Different side effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: a pilot study

OBJECTIVE: The purpose of this study was to compare the side effect +profiles of clozapine and risperidone. METHOD: The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports. RESULTS: Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment. CONCLUSIONS: In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.     

Immunohistochemistry diagnosis of fungal infections

BACKGROUND: A potential beneficial outcome of treatment with certain of the atypical neuroleptics is the reduced risk of cognitive impairment, stemming from purported low affinity for cholinergic receptors. In vitro experiments have shown that clozapine is highly anticholinergic and risperidone is minimally so. In vivo tests of the anticholinergic burden imposed by these medications and its potential cognitive consequences are needed. This study examines anticholinergic burden in schizophrenia patients taking clozapine and risperidone and tests whether this burden is associated with cognitive deficits. METHOD: Serum anticholinergic levels were determined in a sample of 22 chronic schizophrenia patients using the radioreceptor assay method of Tune and Coyle (1980). Fifteen patients received clozapine; 7 received risperidone. Mean +/- SD age of the sample, comprising 12 men and 10 women (68% white), was 44.7 +/- 8.4 years. Mean +/- SD age at onset of schizophrenia illness was 23.5 +/- 7.4 years. Two anticholinergic assays based on blood samples collected 1 week apart were available on each patient. RESULTS: Data indicated that clozapine patients had significantly (p < .001) higher anticholinergic levels at both collection points, and levels for both drugs remained stable over time. The clozapine and risperidone patients had essentially equivalent scores on the cognitive measure. CONCLUSION: These data suggest that anticholinergicity distinguishes clozapine and risperidone in vivo but that this effect is not associated with differences in global cognitive functioning. Results suggest that clozapine, despite producing moderately high in vivo serum anticholinergic levels, still holds clinical advantage over standard neuroleptics in terms of cognitive side effects. Reasons for this lowered risk of cognitive impairment are discussed.     

Clinical and neurocognitive effects of clozapine and risperidone in treatment-refractory schizophrenic patients: a prospective study

BACKGROUND: Few controlled studies have compared the efficacy of clozapine and risperidone in treatment-refractory schizophrenic patients. The present study investigates the efficacy of both clozapine and risperidone on psychopathologic and neurocognitive measures in a prospective 12-week open-label trial in treatment-refractory schizophrenic patients from state psychiatric hospitals. METHOD: Thirty-five DSM-IV schizophrenic patients with a documented history of nonresponse to typical neuroleptics were treated with either clozapine or risperidone. Response was assessed every 2 weeks by independent raters with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, neurologic rating scales, and plasma drug levels. Neurocognitive tests were administered at baseline and week 12. RESULTS: Both clozapine and risperidone brought about significant (p < .003) overall improvement in psychopathology. However, clozapine was numerically superior to risperidone on PANSS total scores and PANSS positive, negative, excitement, and cognitive factors. Extrapyramidal side effects were minimal for clozapine, whereas some were present for risperidone. Patients taking risperidone improved significantly in the beginning stages of the study and remained stable thereafter. Patients taking clozapine showed a gradual improvement that occurred over the entire length of the trial. Neurocognitive measures showed minimal improvement and did not differentiate between the 2 medication groups. CONCLUSION: Both clozapine and risperidone were comparably effective across a wide spectrum of psychopathologic measures. While the efficacy of clozapine was only numerically superior to that of risperidone, it was associated with fewer extrapyramidal side effects and with progressive improvement over the 12-week treatment period, suggesting that in longer trials clozapine may prove to be superior to risperidone in neuroleptic-refractory patients.     

Recent advances in the pharmacotherapy of schizophrenia

The limitations of standard antipsychotics have spurred a search for novel agents that are effective against both positive and negative symptoms of schizophrenia but do not produce the extrapyramidal side effects frequently associated with the older medications. Such agents might more effectively prevent relapse, because of enhanced efficacy for the full spectrum of schizophrenic symptoms and improved tolerability--and hence greater medication compliance. Findings concerning the new antipsychotics currently available, clozapine and risperidone, are reviewed, and clozapine's usefulness as a first-line treatment is evaluated. Although serious side effects and the need for weekly blood monitoring may limit clozapine's use as a first-line treatment, risperidone appears promising in this role. Preclinical and clinical studies of new antipsychotic medications recently submitted for approval (olanzapine and sertindole) or in phase III development (quetiapine and ziprasidone) are also reviewed. The findings are encouraging, and researchers hope that some of these new agents may prove valuable as first-line treatments for schizophrenia. Pharmacoeconomic studies comparing clozapine and risperidone to the standard neuroleptics indicate that these newer drugs appear likely to lower the overall cost of treatment for schizophrenia, primarily by reducing rates of relapse and rehospitalization.     

Effects of switching inpatients with treatment-resistant schizophrenia from clozapine to risperidone

A prospective, open-label study in a 400-bed state psychiatric hospital evaluated change in therapeutic response among ten patients with treatment-resistant schizophrenia who were switched from clozapine to risperidone. Drug effects were examined before discontinuation of clozapine and at three, six, nine, and 12 weeks of risperidone treatment. No patients improved, and five discontinued treatment due to exacerbation of psychosis or adverse effects. Changes in scores on the Positive and Negative Syndrome Scale, the Brief Psychiatric Rating Scale, and the Barnes Akathisia Scale indicated clinically significant worsening of symptoms. The findings do not support replacing clozapine with risperidone for patients with treatment-resistant schizophrenia.     

Semi-automatic computer construction of three-dimensional shapes for the finite element method

Seven patients with idiopathic Parkinson's disease, aged 62 to 76 years, average duration of the disease approximately eleven years, suffering from severe hallucinosis and paranoid delusions of different degree, in whom conventional therapeutic strategies (administration of benzodiazepines and mild neuroleptics) had no antipsychotic effect, received clozapine, a non-classical highly potent neuroleptic, while blood count was strictly monitored. Paranoid ideas disappeared in all seven patients after a maximum of four days administration of 25-125 mg/day. No deterioration of parkinsonian symptoms, quantified according to UPDRS was seen. Given the protection of clozapine, we could increase the L-dopa dose in two cases, thereby improving the patients' motor function. Blood count showed no abnormalities in any of the patients during an average observation period of seventeen months. Our results support the assumption that clozapine has a potent antipsychotic effect in the treatment of psychotic decompensation in advanced Parkinson's disease in carefully selected patients. We saw no negative influence of the neuroleptic on extrapyramidal symptoms.     

Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response

OBJECTIVE: Clozapine and risperidone were the first two "second-generation" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents. METHOD: After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents. RESULTS: Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone. CONCLUSIONS: The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed.     

Treatment refractory schizophrenia: how should we proceed?

A substantial portion of schizophrenic patients demonstrate suboptimal response to conventional antipsychotics. These agents are primarily effective in the treatment of psychotic symptoms; their efficacy in other domains of psychopathology such as negative symptoms, chronic aggressive behavior, and cognitive deficits, is limited or non-existent. In this group of refractory patients, the novel atypical antipsychotic clozapine has demonstrated robust efficacy, with response rates approaching 60% after twelve weeks of treatment. Efficacy of clozapine extends to symptom domains other than psychosis, including negative symptoms, mood stabilization, aggressive behavior and compulsive water drinking. Several novel agents, each of which shares some, but not all, of the preclinical and clinical characteristics that make clozapine so unique, have been introduced in the last 4 years. These agents demonstrate a broader spectrum of efficacy and an improved side effect profile in non-refractory patients. Initial data on their efficacy in refractory patients suggests that olanzapine does not achieve overall superior efficacy in this patient population compared to conventional agents although there is some evidence of relatively greater efficacy in negative symptoms and aggressivity. Several studies suggest that the efficacy of risperidone is superior to that of conventional agents in refractory patients. Preliminary conclusions are not possible for quetiapine because of a paucity of data in the literature. The literature supports a risperidone trial prior to a clozapine trial in a treatment algorithm for refractory patients because of its more favorable risk/benefit profile.     

Analysis of the B7 costimulatory pathway in allograft rejection

Stimulus control induced by (-)-2,5-dimethoxy-4-methylamphetamine (DOM) is believed to be mediated by agonism at 5-HT2A receptors. We hypothesized that blockade of (-) DOM-induced stimulus control may thus prove useful in the pre-clinical characterization of novel antipsychotic agents by providing an in vivo index of antagonism at that receptor. A previous study (Fiorella et al., 1995a) observed no antagonism by typical agents such as haloperidol and thioridazine, partial antagonism by the atypical agent, clozapine, and full antagonism by risperidone, a second atypical antipsychotic. The present investigation extends these observations to include seven additional drugs: SCH 23390, sulpiride, amperozide, melperone, octoclothepin, tiospirone and ritanserin. Of the drugs tested in rats in which (-) DOM-induced stimulus control had reliably been established, only tiospirone and ritanserin produced complete antagonism of the (-) DOM stimulus. Intermediate levels of antagonism were observed following treatment with amperozide, melperone, and octoclothepin. Finally, SCH 23390 and sulpiride yielded no evidence of antagonistic activity in (-) DOM-trained animals. Because clozapine and risperidone are both classified as atypical antipsychotics yet yield different degrees of antagonism of (-) DOM-induced stimulus control, we tested the substitution of risperidone for clozapine in rats trained with clozapine as a discriminative stimulus. No significant substitution was observed. In conclusion it appears that complete or partial antagonism of the (-) DOM stimulus serves as an effective pre-clinical means of identifying antipsychotics with significant 5-HT2A antagonist properties. However, the failure of risperidone to substitute for clozapine in pigeons (Hoenicke et al., 1992) and in rats (present study) suggests that despite their shared 5-HT2A antagonist properties, clozapine and risperidone differ with respect to their stimulus effects.     

Risperidone as an adjunct to clozapine therapy in chronic schizophrenics

BACKGROUND: Some treatment-resistant schizophrenic patients improve enough to remain out of the hospital but continue to have significant positive or negative symptoms. METHOD: The goal of this study was to assess the safety and potential efficacy of risperidone as an adjunct for schizophrenic patients treated with clozapine. In an open 4-week trial involving 12 DSM-III-R-diagnosed patients, the addition of risperidone to clozapine was well tolerated and did not affect serum clozapine concentrations significantly. RESULTS: Total Brief Psychiatric Rating Scale (BPRS) scores and subscales measuring positive symptoms, negative symptoms, and depressive symptoms were significantly reduced from baseline. Ten of 12 participants had a 20% or greater reduction in the total BPRS score. CONCLUSION: In this open trial, the addition of risperidone to clozapine was well tolerated and produced significant reduction of symptoms, suggesting that this may be a useful clinical approach. Because this was an open trial, the improvement we observed must be replicated in a controlled trial.     

Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence

The pharmacological properties of the novel antipsychotic drugs (APDs) risperidone, sertindole, olanzapine, quetiapine, ziprasidone, remoxipride, and amperozide are reviewed and compared with haloperidol and clozapine. Focus is made on their receptor profiles, their effects in animal models used for evaluation of antipsychotic activity, and extrapyramidal side effects (EPS). In addition, the contrasting actions of these compounds on animal models of cognition, anxiety, and depression are briefly reviewed. The available evidence indicates that novel APDs and clozapine can be differentiated from haloperidol, particularly in models of EPS and cognitive side effects. However, among the group of novel APDs there are many individual differences in models reflecting limbic versus striatal inhibition of dopamine function: clozapine and sertindole show the largest limbic selectivity, followed by quetiapine, ziprasidone, olanzapine and remoxipride, whereas risperidone in many respects has a profile that resembles haloperidol. To date, the results of clinical studies have confirmed the predictions of lower incidence or absence of EPS after administration of novel APDs in doses which demonstrate antipsychotic efficacy.     

Resolution of metastatic calcification in the paws of a cat with successful dietary management of renal hyperparathyroidism

BACKGROUND: Clozapine is an atypical antipsychotic drug indicated for patients with schizophrenia in whom traditional antipsychotic drugs (such as haloperidol or the phenothiazines) are ineffective, or in those who experience intolerable adverse effects. Clozapine treatment may be complicated by the development of life-threatening agranulocytosis, so regular haematological monitoring is required. OBJECTIVES: To determine the incidence of clozapine-induced agranulocytosis in Australia and the importance of monitoring white blood cell counts in patients treated with clozapine. DESIGN: Review of haematological monitoring for the first three years (June 1993-July 1996) of operation of the Australian Clozaril (clozapine; Novartis Australia) Patient Monitoring System (CPMS) central database. RESULTS: In the 4061 patients prospectively monitored by the CPMS, the incidence of agranulocytosis, neutropenia and leukopenia combined was 2.6% (n = 104); the incidence of agranulocytosis was 0.9% (n = 37). So far there have been no deaths in Australia from the complications of clozapine-induced agranulocytosis. CONCLUSION: The incidence of agranulocytosis and neutropenia associated with clozapine use in Australia is similar to that in the rest of the world. Monitoring the white blood cell counts of patients being treated with clozapine ensures minimal risk to patients who develop agranulocytosis.     

Iodine-123-iodobenzamide SPECT assessment of dopamine D2 receptor occupancy in riperidone-treated schizophrenic patients

The recently introduced neuroleptic, risperidone, was expected to block fewer dopamine D2 receptors than typical neuroleptics (e.g., haloperidol), but at comparable potency. The aim of this study was to evaluate the degree of dopamine D2 receptor occupancy in relation to the neuroleptic dosage and to correlate the findings with the presence of extrapyramidal symptoms (EPS). Additionally, the data were compared to previous iodobenzamide (IBZM) SPECT findings in patients treated with other neuroleptics, haloperidol and clozapine. METHODS: In 20 patients with schizophrenia [Diagnostic and Statistical Manual of Mental Disorders (Third Edition-Revised)] treated with mean daily doses of risperidone ranging from 0.029 to 0.128 mg/kg body weight, SPECT was performed 2 hr after intravenous injection of 185 MBq 123I-IBZM, a selective dopamine D2 receptor ligand. Striatal IBZM binding was assessed by calculating a striatal/frontal cortex ratio, expressed as a percentage of the control value. RESULTS: Selective dopamine D2 receptor binding of the ligand was reduced in all treated patients, with binding values ranging from 7% to 68%. The degree of occupancy displayed an exponential dose-response relationship (r = -0.86; p < 0.0001). The slope of the curve was between those of haloperidol and clozapine but was closer and more similar in shape to the curve of haloperidol. Extrapyramidal symptoms were observed in 8 of 20 patients with binding values between 7% and 47%. However, there was no clear relationship between the degree of receptor occupancy and the presence of EPS. CONCLUSION: The findings suggest an exponential dose-response relationship between the daily dosage of risperidone and the dopamine D2 receptor occupancy. The blockade of specific striatal IBZM binding found under therapy with risperidone is between those of haloperidol and clozapine. The dose-response curve for risperidone, however, shows greater similarity to that of haloperidol.     

Reduced number of circulating monocytes after institution of insulin therapy--relevance for development of atherosclerosis in diabetics?

Twelve patients with Type II diabetes mellitus, insufficiently controlled with oral hypoglycemic agents, were studied before, after 2 months, and after 4 months on insulin therapy. For comparison the same variables were also studied in 10 healthy subjects. From the start, in the diabetic group, the authors found alterations in the hemorheologic parameters indicated by increased values for whole blood viscosity, plasma viscosity, red cell transit time (RCTT), and decreased values for white cell initial relative filtration rate (IrFR). In hematologic parameters they found increased values for mean corpuscular volume (MCV), leukocyte count, counts of neutrophils and monocytes, and a decreased count of lymphocytes. They also found increased values in the lipid parameters P-triglycerides and Apo B/Apo A-I ratio, risk factors of coronary atherosclerosis. After 4 months of insulin treatment whole blood and plasma viscosity were still increased, but there was a partial improvement of lipoprotein abnormalities. Red and white cell filterability, however, tended to normalize. These results indicate that changes in blood cell filterability do not necessarily influence in vitro measurements of blood viscosity. The change in RCTT during the insulin treatment was associated with a decreased MCV and the change in white cell IrFR with a decrease in the number of monocytes. This change of white cell filterability during insulin therapy, probably due to a reduced number of monocytes, may be of interest in the study of atherosclerosis and circulatory disease in diabetics.     

Use of atypical neuroleptics in child and adolescent psychiatry

BACKGROUND: This article reviews the published clinical experience with atypical neuroleptics in children and adolescents. METHOD: A computerized literature search was conducted (MEDLINE, 1974-1998) to retrieve all reports on the use of atypical neuroleptics in children and adolescents. A hand search was performed as well. All relevant clinical data were collated by type of drug. RESULTS: We found 5 blind placebo-controlled clinical trials (105 patients), 24 open-label clinical trials (387 patients), and 33 case series (115 patients) describing the use of the atypical neuroleptics clozapine, risperidone, olanzapine, sulpiride, tiapride, amisulpride, remoxipride, and clothiapine in children and adolescents. Some of these agents, especially clozapine, risperidone, and olanzapine, were found to be efficacious in the treatment of schizophrenia, bipolar disorders, and pervasive developmental disorders. The role of atypical neuroleptics as augmenters of serotonin reuptake inhibitors in obsessive-compulsive disorder is unclear. Risperidone appears to possess anti-tic properties in patients with Tourette's disorder. CONCLUSION: The most convincing evidence of the efficacy of atypical neuroleptics in children and adolescents concerns clozapine in the treatment of schizophrenia. Data on other atypical neuroleptics in other disorders are still sparse, and further research is needed. Some of the atypical neuroleptics may become the first-line treatment for childhood schizophrenia and pervasive developmental disorders.     

Hantavirus pulmonary syndrome in a Chilean patient with recent travel in Bolivia

The cost, side effect profile, and required weekly blood draws associated with clozapine may dissuade some clinicians from prescribing this atypical neuroleptic to mentally retarded patients. All publications on clozapine use in mentally retarded patients are reviewed and the treatment of 10 such patients is described, bringing the total number of published cases to 84. Clozapine is efficacious and well tolerated in this population and should be considered for those patients with psychosis or bipolar illness who are intolerant of or unresponsive to other agents.     

Xeroderma pigmentosum

MAIN CLINICAL FEATURES: Xeroderma pigmentosum is a rare, recessive disorder clinically characterized by extreme photosensitivity, pigmented abnormalities of the skin-exposed areas, and frequent ocular and neurological abnormalities. Xeroderma pigmentosum syndrome is associated with an estimated 2000-fold increase in the risk to develop skin cancer (basal cell carcinoma, squamous cell carcinoma and melanoma). A HETEROGENEOUS DISEASE: Skin or blood cells from Xeroderma pigmentosum patients are hypersensitive to killing by ultraviolet and hypermutable after ultraviolet C treatment Cell fusion experiments based on complementation of repair synthesis have recognized the presence of seven Xeroderma pigmentosum groups which exhibit various defects in the initial steps of the DNA nucleotide excision repair pathway. A variant Xeroderma pigmentosum form has been found to be normal in nucleotide excision repair but abnormal in a poorly to be normal in nucleotide excision repair but abnormal in a poorly understood postreplication repair process. PATHOPHYSIOLOGY: The Xeroderma pigmentosum complementation groups differ in terms of severity of clinical, cellular and genetic features. Molecular and biochemical studies of the Xeroderma pigmentosum syndrome have led to a better understanding of the mechanisms of ultraviolet-induced sensitivity and the mechanism of cancer development after ultraviolet exposure.     

Health status and health care costs for publicly funded patients with schizophrenia started on clozapine

OBJECTIVE: The study examined the effect of clozapine treatment on the health care costs and health status of people with schizophrenia who are supported by public funds. METHODS: Thirty-three patients with schizophrenia hospitalized in a state facility were interviewed within one week of starting clozapine and six months later. Health status was assessed with four clinical rating scales measuring severity of psychopathology, negative symptoms, depression, and quality of life. Cost and health care utilization data were collected for the six months before and after initiation of clozapine. RESULTS: Only 52 percent of the subjects stayed on clozapine for six months. Subjects who continued on clozapine were more likely to be discharged within six months than those who did not continue. Six months after clozapine was started, health care costs showed a sayings of $11,464 per person, even after adjustment for pretreatment costs, and health status was improved. CONCLUSIONS: For subjects who continued on clozapine for six months, clozapine treatment was associated with reduced days of psychiatric hospital care, reduced overall costs despite increased outpatient treatment and residential costs, and improved health status.     

The common marmoset (Callithrix jacchus) as a model for neuroleptic-induced acute dystonia

To examine whether acute dystonia is induced by neuroleptic treatment, common marmosets were treated with haloperidol orally twice a week over 25 weeks until dystonic behavior was elicited. Movement disorders such as acute dystonia were observed 6 weeks after the initial treatment, and had appeared in all treated animals by 25 weeks. Once these movement disorders were induced, they consistently reappeared after further treatment with haloperidol, and once haloperidol dosing was discontinued, the episodes vanished. Then, various neuroleptic drugs (bromperidol, chlorpromazine, risperidone thioridazine, sulpiride, tiapride, and clozapine) or a nonneuroleptic drug (diazepam) were administered orally instead of haloperidol in the above animals. All the neuroleptic drugs except for clozapine elicited similar abnormal behavior, while diazepam failed to induce any dystonia. An anticholinergic drug, trihexyphenidyl, which is known to reduce acute dystonia in patients, was also given orally to the above haloperidol-sensitized animals, followed by further treatment with haloperidol 30 min later. This clearly suppressed the induction of dystonia by haloperidol. The similarity between these findings for haloperidol-pretreated common marmosets and clinical findings suggests that the present model is useful for predicting the potential of antipsychotics to induce acute dystonia in humans.     

Agranulocytosis induced by vancomycin or ticarcillin/clavulanate

OBJECTIVE: To reacquaint clinicians with a reportedly rare adverse event of agranulocytosis occurring after long-term administration of vancomycin and ticarcillin/clavulanate, with a subsequent review of other reported cases in the literature. CASE SUMMARY: A 45-year-old white woman with spina bifida developed agranulocytosis (2.7 x 10(3)/mm3 white blood cells with only 3% polymorphonuclear leukocytes and no reported eosinophils or basophils) after long-term administration of vancomycin and ticarcillin/clavulanate for decubitus ulcers and chronic osteomyelitis. Consequently, the cell counts rebounded rapidly on discontinuation of both medications and returned to normal within 1 week. DISCUSSION: The incidence of vancomycin-associated neutropenia is presumably rare, but the increased use of vancomycin may disclose a more frequent occurrence. It is suggested that the mechanism for the reaction is immunologically mediated, yet this remains unclear. Although it is difficult to determine the causative agent in this case, vancomycin was most suspect clinically. Ticarcillin/clavulanate is less likely because our patient has since been readmitted and treated with oxacillin, imipenem/cilastatin, and amoxicillin/clavulanate without affecting the white blood cell count. In that regard, it could be reasoned that an immunologic reaction to ticarcillin would have resulted in a similar outcome with other penicillins. CONCLUSIONS: This case serves as a reminder to clinicians that patients receiving long-term treatment with vancomycin should have their white blood cell count monitored at least weekly.