Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS

OBJECTIVE: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. DESIGN: A phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine. SETTING: Eight clinical sites in the United States. PATIENTS: Forty-two adult HIV-infected patients with confirmed or presumed acute TE. METHODS: Patients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy. MAIN OUTCOME MEASURES: Patient response was evaluated clinically and radiologically. RESULTS: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose. CONCLUSION: The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.     

Clinicians' perceptions of the problem of antimicrobial resistance in health care facilities

BACKGROUND: Many clinicians do not comply with guidelines regarding antimicrobial resistance (AR). In response, the Centers for Disease Control and Prevention developed a national Campaign to Prevent Antimicrobial Resistance in Healthcare Settings that presents 4 strategies and 12 evidence-based steps. METHODS: To assess clinicians' perceptions of AR, barriers and facilitators to preventing AR, and how best to reach clinicians, a questionnaire and 4 focus groups were conducted after presentation of the Campaign at 4 Pittsburgh Regional Healthcare Initiative hospitals. RESULTS: One hundred seventeen clinicians completed the questionnaire; 28 participated in the focus groups. Clinicians were significantly more likely to perceive that AR was a problem nationally than in their own institution (95% vs 77%; P<.001) or practice (95% vs 65%; P =.002), consistent with focus group results (93% nationally vs 46% institution or practice). The 3 Campaign steps with the most barriers to implementation were "Treat infection, not colonization" (35%), "Stop treatment when infection is cured or unlikely" (35%), and "Practice antimicrobial control" (33%). Clinicians in the focus groups cited the additional barriers of the health care culture, lack of knowledge, and the nursing shortage; facilitators included education, information technology, and consults. Computer programs, posters, and local data were suggested for reaching clinicians about AR. CONCLUSIONS: Clinicians perceive AR to be a complex national problem but less relevant to their own institution or practice. Providing clinicians with information and steps for preventing AR, as in the Campaign, may affect their perceptions of the problem and motivate them to take actions to ensure patient safety.     

Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome

OBJECTIVES: Bowel urgency is one of the most bothersome symptoms for nonconstipated IBS patients. The efficacy of alosetron in control of bowel urgency and Global Improvement of IBS symptoms were evaluated in a multicenter double-blind, randomized, placebo-controlled study. METHODS: Female IBS patients with lack of satisfactory control of bowel urgency were randomized 2:1 to alosetron 1 mg twice daily or placebo treatment groups. The primary endpoint was the proportion of days with satisfactory control of bowel urgency during the 12-wk treatment period and 2-wk follow-up period. Secondary endpoints included IBS Global Improvement (responder defined as patient-reported moderate or substantial improvement in IBS symptoms) and improvements in bowel function (stool frequency, consistency, and sensation of incomplete evacuation). RESULTS: A total of 801 women were randomized to the alosetron (n = 532) or placebo groups (n = 269). Physicians classified 98% of patients with diarrhea-predominant IBS. Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period (73% vs 57%, p < 0.001). A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 (76% vs 44%, p < 0.001). IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 (88% vs 48%) as well as firmer stools, fewer stools/day, and fewer days with incomplete evacuation compared with nonresponders. Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients. Constipation was the most commonly reported adverse event.     

Renal Complications and Their Prognosis in Korean Patients with Middle East Respiratory Syndrome-Coronavirus from the Central MERS-CoV Designated Hospital

Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.     

Patient priorities and needs for diabetes care among urban African American adults

PURPOSE: This study was conducted to determine diabetes care priorities and needs in a group of urban African American adults with type 2 diabetes mellitus. METHODS: One hundred nineteen African American adults with type 2 diabetes, aged 35 to 75, received behavioral/educational interventions from a nurse case manager, a community health worker, or both. Priorities and needs were assessed during 3 intervention visits. RESULTS: The most frequently reported priorities for diabetes care were glucose self-monitoring (61%), medication adherence (47%), and healthy eating (36%). The most frequently addressed diabetes needs were glucose self-monitoring and medication adherence. Most of the intervention visits (77%) addressed non-diabetes-related health issues such as cardiovascular disease (36%) and social issues such as family responsibilities (30%). CONCLUSIONS: Participants' self-reported priorities for diabetes care directly reflected the diabetes needs addressed. Needs beyond the focus of traditional diabetes care (social issues and insurance) are important to address in urban African Americans with type 2 diabetes. Interventions designed to address comprehensive health and social needs should be included in treatment and educational plans for this population.