Adherence with bisphosphonate therapy and change in bone mineral density among women with osteoporosis or osteopenia in clinical practice.

UNLABELLED: In clinical practice, adherence with bisphosphonate therapy varies greatly among women with osteoporosis or osteopenia. Our study suggests that better adherence with bisphosphonates confers tangible benefits in terms of graded increases in bone mineral density. Interventions to improve drug adherence should be an important component of disease management. INTRODUCTION: In clinical trials, bisphosphonates have been found to increase bone mineral density (BMD) in women with osteoporosis or osteopenia. In clinical practice, where drug adherence is more variable, change in BMD with bisphosphonate therapy-overall and by level of adherence-is largely unknown. METHODS: A retrospective cohort study was conducted at Henry Ford Health System (Detroit, MI, USA). Study subjects were women who had low BMD at the left total hip (T-score<-1.0), began oral bisphosphonate therapy, and had ≥1 BMD measurements at the left total hip≥6 months following treatment initiation. Change in BMD was calculated between the most recent pretreatment scan and the first follow-up scan. Adherence (i.e., medication possession ratio (MPR)) was measured from therapy initiation to the first follow-up scan. RESULTS: Among 644 subjects, mean age was 66 years, pretreatment BMD was 0.73 g/cm2, and pretreatment T-score was -1.8. Over a mean follow-up of 27.1 months, mean MPR was 0.57 (95% CI, 0.54 and 0.59), and mean percentage change in BMD was 1.5% (1.1 and 1.9%). Within the MPR strata (five consecutive equi-intervals, from low (0-0.19) to high (0.80-1.0)), mean change in BMD was -0.8% (-1.6 and 0.1%), 0.7% (-0.3 and 1.7%), 2.1% (1.1 and 3.0%), 2.1% (1.4 and 2.9%), and 2.9% (2.3 and 3.5%), respectively. In adjusted analyses, percentage change in BMD was higher (by 1.4-3.4%, p<0.05 for all) in the highest four MPR intervals, respectively, versus MPR 0-0.19. CONCLUSIONS: Among women with osteoporosis or osteopenia in clinical practice, better adherence with bisphosphonates appears to confer tangible benefits in terms of increases in BMD.

Development of a standardized susceptibility test for campylobacter with quality-control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem.

A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O2, and 85% N2. Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36 degrees C for 48 hr and 42 degrees C for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at both temperatures, 95-100% of the QC MIC results fell within recommended QC ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C. lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni and C. coli could be reliably tested under both test conditions, growth of C. jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when incubated at 42 degrees C. Therefore, it is recommended that these species only be tested at 36 degrees C.

Comparative serum bactericidal activity of clarithromycin and azithromycin against macrolide-sensitive and resistant strains of Streptococcus pneumoniae.

The serum pharmacodynamics of clarithromycin and azithromycin were studied against isolates of S. pneumoniae, including efflux resistant (M. phenotype) strains, by analyzing their serum bactericidal activity (SBA) over time. Normal healthy subjects were given a single 500 mg oral dose of these macrolides and serum samples were collected over 12 hrs. Paired isolates with MICs ranging from 0.25 ug/ml to 8.0 ug/ml were analyzed. Prolonged (at least 6 hrs) SBA was observed with clarithromycin for strains with MICs < or = 2.0 ug/ml. No SBA was observed in strains with MICs >or = 4.0 ug/ml. Azithromycin exhibited SBA for at least 6 hrs for strains up to a MIC = 0.5 ug/ml. No SBA was observed for isolates with MICs > or = 1.0 ug/ml. In contrast to azithromycin, clarithromycin exhibited SBA for at least one-half of its normal dosing interval against S. pneumoniae strains well above its current susceptibility breakpoint concentration of 0.25 microg/ml. These findings may have relevance to the ongoing debate as to the appropriate susceptibility breakpoints for the newer macrolides.

Is where we are where we were going? A dialogue of two generations.

This article provides the dialogue of a discussion between prominent family physicians from two generations. One, from the first generation of family physicians, was a founder of the specialty who provides insights into the origins of the specialty, its goals and aspirations, and possible future directions. The other, from a younger generation, has been a leader in managed care and its effects on family medicine; this physician discusses future changes in the health care systems and reflects on whether or not family practice will be able to adapt to those changes.

Urinary pharmacodynamics of low-dose ciprofloxacin and ofloxacin.

The incidence of resistant uropathogens to the fluoroquinolones is increasing, but their effectiveness in the urine against these strains is unknown. In this investigation, we studied the urinary pharmacodynamics of ciprofloxacin (100 mg) and ofloxacin (200 mg) against urinary isolates that were moderately resistant to ciprofloxacin (Escherichia coli, MIC = 4; Klebsiella pneumoniae, MIC = 4. Staphylococcus saprophyticus, MIC = 8) and ofloxacin. Seven healthy female volunteers received three doses (one dose every 12 h) of ciprofloxacin and ofloxacin in a randomized, crossover design with a 1-week washout period between regimens. Urine bactericidal activity was determined after the first and third dose of each drug. Both ciprofloxacin and ofloxacin exhibited prolonged (> or = 6 h) urine bactericidal activity against the E. coli and K. pneumoniae isolates after the first dose. No bactericidal activity was demonstrated for ciprofloxacin against the S. saprophyticus strain. In contrast, ofloxacin exhibited urine bactericidal activity for 8 h against this isolate. Similar findings were observed after the third dose, with the exception that ciprofloxacin exhibited a short period (4 h) of bactericidal activity against the S. saprophyticus strain. In summary, low-dose regimens of ciprofloxacin and ofloxacin exhibited prolonged bactericidal activity against moderately resistant strains of common bacterial uropathogens. Only ofloxacin demonstrated bactericidal activity in the urine during the first dosing interval against a moderately resistant isolate of S. saprophyticus.

Pharmacodynamic activity of five oral cephalosporins against Haemophilus influenzae.

STUDY OBJECTIVES: To determine the time above minimum inhibitory concentration (T > MIC) and serum bactericidal activity of five oral cephalosporins against two strains of Haemophilus influenzae. DESIGN: Randomized, crossover study. SETTING: University-associated research center. SUBJECTS: Ten healthy volunteers. INTERVENTIONS: Each subject received a single dose of cefpodoxime 200 mg, cefuroxime 500 mg, cefaclor 500 mg, cefprozil 500 mg, or loracarbef 400 mg each week for 5 weeks. Blood for serum levels was obtained at time zero and 1, 2, 3, 4, 6, 8, and 12 hours after each dose. MEASUREMENTS AND MAIN RESULTS: Cefpodoxime produced serum concentrations above the MIC for more than 90% of the time for both beta-lactamase-negative and -positive strains of H. influenzae. Moreover, it had serum bactericidal activity for 12 hours against both isolates. Cefuroxime was the second most active cephalosporin, with serum concentrations above the MIC of both isolates for 60% of the time. Cefuroxime provided serum bactericidal activity for 12 hours against the beta-lactamase-negative strain and 6 hours against the beta-lactamase-positive strain of H. influenzae. Even though the T > MIC was less than 50% of the study period for the other cephalosporins, all but cefaclor provided serum bactericidal activity for 12 hours against the beta-lactamase-negative isolate. Cefaclor provided measurable serum bactericidal activity for only 3 hours. The duration of serum bactericidal activity of cefprozil, loracarbef, and cefaclor against the beta-lactamase-positive isolate was 4, 2, and 0 hours, respectively. CONCLUSION: Cefpodoxime was the most active cephalosporin studied based on T > MIC and serum bactericidal activity against isolates of H. influenzae.

Prevention of recurrent vaginal candidiasis with weekly terconazole cream.

OBJECTIVE: To investigate the prophylactic use of weekly terconazole 0.8% cream to prevent recurrent episodes of candidal vaginitis. DESIGN: Women with a documented history of recurrent candidal vaginitis (> or = 4 recurrences/y) were enrolled into a secondary prevention trial. None of these women were HIV positive, pregnant, diabetic, or immunosuppressed. Patients were initially treated for a symptomatic episode of candidal vaginitis and then started on weekly applications of terconazole 0.8% cream for 26 weeks. These women were then followed for an additional 26 weeks after therapy. SETTING: A university-affiliated medical school. PARTICIPANTS: The study population consisted of 22 healthy women aged 19-41 years. MAIN OUTCOME MEASURES: Patients were interviewed by phone each week concerning symptoms and compliance. They were also reminded to notify the study investigators any time vaginal symptoms of candidiasis occurred. Patients were examined whenever they developed vaginal symptoms and were treated on the basis of microscopic and culture results. RESULTS: Ten patients had 14 symptomatic cases of vaginitis during the prophylactic phase of the study, but Candida spp. were isolated during only 4 of these episodes. One episode was due to bacterial vaginosis and no pathogenic organisms were found in 9 of these cases. Eighteen of the 20 patients who completed the prophylactic phase were followed after therapy and 14 (78%) of these patients had a current case of candidal vaginitis. This incidence of infection was statistically higher than that observed during the treatment period (p < 0.001). CONCLUSIONS: Weekly applications of terconazole 0.8% cream were effective in preventing recurrent episodes of candidal vaginitis and were well tolerated.