20 Proc. roy. Soc. Med. Volume 70 1977 Supplement 1
Miconazole in Systemic Candidosis by Dr M Hatala (Institutefor Clinical and Experimental Medicine, Prague, Czechoslovakia)
(paper delivered by Mr M Becvar) In the past two decades the occurrence of mycotic infections has increased with the growing use of antibiotic, cytostatic and immunosuppressant agents. In spite of considerable progress, many therapeutic problems still remain unsolved. This is due mainly to a lack of suitable antimycotic compounds. Imidazole compounds are a group of chemotherapeutic agents having an antifungal effect. Besides being applied locally, they are chiefly used in the management of systemic mycoses. So far there is limited clinical experience with their therapeutic possibilities. One of these drugs, miconazole, was recently used in the treatment of systemic candidosis in 7 patients. This communication reports the results obtained. Miconazole was given either, both orally and intravenously, or orally alone after termination or parenteral administration. Its potential adverse effects together with hmematological, biochemical and other parameters were observed during the therapy. However, their precise evaluation is problematic, since miconazole was administered in combination with other drugs such as antibiotics, immunosuppressants and antituberculotics which alone, or through interaction with miconazole, may influence the studied para-
Mr M Becvar Case 2 (Table 2) R E, a 44-year-old renal transplant patient was readmitted three months after transplantation with raised temperature and thrombophlebitis in the left leg. He was put on erythromycin. His condition was
complicated by pulmonary embolia and bronchopneumonia associated with severe respiratory insufficiency. Staphylococcus aureus was cultured from the blood and sputum culture repeatedly showed a massive number of C. albicans and klebsiella. The patient was treated with gentamycin, kanamycin, oxacillin, cephalexin and trimethoprim, in that order. Azathioprine therapy was interrupted and antibiotic therapy combined with miconazole was initiated, the latter lasting for 16 days. Despite the fact that the clinical symptoms of bronchopneumonia subsided during therapy, the patient died of subacute meters. ulcerothrombotic endocarditis and septic infarction of the lungs and spleen, with the presence of staphylococci. Culture and microscopy of homogenized lungs Case 1 (Table 1) K V, a 61-year-old renal transplant patient was and spleen did not confirm the presence of candida. treated with gentamycin and nalidixin two weeks after Miconazole was well tolerated by the patient. operation for colibacillary and pseudomonas infection of the urogenital tract and proteus infection of the unhealed wound. The patient had high temperatures and severe cachexia. During therapy a massive finding of Candida albicans occurred in the urine, stool and repeatedly in the wound. To prevent generalization of the mycotic infection in this immunosuppressed patient, miconazole was administered for 13 days. In addition, the drug was applied locally into the wound for 26 days. The wound healed and findings in the wound and stool became mycologically negative. Insignificant numbers of C. albicans persisted for a limited period after the termination of therapy in cultures of urine. Candidal infection did not generalize, the clinical status normalized and the patient was dismissed in good condition. Miconazole did not elicit any adverse effects.
Case 3 (Table 3) H I, a 23-year-old woman with a transplanted kidney was hospitalized a year after transplantation with suspected 'transplant lung' associated with persistent cough, purulent expectoration and respiratory insufficiency. She was treated with septrin, oxacillin, streptomycin and high doses of hydrocortisone. Despite this therapy, severe respiratory insufficiency with purulent expectoration persisted; culture and laryngeal swabs repeatedly revealed the presence of massive numbers of C. albicans. To prevent generalization of mycotic infection, gentamycin therapy was combined with miconazole given intravenously through a permanent catheter in the subclavian vein. This therapy lasting 11 days was discontinued to avoid superinfection and the combination of gentamycin and miconazole was administered,
21
Systemic Mycoses
Table I Patient K V, male aged 61, kidney transplant
Miconazole treatment Diagnosis Infection of urogenital tract and wound (high fever, cachexia)
Cultures (1) Before miconazole: Urine: E. coli, P. aeruginosa, C. albicans
Other drugs Azathioprine, prednisone, gentamycin, nalidixin
Route, dose (mg) Intravenous, 600 Oral, 750-1500 Local
Total dose (g) 9.6
Duration Assessment (days) oj treatmenit 13 Good
10.5
Side-
effects None
9
26
Wound: proteus, C. albicans Stool: C. albicans (2) After miconazole: Urine: a decreased amount of C. albicans
Table 2 Patient R E, male aged 44, kidney tranplant
Miconazole treatment Other drugs Cultures Thrombophlebitis (I) Before miconazole: Azathioprine, crural (fever, pain) prednisone, S. aureus erythromycin, Pulmonary embolism gentamycin, Sputum: kanamycin, Bronchopneumonia Klebsiella, C. albicans oxacillin, (respiratory trimethoprim insufficiency) (2) After miconazole: Azathioprine Lungs and spleen negative Diagnosis
Total Route, dose (mg) dose (g) 9.6 Intravenous, 600
Duration Side(days) effects None 16
Oral,
10
20.0
2000
This patient died. Diagnosis: endocarditis ulcerothrombotica infarctus embolico-mycetici pulmonarius et lienis
Table 3 Patient H I, female aged 23, kidney transplant
Miconazole treatment Diagnosis
Respiratory insufficiency (purulent cough) 'Transplant lung'
Cultures (1) Before miconazole: Sputum: E. coli, Enterobacter, Klebsiella Sputum: C. albicans Larynx: C. albicans
(2) After miconazole: Mycology negative
Other drugs
Azathioprine, prednisone, trimethoprim, oxacillin, streptomycin, hydrocortisone, gentamycin Trimethoprim
Total Route, dose (mg) dose (g) Intra6.6 venous, 600 54.0 Oral, 2000
Duration Assessment Sideof treatment effects (days) 11 Good Pathological renal and liver function test (chronic rejection 27 nephropathy)
Table 4 Patient P M, male aged 22, kidney transplant Miconazole treatment Diagnosis Kidney rejection, infection of urogenital tract (fever)
Cultures (1) Before miconazole: Urine: P. wruginosa C. albicans Proteus (2) After miconazole: Urine: a decreased amount of C. albicans
Other drugs Azathioprine, prednisone, gentamycin, amphotericin, nalidixin,
trimethoprim
Total Route, dose (mg) dose (g) 7 Intravenous 600-1000 30 Oral, 3000
Duration Assessment treatment (days) 11 Good 10
Side-
effects None
22 Proc. roy. Soc. Med. Volume 70 1977 Supplement I Table 5 Patient S M, female aged 44, malignant lymphogranuloma (stage IV) Miconazole treatment Diagnosis Irradiation Bronchopneumonia bilateral interstitial Suspected pulmonary tuberculosis (high fever, X-ray positive)
Cultures (1) Before miconazole: Sputum: C. albicans Mesopharynx: C. albicans (2) After miconazole: 14 days Sputum: C. albicans
Total Route, dose (mg) dose (g) 6 IntraIsoniazid, venous rifampicin, streptomycin, 600 7 Oral, prednisone 500 Other drugs
Duration (days) 10
Assessment SIdeof treatment effects Leukopenia Good
14
The patient died after one month, from primary disease
Table 6 Patient R R, male aged 45, congenital stenosis of pilmonary lingula
Miconazole treatment Diagnosis Viral pneumonia Bacterial
bronchopneumonia (X-ray positive)
Other drugs Cultures (1) Before miconazole: Cephalexin Sputum: C. albicans Mesopharynx: C. albicans (2) After miconazole: Sputum, mesopharynx, bronchi: Mycologically negative
Total Route, dose (mg) dose (g) 7.8 Intravenous, 600 19.0 Oral, 500
Duration Assessment Sideoftreatment effects (days) Erythema and Good 13
lymphaedema in the region of application 38
Table 7 Patient Z H, female aged 24, staphylococcal pneumonia
Miconazole treatment Cultures (1) Before miconazole: Sputum: Staph. aureus, C. albicans (fever Blood: C. albicans respiratory Urine: C. albicans insufficiency X-ray positive) Stool: C. albicans Tracheotomy (2) After miconazole: Artificial Mycologically negative ventilation Diagnosis Bilateral pneumonia
Route, Other drugs IntraPenicillin, venous streptomycin, cephalexin, gentamycin, chloramphenicol, oxacillin
Total dose (g) 8.4
(days)
Assessment Sideof treatment effects
14
Good
Duration
None
(high fever)
Candid3mia
the latter being given orally. Following clinical improvement of respiratory insufficiency all medication but septrin was discontinued. Culture of the sputum continued to be negative. A month after termination of the antimycotic therapy the patient was discharged in a good clinical state. Reduced renal function and pathological changes in SGOT and SGPT values developed during miconazole therapy. A gradual decrease in renal function, diagnosed as chronic rejection nephropathy had, however, been observed before the onset of antimycotic therapy. Case 4 (Table 4) P M, a male renal transplant patient aged 22 was treated for early graft rejection with high doses of corticoids and for concomitant significant proteus and pseudomonas infection with gentamycin. A significant
candidal infection (accompanied by high temperature) was detected in the urine during therapy. Amphotericin therapy having failed, miconazole was given for 12 days. The concomitant significant proteus bacteruria wastreatedwith nalidixin and trimethoprim. The patient's clinical state improved but without complete mycological clearance of the urine. Therapy with miconazole was well tolerated by the patient. Four months later he was again hospitalized for a high temperature with diagnosis of bacillary meningitis. Specific therapy with isoniazid, tibutol and rifampicin was initiated. C. albicans was repeatedly demonstrated in liquor. Intravenous therapy with miconazole was therefore initiated. After 13 days, treatment had to be discontinued because of nausea, vomiting and hyperpyrexia. Animia, leukopenia and changes in the SPGT liver test appeared. The finding in liquor remained positive.
Systemic Mycoses Case 5 (Table 5) S M, a 44-year-old woman with Hodgkin's disease (stage IV) was hospitalized after regional irradiation for severe bilateral interstitial mycotic bronchopneumonia with high temperature and positive X-ray. C. albicans was repeatedly cultured from sputum and mesopharyngeal swabs. The patient was therefore treated with miconazole, first given intravenously for 10 days and thereafter orally for -two weeks. She also received antituberculostatics and prednisone. The clinical state normalized and the high temperature disappeared. For technical reasons, the patient was transferred to another hospital where she died about a month later of the primary disease, with a white blood cell count of 200/mms before death. Miconazole did not elicit any adverse effects. Case 6 (Table 6) R R, a 45-year-old man with bronchial congenital stenosis of the pulmonary lingula was admitted with bacterial bronchopneumonia after viral disease. He was treated with miconazole for a repeated massive finding of C. albicans in the sputum and mesopharynx After 13 days, intravenous administration was discontinued owing to erythema and lymphiedema at the site of application. Thereafter, miconazole was given orally for another 38 days. This route of application did not produce any adverse effects. The patient's clinical status normalized. Findings in the sputum and mesopharynx were negative, including both X-ray and bronchoscopy investigations. Case 7 (Table 7) Z H, a 24-year-old woman, was hospitalized for
extensive bilateral staphylococcal pneumonia resulting in severe acute respiratory insufficiency. Massive antibiotic medication, i.e. penicillin, streptomycin, chloramphenicol, oxacillin and gentamycin, was therefore initiated. The patient's condition required tracheotomy and artificial ventilation using positive expiration pressure. The primary disease was associated with massive C. albicans and C. krusei infection in the sputum, stool, urine and blood together with high temperature. Her state was diagnosed as generalized candidosis. Intravenous therapy with miconazole was therefore started and continued for two weeks, which led to clinical normalization and negative findings in all the above mentioned materials. The therapy did not produce any adverse effects. Judging by the results obtained, it seems that miconazole is an effective antimycotic drug and currently our most valuable medication for the treatment of severe systemic mycotic infections.
Summary Results are reported on the effect of miconazole together with concurrent medication in the treatment of 7 patients with systemic candidiasis. Two patients were discharged from hospital in good condition. In two others, the clinical status normalized. One patient's status improved but he was subsequently readmitted. Two patients died. The excellent tolerance of miconazole by all patients was a particular feature of this trial.
23
DISCUSSION
Dr R P Mouton (Utrecht) wondered whether the dose of 500 mg of miconazole given orally after initial intravenous treatment would produce high enough blood levels. He asked whether any blood level estimations had been performed. Dr Hatala said the blood levels had not been checked in these patients. All of the patients were very severe cases. The aim was the sterilization of gastrointestinal tract. In reply to Dr Mouton's further question, whether 500 mg of miconazole orally after intravenous treatment had any influence on gastrointestinal candida, Dr Hatala said they believed that it was more effective when given both orally and intravenously, but confirmed that they had continued the therapy after two weeks with oral miconazole only.
Professor K Bartmann ( Wuelfrath) noted that they had isolated candida from sputum in 3 of their cases, and asked how, after massive antibacterial treatment, they could differentiate between colonization and infection in these cases. Dr Hatala said that culture was performed immediately after the termination of therapy. In a case of repeated proof of the presence of infection, accompanied by clinical manifestation, they continued the treatment. Dr 0 Heltberg (Vefle) asked when sputum was characterized as being general sputum or, in some cases, sputum from the mesopharynx, how did Dr Hatala differentiate between them. Was the distinction based on microscopy or on the way in which the sputum was obtained?
Professor Vanbreuseghem (Chairman) added that this was the same as deciding whether Candida albicans was a contaminant or an invasive organism. Dr Hatala said the distinction was based on the smear resulting from the bronchoscopy findings.
Miconazole in Systemic Candidosis by Dr M Hatala (Institutefor Clinical and Experimental Medicine, Prague, Czechoslovakia)
(paper delivered by Mr M Becvar) In the past two decades the occurrence of mycotic infections has increased with the growing use of antibiotic, cytostatic and immunosuppressant agents. In spite of considerable progress, many therapeutic problems still remain unsolved. This is due mainly to a lack of suitable antimycotic compounds. Imidazole compounds are a group of chemotherapeutic agents having an antifungal effect. Besides being applied locally, they are chiefly used in the management of systemic mycoses. So far there is limited clinical experience with their therapeutic possibilities. One of these drugs, miconazole, was recently used in the treatment of systemic candidosis in 7 patients. This communication reports the results obtained. Miconazole was given either, both orally and intravenously, or orally alone after termination or parenteral administration. Its potential adverse effects together with hmematological, biochemical and other parameters were observed during the therapy. However, their precise evaluation is problematic, since miconazole was administered in combination with other drugs such as antibiotics, immunosuppressants and antituberculotics which alone, or through interaction with miconazole, may influence the studied para-
Mr M Becvar Case 2 (Table 2) R E, a 44-year-old renal transplant patient was readmitted three months after transplantation with raised temperature and thrombophlebitis in the left leg. He was put on erythromycin. His condition was
complicated by pulmonary embolia and bronchopneumonia associated with severe respiratory insufficiency. Staphylococcus aureus was cultured from the blood and sputum culture repeatedly showed a massive number of C. albicans and klebsiella. The patient was treated with gentamycin, kanamycin, oxacillin, cephalexin and trimethoprim, in that order. Azathioprine therapy was interrupted and antibiotic therapy combined with miconazole was initiated, the latter lasting for 16 days. Despite the fact that the clinical symptoms of bronchopneumonia subsided during therapy, the patient died of subacute meters. ulcerothrombotic endocarditis and septic infarction of the lungs and spleen, with the presence of staphylococci. Culture and microscopy of homogenized lungs Case 1 (Table 1) K V, a 61-year-old renal transplant patient was and spleen did not confirm the presence of candida. treated with gentamycin and nalidixin two weeks after Miconazole was well tolerated by the patient. operation for colibacillary and pseudomonas infection of the urogenital tract and proteus infection of the unhealed wound. The patient had high temperatures and severe cachexia. During therapy a massive finding of Candida albicans occurred in the urine, stool and repeatedly in the wound. To prevent generalization of the mycotic infection in this immunosuppressed patient, miconazole was administered for 13 days. In addition, the drug was applied locally into the wound for 26 days. The wound healed and findings in the wound and stool became mycologically negative. Insignificant numbers of C. albicans persisted for a limited period after the termination of therapy in cultures of urine. Candidal infection did not generalize, the clinical status normalized and the patient was dismissed in good condition. Miconazole did not elicit any adverse effects.
Case 3 (Table 3) H I, a 23-year-old woman with a transplanted kidney was hospitalized a year after transplantation with suspected 'transplant lung' associated with persistent cough, purulent expectoration and respiratory insufficiency. She was treated with septrin, oxacillin, streptomycin and high doses of hydrocortisone. Despite this therapy, severe respiratory insufficiency with purulent expectoration persisted; culture and laryngeal swabs repeatedly revealed the presence of massive numbers of C. albicans. To prevent generalization of mycotic infection, gentamycin therapy was combined with miconazole given intravenously through a permanent catheter in the subclavian vein. This therapy lasting 11 days was discontinued to avoid superinfection and the combination of gentamycin and miconazole was administered,
21
Systemic Mycoses
Table I Patient K V, male aged 61, kidney transplant
Miconazole treatment Diagnosis Infection of urogenital tract and wound (high fever, cachexia)
Cultures (1) Before miconazole: Urine: E. coli, P. aeruginosa, C. albicans
Other drugs Azathioprine, prednisone, gentamycin, nalidixin
Route, dose (mg) Intravenous, 600 Oral, 750-1500 Local
Total dose (g) 9.6
Duration Assessment (days) oj treatmenit 13 Good
10.5
Side-
effects None
9
26
Wound: proteus, C. albicans Stool: C. albicans (2) After miconazole: Urine: a decreased amount of C. albicans
Table 2 Patient R E, male aged 44, kidney tranplant
Miconazole treatment Other drugs Cultures Thrombophlebitis (I) Before miconazole: Azathioprine, crural (fever, pain) prednisone, S. aureus erythromycin, Pulmonary embolism gentamycin, Sputum: kanamycin, Bronchopneumonia Klebsiella, C. albicans oxacillin, (respiratory trimethoprim insufficiency) (2) After miconazole: Azathioprine Lungs and spleen negative Diagnosis
Total Route, dose (mg) dose (g) 9.6 Intravenous, 600
Duration Side(days) effects None 16
Oral,
10
20.0
2000
This patient died. Diagnosis: endocarditis ulcerothrombotica infarctus embolico-mycetici pulmonarius et lienis
Table 3 Patient H I, female aged 23, kidney transplant
Miconazole treatment Diagnosis
Respiratory insufficiency (purulent cough) 'Transplant lung'
Cultures (1) Before miconazole: Sputum: E. coli, Enterobacter, Klebsiella Sputum: C. albicans Larynx: C. albicans
(2) After miconazole: Mycology negative
Other drugs
Azathioprine, prednisone, trimethoprim, oxacillin, streptomycin, hydrocortisone, gentamycin Trimethoprim
Total Route, dose (mg) dose (g) Intra6.6 venous, 600 54.0 Oral, 2000
Duration Assessment Sideof treatment effects (days) 11 Good Pathological renal and liver function test (chronic rejection 27 nephropathy)
Table 4 Patient P M, male aged 22, kidney transplant Miconazole treatment Diagnosis Kidney rejection, infection of urogenital tract (fever)
Cultures (1) Before miconazole: Urine: P. wruginosa C. albicans Proteus (2) After miconazole: Urine: a decreased amount of C. albicans
Other drugs Azathioprine, prednisone, gentamycin, amphotericin, nalidixin,
trimethoprim
Total Route, dose (mg) dose (g) 7 Intravenous 600-1000 30 Oral, 3000
Duration Assessment treatment (days) 11 Good 10
Side-
effects None
22 Proc. roy. Soc. Med. Volume 70 1977 Supplement I Table 5 Patient S M, female aged 44, malignant lymphogranuloma (stage IV) Miconazole treatment Diagnosis Irradiation Bronchopneumonia bilateral interstitial Suspected pulmonary tuberculosis (high fever, X-ray positive)
Cultures (1) Before miconazole: Sputum: C. albicans Mesopharynx: C. albicans (2) After miconazole: 14 days Sputum: C. albicans
Total Route, dose (mg) dose (g) 6 IntraIsoniazid, venous rifampicin, streptomycin, 600 7 Oral, prednisone 500 Other drugs
Duration (days) 10
Assessment SIdeof treatment effects Leukopenia Good
14
The patient died after one month, from primary disease
Table 6 Patient R R, male aged 45, congenital stenosis of pilmonary lingula
Miconazole treatment Diagnosis Viral pneumonia Bacterial
bronchopneumonia (X-ray positive)
Other drugs Cultures (1) Before miconazole: Cephalexin Sputum: C. albicans Mesopharynx: C. albicans (2) After miconazole: Sputum, mesopharynx, bronchi: Mycologically negative
Total Route, dose (mg) dose (g) 7.8 Intravenous, 600 19.0 Oral, 500
Duration Assessment Sideoftreatment effects (days) Erythema and Good 13
lymphaedema in the region of application 38
Table 7 Patient Z H, female aged 24, staphylococcal pneumonia
Miconazole treatment Cultures (1) Before miconazole: Sputum: Staph. aureus, C. albicans (fever Blood: C. albicans respiratory Urine: C. albicans insufficiency X-ray positive) Stool: C. albicans Tracheotomy (2) After miconazole: Artificial Mycologically negative ventilation Diagnosis Bilateral pneumonia
Route, Other drugs IntraPenicillin, venous streptomycin, cephalexin, gentamycin, chloramphenicol, oxacillin
Total dose (g) 8.4
(days)
Assessment Sideof treatment effects
14
Good
Duration
None
(high fever)
Candid3mia
the latter being given orally. Following clinical improvement of respiratory insufficiency all medication but septrin was discontinued. Culture of the sputum continued to be negative. A month after termination of the antimycotic therapy the patient was discharged in a good clinical state. Reduced renal function and pathological changes in SGOT and SGPT values developed during miconazole therapy. A gradual decrease in renal function, diagnosed as chronic rejection nephropathy had, however, been observed before the onset of antimycotic therapy. Case 4 (Table 4) P M, a male renal transplant patient aged 22 was treated for early graft rejection with high doses of corticoids and for concomitant significant proteus and pseudomonas infection with gentamycin. A significant
candidal infection (accompanied by high temperature) was detected in the urine during therapy. Amphotericin therapy having failed, miconazole was given for 12 days. The concomitant significant proteus bacteruria wastreatedwith nalidixin and trimethoprim. The patient's clinical state improved but without complete mycological clearance of the urine. Therapy with miconazole was well tolerated by the patient. Four months later he was again hospitalized for a high temperature with diagnosis of bacillary meningitis. Specific therapy with isoniazid, tibutol and rifampicin was initiated. C. albicans was repeatedly demonstrated in liquor. Intravenous therapy with miconazole was therefore initiated. After 13 days, treatment had to be discontinued because of nausea, vomiting and hyperpyrexia. Animia, leukopenia and changes in the SPGT liver test appeared. The finding in liquor remained positive.
Systemic Mycoses Case 5 (Table 5) S M, a 44-year-old woman with Hodgkin's disease (stage IV) was hospitalized after regional irradiation for severe bilateral interstitial mycotic bronchopneumonia with high temperature and positive X-ray. C. albicans was repeatedly cultured from sputum and mesopharyngeal swabs. The patient was therefore treated with miconazole, first given intravenously for 10 days and thereafter orally for -two weeks. She also received antituberculostatics and prednisone. The clinical state normalized and the high temperature disappeared. For technical reasons, the patient was transferred to another hospital where she died about a month later of the primary disease, with a white blood cell count of 200/mms before death. Miconazole did not elicit any adverse effects. Case 6 (Table 6) R R, a 45-year-old man with bronchial congenital stenosis of the pulmonary lingula was admitted with bacterial bronchopneumonia after viral disease. He was treated with miconazole for a repeated massive finding of C. albicans in the sputum and mesopharynx After 13 days, intravenous administration was discontinued owing to erythema and lymphiedema at the site of application. Thereafter, miconazole was given orally for another 38 days. This route of application did not produce any adverse effects. The patient's clinical status normalized. Findings in the sputum and mesopharynx were negative, including both X-ray and bronchoscopy investigations. Case 7 (Table 7) Z H, a 24-year-old woman, was hospitalized for
extensive bilateral staphylococcal pneumonia resulting in severe acute respiratory insufficiency. Massive antibiotic medication, i.e. penicillin, streptomycin, chloramphenicol, oxacillin and gentamycin, was therefore initiated. The patient's condition required tracheotomy and artificial ventilation using positive expiration pressure. The primary disease was associated with massive C. albicans and C. krusei infection in the sputum, stool, urine and blood together with high temperature. Her state was diagnosed as generalized candidosis. Intravenous therapy with miconazole was therefore started and continued for two weeks, which led to clinical normalization and negative findings in all the above mentioned materials. The therapy did not produce any adverse effects. Judging by the results obtained, it seems that miconazole is an effective antimycotic drug and currently our most valuable medication for the treatment of severe systemic mycotic infections.
Summary Results are reported on the effect of miconazole together with concurrent medication in the treatment of 7 patients with systemic candidiasis. Two patients were discharged from hospital in good condition. In two others, the clinical status normalized. One patient's status improved but he was subsequently readmitted. Two patients died. The excellent tolerance of miconazole by all patients was a particular feature of this trial.
23
DISCUSSION
Dr R P Mouton (Utrecht) wondered whether the dose of 500 mg of miconazole given orally after initial intravenous treatment would produce high enough blood levels. He asked whether any blood level estimations had been performed. Dr Hatala said the blood levels had not been checked in these patients. All of the patients were very severe cases. The aim was the sterilization of gastrointestinal tract. In reply to Dr Mouton's further question, whether 500 mg of miconazole orally after intravenous treatment had any influence on gastrointestinal candida, Dr Hatala said they believed that it was more effective when given both orally and intravenously, but confirmed that they had continued the therapy after two weeks with oral miconazole only.
Professor K Bartmann ( Wuelfrath) noted that they had isolated candida from sputum in 3 of their cases, and asked how, after massive antibacterial treatment, they could differentiate between colonization and infection in these cases. Dr Hatala said that culture was performed immediately after the termination of therapy. In a case of repeated proof of the presence of infection, accompanied by clinical manifestation, they continued the treatment. Dr 0 Heltberg (Vefle) asked when sputum was characterized as being general sputum or, in some cases, sputum from the mesopharynx, how did Dr Hatala differentiate between them. Was the distinction based on microscopy or on the way in which the sputum was obtained?
Professor Vanbreuseghem (Chairman) added that this was the same as deciding whether Candida albicans was a contaminant or an invasive organism. Dr Hatala said the distinction was based on the smear resulting from the bronchoscopy findings.
