Population pharmacokinetics of continuous infusion ceftazidime.

OBJECTIVE: The purpose of this study was to develop and validate a model that predicts clearance and steady-state ceftazidime concentrations during continuous infusion. DESIGN: This was a prospective clinical observational trial. Two models describing drug clearance during the continuous infusion of ceftazidime to infected patients were developed. The first model included inter- and intraindividual variability (IIV) while the second extended the first model by including interoccasional variability (IOV). SETTING: This was a study of patients in a US hospital between January and June 1996. PATIENTS AND PARTICIPANTS: The analysis included 39 patients aged > 18 years with infections at various sites. INTERVENTIONS: Patients received ceftazidime as either a 1000 or 2000mg loading dose followed by a continuous infusion of 1000 to 4000 mg/day. Serum samples were collected under approximate steady-state conditions and ceftazidime concentrations were analysed using high performance liquid chromatography. The models were fitted to the data using a nonlinear mixed effects model as implemented in the NONMEM program. RESULTS: 75 serum concentration measurements were included in the analysis. The routinely available clinical variables bodyweight, age, gender and serum creatinine were found to be statistically independent predictors of ceftazidime clearance. The IIV model was cross validated yielding a mean prediction error (with a 95% confidence interval) of -0.51 mg/L (-2.5 to 1.4 mg/L) and a mean absolute prediction error of 6.5 mg/L (5.3 to 7.8 mg/L). CONCLUSION: We have developed and validated a model to estimate ceftazidime concentrations during continuous infusion using commonly available clinical information. Additional work is needed to compare outcomes of patients receiving continuous and intermittently administered ceftazidime, and to define the optimal target steady-state ceftazidime concentrations during continuous infusion.

Rhodococcus equi pneumonia: case report and literature review.

OBJECTIVE: To present a case of Rhodococcus equi (RE) pneumonia and discuss its pathophysiology and treatment. CASE SUMMARY: An HIV-positive patient presented with pneumonia. A lung biopsy was performed after sputum and thoracentesis cultures failed to identify a pathogen. The lung biopsy revealed an unidentifiable, diphtheroid-like, gram-positive rod. A bronchoscopy performed five days after the lung biopsy produced the same diphtheroid-like, gram-positive rod. The patient was treated with several injectable antibiotics, but emergence of resistance to two of the antibiotics was suspected. Two weeks after the bacterial isolate was sent to a reference laboratory, it was identified as RE. The patient was discharged on oral antibiotics and experienced no recurrence of RE pneumonia. CONCLUSIONS: RE can be difficult to identify in the microbiology laboratory, or it may be assumed to be a colonizing diphtheroid. The isolation of difficult-to-identify, gram-positive rods, or diphtheroids, from a pulmonary source in a patient with decreased cell-mediated immunity should cause one to suspect RE. RE has been noted to develop resistance to beta-lactam antibiotics during therapy. A prolonged course of combination antibiotic therapy directed at the intracellular component of infection is necessary.

Proposed criteria for preoperative endoscopic retrograde cholangiography in candidates for laparoscopic cholecystectomy.

BACKGROUND: There has been a dramatic increase in the number of endoscopic retrograde cholangiograms (ERC) performed on patients who are candidates for laparoscopic cholecystectomy (LC). The majority of these procedures result in normal findings. This study is an attempt to determine useful clinical criteria and strategy for predicting the presence or absence of common bile duct stones (CBDS) and the need for ERC in patients who are candidates for LC. METHODS: The observational portion of this study explored laboratory and ultrasound data from 134 consecutive patients who had undergone preoperative ERC, followed by LC, over a 4-year period. The data were then analyzed by multivariate logistic regression to determine the best models for predicting the presence or absence of stones in the common bile duct. Models using gamma glutamyl transpeptidase (GGT), alkaline phophatase (AP), common bile duct diameter (CBDIA), and amylase (AMY) were then evaluated retrospectively in 36 additional patients (validation group). RESULTS: A model based on GGT and common bile duct diameter as positive predictors and amylase as a negative predictor correctly classified 78% of the patients in the validation group. This model resulted in a negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity of 0.88, 0.68, 0.87, and 0.71, respectively. The model utilizing AP was almost as effective. This model resulted in a NPV, PPV, sensitivity, and specificity of 0.83, 0.67, 0.80, and 0.71, respectively. CONCLUSIONS: Although a number of laboratory values and imaging techniques correlate with the presence or absence of CBDS, our study confirms that individually they have poor predictive value. Our data and models suggest that elevated serum amylase is a negative predictor for CBDS. Elevated GGT and/or AP with widened CBDIA and normal AMY strongly suggest the presence of CBDS and the need for preoperative ERC. Elevated GGT, AP, or widened CBDIA with elevated amylase, in the absence of clinical pancreatitis, may suggest that small stones have passed through the ampulla of Vater and that the CBD is generally cleared of stones.