- Email: [email protected]
Treatment of Candiduria Re: Genitourinary Fungal Infections, by Stephen Michigan, J. Urol., 116: 390–397, 1976 and Genitourinary Candidiasis: Diagnosis and Treatment, by Gilbert J. Wise, Philip Goldberg and Philip J. Kozinn, J. Urol., 116: 778–780, 1976
Vol. 117, June
THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
Printed in U.S .A.
Letters to the Editor PHENOXYBENZAMINE
TREATMENT OF CANDIDURIA
To the Editor. Recent literature has included many reports on the use of phenoxybenzamine (Dibenzyline) for the treatment of neurogenic bladders. Since introducing this drug in 1970 for the treatment of atonic neurogenic bladders, 1 I have used it in a large number of patients and wish to define its indications. Since the Food and Drug Administration has not given approval for phenoxybenzamine to be used in the treatment of bladder disorders, I believe that patients should be informed that the use of this drug for bladder dysfunction is experimental, although the drug itself has been used widely for the control of high blood pressure. The dosage ofphenoxybenzamine rarely needs to exceed 10 mg. a day, and 30 mg. a day commonly produces adverse effects such as sweating, dryness of the mouth and tachycardia. At 10 mg. a day there are rare, mild side effects. Postural hypotension is uncommon and dryness of the mouth occurs occasionally. If used for long periods the dosage needed is often only 10 mg. 2 to 3 times a week. It takes 4 to 5 days before an effective drug level is reached in the body, and one would not expect to see any effect on the bladder for this period. In normal people contraction of the detrusor opens the internal sphincter and allows voiding to proceed. There is passive relaxation of the internal sphincter. However, if the detrusor muscle does not contract, as in patients with atonic or hypotonic neurogenic bladders owing to spinal cord injury, anticholinergic drugs, diabetes and so forth, then the internal sphincter is not opened and this impedes bladder emptying. This is why patients with atonic bladders have large volumes of residual urine. Since the internal sphincter contracts under alpha-sympathetic stimulation, relaxation of the internal sphincter can be achieved by an alpha-sympathetic blocking agent, such as phenoxybenzamine or reserpine. The patient still must strain (Crede method) to void but improved bladder emptying is achieved. These drugs, then, are useful for the patient with an a tonic or hypotonic neurogenic bladder but have no value in patients with a spastic bladder. These drugs have no effect on the external sphincter (somatic innervation) or on the detrusor (parasympathetic innervation). Phcnvxybenzamine has bee!!. an extre!llely effective drug with minimal side effects when used for patients with poor detrusor contraction and obstruction at the internal sphincter. One patient has taken phenoxybenzamine for 6 years because of a cauda equina lesion causing an atonic bladder. The patient has been asymptomatic except for straining to void. I, also, have had occasional success using phenoxybenzamine in patients who have prostatic obstruction requiring catheter drainage and who have limited life expectancy. Catheter removal 4 or 5 days after starting phenoxybenzamine therapy has resulted in adequate voiding for a few months in these patients. As with any medication or operation, proper patient selection for appropriate indications must be used in order to achieve therapeutic success. Respectfully, Francis J. Kleeman 2000 Washington St. Newton Lower Falls, Massachusetis 02162 1. Kleeman, F. J.: The physiology of the internal urinary sphincter. J. Urol., 104: 549, 1970.
814
RE: GENITOURINARY FUNGAL INFECTIONS
Stephen Michigan J. Urol., 116: 390-397, 1976
and GENITOURINARY CANDIDIASIS: DIAGNOSIS AND TREATMENT
Gilbert J. Wise, Philip Goldberg and Philip J. Kozinn J. Urol., 116: 778-780, 1976 To the Editor. I enjoyed the excellent articles by Wise and associates, and Michigan on the diagnosis and treatment of candiduria in debilitated patients. Fungicidal studies of Candida albicans and other Candida species have shown that approximately 45 per cent of these yeasts are resistant to 100 mg. 5-flucytosine (5-FC) after 48 to 72 hours of incubation.1. 2 Two-thirds of Candida parapsilosis isolates were resistant to 100 mg. per ml. 1 As indicated by Wise and associates there was a 43 per cent failure rate in their candiduria patients who were treated with 5-FC alone. Also, as noted by Michigan, antibiotic resistance to 5-FC may develop while the patient is on therapy, although this occurs more frequently with Cryptococcus rather than with Candida.2 I emphasize these points because of my observation that many physicians use 5-FC frequently as the drug of first choice for candiduria. Few microbiology laboratories do Candida fungicidal sensitivity testing with a synthetic L-cysteine free medium and, therefore, most clinicians will not have reliable sensitivity data available to them. Therefore, "in patients who are severely debilitated, have grave underlying illnesses, or whose condition seriously deteriorates," I agree with Michigan that they are at risk to suffer a life-threatening fungal infection. However, in those patients who require treatment I would suggest the primary use of amphotericin B either by urinary irrigation or systemically; with 5-FC or rifampin to be used principally as combination synergistic drugs. Respectfully, Francis D. Pien Straub Clinic and Hospital Honolulu, Hawaii 96813 1. Shadomy, S., Kirchoff, C. B. and Ingroff, A. E.: In vitro activity
of 5-fluorocytosine against Candida and Torulopsis species. Antimicrob. Agents Chemother., 3: 9, 1973. 2. Shadomy, S.: Further in vitro studies with 5-fluorocytosine. Infec. Immunol., 2: 484, 1970.
Reply by Gilbert J. Wise. I would agree with Doctor Pien that in vitro fungicidal sensitivity testing is most ideal if available. However, our experience with the 5-FC indicates that its side effects are few and far between in contrast to the intravenous administration of amphotericin B, which often makes the patient feel quite toxic. Thus, I believe that if in vitro sensitivities are not available the empiric use of 5-FC in doses of 150 to 200 mg. per kg. per day would be appropriate in the treatment of disseminated or deep-seated urinary candidal infection.
THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
Printed in U.S .A.
Letters to the Editor PHENOXYBENZAMINE
TREATMENT OF CANDIDURIA
To the Editor. Recent literature has included many reports on the use of phenoxybenzamine (Dibenzyline) for the treatment of neurogenic bladders. Since introducing this drug in 1970 for the treatment of atonic neurogenic bladders, 1 I have used it in a large number of patients and wish to define its indications. Since the Food and Drug Administration has not given approval for phenoxybenzamine to be used in the treatment of bladder disorders, I believe that patients should be informed that the use of this drug for bladder dysfunction is experimental, although the drug itself has been used widely for the control of high blood pressure. The dosage ofphenoxybenzamine rarely needs to exceed 10 mg. a day, and 30 mg. a day commonly produces adverse effects such as sweating, dryness of the mouth and tachycardia. At 10 mg. a day there are rare, mild side effects. Postural hypotension is uncommon and dryness of the mouth occurs occasionally. If used for long periods the dosage needed is often only 10 mg. 2 to 3 times a week. It takes 4 to 5 days before an effective drug level is reached in the body, and one would not expect to see any effect on the bladder for this period. In normal people contraction of the detrusor opens the internal sphincter and allows voiding to proceed. There is passive relaxation of the internal sphincter. However, if the detrusor muscle does not contract, as in patients with atonic or hypotonic neurogenic bladders owing to spinal cord injury, anticholinergic drugs, diabetes and so forth, then the internal sphincter is not opened and this impedes bladder emptying. This is why patients with atonic bladders have large volumes of residual urine. Since the internal sphincter contracts under alpha-sympathetic stimulation, relaxation of the internal sphincter can be achieved by an alpha-sympathetic blocking agent, such as phenoxybenzamine or reserpine. The patient still must strain (Crede method) to void but improved bladder emptying is achieved. These drugs, then, are useful for the patient with an a tonic or hypotonic neurogenic bladder but have no value in patients with a spastic bladder. These drugs have no effect on the external sphincter (somatic innervation) or on the detrusor (parasympathetic innervation). Phcnvxybenzamine has bee!!. an extre!llely effective drug with minimal side effects when used for patients with poor detrusor contraction and obstruction at the internal sphincter. One patient has taken phenoxybenzamine for 6 years because of a cauda equina lesion causing an atonic bladder. The patient has been asymptomatic except for straining to void. I, also, have had occasional success using phenoxybenzamine in patients who have prostatic obstruction requiring catheter drainage and who have limited life expectancy. Catheter removal 4 or 5 days after starting phenoxybenzamine therapy has resulted in adequate voiding for a few months in these patients. As with any medication or operation, proper patient selection for appropriate indications must be used in order to achieve therapeutic success. Respectfully, Francis J. Kleeman 2000 Washington St. Newton Lower Falls, Massachusetis 02162 1. Kleeman, F. J.: The physiology of the internal urinary sphincter. J. Urol., 104: 549, 1970.
814
RE: GENITOURINARY FUNGAL INFECTIONS
Stephen Michigan J. Urol., 116: 390-397, 1976
and GENITOURINARY CANDIDIASIS: DIAGNOSIS AND TREATMENT
Gilbert J. Wise, Philip Goldberg and Philip J. Kozinn J. Urol., 116: 778-780, 1976 To the Editor. I enjoyed the excellent articles by Wise and associates, and Michigan on the diagnosis and treatment of candiduria in debilitated patients. Fungicidal studies of Candida albicans and other Candida species have shown that approximately 45 per cent of these yeasts are resistant to 100 mg. 5-flucytosine (5-FC) after 48 to 72 hours of incubation.1. 2 Two-thirds of Candida parapsilosis isolates were resistant to 100 mg. per ml. 1 As indicated by Wise and associates there was a 43 per cent failure rate in their candiduria patients who were treated with 5-FC alone. Also, as noted by Michigan, antibiotic resistance to 5-FC may develop while the patient is on therapy, although this occurs more frequently with Cryptococcus rather than with Candida.2 I emphasize these points because of my observation that many physicians use 5-FC frequently as the drug of first choice for candiduria. Few microbiology laboratories do Candida fungicidal sensitivity testing with a synthetic L-cysteine free medium and, therefore, most clinicians will not have reliable sensitivity data available to them. Therefore, "in patients who are severely debilitated, have grave underlying illnesses, or whose condition seriously deteriorates," I agree with Michigan that they are at risk to suffer a life-threatening fungal infection. However, in those patients who require treatment I would suggest the primary use of amphotericin B either by urinary irrigation or systemically; with 5-FC or rifampin to be used principally as combination synergistic drugs. Respectfully, Francis D. Pien Straub Clinic and Hospital Honolulu, Hawaii 96813 1. Shadomy, S., Kirchoff, C. B. and Ingroff, A. E.: In vitro activity
of 5-fluorocytosine against Candida and Torulopsis species. Antimicrob. Agents Chemother., 3: 9, 1973. 2. Shadomy, S.: Further in vitro studies with 5-fluorocytosine. Infec. Immunol., 2: 484, 1970.
Reply by Gilbert J. Wise. I would agree with Doctor Pien that in vitro fungicidal sensitivity testing is most ideal if available. However, our experience with the 5-FC indicates that its side effects are few and far between in contrast to the intravenous administration of amphotericin B, which often makes the patient feel quite toxic. Thus, I believe that if in vitro sensitivities are not available the empiric use of 5-FC in doses of 150 to 200 mg. per kg. per day would be appropriate in the treatment of disseminated or deep-seated urinary candidal infection.