A rapid host-protein test for differentiating bacterial from viral infection: Apollo diagnostic accuracy study.

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.

Increasing Incidence of Streptococcus anginosus Group Intracranial Infections Associated With Sinusitis, Otitis Media, and Mastoiditis in Children.

BACKGROUND: The Streptococcus anginosus group (SAG) pathogens have the potential to cause head and neck space infections, including intracranial abscesses. Several centers noted an increase in intracranial abscesses in children during the SARS-CoV-2 pandemic, prompting a Centers for Disease Control and Prevention health alert in May 2022. We examined the epidemiology of pediatric intracranial abscesses at a tertiary care center with a focus on SAG pre- and post-pandemic. METHODS: Cases of intracranial abscesses of any microbiologic etiology admitted from January 2011 to December 2022 were identified using International Classification of Diseases 10 codes. Subjects were cross-referenced with culture results from the microbiology laboratory at Texas Children's Hospital. Cases included were those associated with either otitis media, mastoiditis or sinusitis and medical records were reviewed. RESULTS: A total of 157 cases were identified and 59.9% (n = 94) were caused by SAG. The incidence of all sinogenic/otogenic intracranial infections (P = 0.002), and SAG-specific infections (P = 0.004), increased from 2011 to 2022. SAG infection was more often associated with multiple surgeries, and these subjects were more likely to require craniotomy or craniectomy. Among sinogenic abscesses, S. intermedius was the most common pathogen, while among otogenic cases, S. pyogenes predominated. From March 2020 to Dec 2022, 9/49 cases tested positive for SARS-CoV-2 (18.4%); characteristics of infection were not significantly different among cases with and without SARS-CoV-2. CONCLUSIONS: Over the last decade, intracranial complications of sinusitis/otitis have been increasing, specifically those caused by SAG; this trend, however, predated the SARS-CoV-2 pandemic. SAG was associated with a greater need for surgical intervention, specifically neurosurgery. Further work is necessary to determine the cause for these rising infections.

Acute Hematogenous Osteomyelitis of the Pelvis in Children.

BACKGROUND: Pelvic involvement has been reported in 3%-14% of acute hematogenous osteomyelitis (AHO) cases in children. One guideline suggests need for a longer antibiotic course in pelvic AHO, however, recent data are lacking. We describe the clinical course of children with pelvic AHO and compare it to nonpelvic AHO. METHODS: A retrospective review of patients with a diagnosis of AHO admitted to Texas Children's Hospital from January 2012 to December 2020 was conducted. Patients 6 months-<19 years old and with ≤14 days of symptoms at admission were eligible. Patients with sickle cell disease or immunocompromised were excluded. Wilcoxon rank-sum test assessed for differences between continuous variables and Fisher exact for categorical variables using STATA 17. RESULTS: We compared 104 cases of pelvic AHO to 314 cases of nonpelvic AHO. Patients had similar microbiology, length of stay and length of antibiotic therapy. Patients with pelvic AHO had pyomyositis identified by magnetic resonance imaging more often (28.8 vs. 9.4%, P < 0.001) and bone abscess less often (22.1 vs. 46.5%, P < 0.001). Rates of chronic complications were comparable between patients with pelvic AHO and nonpelvic AHO (8.4% vs. 15.1%, P = 0.1). Nineteen patients (18.3%) with pelvic AHO received ≤30 antibiotic days without complications, but they had less need for intensive care or bone abscesses than patients treated longer. CONCLUSIONS: Pelvic AHO in children may be more frequent than previously reported but is not associated with more complications. Four weeks of therapy may be sufficient in selected patients. Prospective studies to compare outcomes with different lengths of therapy are needed.

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 at 2 Children's Hospitals.

Background: Invasive infections caused by Streptococcus pyogenes (invasive group A streptococcus [iGAS]) and Streptococcus pneumoniae (invasive pneumococcal disease [IPD]) decreased substantially at the beginning of the COVID-19 pandemic. Our study sought to evaluate the extent of this decrease and the trends of these infections since reversion of societal adjustments incident to the pandemic. We also wanted to compare the frequency of these infections with invasive community-onset Staphylococcus aureus (I-CO-SA) infections and common respiratory viral infections in this period. Methods: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution. Results: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In 2022, RSV and influenza infection rates increased to prepandemic winter season rates, coinciding with a return to prepandemic rates of IPD (225% increase from 2021 to 2022) and a surge above prepandemic rates of iGAS infections (543% increase from 2021 to 2022). Conclusions: The COVID-19 pandemic had an unexpected influence on IPD and iGAS infections that was temporally related to changes in rates of viral infections.

Assessing Risk for Complications in Acute Hematogenous Osteomyelitis in Children: Validation of 2 Predictive Scores.

BACKGROUND: Acute hematogenous osteomyelitis (AHO) can be associated with severe complications which can be difficult to predict in the clinical setting. The previously published predictive acute complication score ("A-SCORE") and chronic complication score ("C-SCORE") show promise, however, further external validation is needed. METHODS: We performed a retrospective study of 418 children with AHO and analyzed the performance of A-SCORE (variables included bone abscess, fever after 48 h of starting antibiotics, suppurative arthritis, disseminated disease, and delayed source control) to predict risk for acute complicated course (treatment failure, prolonged admission, and/or need for ≥2 bone debridements) and C-SCORE (includes disseminated disease, bone debridement, and CRP ≥10 mg/dL at 2-4 days after starting antibiotics) to predict chronic complications (growth restriction, pathologic fracture, chronic osteomyelitis, avascular necrosis, joint deformity, and/or frozen joint). RESULTS: An acute complicated course occurred in 106/418 (25.4%); 51/380 (13.5%) with complete follow-up data had a chronic complication. The A-SCORE performed with similar specificity (78%) and negative predictive value (NPV) (92%), and higher sensitivity (81%) and increased area under the receiver operating curve (AUC) (0.87) in our population. The C-SCORE performed with similar sensitivity (64%) and NPV (94%) but had lower specificity (86%) and AUC (0.71) than originally reported. Other variables associated with development of complications such as tibia involvement and bacteremia ≥2 days were identified but did not result in significantly improved predictive scores. CONCLUSIONS: Predictive A-SCORE and C-SCORE for AHO complications in children may help guide acute management and long-term follow-up decisions. Prospective studies are needed to determine their applicability.

Pediatric Swine Model of Methicillin-Resistant Staphylococcus aureus Sepsis-Induced Coagulopathy, Disseminated Microvascular Thrombosis, and Organ Injuries.

Sepsis-induced coagulopathy leading to disseminated microvascular thrombosis is associated with high mortality and has no existing therapy. Despite the high prevalence of Gram-positive bacterial sepsis, especially methicillin-resistant Staphylococcus aureus (MRSA), there is a paucity of published Gram-positive pediatric sepsis models. Large animal models replicating sepsis-induced coagulopathy are needed to test new therapeutics before human clinical trials. HYPOTHESIS: Our objective is to develop a pediatric sepsis-induced coagulopathy swine model that last 70 hours. METHODS AND MODELS: Ten 3 weeks old piglets, implanted with telemetry devices for continuous hemodynamic monitoring, were IV injected with MRSA (n = 6) (USA300, Texas Children's Hospital 1516 strain) at 1 × 109 colony forming units/kg or saline (n = 4). Fluid resuscitation was given for heart rate greater than 50% or mean arterial blood pressure less than 30% from baseline. Acetaminophen and dextrose were provided as indicated. Point-of-care complete blood count, prothrombin time (PT), activated thromboplastin time, d-dimer, fibrinogen, and specialized coagulation assays were performed at pre- and post-injection, at 0, 24, 48, 60, and 70 hours. Piglets were euthanized and necropsies performed. RESULTS: Compared with the saline treated piglets (control), the septic piglets within 24 hours had significantly lower neurologic and respiratory scores. Over time, PT, d-dimer, and fibrinogen increased, while platelet counts and activities of factors V, VII, protein C, antithrombin, and a disintegrin and metalloproteinase with thrombospondin-1 motifs (13th member of the family) (ADAMTS-13) decreased significantly in septic piglets compared with control. Histopathologic examination showed minor focal organ injuries including microvascular thrombi and necrosis in the kidney and liver of septic piglets. INTERPRETATIONS AND CONCLUSIONS: We established a 70-hour swine model of MRSA sepsis-induced coagulopathy with signs of consumptive coagulopathy, disseminated microvascular thrombosis, and early organ injuries with histological minor focal organ injuries. This model is clinically relevant to pediatric sepsis and can be used to study dysregulated host immune response and coagulopathy to infection, identify potential early biomarkers, and to test new therapeutics.

New Antibiotics for Staphylococcus aureus Infection: An Update from the World Association of Infectious Diseases and Immunological Disorders (WAidid) and the Italian Society of Anti-Infective Therapy (SITA).

Staphylococcus aureus is an extremely virulent pathogen that is capable of quickly evolving and developing antibiotic resistance. To overcome this problem, new antibiotics have been developed. Some of these have been licenced for use in clinical practice, mainly for the treatment of adults with acute skin and soft tissue infections, in addition to both community-acquired pneumonia (CAP) and nosocomial pneumonia (hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia). In this paper, the main characteristics and clinical use of new licenced anti-staphylococcal drugs have been discussed. In vitro studies have demonstrated that some new anti-staphylococcal antibiotics have better antimicrobial activity and, at least in certain cases, more favourable pharmacokinetic properties and higher safety and tolerability than the presently available anti-staphylococcal drugs. This suggests that they may have a potential use in reducing the risk of failure of S. aureus therapy. However, an in-depth analysis of microbiological and clinical studies carried out with these new drugs seems to indicate that further studies need to be conducted before the problem of resistance of S. aureus to the antibiotics available today can be completely solved. Considering the overall available research, the drugs that are active against S. aureus appear to present a great therapeutic opportunity for overcoming resistance to traditional therapy. There are advantages in the pharmacokinetic characteristics of some of these drugs and they have the potential to reduce hospital stays and economic costs associated with their use.

Association of qacA/B and smr Carriage with Staphylococcus aureus Survival following Exposure to Antiseptics in an Ex Vivo Venous Catheter Disinfection Model.

Many health care centers have reported an association between Staphylococcus aureus isolates bearing efflux pump genes and an elevated MIC/minimal bactericidal concentration (MBC) to chlorhexidine gluconate (CHG) and other antiseptics. The significance of these organisms is uncertain, given that their MIC/MBC is typically far lower than the CHG concentration in most commercial preparations. We sought to evaluate the relationship between carriage of the efflux pump genes qacA/B and smr in S. aureus and the efficacy of CHG-based antisepsis in a venous catheter disinfection model. S. aureus isolates with and without smr and/or qacA/B were utilized. The CHG MICs were determined. Venous catheter hubs were inoculated and exposed to CHG, isopropanol, and CHG-isopropanol combinations. The microbiocidal effect was calculated as the percent reduction in CFU following exposure to the antiseptic relative to the control. The qacA/B- and smr-positive isolates had modest elevations in the CHG MIC90 compared to the qacA/B- and smr-negative isolates (0.125 mcg/ml vs. 0.06 mcg/ml, respectively). However, the CHG microbiocidal effect was significantly lower for qacA/B- and/or smr-positive strains than for susceptible isolates, even when the isolates were exposed to CHG concentrations up to 400 µg/mL (0.04%); this finding was most notable for isolates bearing both qacA/B and smr (89.3% versus 99.9% for the qacA/B- and smr-negative isolates; P = 0.04). Reductions in the median microbiocidal effect were also observed when these qacA/B- and smr-positive isolates were exposed to a solution of 400 µg/mL (0.04%) CHG and 70% isopropanol (89.5% versus 100% for the qacA/B- and smr-negative isolates; P = 0.002). qacA/B- and smr-positive S. aureus isolates have a survival advantage in the presence of CHG concentrations exceeding the MIC. These data suggest that traditional MIC/MBC testing may underestimate the ability of these organisms to resist the effects of CHG. IMPORTANCE Antiseptic agents, including chlorhexidine gluconate (CHG), are commonly utilized in the health care environment to reduce rates of health care-associated infections. A number of efflux pump genes, including smr and qacA/B, have been reported in Staphylococcus aureus isolates that are associated with higher MICs and minimum bactericidal concentrations (MBCs) to CHG. Several health care centers have reported an increase in the prevalence of these S. aureus strains following an escalation of CHG use in the hospital environment. The clinical significance of these organisms, however, is uncertain, given that the CHG MIC/MBC is far below the concentration in commercial preparations. We present the results of a novel surface disinfection assay utilizing venous catheter hubs. We found that qacA/B-positive and smr-positive S. aureus isolates resist killing by CHG at concentrations far exceeding the MIC/MBC in our model. These findings highlight that traditional MIC/MBC testing is insufficient to evaluate susceptibility to antimicrobials acting on medical devices.

Predictive Factors to Guide Empiric Antimicrobial Therapy of Acute Hematogenous Osteomyelitis in Children.

BACKGROUND: Acute hematogenous osteomyelitis (AHO) is a serious infection in children. Pediatric Infectious Diseases Society guidelines recommend empiric methicillin-resistant Staphylococcus aureus (MRSA) therapy in regions where MRSA accounts for more than 10-20% of all staphylococcal osteomyelitis. We sought to examine factors present at the time of admission which may predict etiology and guide empiric treatment for pediatric AHO in a region with endemic MRSA. METHODS: We reviewed admissions with International Classification of Diseases 9/10 codes for AHO from 2011 to 2020 in otherwise healthy children. Medical records were reviewed for clinical and laboratory parameters present on the day of admission. Logistic regression was used to determine clinical variables independently associated with (1) MRSA infection and (2) non- Staphylococcus aureus infection. RESULTS: A total of 545 cases were included. An organism was identified in 77.1% of cases and S. aureus was the most common (66.2%); 18.9% of all AHO cases were MRSA. Organisms besides S. aureus were identified in 10.8% of cases. CRP >7 mg/dL, subperiosteal abscess, history of any prior skin or soft tissue infection (SSTI) and need for intensive care unit admission were independently associated with MRSA infection. Vancomycin was used as an empiric treatment in 57.6% of cases. If the above criteria were relied upon to predict MRSA AHO, empiric vancomycin use could have been reduced by 25%. CONCLUSIONS: Critical illness, CRP >7 mg/dL at the time of presentation, subperiosteal abscess and history of SSTI are suggestive of MRSA AHO, and could be considered when planning empiric therapy. Further work is needed to validate these findings before wider implementation.

Going Back in Time: Increasing Penicillin Susceptibility among Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children's and St. Louis Children's Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ ß-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin MIC determination. blaZ negative isolates with penicillin MIC ≤ 0.125 µg/mL were considered PSSA. Multilocus sequence typing (MLST) was conducted on a subset of isolates. A total of 329 unique isolates were included in the study. The median patient age was 9.2 years (IQR:5.1 to 12.2). Overall, 6.7% of isolates were penicillin susceptible. No PSSA were detected prior to 2015 but increased yearly thereafter. By the final study year, 20.4% of isolates were PSSA (P = 0.001). PSSA were similar to penicillin-resistant MSSA (PR-MSSA) isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. PSSA were of distinct sequence types compared to PR-MSSA. PSSA appears to be increasing among OAI in U.S. children. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. The potential for use of penicillin treatment in PSSA OAI warrants further study.

Amoxicillin and penicillin G dosing in pediatric community-acquired pneumococcal pneumonia in the era of conjugate pneumococcal vaccines.

BACKGROUND: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data. METHODS: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%-50% of the dosing interval. RESULTS: In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard-dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high-dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%-50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens. CONCLUSION: Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.

Reduced Ceftaroline Susceptibility among Invasive MRSA Infections in Children: a Clinical and Genomic Investigation.

Ceftaroline represents an attractive therapy option for methicillin-resistant Staphylococcus aureus (MRSA). Little data is available, however, regarding the frequency of reduced susceptibility (RS) to ceftaroline among pediatric MRSA infections. We screened invasive MRSA isolates at a tertiary children's hospital for ceftaroline RS. Ceftaroline RS occurred in 2.9% of isolates and only among health care associated infections. Ceftaroline RS isolates were more often clindamycin-resistant. Sequencing data indicated the predominance of the CC5 lineage among ceftaroline RS isolates.

Decrease in Pediatric Invasive Pneumococcal Disease During the COVID-19 Pandemic.

Measures to limit SARS-CoV-2 transmission in 2020 reduced other viral infections. Among 7 US children's hospitals, invasive pneumococcal disease cumulative incidence decreased by 46% in 2020 vs 2017-2019. Limited droplet transmission of pneumococci and preceding viral pathogens may be responsible.

Molecular Epidemiology of Contemporary Invasive Haemophilus influenzae Isolates in Texas Children.

Although vaccination has reduced the incidence of Haemophilus influenzae type b, nontypeable H. influenzae and other encapsulated types remain a health threat. Little is known regarding the contemporary molecular epidemiology of these organisms. We conducted multilocus sequence typing on invasive H. influenzae during a period of increasing incidence.

The Indirect Impact of the SARS-CoV-2 Pandemic on Invasive Group a Streptococcus, Streptococcus Pneumoniae and Staphylococcus Aureus Infections in Houston Area Children.

Masking and social distancing have been adopted to mitigate the severe acute respiratory syndrome coronavirus 2 pandemic. We evaluated the indirect impact of severe acute respiratory syndrome coronavirus 2 prevention strategies on invasive Staphylococcus aureus, Streptococcus pneumoniae (pneumococcus) and Group A Streptococcus in Houston area children. We observed a decline in invasive pneumococcal disease and invasive Group A Streptococcus temporally associated with social distancing/masking/school closures.

Follow-up Blood Cultures in Children With Staphylococcus aureus Bacteremia.

BACKGROUND: Staphylococcus aureus is a common pathogen seen in pediatric bloodstream infections. Currently, no evidence-based recommendations are used to guide decisions on the number of follow-up blood cultures (FUBCs) needed to demonstrate infection clearance. Unnecessary cultures increase the risk of false-positives, add to health care costs, and create additional trauma to children and their families. In this study, we examined risk factors for persistent S aureus bacteremia (SAB) and intermittent positive blood cultures (positive cultures obtained after a documented negative FUBC result) to determine the number of FUBCs needed to demonstrate infection clearance in children. METHODS: Patients ≤18 years who were hospitalized with SAB at Texas Children's Hospital in 2018 were reviewed. We assessed the impact of an infectious disease diagnosis (central line-associated bloodstream infection, osteomyelitis, soft tissue infection, endocarditis, etc) and medical comorbidities on bacteremia duration. Patients with intermittent positive blood cultures were studied to determine the characteristics of this group and overall frequency of reversion to positive cultures. RESULTS: A total of 122 subjects met the inclusion criteria. The median duration of bacteremia was 1 day (interquartile range: 1-2 days). Only 19 patients (16%) had bacteremia lasting ≥3 days, all of whom had a diagnosis of central line-associated bloodstream infection, osteomyelitis, or endocarditis. Intermittent positive cultures occurred in 5% of patients, with positive cultures after 2 negative FUBC results seen in <1% of patients. Intermittent positive cultures were strongly associated with osteomyelitis and endocarditis. CONCLUSIONS: On the basis of our sample of children with SAB, additional blood cultures to document sterility are not necessary after 2 FUBC results are negative in well-appearing patients.

Vancomycin Therapeutic Drug Monitoring in Children: New Recommendations, Similar Challenges.

The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists have recently published revised guidelines for the therapeutic monitoring of vancomycin. Previous iterations of the guideline largely focused on targeting vancomycin trough concentrations (VTCs) in the range of 15 to 20 mg/L for therapeutic efficacy. The revised guidelines shift the focus of therapeutic monitoring directly to AUC/MIC-based therapeutic monitoring for children, with a suggestion of a goal AUC/MIC 400 to 800. The primary hesitation in applying these recommendations to children stems from the absence of pediatric clinical data demonstrating correlations with clinical outcomes and either VTC or AUC and no benefit in other secondary outcomes (e.g., recurrence, duration of bacteremia). One can glean indirectly from this that such aggressive dosing and monitoring strategies are unnecessary to achieve therapeutic success in the majority of children with serious methicillin-resistant Staphylococcus aureus infections. Providers should carefully weigh the potential unknown benefits of targeting vancomycin AUC 400 to 800 mg*hr/L in children with the known risks of acute kidney injury associated with increasing the dose of vancomycin as well as the substantial time, effort, and costs of this process.