Dec, 2018

The impact of clinical pathways on antibiotic prescribing for acute otitis media and pharyngitis in the emergency department


Authors: Dona D, Baraldi M, Brigadoi G, et al.

Published in: Pediatr Infect Dis J. 2018;37(9):901-907.

Background Although Italian pediatric antimicrobial prescription rates are among the highest in Europe, little action has been taken to improve the appropriateness of antimicrobial prescriptions. The primary aim of this study was to assess changes in antibiotic prescription before and after acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis Clinical Pathway (CP) implementation; secondary aims were to compare treatment failures and to assess change in the total antibiotics costs before and after CP implementation.

Methods Pre-post quasi-experimental study comparing the 6-month period before CP implementation (baseline period: October 15, 2014, through April 15, 2015) to the 6 months after intervention (postintervention: October 15, 2015, through April 15, 2016).

Results Two hundred ninety-five pre- and 278 post intervention emergency department visits were associated with AOM. After CP implementation, there was an increase in “wait and see” approach and a decrease in overall prescription of broad-spectrum antibiotics from 53.2% to 32.4% (P < 0.001). One hundred fifty-one pre- and 166 post implementation clinic visits were associated with GAS pharyngitis, with a decrease in broad-spectrum prescription after CP implementation (46.4% vs. 6.6%; P < 0.001). For both conditions, no difference was found in treatment failure, and total antibiotics cost was significantly reduced after CP implementation, with a decrease especially in broad-spectrum antibiotics costs.

Conclusions A reduction in broad-spectrum antibiotic prescriptions and a reduction in the total cost of antibiotics for AOM and GAS pharyngitis along with an increase in “wait and see” prescribing for AOM indicate effectiveness of CP for antimicrobial stewardship in this setting.


Apr, 2018

Plasma and CSF pharmacokinetics of meropenem in neonates and young infants : results from the NeoMero studies


Authors: Germovesk E, Lutsar I, Kipepr K, et al.; for NeoMero Consortium

Published in: J Antimicrob Chemother. 2018;73(7):1908-1916

Background Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking.

Objectives To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS).

Methods Data were collected in two recently conducted studies, i.e. Neo-Mero-1 (neonatal LOS) and Neo-Mero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed.

Results A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome.

Conclusions Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.



Apr, 2018

Surveillance for control of antimicrobial resistance


Authors: Tacconelli E, Sifakis F, Harbarth S, et al; for EPI-Net COMBACTE-MAGNET Group

Published in: Lancet Infect Dis. 2018;18(3):e99-e106.

Abstract Antimicrobial resistance poses a growing threat to public health and the provision of health care. Its surveillance should provide up-to-date and relevant information to monitor the appropriateness of therapy guidelines, antibiotic formulary, antibiotic stewardship programmes, public health interventions, infection control policies, and antimicrobial development. In Europe, although the European Antimicrobial Resistance Surveillance Network provides annual reports on monitored resistant bacteria, national surveillance efforts are still fragmented and heterogeneous, and have substantial structural problems and issues with laboratory data. Most incidence and prevalence data cannot be linked with relevant epidemiological, clinical, or outcome data. Genetic typing, to establish whether trends of antimicrobial resistance are caused by spread of resistant strains or by transfer of resistance determinants among different strains and species, is not routinely done. Furthermore, laboratory-based surveillance using only clinical samples is not likely to be useful as an early warning system for emerging pathogens and resistance mechanisms. Insufficient coordination of surveillance systems of human antimicrobial resistance with animal surveillance systems is even more concerning. Because results from food surveillance are considered commercially sensitive, they are rarely released publicly by regulators. Inaccurate or incomplete surveillance data delay a translational approach to the threat of antimicrobial resistance and inhibit the identification of relevant target microorganisms and populations for research and the revitalisation of dormant drug-discovery programmes. High-quality, comprehensive, and real-time surveillance data are essential to reduce the burden of antimicrobial resistance. Improvement of national antimicrobial resistance surveillance systems and better alignment between human and veterinary surveillance systems in Europe must become a scientific and political priority, coordinated with international stakeholders within a global approach to reduce the burden of antimicrobial resistance.


Apr, 2018

Effects of clinical pathway implementation on antibiotic prescription for pediatric community-acquired pneumonia


Authors: Donà D, Zingarella S, Gastaldi A, et al.

Published in: PLoS One. 2018;13(2):e0193581. 

Background Italian pediatric antimicrobial prescription rates are among the highest in Europe. As a first step in an Antimicrobial Stewardship Program, we implemented a Clinical Pathway (CP) for Community Acquired Pneumonia with the aim of decreasing overall prescription of antibiotics, especially broad-spectrum.

Materials and Methods The CP was implemented on 10/01/2015. We collected antibiotic prescribing and outcomes data from children aged 3 months-15 years diagnosed with CAP from 10/15/2014 to 04/15/2015 (pre-intervention period) and from 10/15/2015 to 04/15/2016 (post-intervention period). We assessed antibiotic prescription differences pre- and post-CP, including rates, breadth of spectrum, and duration of therapy. We also compared length of hospital stay for inpatients and treatment failure for inpatients and outpatients. Chi-square and Fisher’s exact test were used to compare categorical variables and Wilcoxon rank sum test was used to compare quantitative outcomes.

Results 120 pre- and 86 post-intervention clinic visits were identified with a diagnosis of CAP. In outpatients, we observed a decrease in broad-spectrum regimens (50% pre-CP vs. 26.8% post-CP, p = 0.02), in particular macrolides, and an increase in narrow-spectrum (amoxicillin) post-CP. Post-CP children received fewer antibiotic courses (median DOT from 10 pre-CP to 8 post-CP, p<0.0001) for fewer days (median LOT from 10 pre-CP to 8 post-CP, p<0.0001) than their pre-CP counterparts. Physicians prescribed narrow-spectrum monotherapy more frequently than broad-spectrum combination therapy (DOT/LOT ratio 1.157 pre-CP vs. 1.065 post-CP). No difference in treatment failure was reported before and after implementation (2.3% pre-CP vs. 11.8% post-CP, p = 0.29). Among inpatients we also noted a decrease in broad-spectrum regimens (100% pre-CP vs. 66.7% post-CP, p = 0.02) and the introduction of narrow-spectrum regimens (0% pre-CP vs. 33.3% post-CP, p = 0.02) post-CP. Hospitalized patients received fewer antibiotic courses post-CP (median DOT from 18.5 pre-CP to 10 post-CP, p = 0.004), while there was no statistical difference in length of therapy (median LOT from 11 pre-CP to 10 post-CP, p = 0.06). Days of broad spectrum therapy were notably lower post-CP (median bsDOT from 17 pre-CP to 4.5 post-CP, p <0.0001). No difference in treatment failure was reported before and after CP implementation (16.7% pre-CP vs. 15.4% post-CP, p = 1).

Conclusions Introduction of a CP for CAP in a Pediatric Emergency Department led to reduction of broad-spectrum antibiotic prescriptions, of combination therapy and of duration of treatment both for outpatients and inpatients.



Dec, 2016

Pharmacodynamics of vancomycin for CoNS infection: experimental basis for optimal use of vancomycin in neonates


Authors: Ramos-Martin R , Johnson A, Livermore J, et al.

Published in: J Antimicrob Ther 2016;71(4):992-1002

Objectives CoNS are the most common cause of neonatal late-onset sepsis. Information on the vancomycin

pharmacokinetics/pharmacodynamics against CoNS is limited. The aim of this study was to characterize vancomycin

pharmacokinetic/pharmacodynamic relationships for CoNS and investigate neonatal optimal dosage


Methods A hollow fibre and a novel rabbit model of neonatal central line-associated bloodstream CoNS

infections were developed. The results were then bridged to neonates by use of population pharmacokinetic

techniques and Monte Carlo simulations.

Results There was a dose-dependent reduction in the total bacterial population and C-reactive protein levels.

The AUC/MIC and Cmax/MIC ratios were strongly linked with total and mutant resistant cell kill. Maximal amplification of resistance was observed in vitro at an fAUC/MIC of 200 mg.h/L. Simulations predicted that neonates, 29 weeks post-menstrual age are underdosed with standard regimens with respect to older age groups.

Conclusions The AUC/MIC and Cmax/MIC ratios are the pharmacodynamic indices that best explain total and

resistant cell kill in CoNS infection. This suggests that less-fractionated regimens are appropriate for clinical

use and continuous infusions may be associated with increased risk of emergence of antimicrobial resistance.

This study has provided the pharmacodynamic evidence to inform an optimized neonatal dosage regimen to

take into a randomized controlled trial


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