- Email: [email protected]
Nitrofurazone in the Treatment of Nonspecific Urethritis in Women
THE JouR:-rAL OF UROLOGY
Vol. 70, No. 6, December 1953 Printed in U.S.A.
NITROFURAZONE IN THE TREATMENT OF NONSPECIFIC URETHRITIS IN WOMEN VERNON H. YOUNGBLOOD From the Surgical Service (Urology), Cabarrus !VIemorial Hospital, Concord, N. C.
Nonspecific, or granular, urethritis is a common finding in women. One only has to keep in mind the possibility of its occurrence, use the panendoscope freely, and he will be rewarded with an increasing number of positive diagnoses. The normal urethra closely resembles in appearance the bladder epithelium. The male prostatic urethra in chronic prostatitis has a characteristic semblance; nonspecific urethritis in women looks similar. The urethra has increased folds, dilated and tortuous blood vessels that easily bleed, an edema that frequently has granulation tissue superimposed, and polyps. There is no one characteristic appearance, but experience in observation, as in all endoscopic work, is necessary to grade the degree and variations of irritation. The symptoms are: frequency, urgency, dysuria, nocturia, incontinence, straining, sense of incomplete emptying, and frequently the patient will say that it is an effort to void. If a man ,vould have any of these symptoms, we would unhesitatingly look first to the urethra as the source of trouble. The same applies to women. The urinary findings are variable, but usually the microscopic examination is negative. The standard treatment over the years has been urethral dilatations and applications of a silver compound. Attention has been directed to foci of infection, particularly in the female genital tract. Irritating foods are usually ,Yithheld. Systemic therapy per se has usually been futile. Under this regimen, improvement can be expected in 6 to 8 weeks. Over the last year, a new treatment has been used. This came about following discouraging results from the dilatation and silver nitrate treatment. Furacin brand (Eaton Laboratories, Inc.) of nitrofurazone has been used by me almost exclusively over the past 2;,f years as an instillation in the bladder for cystitis. When used in a dilution of 1 : 10 in saline, it has been nonirritating and highly effective. As a result of its effectiveness in cystitis, silver compounds, acriflavine, potassium permanganate and others have been abandoned. However, Furacin solution instilled into the bladder, though effective in urethritis, was not completely satisfactory. Direct applications were then made to the urethra, and this method of application is the basis for this report. Furacin is an antibacterial agent with high potency in high dilutions. This nitrofuran compound has been proved by others to be bactericidal to most all common organisms found in the urinary tract, in much greater dilution than the 1: 500 strength used as described below. A notable exception, hmvever, is Proteus. The method of use at first was the application of Furacin soluble dressing on a cotton applicator to the urethra. The patient was then taught to insert the appliAccepted for publication December 5, 1952. 926
927
NONSPECIFIC -URETHRITIS
cator herself, two times each day, following a sitz bath. The patient was placed on forced fluids 1Yith restriction of irritating foods and drinks such as carbcmated drinks, alcohol, citrus etc. The vagina was routinely examined, and ,yhere treatment wa8 it ,rns presc:ribed. Bladder or renal abnormalitieR were irnated when present. If a urethral stricture was present, dilatations were done. From April Hl52 to October 1, 1952, the diagnosis of nonspecific urethri1ifi was made 94 times. Of this number, forty were sufficiently studied and follmrnd for satisfactory others stated they were symptom-free and behen~d that they lleeded no further treatment Not induded in this surYey, hut included in the total number of diagnoses, were 2 ca:c;es of urethral diverticulum, l car,,e of hypertrophy of the para-urethral glands ,-rith urinary retention, and G cases whose other renal or bladder abnormalities overshadowed the urethritis and in whom urethritis \\-as more or less inC'identaL Diabetes was a8sociated i11 1 case, chorio-epithelioma in another. The cases i11 this 8urvey were treated in the officf:. The symptoms (many had multiple symptoms) were: Cases
Per Crnt
Frequency.
36
Dysuria
:m
lJrgenc~r
27 26
(fJO) (7fi) (68)
Nocturi11. Difficultc· in initinting; and passing urinary stream. Rtress ineonlinence l;rgency incoutirwnee Pain in abclomen Backache Pressure in bladder Pain in lmrnr nbdominal quadnmt (localized). Pa.in in hips nncl thighs
(ofil
:26
(65)
4
(10)
4
(10)
1 l
un
(:j)
]
(:3)
(3) (:3)
The duration of varied from 1 day to 18 yearn. Seven patients had symptoms for one or more years, eleven had symptoms from l to 12 mo11ths, fourteen from 1 to+ and eight from 1 to 7 The urinary findings \H're · Normal. Occnsiorrnl to 1-2 REC per high power field. Occnsionnl to 1-·2 pus cells per high power field .. [nnumerable pus cells. Positive sugnr
Cases
Per cent
26
(65) (15) (5) (5) (~)
(l
2 2 l
Uri11e cultures sho,n:'d no gro,Yth in 22, unidentified streptococcus, 2; coccus viridans, 2; non-hemolytic gram po8itive micrococci, ct; spore-forming bacilli, cl; Proteus, +; non-hemolytic streptococcus, 4; and coliform, ft An in-· terestiug finding, but not accurately tabulated, 1Yas the presence of mucus on micro:wopic examination. Thi,~ ,vas not looked for but because of its presence became The urethral changes ,,-ere graded as to degree of irritation: Cases
Minimal .. i\IoclernJe. _\far keel (urethra.! s( rict.ure was present in four cases)
Per cenl
1
(:3
ll 28
(27 (70
928
VERNON II. YOUNGBLOOD
Bladder findings were: :'formal. Trigonitis. Cystocele. Acute cystitis ... Caruncle ..
Cases
Per cent
20 13 3
(50) (33) (8) (5) (8)
2 3
The upper urinary tract was studied in thirteen cases. The findings were: Kidney stone U reteral stone (also had renal stone). . Stricture of ureter, postoperative .. Xegativc. ~ ot studied ..
2 l.
1 10
27
Furacin ,ms applied to the urethra two times daily but occasionally, when symptoms had nearly dis!1ppeared, once daily. After this study started, the makers of Furacin kindly supplied a new dosage form, Furacin urethral suppositories. This made the drug much easier to administer and no patient had more than minimal difficulty iu its use. These suppositories contain Furacin 0.2 per cent \Yith the topical anesthetic, diperodon hydrochloride 2 per cent in a ,rnter dispersible base. The length of treatment was: 16 cases clays 3 cases weeks 18 cases 1 case 3 weeks 4 weeks 1 case 1 case intermittently 5 months (2 patients had repeated courses of treatment; one, 1 week; one, 2 weeks) 1 week
10 2
Furacin solution K. N. R. in a 1: 10 dilution of stock drug was instilled into the bladder at each weekly office visit thereafter. Sitz baths were prescribed \Yith the urethral applications. The results showed that twenty-eight were entirely symptom free at the end of the treatment and t,velve improved. Many of the patients who were improved probably could have been termed cured had they been seen again. The urethra by endoscopic examination in every case was improved, though there was no close parallelism with the symptoms. In other words, the patients became symptom-free before the endoscopic findings were normal or stationary. One patient was treated for 3 months with only moderate improvement; she has been advised to have a marked cysto-urethrocele and old perineal laceration repaired. Another patient did not improve until Banthine ,vas used in association with the Furacin treatment. DISCUSSION
Burns and Butt, in describing their results with chronic urethritis using bladder irrigations, sounds, and silver nitrate to the urethra, found complete relief of symptoms in 90 per cent in 6 to 8 weeks. Spence used the same treatment in
NONSPECIFIC URETJIRI'rIS
half of his cases and electrocoagulation in ahout half. He doeci 11ot giYe the Lime for improvement but infers a period of treatment of about 4 to G weekci or louget·, The treatment described uciing Fumein requires a minimum of office viciits, does away ,Yith the pain of methral dilatatioJls and silver nitrate applicationcJ, Symptomatic improvement has been noticed as early as 1 day after beginning treatment, and the a vet'age period of treatment iR 13 days. The patient can easily use the medication at home hernelf. SUIVlj\L\RY
The nse of Furacin urethral c;uppositories in the treatment of nonspecific urethritis in women has heeu presented, The treatment period is shorter and more comfortable than 1,'ith the conventional method of sounds and si]yer preparn-tiom,. A.DDENDUM
Since the paper 1yas submitted, more than :300 additional cacies of urethritis have been treated with Furncin urethral suppositories. The findings in these eases lrn,·e heeu parallel to the ones discussed aboyc. Oue case of urethral diverticnlum and 2 rase:-, of aberrant ureteral orifices haYe been foulld. Three cases of serrnitiYity to the medication ha Ye also occurred. This has not beeu manifested on the endoscopic findings but in each case has bee11 n1lYal irritation. All eases responded t.o discontinuance of the drug and local applications uf pyrihenzamine oinment. Seycral caseB of urethritis in men that have been refractory to all other treatment have improYed ,,·ith Furacin urethral suppositories. The suppository method of medication has proved its ,rnrth. Several ease:-; of marked granular changes in the urethra have 11ot responded to Furncin uretlml auppm,itories. These ha.-ve responded slmvly to the old treatment of that of 10 per- ('eHt silver nitrate applications to the methra. ·with this in mind, sih·er rntrate suppositories are now in the process of manufacture for clinical trial.
Kannapolis Highway, Concord, N. C. REFERENCES
K: J. Urol., 30: 263, 19:33, B1-;RNs, EDu.rn AND B,;TT, A. J., South. Surg., 12: 352, Hl46. CARSON, R. B.: Urol. & Cutan. Rev., 51: 23, Hl47. F1mGusoN, CHARLES AND Niru.JcR, C. D.: ,J. UroL, 67: 762, 1952, FOLSOM, A. I. A:\'D O'BREJN, H. A,: J,A.M.1L, 128: 408, 1945. HEcKv!L, X J.: J. UroL, 35: 520, HJ36, HERB UT, l'. A.: Urological Pathology. Philadelphia: Lea and F'ebiger, 1952, vol. l, JJ, 56. LEBF~R.HA-'i, P. IL. UroL & Cut.an. Rev., 41: 584, 1937. Lr;\'TG~~N, CHARLES AND HERBUT·, P, A.: J. Urol., 55: 298, 1046. RoE:\i, P.R. Al'.'D STEPT, R.R.: Am, J. Dis. Child,, 72: 52D, 1946. SPENCE, H. lvL: J. Oro!., 43: 199, lD40. SwEE'rs"rn, T. H. JR. AND HARRISON, J, A.: J. UroL, 65: 684, 1951. ZunrEm11AK, L J.: Ne11· Eug, J. Med., 222: 221, 1940, BERRY,>:,.
Vol. 70, No. 6, December 1953 Printed in U.S.A.
NITROFURAZONE IN THE TREATMENT OF NONSPECIFIC URETHRITIS IN WOMEN VERNON H. YOUNGBLOOD From the Surgical Service (Urology), Cabarrus !VIemorial Hospital, Concord, N. C.
Nonspecific, or granular, urethritis is a common finding in women. One only has to keep in mind the possibility of its occurrence, use the panendoscope freely, and he will be rewarded with an increasing number of positive diagnoses. The normal urethra closely resembles in appearance the bladder epithelium. The male prostatic urethra in chronic prostatitis has a characteristic semblance; nonspecific urethritis in women looks similar. The urethra has increased folds, dilated and tortuous blood vessels that easily bleed, an edema that frequently has granulation tissue superimposed, and polyps. There is no one characteristic appearance, but experience in observation, as in all endoscopic work, is necessary to grade the degree and variations of irritation. The symptoms are: frequency, urgency, dysuria, nocturia, incontinence, straining, sense of incomplete emptying, and frequently the patient will say that it is an effort to void. If a man ,vould have any of these symptoms, we would unhesitatingly look first to the urethra as the source of trouble. The same applies to women. The urinary findings are variable, but usually the microscopic examination is negative. The standard treatment over the years has been urethral dilatations and applications of a silver compound. Attention has been directed to foci of infection, particularly in the female genital tract. Irritating foods are usually ,Yithheld. Systemic therapy per se has usually been futile. Under this regimen, improvement can be expected in 6 to 8 weeks. Over the last year, a new treatment has been used. This came about following discouraging results from the dilatation and silver nitrate treatment. Furacin brand (Eaton Laboratories, Inc.) of nitrofurazone has been used by me almost exclusively over the past 2;,f years as an instillation in the bladder for cystitis. When used in a dilution of 1 : 10 in saline, it has been nonirritating and highly effective. As a result of its effectiveness in cystitis, silver compounds, acriflavine, potassium permanganate and others have been abandoned. However, Furacin solution instilled into the bladder, though effective in urethritis, was not completely satisfactory. Direct applications were then made to the urethra, and this method of application is the basis for this report. Furacin is an antibacterial agent with high potency in high dilutions. This nitrofuran compound has been proved by others to be bactericidal to most all common organisms found in the urinary tract, in much greater dilution than the 1: 500 strength used as described below. A notable exception, hmvever, is Proteus. The method of use at first was the application of Furacin soluble dressing on a cotton applicator to the urethra. The patient was then taught to insert the appliAccepted for publication December 5, 1952. 926
927
NONSPECIFIC -URETHRITIS
cator herself, two times each day, following a sitz bath. The patient was placed on forced fluids 1Yith restriction of irritating foods and drinks such as carbcmated drinks, alcohol, citrus etc. The vagina was routinely examined, and ,yhere treatment wa8 it ,rns presc:ribed. Bladder or renal abnormalitieR were irnated when present. If a urethral stricture was present, dilatations were done. From April Hl52 to October 1, 1952, the diagnosis of nonspecific urethri1ifi was made 94 times. Of this number, forty were sufficiently studied and follmrnd for satisfactory others stated they were symptom-free and behen~d that they lleeded no further treatment Not induded in this surYey, hut included in the total number of diagnoses, were 2 ca:c;es of urethral diverticulum, l car,,e of hypertrophy of the para-urethral glands ,-rith urinary retention, and G cases whose other renal or bladder abnormalities overshadowed the urethritis and in whom urethritis \\-as more or less inC'identaL Diabetes was a8sociated i11 1 case, chorio-epithelioma in another. The cases i11 this 8urvey were treated in the officf:. The symptoms (many had multiple symptoms) were: Cases
Per Crnt
Frequency.
36
Dysuria
:m
lJrgenc~r
27 26
(fJO) (7fi) (68)
Nocturi11. Difficultc· in initinting; and passing urinary stream. Rtress ineonlinence l;rgency incoutirwnee Pain in abclomen Backache Pressure in bladder Pain in lmrnr nbdominal quadnmt (localized). Pa.in in hips nncl thighs
(ofil
:26
(65)
4
(10)
4
(10)
1 l
un
(:j)
]
(:3)
(3) (:3)
The duration of varied from 1 day to 18 yearn. Seven patients had symptoms for one or more years, eleven had symptoms from l to 12 mo11ths, fourteen from 1 to+ and eight from 1 to 7 The urinary findings \H're · Normal. Occnsiorrnl to 1-2 REC per high power field. Occnsionnl to 1-·2 pus cells per high power field .. [nnumerable pus cells. Positive sugnr
Cases
Per cent
26
(65) (15) (5) (5) (~)
(l
2 2 l
Uri11e cultures sho,n:'d no gro,Yth in 22, unidentified streptococcus, 2; coccus viridans, 2; non-hemolytic gram po8itive micrococci, ct; spore-forming bacilli, cl; Proteus, +; non-hemolytic streptococcus, 4; and coliform, ft An in-· terestiug finding, but not accurately tabulated, 1Yas the presence of mucus on micro:wopic examination. Thi,~ ,vas not looked for but because of its presence became The urethral changes ,,-ere graded as to degree of irritation: Cases
Minimal .. i\IoclernJe. _\far keel (urethra.! s( rict.ure was present in four cases)
Per cenl
1
(:3
ll 28
(27 (70
928
VERNON II. YOUNGBLOOD
Bladder findings were: :'formal. Trigonitis. Cystocele. Acute cystitis ... Caruncle ..
Cases
Per cent
20 13 3
(50) (33) (8) (5) (8)
2 3
The upper urinary tract was studied in thirteen cases. The findings were: Kidney stone U reteral stone (also had renal stone). . Stricture of ureter, postoperative .. Xegativc. ~ ot studied ..
2 l.
1 10
27
Furacin ,ms applied to the urethra two times daily but occasionally, when symptoms had nearly dis!1ppeared, once daily. After this study started, the makers of Furacin kindly supplied a new dosage form, Furacin urethral suppositories. This made the drug much easier to administer and no patient had more than minimal difficulty iu its use. These suppositories contain Furacin 0.2 per cent \Yith the topical anesthetic, diperodon hydrochloride 2 per cent in a ,rnter dispersible base. The length of treatment was: 16 cases clays 3 cases weeks 18 cases 1 case 3 weeks 4 weeks 1 case 1 case intermittently 5 months (2 patients had repeated courses of treatment; one, 1 week; one, 2 weeks) 1 week
10 2
Furacin solution K. N. R. in a 1: 10 dilution of stock drug was instilled into the bladder at each weekly office visit thereafter. Sitz baths were prescribed \Yith the urethral applications. The results showed that twenty-eight were entirely symptom free at the end of the treatment and t,velve improved. Many of the patients who were improved probably could have been termed cured had they been seen again. The urethra by endoscopic examination in every case was improved, though there was no close parallelism with the symptoms. In other words, the patients became symptom-free before the endoscopic findings were normal or stationary. One patient was treated for 3 months with only moderate improvement; she has been advised to have a marked cysto-urethrocele and old perineal laceration repaired. Another patient did not improve until Banthine ,vas used in association with the Furacin treatment. DISCUSSION
Burns and Butt, in describing their results with chronic urethritis using bladder irrigations, sounds, and silver nitrate to the urethra, found complete relief of symptoms in 90 per cent in 6 to 8 weeks. Spence used the same treatment in
NONSPECIFIC URETJIRI'rIS
half of his cases and electrocoagulation in ahout half. He doeci 11ot giYe the Lime for improvement but infers a period of treatment of about 4 to G weekci or louget·, The treatment described uciing Fumein requires a minimum of office viciits, does away ,Yith the pain of methral dilatatioJls and silver nitrate applicationcJ, Symptomatic improvement has been noticed as early as 1 day after beginning treatment, and the a vet'age period of treatment iR 13 days. The patient can easily use the medication at home hernelf. SUIVlj\L\RY
The nse of Furacin urethral c;uppositories in the treatment of nonspecific urethritis in women has heeu presented, The treatment period is shorter and more comfortable than 1,'ith the conventional method of sounds and si]yer preparn-tiom,. A.DDENDUM
Since the paper 1yas submitted, more than :300 additional cacies of urethritis have been treated with Furncin urethral suppositories. The findings in these eases lrn,·e heeu parallel to the ones discussed aboyc. Oue case of urethral diverticnlum and 2 rase:-, of aberrant ureteral orifices haYe been foulld. Three cases of serrnitiYity to the medication ha Ye also occurred. This has not beeu manifested on the endoscopic findings but in each case has bee11 n1lYal irritation. All eases responded t.o discontinuance of the drug and local applications uf pyrihenzamine oinment. Seycral caseB of urethritis in men that have been refractory to all other treatment have improYed ,,·ith Furacin urethral suppositories. The suppository method of medication has proved its ,rnrth. Several ease:-; of marked granular changes in the urethra have 11ot responded to Furncin uretlml auppm,itories. These ha.-ve responded slmvly to the old treatment of that of 10 per- ('eHt silver nitrate applications to the methra. ·with this in mind, sih·er rntrate suppositories are now in the process of manufacture for clinical trial.
Kannapolis Highway, Concord, N. C. REFERENCES
K: J. Urol., 30: 263, 19:33, B1-;RNs, EDu.rn AND B,;TT, A. J., South. Surg., 12: 352, Hl46. CARSON, R. B.: Urol. & Cutan. Rev., 51: 23, Hl47. F1mGusoN, CHARLES AND Niru.JcR, C. D.: ,J. UroL, 67: 762, 1952, FOLSOM, A. I. A:\'D O'BREJN, H. A,: J,A.M.1L, 128: 408, 1945. HEcKv!L, X J.: J. UroL, 35: 520, HJ36, HERB UT, l'. A.: Urological Pathology. Philadelphia: Lea and F'ebiger, 1952, vol. l, JJ, 56. LEBF~R.HA-'i, P. IL. UroL & Cut.an. Rev., 41: 584, 1937. Lr;\'TG~~N, CHARLES AND HERBUT·, P, A.: J. Urol., 55: 298, 1046. RoE:\i, P.R. Al'.'D STEPT, R.R.: Am, J. Dis. Child,, 72: 52D, 1946. SPENCE, H. lvL: J. Oro!., 43: 199, lD40. SwEE'rs"rn, T. H. JR. AND HARRISON, J, A.: J. UroL, 65: 684, 1951. ZunrEm11AK, L J.: Ne11· Eug, J. Med., 222: 221, 1940, BERRY,>:,.