Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs. oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015 Feb;169(2):120-8.
Damon Jones, MD PGY-3
Jane Stremming, MD PGY-3
- Osteomyelitis is a relatively uncommon infection in pediatrics
- Incidence of about 2 – 13/100,000 in developed countries, higher in developing countries
- Mean age of diagnosis is 6.6 years
- 40% occur in pre-school aged children
- Male: Female 1.82:1
- Risk factors include blunt trauma (30%) and recent systemic infection (37%)
- No identified risk factors in nearly half of all cases (47%)
- Presenting symptoms include pain (81%), localized signs symptoms (70%), fever (62%), reduced ROM (50%), and reduced weight bearing (50%)
- ESR and CRP usually elevated on presentation (91 and 81%, respectively)
- WBC elevated in only 36% of cases
Liu X, Olsen J, Pedersen LH, et al. Antidepressant use during pregnancy and asthma in the offspring. Pediatrics. 2015 Apr;135(4):e911-7.
BACKGROUND AND OBJECTIVES: It has been suggested that maternal depression during pregnancy is associated with asthma in the offspring, but the role of medical treatment of depression is not known. Our goal was to examine whether prenatal antidepressant use increases the risk of asthma in the offspring.
McNab S, Duke T, South M, et al. 140 mmol/L of sodium versus 77 mmol/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial. Lancet. 2014 Nov 28.
BACKGROUND: Use of hypotonic intravenous fluid to maintain hydration in children in hospital has been associated with hyponatraemia, leading to neurological morbidity and mortality. We aimed to assess whether use of fluid solutions with a higher sodium concentration reduced the risk of hyponatraemia compared with use of hypotonic solutions.
Fielding-Singh V, Hong DK, Harris SJ, Hamilton JR, Schroeder AR. Ruling out bacteremia and bacterial meningitis in infants less than one month of age: is 48 hours of hospitalization necessary? Hosp Pediatr. 2013 Oct;3(4):355-61.
Full-text for Children’s users.
OBJECTIVE: The appropriate duration of hospitalization for infants ≤ 30 days admitted for fever or other concerns for a serious bacterial infection is an understudied area. We sought to determine the risk of a positive, pathogenic bacterial culture of blood or cerebrospinal fluid (CSF) in this population beyond 24 hours after collection.
METHODS: This study was a retrospective review of 1145 infants aged ≤30 days who had a blood or CSF culture from 1999 to 2010 at Santa Clara Valley Medical Center, a county health system in San Jose, California. Time to notification and the probability of a positive culture result after 24 hours were calculated. Infants were considered high risk if they had either a white blood cell count <5000 or >15 000 per µL, a band count >1500 per µL, or an abnormal urinalysis.
RESULTS: We identified 1876 cultures (1244 blood, 632 CSF) in 1145 infants aged ≤30 days; 901 (79%) of 1145 were hospitalized and 408 (45%) of 901 hospitalizations were for fever without source (FWS). Thirty-one (2.7%) of the 1145 infants had pathogenic cultures; 6 of 1145 infants (0.5% [95% confidence interval: 0.2-1.1]) had a time to notification >24 hours. All 6 patients had FWS (1.5% of hospitalized FWS sample) and met high-risk criteria on presentation. No low-risk patients had a time to notification >24 hours. Low-risk characteristics were found in 57% (232 of 408) of the entire hospitalized FWS population.
CONCLUSIONS: Low-risk infants hospitalized for FWS or other concerns for serious bacterial infection may not need hospitalization for a full 48 hours simply to rule out bacteremia and bacterial meningitis.
Deidra Ansah, MD
Bhavya Doshi, MD
- Determine the probability of positive pathogenic blood and CSF culture after 24 hours in infants less than or equal to 30 days of age hospitalized outside of the ICU setting for suspected serious bacterial infection.
- Assess whether stratifying infants into high and low risk categories based on presentation modifies the above probability.
- Retrospective cohort from pediatric ward of community hospital from Jan 1999 – Dec 2010
- All infants < 30 days of age who had blood and/or CSF cultures performed in clinics, ED or ward.
- Excluded patients with cultures sent from NICU, PICU, those with indwelling central lines, lack of temperature > 38 by any method, or whose initial evaluation was at an outside facility.
- Narrowed to those admitted for fever without source
- In the end, 1145 infants with 1876 cultures were studied (1244 blood, 632 CSF cultures). 408/1145 infants were admitted for fever without source.
- Bacterial growth present in 196/1876 cultures from 189 infants
- Contaminants comprised 135/1244 blood cultures and 28/632 CSF cultures
- 74% of contaminants were coagulase-negative staphylococci
- True pathogens for bacteremia included E. coli, S. aureus, Enterococcus, and Group B streptococcus. True pathogens for bacterial meningitis included E. coli and Enterococcus.
- Time to notification was greater for contaminants than pathogens (45.3 vs 24.5 hours, p < 0.001)
- 25 of 31 infants had positive culture with time to notification < 24 hours, 6 of 31 grew after 24 hours
- All 6 were classified as high risk (positive UA, elevated WBC, ill-appearing)
- Of 6 with TTN > 24 hours, 3/6 had notification between 24-48 hours
- The number needed to treat for all fever without source patients in this study was 17 (i.e. 17 infants would need to be hospitalized and treated with IV antibiotics to prevent one missed infant)
- This number increased to 67 if narrowed to NNT for infants staying in the hospital beyond 24 hours.
- Study is limited by classification of pathogens vs. contaminants by one Pediatric ID specialist looking only at microbiological diagnosis, lack of evaluation of nasopharyngeal viral testing, questionable overestimation of time to notification due to lack of reporting overnight, lack of evaluation of urine cultures, and overlap of the confidence intervals for high and low risk infants’ rates of positive cultures.
Take Away Points:
- Bacteremia and bacterial meningitis are rare in well appearing infants
- Absolute risk of a positive culture > 24 hours is 1.5% in infants with high risk attribute
- Study cites a risk of positive culture > 24 hours in low risk infants is 0% but cannot trust zeros in statistics.
- Decision eventually lies in clinical judgment and risk aversion.
Rhedin S, Lindstrand A, Rotzén-Östlund M, et al. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics. 2014 Mar;133(3):e538-45.
Full-text for Children’s and Emory users.
BACKGROUND: Acute respiratory illness (ARI) accounts for a large proportion of all visits to pediatric health facilities. Quantitative real-time polymerase chain reaction (qPCR) analyses allow sensitive detection of viral nucleic acids, but it is not clear to what extent specific viruses contribute to disease because many viruses have been detected in asymptomatic children. Better understanding of how to interpret viral findings is important to reduce unnecessary use of antibiotics.
OBJECTIVE: To compare viral qPCR findings from children with ARI versus asymptomatic control subjects.
METHODS: Nasopharyngeal aspirates were collected from children aged ≤5 years with ARI and from individually matched, asymptomatic, population-based control subjects during a noninfluenza season. Samples were analyzed by using qPCR for 16 viruses.
RESULTS: Respiratory viruses were detected in 72.3% of the case patients (n = 151) and 35.4% of the control subjects (n = 74) (P = .001). Rhinovirus was the most common finding in both case patients and control subjects (47.9% and 21.5%, respectively), with a population-attributable proportion of 0.39 (95% confidence interval: 0.01 to 0.62). Metapneumovirus, parainfluenza viruses, and respiratory syncytial virus were highly overrepresented in case patients. Bocavirus was associated with ARI even after adjustment for coinfections with other viruses and was associated with severe disease. Enterovirus and coronavirus were equally common in case patients and control subjects.
CONCLUSIONS: qPCR detection of respiratory syncytial virus, metapneumovirus, or parainfluenza viruses in children with ARI is likely to be causative of disease; detection of several other respiratory viruses must be interpreted with caution due to high detection rates in asymptomatic children.
Liesl Windsor, MD
Neil Cella, MD
A clinical scenario:
- 18 month old male ex 27 weeks with h/oCLD, developmental delay, and G-tube presenting with:
- 3 days fever
- Very worried caregivers – last respiratory illness ended up as intubation
- Runny nose, cough and emesis
- Increased oxygen requirement from ¼ LPM to 1 LPM
- Less active and more fussy, attends medically fragile daycare
- Exam – TMs clear, nasal congestion, normal cardiac exam, mild tachypnea, no retractions, no wheeze, crackles bilaterally, no focally decreased breath sounds
- CXR – RUL atelectasis versus focal pneumonia
- Admitted for hypoxia – ED sent VRP and it has come back positive for Adenovirus. Does this help in antibiotic decision making on admission?
- Matched Case-Control Study
- Cases – children aged less than or equal to 5 years with one or more of the following:
- Coryza, sore throat, earache, cough, sputum production, or dyspnea
- Only included in study once; enrolled from September 2011 to January 2012
- Matched controls
- According to calendar time(+ or – 14 days) and age(+ or – 6 months)
- Enrolled from local swedish vaccination program
- Excluded if reports of respiratory disease in prior 7 days
- If no match found, controls expanded to +/- 30 days and +/- 12 months
What do we think of this study design?
- These authors have used this phrase “case-control” study, but it is more of a cohort
- Advantages – practical and affordable
- Disadvantages – retrospective nature, difficult to match control group
Strengths of study:
- Observational design
- Attempted to match
- Sample size?
- Impact of journal
- Clinically relevant
Weaknesses of study:
- Observational Design – unable to choose the patients that will be affected
- Compared two different groups
- Controls were younger and more frequently female; less attended day care; more breast fed; less had asthma; less were being treated with antibiotics; less were children of higher educated parents
- No follow up – early detection in controls? Asymptomatic carriage? No microbiological investigation for bacteria
- Qualitative versus quantitative PCR
Return to case and further questions:
- In this study, adenovirus detection in cases did not differ significantly from controls
- We can only apply results to diagnosis and all management questions are not related to this study
- Still, would Adenovirus positivity stop us from treating him for bacterial super-infection?
- If he was Parainfluenza+ or co-infected, would this stop us from treating him for super-infected pneumonia?
- Is there value in a diagnosis beyond management? Very worried parents? Epidemiology at an academic center?
- Will cost come down with time?
Jacobs JD, Foster M, Wan J, Pershad J. 7% hypertonic saline in acute bronchiolitis: a randomized controlled trial. Pediatrics. 2014 Jan;133(1):e8-13.
Full-text for Children’s and Emory users.
BACKGROUND: Research suggests that hypertonic saline (HS) may improve mucous flow in infants with acute bronchiolitis. Data suggest a trend favoring reduced length of hospital stay and improved pulmonary scores with increasing concentration of nebulized solution to 3% and 5% saline as compared with 0.9% saline mixed with epinephrine. To our knowledge, 7% HS has not been previously investigated.
METHODS: We conducted a prospective, double-blind, randomized controlled trial in 101 infants presenting with moderate to severe acute bronchiolitis. Subjects received either 7% saline or 0.9% saline, both with epinephrine. Our primary outcome was a change in bronchiolitis severity score (BSS), obtained before and after treatment, and at the time of disposition from the emergency department (ED). Secondary outcomes measured were hospitalization rate, proportion of admitted patients discharged at 23 hours, and ED and inpatient length of stay.
RESULTS: At baseline, study groups were similar in demographic and clinical characteristics. The decrease in mean BSS was not statistically significant between groups (2.6 vs 2.4 for HS and control groups, respectively). The difference between the groups in proportion of admitted patients (42% in HS versus 49% in normal saline), ED or inpatient length of stay, and proportion of admitted patients discharged at 23 hours was not statistically significant.
CONCLUSIONS: In moderate to severe acute bronchiolitis, inhalation of 7% HS with epinephrine does not appear to confer any clinically significant decrease in BSS when compared with 0.9% saline with epinephrine.
Natalie Metzig, MD
Tiffany Bell Vinet, MD
- Assess effectiveness of hypertonic saline 7% on lowering clinical severity of illness, admission rate or length of stay
- Previous data suggest these are lower with 3% and 5% hypertonic saline, no studies evaluating 7%
- Prospective, double-blind, randomized controlled trial
- 101 infants with moderate to severe acute bronchiolitis being treated in ED were included in study
- Given HTS 7% w/ epinephrine (52) or 0.9% saline with epinephrine (49)
- Primary outcome was bronchiolitis severity score (BSS) before and after treatment
- Secondary outcomes were hospitalization rate, proportion of admitted patients d/c’ed at 23 hours, and length of ED and inpatient stays
- Decrease in mean BSS was not statistically significant between groups
- Proportion of admitted patients, ED or inpatient length of stay, and proportion discharged at 23 hours was not statistically significant between groups
- Bronchiolitis is the most common lower respiratory infection of infants and young children
- Annual inpatient disease burden exceeds cost of any respiratory disease in US in children < 2 yo
- Many treatments have been investigated, and only few have been shown to be effective
- Mainstay of treatment is supportive care with oxygen as needed and hydration
- Currently, corticosteroids and bronchodilators not recommended
- Some evidence epinephrine may be more efficacious compared to bronchodilators
- Nebulized HTS shown promise
- All studies to date on 3% HTS have shown it to be safe and reduced length of hospital stay and improve clinical severity score
- BSS is an objective tool that has been previously validated and used modified BSS
- Modified BSS has been used in this institution since 2006
- Assessed correlation before beginning study and correlation was high
- 2 groups were similar in all clinical and historical characteristics
- Difference in proportion who received albuterol or supplemental O2 was not statistically significant
- Randomized controlled trial, double-blind study
Limitations and Future Studies
- Use of 7% HS with racemic epinephrine ONLY
- Study results can only be interpreted as HTS does not show significant effect when used with racemic epinephrine
- Does interaction play a role in outcome of study?
- Would it work alone? Would it work with another medication such as albuterol?
- Frequency of treatment
- Q6H therapy from admission, throughout stay (what if Q4H?)
- Severity of illness
- (most were moderately ill, excluded most severely ill patients)
- Would need a large-scale study to capture severely ill patients
- Possibly separate trials based on severity
- Can use data from this study to determine appropriate sample size for additional studies
- Natural history of the disease
- Average patient was on day 3 of illness.
- Would it help to treat sooner? Were they getting better on their own?
- Future study could look at patients on day 1 or 2 of illness.
- Not much changed.
- Supportive care is still primary management (airway management and rehydration as needed)
- No evidence 7% is better when used with racemic epinephrine,
- You can continue with 3-5% if use Hypertonic Saline as deemed fit.
- Mainstay of bronchiolitis management is supportive care
- Some evidence that 3%-5% hypertonic saline nebs may decrease BSS and hospital length of stay
- Research on 7% HTS is limited. This study suggests no significant improvement of patients received 7% HTS compared to normal saline when used with epinephrine.
- Further research into Hypertonic Saline nebs is needed in the future.
MacKenzie MJ, Nicklas E, Waldfogel J, Brooks-Gunn J. Spanking and child development across the first decade of life. Pediatrics. 2013 Nov;132(5):e1118-25.
Full-text for Children’s and Emory users.
OBJECTIVE: To examine the prevalence of maternal and paternal spanking of children at 3 and 5 years of age and the associations between spanking and children’s externalizing behavior and receptive vocabulary through age 9.
METHODS: The Fragile Families and Child Well-Being Study, a longitudinal birth cohort study of children in 20 medium to large US cities, was used. Parental reports of spanking were assessed at age 3 and 5, along with child externalizing behavior and receptive vocabulary at age 9 (N = 1933). The data set also included an extensive set of child and family controls (including earlier measures of the child outcomes).
RESULTS: Overall, 57% of mothers and 40% of fathers engaged in spanking when children were age 3, and 52% of mothers and 33% of fathers engaged in spanking at age 5. Maternal spanking at age 5, even at low levels, was associated with higher levels of child externalizing behavior at age 9, even after an array of risks and earlier child behavior were controlled for. Father’s high-frequency spanking at age 5 was associated with lower child receptive vocabulary scores at age 9.
CONCLUSIONS: Spanking remains a typical rearing experience for American children. These results demonstrate negative effects of spanking on child behavioral and cognitive development in a longitudinal sample from birth through 9 years of age.
Amy Tang, MD
Tracie Walker, MD
Importance of study:
- Corporal punishment remains a common parenting tool
- Some countries have banned spanking
- Germany, Costa Rica, Sweden, Spain, Greece, Ukraine…
- AAP recommends other methods of discipline
- There have been studies showing an association between spanking and higher levels of aggression in children
Strengths of study design:
- Followed sequential families through age 9 → longitudional data
- Followed families with and without fathers
- Diverse population with multiple cities
- Large subject number
Weaknesses of study design:
- Only used families with continued data through 9 yo, could have lost many unstable and risky families
- Reporter bias: selective reasoning or suppression of information
- Sampling bias: more stable families responded to every call/visit
What this study adds:
- Controlling for multiple different measures of stress and socioeconomic variables
- Child and family characteristics (gender, age, birth order, maternal age at birth, marital status, maternal race/ethnicity, maternal education, household income to needs ratio, number of adults in household, number of other children in household, maternal prenatal drugs, alcohol, or smoking, supportive birth father, prenatal care, etc.)
- Maternal factors: health and cognition, stress level, impulsivity, presence of depression or anxiety
- Earlier child behavior and temperament
- Longitudinal data – association between spanking at ages 3 and 5 with outcomes at age 9
- Previous studies only went up to age 5
- Cognitive developmental outcomes
- Looks at both behavioral AND cognitive development
- Previous studies had already established a link between spanking and later aggressive behavior
- Effects of paternal spanking
- High frequency (>2x/wk) paternal spanking at age 5 predicted lower receptive language scores later on
- Effect not seen with maternal spanking or with less frequent spanking or spanking at age 3
- Measures for child externalizing behaviors rely on maternal report – room for parental bias
- Negative perception of child → negative maternal ratings AND spanking
- Study population as a whole – disadvantaged urban population
- Sample for vocabulary testing analysis was a subgroup within the externalizing behavior group
- The vocabulary testing group as a whole had more resources and more stability in general – presence of father figure?
- Applicability to the general population?
- AAP recommends that physicians counsel parents on the use of discipline for their children
- What to use instead:
- Positive reinforcement strategies
- Other types of punishment: time outs, removal of privileges
- Need for a secure, loving relationship
- Could use this paper part of your discussion with families about avoiding physical punishment
- Other outcomes associated with spanking?
- What kind of discipline really is most effective?
- Role of extended family members and other care-givers (daycare, babysitters)?
Ceroni D, Dubois-Ferriere V, Cherkaoui A, Gesuele R, Combescure C, Lamah L, Manzano S, Hibbs J, Schrenzel J. Detection of Kingella kingae osteoarticular infections in children by oropharyngeal swab PCR. Pediatrics. 2013 Jan;131(1):e230-5.
Full-text for Children’s and Emory users.
OBJECTIVE: The purpose of this study was to investigate if oropharyngeal swab polymerase chain reaction (PCR) could predict osteoarticular infection (OAI) due to Kingella kingae in young children.
METHODS: One hundred twenty-three consecutive children aged 6 to 48 months presenting with atraumatic osteoarticular complaints were prospectively studied. All had a clinical evaluation, imaging, and blood samples. Blood and oropharyngeal specimens were tested with a PCR assay specific for K kingae. OAI was defined as bone, joint, or blood detection of pathogenic bacteria, or MRI consistent with infection in the absence of positive microbiology. K kingae OAI was defined by blood, bone, or synovial fluid positivity for the organism by culture or PCR.
RESULTS: Forty children met the OAI case definition; 30 had K kingae OAI, 1 had another organism, and 9 had no microbiologic diagnosis. All 30 oropharyngeal swabs from the K kingae case patients and 8 swabs from the 84 patients without OAI or with OAI caused by another organism were positive. The sensitivity and specificity of the oropharyngeal swab PCR assay for K kingae were 100% and 90.5%, respectively.
CONCLUSIONS: Detection of K kingae DNA in oropharyngeal swabs of children with clinical findings of OAI is predictive of K kingae OAI. If these findings are replicated in other settings, detection of K kingae by oropharyngeal swab PCR could improve the recognition of OAI.
Reviewed by Kristina Betters, MD and Amelia Thompson, MD
- Kingella kingae is a leading cause of osteoarticular infections in children less than 48 months of age
- Kingella kingae is very difficult to isolate in cultures- often causative organism in culture negative osteoarticular infections; often PCR of joint fluid/aspirate needed to ascertain diagnosis
- Investigators attempting to use oral pharyngeal PCR as non-invasive diagnostic test for diagnosing K. kingae osteoarticular infections
- All subjects tested presented with concern for osteoarticular infection (no healthy controls in study)
- In study population very high rate of K. kingae infection (and low staph infection rate). May not be applicable to our treatment population in Atlanta.
- Oral pharyngeal PCR had high sensitivity/specificity, but somewhat low sample size and lower positive predictive value and negative predictive value
- Potential future directions: determining asymptomatic oral carriage rate of K. kingae, increasing sample size, expanding to multi-center trial for more heterogeneous sample
Qureshi F, Zaritsky A, Poirier MP. Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma. J Pediatr. 2001 Jul;139(1):20-6.
Full-text for Children’s and Emory users.
OBJECTIVE: The objective was to determine whether 2 days of oral dexamethasone (DEX) is more effective than 5 days of oral prednisone/prednisolone (PRED) in improving symptoms and preventing relapse in children with acute asthma.
STUDY DESIGN: This was a prospective randomized trial of children (2 to 18 years old) who presented to the emergency department with acute asthma. PRED 2 mg/kg, maximum 60 mg (odd days) or DEX 0.6 mg/kg, maximum 16 mg (even days) was used. At discharge children in the PRED group were prescribed 4 daily doses (1 mg/kg/d, maximum 60 mg); children in the DEX group received a prepackaged dose (0.6 mg/kg, maximum 16 mg) to take the next day. The primary outcome was relapse within 10 days.
RESULTS: When DEX was compared with PRED, relapse rates (7.4% of 272 vs 6.9% of 261), hospitalization rates from the emergency department (11% vs 12%) or after relapse (20% vs 17%), and symptom persistence at 10 days (22% vs 21%) were similar. In the PRED group more children were excluded for vomiting in the emergency department (3% vs 0.3%; P =.008), more parents were noncompliant (4% vs. 0.4%; P =.004), and more children missed > or =2 days of school (19.5% vs. 13.2%; P =.05).
CONCLUSION: In children with acute asthma, 2 doses of dexamethasone provide similar efficacy with improved compliance and fewer side effects than 5 doses of prednisone.
Reviewed by Rebecca Sanders, MD and Young Shim, MD
- For pediatric patients presenting with status asthmaticus (requiring at least 2 nebulized albuterol treatments) no significant difference in relapse rates were noted between 2 days of dexamethasone (0.6 mg/kg) vs 5 days of prednisone (2 mg/kg x 1 then 1 mg/kg x 4 more days) treatment groups
- People were however more compliant in taking 2 days of dexamethasone compared to PRED (although this did not effect relapse rate)
- Dexamethasone treatment group were less likely to miss ≥ 2 days of school compared to prednisone group
- Children were more likely to vomit prednisone (though this analysis was from excluded group)