Intravenous azithromycin-induced ototoxicity.

Intravenous azithromycin is increasingly administered for treatment of hospitalized patients with community-acquired pneumonia. Macrolide antibiotics cause ototoxicity, which occurs most frequently when high serum concentrations are achieved. Current dosing guidelines for intravenous azithromycin can result in much higher serum concentrations than is seen with oral administration. We describe a 47-year-old woman who developed complete deafness after receiving 8 days of intravenous azithromycin.

Spontaneous resolution of rhodococcal pulmonary infection in a liver transplant recipient.

Pulmonary infection by Rhodococcus equi is characterized by indolent infection in an immunocompromised host with a propensity to form cavitary lesions. Mortality can be greater than 50%; treatment involves prolonged therapy with multiple antibiotics and, occasionally, surgical resection. Recurrence is common. We report a case of a liver transplant patient with a pulmonary nodule caused by R equi; the nodule followed a benign clinical course and resolved spontaneously. This case illustrates that the spectrum of disease caused by R equi is not fully appreciated and that significant pitfalls complicate the diagnosis and management of infection by this unusual and probably underrecognized pathogen.

A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough.

OBJECTIVE: Recent studies suggest an association between chronic cough and gastroesophageal reflux. Our study aims were 1) to define the prevalence of acid reflux induced cough in the general community, 2) to examine the ability of esophageal testing to identify gastroesophageal reflux related cough, and 3) to assess the utility of omeprazole in a chronic cough algorithm. METHODS: Patients with chronic cough of unknown etiology, who were mostly from the community, were evaluated. Subjects underwent a chest x-ray, methacholine challenge test, and empiric trial of postnasal drip therapy, and completed daily cough symptom diaries subjectively evaluating cough frequency and severity on a graded scale of 0-4 (combined maximum 8). After excluding other causes of cough, the remaining patients underwent esophageal and pH testing. Those testing positive were randomized to omeprazole 40 mg b.i.d. or placebo for 12 weeks. Follow-up was 1 yr. RESULTS: A total of 71 patients were screened; 48 were excluded. Twenty-three patients were evaluated for gastroesophageal reflux disease; six (26%) were eventually determined to have an acid-related cough. Of these patients, 17 had a positive pH test, six (35%) of whom showed a striking improvement or resolution of their cough during omeprazole treatment which was sustained for up to 1 yr. Six had a negative pH test, none of whom responded to omeprazole therapy. No significant differences were seen between responders (n = 6) and nonresponders (n = 11) for demographic factors, baseline symptom frequency and duration, or physiological parameters (motility/pH). CONCLUSIONS: Acid-related chronic cough was present in 26% (six of 23) of patients evaluated for gastroesophageal reflux disease. Esophageal testing does not reliably identify patients with acid induced chronic cough responsive to proton pump inhibitor therapy. We suggest that the best diagnostic and therapeutic approach, after excluding asthma and postnasal drip syndrome, is empiric treatment for 2 wk with a high dose proton pump inhibitor.

The humoral immune response to influenza vaccination in lung transplant patients.

The purpose of this study was to evaluate the humoral immune response to influenza vaccination in lung transplant recipients. Antibody levels to the three viral antigens included in the 1999-2000 trivalent influenza vaccine (A/Sydney/5/97-like (H3N2), A/Beijing262/95-like (H1N1), and B/Yamanashi/16/ 98) were measured before and 4 weeks postvaccination in 43 lung transplant recipients and 21 healthy adult controls. The ability to develop protective antibody levels, a serological response, and the magnitude of change in levels were assessed. The humoral immune response to influenza vaccination was significantly lower in the transplant group for all three viral antigens. To A/Sydney, 95% of the control group and 40% of the transplant group developed protective levels (p=0.0009); to A/Beijing, 71% of the control group and 30% of the transplant group developed protective levels (p=0.004); and to B/Yamanashi, 48% of the control group and 19% of the transplant group developed protective levels (p=0.02). Those receiving cyclosporine had lower antibody responses when compared to those receiving tacrolimus (r=-0.3056, p=0.0463). The humoral immune response to influenza vaccination in lung transplant recipients is poor. Lung transplant recipients receiving cyclosporine may have a lower antibody response than those receiving tacrolimus. Alternative prevention strategies may be needed.

Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients.

BACKGROUND: Invasive aspergillosis is a major cause of morbidity and mortality in lung transplant recipients (LTR), occurring in up to 15% of patients post-transplant. The 14% aspergillus incidence at the Cleveland Clinic Foundation prompted institution of universal prophylaxis with oral itraconazole (ICZ) in 1997. We report our experience with two protocols of ICZ administration in non-cystic fibrosis LTR and the interaction with cyclosporine (CSA). METHODS: Group 1 patients (n=12) were administered ICZ capsules in a fasting or fed state, with or without a histamine-2 (H-2) receptor antagonist or proton pump inhibitor. Group 2 patients (n=12) received the same protocol as group I, but in a fed state with a carbonated beverage (cola) to increase acidity in the stomach to enhance absorption of ICZ. The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n=10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, concentration, cost, and random ICZ levels were documented over a 4-month period of time and compared using generalized estimating equations. RESULTS: The daily CSA mg/kg/d dose decreased over time in all three groups, but no differences were found between the three groups. The CSA dosing interval over time was significantly prolonged in group 2 compared to group 1 or the control group (p< or =0.003). Over time, there was no difference in CSA concentration between all groups. There was no difference in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control group (p=0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p=0.019). CONCLUSIONS: ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolongation of CSA dosing interval. Although daily CSA dosage trended lower in group 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend verifying ICZ absorption with an itraconazole level, especially when CSA intervals are not prolonged.

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.

BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.