Session III Y. Kumamoto
Single-Dose Treatment of Female Acute Uncomplicated Cystitis Female acute uncomplicated cystitis is regarded as a urinary tract infection which is relatively easy to treat. At the first meeting of this international symposium, held in 1989, I reported that the administration of talampicillin or cephalexin for three days in a dosage of 125 mg/day, which is only 1/10 of the usual dosage, is clinically efficacious in 90% of patients. However, with an antibiotic at such a low dosage this disease readily recurs. Even after treatment, the causative bacterium may remain in the urethra near the bladder. If the bacterial population has not been suppressed below a level resulting in natural disappearance, the microbes will proliferate again, and cystitis will recur. What dosage and administration period are necessary to prevent recurrence? Figure 1 compares three protocols for treatment, using antibiotics with varying half-lives. In our experience, if the concentration of the antibiotic in the urine was higher than the MIC for the urinary isolate, recurrence of the disease was best prevented by protocol C, which employed the lowest dose but the longest administration period among the three protocols. New quinolones, which have been developed recently, show potent antimicrobial action against the causative pathogens of cystitis, and, in addition, have a broad antimicrobial spectrum. Moreover, their half-lives are longer than the conventional antibiotics, and thus even a single dose can maintain an effective urinary concentration for quite a long time. Administration of a single 300 mg dose of ofloxacin (OFLX) is capable of maintaining the MIC90 against Escherichia cell for 74 h, or three days (Figure 2). In the case of sparfloxacin (SPFX), which has a longer half-life than OFLX, an effective urinary concentration is maintained for 138 h, or almost six days if it is administered in a dose of 200 mg (Figure 3). Thus, a single
t
High dose
A
Dose of antibiotics
C
Treatment period
(day)
Figure 1: Methods of antibiotic administration for female acute uncomplicated cystitis.
1000
glee 8
10
E 8
g 1
~ l
.1
O.05Jlg/m;M l IC agai aonst
E.cotl
J
f'x .01 ~ 0
~ 12
24
36
48
60
96
100 120 132 144 ~56 168
Time after administration
(hr)
Figure 2: Changes in urinary concentration after OFLX 300 mg oral administration. 1000
1°°1_
U 8
.1 ! .
0
1
~
~
~
Time alter administration
(hr) ~1
12() 132 ~144
156 16;
Figure 3: Changes in urinary concentration after SPFX 100 and 200 mg oral administration.
administration of a new quinolone at a high dose does not cause any adverse effects but is capable of maintaining an effective urinary concentration for a period sufficient to prevent recurrence of the disease as described above. In this sense, new quinolones are very attractive antibiotics from the clinical standpoint. We performed five studies with single-dose oral therapy in acute uncomplicated cystitis in women using 300 mg of OFLX, 200 mg antimicrobial potency equivalent to 400 mg of OFLX of DR-3355 (an l-isomer of OFLX), 100 mg and 200 mg of SPFX, and 200 mg of cefixime (CFIX), an oral cephem with a shorter half-life, faster urinary excretion (Figure 4) and different mode of action as compared to the quinolones. The results are summarized in Table 1. After receiving 300 mg of OFLX, seven (9.2%) patients required the administration of another drug on day 14 or earlier. Following the administration of the other newer
Y. Kumarnoto, M. D., Dept. of Urology, Sapporo Medical College, Nishi-17, Minami-1, Chuo-ku, Sapporo 060, Japan.
Infection 20 (1992) Suppl. 3 © MMV Medizin Verlag GmbH MOnchen, Miinchen 1992
S 173
Y. Kumamote: Therapy of Female Acute Uncomplicated Cystitis 1000-
100
Table 1 : Summary of clinical results in single-dose treatment of female acute uncomplicated cystitis.
•
10. ~
\
I O,78pglml;MlCgoagainst E.coll
i OFLX 300 mg 12
24 , 36
48
"rlme afteradmlnlstrallon (hr) Concentration~g/ml)
Figure 4: Changes in urinary concentration after CFIX 200 mg oral administration.
quinolones these rates were lower, ranging from 2.4% (200 mg SPFX) to 4.0% (100 mg SPFX). After oral treatment with cefixime 28% of the patients already required administration of another drug on day 7 or earlier.
~
76
0
4
3
7 (9.2%)
DR-3355 200 mg
76
0
2
0
2 (2.6%)
SPFX 100 mg
49
1
0
1
2 (4.0%)
SPFX 200 mg
42
0
0
1
1 (2.4%)
[ CFIX 200 mg
125
[
4
[
4
[
I~(~1
OFLX = ofloxacin; SPFX = sparfloxacin; CFIX = cefixime.
female acute uncomplicated cystitis, it does not appear to be necessary to achieve a very high urinary antibiotic concentration. However, a high clinical efficacy rate with a low recurrence rate can be achieved by maintaining the urinary antibiotic concentration at a level higher than the effective concentration of the drug for about five days.
Conclusion
On the basis of our results with single-dose treatment of
S 174
Infection 20 (1992) Suppl. 3 © MMV Medizin Verlag GmbH Miinchen, Mfinchen 1992
Single-Dose Treatment of Female Acute Uncomplicated Cystitis Female acute uncomplicated cystitis is regarded as a urinary tract infection which is relatively easy to treat. At the first meeting of this international symposium, held in 1989, I reported that the administration of talampicillin or cephalexin for three days in a dosage of 125 mg/day, which is only 1/10 of the usual dosage, is clinically efficacious in 90% of patients. However, with an antibiotic at such a low dosage this disease readily recurs. Even after treatment, the causative bacterium may remain in the urethra near the bladder. If the bacterial population has not been suppressed below a level resulting in natural disappearance, the microbes will proliferate again, and cystitis will recur. What dosage and administration period are necessary to prevent recurrence? Figure 1 compares three protocols for treatment, using antibiotics with varying half-lives. In our experience, if the concentration of the antibiotic in the urine was higher than the MIC for the urinary isolate, recurrence of the disease was best prevented by protocol C, which employed the lowest dose but the longest administration period among the three protocols. New quinolones, which have been developed recently, show potent antimicrobial action against the causative pathogens of cystitis, and, in addition, have a broad antimicrobial spectrum. Moreover, their half-lives are longer than the conventional antibiotics, and thus even a single dose can maintain an effective urinary concentration for quite a long time. Administration of a single 300 mg dose of ofloxacin (OFLX) is capable of maintaining the MIC90 against Escherichia cell for 74 h, or three days (Figure 2). In the case of sparfloxacin (SPFX), which has a longer half-life than OFLX, an effective urinary concentration is maintained for 138 h, or almost six days if it is administered in a dose of 200 mg (Figure 3). Thus, a single
t
High dose
A
Dose of antibiotics
C
Treatment period
(day)
Figure 1: Methods of antibiotic administration for female acute uncomplicated cystitis.
1000
glee 8
10
E 8
g 1
~ l
.1
O.05Jlg/m;M l IC agai aonst
E.cotl
J
f'x .01 ~ 0
~ 12
24
36
48
60
96
100 120 132 144 ~56 168
Time after administration
(hr)
Figure 2: Changes in urinary concentration after OFLX 300 mg oral administration. 1000
1°°1_
U 8
.1 ! .
0
1
~
~
~
Time alter administration
(hr) ~1
12() 132 ~144
156 16;
Figure 3: Changes in urinary concentration after SPFX 100 and 200 mg oral administration.
administration of a new quinolone at a high dose does not cause any adverse effects but is capable of maintaining an effective urinary concentration for a period sufficient to prevent recurrence of the disease as described above. In this sense, new quinolones are very attractive antibiotics from the clinical standpoint. We performed five studies with single-dose oral therapy in acute uncomplicated cystitis in women using 300 mg of OFLX, 200 mg antimicrobial potency equivalent to 400 mg of OFLX of DR-3355 (an l-isomer of OFLX), 100 mg and 200 mg of SPFX, and 200 mg of cefixime (CFIX), an oral cephem with a shorter half-life, faster urinary excretion (Figure 4) and different mode of action as compared to the quinolones. The results are summarized in Table 1. After receiving 300 mg of OFLX, seven (9.2%) patients required the administration of another drug on day 14 or earlier. Following the administration of the other newer
Y. Kumarnoto, M. D., Dept. of Urology, Sapporo Medical College, Nishi-17, Minami-1, Chuo-ku, Sapporo 060, Japan.
Infection 20 (1992) Suppl. 3 © MMV Medizin Verlag GmbH MOnchen, Miinchen 1992
S 173
Y. Kumamote: Therapy of Female Acute Uncomplicated Cystitis 1000-
100
Table 1 : Summary of clinical results in single-dose treatment of female acute uncomplicated cystitis.
•
10. ~
\
I O,78pglml;MlCgoagainst E.coll
i OFLX 300 mg 12
24 , 36
48
"rlme afteradmlnlstrallon (hr) Concentration~g/ml)
Figure 4: Changes in urinary concentration after CFIX 200 mg oral administration.
quinolones these rates were lower, ranging from 2.4% (200 mg SPFX) to 4.0% (100 mg SPFX). After oral treatment with cefixime 28% of the patients already required administration of another drug on day 7 or earlier.
~
76
0
4
3
7 (9.2%)
DR-3355 200 mg
76
0
2
0
2 (2.6%)
SPFX 100 mg
49
1
0
1
2 (4.0%)
SPFX 200 mg
42
0
0
1
1 (2.4%)
[ CFIX 200 mg
125
[
4
[
4
[
I~(~1
OFLX = ofloxacin; SPFX = sparfloxacin; CFIX = cefixime.
female acute uncomplicated cystitis, it does not appear to be necessary to achieve a very high urinary antibiotic concentration. However, a high clinical efficacy rate with a low recurrence rate can be achieved by maintaining the urinary antibiotic concentration at a level higher than the effective concentration of the drug for about five days.
Conclusion
On the basis of our results with single-dose treatment of
S 174
Infection 20 (1992) Suppl. 3 © MMV Medizin Verlag GmbH Miinchen, Mfinchen 1992
