Antibiotic impregnated catheters and intrathecal antibiotics for CSF shunt infection prevention in children undergoing low-risk CSF shunt surgery.

BACKGROUND: Cerebrospinal fluid (CSF) shunts allow children with hydrocephalus to survive and avoid brain injury (J Neurosurg 107:345-57, 2007; Childs Nerv Syst 12:192-9, 1996). The Hydrocephalus Clinical Research Network implemented non-randomized quality improvement protocols that were shown to decrease infection rates compared to pre-operative prophylactic intravenous antibiotics alone (standard care): initially with intrathecal (IT) antibiotics between 2007-2009 (J Neurosurg Pediatr 8:22-9, 2011), followed by antibiotic impregnated catheters (AIC) in 2012-2013 (J Neurosurg Pediatr 17:391-6, 2016). No large scale studies have compared infection prevention between the techniques in children. Our objectives were to compare the risk of infection following the use of IT antibiotics, AIC, and standard care during low-risk CSF shunt surgery (i.e., initial CSF shunt placement and revisions) in children. METHODS: A retrospective observational cohort study at 6 tertiary care children's hospitals was conducted using Pediatric Health Information System + (PHIS +) data augmented with manual chart review. The study population included children ≤ 18 years who underwent initial shunt placement between 01/2007 and 12/2012. Infection and subsequent CSF shunt surgery data were collected through 12/2015. Propensity score adjustment for regression analysis was developed based on site, procedure type, and year; surgeon was treated as a random effect. RESULTS: A total of 1723 children underwent initial shunt placement between 2007-2012, with 1371 subsequent shunt revisions and 138 shunt infections. Propensity adjusted regression demonstrated no statistically significant difference in odds of shunt infection between IT antibiotics (OR 1.22, 95% CI 0.82-1.81, p = 0.3) and AICs (OR 0.91, 95% CI 0.56-1.49, p = 0.7) compared to standard care. CONCLUSION: In a large, observational multicenter cohort, IT antibiotics and AICs do not confer a statistically significant risk reduction compared to standard care for pediatric patients undergoing low-risk (i.e., initial or revision) shunt surgeries.

Utilization trends in cerebrospinal fluid shunt infection prevention techniques in the United States from 2007 to 2015.

OBJECTIVE: The objective of this study was to describe trends in the utilization of infection prevention techniques (standard care, intrathecal [IT] antibiotics, antibiotic-impregnated catheters [AICs], and combination of IT antibiotics and AICs) among participating hospitals over time. METHODS: This retrospective cohort study at six large children's hospitals between 2007 and 2015 included children ≤ 18 years of age who underwent initial shunt placement between 2007 and 2012. Pediatric Health Information System + (PHIS+) data were augmented with chart review data for all shunt surgeries that occurred prior to the first shunt infection. The Pearson chi-square test was used to test for differences in outcomes. RESULTS: In total, 1723 eligible children had initial shunt placement between 2007 and 2012, with 3094 shunt surgeries through 2015. Differences were noted between hospitals in gestational age, etiology of hydrocephalus, and race and ethnicity, but not sex, weight at surgery, and previous surgeries. Utilization of infection prevention techniques varied across participating hospitals. Hydrocephalus Clinical Research Network hospitals used more IT antibiotics in 2007-2011; after 2012, increasing adoption of AICs was observed in most hospitals. CONCLUSIONS: A consistent trend of decreasing IT antibiotic use and increased AIC utilization was observed after 2012, except for hospital B, which consistently used AICs.

Associations of Standard Care, Intrathecal Antibiotics, and Antibiotic-Impregnated Catheters With Cerebrospinal Fluid Shunt Infection Organisms and Resistance.

BACKGROUND: Infection prevention techniques used during cerebrospinal fluid (CSF) shunt surgery include: (1) standard perioperative intravenous antibiotics, (2) intrathecal (IT) antibiotics, (3) antibiotic-impregnated catheter (AIC) shunt tubing, or (4) Both IT and AIC. These techniques have not been assessed against one another for their impact on the infecting organisms and patterns of antimicrobial resistance. METHODS: We performed a retrospective longitudinal observational cohort study of children with initial CSF shunt placement between January 2007 and December 2012 at 6 US hospitals. Data were collected electronically from the Pediatric Health Information Systems+ (PHIS+) database, and augmented with standardized chart review. Only subjects with positive CSF cultures were included in this study. RESULTS: Of 1,723 children whose initial shunt placement occurred during the study period, 196 (11%) developed infection, with 157 (80%) having positive CSF cultures. Of these 157 subjects, 69 (44%) received standard care, 28 (18%) received AIC, 55 (35%) received IT antibiotics, and 5 (3%) received Both at the preceding surgery. The most common organisms involved in monomicrobial infections were Staphylococcus aureus (38, 24%), coagulase-negative staphylococci (36, 23%), and Cutibacterium acnes (6, 4%). Compared with standard care, the other infection prevention techniques were not significantly associated with changes to infecting organisms; AIC was associated with decreased odds of methicillin resistance among coagulase-negative staphylococci. CONCLUSIONS: Because no association was found between infection prevention technique and infecting organisms when compared to standard care, other considerations such as tolerability, availability, and cost should inform decisions about infection prevention during CSF shunt placement surgery.

Impact of Early Oral Antibiotic Therapy in Infants With Bacteremic Urinary Tract Infections.

OBJECTIVES: To determine the effect of early conversion to oral antibiotics in infants ≤90 days with gram-negative bacteremia and concomitant urinary tract infection on hospital length of stay (LOS) and 30-day revisits for urinary tract infection. DESIGN: This retrospective cohort study included infants ≤ 90 days who had concomitant positive blood and urine cultures with gram-negative bacteremia at 22 hospitals from January 1, 2002 through January 31, 2020. Early oral conversion was defined as a maximum intravenous (IV) duration of 4 days. We conducted a noninferiority test to compare early oral conversion to long IV therapy. A propensity score framework was used to assess comparisons in survey-weighted regression models using matched weights. RESULTS: Among 174 infants, 73 infants received early oral conversion. The LOS was shorter in infants receiving early oral conversion compared to long IV therapy (median 2 days [interquartile range 2, 3] vs 4 days [3, 5]), descriptively (P < .001) and in noninferiority analysis (ratio = 0.43; 90% CI 0.35, 0.53, P < .001). Thirty-day revisits occurred in 5 of 174 (2.8%) of total patients. Early oral conversion did not meet our noninferiority criteria for the 30-day revisits (odds ratio: 4.22, 90%; confidence interval: 0.83, 21.34, P = .91). CONCLUSIONS: Early oral conversion was associated with shorter LOS. The rate of 30-day revisit rates overall was low.

Follow-Up Blood Cultures in Young Infants With Bacteremic Urinary Tract Infections.

BACKGROUND AND OBJECTIVES: Researchers in previous studies suggest that the clinical yield of follow-up blood cultures (FUBCs) is low in infants with bacteremic urinary tract infection (UTI) because persistent bacteremia is rare; however, no researchers have analyzed the practice of routinely obtaining FUBCs. In our study, we evaluate outcomes in infants with FUBCs, examine opportunities for improvement of blood culture practices, and add important information to inform both clinical practice as well as further study. DESIGN: This retrospective cohort study included infants <90 days of age with bacteremia and UTI with the same pathogen at 22 hospitals that make up Intermountain Healthcare between 2002 to 2020. Infants with culture proven meningitis, osteomyelitis, central line infection, and infections occurring during NICU hospitalization were excluded. RESULTS: Total number of patients with bacteremic UTI was 174, 153 (88%) patients had at least 1 FUBC, 14 of 153 (9%) had a positive FUBC with same organism, and 4 of 153 (3%) were contaminants. The length of stay was longer for patients with positive FUBCs. Patients with Escherichia coli are more likely to have a negative FUBC. Readmissions within 30 days were similar among infants with positive FUBCs, negative FUBCs, and no FUBCs. CONCLUSIONS: FUBCs in infants with bacteremic UTI should not be routinely performed, especially for E coli, and it is unclear whether FUBCs improve outcomes.

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.

BACKGROUND: In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. CONCLUSIONS: Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. RESULTS: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

Oral Step-Down Therapy With Levofloxacin for Febrile Neutropenia in Children With Cancer.

BACKGROUND: Although febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline. METHODS: We performed a quasi-experimental, pre-post study of discharge FN treatment at a stand-alone children's hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014). RESULTS: In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03-.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17-.93]) compared to the preintervention time period. CONCLUSIONS: Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics.

Multicenter Initial Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

Antibiotic Timing in Pediatric Septic Shock.

BACKGROUND AND OBJECTIVES: National guidelines advocate for the administration of antibiotics within 1 hour to children with septic shock, although there is variance in the pediatric evidence-based literature supporting this benchmark. Our objective for this study was to describe the association of target time to antibiotic administration (TTAA) with outcomes of children treated for suspected septic shock in a pediatric emergency department. Septic shock is suspected when signs of perfusion and/or hypotension are present. The primary outcome was mortality. Secondary outcomes included PICU admission, hospital and PICU length of stay, and organ dysfunction resolution by hospital day 2. METHODS: We conducted a retrospective study of children <18 years of age admitted from the pediatric emergency department and treated for suspected septic shock between February 1, 2007, and December 31, 2015. Associations between TTAA and outcomes were evaluated by using multivariable linear and logistic regression models obtained from stepwise selection. RESULTS: Of 1377 patients, 47% were boys with a median age of 4.0 (interquartile range 1.4-11.6) years, 1.5% (20) died, 90% were compliant with TTAA goals, 40% required PICU admission, 38% had ≥2 unique complex chronic conditions, 71% received antibiotics in ≤2 hours, and 30% had a culture-positive bacterial etiology. There were no significant associations between TTAA and outcomes. CONCLUSIONS: We found no association with TTAA and any clinical outcomes, adding to the growing body of literature questioning the timing benchmark of antibiotic administration. Although the importance of antibiotics is not in question, elucidating the target TTAA may improve resource use and decrease inappropriate or unnecessary antibiotic exposure.

Intravenous Vancomycin Therapeutic Drug Monitoring in Children: Evaluation of a Pharmacy-Driven Protocol and Collaborative Practice Agreement.

BACKGROUND: Vancomycin optimization is challenging, requiring careful therapeutic drug monitoring (TDM) to avoid toxicity and ensure an efficacious concentration. Most prescriptions are empiric and often discontinued within 72 hours, which makes early TDM unnecessary. Although TDM using trough levels is common, the area under the concentration-time curve (AUC) is the preferred pharmacodynamic target. We studied the effect of a pharmacy-driven vancomycin collaborative practice agreement (CPA) at a children's hospital that delayed TDM up to 72 hours and targeted a 2-point 24-hour AUC of ≥400 mg × h/L. METHODS: We retrospectively reviewed vancomycin courses in patients aged ≥30 days who received vancomycin between April 1, 2011, and August 30, 2017. We implemented the CPA on June 1, 2014. Outcomes included CPA use, use of TDM, dosage adjustments, and development of acute kidney injury; we compared courses given while monitoring only trough levels (TO-TDM) with those given while using the CPA (AUC-TDM). We performed interrupted time series analyses to account for preintervention trends. RESULTS: We included 2379 courses in the TO-TDM period and 2155 in the AUC-TDM period. During AUC-TDM, 87% of the courses were managed by the CPA. In adjusted interrupted time series analyses, CPA implementation was associated with an initial change in level of -0.265 (95% confidence interval [CI], -0.336 to -0.189) TDM and an initial change in level of -0.332 (95% CI, -0.506 to -0.163) dosage adjustments. The 1-year risk of acute kidney injury decreased after CPA implementation (odds ratio, 0.695 [95% CI, 0.539-0.91]). CONCLUSION: The pharmacy-driven vancomycin CPA resulted in less monitoring and fewer dose adjustments without increasing AKI.

Changing trends in IVIG use in pediatric patients: A retrospective review of practices in a network of major USA pediatric hospitals.

The use of immunoglobulins is gradually increasing. Intravenous immunoglobulins (IVIG) are used as replacement therapy for primary and secondary immune deficiencies, and as an anti-inflammatory and immunomodulatory medication for the treatment of neurologic, dermatologic, and rheumatologic diseases. The objective of this study was to analyze trends in the IVIG use in pediatric patients hospitalized to 47 US-based children's hospitals from 2007 to 2014. IVIG was used for the treatment of >2300 primary diagnoses in 53,648 unique patients. The number of IVIG admissions increased by 30.2% during the study period, while the mean rate of IVIG admissions/100,000 admissions increased only 5.8%. Most patients receiving IVIG were children and adolescents. IVIG was frequently used off-label or for the treatment of FDA-approved indications in children under two years of age and BMT patients <20 years of age. Primary immune deficiencies represented only 1.2% of all IVIG admissions. Pediatric patients with mucocutaneous lymph node syndrome (Kawasaki disease, KD) and idiopathic thrombocytopenic purpura (ITP) were two primary consumers of the IVIG. Another top-ranked indications were acute infectious polyneuritis (Guillain-Barré syndrome, GBS) and prophylaxis of infections in patients receiving antineoplastic chemotherapy. IVIG usage is a dynamic process guided by emerging evidence and FDA approval for new indications. IVIG was mostly prescribed for treatment of diseases with pathologic immune responses to foreign of self-antigens. These indications usually, require higher amounts of IVIG per admission. More studies are needed to understand whether IVIG treatments of off-label indications are effective and cost-efficient.

Evaluation of Discharge Antibiotic Prescribing at a Freestanding Children's Hospital: Opportunities for Stewardship.

We conducted a retrospective study to evaluate suboptimal discharge antibiotic prescribing at a children's hospital and found that 27% of the prescriptions were suboptimal. Thirty-three percent of the patients who might have qualified for solid dosage forms received liquid dosages instead. Our findings suggest that opportunities exist for discharge antibiotic-stewardship and pill-swallowing programs.

Outpatient Parenteral Antimicrobial Therapy in Young Infants.

We examined clinical outcomes for 53 young infants (<3 months of age) treated with outpatient parenteral antimicrobial therapy after discharge from a freestanding children's hospital. None of the patients experienced treatment failure or disease progression; 9% of them experienced a catheter-related complication, but this percentage is not different than that for older children.

Pediatric lateral neck infections - Computed tomography vs ultrasound on initial evaluation.

OBJECTIVE: Review the evaluation of children with a deep lateral neck infection and define the impact of initial imaging modality on outcomes and costs. METHOD: Case series, pediatric patients <18 years of age admitted to a tertiary care hospital with lateral neck infection between 01/01/14-05/31/16 as identified by ICD-9 and ICD-10 codes: 289.3 (lymphadenitis, unspecified), 682.1 (cellulitis and abscess of neck), 683 (acute lymphadenitis), I88.9 (nonspecific lymphadenitis, unspecified), L02.11 (cutaneous abscess of neck), L03.221 (cellulitis of neck), and L03.222 (acute lymphangitis of neck). Patients were divided into two groups based on initial imaging modality: primary ultrasound or primary computed tomography. Differences in length of stay, type and total number of imaging studies obtained, number of procedures, hospital readmission, and hospital cost were compared between cohorts. RESULTS: There were 40 (31%) primary ultrasound and 88 (69%) primary computed tomography patients (128 total). Median length of stay was 46 (IQR: 25,90) hours (1.9 days) for primary ultrasound and 63 (IQR: 39,88) hours (2.6 days) for primary computed tomography patients (p = 0.33). Drainage was performed in 48% of both groups. Additional imaging occurred in 17 (43%) primary ultrasound and 18 (20%) primary computed tomography patients (p = 0.02). Readmission occurred in 8 patients (6.3%). Retropharyngeal infection was encountered in 13 patients (10%); this was only discovered in patients who had a computed tomography performed. Median cost per primary ultrasound patients was $5363 (IQR: 3011, 7920) and $5992 (IQR: 3450, 8060) for primary computed tomography patients. CONCLUSIONS: The primary imaging modality (ultrasound or computed tomography) used to work-up children with a lateral neck infection did not impact length of stay or hospital cost. However, a significant subset had a coexisting retropharyngeal infection that was only identified on computed tomography. Future studies are needed to identify appropriate criteria for imaging in the work-up of lateral neck infections.

Rhinovirus in Febrile Infants and Risk of Bacterial Infection.

BACKGROUND: Febrile infants with viral respiratory infections have a reduced risk of bacterial infection compared with virus-negative infants. The risk of concomitant bacterial infection in febrile infants positive for human rhinovirus (HRV) by polymerase chain reaction (PCR) is unknown. METHODS: Infants 1-90 days old managed using the care process model for well-appearing febrile infants and with respiratory viral testing by PCR (RVPCR) in the emergency department or inpatient setting of 22 hospitals in the Intermountain Healthcare system from 2007-2016 were identified. Relative risk (RR) of bacterial infection was calculated for infants with HRV, non-HRV viruses, or no virus detected. RESULTS: Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%) were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial infection was identified in 9.5%. Febrile infants with HRV detected were more likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%; P < .001; RR 2.12 [95% CI 1.43-3.15]). Risk of urinary tract infection was not significantly different for HRV-positive infants at any age, nor was risk of invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully different for infants 1-28 day olds. Infants 29-90 days old with HRV had a decreased likelihood of IBI (RR 0.52 [95% CI 0.34-0.80]). CONCLUSIONS: HRV is common in febrile infants. Detection did not alter risk of concomitant urinary tract infection at any age or risk of IBI in infants 1-28 days old. HRV detection may be relevant in considering risk of IBI for infants 29-90 days of age.

Impact of Antimicrobial Stewardship for Pediatric Outpatient Parenteral Antibiotic Therapy.

We developed an outpatient parenteral antibiotic therapy (OPAT) stewardship program in a freestanding children's hospital to improve the appropriateness of OPAT prescribing. Introduction of the program enabled expert review of nearly 90% of the patients being prepared for discharge with OPAT and was associated with a 24% reduction in OPAT use.

Reducing Pediatric Sternal Wound Infections: A Quality Improvement Project.

OBJECTIVES: To evaluate whether a quality improvement intervention reduces sternal wound infection rates in children after cardiac surgery. DESIGN: This is a pre- and postintervention quality improvement study. SETTING: A 16-bed cardiac ICU in a university-affiliated pediatric tertiary care children's hospital. PATIENTS: All patients undergoing cardiac surgery via median sternotomy from January 2010 to December 2014 are included. The sternal wound infection rates for primary closure and delayed sternal closure are reported per 100 sternotomies. The hospital-acquired infection records were used to identify preintervention cases, while postintervention cases were collected prospectively. INTERVENTION: Implementation of a sternal wound prevention bundle during the preoperative, intraoperative, and postoperative periods for cardiac surgical cases. MEASUREMENTS AND MAIN RESULTS: During the preintervention period, 32 patients (3.8%) developed sternal wound infection, whereas only 19 (2.1%) developed sternal wound infection during the postintervention period (p = 0.04). The rates of sternal wound infection following primary closure were not significantly different pre- and postintervention (2.4% vs 1.6%; p = 0.35). However, patients with delayed sternal closure had significantly lower postintervention infection rates (10.6% vs 3.9%; p = 0.02). CONCLUSIONS: Implementation of a sternal wound prevention bundle during the perioperative period was associated with lower sternal wound infection rates in surgeries with delayed sternal closure.

A Retrospective Study of the Impact of Rapid Diagnostic Testing on Time to Pathogen Identification and Antibiotic Use for Children with Positive Blood Cultures.

INTRODUCTION: Rapid identification of bloodstream pathogens provides crucial information that can improve the choice of antimicrobial therapy for children. Previous impact studies have primarily focused on adults. Our objective was to evaluate the impact of rapid testing in a children's hospital on time to organism identification and antibiotic use in the setting of an established antimicrobial stewardship program. METHODS: We conducted a retrospective study over three consecutive time periods (spanning January 2013-August 2015) as our hospital sequentially introduced two rapid testing methods for positive blood cultures. An antimicrobial stewardship program was active throughout the study. In the baseline period, no rapid diagnostic methods were routinely utilized. In the second period (PNAFISH), a fluorescent in situ hybridization test was implemented for gram-positive organisms and in the third a rapid multiplex PCR (rmPCR) test was employed. For children with positive blood cultures, time to organism identification use and duration of select antimicrobial therapies were compared between periods. RESULTS: Positive blood cultures were analyzed. Median overall time to organism identification was 23, 11, and 0 h in the baseline, PNAFISH, and rmPCR periods, respectively (p < 0.001 for both PNAFISH and rmPCR vs. baseline). For gram-negative organisms, only rmPCR performed significantly faster than baseline (p < 0.001). The duration of vancomycin use for coagulase-negative staphylococci was shorter in both the PNAFISH and rmPCR periods (mean 31 h in the baseline period, 12 and 14 h in the PNAFISH and rmPCR periods, respectively). For MSSA bacteremia, use of vancomycin was significantly decreased only in the rmPCR period (32% of patients vs. 64 and 72% in the baseline and PNAFISH periods; mean duration of 9 h vs. 30 and 26 h). There was no difference in use or duration of broad-spectrum gram-negative therapy across the three time periods. CONCLUSION: Rapid diagnostic testing for children with positive blood cultures results in faster time to identification and can influence antibiotic prescribing in the setting of active antimicrobial stewardship particularly for gram-positive pathogens. FUNDING: Merck.

Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections.

INTRODUCTION: Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections (IFI), including aspergillosis, candidiasis, Scedosporium infection, and Fusarium infection. IFI often occur in immunocompromised patients, leading to increased morbidity and mortality. AREAS COVERED: The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies. Studies have demonstrated superior clinical response when an AUC/MIC >25 or Cmin/MIC >1 is attained in adult patients, correlating to a trough concentration range as narrow as 2-4.5 mg/L; however, these targets are poorly established in the pediatric population. Topics in this discussion include voriconazole use in multiple age groups, predisposing patient factors for IFI, and considerations for clinicians managing IFI. Expert commentary: The relationship between voriconazole dosing and exposure is not well defined due to the large inter- and intra-subject variability. Development of comprehensive decision support tools for individualizing dosing, particularly in children who require higher dosing, will help to increase the probability of achieving therapeutic efficacy and decrease sub-therapeutic dosing and adverse events.