Evaluation of broad-spectrum beta-lactam prescriptions (except carbapenems) in a French teaching hospital.

OBJECTIVES: We aimed to assess broad-spectrum beta-lactam prescriptions (except carbapenems) in a French teaching hospital and the impact of controlled dispensing, antimicrobial management team, and antibiotic treatment reassessment on Day 2-3. PATIENTS AND METHODS: We performed a point-prevalence study in all hospital units and analyzed curative antibiotic broad-spectrum beta-lactam prescriptions. The assessment focused on indication, dosing, combinations, revaluation on Day 2-3, and treatment duration. RESULTS: Sixty-seven broad-spectrum beta-lactam prescriptions were identified. The main prescriptions were amoxicillin-clavulanic acid (37%, n=25), ceftriaxone (36%, n=24), and piperacillin-tazobactam (16%, n=11). Indications, doses, combinations, and reassessment on Day 2-3 were appropriate, respectively 90% (n=60), 96% (n=64), 94% (33/35 combinations), and 88% (n=59). However, appropriate treatment durations amounted to only 63% (n=42). The benefit of controlled dispensing was observed in terms of overall antibiotic treatment duration: 86% versus 51% adequacy for uncontrolled dispensing of beta-lactams (P=0.02). The antimicrobial management team improved the antibiotic treatment duration: 73% of appropriate durations versus 44% for beta-lactams not monitored by the team, but this difference was not significant. CONCLUSION: Broad-spectrum beta-lactams were usually well prescribed but the adequacy of treatment duration could be improved, especially by reinforcing the monitoring of prescriptions.

Reduced anthropogenic aerosol radiative forcing caused by biogenic new particle formation.

The magnitude of aerosol radiative forcing caused by anthropogenic emissions depends on the baseline state of the atmosphere under pristine preindustrial conditions. Measurements show that particle formation in atmospheric conditions can occur solely from biogenic vapors. Here, we evaluate the potential effect of this source of particles on preindustrial cloud condensation nuclei (CCN) concentrations and aerosol-cloud radiative forcing over the industrial period. Model simulations show that the pure biogenic particle formation mechanism has a much larger relative effect on CCN concentrations in the preindustrial atmosphere than in the present atmosphere because of the lower aerosol concentrations. Consequently, preindustrial cloud albedo is increased more than under present day conditions, and therefore the cooling forcing of anthropogenic aerosols is reduced. The mechanism increases CCN concentrations by 20-100% over a large fraction of the preindustrial lower atmosphere, and the magnitude of annual global mean radiative forcing caused by changes of cloud albedo since 1750 is reduced by [Formula: see text] (27%) to [Formula: see text] Model uncertainties, relatively slow formation rates, and limited available ambient measurements make it difficult to establish the significance of a mechanism that has its dominant effect under preindustrial conditions. Our simulations predict more particle formation in the Amazon than is observed. However, the first observation of pure organic nucleation has now been reported for the free troposphere. Given the potentially significant effect on anthropogenic forcing, effort should be made to better understand such naturally driven aerosol processes.

Audit of carbapenem prescriptions comparing 2 assessment periods.

OBJECTIVE: The emergence of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae has resulted in the increase of carbapenem prescriptions. The objective of our study was to determine the appropriateness of carbapenem prescriptions from initiation to reassessment of treatment, between 2009 and 2011. PATIENTS AND METHOD: A questionnaire drafted by infectious diseases specialists (IDS) and microbiologists was used to collect clinical and microbiological data concerning carbapenem prescriptions in 2009 and 2011. An IDS then compared the results to assess carbapenem prescription compliance with our hospital's local recommendations. RESULTS: Seventy-one prescriptions were included in 2009 and 32 in 2011. The carbapenem treatment had been most frequently probabilistic to treat nosocomial infections. The microbiological data revealed that the number of multidrug-resistant (MDR) infections had increased between 2009 and 2011, especially infections involving ESBL-producing Enterobacteriaceae. At treatment reassessment, in 2009 and 2011, 15 (21%) and 12 (38%) carbapenem prescriptions were appropriate and continued. Overall, when comparing the 2 periods, prescriptions complied with local guidelines from initiation to reassessment of treatment without any statistically significant difference (68% in 2009 and 75% in 2011). CONCLUSION: Our study results showed that MDR infections had increased and especially infections due to ESBL-producing Enterobacteriaceae; this was consistent with epidemiological data. We also proved that most carbapenem prescriptions were compliant with recommendations. The increased mobile IDS interventions in medical and surgical departments helped reach this rate of compliance. Carbapenem stewardship may be promoted even in a difficult epidemiological context, especially with IDS interventions for the duration of treatment or at treatment reassessment.

A retrospective study of daptomycin use in a Paris teaching-hospital.

OBJECTIVE: We retrospectively studied daptomycin use during 2010 at the Bichat-Claude-Bernard teaching-hospital (Paris) to observe the evolution of daptomycin prescriptions. PATIENTS AND METHODS: Twenty-one patients were included and several parameters were documented: site of infection, bacterial species involved, reason for daptomycin use, dose and clinical outcome. RESULTS: Ninety-five percent of daptomycin prescritions were off-label and most did not comply with local guidelines. Fifteen of the 21 patients were cured (71%), including 9 patients of the 12 with off-label and off-local recommendation prescriptions (75%). Osteitis and Enterococcus spp endocarditis were the new indications. Daptomycin was increasingly used at higher doses: 52% of our patients were given doses above 6mg/kg. Staphylococcus spp. was the most frequent pathogen responsible for infection is our patients, followed by Enterococcus spp. CONCLUSION: Daptomycin use is likely to evolve because of its effectiveness in the treatment of osteitis, left-sided and Enterococcus spp. infective endocarditis. It is generally used at higher doses, which are well tolerated. However, therapeutic monitoring needs to be developed. The antibiotic commission of our hospital gave new recommendations for daptomycin use in 2011.

Stability assessment of ketoconazole in aqueous formulations.

Ketoconazole is an imidazole antifungal agent. It has a wide antifungal spectrum and possesses some antibacterial activity. In inappropriate formulations, especially in aqueous media, ketoconazole molecules may be unsteady. The stability of ketoconazole in aqueous media was assessed as a function of pH, antioxidant and ketoconazole concentrations. It was found that ketoconazole was least stable at pH 1 among the pH values studied (pH 1-9). Since the major degradation pathway was specific acid catalysis, based upon the transition-state theory, the entropy (DeltaS) of the activation was calculated and found to be negative indicating that the activated complex was more constrained than the individual species. The free energy of activation (DeltaG) was estimated to be 30 kcal mol(-1). The viscosity of the formulation was found to be more stable at high pH because carbopol is stable at basic pH and protected ketoconazole. It appears that the amount of ketoconazole in the formulation has a low influence on the degradation mechanisms. The increase of the butylated hydroxytoluene antioxidant levels from 0.05 to 0.4%, adversely affected the stability of ketoconazole. In conclusion, the expected shelf life of the final ketoconazole formulation (pH 7, 0.1% butylated hydroxytoluene) was 15 months.

Assessment of the performance of electrocardiographic computer programs with the use of a reference data base.

To allow an exchange of measurements and criteria between different electrocardiographic (ECG) computer programs, an international cooperative project has been initiated aimed at standardization of computer-derived ECG measurements. To this end an ECG reference library of 250 ECGs with selected abnormalities was established and a comprehensive reviewing scheme was devised for the visual determination of the onsets and offsets of P, QRS, and T waves. This task was performed by a group of cardiologists on highly amplified, selected complexes from the library of ECGs. With use of a modified Delphi approach, individual outlying point estimates were eliminated in four successive rounds. In this way final referee estimates were obtained that proved to be highly reproducible and precise. This reference data base was used to study measurement results obtained with nine vectorcardiographic and 10 standard 12-lead ECG analysis programs. The medians of program determinations of P, QRS, and T wave onsets and offsets were close to the final referee estimates. However, an important variability could be demonstrated between measurements from individual programs and mean differences from the referee estimates amounted to 10 msec for QRS for certain programs. In addition, the variances of all programs with respect to the referee point estimates were variable. Some programs proved to be more accurate and stable when the data from high- vs low-noise recordings were analyzed. Average Q wave durations calculated from ECGs for which programs agreed on the presence of a Q or QS wave differed by more than 8 msec in several program-to-program comparisons. Such differences may have important consequences with respect to diagnostic performance. Various factors that might explain these differences have been determined. The present study demonstrates that to allow an exchange of results and diagnostic criteria between different ECG computer programs, definitions, minimum wave requirements, and measurement procedures urgently need to be standardized.