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The objective was to evaluate the analytical performance of a new point-of-need platform for rapid and accurate measurement of a host-protein score that differentiates between bacterial and viral infection. The system comprises a dedicated test cartridge (MeMed BV®) and an analyzer (MeMed Key®). In each run, three host proteins (TRAIL, IP-10 and CRP) are measured quantitatively and a combinational score (0-100) computed that indicates the likelihood of Bacterial versus Viral infection (BV score). Serum samples collected from patients with acute infection representing viral (0 ≤ score 35), equivocal (35 ≤ score ≤ 65), or bacterial (65 score ≤ 100) scores based on pre-defined score cutoffs were employed for the analytical evaluation studies as well as samples from healthy individuals. To assess reproducibility, triplicate runs were conducted at 3 different sites, on 2 analyzers per site over 5 non-consecutive days. Lower limit of quantitation (LLoQ) and analytical measurement range were established utilizing recombinant proteins. Sample stability was evaluated using patient samples representative of BV score range (0-100). MeMed Key® and MeMed BV® passed the acceptance criteria for each study. In the reproducibility study, TRAIL, IP-10 and CRP measurements ranged with coefficient of variation from 9.7 to 12.7%, 4.6 to 6.2% and 5.0 to 11.6%, respectively. LLoQ concentrations were established as 15 pg/mL, 100 pg/mL and 1 mg/L for TRAIL, IP-10 and CRP, respectively. In summary, the analytical performance reported here, along with diagnostic accuracy established in the Apollo clinical validation study (NCT04690569), supports that MeMed BV® run on MeMed Key® can serve as a tool to assist clinicians in differentiating between bacterial and viral infection.

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.

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 β-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.

Background The clinical presentation and management of acute hematogenous osteomyelitis (AHO) in children can vary significantly. Scores to predict acute complications utilize prolonged fever after antibiotics, bone abscess, suppurative arthritis, disseminated infection and delayed source control. By contrast, elevated CRP after 48-96 hours of therapy, disseminated disease and bone debridement are predictive of chronic complications. Such scoring systems have undergone limited validation. We examined factors associated with acute and chronic AHO complications at our center to identify other variables that may enhance published scores. Methods A retrospective chart review was conducted of all children 6 mo-18 years with AHO and with acute symptoms of < 14 days at Texas Children’s Hospital from January 2012 through December 2020. An acute complicated course was defined as treatment failure within 6 weeks of starting antibiotics, > 2 bone debridements, prolonged admission ( >14 days) and acute avascular necrosis. Chronic complications included growth arrest or limb leg discrepancy, pathologic fracture, avascular necrosis, chronic osteomyelitis or frozen joint. Statistical analysis was completed using STATA 17. Results 418 patients met the inclusion criteria. 106 (25.4%) had an acute complicated course. 51 (13.5%) of 377 followed had a chronic complication. Clinical factors associated with acute and chronic complications were very similar. Factors associated with either an acute complicated course (Figure 1) or chronic orthopedic complications (Figure 2) included: older age, tibia involvement, infection due to S. aureus/MRSA, presence of multifocal or disseminated infection, DVT, fever > 48 hours of antibiotic therapy, admission laboratory values including higher absolute neutrophil count (ANC) and higher CRP, ICU admission, associated suppurative arthritis, bacteremia, bone abscess, surgical debridement and delayed source control. Conclusion In children with AHO, risk factors for acute and chronic complications are highly similar. Older age, tibia involvement, MRSA, higher ANC and bacteremia were linked to complications in our population and will be assessed in current clinical scoring systems which may help guide management. Disclosures Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality: Grant/Research Support|Allergan: Provided reagents for unrelated research|Nabriva: Site investigator for multicenter clinical trial Kristina G. Hulten, PhD, Me-med: Grant/Research Support|Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support.

Background Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. By the 1960s, these strains became the dominant staphylococci in clinical practice. However, a number of centers have recently described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). In our center we have recently observed the emergence of PSSA in osteoarticular infections. Little data are available regarding the prevalence or impact of PSSA in pediatric skin-and-soft-tissue infections (SSTI). Methods MSSA SSTI isolates were obtained through an ongoing surveillance study at Texas Children’s (TCH) from 1/2017-12/2021. Twenty community-acquired MSSA SSTI isolates were chosen at random from every six-month interval during the study period, for a total of 200 isolates to be screened. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were blaZ negative and had a penicillin MIC ≤ 0.125 μg/ml were regarded as PSSA with the remainder regarded as penicillin-resistant MSSA (PR-MSSA). Results During the study period 1701 MSSA SSTI isolates were collected with 200 examined for penicillin susceptibility. The overall median age of subjects was 4.1 years (IQR: 1.6-10.4). PSSA accounted for 9% of isolates during the study period; the annual frequency of PSSA varied from 5-17.5%. PSSA and PR-MSSA cases were similar with respect to age, demographics, anatomic site of infection and rates of prior antibiotic exposure. Subjects with SSTI secondary to PSSA more often had a prior history of SSTI, a diagnosis of abscess and were more often admitted to the hospital (Figure). Among PSSA, 94.4% belonged to agrI and 33.3% were PVL positive. Penicillin-Susceptible S. aureus (PSSA) vs. Penicillin-Resistant Methicillin-Susceptible S. aureus (PR-MSSA) Pediatric SSTI Isolates Comparison of the clinical features of PSSA and PR-MSSA SSTI isolates. PSSA were significantly associated with the diagnosis of abscess as well as hospital admission. Conclusion PSSA account for a small but significant proportion of MSSA SSTI in children. Clinically distinguishing patients with PSSA and PR-MSSA is challenging. However, PSSA SSTI were associated with a greater rate of abscess formation and hospital admission, suggesting a high clinical impact of these infections. Further studies are needed to understand the optimal management of these infections. Disclosures Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality: Grant/Research Support|Allergan: Provided reagents for unrelated research|Nabriva: Site investigator for multicenter clinical trial Kristina G. Hulten, PhD, Me-med: Grant/Research Support|Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support.

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.Using NONMEM v7.3, Monte Carlo simulations (N=10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 hours (standard-dose), AMOX 45 mg/kg/dose PO every 12 hours (high-dose), and PENG 62,500 units/kg/day IV every 6 hours 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 (%fTMIC) across the population of pneumococci for 30-50% of the dosing interval.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 with CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fTMIC in the serum at the susceptible MICs, standard-dose AMOX achieved4% PTA (CLSI) and86% PTA (EUCAST); high-dose AMOX achieved73% PTA (CLSI) and99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved71%,93%, and 100% PTA, respectively, in the serum at 30-50%fTMIC 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.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.

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.

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.

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.

We report 2 infants hospitalized with Cronobacter sakazakii meningitis. Each infant had exposure to powdered infant formula at home. Both infants survived, but 1 infant had a subdural empyema drained and developed left sensorineural hearing loss. Early advanced brain imaging is recommended in infants with C. sakazakii meningitis. Reporting to state and federal public health officials may help identify outbreaks.

All patients with Helicobacter pylori infection should be offered eradication therapy. However, antimicrobial resistance has undermined the success rate of most current eradication therapies. This ...

The molecular epidemiology of Staphylococcus aureus strains causing staphylococcal scalded skin syndrome (SSSS) in the United States has not been described. We analyzed patient and S. aureus isolate characteristics associated with SSSS in children at Texas Children's Hospital.Patients with SSSS were identified by ICD9/10 codes and available S. aureus isolates were identified from an ongoing S. aureus surveillance study. Medical records were reviewed for 58 patients with available S. aureus isolates. Isolate analyses included PCR for agr group, pvl (lukSF-PV), tst, eta and etb, pulsed-field gel electrophoresis, multi-locus sequence typing and antimicrobial susceptibilities.Cases of SSSS increased from 2.3/10,000 admissions in 2008 to 52.6/10,000 admissions in 2017 (P0.0001). The 58 study cases (57 methicillin-susceptible S. aureus, 1 MRSA) with isolates were from 2013 to 2017. The majority (88%) of isolates was of clonal cluster (CC) 121, agr group IV, pvl, tst and carried eta and/or etb and 26% were clindamycin resistant. Twelve ST121 isolates had high level resistance to mupirocin. Patients were treated with standard supportive care plus systemic antibiotics [clindamycin alone or in combination with another antibiotic (n = 44)]. One patient had a recurrent SSSS and one patient was transferred to a burn unit on day 3.Cases of SSSS are increasing at our hospital. Most S. aureus strains isolated were of one CC, CC121 and carried eta and etb. Supportive care plus clindamycin was effective treatment. We speculate that CC121 was recently introduced to our region and is responsible for the increasing numbers of SSSS cases observed at Texas Children's Hospital.

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.

Background and aims: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. Methods: We induced experimental colitis in 8– 12-week-old C57BL/6 mice using 2–3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple-Bacteroides cocktail, individual Bacteroides strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to 16S rRNA gene profiling of fecal and mucosal microbiomes. Results: Triple-Bacteroides combination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatus ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while the presence of Akkermansia correlated with treatment failure. However, the therapeutic benefit associated with high Bacteroides abundance was negated in the presence of Streptococcus. Conclusions: Bacteroides ovatus monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of Bacteroides ovatus ATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.

Most cases of pediatric osteoarticular infections (OAIs) are hematogenous in nature and caused by Staphylococcus aureus. OAI in children can also occur through direct inoculation of microorganisms secondary to penetrating or open trauma. No studies in the United States have evaluated the microbiology or outcomes of trauma-related OAI (TROAI) in children in the era of community-acquired methicillin-resistant S. aureus (CA-MRSA).Cases were identified from the inpatient infectious diseases consultation database at Texas Children's Hospital from January 2011 to December 2016. TROAI cases were those in which OAI developed following a clear history of penetrating trauma, open fracture, crush injury or traumatic amputation. Only cases with radiographic evidence of bone abscess, gross appearance of infection at the time of surgery and/or positive cultures from bone or joint were included. Complications included recurrence of infection, pathologic fracture or chronic osteomyelitis.During the study period, 692 consultations for OAI were performed, with 34 meeting inclusion criteria. In 68%, at least 1 organism was isolated, and the most commonly isolated organisms were S. aureus (32% overall, 21% MRSA) and Enterobacter cloacae (24%). Polymicrobial infections occurred in 38% of patients. Eighty-five percentage of patients had at least 1 surgical procedure, and 38% underwent ≥ 2 procedures. Eighty-two percentage of patients were discharged on oral therapy. Complications developed in 15% of patients and were more commonly associated with E. cloacae (80% vs. 14%, P = 0.007) and fungi (P = 0.03).TROAI are relatively uncommon in children but cause significant morbidity. While MRSA contributes substantially to TROAI, the highly diverse microbiology emphasizes the importance of obtaining cultures for microbiologic diagnosis and management. Clinicians should be aware of the frequency of E. cloacae in TROAI and its high risk for sequelae.

Background Enterobacter species are an important cause of healthcare-associated bloodstream infections (BSI) in children. Up to 19% of adult patients with Enterobacter BSI have recurrence of infection resistant to third-generation cephalosporins (3GCs) while on therapy with a 3GC. Data are lacking regarding the incidence of and risk factors for recurrence of infection in children with Enterobacter BSI. Methods We conducted a retrospective case-control study of patients aged ≤21 years old admitted to Texas Children’s Hospital from January 2012 through December 2018 with Enterobacter BSI. The primary outcome was microbiologic failure from 72 hours to 30 days after the initial BSI (cases). The secondary outcome was isolation of a 3GC non-susceptible Enterobacter sp. from a patient with an initial 3GC-susceptible isolate. Results Twelve patients (6.7%) had microbiologic failure compared to 167 controls without microbiologic failure. Of the 138 patients (77.1%) with an Enterobacter sp. isolate that was initially susceptible to 3GCs, 3 (2.2%) developed a subsequent infection with a non-susceptible isolate. Predictors of microbiologic failure were having an alternative primary site of infection besides bacteremia without a focus or an urinary tract infection (OR, 9.64; 95% CI, 1.77–52.31; P < 0.01) and inadequate source control (OR, 22.16; 95% CI, 5.26–93.36; P < 0.001). Conclusions Source of infection and adequacy of source control are important considerations in preventing microbiologic failure. In-vitro susceptibilities can be used to select an antibiotic regimen for the treatment of Enterobacter BSI in children.

We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. Systemwide patient evaluation processes allowed for prompt identification and management of patients with COVID-19.

BackgroundInvasive Staphylococcus aureus infections are a common cause of morbidity and mortality in children. In the early 2000's the proportion of infections due the methicillin-resistant S. aureus (MRSA) increased rapidly. We described the clinical and molecular epidemiology of invasive S. aureus disease in a pediatric population.MethodsWe prospectively identified children in Utah with invasive S. aureus infections. Medical records were reviewed to determine diagnosis and clinical characteristics. Isolates were genotyped using multi-locus sequence typing. The presence of genes encoding the Panton-Valentine leukocidin (PVL) was determined using polymerase chain reaction.ResultsOver a 4-year period between January 2009 and December 2012, we identified 357 children, hospitalized at Primary Children's Hospital, with invasive S. aureus infections and isolates available for the study. Methicillin-susceptible S. aureus (MSSA) caused 79% of disease, while MRSA caused only 21% of disease. Mortality associated with invasive S. aureus infection was 3.6%. The most common diagnoses were osteoarticular infections (38%) followed by central line associated blood stream infections (19%) and pneumonia (12%). We identified 41 multi-locus sequence types. The majority of isolates belonged to 6 predominant clonal complexes (CC5, CC8, CC15, CC30, CC45, CC59). PVL was present in a minority (16%) of isolates, of which most were ST8 MRSA.ConclusionsMSSA was the primary cause of invasive S. aureus infections at our institution throughout the study period. A limited number of predominant strains accounted for the majority of invasive disease. The classic virulence factor PVL was uncommon in MSSA isolates. Further study is needed to improve our understanding of S. aureus virulence and disease pathogenesis.

Background Starting in the late 1940s-1950s Staphylococcus aureus isolates gained resistance to penicillin largely through the acquisition of β-lactamases. In recent years, 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 prevalence or clinical significance of PSSA in children. Acute hematogenous osteoarticular infections (AHOAIs, including osteomyelitis and septic arthritis) are the most common manifestation of invasive S. aureus disease in children. We investigated the prevalence of penicillin susceptibility among MSSA AHOAI isolates at two children’s hospitals. Methods MSSA AHOAI isolates were obtained through surveillance studies at Texas Children’s (TCH) and St. Louis Children’s Hospitals (SLCH) from 1/2011- 12/2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were blaZ negative and had a penicillin MIC ≤ 0.125 μg/ml were regarded as PSSA. Results 329 unique isolates were available and included in the study. The median patient age was 9.2 years (IQR: 5.1-12.2). Overall, 22 isolates were found to be penicillin susceptible (6.7%). No PSSA isolates were detected prior to 2015 but increased yearly thereafter; by the final study year 20.4% of isolates were PSSA (p=0.001, Figure 1). Patients with PSSA isolates were slightly older than those with resistant isolates (median age 11.8 years vs. 9.1 years, p=0.08) and PSSA were more commonly identified at SLCH (12.9% vs. 5.2%, p=0.04). PSSA were similar to penicillin-resistant isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. For PSSA, the MIC90 for penicillin (0.06 μg/ml) was much lower than that for other β-lactams (Figure 2). The figure describes the relative frequency of penicillin susceptible S. aureus (PSSA) over time among MSSA osteoarticular infection isolates in children. Distribution of MICs to penicillin, ampicillin, cefazolin, cephalexin and oxacillin among PSSA isolates. Conclusion PSSA appears to be increasing among AHOAI isolates in US children, although geographic variability does occur. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. Penicillin susceptibility testing may serve as an avenue for future stewardship intervention in staphylococcal infections. Disclosures Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality (Research Grant or Support)Allergan (Grant/Research Support)Nabriva (Grant/Research Support, Other Financial or Material Support, Site PI for a multicenter trial) Kristina G. Hulten, PhD, Pfizer (Research Grant or Support) Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support)

Background & Aims The decline in Helicobacter pylori cure rates emphasizes the need for readily available methods to determine antimicrobial susceptibility. Our aim was to compare targeted next-generation sequencing (NGS) and culture-based H pylori susceptibility testing using clinical isolates and paired formalin-fixed, paraffin-embedded (FFPE) gastric biopsies. Methods H pylori isolates and FFPE tissues were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNA, gyrA, 16S rRNA, pbp1, rpoB and rdxA. Agreement was quantified using κ statistics. Results Paired comparisons included 170 isolates and FFPE tissue for amoxicillin, clarithromycin, metronidazole, and rifabutin and 57 isolates and FFPE tissue for levofloxacin and tetracycline. Agreement between agar dilution and NGS from culture isolates was very good for clarithromycin (κ = 0.90012), good for levofloxacin (κ = 0.78161) and fair for metronidazole (κ = 0.55880), and amoxicillin (κ = 0.21400). Only 1 isolate was resistant to tetracycline (culture) and 1 to rifabutin (NGS). Comparison of NGS from tissue blocks and agar dilution from isolates from the same stomachs demonstrated good accuracy to predict resistance for clarithromycin (94.1%), amoxicillin (95.9%), metronidazole (77%), levofloxacin (87.7%), and tetracycline (98.2%). Lack of resistance precluded comparisons for tetracycline and rifabutin. Conclusions Compared with agar dilution, NGS reliably determined resistance to clarithromycin, levofloxacin, rifabutin, and tetracycline from clinical isolates and formalin-fixed gastric tissue. Consistency was fair for metronidazole and amoxicillin. Culture-based testing can predict treatment outcomes with clarithromycin and levofloxacin. Studies are needed to compare the relative ability of both methods to predict treatment outcomes for other antibiotics.

Septic arthritis (SA) and acute osteomyelitis (AO) are among the most common serious bacterial infections of childhood. Knowledge of the microbiology of SA is critical to treatment. Awareness of the presence of attendant AO is also important to guide clinical management. We sought to describe the current microbiology of SA in children and clinical features associated with coexisting AO.Patients with SA were identified from the infectious diseases consult service records from 2010 to 2014. Patients with penetrating/open trauma and orthopedic hardware in situ were excluded.A total of 168 patients with SA were included. The most common causative organism was Staphylococcus aureus accounting for 47.7% of cases (29.1% were methicillin-susceptible S. aureus and 18.5% were methicillin-resistant S. aureus), followed by group A streptococcus (GAS, 8.9%). The proportion of cases due to GAS increased from 2011 to 2014 (3.3%-16.7%; P = 0.1). One hundred eight (64.3%) patients had concurrent AO. The presence of osteomyelitis was associated with older median age (5.9 vs. 2.4 years; P = 0.04), a longer duration of symptoms (5 vs. 2.5 days; P0.001), S. aureus (62.1% vs. 21.7%; P0.001), bacteremia (46.2% vs. 20.3%; P = 0.001), a longer duration of fever after admission (5 vs. 2 days; P0.001) and a longer length of stay (10 vs. 6 days; P0.001).Methicillin-resistant S. aureus continues to be an important cause of SA though GAS may be increasing in frequency. The presence of concomitant osteomyelitis is higher than previously reported and associated with older age, a longer duration of symptoms and fever, bacteremia and S. aureus.

Background The emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in the late 1990s-early 2000s complicated the empiric management of suspected staphylococcal infection in children. Rising clindamycin resistance rates in many communities adds further to management challenges. Ceftaroline, an anti-MRSA cephalosporin, represents an attractive therapy option. Little data are available, however, regarding the frequency of reduced susceptibility (RS) to ceftaroline among MRSA isolates from a general pediatric population. Methods Isolates were selected from an ongoing S. aureus surveillance study at Texas Children’s Hospital. Invasive MRSA isolates from 2015-2018 were included. Isolates were initially screened for ceftaroline RS with E-test; all isolates with a ceftaroline E-test MIC ≥ 1.5µg/ml underwent ceftaroline broth dilution. Ceftaroline RS was regarded as an MIC ≥ 2 µg/ml; full ceftaroline resistance was defined as an MIC ≥ 8 μg/ml. Accessory gene regulator (agr) groups were characterized by PCR. Results 201 viable isolates were included. The ceftaroline MIC50 and MIC90 were 0.5 and 1 µg/ml, respectively (Figure 1). Six isolates had MIC ≥ 2 µg/ml (2.9%) with two having MIC ≥ 8 µg/ml (0.9%). All ceftaroline RS isolates were from healthcare associated infections. Ceftaroline RS isolates were more often associated with clindamycin-resistance and agr group II (Figure 2). Infections with ceftaroline RS were associated with central venous lines, recent ICU admission, preceding antibiotic exposure (specifically cephalosporins) and prior MRSA infection. One subject with MRSA CLABSI had a ceftaroline susceptible MRSA infection followed < 1 month later by a ceftaroline resistant infection (MIC =32 μg/ml); the isolates were identical by PFGE. Only 3 subjects had previously received ceftaroline, none of which subsequently developed a ceftaroline RS isolate. Figure 1. Ceftaroline MIC Distribution Figure 2. Clinical And Microbiologic Associations with Reduced Ceftaroline Susceptibility Conclusion Ceftaroline RS occurs in 2.9% of invasive MRSA isolates in children and is most prominent among healthcare-associated infections. These isolates were associated with clindamycin resistance and agr group II. While ceftaroline RS is rare among invasive MRSA infections, the lack of preceding ceftaroline exposure is concerning and warrants careful surveillance. Disclosures Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support) Jonathon C. McNeil, MD, Allergan (Research Grant or Support, Allergan provided ceftaroline powder for use in studies described in this abstract)

Background The 2011 IDSA/PIDS Clinical Practice Guidelines for the Management of Community-acquired Pneumonia (CAP) in Children Older than 3 months recommended empiric treatment with either ampicillin/penicillin or ceftriaxone based on PCV13 vaccine status and the local antibiotic susceptibilities of IPD isolates. No study has addressed differences in antibiotic susceptibilities for isolates from children with pneumococcal pneumonia (PP) based on PCV13 status. Methods Investigators from 8 US children’s hospitals identified infants and children with IPD between 1/1/2014 and 12/31/2019. IPD was documented by positive cultures from a normally sterile site. PP diagnosis required an abnormal chest radiograph. Clinical data were recorded and isolates analyzed for serotype (ST) by the capsular swelling method and antimicrobial susceptibilities by standard methods. Administration of PCV7/13 was documented through the patient’s medical records, health care provider or a vaccine registry. Fisher Exact was performed; p< 0.05 was significant. Results 690 IPD patients with isolates were available (0–18 y); 24% (166/690) of the isolates were PCV13 STs (ST3-75, ST19F-45, ST19A-36, ST7F-5, other STs-5). The most common non-PCV13 ST isolates were ST35B-60, ST23B-59, ST33F-47, ST22F-43, ST15C-35, ST23A-27, ST15B-26, ST10A-26, ST15A-23. Of non-PCV13 isolates, 41% (217/524) were among the 7 additional STs in PCV20. For children with PP (n=157), the distributions of penicillin (Table) (p=0.8) and ceftriaxone MICs were no different for isolates obtained from children regardless of prior PCV13 doses. Less than 7% of PP isolates were resistant to penicillin (MIC >2 µg/mL). Table. Minimal inhibitory concentrations (MIC) of pneumococcal isolates related to the number of PCV13 doses each patient received prior to pneumococcal pneumonia (PP). Number of PCV13 doses Conclusion PCV13 status should not modify empiric antibiotics for children with suspected pneumococcal CAP. 41% of non-PCV13 IPD isolates were among the 7 additional PCV20 STs. Disclosures Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support) Tina Q. Tan, MD, Pfizer (Grant/Research Support, Other Financial or Material Support, Chair, DMSB for PCV20 vaccine) Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member)

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in the United States in 2010. We describe invasive pneumococcal disease (IPD) in children at 8 children’s hospitals in the US from 2014 to 2017. METHODS: Children with IPD occurring from 2014 to 2017 were identified from a prospective study. Demographic and clinical data, including results of any immune evaluation along with the number and dates of previous pneumococcal conjugate vaccines administered, were recorded on case report forms. Isolate serotypes were determined in a central laboratory. Pneumococcal conjugate vaccine doses were counted if IPD occurred ≥2 weeks after a dose. RESULTS: PCV13 serotypes accounted for 23.9% (115 out of 482) of IPD isolates from 2014 to 2017. Serotypes 3, 19A, and 19F accounted for 91% of PCV13 serotypes. The most common non-PCV13 serotypes were 35B, 23B, 33F, and 22F. An underlying condition was significantly (P < .0001) more common in children with IPD due to non-PCV13 serotypes (200 out of 367, 54.5%) than for children with PCV13 serotypes (27 out of 115, 23.5%). An immune evaluation was undertaken in 28 children who received ≥2 PCV13 doses before IPD caused by a PCV13 serotype. Only 1 was found to have an immunodeficiency. CONCLUSIONS: PCV13 serotypes (especially serotypes 3, 19A, and 19F) continue to account for nearly a quarter of IPD in US children 4 to 7 years after PCV13 was introduced. Underlying conditions are more common in children with non-PCV13 serotype IPD. Immune evaluations in otherwise healthy children with PCV13 serotype IPD despite receiving ≥2 PCV13 doses did not identify an immunodeficiency.

Staphylococcus aureus is a significant cause of implant-associated infections (IAIs). Data detailing the optimal treatment of IAIs are lacking in children. We describe the clinical features and outcomes of pediatric patients with S. aureus IAIs seen at Texas Children's Hospital.Patients and their isolates were identified from a S. aureus surveillance database from 2008 to 2016 in Houston, TX. Demographic and clinical data were collected retrospectively. Fisher's exact was used for statistical analysis.Forty-five patients with 47 IAIs were identified. Most patients had an infected orthopedic implant: 22 (47%) spinal rods and 19 (40%) with other orthopedic hardware. Thirty (64%) IAIs developed within 90 days of implant placement. Six patients had polymicrobial infections and 3 patients were bacteremic. Of the 47 IAI isolates, 34 (72%) were methicillin-susceptible S. aureus (MSSA) and 13 (28%) were methicillin-resistant S. aureus. All children underwent surgical irrigation, debridement and antibiotic therapy. Of the 47 IAI episodes, 22 of the implants were removed at time of initial presentation, 7 implants had delayed removal, and 18 implants remained in place. Successful treatment was achieved in all patients with immediate implant removal (22/22) and in 83% of patients with implant retention (15/18), including 10 patients with early postoperative infections (3 months) and 5 patients with late postoperative infections (3 months). Four patients had recurrence of infection.The majority of S. aureus IAIs were methicillin-susceptible S. aureus. All children with immediate implant removal and most children with retained implants were treated successfully with surgery and antibiotic therapy.

Objective:The smr and qacA/B genes in Staphylococcus aureus confer tolerance to antiseptics and are associated with nosocomial acquisition of infection and underlying medical conditions. Such antiseptic tolerance (AT) genes have also been reported in coagulase-negative staphylococci (CoNS) and enterococci, however, few data are available regarding their prevalence. We sought to describe the frequency of AT genes among bloodstream isolates of S. aureus, CoNS and enterococci at Texas Children’s Hospital (TCH).Methods:Banked CoNS, S. aureus and enterococci isolated from blood cultures collected bewteen October 1, 2016, and October 1, 2017, were obtained from the TCH clinical microbiology laboratory. All isolates underwent polymerase chain reaction (PCR) assay for the qacA/B and smr genes. Medical records were reviewed for all cases.Results:In total, 103 CoNS, 19 Enterococcus spp, and 119 S. aureus isolates were included in the study, and 80.6% of the CoNS possessed at least 1 AT gene compared to 37% of S. aureus and 43.8% of E. faecalis isolates (P < .001). Among CoNS bloodstream isolates, the presence of either AT gene was strongly associated with nosocomial infection (P < .001). The AT genes in S. aureus were associated with nosocomial infection (P = .025) as well as the diagnosis of central-line–associated bloodstream infection (CLABSI; P = .04) and recent hospitalizations (P < .001). We found no correlation with genotypic AT in E. faecalis and any clinical variable we examined.Conclusions:Antiseptic tolerance is common among bloodstream staphylococci and E. faecalis isolates at TCH. Among CoNS, the presence of AT genes is strongly correlated with nosocomial acquisition of infection, consistent with previous studies in S. aureus. These data suggest that the healthcare environment contributes to AT among staphylococci.

Background Staphylococcus aureus is the most common cause of acute hematogenous osteoarticular infections (AHOAIs) in children. The risk factors for the development of orthopedic complications (OC) after AHOAI are poorly understood. We sought to describe clinical and microbiologic variables present on the index admission that may predict OC in S. aureus AHOAI. Methods Staphylococcus aureus AHOAI cases were identified from 2011–2017 at Texas Children’s Hospital and reviewed for the development of OC. OC included chronic osteomyelitis, growth arrest, avascular necrosis, chronic dislocation, and pathologic fracture. All S. aureus isolates were characterized by pulsed-field gel electrophoresis and agr group. Results A total of 286 cases were examined of which 27 patients (9.4%) developed OC. Patients who developed OC more often had infection with an agr group III organism (P = .04), bacteremia (P = .04), delayed source control (P < .001), ≥2 surgical procedures (P < .001), intensive care unit admission (P = .09), and fever >4 days after admission (P = .008). There was no association with OC and patient age, methicillin resistance, or choice/route of antibiotics. In multivariable analyses of OC, infection with agr group III S. aureus, prolonged fever, and delayed source control remained statistically significant. Conclusions OC develop following S. aureus AHOAI in 9.4% of cases. Although the development of OC is likely multifactorial, agr group III organisms, prolonged fever, and delayed source control are independently associated with OC. Moreover, early aggressive surgical source control may be beneficial in children with S. aureus AHOAI.

BackgroundMicrobial surface component recognizing adhesive matrix molecules (MSCRAMMs) facilitate Staphylococcus aureus adherence to host tissue. We hypothesized that S. aureus isolates from implant-associated infections (IAIs) would differ in MSCRAMM profile and biofilm formation in vitro compared to skin and soft tissue infection (SSTI) isolates.MethodsPediatric patients and their isolates were identified retrospectively. IAI and SSTI isolates were matched (1:4). Pulsed field gel electrophoresis was performed to group isolates as USA300 vs. non-USA300. Whole genome sequencing was performed and raw sequence data were interrogated for presence of MSCRAMMs (clfA, clfB, cna, ebh, efb, fnbpA, fnbpB, isdA, isdB, sdrC, sdrD, sdrE), biofilm-associated (icaA,D,B,C), and Panton-Valentine leukocidin (lukSF-PV) genes, accessory gene regulator group, and multilocus sequence types. In vitro biofilm formation was assessed for 47 IAI and 47 SSTI isolates using a microtiter plate assay. Conditional logistic regression was performed for analysis of matched data (STATA11, College Station, TX).ResultsForty-seven IAI and 188 SSTI isolates were studied. IAI isolates were more often methicillin susceptible S. aureus and non-USA300 vs. SSTI isolates [34 (72%) vs. 79 (42%), p = 0.001 and 38 (81%) vs. 57 (30%) p ConclusionsS. aureus IAI isolates were significantly more likely to be MSSA and non-USA300 than SSTI isolates. Carriage of MSCRAMMs and biofilm formation did not differ significantly between isolates. Evaluation of genetic polymorphisms and gene expression profiles are needed to further delineate the role of adhesins in the pathogenesis of IAIs.

Strains of methicillin-resistant Staphylococcus aureus (MRSA), particularly those belonging to the USA300 pulsotype, have been well described to cause severe osteoarticular infections (OAIs). A vancomycin MIC of ≥1.5 μg/ml has been demonstrated to contribute to disease severity in adults with MRSA and even methicillin-susceptible S. aureus (MSSA) bacteremia. Little data exist describing the outcomes of MSSA OAIs in terms of molecular characteristics and vancomycin MIC. All patients/isolates were chosen from a surveillance study at Texas Children's Hospital (TCH). S. aureus OAI isolates were identified from 2011 to 2016 and subjected to vancomycin Etests, pulsed-field gel electrophoresis (PFGE), and PCR to determine Panton-Valentine leucocidin (PVL) production and agr group. Two hundred fifty-two cases of S. aureus OAI were identified; 183 cases were MSSA (72.6%). During the study period, a decrease in the proportion of cases secondary to MRSA was observed, declining from 37.8% to 15.9% ( P = 0.02). Of the MSSA isolates, 26.2% and 23.5% were USA300 and PVL positive, respectively. An increase in the proportion of MSSA isolates with a vancomycin MIC of ≥1.5 μg/ml occurred in the study period ( P = 0.004). In MSSA, an elevated vancomycin MIC was associated with multiple surgical procedures and venous thromboses, even when adjusting for empirical β-lactam use. An increase in vancomycin MIC was noted among isolates belonging to agr group 4 during the study period. Methicillin resistance is declining among S. aureus OAI isolates at TCH. Simultaneously, vancomycin Etest MICs are increasing among MSSA isolates. Vancomycin MICs of ≥2 μg/ml are associated with adverse clinical outcomes in MSSA irrespective of antibiotic choice, suggesting that this may be a surrogate for organism virulence.

Background Select methicillin-susceptible Staphylococcus aureus (MSSA) strains may produce β-lactamases with an affinity for first-generation cephalosporins (1GC). In the setting of a high inoculum, these β-lactamases may promote clinically meaningful cleavage of 1GCs, potentially resulting in antibiotic failure, a phenomenon known as the cefazolin inoculum effect (CIE). Acute hematogenous osteoarticular infections (AHOAIs, including osteomyelitis and septic arthritis) are the most common manifestation of invasive S. aureus infection in children. We evaluated the prevalence and potential impact of CIE among MSSA AHOAI isolates at two children’s hospitals. Methods MSSA AHOAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2018. Isolates were tested for CIE via a macrobroth dilution assay with an inoculum of 107 CFU/mL; CIE was defined as a cefazolin MIC ≥16 µg/mL. Isolates were characterized by accessary gene regulator group (agr). The subsequent development of chronic osteomyelitis (CO) was regarded as a clinically important outcome. Results A total of 287 cases were included and the median patient age was 8.6 years. 14.3% of isolates exhibited CIE; CIE prevalence was similar across study sites. 74.6% of patients received a 1GC as definitive therapy. CIE isolates were more often resistant to clindamycin, belonged to agr III and associated with CO (Figure 1); a numerically higher rate of CO was observed with CIE isolates regardless of definitive antibiotic choice (Figure 2). In multivariable analyses, bone abscesses, agr III, positive blood cultures, multiple surgeries, and delayed source control but not CIE were independently associated with CO (Figure 3); similar results were seen if analyses were restricted to only those receiving 1GC. Conclusion CIE is exhibited by 14.3% of MSSA AHOAI isolates in children. CIE is associated with agr III and clindamycin-resistant strains. agr III strains are independently associated with CO; thus negative outcomes reported with CIE may more accurately reflect strain-dependent virulence factors rather than true antibiotic failure. Further studies are necessary to better understand the clinical significance of these findings. Disclosures All Authors: No reported Disclosures.

Background Staphylococcus aureus is the most common cause of acute hematogenous osteoarticular infections (AHOAIs) in children. While the vast majority of patients do well, a small proportion experience significant morbidity, including chronic infection and pathologic fractures. We sought to describe clinical and microbiologic variables present on the index admission that may predict long-term orthopedic complications (OC). Methods Cases of S. aureus AHOAI were identified from 2011 to 2016 at Texas Children’s Hospital (TCH). All cases were reviewed for the development of OC until April 1, 2018. OC included chronic osteomyelitis (CO), growth arrest/limb length discrepancy, avascular necrosis, chronic dislocation, and pathologic fracture (PF) with or without angular deformity. All S. aureus isolates were characterized by PCR for Panton–Valentine Leukocidin (PVL) genes and agr group. Statistical Analyses were performed with STATA. Results A total of 252 cases were identified meeting inclusion criteria (figure). Twenty-four (9.5%) developed OC; of which, 50% were CO and 25% PF. Patients who developed CO more often had positive blood cultures during the index admission (P < 0.001), surgical drainage after hospital day 2 (33.3% vs. 8.8%, P = 0.02) as well as a longer time to 50% reduction in C-reactive protein (CRP, 9 vs. 7 days, P = 0.01). Patients who developed PF more often had infection due to PVL-positive organisms (83.3% vs. 38.6%, P = 0.03) and had a longer duration of fever after admission (9.5 vs. 2.5 days, P = 0.03). Overall, OC were associated with ICU admission (P = 0.04), a slower decline in CRP (P = 0.02) and a greater proportion of patients with surgery after hospital day 2 (P = 0.04) as well as infection secondary to agr III isolates (P = 0.03). There was no statistically significant relationship between OC and patient age, affected bone, time to initiation of effective antimicrobial therapy, duration of intravenous therapy, or final antibiotic choice. Conclusion Patients with S. aureus AHOAI with a delay in source control, slow decline in CRP, prolonged fever or ICU admission are at higher risk of OC. While nonspecific, these findings suggest that such patients may warrant especially cautious clinical follow-up to identify sequelae early. Large multicenter studies are needed to better predict OC in this setting. Disclosures All authors: No reported disclosures.

Background Adhesins or microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) and the ica locus help mediate S. aureus adherence to host tissue and biofilm formation and are thought to play important roles in the pathogenesis of device related infections (DRIs). We hypothesized that S. aureus isolates from pediatric DRIs differ in MSCRAMM and biofilm-associated gene profiles and display greater strain diversity compared with skin and soft-tissue infection (SSTI) isolates. Methods Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children’s Hospital, 2008–2016. Clinical data were collected retrospectively. Age and date of infection matched SSTI control isolates were selected 4:1. Isolates were genotyped by pulsed-field gel electrophoresis. Whole genome sequencing was performed (Illumina MiSeq). Data were analyzed with CLC Genomics Workbench for the presence of MSCRAMMS (clfA, clfB, ebh, fbp, fnbpA, fnbpB, isdA, isdB, sdrC, sdrD, sdrE), biofilm-associated genes (icaA,D,B,C), accessory gene regulator group, and by multilocus-sequence typing (MLST) with eBurst analysis (www.phyloviz.net). Conditional logistic regression and Fisher’s exact were used for analysis (STATA11). Results Forty-five patients with 47 DRIs were identified (Table 1). Isolates from 47 DRIs and 188 SSTIs were analyzed for the presence of MSCRAMM and biofilm-associated genes. clfA, clfB, fbp, isdA, isdB, and icaA,D,B,C were present among DRIs and SSTIs more than 98% of the time. Isolates from DRIs or SSTIs did not differ significantly in carriage of MSCRAMMs or the ica locus. DRIs were MSSA (34, 72%), nonUSA300 (39, 83%), and belonged to 19 sequence types (STs). SSTIs were MSSA (79, 42%), nonUSA300 (57, 30%), and belonged to 39 STs (Table 2). Among DRI isolates, STs 5 and 8 were most common (23% each, Figure 1). SSTI isolates were predominately ST8 (68%). Conclusion S. aureus isolates from DRIs were significantly more likely to be MSSA and nonUSA300 (P < 0.0001 for both) compared with SSTIs. The majority of S. aureus isolates harbored all MSCRAMM and biofilm-associated genes analyzed. Evaluating genetic polymorphisms and gene expression profiles may clarify the role of adhesion genes in the pathogenesis of DRIs vs. SSTIs. Disclosures All authors: No reported disclosures.

Background The presence of the smr and qacA/B genes in Staphylococcus aureus have been correlated with reduced susceptibility to antiseptics. Recently, S. aureus bearing these genes have been reported to be associated with nosocomial acquisition of infection and underlying medical conditions. Antiseptic tolerance (AT) genes have also been reported in coagulase negative staphylococci (CoNS) and enterococci; however, little data are available regarding their prevalence. We sought to describe the frequency of smr and qacA/B among bloodstream isolates of S. aureus, CoNS and enterococci obtained at Texas Children’s Hospital (TCH). Methods Banked CoNS, S. aureus and enterococci isolated from blood cultures collected from October 1, 2016 to October 1, 2017 were obtained from the TCH clinical microbiology laboratory. All isolates underwent PCR for the qacA/B and smr genes. CoNS and enterococci were identified to the species level with MALDI-TOF mass spectrometry. Medical records were reviewed for all cases; CoNS were considered true pathogens if >1 blood culture was positive. Results 268 CoNS, 19 Enterococcus spp. and 116 S. aureus isolates were identified and included (Figure 1). 83.2% of CoNS possessed at least one AT gene compared with 36.2% of S. aureus and 31.5% of enterococci (P < 0.001, Figure 2). Neither antiseptic gene was detected in E. faecium isolates (n = 4) compared with 43.8% of E. faecalis (P = 0.2). Among CoNS, methicillin-resistance was found more commonly among qacA/B-positive (77.2% vs. 40%, P = 0.04) and smr-positive isolates (93.8% vs. 60.5%, P = 0.02). 38.4% of CoNS bloodstream isolates were considered true infections; among these, the presence of either AT gene was strongly associated with nosocomial infection (P < 0.001). AT genes in S. aureus were associated with nosocomial infection (P = 0.007) as well as the diagnosis of CLA-BSI (P = 0.001). There was no correlation with genotypic AT in enterococci and any examined clinical variable. Conclusion AT is common among bloodstream staphylococci and E. faecalis isolates at TCH. Among CoNS, the presence of AT genes is strongly correlated with nosocomial acquisition of infection consistent with previous studies in S. aureus. These data suggest that the healthcare environment contributes to AT among staphylococci. Disclosures All authors: No reported disclosures.

Background The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis (PM) in US children is unknown. We compared the serotype distribution, antibiotic susceptibility, hospital course, and outcomes of children with PM 3 years before and 3 years after the introduction of PCV13. Methods We identified patients ≤ 18 years of age with PM at 8 children's hospitals in the United States. Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Clinical data were abstracted from medical records. Patients were divided into 3 subgroups: pre-PCV13 (2007-2009), transitional year (2010), and post-PCV13 (2011-2013). Categorical variables were analyzed by the χ(2) test and continuous variables by the Mann--Whitney U test. Results During the study period, 173 of 1207 episodes (14%) of invasive pneumococcal disease were identified as PM; 76 of 645 (12%) were during 2007-2009 and 69 of 394 (18%) during 2011-2013 (50% increase; P = .03). The proportion of PCV13 serotype cases decreased from 54% in 2007-2009 to 27% in 2011-2013 (P = .001). Non-PCV13 serotype cases represented 73% of the isolates in 2011-2013. Isolates with ceftriaxone minimum inhibitory concentration ≥ 1 µg/mL decreased (13% to 3%) from 2007-2009 to 2011-2013 (P = .03). No significant differences were identified for hospital course or outcome, with the exception that a greater proportion of patients had subdural empyema and hemiparesis in 2011-2013. Conclusions After the introduction of PCV13, the number of cases of PM in children remained unchanged compared with 2007-2009, although the proportion of PCV13 serotypes decreased significantly. Serotype 19A continued to be the most common serotype in 2011-2013. Antibiotic resistance decreased significantly. Morbidity and case-fatality rate due to PM remain substantial.

BACKGROUND The epidemiology of community acquired (CA) Staphylococcus aureus infections is changing in the United States. We investigated the current epidemiology of S. aureus infections at Texas Children's Hospital. METHODS Patients with CA-S. aureus skin and soft tissue and invasive infections were retrospectively identified from January 1, 2007 to December 31, 2014. Invasive CA-MSSA isolates were characterized by pulsed field gel electrophoresis, Spa typing, agr type and presence of lukSF-PV (pvl) genes. Medical records were reviewed. Statistical analyses included Fisher exact, χ for trend and Wilcoxon tests. RESULTS CA-MRSA infections decreased by 60.4% (1461-578 infections) from 2007 to 2014 (P < 0.0001), while CA-MSSA infections averaged 550 infections annually. Invasive CA-MRSA infections decreased by 67.2% from 61 to 20 infections (P < 0.0001); invasive CA-MSSA averaged 44 infections annually. Among 296 invasive CA-MSSA isolates, 74 (25%) isolates were USA300 and 88 (30%) were pvl+. USA300 declined among invasive CA-MSSA over time (P < 0.008). Musculoskeletal infections were most common (242/296, 82%); 52/242 (21.5%) isolates were USA300 and 62/242 (25.6%) pvl+. All 18 isolates from musculoskeletal infections with deep venous thrombosis and/or septic shock were pvl+ and 16/18 (88.9%) were USA300. Pneumonia isolates were mainly USA300 (8, 66.7%) and pvl+ (11, 91.7%). CONCLUSIONS MSSA now cause the majority of invasive CA-S. aureus infections at our institution. Molecular analysis of invasive CA-MSSA isolates suggests strain diversity with USA300 on the decline and that disease presentations are to some extent strain specific. Changes in the CA-S. aureus epidemiology may, in part, be related to changes in immunity to the USA300 clone in the general population.

Pneumococcal osteoarticular infections (OAIs) are an uncommon manifestation of invasive pneumococcal disease (IPD). We describe the demographic characteristics, hospitalization rate, serotype distribution and antibiotic susceptibility of children with pneumococcal OAI over a 16-year period.We identified patients ≤18 years old with pneumococcal OAI at 8 children's hospitals in the United States (2000-2015). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory.We identified 97 (3.3%) patients with pneumococcal OAI out of 2943 patients with IPD. Over 60% of the children were2 years old. Septic arthritis (56.7%, 55/97) was the most common pneumococcal OAI, followed by osteomyelitis (25.8%, 25/97) and septic arthritis with concomitant osteomyelitis (17.5%, 17/97). Hospitalization for pneumococcal OAI overall decreased from 6.8 [95% confidence interval (CI): 5.2-8.6] to 4.4 (95% CI: 3.0-6.3) per 100,000 admissions from 2000-2009 to 2010-2015 (-35%, P = 0.05). Hospitalization for pneumococcal OAI caused by PCV13 serotypes decreased from 4.6 (95% CI: 3.4-6.2) to 0.9 (95% CI: 0.3-1.9) per 100,000 admissions from 2000-2009 to 2010-2015 (-87%, P0.0001). Overall, 12% of isolates had a penicillin minimal inhibitory concentration2 µg/mL, 3% a ceftriaxone minimal inhibitory concentration1 µg/mL and 15% were clindamycin resistant; these proportions remained unchanged after the introduction of PCV13. Serotypes 19A and 35B were responsible for penicillin and ceftriaxone nonsusceptible isolates in 2010-2015.Pneumococcal OAI represents 3% of all IPD, affecting mainly healthy infants and young children. Hospitalization for pneumococcal OAI caused by PCV13 serotypes dramatically decreased (-87%) after the introduction of PCV13.

Central nervous system (CNS) infections caused by Staphylococcus aureus are uncommon in pediatric patients. We review the epidemiology, clinical features and treatment in 68 patients with a S. aureus CNS infection evaluated at Texas Children's Hospital.Cases of CNS infection in children with positive cerebrospinal fluid cultures or spinal epidural abscess (SEA) for S. aureus at Texas Children's Hospital from 2001 to 2013 were reviewed.Seventy cases of S. aureus CNS infection occurred in 68 patients. Forty-nine cases (70%) were secondary to a CNS device, 5 (7.1%) were postoperative meningitis, 9 (12.8%) were hematogenous meningitis and 7 (10%) were SEAs. Forty-seven (67.2%) were caused by methicillin-sensitive S. aureus (MSSA) and 23 (32.8%) by methicillin-resistant S. aureus (MRSA). Community-acquired infections were more often caused by MRSA that was clone USA300/pvl. Most patients were treated with nafcillin (MSSA) or vancomycin (MRSA) with or without rifampin. Among patients with MRSA infection, 50% had a serum vancomycin trough obtained with the median level being 10.6 μg/mL (range: 5.4-15.7 μg/mL). Only 1 death was associated with S. aureus infection.The epidemiology of invasive of S. aureus infections continues to evolve with MSSA accounting for most of the infections in this series. The majority of cases were associated with neurosurgical procedures; however, hematogenous S. aureus meningitis and SEA occurred as community-acquired infections in patients without predisposing factors. Patients with MRSA CNS infections had a favorable response to vancomycin, but the beneficial effect of combination therapy or targeting vancomycin trough concentrations of 15-20 μg/mL remains unclear.

Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 μg/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes.Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). HCA S. aureus bacteremia isolates from 2003 to 2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine.Three hundred forty-one isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ≥ 2 μg/mL (from 32.7% to 5.6%; P0.001). However, the proportion of MSSA isolates with MIC ≥ 2 μg/mL increased (from 2.9% to 9%; P = 0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough15 versus15 μg/mL. A vancomycin trough15 μg/mL was, however, an independent risk factor for AKI.Vancomycin MICs are shifting among HCA S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric HCA S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.

We identified 53 infants aged 0-60 days with invasive pneumococcal disease (IPD) at 8 children's hospitals in the United States (2005-2015). After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13), IPD caused by PCV13 serotypes decreased ~30% providing some evidence of indirect protection. However, approximately 60% of IPD was still caused by PCV13 serotypes.

Staphylococcus aureus possessing either the smr gene or the qacA/B genes is associated with decreased susceptibility to chlorhexidine gluconate (CHG) and other antiseptics. Previous studies of antiseptic-tolerant staphylococci have focused largely on high-risk populations, and the exact role of health care exposure in the acquisition of these organisms is unclear. We sought to describe the risk factors and features of infection caused by antiseptic-tolerant S. aureus in a general pediatric population. Isolates were selected from an ongoing S. aureus surveillance study. Every third sequential isolate in the year 2014 was selected for inclusion. All isolates underwent PCR for the genes qacA/B and smr . Medical records were reviewed. Five hundred six isolates were included in the study, with 377 (74.3%) being community acquired. One hundred (19.8%) isolates were smr positive and 79 (15.6%) qacA/B positive. In univariable analyses, the presence of either gene was associated with underlying medical conditions, nosocomial acquisition, recent hospitalization, central venous lines, and CHG exposure. In multivariable analyses, only differences between patients with chronic medical conditions (odds ratio [OR] = 1.72; 95% confidence interval [CI], 1.22 to 2.64) and nosocomial acquisition (OR = 2.48; 95% CI, 1.16 to 8.17) remained statistically significant. Among patients without risk factors, 27.9% had infection with an antiseptic-tolerant isolate. smr - or qacA/B -positive S. aureus isolates are common in children and are independently associated with nosocomial acquisition and underlying medical conditions. These findings imply a role for the health care environment in acquisition of these organisms. However, genotypic antiseptic tolerance was seen in >25% of healthy children with an S. aureus infection, indicating that these organism are prevalent in the community as well.

The widespread use of the 7-valent pneumococcal conjugate vaccine has been associated with epidemiologic changes of mucosal and invasive pneumococcal disease. No study describes the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on chronic sinusitis in children. We describe changes in epidemiology of Streptococcus pneumoniae chronic sinusitis after the introduction of PCV13 at Texas Children's Hospital.We identified patients18 years with positive sinus culture for S. pneumoniae who underwent endoscopic sinus surgery because of chronic sinusitis from August 2008 to December 2013 at Texas Children's Hospital. Isolates were serotyped by the capsular swelling method. Demographic and clinical information was collected retrospectively. The χ test and Fisher's exact test were used to analyze dichotomous variables.We identified 91 cases of chronic sinusitis with positive sinus culture for S. pneumoniae. Sixty-one (67%) isolates were non-PCV13 serotypes. PCV13 cases decreased 31% in the post-PCV13 period (P = 0.003). Serotype 19A decreased 27% in the post-PCV13 period (P = 0.007), but accounted for all the isolates with penicillin minimal inhibitory concentration ≥ 4 μg/mL and ceftriaxone minimal inhibitory concentration ≥ 2 μg/mL. Serotypes 19A (38%) and 15C (17%) were the most common in the pre- and post-PCV13 periods, respectively. The most common organism co-isolated was Haemophilus influenzae (52%). Isolation of Prevotella spp. increased in the post-PCV13 period (P = 0.02).S. pneumoniae continues to represent an important pathogen in chronic sinusitis in children5 years of age. After the introduction of PCV13, S. pneumoniae isolation declined in children with chronic sinusitis at Texas Children's Hospital. We also observed a substantial reduction of PCV13 serotypes, predominantly serotype 19A.

Lactobacillus spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100 Lactobacillus isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥10 5 CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each Lactobacillus sp. We identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While Lactobacillus rhamnosus , Lactobacillus gasseri , and Lactobacillus paracasei were associated with infections, L. gasseri was also a common colonizing/contaminating species. Lactobacillus casei , Lactobacillus johnsonii , and Lactobacillus delbrueckii were associated with at least one infection. Species commonly used in probiotic products (e.g., L. rhamnosus and L. casei ) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of Lactobacillus spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each Lactobacillus sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry.

Background Periorbital and orbital cellulitis cause significant pediatric morbidity. Here, we define the clinical features of and characterize isolates from children with periorbital or orbital cellulitis caused by Staphylococcus aureus at Texas Children's Hospital in Houston. Methods Patients were identified from a prospective S aureus study database from January 2002 to July 2015. Demographic and clinical data were collected retrospectively. Isolates were genotyped by pulsed-field gel electrophoresis, and Panton-Valentine leukocidin (lukSF-PV [pvl]) genes were detected by quantitative polymerase chain reaction. Data were analyzed with the Fisher exact or Wilcoxon rank-sum test. Results Eighty-five patients with periorbital (n = 58) or orbital (n = 27) cellulitis were identified. We found 57 (67%) methicillin-resistant S aureus (MRSA) isolates, 72 (85%) pvl-positive (pvl+) isolates, and 66 (78%) USA300 isolates. No differences in clinical characteristics were found when we compared MRSA to methicillin-susceptible (MSSA) infections or USA300 to non-USA300 infections. Patients with orbital cellulitis were hospitalized a median of 12 days (range, 2-28 days) and received antibiotics for 21 days (range, 10-32 days). Twelve (44%) patients with orbital cellulitis received steroids. Steroid treatment did not affect the length of hospitalization or duration of antibiotic treatment. Six (7%) patients with orbital cellulitis were bacteremic. Patients with periorbital cellulitis were hospitalized for a median of 3 days (range, 0-17 days) and received antibiotics for 11 days (range, 7-32 days). According to computed tomography (CT), 19 (70%) patients with orbital cellulitis and 11 (41%) with periorbital cellulitis had sinusitis. Conclusions The majority of periorbital and orbital S aureus infections at Texas Children's Hospital were caused by MRSA, and no change was observed over time. Empirical antibiotic treatment should include coverage for MRSA. PVL might be an important virulence factor in these presentations. S aureus is associated with sinusitis and its complications.