Comparison of vancomycin pharmacodynamics (1 g every 12 or 24 h) against methicillin-resistant staphylococci

This study compared the duration of serum bactericidal activity for vancomycin, 1 g every 12 or 24 h at steady state, against methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MR-CNS). All four test isolates were susceptible to vancomycin with minimal inhibitory concentration (MIC) values of either 2 or 4 mg/l. Serum bactericidal titres (SBTs) were run in duplicate and serum bactericidal activity (SBA) was defined as the time points at which all subject SBTs were greater than or equal to 1:2. For the every 12-h regimen, SBA was 10-12 h. With the every 24-h regimen, the duration of SBA was 10-16 h for MRSA and 8-10 h for MR-CNS. The pharmacodynamic data suggest that for those with good renal function a Q12h dosing interval is most appropriate for MR-CNS or staphylococcal isolates with MICs of 4.     

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). Design . Open-label, randomized, two-way crossover trial. Setting . Outpatient clinical research center affiliated with a community-based teaching hospital. Patients . Ten individuals diagnosed with the acquired immunodeficiency syndrome (AIDS) with CD4+ counts less than 200 cells/mm³, receiving TMP-SMX one double-strength tablet 3 times/week as prophylaxis for Pneumocystis carinii pneumonia (PCP), and without documented gastroenteropathy or diarrhea agreed to participate in the trial. One patient withdrew from the study secondary to development of symptomatic PCP. Data were available for analysis from the remaining nine subjects. Interventions . Participants received TMP 160 mg and SMX 800 mg orally or intravenously during two study periods. Following dose administration, blood samples were collected at predetermined time points over 36 hours. Measurements and Main Results . Analysis of TMP-SMX pharmacokinetic parameters (half-life, total body clearance, area under the serum concentration versus time curve, and peak concentration) failed to reveal any significant differences between intravenous and oral preparations. The calculated bioavailabilities of oral TMP and SMX (mean ± SD) were 102.7% ± 19.8% and 109.4% ± 19.4%, respectively. Conclusion . The absorption of TMP-SMX is not adversely affected by HIV infection in the absence of HIV-induced gastroenteropathy or diarrhea.     

Needle catheter jejunostomy versus "Witzel" tube jejunostomy for early postoperative enteral nutrition in surgical patients. Prospective randomized study

Malnutrition in surgical patients can be present since their admission into hospital or can appear in the postoperative period. Early postoperative enteral nutrition (EPEN) is recommended to these patients as often as possible. In cases where the patients are severely malnourished with major digestive surgical interventions which we estimate that will be unable to feed orally efficient minimum 7-10 days postoperatively, we recommend EPEN on jejunostomy. Prospective randomized evaluation of 37 patients (75.6% severely malnourished): 19 with needle catheter jejunostomy (NCJ), group A, respectively 18 with standard "Witzel" tube jejunostomy (STJ), group B. 22 patients presented malignant tumors and 15 serious benign problems. On 7 patients the jejunostomy was done at the reoperation. Postoperative major complications were observed on 54.05% of the patients (independent of the jejunostomy) and the postoperative mortality rate was of 13.33% on the patients that had jejunostomy and EPEN on their first operation, and 57.14 respectively on the patients where jejunostomy was done at the reoperation. The two groups were similar with respect to age, sex, length of EPEN and hospital stay, presence of malnutrition, complications and mortality. Postoperative complications were statistically more frequent in anemic patients (68.8%) respectively anemic and severely malnourished (76.47). Minor complication related to the jejunostomy occurred in 5.6% of the group A and 22.2% of the group B. NCJ was done rapidly the same as STJ (7 min vs. 15 min). In conclusion, EPEN on jejunostomy on surgically malnourished patients, who have suffered major superior digestive interventions is beneficial. Postoperative complications have been more frequent on anemic and severely malnourished. NCJ is easier to perform and safer.     

The importance of potency and durability in HIV patient antiretroviral therapy preferences: a telephone survey

Patients who were receiving or had received antiretroviral therapy (ART) participated in 45-minute telephone interviews to evaluate the importance of major treatment attributes. A Likert scale was used to quantify and rate the importance of 9 ART attributes. Trade-off exercises allowed participants to select a preferred hypothetical ART regimen from two options based on daily dosing and varied efficacy. Participants were asked to assume that all else about the medications was the same. A total of 387 patients were surveyed (72% male; 44% African American, 41% Hispanic; 28% with no high school diploma, 29% high school graduate, 25% college with no degree; 46% infected through men who have sex with men [MSM], 19% infected through injection drug use [IDU]). Efficacy attributes (lowering viral load, raising CD4, durability) were rated as "most important" or "very important" by significantly more patients than other attributes (resistance profile, appearance side effects, gastrointestinal side effects, dosing frequency, pill burden, cholesterol side effects). Similar results were seen for subgroups analyzed by gender, ethnicity, age, line of therapy, region, and route of infection. In the second set of questions, 92% of patients preferred more effective twice-daily regimens over less effective once-daily regimens, and 89% preferred more durable twice-daily regimens over less durable once-daily regimens. Results suggest that potency, immune improvement, and durability of ART regimens are more important to HIV patients than other attributes such as side effects, dosing frequency, or pill burden. These results, in conjunction with other studies, suggest that patients prioritize viral suppression, immune improvement, and regimen durability more highly than regimen convenience.     

Pharmacokinetic properties and stability of continuous-infusion meropenem in adults with cystic fibrosis

BACKGROUND: Meropenem is commonly used to treat lung infections in adults with cystic fibrosis (CF). Although continuous infusion is the ideal method to maximize the pharmacodynamic properties of this betalactam antibiotic, meropenem is stable for only approximately 4 to 6 hours at room temperature, and its pharmacokinetic (PK) properties, when administered by continuous infusion to patients with CF, are largely unknown. OBJECTIVE: This study was undertaken to determine the PK properties and stability of meropenem when administered to adults with CF by a continuous ambulatory drug-delivery infusion pump stored in a cold pouch between 2 freezer packs. METHODS: This open-label, multidose, randomized, crossover PK study was conducted at the Clinical Research Center at Hartford Hospital (Hartford, Connecticut). Adults aged > or = 18 years with CF were eligible. Study participants were randomized to receive meropenem 125 mg/h or 250 mg/h (equivalent to 3 g and 6 g, respectively, over 24 hours) by continuous IV infusion for 12 hours. Serum samples were collected throughout the infusion and then for 6 hours after infusion to determine the PK properties (volume of distribution [V(d)], elimination rate constant, total body clearance [CL], terminal half-life [t 1/2], and steady-state concentration [C(ss)]). Serum meropenem concentrations were assayed using high-performance liquid chromatography, and PK profiles were determined using compartmental analysis. Meropenem stability was ascertained by sampling the drug directly from the infusion pump at prespecified time points. Meropenem tolerability was assessed throughout the study by questioning subjects on how they felt. In addition, laboratory values of serum chemistries and liver enzymes were compared with baseline values. RESULTS: Seven adult volunteers with CF (4 women, 3 men; mean [SD] age, 27 [10] years [range, 19-46 years]) participated in the study. Mean (SD) C(ss) values were 8.31 (0.68) mg/L and 18.50 (3.31) mg/L for the 125-mg/h and 250-mg/h infusion rates, respectively. V(d), CL, and t 1/2 were dose independent and similar between the 2 infusion rates. Meropenem stability was maintained over 12 and 24 hours. Meropenem by continuous infusion was well tolerated. One patient complained of a headache during the study. CONCLUSIONS: In this study of adults with CF, meropenem infusion rates of 125 mg/h and 250 mg/h provided serum drug concentrations greater than the minimum inhibitory concentration for pathogens considered meropenem susceptible (< or =4 microg/mL) and intermediately resistant (8 microg/mL), respectively.     

Prevalence of extended spectrum beta-lactamase producing Escherichia coli and Klebsiella isolates in a large community teaching hospital in Connecticut

The prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESC) and Klebsiella (KS) among consecutive non-urine isolates were evaluated. Twenty-four of 392 isolates produced ESBLs. Among these half were from respiratory sites and all were susceptible to meropenem. Pulse field-gel electrophoresis (PFGE) showed 12 clonally distinct ESBLs and iso-electric focusing (IEF) revealed that most (83%) produced multiple enzymes.     

The role of gender in the long-term prognosis of patients with myocardial infarction submitted to fibrinolytic treatment

PURPOSE: To determine the role of gender in short- and long-term survival after a thrombolytic-treated myocardial infarction. METHODS: A total of 686 consecutive patients with ST-elevation acute myocardial infarction, admitted to a single center and treated with intravenous streptokinase, were studied prospectively and consecutively. Assessment of clinical and in-hospital variables permitted comparison of baseline characteristics and both in-hospital and long-term survival between men and women. RESULTS: A significantly (odds ratio=0.48, P=0.009) lower 14-day mortality rate for males (8.5%) relative to females (16%) was noted. However, this difference became non-significant after adjustment for age (odds-ratio male/female=0.62, P=0.097) or age and other variables (odds ratio=0.71, P=0.17). At the end of the follow-up (up to 12 years), survival rates for the whole population were 59.6% and 54.4% for men and women, respectively (chi-square=1.4, P=0.24); excluding in-hospital deaths, the rates were 65.1% and 64.8%, respectively (chi-square=0.21, P=0.65). CONCLUSIONS: In the short-term follow-up, women have a significantly higher mortality relative to men in an unadjusted analysis. This difference became non-significant after adjusting for age, or age and other variables. In the long-term follow-up, sex was not correlated with prognosis.     

Pharmacodynamics of meropenem and imipenem against Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa

STUDY OBJECTIVE: To compare the pharmacodynamics of meropenem and imipenem, both administered as 500 mg every 6 hours, against populations of Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa. DESIGN: Ten thousand-subject Monte Carlo simulation. INTERVENTION: Variability in total body clearance (ClT), volume of distribution as calculated by the terminal elimination rate (Vdbeta), and minimum inhibitory concentration (MIC) distributions (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, A. baumannii, P. aeruginosa) were derived from the literature for both meropenem and imipenem. For the free drug concentrations, the percentage of the dosing interval that the drug concentrations remain above the MIC (%T>MIC) for each carbapenem-bacteria combination was calculated for 10,000 iterations, substituting a different ClT, Vdbeta, fraction of unbound drug, and MIC into the equation each time based on the probability distribution for each parameter. Probabilities of attaining targets of 30%, 50%, and 100% T>MIC were calculated. MEASUREMENTS AND MAIN RESULTS: Meropenem free drug %T>MIC exposure was significantly greater than that of imipenem against Enterobacteriaceae and P. aeruginosa, whereas imipenem exposure was greater for A. baumannii. For both agents, free drug %T>MIC exposure was greatest against Enterobacteriaceae and less for A. baumannii and P. aeruginosa. Probabilities of target attainment for 30% and 50% T>MIC were similar between drugs for most bacteria. At 100% T>MIC, meropenem target attainments were greater than those of imipenem against Enterobacteriaceae and P. aeruginosa, and imipenem attainment was higher for A. baumannii. CONCLUSION: The probability of attaining lower pharmacodynamic targets for most gram-negative bacteria is similar for these carbapenems; however, differences become apparent as the pharmacodynamic requirement increases. Further study of the benefits of achieving this pharmacodynamic breakpoint with a higher probability of attaining targets is necessary.