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An acute psychotic disorder caused by pefloxacin: A case report
Prcg. Newo-PsychopharmacoL
&Bid
Psychiat.
Copyright 0
1996. Vol. 20. pp. 343-347 1996 Elsevier Science Inc.
SSDIO279-5946(95)00314-2
ELSEVIER
0276 - 6646/96 $32.00
AN ACUTE PSYCHOTIC DISORDER CAUSED BY PEFLOXACIN: A CASE REPORT BERND HEOLINGER. BERNHARD HELLWIG. URBAN SESTER. J6RG WALDEN and MATTHlAS BERGER Department of Psychiatry, University of Freiburg, HauptstraOe, Freiburg, Germany
(Final form, October 1995)
Abstract HeDlinger. Bemd. Bernhard Hellwig, Urban Sester. Jiirg Walden and Matthias Berger: An Acute Psychotic Disorder Caused by Pefloxacin: A Case Report. Prog. Neuro-Psychopharmacol & Biol.Psychiat. 1996.201
I. The patient, a 59 year old woman, developped a state of acute excitatton several hours after the administration of 400 mg of the fluorquinolone pefloxacin in combination with 1000 mg paracetamol. Nine days later. after a total dosage of pefloxacin of 800 mg, she was admitted to our hospital with a psychotic disorder. 2. There was a full remission of symptoms after treatment with perazine up to a dosage of 500 mgiday. 3. Three years ago, the patient had developped a manic state under a medication with corticosteroids. 4. So far. the mechanism of - in this case - long-lasting central nervous side effects of fluorquinolones is not known. In pattents with increased vulnerability of the CNS or in advanced age the application of fluorquinolones should be considered critically, in particular in combination with non-steroidal antimflammatory drugs. Kevwords: fluorquinolones, paracetamol, pefloxacin, perazine. psychosis
Introduction
Since the early 1980s fluorquinolones
such as norfIoxacin, ofloxacin. ctprofloxacin, or pefloxacin have been
used mainly in the treatment of urinary tract infections. Fluorquinolones are also called ‘gyrase-inhibitors’ because of their inhibiting effect on bacterial DNA-gyrases. By controlling the formation of ..supercoils“ the DNA-gyrase is a crucial factor in the synthesis. transcription and recombination of DNA. Pefloxacin is quickly and almost completely absorbed when administered orally. Its half life (1 I h) is by far the longest of the substances mentioned above. It may be significantly prolonged by a pathological liver conditton. About 10% of the patients treated with fluorqumolones develop side effects, most commonly gastrointestinal symptoms. CNS disturbances such as increased excitability, insomnia or dizzmess have been observed. Confusion, psychotic syndromes, hallucinations
or epileptic seizures (Simpson and Brodie 1985) have heen
rarely described.
Case Report
Our patient A. T.. a 59 year old woman, was treated by her general practitioner with pefloxacin (2 x 400 mg in 2 days) and paracetamol (1000 mg) because of an urinary tract infection. Several hours after the first drug 343
344
B. HeBlinger
et al.
intake the patient was in a state of exitation wtth euphorta. During the following days she had also dtfficulty m sleepmg and concentrating. According to the patient’s family she was intermittently conmsed. Nine days after the administration of a total dosage of 800 mg pefloxacin she was admitted to our hospttal. The patient was then fully oriented. She was in a state of psychomotor agttation. Thinking was incoherent and assoctations were loosenend. Her behaviour was partly bizarre. There were ideas of reference. The panent denied hallucinattons. hallucinations.
Two independent psychiatrists had the impression the patient was having acusncal
The affect was labile, but predominantly
euphoric.
Three years ago the patient had received corticosteroids because of a bullous exanthema. According to her family she developped then a manic syndrome which disappeared without psychiatrtc treatment several days after discontinuation of the corticosteroids. Since that time she never got corttcosteroids. There were no sertous illnesses in the patient’s history, in particular no psychiatric disorders. Also in the family history, psychiatrtc disorders had not occurred. The patient had not left Europe for 21 years. before she had lived a number of years m Africa and South America. According to the patient’s general practitioner the urmary tract infection was accompanied by a slight increase of the transaminases.
whtch may have been caused by the consumption of %
to % I wine per day for a period of several months. The physical examination of the pattent was normal. Extensive laboratory tests gave no signs of a significant liver impairment. An EEG, an ECG and a cramal CT scan did not reveal any significant abnormalities.
Therapv Under a medication with perazine up to a dosage of 500 mg/day there was first a considerable tmprovement of the thought disorders and the bizarre behaviour. After three days of treatment the panent was in a hypomanic state. and after nine days the medication was stopped, since there was a complete remission of symptoms. Due to a relapse of the hypomanic state the patient received 100 mg perazine for another 3 days. Again, the psychopathological
picture stabilized quickly. 10 days after tapering off the medication the patient left our
hospital in a state of complete remission.
Discussion Fluorquinolones penetrate into the cerebrospinal fluid. A good passage into the cerebrospmal fluid could be shown for pefloxacin (Wolff et al. 1984, Dow et al. 1986) as well as for ofloxacin (Stahl et al. 1986. Stiibner et al. 1986). Boerema et al. (1986) reported that 34 out of 104 patients who were treated with a daily dosage of 2 x 400 mg pefloxacin for a period of 10 days developped side effects, 50% of which were gastrointestinal,
17%
neurological (not specified in more detail) and 17% allergic. 9% of these side effects were clearly due to pefloxacin. In 4 patients side effects were considered as severe. 3 out of these 4 patients were older than average, the average age of the 104 patients being above 60 years. Lauwers et al. (1986) treated 16 patients in an intensive care unit (age median: 65 years) intravenously with 400 mg pefloxacin two to three times per day. Treatment was continued for an average of 11 days. Side effects were not observed in this study.
Acute
Psychotic
Disorder
by Pefloxacin:
Case Report
345
In 13717 patients treated with ofloxacin (Blomer et al. 1986) there were 577 different side effects. most commonly gastromtestmal
ones. In 124 cases the central nervous system was affected. mainly by headaches and
msomnla (“=X4). Hallucinations (n=l), nightmares (n=l), confusion (“=I) and depression (n=2) were rare. Koverech et al. (1986) treated 2003 patients m Italy with ofloxacin. 4.Y t % of these developped gastrOmtestmal side effects. 0.7% of the patlents reported neurological symptoms. usually headaches and insomma. The side effects were more frequent in patients older than 5 I years. The average age of patients with neurological side effects was 68.8 years. Judson et al. (1986) treated 30 female patients because of a sexually transmitted disease with a daily dosage of2 x 300 rn!: otloxacin for 7 days. 5 of these patients developped headaches. and 4 msomma. In I3 out of 62 patients who received fleroxacin (200 to 600 mg for IO days) therapy was stopped because of side effects (Wolthagen et al. 1990). The frequency of side effects increased with the dosage. The ade effects descr&ed were sickness (n=9), photosensibility fn=l), insomnia (n=l). oligurm (n=l) and psychosis (n=l). Ttus psychosis which was not specified in more detail occurred in a 30 year old woman who suffered from a systermc lupus erythematodes. and who had experienced a psychotic episode before. A contribunon of tleroxacm (600 mgiday) to the exacerbation of the psychosis could not be excluded. Wolfson and Hooper (1991) reported in a review (cf. also Ball 1989) that central nervous side effects occurred in
I to 7% of the patients treated with fluorquinolones. The symptoms most commonly described were
headache. dizziness. agitation and insomnia. There are only single cases with hallucinations.
delirant
syndromes or psychoses. Epileptic seizures were rarely observed, usually in patients with preexisting CNS disorders. From rhe studies described above it can be inferred that side effects occur as a iimction of the sinyle and the total dosage of fluorquinolones. Apparently. there are no si_enificant differences in the central nervous side effects of different fluorquinolones. As to the mechanism of action of fluorquinolones on the CNS Stein (1991) pointed out that fluorqumolones rnlzht cause. dependant on their concentration,
a competitive ininbition at postsqnapnc GABA receptors.
Moreover. they may decrease the GABA release at synapses. In combination with non-steroidal antiinflammatory drugs the inhibition of GABA receptors may be enhanced which could explain the increased frequency of epileptic seizures under co-administration
of enoxacin and fenbufen. There are also suggestions
that the combination of fluorquinolones with non-steroidal anti-inflammatory dopaminergic neurotransmission
drugs may influence the
(Christ et al. 1989). This is of interest in relation to psychotic disorders
occurring under treatment with fluorquinolones. In the case described above there is a clear temporal coincidence between the drug intake and the onset of psychotic symptoms. This renders a causal relationship very likely. It is remarkable that the psychosis became progressively more severe up to 9 days after the last drug intake although the half life of perfloxacin is only I I h. Thus. the medication mainly seemed to trigger the psychosis.
McCue and Zandt (1991) and Reeves (1992)
reported that symptomatology and drug intake run m parallel. It is unclear whether the rapid remission of symptoms in our patient was spontaneous or due to the neurolepnc medication. The relapse atier tapering off the neuroleptics speaks in favour of a drug effect. However, McCue and Zandt (1991) reported that the psychoses they observed under a co-medication of ciprofloxacin and trimethoprim-sulfamethoxazol
did not
346
B. HeBlinger
et al.
ream to neuroleptics (haloperidole or thiothixene), but disappeared a few days after discontmuanon of the medicanon. In a study by Rewes (I YY2)there was a remission of a schizophrenic symptomatology within 3 days after stop of ciprofloxacin and treatment with thiothixene. In her history, our 59 year old pattern had aiready reacted to a medication wrth corticosteroids with a manic syndrome. which points out to an increased vulnerability ofher CNS to psychotropic substances. It cannot be decided whether pefloxacin alone or the combination with paracetamol caused the psychosis. For the reasons desribed above there may have been an enhancing effect of paracetamol.
Conclusions In pattents with a history of increased vulnerability of the CNS or those in advanced age the indication for the use of fluorchinolones should be considered critically. in particular in combination with non-steroidal antiintlammatory drugs. Central nervous side effects of fluorquinolones may be long-lasting, i.e. they may continue even days after the medication has been stopped.
BALL P. (1989) Adverse reactions and interactions offluoroquinolones.
Clin.lnvest.Med.. e
28-34
BLOMER R.. BRUCH K., KRAUSS H.and WACHEK W. (1986) Safety of Ofloxacin - Adverse drug reactions Reported During Pase-Ii Studies in Europe and in Japan. Infection. 14. Suopl. 4: S 332-S 334 BOEREMA J.B.J.. PAUWELS R., SCHEEPERS J. and CROMBACH W. (I 986) Eficacy and safety of pefloxacin in the treatment of patients with complicated urinary tract infecnons. Journal of Antimicrobial Chemotherapy. 17, Supo1.B: 103-109 CHRIST W., GINDLER K., GRUENE S.. HECKER W.: JACOBSEN M.. JUNGE H. and PARK H. (1989) Interactions of Quinolones with Opioids and Fenbufen, a Nonsteroidal Antiinflammatory Drug: Involvement of Dopaminergic Neurotransmission. Reviews of Infectious Diseases. I I. Suppl.5: S 1393-S 1394 DOW J.. CHAZAL J., FRYDMAN A.M., JANNY P., WOEHRLE R.. DJEBBAR F. and GAILLOT J. (1986) Transfer kinetics of pefloxacin into cerebra-spinal fluid after one hour iv infusion of 400 mg in man. Journal of Antimicrobial Chemotherapy, II: 8 I-87 JUDSON F.N.. BEALS B.S. and TACK K.J. (1986) Clinical Experience with Ofloxacin in Sexually Transmitted Disease. Infection. 14. SuppI.4: S 309-S 3 10 KOVERECH A.. PICARI M.. GRANATA F.. FOSTMI R.. TONIOLO D. and RECHIA G. (1986) Safety Protile of Ofloxacin: The Italian Data Base. Infection, 14, Suopl.4: S 335-S 337 LAUWERS S., VMCKEN W., NAESSENS A. and PIERARD D. (1986) Efficacy and safety of pefloxacin in the treatment of severe infections in patients hospitalized in intensive care units. Journal of Antimicrobial Chemotherapy, 17. Supol.B: I I I-I 15 McCUE J.D. and ZANDT J.R. (1991) Acute Psychosis associated with the use of ciprofloxacin and trimethoprim-sulfamethoxazole. Am.J.of Medicine.3: 528-9 REEVES R.R.( 1992) Ciprotloxazin-induced
psychosis. Annals of Pharmacotherapy,
2: 930-93
SIMPSON K.J. and BRODIE M.J (1985) Convulsions related to enoxacin. The Lancer. July:
I 161
Acute
Psychotic
Disorder
by Pefloxacin:
Case Report
STAHL J.P., CROIZE J.. LEFEBVRE M.A.. BRU J.P.. GUYOT A.. LEDUC D.. FOURTILLAN J.B. and MICAUD M. (1986) Diffusion of Otloxacin into the Cerebrospinal Fluid in Patients with Bacterial Meningitis. Infection. 14 Suppl.4: 254-255 STEIN (1991) Drug interactions with Fluoroquinolones. 81 S-85 S
The American Journal of Medicine. 91 (suopl.bA):
STLJBNER G.. WEINRICH W. and BRANDS U. (1986) Study of the cerebrosptnal Fluid Penetrability of Ofloxacin. Infection. 14 Supol.4: 250-253 WOLFF M.. REGNIER B.. DALDOSS C.. NKAM M. and VACHON F. (1984) Penetration of Pefloxacm mto Cerebrospinal Fluid of Patients with Meningitis. Antimicrobial Agents And Chemotherapy,&289-291 WOLFHAGEN M.J.. HOEPELMAN A.I. and VERHOEF J.(1990) Double-blind. dose-range-finding study of fleroxacin for treatment of complicated urinary tract infections, Antimicrobial Agents & Chemotherapy. a 409-4 I2 WOLFSON J.S. and HOOPER D.C. (1991) Overview of Fluoroquinolone Safety. The America Journal of Medicine. 9l(suool 6A): IS3 S-161 S
Inquiries and reprint requests should be addressed to: Dr.Bemd HeDlinger Psychiatrische Untversitatsklinik HauptstraBe 5 79 IO4 Freiburg Germany
347
&Bid
Psychiat.
Copyright 0
1996. Vol. 20. pp. 343-347 1996 Elsevier Science Inc.
SSDIO279-5946(95)00314-2
ELSEVIER
0276 - 6646/96 $32.00
AN ACUTE PSYCHOTIC DISORDER CAUSED BY PEFLOXACIN: A CASE REPORT BERND HEOLINGER. BERNHARD HELLWIG. URBAN SESTER. J6RG WALDEN and MATTHlAS BERGER Department of Psychiatry, University of Freiburg, HauptstraOe, Freiburg, Germany
(Final form, October 1995)
Abstract HeDlinger. Bemd. Bernhard Hellwig, Urban Sester. Jiirg Walden and Matthias Berger: An Acute Psychotic Disorder Caused by Pefloxacin: A Case Report. Prog. Neuro-Psychopharmacol & Biol.Psychiat. 1996.201
I. The patient, a 59 year old woman, developped a state of acute excitatton several hours after the administration of 400 mg of the fluorquinolone pefloxacin in combination with 1000 mg paracetamol. Nine days later. after a total dosage of pefloxacin of 800 mg, she was admitted to our hospital with a psychotic disorder. 2. There was a full remission of symptoms after treatment with perazine up to a dosage of 500 mgiday. 3. Three years ago, the patient had developped a manic state under a medication with corticosteroids. 4. So far. the mechanism of - in this case - long-lasting central nervous side effects of fluorquinolones is not known. In pattents with increased vulnerability of the CNS or in advanced age the application of fluorquinolones should be considered critically, in particular in combination with non-steroidal antimflammatory drugs. Kevwords: fluorquinolones, paracetamol, pefloxacin, perazine. psychosis
Introduction
Since the early 1980s fluorquinolones
such as norfIoxacin, ofloxacin. ctprofloxacin, or pefloxacin have been
used mainly in the treatment of urinary tract infections. Fluorquinolones are also called ‘gyrase-inhibitors’ because of their inhibiting effect on bacterial DNA-gyrases. By controlling the formation of ..supercoils“ the DNA-gyrase is a crucial factor in the synthesis. transcription and recombination of DNA. Pefloxacin is quickly and almost completely absorbed when administered orally. Its half life (1 I h) is by far the longest of the substances mentioned above. It may be significantly prolonged by a pathological liver conditton. About 10% of the patients treated with fluorqumolones develop side effects, most commonly gastrointestinal symptoms. CNS disturbances such as increased excitability, insomnia or dizzmess have been observed. Confusion, psychotic syndromes, hallucinations
or epileptic seizures (Simpson and Brodie 1985) have heen
rarely described.
Case Report
Our patient A. T.. a 59 year old woman, was treated by her general practitioner with pefloxacin (2 x 400 mg in 2 days) and paracetamol (1000 mg) because of an urinary tract infection. Several hours after the first drug 343
344
B. HeBlinger
et al.
intake the patient was in a state of exitation wtth euphorta. During the following days she had also dtfficulty m sleepmg and concentrating. According to the patient’s family she was intermittently conmsed. Nine days after the administration of a total dosage of 800 mg pefloxacin she was admitted to our hospttal. The patient was then fully oriented. She was in a state of psychomotor agttation. Thinking was incoherent and assoctations were loosenend. Her behaviour was partly bizarre. There were ideas of reference. The panent denied hallucinattons. hallucinations.
Two independent psychiatrists had the impression the patient was having acusncal
The affect was labile, but predominantly
euphoric.
Three years ago the patient had received corticosteroids because of a bullous exanthema. According to her family she developped then a manic syndrome which disappeared without psychiatrtc treatment several days after discontinuation of the corticosteroids. Since that time she never got corttcosteroids. There were no sertous illnesses in the patient’s history, in particular no psychiatric disorders. Also in the family history, psychiatrtc disorders had not occurred. The patient had not left Europe for 21 years. before she had lived a number of years m Africa and South America. According to the patient’s general practitioner the urmary tract infection was accompanied by a slight increase of the transaminases.
whtch may have been caused by the consumption of %
to % I wine per day for a period of several months. The physical examination of the pattent was normal. Extensive laboratory tests gave no signs of a significant liver impairment. An EEG, an ECG and a cramal CT scan did not reveal any significant abnormalities.
Therapv Under a medication with perazine up to a dosage of 500 mg/day there was first a considerable tmprovement of the thought disorders and the bizarre behaviour. After three days of treatment the panent was in a hypomanic state. and after nine days the medication was stopped, since there was a complete remission of symptoms. Due to a relapse of the hypomanic state the patient received 100 mg perazine for another 3 days. Again, the psychopathological
picture stabilized quickly. 10 days after tapering off the medication the patient left our
hospital in a state of complete remission.
Discussion Fluorquinolones penetrate into the cerebrospinal fluid. A good passage into the cerebrospmal fluid could be shown for pefloxacin (Wolff et al. 1984, Dow et al. 1986) as well as for ofloxacin (Stahl et al. 1986. Stiibner et al. 1986). Boerema et al. (1986) reported that 34 out of 104 patients who were treated with a daily dosage of 2 x 400 mg pefloxacin for a period of 10 days developped side effects, 50% of which were gastrointestinal,
17%
neurological (not specified in more detail) and 17% allergic. 9% of these side effects were clearly due to pefloxacin. In 4 patients side effects were considered as severe. 3 out of these 4 patients were older than average, the average age of the 104 patients being above 60 years. Lauwers et al. (1986) treated 16 patients in an intensive care unit (age median: 65 years) intravenously with 400 mg pefloxacin two to three times per day. Treatment was continued for an average of 11 days. Side effects were not observed in this study.
Acute
Psychotic
Disorder
by Pefloxacin:
Case Report
345
In 13717 patients treated with ofloxacin (Blomer et al. 1986) there were 577 different side effects. most commonly gastromtestmal
ones. In 124 cases the central nervous system was affected. mainly by headaches and
msomnla (“=X4). Hallucinations (n=l), nightmares (n=l), confusion (“=I) and depression (n=2) were rare. Koverech et al. (1986) treated 2003 patients m Italy with ofloxacin. 4.Y t % of these developped gastrOmtestmal side effects. 0.7% of the patlents reported neurological symptoms. usually headaches and insomma. The side effects were more frequent in patients older than 5 I years. The average age of patients with neurological side effects was 68.8 years. Judson et al. (1986) treated 30 female patients because of a sexually transmitted disease with a daily dosage of2 x 300 rn!: otloxacin for 7 days. 5 of these patients developped headaches. and 4 msomma. In I3 out of 62 patients who received fleroxacin (200 to 600 mg for IO days) therapy was stopped because of side effects (Wolthagen et al. 1990). The frequency of side effects increased with the dosage. The ade effects descr&ed were sickness (n=9), photosensibility fn=l), insomnia (n=l). oligurm (n=l) and psychosis (n=l). Ttus psychosis which was not specified in more detail occurred in a 30 year old woman who suffered from a systermc lupus erythematodes. and who had experienced a psychotic episode before. A contribunon of tleroxacm (600 mgiday) to the exacerbation of the psychosis could not be excluded. Wolfson and Hooper (1991) reported in a review (cf. also Ball 1989) that central nervous side effects occurred in
I to 7% of the patients treated with fluorquinolones. The symptoms most commonly described were
headache. dizziness. agitation and insomnia. There are only single cases with hallucinations.
delirant
syndromes or psychoses. Epileptic seizures were rarely observed, usually in patients with preexisting CNS disorders. From rhe studies described above it can be inferred that side effects occur as a iimction of the sinyle and the total dosage of fluorquinolones. Apparently. there are no si_enificant differences in the central nervous side effects of different fluorquinolones. As to the mechanism of action of fluorquinolones on the CNS Stein (1991) pointed out that fluorqumolones rnlzht cause. dependant on their concentration,
a competitive ininbition at postsqnapnc GABA receptors.
Moreover. they may decrease the GABA release at synapses. In combination with non-steroidal antiinflammatory drugs the inhibition of GABA receptors may be enhanced which could explain the increased frequency of epileptic seizures under co-administration
of enoxacin and fenbufen. There are also suggestions
that the combination of fluorquinolones with non-steroidal anti-inflammatory dopaminergic neurotransmission
drugs may influence the
(Christ et al. 1989). This is of interest in relation to psychotic disorders
occurring under treatment with fluorquinolones. In the case described above there is a clear temporal coincidence between the drug intake and the onset of psychotic symptoms. This renders a causal relationship very likely. It is remarkable that the psychosis became progressively more severe up to 9 days after the last drug intake although the half life of perfloxacin is only I I h. Thus. the medication mainly seemed to trigger the psychosis.
McCue and Zandt (1991) and Reeves (1992)
reported that symptomatology and drug intake run m parallel. It is unclear whether the rapid remission of symptoms in our patient was spontaneous or due to the neurolepnc medication. The relapse atier tapering off the neuroleptics speaks in favour of a drug effect. However, McCue and Zandt (1991) reported that the psychoses they observed under a co-medication of ciprofloxacin and trimethoprim-sulfamethoxazol
did not
346
B. HeBlinger
et al.
ream to neuroleptics (haloperidole or thiothixene), but disappeared a few days after discontmuanon of the medicanon. In a study by Rewes (I YY2)there was a remission of a schizophrenic symptomatology within 3 days after stop of ciprofloxacin and treatment with thiothixene. In her history, our 59 year old pattern had aiready reacted to a medication wrth corticosteroids with a manic syndrome. which points out to an increased vulnerability ofher CNS to psychotropic substances. It cannot be decided whether pefloxacin alone or the combination with paracetamol caused the psychosis. For the reasons desribed above there may have been an enhancing effect of paracetamol.
Conclusions In pattents with a history of increased vulnerability of the CNS or those in advanced age the indication for the use of fluorchinolones should be considered critically. in particular in combination with non-steroidal antiintlammatory drugs. Central nervous side effects of fluorquinolones may be long-lasting, i.e. they may continue even days after the medication has been stopped.
BALL P. (1989) Adverse reactions and interactions offluoroquinolones.
Clin.lnvest.Med.. e
28-34
BLOMER R.. BRUCH K., KRAUSS H.and WACHEK W. (1986) Safety of Ofloxacin - Adverse drug reactions Reported During Pase-Ii Studies in Europe and in Japan. Infection. 14. Suopl. 4: S 332-S 334 BOEREMA J.B.J.. PAUWELS R., SCHEEPERS J. and CROMBACH W. (I 986) Eficacy and safety of pefloxacin in the treatment of patients with complicated urinary tract infecnons. Journal of Antimicrobial Chemotherapy. 17, Supo1.B: 103-109 CHRIST W., GINDLER K., GRUENE S.. HECKER W.: JACOBSEN M.. JUNGE H. and PARK H. (1989) Interactions of Quinolones with Opioids and Fenbufen, a Nonsteroidal Antiinflammatory Drug: Involvement of Dopaminergic Neurotransmission. Reviews of Infectious Diseases. I I. Suppl.5: S 1393-S 1394 DOW J.. CHAZAL J., FRYDMAN A.M., JANNY P., WOEHRLE R.. DJEBBAR F. and GAILLOT J. (1986) Transfer kinetics of pefloxacin into cerebra-spinal fluid after one hour iv infusion of 400 mg in man. Journal of Antimicrobial Chemotherapy, II: 8 I-87 JUDSON F.N.. BEALS B.S. and TACK K.J. (1986) Clinical Experience with Ofloxacin in Sexually Transmitted Disease. Infection. 14. SuppI.4: S 309-S 3 10 KOVERECH A.. PICARI M.. GRANATA F.. FOSTMI R.. TONIOLO D. and RECHIA G. (1986) Safety Protile of Ofloxacin: The Italian Data Base. Infection, 14, Suopl.4: S 335-S 337 LAUWERS S., VMCKEN W., NAESSENS A. and PIERARD D. (1986) Efficacy and safety of pefloxacin in the treatment of severe infections in patients hospitalized in intensive care units. Journal of Antimicrobial Chemotherapy, 17. Supol.B: I I I-I 15 McCUE J.D. and ZANDT J.R. (1991) Acute Psychosis associated with the use of ciprofloxacin and trimethoprim-sulfamethoxazole. Am.J.of Medicine.3: 528-9 REEVES R.R.( 1992) Ciprotloxazin-induced
psychosis. Annals of Pharmacotherapy,
2: 930-93
SIMPSON K.J. and BRODIE M.J (1985) Convulsions related to enoxacin. The Lancer. July:
I 161
Acute
Psychotic
Disorder
by Pefloxacin:
Case Report
STAHL J.P., CROIZE J.. LEFEBVRE M.A.. BRU J.P.. GUYOT A.. LEDUC D.. FOURTILLAN J.B. and MICAUD M. (1986) Diffusion of Otloxacin into the Cerebrospinal Fluid in Patients with Bacterial Meningitis. Infection. 14 Suppl.4: 254-255 STEIN (1991) Drug interactions with Fluoroquinolones. 81 S-85 S
The American Journal of Medicine. 91 (suopl.bA):
STLJBNER G.. WEINRICH W. and BRANDS U. (1986) Study of the cerebrosptnal Fluid Penetrability of Ofloxacin. Infection. 14 Supol.4: 250-253 WOLFF M.. REGNIER B.. DALDOSS C.. NKAM M. and VACHON F. (1984) Penetration of Pefloxacm mto Cerebrospinal Fluid of Patients with Meningitis. Antimicrobial Agents And Chemotherapy,&289-291 WOLFHAGEN M.J.. HOEPELMAN A.I. and VERHOEF J.(1990) Double-blind. dose-range-finding study of fleroxacin for treatment of complicated urinary tract infections, Antimicrobial Agents & Chemotherapy. a 409-4 I2 WOLFSON J.S. and HOOPER D.C. (1991) Overview of Fluoroquinolone Safety. The America Journal of Medicine. 9l(suool 6A): IS3 S-161 S
Inquiries and reprint requests should be addressed to: Dr.Bemd HeDlinger Psychiatrische Untversitatsklinik HauptstraBe 5 79 IO4 Freiburg Germany
347