Reliability of assessment of adherence to an antimicrobial treatment guideline.

Assessment procedures for adherence to a guideline must be reliable and credible. The aim of this study was to explore the reliability of assessment of adherence, taking account of the professional backgrounds of the observers. A secondary analysis explored the impact of case characteristics on assessment. Six observers (two hospital pharmacists, two internists and two clinical microbiologists) assessed a random sample of 22 prescriptions made to infectious disease cases admitted to a department of internal medicine between February and August 2001. Agreement between observers with regard to adherence of these prescriptions to guideline recommendations concerning drug choice, duration of treatment, dosage and route of administration was measured using Cohen's kappa. Case characteristics were compared between cases where observers agreed and disagreed with two-sided Fisher's exact test. Agreement between all professionals was moderate for drug choice (0.59), fair for duration of therapy (0.36), moderate for dosage (0.48), and fair for route of administration (0.37). Agreement on drug choice was good within (0.75 and 0.83) and between (0.74) the internists and the hospital pharmacists, but was less within (0.31) the clinical microbiologists and between the clinical microbiologists and the internists (0.44) and the hospital pharmacists (0.42). Within the clinical microbiologists, agreement was good for dosage (0.79) and route of administration (0.66). There was frequent disagreement between observers regarding cases with combination therapy and non-immunocompromised patients. Despite the small number of cases, our results suggest that internists and hospital pharmacists can reliably be used to assess adherence for drug choice. The level of agreement seems to be affected by combination therapy and the immune status of the patient.

Improving compliance with hospital antibiotic guidelines: a time-series intervention analysis.

OBJECTIVES: This study investigated the impact of a combined intervention strategy to improve antimicrobial prescribing at University Hospital Groningen. For the intervention, the antimicrobial treatment guidelines were updated and disseminated in paperback and electronic format. The credibility of the guidelines was improved by consultation with users. In a second phase, academic detailing (AD) was used to improve specific areas of low compliance with the guidelines. MATERIALS AND METHODS: Prescribing data were prospectively collected for 2869 patients receiving 7471 prescriptions for an antimicrobial for an infection covered by the guidelines between July 2001 and September 2003. After collection of baseline data, the guidelines were actively disseminated in February 2002. Next, after a 5 month interval, a second intervention, i.e. an AD approach, addressed suboptimal prescribing of ciprofloxacin and co-amoxiclav. Segmented regression analysis was used to analyse the interrupted time-series data. RESULTS: At baseline, compliance with the drug choice guidelines was 67%. The first intervention showed a significant change in the level of compliance of +15.5% (95% CI: 8%; 23%). AD did not lead to statistically significant additional changes in already high levels +12.5% (95% CI:-3%; 28%) of compliance. Post-intervention compliance was stable at 86%. CONCLUSIONS: Updating the guidelines in close collaboration with the specialists involved followed by active dissemination proved to be an efficient way to improve compliance with guideline recommendations. An 86% compliance level was achieved in this study without compulsory measures. A ceiling effect may have limited the added value of AD.

Selective decontamination of the digestive tract to prevent postoperative infection: a randomized placebo-controlled trial in liver transplant patients.

OBJECTIVE: To determine the efficacy of selective decontamination of the digestive tract (SDD) in patients undergoing elective transplantation of the liver. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Two academic teaching hospitals. PATIENTS: Adult patients undergoing elective liver transplantation: 26 patients receiving SDD and 29 patients receiving a placebo. INTERVENTIONS: Patients undergoing SDD were administered 400 mg of norfloxacin once daily as soon as they were accepted for transplantation. Postoperative treatment for this group consisted of 2 mg of colistin, 1.8 mg of tobramycin, and 10 mg of amphotericin B, four times daily, combined with an oral paste containing a 2% solution of the same drugs until postoperative day 30. Prophylactic intravenous administration of antibiotics was not part of the SDD regimen in this study. Control patients were given a similar regimen with placebo drugs. MEASUREMENTS: The mean number of postoperative bacterial and fungal infections in the first 30 days after transplantation was the primary efficacy end point. Days on a ventilator, days spent in the intensive care unit, and medical costs were registered as secondary outcome variables. MAIN RESULTS: Of the 26 patients undergoing SDD, 22 (84.5%) developed an infection in the postoperative study period; in the placebo group (n = 29), these numbers were not significantly different (25 patients, 86%). The mean number of postoperative infectious episodes per patient was also not significantly different: 1.77 (SDD) vs. 1.93 (placebo). Infections involving Gram-negative aerobic bacteria and Candida species were significantly less frequent in patients receiving SDD (p <.001 and p <.05). Total costs were higher in the group receiving SDD. CONCLUSIONS: Selective decontamination of the digestive tract does not prevent infection in patients undergoing elective liver transplantation and increases the cost of their care. It does, however, affect the type of infection. Infections with Gram-negative bacilli and with Candida species are replaced by infections with Gram-positive cocci.

A prospective, randomized, double-blinded, placebo-controlled trial of empirical teicoplanin in febrile neutropenia with persistent fever after imipenem monotherapy.

Glycopeptide antibiotics are used extensively in the empirical treatment of febrile patients with neutropenia. To come to a more rational and restricted application of these expensive drugs and to reduce the risk of emergence of resistance, we carried out a prospective, double-blinded, placebo-controlled single-centre study to investigate whether the addition of teicoplanin improved the outcome of neutropenic patients who remained febrile after 72-96 h of imipenem monotherapy. Patients with known infections caused by imipenem-resistant microorganisms were excluded. From the 114 evaluable episodes (out of a total of 125) in 105 patients who met the eligibility criteria, 56 episodes were randomized to receive teicoplanin and 58 to placebo. At 72 h after the start of the assigned intervention, 52 (45.6%) of the patients were afebrile; at the end of the aplastic phase, 10 (8.8%) had succumbed. There was no difference between the two study arms. When febrile episodes were subdivided between microbiologically documented infections, clinically documented infections and fevers of unknown origin, again no significant differences were observed. With the exception of methicillin-resistant bacteria, Gram-positive infections seemed to respond well to imipenem monotherapy. It is concluded that the addition of teicoplanin on empirical grounds, i.e. for persistent fever only, is not necessary and that the use of glycopeptides should be restricted to well-defined clinical situations where methicillin-resistant bacteria are involved. Furthermore, it seems that many neutropenic patients respond slowly over more than 72-96 h even when they are treated with antibacterial drugs such as imipenem that are effective against the causative microorganism.

Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long-chain fatty acids.

BACKGROUND: Pancreatic enzyme replacement therapy frequently fails to correct intestinal fat malabsorption completely in cystic fibrosis (CF) patients. The reason for this failure is unknown. OBJECTIVE: We investigated whether fat malabsorption in CF patients treated with pancreatic enzymes is caused by insufficient lipolysis of triacylglycerols or by defective intestinal uptake of long-chain fatty acids. DESIGN: Lipolysis was determined on the basis of breath 13CO2 recovery in 10 CF patients receiving pancreatic enzyme replacement therapy after they ingested 1.3-distearoyl,2[1-13C]octanoyl glycerol ([13C]MTG). Intestinal uptake of long-chain fatty acids was determined by analyzing plasma [13C]linoleic acid ([13C]LA) concentrations after patients ingested [13C]LA. For 3 d, dietary intakes were recorded and feces were collected. RESULTS: Fecal fat excretion ranged from 5.1 to 27.8 g/d (mean+/-SD: 11.1+/-7.0 g/d) and fat absorption ranged from 79% to 93% (89+/-5%). There was no relation between breath 13CO2 recovery and dietary fat absorption (r = 0.04) after ingestion of [13C]MTG. In contrast, there was a strong relation between 8-h plasma [13C]LA concentrations and dietary fat absorption (r = 0.88, P < 0.001). CONCLUSION: Our results suggest that continuing fat malabsorption in CF patients receiving enzyme replacement therapy is not likely due to insufficient lipolytic enzyme activity, but rather to incomplete intraluminal solubilization of long-chain fatty acids, reduced mucosal uptake of long-chain fatty acids, or both.

Antibiotic utilisation for hospitalised paediatric patients.

Antibiotics are among the most commonly prescribed drugs in paediatrics. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies are warranted. Before such policies can be implemented, detailed knowledge of antibiotic prescribing patterns is important. In this combined retrospective and prospective study the utilisation of antibiotics in a paediatric university hospital over three consecutive years has been analysed. Over an 8-week period (1 November-22 December) in 1994, 1995 and 1996 patient charts were reviewed with regard to antibiotic prescription (generic class, dose, duration and indication). A total of 1120 patients were admitted during the study periods. Antibiotics were prescribed at least once for 36% of hospitalised children, although only 12.3% of the patients receiving antibiotics had a proven bacterial infection. During a single hospitalisation 13, 4.7, 2.6, and 2.7% of all children received 2, 3, 4 or more than four antibiotics, respectively. Infants less than 2 years received antibiotics more frequently than older children (25 and 11% respectively, P=0.0256). More children admitted to the intensive care unit received antibiotics compared with patients admitted on medium care units (49.7 and 29.3% respectively, P < 0.0001). They received more often several different antibiotic courses (2.6 courses per patient versus 1.9 courses per patient, P < 0.0001). These children were also given more often intravenous rather than oral antibiotics (P < 0.0001) Significant differences could be found between the generic classes of antibiotics prescribed to children admitted to the intensive care unit and the medium care. However high variability in dose and duration of antibiotic therapy for the same clinical indication was shown. A high percentage of all hospitalised children receive antibiotics. In most cases antibiotics are started on an empirical basis, without proof of a bacterial infection, either before the start of therapy or afterwards. The fact that children admitted to intensive care units and patients of younger age groups are at special risk of receiving multiple courses of antibiotics, together with the knowledge that antibiotic resistance develops in this setting, suggest that strategies to control antibiotic use should focus on these patient populations.

Shift in antibiotic prescribing patterns in relation to antibiotic expenditure in paediatrics.

UNLABELLED: In paediatrics, antibiotics are among the most commonly prescribed drugs. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies are warranted. Before such a policy can be implemented, detailed knowledge of antibiotic prescribing patterns and related costs is important. In this study a shift of antibiotic prescription patterns over time is described in relation to hospital antibiotic expenditure. CONCLUSIONS: A considerable shift in prescription patterns towards more expensive and broader spectrum antibiotics occurs in paediatrics, carrying a risk for the development of antibiotic resistance among the most prevalent micro-organisms in this age group.

A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis.

OBJECTIVE: To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC). PATIENTS AND METHODS: Twenty patients who fulfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study; 10 received intravesical PPS (300 mg in 50 mL of 0.9% sodium chloride) applied twice a week for 3 months and the other 10 received a placebo. Symptomatic relief and objective variables (bladder capacity voiding volumes and urinary frequency) were assessed after 3 months and the long-term outcome of those continuing treatment was determined. RESULTS: Of the patients treated with PPS, four gained significant symptomatic relief compared with only two receiving placebo. Only the urodynamic bladder capacity showed a statistically significant increase in patients treated with PPS (P = 0.047). At 18 months from the start of the study, the symptoms were relieved in eight patients while still receiving PPS instillations and in four without treatment. CONCLUSIONS: These results suggest that intravesical PPS is an effective option for the treatment of IC and shows that the intravesical application of PPS is a safe treatment with no important side-effects.

Creation of four consecutive instantaneous steady-state plasma concentration plateaus of theophylline and enprofylline by repeated infusions with exponentially decreasing delivery rates.

Repeated exponentially decreasing infusions have been used to administer theophylline and enprofylline to show whether it would be feasible to create consecutive plasma concentration plateaus within a few hours. The infusions were carried out on two separate days in 8 stable asthmatics. Before the infusion experiments, the pharmacokinetics of the substances in the individual subjects were determined on a separate day. Plasma concentration rose to the desired level within 5 min after the start of the infusion at each dose level and a stable plasma concentration plateau was maintained during the following 90 min of the infusion. It was possible to achieve 4 subsequent concentration plateaus within a 6 h period. Use of this infusion method resulted in predictable plasma concentrations at all levels and so the method appears safe when the required plasma concentrations are below the toxic level. Apart from clinical situations where effective dosages of drugs must be administered rapidly, the method showed be useful in pharmacological dose-response studies.