Septic shock and community-acquired pneumonia associated with etanercept therapy.

OBJECTIVE: To report a case of septic shock and community-acquired pneumonia in a patient with psoriatic arthritis receiving treatment with etanercept. PATIENT DETAILS: A 65-year-old woman diagnosed as having psoriatic arthritis had received treatment with etanercept. Chest X-ray studies were normal and the tuberculin skin test was negative. Two months after etanercept therapy, the patient presented to our emergency department with fever, cough, chest pain and generalized weakness. Chest radiography revealed a right pulmonary infiltrate. Her condition rapidly deteriorated and she went into shock with a further drop in her blood pressure, tachycardia and tachypnea. She was intubated, mechanically ventilated and was treated with fluids, cardioversion and amiodarone. Empiric therapy with levofloxacin, amikacin and cefepime were initiated. In the urinalysis, the result of a rapid test for Streptococcus pneumoniae was positive. Etanercept treatment was suspended due to a possible adverse reaction associated with this drug. At the start of therapy her clinical condition improved slowly. On Day 28, the patient was afebrile and she was discharged from the intensive care unit. DISCUSSION: Most of the infections associated with etanercept therapy have been reported in patients with rheumatoid arthritis. Based on our observations, etanercept was the possible offender in the development of septic shock and respiratory failure in community-acquired pneumonia. There was a temporal relationship between exposure to the drug and onset of symptoms. Etanercept was the only drug administered before the septic shock developed. Based on the Naranjo algorithm, the adverse reaction could be considered possible. CONCLUSION: Patients initiated on etanercept should be counseled and receive appropriate screening before drug initiation. All febrile and newly occurring concomitant illnesses should be promptly evaluated. General practitioners should discontinue etanercept treatment and institute prompt and aggressive intervention if infection develops.

Exacerbation of psoriatic skin lesions in a patient with psoriatic arthritis receiving adalimumab.

OBJECTIVE: To report a case of a patient with psoriatic arthritis (PsA) receiving adalimumab, who developed an exacerbation of palmoplantaris pustulosa psoriasis. CASE SUMMARY: A 38-year-old woman diagnosed with PsA had received treatment with non-steroidal antiinflammatory drugs. Two months prior to admission, the patient had a Disease Activity Score of 3.8; diclofenac therapy was suspended and physicians considered treatment with adalimumab. Chest X-rays were normal and the tuberculin skin test was negative. Treatment with adalimumab was started. After the third dose of adalimumab, the patient developed an exacerbation of psoriatic skin lesions on palms and soles. The clinical course was consistent with an exacerbation of palmoplantaris pustulosa psoriasis. Adalimumab treatment was suspended. The patient was treated with oral methotrexate 2.5 mg once weekly. One month after methrotexate was started, the patient developed a severe alopecia. Methrotexate therapy was suspended. Three months later, the patient continued with psoriatic skin lesions on palms and soles. Treatment with Psoralen and ultraviolet A therapy was initiated and the patient condition improved without occurrence of psoriatic skin lesions in the next 4 months. DISCUSSION: Cases of worsening or exacerbation of psoriatic skin lesions induced by anti-tumour necrosis factor (TNF) agents in patients diagnosed PsA are infrequently described in the literature. The most likely cause of the exacerbation of palmoplantaris pustulosa psoriasis in this case was considered to be adalimumab because of the close temporal relationship between exposure to the drug and onset of symptoms. Adalimumab was the only identifiable precipitant that the patient encountered before the exacerbation of psoriasis developed. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered probable. CONCLUSIONS: Patients initiated on adalimumab therapy should be closely monitored for the development of exacerbation of psoriasis. Clinicians should be aware of this rare adverse effect of this anti-TNF drug.

Kinetic alteration of theophylline at therapeutic doses.

OBJECTIVE: To report a case of a patient diagnosed as having bronchial asthma treated with intravenous infusion of theophylline, who presented an episode of altered theophylline metabolism with a disproportionately increase in serum concentrations together with tachycardia and symptoms of intoxication. CASE SUMMARY: A 51-year-old white woman with a history of bronchial asthma was treated with intravenous infusion of theophylline in an Intensive Care Unit. Bayesian pharmacokinetic approach for dose individualization was done and linear kinetics of theophylline were observed. At therapeutic dose, an alteration of theophylline metabolism had happened, that induced a decrease on the theophylline clearance coinciding with an increase of dose. The serum concentration at this dose was 23.9 microg/ml and this was associated with symptoms compatible with intoxication by theophylline. All factors that could change theophylline elimination were analyzed. A possible drug interaction, hypothyroidism and cardiac failure were ruled out. Clinical hepatic insufficiency was not determined, but an increase of hepatic enzymes was observed. Theophylline infusion was suspended during 5 hours, the serum levels returned to therapeutic values and hepatic enzymes returned to their initial values. DISCUSSION: Episodes of anormal theophylline kinetics may occur, even with doses and serum concentrations considered to be therapeutic, especially in critically ill patients or those whose physical condition has deteriorated. This makes it necessary to carry out therapeutic drug monitoring of theophylline in this group of the population.

Evaluation of once daily tobramycin dosing in critically ill patients through Bayesian simulation.

OBJECTIVE: To evaluate if once-daily dose (ODD) regimens of tobramycin attain pharmacodynamic goals using individualized pharmacokinetic monitoring of critically ill patients with creatinine clearance (Clcr) over 60 mL/min. METHODS: Fifty-one adult critically ill patients treated with intravenous tobramycin with ODD were included in the study. The effect of dosing using the proposed method was compared with a weight-based (7 mg/kg) dosing method. Pharmacokinetics parameters, peak concentration (Cpeak), minimum concentration (Cmin) and the time below the minimum inhibitory concentration (MIC) were estimated using Bayesian analysis. Pharmacodynamic parameters used to evaluate both dosing regimens were Cpeak/MIC ratio and, secondly, time below MIC (T< MIC). RESULTS: The median dose of tobramycin administrated in our hospital was too low for achieving pharmacodynamic goals. In contrast, the weight-based (7 mg/kg) method produced an adequate Cpeak/MIC ratio but an increase of the dose would not reduce the secondary pharmacodynamic index T60 mL/min achieved the Cpeak/MIC target values of 10. However in critically ill patients with Clcr>80 mL/min, T