Jack W. Ross

Experience with a once-daily aminoglycoside program administered to 2,184 adult patients.

Once-daily aminoglycoside (ODA) regimens have been instituted to maximize bacterial killing by optimizing the peak concentration/MIC ratio and to reduce the potential for toxicity. We initiated an ODA program at our institution that utilizes a fixed 7-mg/kg intravenous dose with a drug administration interval based on estimated creatinine clearance: > or = 60 ml/min every 24 h (q24h), 59 to 40 ml/min q36h, and 39 to 20 ml/min q48h. Subsequent interval adjustments are made by using a single concentration in serum and a nomogram designed for monitoring of ODA therapy. Since initiation of the program, 2,184 patients have received this ODA regimen. The median dose was 450 (range, 200 to 925) mg, while the median length of therapy was 3 (range, 1 to 26) days. The median age of the population was 46 (range, 13 to 97) years. Gentamicin accounted for 94% of the aminoglycoside use, and the majority (77%) of patients received the drug q24h. The 36-, 48-, and > 48-h intervals were used for 15, 6, and 2% of this population, respectively. Three patients exhibited clinically apparent ototoxicity. Twenty-seven patients (1.2%) developed nephrotoxicity (the Hartford Hospital historical rate is approximately 3 to 5%) after a median of 7 (range, 3 to 19) days of therapy. On the basis of a prospective evaluation of 58 patients and follow-up of additional patients via clinician reports, we have noted no apparent alterations in clinical response with our ODA program. This ODA program appears to be clinically effective, reduces the incidence of nephrotoxicity, and provides a cost-effective method for administration of aminoglycosides by reducing ancillary service time and serum aminoglycoside determinations.

Adherence to Highly Active Antiretroviral Therapy Predicts Virologic Outcome at an Inner-City Human Immunodeficiency Virus Clinic

This studys hypothesis is that human immunodeficiency virus-infected patients in the inner city (predominantly injection drug users and ethnic minorities) do not take highly active antiretroviral therapy (HAART) as prescribed and that nonadherence leads to virologic failure. A prospective, observational, 3-month study of adherence to HAART was undertaken at an inner-city clinic. There were 40 subjects [110 subject-months]; 30 were male, 10 were female, 75% were Hispanic, 23% were African American, 68% were injection drug users, and 68% were receiving triple therapy. At 3 months, adherence, which was determined by use of the Medication Event Monitoring System (Aprex) was significantly associated with virologic success: lower virus loads were associated with a rate of adherence of >80% (P<.05). Although nonadherence predicted virologic failure, virologic success was not always predicted by adherence: 11 (27.5%) of 40 subjects with suboptimal adherence rates (<90%) had complete virologic suppression.

Patterns of adherence to antiretroviral medications: the value of electronic monitoring

Objective: To investigate the patterns of intra-subject (between medication) adherence to antiretroviral therapy. Design: A prospective, observational, 3-month study of adherence to antiretroviral therapy at an inner-city clinic in 40 HIV-infected subjects. Methods: Adherence was monitored monthly by the use of medication event monitoring system (Aprex) caps placed on each antiretroviral drug in a subjects regimen. Agreement between different drug classes and dosing schedules, for each subject, was quantified by estimating the mean difference in adherence, with 95% limits of agreement. An analysis of variance model was used to estimate the variance of the differences. Individual dosing calendars were examined for each subject. Results: The dosing schedule was a strong predictor of intra-subject adherence. Regardless of the subjects overall adherence rate, high or low, when subjects missed a dose of one medication, they missed a dose of both medications taken at that dosing time. Conversely, when medications were scheduled to be taken together, regardless of the drug class, the medications were taken at the same times. The majority of the subjects took medications at obviously incorrect times. Problematical adherence was related to thrice-daily dosing and food restrictions. Conclusion: This is the first report objectively to quantify intra-subject adherence to antiretroviral therapy and report the findings in detail. We observed clear patterns of drug-taking behavior among the subjects in our study. To the extent that medication scheduling is a controllable factor, our report provides an insight into specific patterns of behavior that may be targets for adherence counseling.

Oral Absorption of Trimethoprim‐Sulfamethoxazole in Patients with AIDS

Study Objective. To determine the bioavailability of trimethoprim‐sulfamethoxazole (TMP‐SMX) in patients infected with the human immunodeficiency virus (HIV).

Pharmacoeconomics of Pneumocystis carinii pneumonia in HIV-infected and HIV-noninfected patients.

SummaryDespite the proven effectiveness of Pneumocystis carinii pneumonia (PCP) prophylaxis in both HIV-infected and HIV-noninfected patients, PCP remains an important cause of serious pulmonary infection. Because PCP is a frequent event requiring inpatient admission at our institution, we conducted a study to define the pharmacoeconomics of this infection and the incidence of adverse events associated with anti-PCP therapy.In a retrospective review, 133 patients (101 HIV-positive, 32 HIV-negative) with documented PCP were identified. Significant differences in age, initial arterial oxygen tension (paO2), intensive care unit admission and mortality were evident between HIV-infected and non—HIV-infected patients; however, there were no differences in the duration of hospitalisation or the duration of anti-PCP therapy. The incidence of biochemical abnormalities was similar between the groups. Leucopenia occurred at an incidence of 52 and 31%, while thrombocytopenia occurred at a rate of 7 and 44%, in HIV-positive and HIV-negative patients, respectively. Drug toxicity or treatment failure necessitated a change of therapy in 43% of HIV-positive and 59% of HIV-negative patients.PCP treatment cost, pharmacy cost, hospital cost and net loss (i.e. the difference between hospital cost and reimbursement) were all significantly greater in HIV-negative than in HIV-positive patients. The duration of anti-PCP therapy and the hospital cost for cotrimoxazole (trimethoprim-sulfamethoxazole)- and pentamidine-treated patients were similar, although the treatment cost and pharmacy cost were statistically different in favour of cotrimoxazole. Overall, cotrimoxazole is an inexpensive treatment option. However, the high incidence of adverse events attributed to this agent often necessitates a change to a more costly therapy.

Antibiotic Utilization and Opportunities for Stewardship Among Hospitalized Patients With Influenza Respiratory Tract Infection

OBJECTIVE Hospitalized influenza patients are often treated with antibiotics empirically while awaiting final diagnosis. The goal of this study was to describe the inappropriate continuation of antibiotics for influenza respiratory tract infections (RTIs). DESIGN We retrospectively studied adults admitted to our institution over 2 respiratory flu seasons with positive influenza RTIs. Inappropriate antibiotic duration (IAD) was defined as antibiotic use for >24 hours after a positive influenza test in patients presenting with <72 hours of RTI symptoms and with no other indications of bacterial infection. RESULTS During the study period, 322 patients included in this study were admitted for influenza RTI. Respiratory cultures were ordered for 50 of these patients (15.5%) and 71 patients (22%) had a positive chest x-ray, but antibiotics were prescribed to 211 patients (65.5%) on admission. Antibiotics were inappropriately continued in 73 patients (34.5%). Patients receiving IAD had a longer length of stay (LOS) (median, 6 days; range, 4-9 days) compared with those whose antibiotics were discontinued appropriately (median, 5 days; range, 3-8 days) and those who were not treated with antibiotics (median, 4 days; range, 3-6 days; P<.001). However, mortality was similar among these 3 groups: 3 patients (4.1%) from the IAD cohort died; 6 patients (4.3%) from the group with an appropriate antibiotic duration died; and 2 patients [1.8%] from the group given no antibiotics died (P=.510). The 30-day readmission rates were similar as well: 9 patients (12.3%) from the IAD group were readmitted within 30 days; 21 patients (15.2%) from the group with appropriate antibiotic duration were readmitted; and 11 patients (9.9%) from the group given no antibiotics were readmitted (P=.455). Total hospital costs were greater in patients treated with IAD (

Electronic and Microbiological Detection, Investigation, and Surveillance for Potential Hospital- Acquired Device Associated Infections at ERCP.

10,645; range,

Disorders of iron metabolism associated with protease inhibitor therapy.

6,485-

Randomized, Crossover Adherence Trial of Azithromycin and Clarithromycin for Mycobacterium avium Complex Prophylaxis in AIDS Patients

18,035) compared with the group treated with appropriate antibiotic duration (

Improving Hand Hygiene:Anonymously Validated Data Driven Approach Producing Sustainable Culture Change Utilizing “One and Up” Accountability Agents across a Healthcare System- a Cost-effective National Best Practice.

7,479; range,