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Background: Antimicrobial use in livestock is one of the factors contributing to selection and spread of resistant microorganisms in the environment. National veterinary antimicrobial consumption monitoring programs are therefore in place in a number of countries in the European Union. However, due to differences in methodology, results on veterinary antimicrobial consumption from these national monitoring programs cannot be compared internationally. International comparison is highly needed to establish regulations on veterinary antimicrobial use and reducing antimicrobial resistance. The aim of this study was to assess differences in the outcomes on veterinary antimicrobial consumption by applying three different sets of nationally established animal defined daily dosages to the same antimicrobial drug delivery dataset of Dutch pigs in 2012. Methods: Delivery information for the complete Dutch pig sector for the year 2012 reported to the Netherlands Veterinary Medicines Authority (SDa) was analysed with three differently and nationally established animal defined daily dosages from the Netherlands and Denmark: the Defined Daily Dosage AnimalNL (DDDANL), the Animal Daily DosageDK (ADDDK) and Defined Animal Daily DosageDK (DADDDK). For each applied Dutch product equivalent, Danish products were identified based on authorization for pigs, active substance (including form), administration route, concentration and dosage regimen. Results: Consumption in number of ADDDK/Y was lower than in number of DDDANL/Y for sows/piglets and finisher pigs, with proportions of 83.3 % and 98.3 %. Use in number of DADDDKK/Y was even lower, 79.7 % for sows/piglets and 88.1 % for finisher pigs compared to number of DDDANL/Y. At therapeutic group level proportions of number of DADDDK/Y to number of DDDANL/Y were 63.6-150.4 % (sows/piglets) and 55.6-171.0 % (finisher pigs). Proportions were > 100 % for the polymyxines (sows/piglets 150.4 % and finisher pigs 149.9 %) and the macrolides/lincosamides (finisher pigs 171.0 %). Conclusions: Differences between nationally established animal defined daily dosages caused by different correction factors for long-acting products and national differences in authorized dosages, have a substantial influence on the results of antimicrobial consumption in pigs. To enable international comparison of veterinary antimicrobial consumption data, harmonized units of measurement, animal weights and animal (sub) categories are needed. [ABSTRACT FROM AUTHOR]

Objectives: (1) To determine the pharmacokinetics of sequential intravenous and enteral fluconazole in the serum of surgical intensive care unit (ICU) patients with deep mycoses. (2) To determine the concentrations of fluconazole reached at the site of infection. (3) To determine if enteral administration of fluconazole, which has an important pharmaco-economic advantage, is justified in this specific patient group.Design: Descriptive, sequential study as a part of a therapeutic drug monitoring programme.Setting: Eighteen-bed surgical ICU in a referral centre.Patients: Fourteen critically ill surgical patients with recent gastro-intestinal (GI) surgery and deep mycosis caused by a fluconazole-susceptible fungus and a calculated creatinine clearance of more than 40 ml/min.Interventions: Fluconazole dosage regimen: 400 mg i. v. every 24 h with an extra dose of 400 mg i.v. after 12 h on day 1. If the clinical condition allowed enteral administration on day 4, the content of two capsules of 200 mg was given via the feeding tube with concomitant enteral feeds.Measurements and Main Results: Serum, exudate from the site of infection and urine samples collected at assumed steady state ( after > or = 5 doses). Fluconazole concentrations were determined by high-performance liquid chromatography (HPLC). The mean area under the concentration curve (AUC0-24 h) in serum after enteral administration did not significantly differ from the AUC0-24 h during intravenous treatment. The elimination half-life was longer compared to healthy volunteers. The mean (95% CI) estimated bioavailability was 124 (90-158)%. The mean (95% CI) area under the concentration time curves (AUCs) achieved in the exudate from the site of infection were 67 (55-79)% of the AUCs reached in serum for both regimens.Conclusions: In critically ill patients with recent GI surgery and/or peritonitis the bioavailability of enteral fluconazole was adequate. The concentrations of fluconazole reached in exudate were lower than those in serum for both regimens, but adequate to treat most cases of deep mycoses in this specific patient group. [ABSTRACT FROM AUTHOR]

During the last few decades, several carbapenems have been developed. The major characteristic of the newer drugs, such as MK-826, is a prolonged half-life. Alternatively, some carbapenems have been developed that can be given orally, such as CS-834 and L-084. Although imipenem and panipenem have to be administered with a co-drug to prevent degradation by the enzyme dehydropeptidase-1 and reduce nephrotoxicity, the newer drugs such as meropenem, biapenem and lenapenem are relatively stable towards that enzyme. Structural modifications have, besides changes in pharmacology, also led to varying antimicrobial properties. For instance, meropenem is relatively more active against Gram-negative organisms than most other carbapenems, but is slightly less active against Gram-positive organisms. Except for half-life and bioavailability, the pharmacokinetic properties of the carbapenems are relatively similar. Distribution is mainly in extracellular body-water, as observed both from the volumes of distribution and from blister studies. Some carbapenems have a better penetration in cerebrospinal fluid than others. In patients with renal dysfunction, doses have to be adjusted, and special care must be taken with imipenem/cilastatin and panipenem/betamipron to prevent accumulation of the co-drugs, as the pharmacokinetic properties of the co-drugs differ from those of the drugs themselves. However, toxicity of the co-drugs has not been shown. The carbapenems differ in proconvulsive activity. Imipenem shows relatively the highest proconvulsive activity, especially at higher concentrations. Pharmacodynamic studies have shown that the major surrogate parameter for antimicrobial efficacy is the percentage of time of the dosage interval above the minimum inhibitory concentration (MIC). The minimum percentage percentage of time above the MIC (TaM) needed for optimal effect is known in animals (30 to 50%), but not in humans. It is probably less than 100%, but may be higher than 50%. Dosage regimens currently in use result in a TaM of about 50% at 4 mg/L, which is the current 'susceptible' breakpoint determined by the National Committee for Clinical Laboratory Standards (NCCLS) for most micro-organisms. Dosage regimens in patients with reduced renal clearance should be based on the TaM. The increased half-life of the newer carbapenems will probably lead to less frequent administration, although continuous infusion may still be the optimal mode of administration for these drugs. The availability of oral carbapenems will have a profound effect on the use of carbapenems in the community. [ABSTRACT FROM AUTHOR]

The most important pharmacodynamic parameter for beta-lactam antibiotics has been shown to be the time above the MIC, which is used as an argument to administer beta-lactam antibiotics by continuous infusion. Studies in vitro and in laboratory animals comparing efficacy of continuous and intermittent infusion of beta-lactam antibiotics generally show continuous infusion to be more efficacious. While comparative trials in humans are scarce and a significant difference was only found in subgroup analysis in one study, several case-reports support the use of continuous infusion. Arguments in favour and against continuous infusion are discussed. Although dose-ranging studies have not yet been performed in humans, the results from in-vitro and in-vivo experiments indicate that 4 x MIC for the infecting bacterium would be the target concentration. Pharmacokinetic studies which have been performed in humans during continuous infusion show that serum concentrations can be predicted from total clearance or, using population pharmacokinetic modelling, the elimination rate constant as obtained during intermittent infusion. A nomogram is presented which allows calculation of the daily dose to obtain the target steady state blood concentrations suggested by the susceptibility of the infecting bacterium, usually 4 x MIC. For bacteria with a low MIC, the daily dose may be substantially lower than that used in conventional dosing regimens, while in infections which are difficult to treat as a result of more resistant bacteria, continuous infusion may be more effective than an equivalent bolus dose. [ABSTRACT FROM AUTHOR]

We investigated the emergence of resistance to 15 anti-pseudomonal antibiotics amongst Pseudomonas aeruginosa isolates from 34 chronically colonized patients with cystic fibrosis by comparing the susceptibilities of strains isolated before 1987 and after 1989 from the same patients. Strains obtained after 1989 from a further 19 patients who were newly colonized served as controls. The 34 pairs of isolates demonstrated a marked increase in resistance which could not be accounted for by a general increase in resistance during the intervening years since the susceptibility patterns of strains isolated before 1987 were similar to those of strains isolated from patients in the control group. There was a strong correlation between this increase in resistance and both the frequency of admissions to and the number of days spent in hospital. Cluster analysis of the changes in susceptibility for individual antibiotics revealed four distinct patterns of resistance: the fluoroquinolones, with the exception of ofloxacin; the aminoglycosides; the ureidopenicillins and aztreonam; and the cephalosporins, carbapenems, carboxypenicillins and ofloxacin. We conclude that the long-term administration of anti-pseudomonal antibiotics to patients who are chronically colonized with P. aeruginosa is associated with the development of resistance. [ABSTRACT FROM AUTHOR]

The pharmacokinetics and penetration into suction blister fluid of meropenem was investigated after intermittent (10 mg/kg/6 h) and during continuous infusion (10 mg/kg/6 h) in eight healthy male volunteers in a crossover fashion. Concentrations in serum, urine and blister fluid were determined by a HPLC method. The pharmacokinetic parameters in serum (±s.d.) r1/v/AUC and clearance after the third dose of intermittent infusion were 62·7 (11·4) min, 43·5 (7·1) mg.h/L and 292·1 (36·8) mL/min respectively. The penetration in blister fluid was rapid and good, with a AUC ratio blister fluid/serum of 84·7 (11·4)% During continuous infusion, from 12 to 18 h after the start of the infusion, the mean concentration in serum was 6·3 (0·7, S.D.) mg/L and in blister fluid 54 (0·7, s.d.) mg/L. The clearance was 338·3 (45·6) mL/min for scrum. Urinary recovery was 61·6 (8·7)% after intermittent and 61·9 (6·9)% after continuous infusion. [ABSTRACT FROM PUBLISHER]

Background: The objective of the study was to estimate the prevalence of gonorrhoea and chlamydial infections and to determine sexual and demographic correlates for these sexually transmitted diseases (STD) among visitors of an STD clinic.Methods: In 1994, a cross-sectional study was carried out among 2984 consecutive visitors of the STD clinic of the University Hospital Rotterdam.Results: The prevalence of chlamydial infection was 12.1% for women and 12.3% for men. For gonorrhoea, prevalence was 3.2% and 6.0%, respectively. For men, gonorrhoea was independently associated with multiple partners in the last month, homosexual activities, a history of gonorrhoea, last sexual contact in the past 4-14 days and casual partners. In contrast, chlamydial infection was less likely to be found in homosexual men and male intravenous drug users. Additionally, chlamydial infection was independently associated with young age, multiple partners in the last 6 months and with last sexual contact in the past 2 months. For women, intravenous drug use (associated with commercial sex work) and a history of trichomoniasis were independent risk factors for gonorrhoea. Independent risk factors for chlamydial infection in women were: young age, two or three sexual partners during life and last sexual contact within 2 months. Chlamydial infection was uncommon in commercial sex workers.Conclusions: The differences in the epidemiological correlates suggest that chlamydial infection is more diffusely spread into the general population than gonorrhoea. Additionally, it is hypothesized that men acquire their chlamydial infection through less stable relationships and subsequently infect their regular female partner. [ABSTRACT FROM AUTHOR]

Focuses on the use of combination chemotherapy for the treatment of invasive infections by Scedosporium prolificans. Other treatment options; Pathogenesis of the disease.