Predictors of Empiric Antibiotic Use in the Emergency Department in Children Without Urinary Tract Infections.

OBJECTIVES: Urinary tract infections (UTIs) are a common diagnosis within the pediatric emergency department (ED). Because of the necessary delay in obtaining urine culture results, clinicians must decide whether to prescribe antibiotics for a suspected UTI before urine culture results. The primary objective of this study was to identify the proportion of children given empiric antibiotics who subsequently did not meet consensus definition of an UTI. The secondary objective was to identify factors associated with return visits to the ED after an index visit for UTI. We also attempted to identify predictors of prescription of empiric antibiotics for children who did not have a UTI. METHODS: This was a retrospective chart review of all patients between the ages of 2 months and 18 years diagnosed with a UTI between July 2016 and June 2017 in the ED of a single urban quaternary care center. Patients were excluded for the following reasons: use of bag for urine collection, subsequent admission to the hospital, receipt of antibiotics within the previous 3 days, use of antibiotics for an indication other than a UTI, and urine culture obtained at an outside facility. RESULTS: Of 404 included patients, 389 (96.2%) were discharged on antibiotics and 243 (62.4%) did not have a UTI. On the multivariate analysis, age ≧ 36 months was associated with increased odds of receiving antibiotics and not having a UTI while both ≥1+ leukocyte esterase and ≥1+ nitrites on urinalysis were associated with decreased odds of receiving antibiotics and not meeting UTI criteria. Sixty-two patients revisited the ED within 30 days of the initial visit, 24 (38.7%) of which met criteria for UTI during the index visit. Prescription of antibiotics at the time of the index visit was associated with decreased odds of reutilization, whereas an extended-spectrum ß-lactamase producing organism cultured from urine at the index visit was associated with increased odds of reutilization. CONCLUSIONS: A high number of patients discharged on empiric antibiotics did not meet criteria for a UTI. We did not identify clinically useful factors that predicted prescription of empiric antibiotics for children who do not have a UTI. We believe that unnecessary antibiotic prescriptions could be substantially decreased by decreasing empiric use of antibiotics coupled with reliable follow-up for positive urine cultures.

Severe Coronavirus Disease-2019 in Children and Young Adults in the Washington, DC, Metropolitan Region.

Despite worldwide spread of severe acute respiratory syndrome coronavirus-2, few publications have reported the potential for severe disease in the pediatric population. We report 177 infected children and young adults, including 44 hospitalized and 9 critically ill patients, with a comparison of patient characteristics between infected hospitalized and nonhospitalized cohorts, as well as critically ill and noncritically ill cohorts. Children <1 year and adolescents and young adults >15 years of age were over-represented among hospitalized patients (P = .07). Adolescents and young adults were over-represented among the critically ill cohort (P = .02).

Stenotrophomonas maltophilia infection among young children in a cardiac intensive care unit: a single institution experience.

Stenotrophomonas maltophilia can present as bacteremia, respiratory tract infection, urinary tract infection, soft tissue and wound infections, bone and joint infections, meningitis, and endocarditis especially in immunosuppressed patients and those with underlying medical conditions. The incidence and impact of S. maltophilia in young children with heart disease are poorly defined. A single center retrospective observational study was conducted in infants <180 days of age with positive S. maltophilia cultures over a period of 5 years. The overall incidence for S. maltophilia infection was 0.8 % (n = 32/3656). Among 32 identified infants, there were 47 episodes of S. maltophilia infection 66 % of infants had prior exposure to broad spectrum antibiotics. 97 % of positive isolates were susceptible to trimethoprim/sulfamethoxazole and 91 % to levofloxacin as well as ticarcillin/clavulanate. Ventilator-free days and absolute lymphocyte count prior to acquiring infection were significantly lower in non-survivors than in survivors. 100 % of survivors had clearance of positive cultures compared to 50 % in non-survivors (p < 0.05). The crude all-cause mortality rate was 37.5 %. All non-survivors had increased length of ICU stay and duration of mechanical ventilation and had delayed clearance of infection and required longer duration of treatment.

Histoplasmosis associated with a bamboo bonfire--Arkansas, October 2011.

On October 27, 2011, the Arkansas Department of Health (ADH) was notified by a northeast Arkansas primary care provider of a cluster of three histoplasmosis cases. On November 4, ADH was notified by a pediatric infectious diseases specialist regarding seven potential cases of pulmonary histoplasmosis associated with a family gathering that included a bonfire that burned bamboo from a grove that had been a red-winged blackbird roost. These reports prompted an outbreak investigation to ensure that the persons involved received appropriate medical care, to identify whether any novel exposures were associated with illness, and to determine whether any factors were associated with hospitalization. The investigation found that, among the 19 attendees at the family gathering, seven were confirmed with histoplasmosis, 11 were probable, and one did not have histoplasmosis.

Complexities of Zika Diagnosis and Evaluation in a U.S. Congenital Zika Program.

The objective of the study was to describe the complexity of diagnosis and evaluation of Zika-exposed pregnant women/fetuses and infants in a U.S. Congenital Zika Program. Pregnant women/fetuses and/or infants referred for clinical evaluation to the Congenital Zika Program at Children's National (Washington, DC) from January 2016 to June 2018 were included. We recorded the timing of maternal Zika-virus (ZIKV) exposure and ZIKV laboratory testing results. Based on laboratory testing, cases were either confirmed, possible, or unlikely ZIKV infection. Prenatal and postnatal imaging by ultrasound and/or magnetic resonance imaging (MRI) were categorized as normal, nonspecific, or as findings of congenital Zika syndrome (CZS). Of 81 women-fetus/infant pairs evaluated, 72 (89%) had confirmed ZIKV exposure; 18% of women were symptomatic; only a minority presented for evaluation within the time frame for laboratory detection. Zika virus could only be confirmed in 29 (40%) cases, was possible in 26 (36%) cases, and was excluded in 17 (24%) cases. Five cases (7%) had prenatal ultrasound and MRI findings of CZS, but in only three was ZIKV confirmed by laboratory testing. Because of timing of exposure to presentation, ZIKV infection could not be excluded in many cases. Neuroimaging found CZS in 7% of cases, and in many patients, there were nonspecific imaging findings that warrant long-term follow-up. Overall, adherence to postnatal recommended follow-up evaluations was modest, representing a barrier to care. These challenges may be instructive to future pediatric multidisciplinary clinics for congenital infectious/noninfectious threats to pregnant women and their infants.

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study.

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

Bronchiolitis clinical practice guidelines implementation: surveillance study of hospitalized children in Jordan.

INTRODUCTION: Bronchiolitis is a leading cause of hospital admissions and death in young children. Clinical practice guidelines (CPG) to diagnose and manage bronchiolitis have helped healthcare providers to avoid unnecessary investigations and interventions and to provide evidence-based treatment. Aim of this study is to determine the effect of implementing CPG for the diagnosis and management of bronchiolitis in a tertiary hospital in Jordan. METHODS: The study compared children (age <24 months) diagnosed with bronchiolitis and who required admission to King Abdullah University Hospital in Irbid during the winter of 2017 (after CPG implementation) and age-matched children admitted in the winter of 2016. The proportion of patients receiving diagnostic tests and treatments in the two groups were compared. RESULTS: Eighty-eight and 91 patients were diagnosed with bronchiolitis before and after CPG implementation, respectively. Respiratory syncytial virus rapid antigen detection testing decreased after CPG implementation [n=64 (72.7%) vs n=46 (50.5%), p=0.002]. However, there was no significant change in terms of other diagnostic tests. The use of nebulized salbutamol [n=44 (50%) vs n=29 (31.9%), p=0.01], hypertonic saline [n=39 (44.3%) vs n=8 (8.8%), p<0.001], and inappropriate antibiotics [n=31 (35.2%) vs n=15 (16.5%), p=0.004] decreased after CPG implementation. There was no difference in mean LOS (standard deviation; SD) between the pre- and post-CPG groups [3.5(2) vs 4 (3.4) days, p=0.19]. The mean cost of stay (SD) was 449.4 (329.1) US dollars for pre-CPG compared to 507.3 (286.1) US dollars for the post-CPG group (p=0.24). CONCLUSION: We observed that the implementation of CPG for bronchiolitis diagnosis and management helped change physicians' behavior toward evidence-based practices. However, adherence to guidelines must be emphasized to improve practices in developing countries, focusing on the rational use of diagnostic testing, and avoiding use of unnecessary medications when managing children with a diagnosis of bronchiolitis.

Previous Traditional Medicine Use for Sore Throat among Children Evaluated for Rheumatic Fever in Northern Uganda.

Timely diagnosis of group A streptococcal (GAS) sore throat coupled with appropriate antibiotic treatment is necessary to prevent serious post-streptococcal complications, including rheumatic fever (RF) and rheumatic heart disease (RHD). Traditional medicine (TM) is a known common adjunct to formal medical care in sub-Saharan Africa. A better understanding of health-seeking behavior for sore throat both within and outside the formal medical system is critical to improving primary prevention efforts of RF and RHD. A prospective mixed-methods study on the use of TM for sore throat was embedded within a larger epidemiological study of RF in Northern Uganda. Children presenting with symptoms of RF were interviewed about recent TM use as well as health services use for sore throat. One hundred children with a median age of 10 years (interquartile range: 6.8-13 years) completed the TM interview with their parent/guardian as part of a research study of RF. Seventeen, or 17%, accessed a TM provider for sore throat as part of the current illness, and 70% accessed TM for sore throat in the past (73% current or past use). Of the 20 parents who witnessed the TM visit, 100% reported use of crude tonsillectomy. Penicillin was the most frequently prescribed medication by TM providers in 52% of participants who were seen by a TM provider. The use of TM among children presenting with symptoms of sore throat in northern Uganda is common and frequently used in tandem with diagnostic services offered through the formal healthcare system. Engagement with TM practitioners may provide an important avenue for designing effective primary prevention and management strategies of RF and reduce the global burden of RHD.

Active Case Finding for Rheumatic Fever in an Endemic Country.

Background Despite the high burden of rheumatic heart disease in sub-Saharan Africa, diagnosis with acute rheumatic fever (ARF) is exceedingly rare. Here, we report the results of the first prospective epidemiologic survey to diagnose and characterize ARF at the community level in Africa. Methods and Results A cross-sectional study was conducted in Lira, Uganda, to inform the design of a broader epidemiologic survey. Key messages were distributed in the community, and children aged 3 to 17 years were included if they had either (1) fever and joint pain, (2) suspicion of carditis, or (3) suspicion of chorea, with ARF diagnoses made by the 2015 Jones Criteria. Over 6 months, 201 children met criteria for participation, with a median age of 11 years (interquartile range, 6.5) and 103 (51%) female. At final diagnosis, 51 children (25%) had definite ARF, 11 (6%) had possible ARF, 2 (1%) had rheumatic heart disease without evidence of ARF, 78 (39%) had a known alternative diagnosis (10 influenza, 62 malaria, 2 sickle cell crises, 2 typhoid fever, 2 congenital heart disease), and 59 (30%) had an unknown alternative diagnosis. Conclusions ARF persists within rheumatic heart disease-endemic communities in Africa, despite the low rates reported in the literature. Early data collection has enabled refinement of our study design to best capture the incidence of ARF and to answer important questions on community sensitization, healthcare worker and teacher education, and simplified diagnostics for low-resource areas. This study also generated data to support further exploration of the relationship between malaria and ARF diagnosis in rheumatic heart disease/malaria-endemic countries.

Cross-sectional study of population-specific streptococcal antibody titres in Uganda.

OBJECTIVE: Despite substantial variation of streptococcal antibody titres among global populations, there is no data on normal values in sub-Saharan Africa. The objective of this study was to establish normal values for antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) antibodies in Uganda. DESIGN: This was an observational cross-sectional study. SETTING: This study was conducted at Mulago National Referral Hospital, which is located in the capital city, Kampala, and includes the Uganda Heart Institute. PATIENTS: Participants (aged 0-50 years) were recruited. Of 428 participants, 22 were excluded from analysis, and 183 (44.4%) of the remaining were children aged 5-15 years. MAIN OUTCOME MEASURES: ASO was measured in-country by nephelometric technique. ADB samples were sent to Australia (PathWest) for analysis by enzyme inhibition assay: 80% upper limit values were established. RESULTS: The median ASO titre in this age group was 220 IU/mL, with the 80th percentile value of 389 IU/mL. The median ADB titre in this age group was 375 IU/mL, with the 80th percentile value of 568 IU/mL. CONCLUSIONS: The estimated Ugandan paediatric population standardised 80% upper-limit-of-normal ASO and ADB titres is higher than many global populations. Appropriateness of using population-specific antibody cutoffs is yet to be determined and has important implications for the sensitivity and specificity of rheumatic fever diagnosis.

The Struggling Infectious Diseases Fellow: Remediation Challenges and Opportunities.

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with a roadmap for addressing common contemporary remediation challenges.

igr Genes and Mycobacterium tuberculosis cholesterol metabolism.

Recently, cholesterol was identified as a physiologically important nutrient for Mycobacterium tuberculosis survival in chronically infected mice. However, it remained unclear precisely when cholesterol is available to the bacterium and what additional bacterial functions are required for its metabolism. Here, we show that the igr locus, which we previously found to be essential for intracellular growth and virulence of M. tuberculosis, is required for cholesterol metabolism. While igr-deficient strains grow identically to the wild type in the presence of short- and long-chain fatty acids, the growth of these bacteria is completely inhibited in the presence of cholesterol. Interestingly, this mutant is still able to respire under cholesterol-dependent growth inhibition, suggesting that the bacteria can metabolize other carbon sources during cholesterol toxicity. Consistent with this hypothesis, we found that the growth-inhibitory effect of cholesterol in vitro depends on cholesterol import, as mutation of the mce4 sterol uptake system partially suppresses this effect. In addition, the Delta igr mutant growth defect during the early phase of disease is completely suppressed by mutating mce4, implicating cholesterol intoxication as the primary mechanism of attenuation. We conclude that M. tuberculosis metabolizes cholesterol throughout infection.

Cesium-induced QT-interval prolongation in an adolescent.

Alternative medicine is becoming increasingly popular, especially with terminally ill patients. Most alternative remedies have not been adequately studied or proven effective for the diseases for which they are promoted. In the worst cases, these therapies are harmful. We describe a 16-year-old girl with metastatic hepatocellular carcinoma who experienced cesium-induced QT-interval prolongation after the start of a cesium chloride-based alternative treatment regimen. She had received seven courses of chemotherapy, with a cumulative doxorubicin dose of 500 mg/m(2) over 5 months, resulting in minimal tumor regression. Against the advice of her oncologist, she abandoned traditional therapy and started an alternative regimen that included cesium chloride supplements. Two weeks later, the patient went to a local emergency department after experiencing two brief syncopal episodes. An electrocardiogram revealed occasional premature ventricular contractions, a QTc interval of 683 msec (normal range for females 450-460 msec), and R on T phenomenon. She was admitted to the hospital and later experienced monomorphic ventricular tachycardia, which resolved spontaneously. Lidocaine therapy was started, and the patient was transferred to a cardiac intensive care unit at our hospital. Her plasma cesium level was 2400 microg/dl (normal < 1 microg/dl), and her family was told to stop her alternative treatment regimen. On hospital day 5, as no additional arrhythmias had occurred, lidocaine was discontinued. Two days later, the patient's QTc interval had decreased to 546 msec, and she was discharged home. Two months later, at a follow-up visit, her serum cesium level was 1800 microg/dl, and her QTc interval was 494 msec. According to the Naranjo adverse drug reaction probability scale, cesium was the probable cause of the patient's arrhythmia. In animal models, cesium chloride has induced cardiac arrhythmias, including torsade de pointes. It inhibits delayed rectifier potassium channels in the myocardium, causing delayed repolarization and QT-interval prolongation. Patients with cancer should be aware that alternative remedies may be harmful and ineffective. Because patients may be unlikely to self-report alternative remedies, health care providers should specifically ask their patients about any alternative treatments they may be taking and should be knowledgeable about their toxicities.

Neonatal nonpolio enterovirus and parechovirus infections.

Nonpolio enteroviruses and parechoviruses are frequent causes of neonatal infection. Clinical manifestations of infection range from asymptomatic infection to mild infection without sequelae to septic shock with muiltiorgan failure. Neonates with clinically apparent infection typically have mothers and/or other contacts with recent symptoms consistent with a viral illness. Severe neonatal infection with nonpolio enterovirus or parechovirus cannot be differentiated clinically from serious bacterial infection. The preferred method for diagnosing neonatal nonpolio enterovirus or parechovirus infection is PCR as it is rapid, sensitive, specific, and commercially available for the detection of virus from various clinical specimens. Investigational agents such as the capsid inhibitors pleconaril and pocapavir show promise for treatment of neonatal enterovirus infections, and other investigational agents are being developed. This review focuses on the epidemiology, diagnosis, and treatment of neonatal nonpolio enterovirus and parechovirus infections.

From paper to practice: Strategies for improving antibiotic stewardship in the pediatric ambulatory setting.

Antibiotic stewardship aims to better patient outcomes, reduce antibiotic resistance, and decrease unnecessary health care costs by improving appropriate antibiotic use. More than half of annual antibiotic expenditures for antibiotics in the United States are prescribed in the ambulatory setting. This review provides a summary of evidence based strategies shown to improve antibiotic prescribing in ambulatory care settings including: providing education to patients and their families, providing education to clinicians regarding best practices for specific conditions, providing communications training to clinicians, implementing disease-specific treatment algorithms, implementing delayed prescribing for acute otitis media, supplying prescribing feedback to providers with peer comparisons, using commitment letters, and prompting providers to justify antibiotic prescribing for diagnoses for which antibiotics are not typically recommended. These various mechanisms to improve stewardship can be tailored to a specific practice's work flow and culture. Interventions should be used in combination to maximize impact. The intent with this review is to provide an overview of strategies that pediatric providers can take from paper to practice.

Clinical characteristics and epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in children with cystic fibrosis from a center with a high MRSA prevalence.

BACKGROUND: We describe the clinical characteristics and epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in children with cystic fibrosis (CF) from the U.S. CF center with the highest MRSA prevalence. METHODS: Medical records of children with CF were retrospectively reviewed from 1997-2009. MRSA clinical isolates from 2007-2009 were analyzed by polymerase chain reaction and pulsed field gel electrophoresis. RESULTS: The prevalence of MRSA was 1% in 1997 and 49% in 2009. Fifty-five children (26%) had persistent MRSA infection. Sixty-eight percent of MRSA isolates were hospital-associated (HA) MRSA, of which 52% were pulsed-field type USA 100. Ninety-three percent of HA MRSA isolates were clindamycin resistant. Twelve children acquired MRSA before 1 year of age, 83% of whom were hospitalized prior to acquisition of MRSA. Ten of 11 sibling pairs carried indistinguishable MRSA strains. Children with persistent MRSA were hospitalized more often (P = .01), required inhaled medications more frequently (P = .01), and had higher rates of Pseudomonas aeruginosa coinfection (P < .001). CONCLUSION: MRSA prevalence in children with CF is increasing, and most children are infected with HA MRSA. Exposure to health care facilities and gastrointestinal surgeries may facilitate early acquisition of MRSA. Siblings carry indistinguishable MRSA strains, indicating household transmission of MRSA. Children with persistent MRSA had worse pulmonary morbidity. Coinfection with MRSA and P aeruginosa is likely associated with further increased pulmonary morbidity.

Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children.

IMPORTANCE: Postdischarge treatment of acute osteomyelitis in children requires weeks of antibiotic therapy, which can be administered orally or intravenously via a peripherally inserted central catheter (PICC). The catheters carry a risk for serious complications, but limited evidence exists on the effectiveness of oral therapy. OBJECTIVE: To compare the effectiveness and adverse outcomes of postdischarge antibiotic therapy administered via the PICC or the oral route. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study comparing PICC and oral therapy for the treatment of acute osteomyelitis. Among children hospitalized from January 1, 2009, through December 31, 2012, at 36 participating children's hospitals, we used discharge codes to identify potentially eligible participants. Results of medical record review confirmed eligibility and defined treatment group allocation and study outcomes. We used within- and across-hospital propensity score-based full matching to adjust for confounding by indication. INTERVENTIONS: Postdischarge administration of antibiotics via the PICC or the oral route. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure. Secondary outcomes included adverse drug reaction, PICC line complication, and a composite of all 3 end points. RESULTS: Among 2060 children and adolescents (hereinafter referred to as children) with osteomyelitis, 1005 received oral antibiotics at discharge, whereas 1055 received PICC-administered antibiotics. The proportion of children treated via the PICC route varied across hospitals from 0 to 100%. In the across-hospital (risk difference, 0.3% [95% CI, -0.1% to 2.5%]) and within-hospital (risk difference, 0.6% [95% CI, -0.2% to 3.0%]) matched analyses, children treated with antibiotics via the oral route (reference group) did not experience more treatment failures than those treated with antibiotics via the PICC route. Rates of adverse drug reaction were low (<4% in both groups) but slightly greater in the PICC group in across-hospital (risk difference, 1.7% [95% CI, 0.1%-3.3%]) and within-hospital (risk difference, 2.1% [95% CI, 0.3%-3.8%]) matched analyses. Among the children in the PICC group, 158 (15.0%) had a PICC complication that required an emergency department visit (n = 96), a rehospitalization (n = 38), or both (n = 24). As a result, the PICC group had a much higher risk of requiring a return visit to the emergency department or for hospitalization for any adverse outcome in across-hospital (risk difference, 14.6% [95% CI, 11.3%-17.9%]) and within-hospital (risk difference, 14.0% [95% CI, 10.5%-17.6%]) matched analyses. CONCLUSIONS AND RELEVANCE: Given the magnitude and seriousness of PICC complications, clinicians should reconsider the practice of treating otherwise healthy children with acute osteomyelitis with prolonged intravenous antibiotics after hospital discharge when an equally effective oral alternative exists.

Impact of individual extracellular proteases on Staphylococcus aureus biofilm formation in diverse clinical isolates and their isogenic sarA mutants.

We demonstrate that the purified Staphylococcus aureus extracellular proteases aureolysin, ScpA, SspA, and SspB limit biofilm formation, with aureolysin having the greatest impact. Using protease-deficient derivatives of LAC, we confirmed that this is due to the individual proteases themselves. Purified aureolysin, and to a lesser extent ScpA and SspB, also promoted dispersal of an established biofilm. Mutation of the genes encoding these proteases also only partially restored biofilm formation in an FPR3757 sarA mutant and had little impact on restoring virulence in a murine bacteremia model. In contrast, eliminating the production of all of these proteases fully restored both biofilm formation and virulence in a sarA mutant generated in the closely related USA300 strain LAC. These results confirm an important role for multiple extracellular proteases in S. aureus pathogenesis and the importance of sarA in repressing their production. Moreover, purified aureolysin limited biofilm formation in 14 of 15 methicillin-resistant isolates and 11 of 15 methicillin-susceptible isolates, while dispersin B had little impact in UAMS-1, LAC, or 29 of 30 contemporary isolates of S. aureus. This suggests that the role of sarA and its impact on protease production is important in diverse strains of S. aureus irrespective of their methicillin resistance status.