Changes in the Use of Antibiotics for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Children: A 5-Year Retrospective, Single Center Study.

Monitoring antibiotic use in the pediatric population is a challenge, especially when determining a relationship between specific pathogens, infections, and antibiotic use. We retrospectively analyzed the consumption of anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs from 2017 to 2021 at Istituto Giannina Gaslini by means of defined daily dose (DDD) adopted for adults by World Health Organization. We observed a statistically significant increase in the use of daptomycin and ceftaroline, combined with a decrease in the use of vancomycin. In the same period, we observed an increase in the proportion of bloodstream infections due to MRSA with vancomycin minimally inhibitory concentration (MIC mg/L) = 1, that represented the 100% of cases in 2021. This aspect was combined with the observation that in the 59% of cases, where vancomycin plasma concentrations were evaluated, it was not possible to achieve a ratio of the 24-h area under the concentration-time curve and MIC (AUC0-24/MIC) of vancomycin ≥ 400 mg/L. This study confirms that DDD can be used in pediatrics to monitor antibiotic consumption in relationship with infections epidemiology. Moreover, it describes the presence of vancomycin MIC creep for MRSA also in pediatrics and the difficulties in obtaining effective vancomycin plasma concentrations in children.

Antibiotic defined daily dose in pediatrics. A single center study to proof the principle that a specific pediatric definition could be not needed.

OBJECTIVES: To evaluate if a specific pediatric defined daily dose (PeDDD) can be replaced with the defined daily dose (DDD) indicated by World Health Organization (WHO). METHODS: The 50th percentile of body weight for age of children admitted from 2016 to 2020 at Istituto Giannina Gaslini, Genoa, Italy, was used to calculate PeDDD for vancomycin at 40mg/kg and meropenem at 60mg/kg. Data obtained were then used to calculate the PeDDD number based on the amount of drugs delivered quarterly from 2012 to 2016. Subsequently the DDD number was calculated for vancomycin at 2g and meropenem at 3g. With these results two curves were generated which were then compared for parallelism and area under the curve (AUC). RESULTS: PeDDD was found to be 2.6 times DDD for both drugs, but both curves obtained were parallel and the AUCs were identical CONCLUSIONS: DDD according to WHO definition could be adopted in pediatrics to measure antibiotic consumption and therefore no specific PeDDD could be needed.

The role of pharmacies in haematopoietic stem cell transplantation process: A nationwide survey by Gruppo Italiano Trapianto di Midollo Osseo.

WHAT IS KNOWN AND OBJECTIVE: The aim of this survey, conducted by the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), was to evaluate the involvement of pharmacists in the haematopoietic stem cell transplant (HSCT) program in Italian adult and paediatric centres. METHODS: A 63-item online questionnaire was developed and sent to the Italian Transplant Programs on behalf of GITMO. RESULTS AND DISCUSSION: Overall, 54.7% of the Italian HSCT centres participated in the survey (88.5% adult, 7.7% paediatric, 3.8% mixed), of which 50% were in public hospitals and 50% affiliated with public universities. Just over 80% declared that a pharmacist is involved in the HSCT centre, and 86.5% reported the presence of a documentation system to signal of adverse events, accessible by physicians, nurses and pharmacists in 57.7%. Chemotherapy drugs were centralized in the pharmacy in 98.1% of HSCT centres, while parenteral nutrition was centralized in 55.8%. The use of off-label drugs was authorized by an internal committee and by the regional health authorities in 88.5% of the centres. On univariate analysis, few statistically significant differences were found on response frequencies between public hospitals and university centres or between HSCT centres performing only autologous stem cell transplantation versus other centres performing autologous and allogeneic stem cell transplantation. WHAT IS NEW AND CONCLUSION: This survey suggests that there is good collaboration between pharmacists and physicians and nurses in Italian HSCT transplantation centres. The enhancement of pharmacists dedicated to HSCT programs could improve some problems, for example, the centralization of parenteral nutrition.

Current research in empirical therapy for febrile neutropenia in cancer patients: what should be necessary and what is going on.

INTRODUCTION: Fever is an important complication in neutropenic patients and standard of care calls for empirical broad-spectrum antibiotics, followed by 'empirical' antifungal therapy in persisting fever. Emergence of infections due to resistant bacteria, especially Gram-negatives, and usefulness of empirical antifungal therapy represent the major concerns in this field. AREAS COVERED: Clinical trials registered in 5 international databases were referred for randomized clinical trials (RCTs) of empirical antibacterial therapy or empirical antifungal therapy in neutropenic cancer patients. The majority of RCTs compared antibiotics without major differences in the spectrum of activity, especially in the wake of the present epidemiology with an increase of infections and mortality due to resistant Gram-negatives; oral therapy and home care were analyzed in 3 RCTs. As regards empirical antifungal therapy, 1 ongoing study is comparing 'standard' empirical treatment vs diagnostic-driven approach. EXPERT OPINION: In an era of increasing antibiotic resistance the comparison of different strategies more than that of different drugs will probably represent the future in studies in this field. The next future will tell us if a diagnostic-driven approach is safe for fungal infections, or if we should continue to treat them only on the basis of the persistence of febrile neutropenia.

Invasive mould infections in newborns and children.

Invasive mould infections represent important complications of different pediatric conditions. Epidemiology and clinical features vary according to the type of underlying conditions that determine the risk of invasive mycosis. No pediatric study has specifically evaluated the efficacy of prophylaxis or therapy invasive moulds infections, while pediatric dosages for the treatment of invasive aspergillosis are available for drugs that produced positive results in clinical trials undertaken in adults.

Catheter-related bacteremia caused by methicillin-resistant coagulase negative staphylococci with elevated minimal inhibitory concentration for vancomycin.

Treatment of bacteremia caused by methicillin-resistant coagulase-negative staphylococci with vancomycin minimum inhibitory concentration ≥2 mg/L frequently requires central venous catheter removal in children with cancer. There are few data supporting efficacy and safety of antibiotic catheter lock or use of daptomycin or linezolid for this indication in children.

Pegfilgrastim in children with severe congenital neutropenia.

Two pediatric patients affected by severe congenital neutropenia (SCN) were treated with 100 mcg/L/dose every 9-12 days within a pilot study (Observatory of the Italian Ministry of Health, Eudract Code 2005-003096-20) on the use of pegfilgrastim in patients with chronic neutropenia. Both children increased their absolute neutrophil count, reduced their infectious load, and improved their quality of life. Serum concentrations of G-CSF observed in pegfilgrastim mirrored those seen in filgrastim. These data suggest that pegfilgrastim may be beneficial in SCN patients with an exposure of hematopoietic cells to G-CSF similar to that on filgrastim.