Gram-negative resistance is increasing in serious infections, including in children. There are many mechanisms of resistance, most commonly beta-lactamases. The most concerning beta-lactamases are ...AmpC, extended spectrum beta-lactamases, and carbapenemases. Efflux pumps and porins are also important in Pseudomonas infections. For some mechanisms of resistance, dose adjustment of antibiotics may help to overcome resistance and effectively treat infections. Therefore, it is important to consider pediatric pharmacokinetic differences when dosing antibiotics to ensure adequate concentrations are reached and maintained. These considerations important for older antibiotics and newer agents.
Antimicrobial stewardship programs (ASPs) have the potential to effectively deescalate unnecessary methicillin-resistant Staphylococcus aureus (MRSA) coverage. This review summarizes literature ...published from 2014 through 2021 describing contemporary ASP methods and their resulting effectiveness at reducing anti-MRSA agent use (ie vancomycin, linezolid, daptomycin, ceftaroline, and clindamycin). This review of the literature examined the following strategies, which had reports of success in either decreasing the use or duration of anti-MRSA agents: prospective review and feedback, antibiotic timeouts, health system or department protocol changes, polymerase chain reaction (PCR) and rapid testing of patient samples. Most of the current literature continue to support most ASP interventions including antibiotic timeouts, pathways, and molecular testing including MRSA nasal PCRs and rapid diagnostic testing can be successful at reducing unnecessary anti-MRSA use.
Acute hematogenous osteomyelitis (AHO), often occurring in young children, is the most frequently diagnosed type of osteomyelitis in pediatric patients. Optimizing antibiotics is essential as delays ...to receipt of appropriate therapy can lead to chronic osteomyelitis, as well as impairments in bone growth and development. Antimicrobial stewardship programs (ASPs) are in a key position to help improve the care of patients with AHO as they contain a pharmacist with expertise in antibiotic drug selection, optimization of dosing, and microbiologic test review. A literature search of the MEDLINE database was conducted from initiation through January 2018. Articles selected for the review focus on pathogen identification, pharmacokinetics and pharmacodynamics, efficacy and safety in children, transition from intravenous to oral therapy, duration of treatment, and antimicrobial stewardship interventions. This review will highlight the potential roles ASPs can have in improving the management of AHO in pediatric patients. These roles include the creation of clinical pathways, improving testing algorithms, antibiotic choice and dosing, intravenous to oral transitions, duration of treatment, and therapy monitoring. Overall, patients are most effectively treated by focusing treatments on age, presentation, local sensitivities, and directed therapy with pathogen identification.
Although antimicrobials are commonly used in children, it is important to remember that they can have a profound impact on this unique patient population. Inadvertent consequences of antiinfective ...use in children include antimicrobial resistance, infection caused by Clostridium difficile, increased risk of obesity, and adverse drug events. In addition, compared with adults, children have different dosing requirements, antimicrobial formulation needs, pharmacokinetics, and antimicrobial susceptibility profiles. Therefore, pediatric-specific antimicrobial stewardship efforts are needed to promote appropriate use of antimicrobials in children. The primary purposes of this review article are to provide a rationale behind pediatric-focused antimicrobial stewardship and to describe currently available evidence regarding the initiatives of pediatric antimicrobial stewardship programs (ASPs). A literature search of the Medline database was performed (from inception through March 2015). The studies included in this review focus on antimicrobial stewardship interventions in inpatient pediatric settings. Ten inpatient studies involving pediatric-focused antimicrobial stewardship interventions were identified from the published literature. Four studies used the core strategy of prospective audit with feedback; two used prior approval. The remaining four used supplemental antimicrobial stewardship strategies (guidelines, clinical pathways, and computerized decision support tools). In general, the interventions resulted in decreased antimicrobial use, reduced antimicrobial costs, and fewer prescribing errors. Children have unique medical needs related to antimicrobials and deserve focused ASP efforts. The literature regarding pediatric antimicrobial stewardship interventions is limited, but published interventions may serve as paradigms for developing pediatric ASPs as demonstrated by the general success of these interventions.
Methicillin-resistant Staphylococcus aureus (MRSA) has become the most prevalent cause of acute hematogenous osteomyelitis (AHO) in pediatric patients. This increase in MRSA is due to the rise in ...community-acquired MRSA. Therefore, it is important that clinicians are aware of the various and upcoming therapies that cover this bacterium. A literature search of the Medline database was performed from creation through January 2018. Articles chosen for the review emphasize well-established MRSA treatment options for pediatric AHO, newer therapies on the horizon, and important pharmacokinetics and pharmacodynamic concepts for treatment. Traditional therapies, including vancomycin and clindamycin, remain effective for the treatment of pediatric AHO. When these agents cannot be used, evidence in AHO has been growing for daptomycin, linezolid, and ceftaroline. Further initial pediatric data with the long-acting lipoglycopeptides show promise and in the future may provide a role in AHO treatment in children.
Background.Human babesiosis is a tickborne malaria-like illness that generally resolves without complication after administration of atovaquone and azithromycin or clindamycin and quinine. Although ...patients experiencing babesiosis that is unresponsive to standard antimicrobial therapy have been described, the pathogenesis, clinical course, and optimal treatment regimen of such cases remain uncertain. Methods.We compared the immunologic status, clinical course, and treatment of 14 case patients who experienced morbidity or death after persistence of Babesia microti infection, despite repeated courses of antibabesial treatment, with those of 46 control subjects whose infection resolved after a single course of standard therapy. This retrospective case-control study was performed in southern New England, New York, and Wisconsin. Results.All case patients were immunosuppressed at the time of acute babesiosis, compared with <10% of the control subjects. Most case patients experienced B cell lymphoma and were asplenic or had received rituximab before babesial illness. The case patients were more likely than control subjects to experience complications, and 3 died. Resolution of persistent infection occurred in 11 patients after 2–10 courses of therapy, including administration of a final antimicrobial regimen for at least 2 weeks after babesia were no longer seen on blood smear. Conclusions.Immunocompromised people who are infected by B. microti are at risk of persistent relapsing illness. Such patients generally require antibabesial treatment for ⩾6 weeks to achieve cure, including 2 weeks after parasites are no longer detected on blood smear.
Orbital and preseptal cellulitis are most commonly caused by organisms that originate in the upper respiratory tract or from the skin. There is significant variation in antibiotics used, but ...ampicillin-sulbactam, ceftriaxone, metronidazole, clindamycin, amoxicillin, amoxicillin-clavulanate, cefuroxime, and vancomycin are often used in the treatment of these infections. The choice of antibiotic, however, is only one consideration. It is also important that antibiotics are dosed to optimize their pharmacodynamic target attainment. Like other serious infections, therapy can be transitioned from initial intravenous therapy to an oral regimen when there are clear signs of clinical and laboratory improvement. The total duration of therapy for these infections have also been decreasing in recent years with durations of approximately 2 weeks becoming more common, even for orbital or subperiosteal infections. Antimicrobial stewardship programs can work closely with providers who manage these infections to create pathways, choose optimal antibiotics and dosage, transition from intravenous to oral therapy, and provide shortest effective durations.
Pediatric pneumonia is one of the most common causes of childhood infection requiring hospitalization and is a substantial driver of antimicrobial use among hospitalized children. About 12-20% of ...pediatric patients hospitalized with community-acquired pneumonia (CAP) require critical care. Additionally, nosocomial pneumonias (i.e. hospital-acquired and ventilator- associated pneumonias) are responsible for 15-53% of hospital-associated infections and are the most common indication for empiric antibiotics in the pediatric intensive care unit.
Respiratory infections, especially pneumonias, are a strong area for antimicrobial stewardship program (ASP) interventions, as they have been shown to improve patient outcomes while reducing inappropriate antimicrobial use, antimicrobial resistance, and overall costs.
Optimizing the selection of appropriate antimicrobial therapies is difficult for pediatric pneumonias because of the ill-defined definitive diagnostic criteria and difficulty differentiating between viral and bacterial etiology.
The aim of this review is to highlight the role of antimicrobial stewardship efforts in the treatment of pneumonias in critically ill children by discussing the emerging role of diagnostic criteria, the etiology of disease, appropriate targeted antimicrobial selection, and the optimization of antibiotic dosing and pharmacodynamic targets.
Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of severe acute respiratory ...syndrome coronavirus 2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C).
A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion.
The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multiorgan involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized.
Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials.
Abstract
Objective:
To characterize pharmacodynamic dosing strategies used at children’s hospitals using a national survey.
Design:
Survey.
Setting:
Children’s hospitals.
Participants:
Volunteer ...sample of antimicrobial stewardship program (ASP) respondents.
Methods:
A nationwide survey was conducted to gain greater insight into the current adoption of nontraditional dosing methods and monitoring of select β-lactam and fluoroquinolone antibiotics used to treat serious gram-negative infections in pediatric populations. The survey was performed through the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative.
Results:
Of the 75 children’s hospitals that responded, 68% of programs reported adoption of pharmacodynamically optimized dosing using prolonged β-lactam infusions and 35% using continuous β-lactam infusions, although use was infrequent. Factors including routine MIC monitoring and formal postgraduate training and board certification of ASP pharmacists were associated with increased utilization of pharmacodynamic dosing. In addition, 60% of programs reported using pharmacodynamically optimized ciprofloxacin and 14% reported using pharmacodynamically optimized levofloxacin. Only 20% of programs monitored β-lactam levels; they commonly cited lack of published guidance, practitioner experience, and laboratomory support as reasons for lack of utilization. Less physician time dedicated to ASP programs was associated with lower adoption of optimized dosing.
Conclusions:
Use of pharmacodynamic dosing through prolonged and continuous infusions of β-lactams have not yet been routinely adopted at children’s hospitals. Further guidance from trials and literature are needed to continue to guide pediatric pharmacodynamic dosing efforts. Children’s hospitals should utilize these data to compare practices and to prioritize further research and education efforts.
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