc diffusion test with 75 of the Gram-negative strains when testing cinoxacin and nalidixic acid are shown in Figure 2.
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
24 8
415
In vitro activity of cinoxacin
T
e.coli
T
1
0
5
0
10
.. . . nJlli Infli i 15
20
25
30
35
40
10
15
20
25
30
35
40
35
40
i i
n
i
P. mirabilis
5 -
n
I
10
lll.l.
mi I III 15 20 25 Inhibitory zone
• i 30
I
Figure 2. Inhibitory zones in disc diffusion tests with cinoxacin (unfilled bars) and nalidixic acid (filled bars) produced by 41 strains of Escherichia coli, 13 strains of Klebsiella pneumoniae and 11 strains of Proteus mirabilis using discs containing 30 ng of the substances. Tests performed on Mueller-Hinton medium.
Discussion In previous studies, the in vitro susceptibility of bacteria to cinoxacin has been tested (Wick, Preston, White & Gordee, 1973; Giamarellou & Jackson, 1975; Kurtz & Turck, 1975; Jones & Fuchs, 1976). All bacterial strains tested in the present investigation were isolated from urine specimens of patients treated for long periods of time with various antibiotics and chemotherapeutics. Thus, the strains of bacteria were obtained from a group of patients in whom the treatment of urinary tract infections often offers therapeutic problems. The antibacterial spectrum of cinoxacin was, as also others have found, similar to that known for nalidixic acid (Goss & Cook, 1975). However, the in vitro activity of cinoxacin was, per unit of weight, generally higher than that of nalidixic acid. Thus, approximately 70% of the strains of Enterobacteriaceae were more susceptible to cinoxacin. In agreement with previous studies (Wick et ah, 1973; Kurtz & Turck, 1975; Jones & Fuchs, 1976), Pseudomonas aeruginosa was found to be more susceptible to cinoxacin than to nalidixic acid. It should be noted, however, that 9 out of 16 strains were inhibited by cinoxacin 512 ug/ml, whereas only 2 of these 16 strains were inhibited by nalidixic acid in the same concentration. Peak concentrations in urine exceeding 500 ug/ml can be obtained during cinoxacin treatment (Colleen, Andersson & Mardh, 1976). Cinoxacin showed a poor activity against group B and D streptococci (MIO512 Ug/ml). S. saprophyticus is a common cause of acute cystourethritis in women of fertile age (Maskell, 1974). It has recently been described that this bacterium also can engage the upper urinary tract and cause recurrent and relapsing urinary tract infections
Downloaded from http://jac.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
1
i
416
P.-A. Mardh, S. Colleen and K.-E. Andersson
Acknowledgements This study was supported by grant no. 16X-4509 from the Swedish Medical Research Council. We wish to acknowledge the supply of cinoxacin from Eli Lilly & Co. and also for their support. References Colleen, S., Andersson, K.-E. & M&rdh, P.-A. Studies on cinoxacin. 3. Concentrations of cinoxacin in serum, urine, and tissues of urological patients. Journal of Antimicrobial Chemotherapy. In press. Giamarellou, H. & Jackson, G. G. Antibacterial activity of cinoxacin in vitro. Antimicrobial Agents and Chemotherapy 7: 688-92 (1975). Goss, W. A., Deitz, W. H. & Cook, T. M. Mechanism of action of nalidixic acid on Escherichia coli. Journal of Bacteriology 88: 1112-8 (1964). Goss, W. A. & Cook, T. M. Nalidixic acid—mode of action. In Antibiotics. Mechanisms of Action of Antimicrobial and Antitumour agents. (Corcoran, J. W. & Hahn, E. F., Eds). Springer Verlag New York (1975). Vol. 3. pp. 174-96. Hovelius, B., Bygren, P., Colleen, S. & Mardh, P.-A. Urinvagsinfektioner orsakade av Staphylococcus saprophyticus, biotyp 3—bakteriologi, epidemiologi och klinik. Hygiea 85: 46 (1976). Jones, R. N. & Fuchs, P. C. In vitro antimicrobial activity of cinoxacin against 2,968 clinical bacterial isolates. Antimicrobial Agents and Chemotherapy 10: 146-9 (1976). Kurtz, S. & Turck, M. In vitro activity of cinoxacin, an organic acid antibacterial. Antimicrobial Agents and Chemotherapy 7: 370-3 (1975). Lumish, R. M. & Norden, C. W. Cinoxacin: in vitro antibacterial studies of a new synthetic organic acid. Antimicrobial Agents and Chemotherapy 4: 415-20 (1975). Mardh, P.-A., Arhammer, M., Colleen, S. & Andersson, K.-E. Studies on cinoxacin. 4. Microcalorimetric investigation of the action of cinoxacin against Escherichia coli. Journal of Antimicrobial Chemotherapy. In press. Maskell, R. Importance of coagulase-negative staphylococci as pathogens in the urinary tract. Lancet, ii: 1155-8 (1974). Pannwalker, A. P., Giamarellou, H. & Jackson, G. G. Efficacy of cinoxacin in urinary tract infections. Antimicrobial Agents and Chemotherapy 9: 502-5 (1975). Washington II, I. A. & Barry, A. L. Dilution test procedures. In Manual of Clinical Microbiology (Lennette, E. H., Spaulding, E. H. & Truant, I. P., Eds). 2nd ed. American Society for Microbiology. Washington, D. S. (1974), pp. 410-7. Wick, W. E., Preston, D. A., White, W. A. & Gordee, R. S. Compound 64716, a new synthetic antibacterial
