Incidence of Invasive Community-Onset Staphylococcus aureus Infections in Children in Central New York Manika Suryadevara, MD, Maria R. Moro, MD, Paula F. Rosenbaum, PhD, Deanna Kiska, PhD, Scott Riddell, PhD, Leonard B. Weiner, MD, and Jana Shaw, MD, MPH We determined the incidence of invasive community-onset Staphylococcus aureus infections, clinical characteristics, and antibiotic susceptibilities in 128 hospitalized children in central New York. The prevalence of invasive S aureus infections in our institution remained <1% between 1996 and 2006, although the proportion of methicillinresistant S aureus infections significantly increased. (J Pediatr 2010;156:152-4)
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ublished data on invasive Staphylococcus aureus (ISA) infection in children consists of small case series1-6 or studies of methicillin-resistant S aureus (MRSA) hospitalization cost.7-9 A single study describing the incidence of ISA infection in US children focused on invasive MRSA alone.10 The impact of MRSA on the incidence and prevalence of ISA infections in children remains unknown; consequently, we calculated the prevalence and incidence of ISA infection in hospitalized children from central New York and described the clinical characteristics and antibiotic susceptibilities.
Methods This retrospective study was approved by the institutional review board of Upstate Medical University and performed at University Hospital in Syracuse, New York (UHS). We compiled a list of S aureus isolates from sterile sites in children <19 years of age, hospitalized between January 1996 and December 2006. We included patients with and without known health care risk factors who met the Centers for Disease Control definition for community-onset S aureus infection when the cultures were obtained <48 hours after hospitalization. ISA was defined as infections of bloodstream, heart, lungs, pleural space, lymph nodes, central nervous system, abdomen, bones, and joints. Patients with abscesses were only included when they had concomitant bacteremia or had a deep-seated abscess. Information documented included patient’s age, sex, date of admission, site of positive cultures, discharge diagnoses, documented underlying conditions, admission to the pediatric intensive care unit, and death from infection. Starting in 2003, the disk approximation test for inducible clindamycin resistance was routinely performed. S aureus isolation and antibiotic susceptibilities were determined by the clinical laboratory at UHS.
ISA MRSA MSSA UHS
Invasive Staphylococcus aureus Methicillin-resistant S aureus Methicillin-sensitive S aureus University Hospital in Syracuse, New York
Analyses were conducted by using SPSS software (SPSS Inc., Chicago, Illinois), with 2-tailed hypotheses and a P value #.05 considered to be significant. Pearson c2 test was used to assess categorical variable associations, and the t test was used for continuous variables. The Mantel-Haenszel test was used to assess the trend in the proportion of MRSA infections with time. Prevalence and incidence figures were calculated in the 11-year study period. The annual prevalence was calculated by dividing the total number of patients infected with methicillin-sensitive S aureus (MSSA) or MRSA by the number of pediatric hospitalizations (30 623 between 1996 and 2006). UHS draws from a 17-county area, with 96% of all pediatric patients coming from 14 counties. Incidence rates were calculated by using year 2000 US Census Bureau population figures (http://factfinder.census.gov/).
Results During the 11-year study period, 128 S aureus isolates were collected. Of these, 115 (90%) were MSSA and 13 (10%) were MRSA. Table I (available at www.jpeds.com) summarizes patient demographic characteristics and underlying conditions. There were a total of 194 discharge diagnoses for patients with MSSA infection and 16 for patients with MRSA infection (Table II; available at www.jpeds.com). Bloodstream infection was the most frequent diagnosis for both MRSA (n = 6) and MSSA (n = 80) infections. Abscess was the only diagnosis significantly associated with MRSA infection (P = .016). Of 86 patients with bloodstream infection, 26 had bacteremia alone, and 60 had other focal infections (Table III; available at www.jpeds.com). Children with MRSA were more likely to have positive culture test results from only 1 site compared with children with MSSA (P < .05). Only 1 infection (MSSA) resulted in death. Seventeen patients required a pediatric intensive care unit stay; all were
From the Department of Pediatrics (M.S., M.M., L.W., J.S.), Department of Pathology (D.K., S.R.), and Department of Public Health and Preventive Medicine (P.R.), Upstate Medical University, Syracuse, NY The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2010 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2009.07.020
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infected with MSSA. Eleven patients had an underlying condition, and 10 patients had a diagnosis of sepsis. All S aureus isolates were susceptible to vancomycin and trimethoprimsulfamethoxazole. Clindamycin susceptibility was observed in only 6 (60%) and 41 (82%) of MRSA and MSSA isolates, respectively, from 2003 to 2006. ISA infections were observed in <1% of all pediatric admissions at UHS from 1996 to 2006. However, the proportion of MRSA in all ISA infections increased from 3% (1/37) from 1996 to 1999 to 17% (10/60) from 2003 to 2006 (P = .023). Overall, the prevalence of ISA infections increased from 35.8 to 47.8 of 10 000 pediatric admissions between the periods of 1996 to 1999 and 2003 to 2006. MRSA prevalence also increased, with an observed frequency of 1.0 to 7.9 of every 10 000 pediatric admissions. In contrast, MSSA prevalence remained constant, ranging from 34.9 to 39.8 of every 10 000 pediatric admissions (Figure). The incidence of MSSA and MRSA infections was highest during the 2003 to 2006 period and in children 0 to 4 years of age (Table IV).
Discussion
60
60
50
50 14
40
40
30
30 21 13
20 10
20
36 2 16
15 0
0 19961999
1
1
8
1
20002002
10 0
20032006
Average prevalence/10,000 admissions
Total number of isolates
Although the prevalence of ISA infections was <1% of pediatric admissions, the proportion of MRSA infections significantly increased. Our findings are in agreement with those of other studies, which have shown an increase of MRSA prevalence in hospitalized patients.2,6-9 Because there is no data on the incidence of pediatric ISA infections in the literature, our study provides baseline values for assessing future trends. Klevens et al reported incidence rates of invasive MRSA infection of 14.9 and 0.7 for every 100 000 people in <1-year-old and 5- to 17-year-old white patients, respectively.10 Because the population estimates used by Klevens et al were not specified, our MRSA incidence rates cannot be directly compared with their findings.
MRSA isolates/underlying condition MRSA isolates/healthy MSSA isolates/underlying condition MSSA isolates/no underlying condition MRSA prevalence
Table IV. Estimated population-based incidence of invasive Staphylococcus aureus infection in children <19 years of age admitted to University Hospital, 1996 to 2006
Study period 1996-1999 2000-2002 2003-2006 Age group (years) 0-4 5-9 10-14 15-18
Incidence S aureus per 100 000
Incidence MSSA per 100 000
Incidence MRSA per 100 000
2.0 2.3 3.3
2.0 2.1 2.7
0.1 0.1 0.5
12.5 2.5 2.4 2.8
8.7 1.7 2.4 1.9
3.8 0.8 0 0.9
*Age group/number of cases total/MSSA/MRSA: 0-4:50/43/7; 5-9:19/17/2; 10-14:25/24/1; 1518:34/31/3.
Although 98% of our patients with ISA infections came from 14 counties, it is possible that our incidence rates represent an underestimate because children may have been admitted to another facility. Although unlikely, the incidence rates may represent an overestimate if cases resided in counties with populations that were not accounted for in the denominator. Only 10% of ISA infection in our patients were caused by MRSA. In other parts of the country, MRSA accounts for as much as 60% of infections in children with ISA disease.2,3 Antibiotic susceptibility alone does not appear to predict the severity of the disease in our population. This view is consistent with a report by Faden et al,11 who showed that antibiotic susceptibility alone was not related to the severity of S aureus skin abscesses in 49 children from Buffalo, New York. Instead, their isolates exhibited related genetic architecture and the presence of the PVL gene and USA300 pulsed field type. Although the significance of PVL and USA300 remain controversial, it would have been useful to characterize our isolates. A planned prospective study will address this limitation. In our study, clindamycin resistance was high compared with other parts of the United States.2,8,11 Facility-wide, from 2003 to 2006, UHS antibiograms showed that 26% of 3334 outpatient MSSA and 49% of 1465 MRSA isolates were resistant to clindamycin, supporting the findings of our study and limiting its usefulness for suspected S aureus infection in our area.
MSSA prevalence S aureus prevalence
Submitted for publication Feb 3, 2009; last revision received June 11, 2009; accepted July 8, 2009. Reprint requests: Dr Jana Shaw, Department of Pediatrics, 750 E Adams St, Syracuse, NY 13210. E-mail:
[email protected].
Study Period The Proportion of MRSA cases increased significantly from 3% (1/37) in 1996-1999 to 17% (10/60) in 2003-2006, p=0.023
Figure. Number of invasive S aureus isolates and prevalence of invasive S aureus infections in children admitted to University Hospital in Syracuse, from 1996 to 2006.
References 1. Sattler CA, Mason EO, Kaplan SL. Prospective comparison of risk factors and demographic and clinical characteristics of community-acquired, methicillin-resistant versus methicillin-susceptible Staphylococcus aureus infection in children. Pediatr Infect Dis J 2002;21:910-6. 153
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2. Kaplan SL, Hulten KG, Gonzalez BE, Hammerman WA, Lamberth L, Versalovic J, et al. Three-year surveillance of community-acquired Staphylococcus aureus infections in children. Clin Infect Dis 2005;40:1785-91. 3. Jaggi P, Paule S, Peterson LR, Tan TQ. Characteristics of Staphylococcus aureus infections in Chicago Pediatric hospital. Emerg Infect Dis 2007; 13:311-4. 4. Zaoutis TE, Toltzis P, Chu J, Abrams T, Dul M, Kim J, et al. Clinical and molecular epidemiology of community-acquired methicillin-resistant S aureus infections among children with risk factors for health care- associated infection: 2001-2003. Pediatr Infect Dis J 2006;25:343-8. 5. Ross AC, Toltzis P, O’Riordan AO, Millstein L, Sands T, Redpath A, et al. Frequeny and risk factors for deep focus of infection in children with S aureus bacteremia. Pediatr Infect Dis J 2008;2008:396-9. 6. McCaskill ML, Mason EO, Kaplan SL, Hammerman W, Lamberth LB, Hulten KG. Increase of the USA300 clone among community-acquired methicillin-susceptible S aureus causing invasive infections. Pediatric Infect Dis J 2007;26:1122-7.
Vol. 156, No. 1 7. Purcell K. Fergie J. Increase in hospitalizations for cellulitid and abscess concurrent with the epidemic of community-acquired methicillin-resistant S aureus infections in children., Presented at 2005 Annual Meeting of the Pediatric Societies; May 2005; Washington, DC. 8. Buckingham SC, McDougal LK, Cathey LD. Emergence of communityassociated methicillin-resistant S aureus at a Memphis, Tennessee, children’s hospital. Pediatr Infect Dis J 2004;23:619-24. 9. Harold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin RE, Boyle-Vavra S, et al. Community-acquired methicillin-resistant S aureus in children with no identified predisposing risk. JAMA 1998;279:593-8. 10. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007;298:1763-71. 11. Faden H, Rose R, Lesse A, Hollands C, Dryja D, Glick PL. Clinical and molecular characteristics of S aureus skin abscesses in children. J Pediatr 2007;151:700-3.
50 Years Ago in THE JOURNAL OF PEDIATRICS The Blood Volume of Infants: Alterations in the First Hours After Birth Sisson TRC, Whalen LE. J Pediatr 1960:56:43-7
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ighty milliliters per kilogram: the newborn’s blood volume. It’s a number that was drummed into me by learned superiors during training. One knows this number instinctively, but rarely question from where it comes. However, it guides much that we do. Sisson and Whalen’s paper is one of the earlier attempts to measure the blood volume of infants, and 80 mL/kg is apparently a bit low! They explored blood volume changes of the first hours after birth in 12 healthy newborns. The methodology used says much about how research ethics have changed in the last 50 years. In the first hours after birth and again 3 hours later, they injected an azo dye into an antecubital or scalp vein. Ten minutes later, 3.5 mL of blood was taken via venipuncture from the femoral vein to measure the dye dilution.try putting that one past your internal review board today! Ethics aside, the results are interesting. They showed a 22% increase in blood volume, from a mean of 88 to 107 mL/kg, and that this was made up of a 20% increase in plasma volume and a 25% increase in red cell volume. The former is easier to rationalize because of what we know about extra-cellular fluid in the newborn. Increasing red cell volume is harder to rationalize, but supported by the finding of a little changed hematocrit level. They speculate that blood must be sequestered in reservoirs in the organs while circulatory transition occurs. The discussion refers to the then common practice of delayed cord clamping and cord milking, arguing against it on the basis that the blood in the placenta is intended for the circulation of ‘‘an organ that is amputated at birth’’ and that it is ‘‘physiologically illogical’’ to transfer this blood to a normal infant. How things come full circle! And should we still be using 80 mL/kg? Well, it’s still a reasonable approximation; since 1960, the numbers for newborn blood volume have been as varied as the methodologies used to measure it.1 Nick Evans, DM, MRCPCH Royal Prince Alfred Hospital University of Sydney Sydney, New South Wales, Australia 10.1016/j.jpeds.2009.08.006
Reference 1. Aladangady N, Leung T, Costeloe K, Delpy D. Measuring circulating blood volume in newborn infants using pulse dye densitometry and indocyanine green. Paediatr Anaesth 2008;18:865-71.
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CLINICAL AND LABORATORY OBSERVATIONS
January 2010
Table I. Demographic information for pediatric patients with invasive Staphylococcus aureus infections admitted to University Hospital in Syracuse, 1996 to 2006
Age (years) 0-4 5-9 10-14 15-18 Mean ( SD) Median Sex Male Female Underlying conditions* Medical device present Immunodeficiency Congenital heart disease End-stage renal disease None
MRSA n = 13 (%)
MSSA n = 115 (%)
S aureus n = 128 (%)
7 (54) 2 (15) 1 (8) 3 (23) 6.7 (7.3) 3
43 (37) 17 (15) 24 (21) 31 (27) 8.2 (6.1) 9
50 (39) 19 (15) 25 (19) 34 (27) 8.1 (6.2) 9
10 (77) 3 (23)
76 (66) 39 (34)
86 (67) 42 (33)
3 (23) 1 (8) 0 (0) 0 (0) 9 (69)
39 (34) 16 (14) 7 (6) 2 (2) 67 (52)
42 (33) 17 (13) 7 (5) 2 (1) 77 (60)
Table III. Focal infections associated with 86 cases of Staphylococcus aureus bacteremia Diagnosis*
MSSA, n
MRSA, n
S aureus, n
Bacteremia alone Septic arthritis Cellulitis Osteomyelitis Catheter-related infection Endo/pericarditis Pneumonia/empyema Abscess Myositis Other
23 15 7 10 11 5 8 4 5 2
3 0 1 0 1 0 0 1 0 0
26 15 8 10 12 5 8 5 5 2
*Diagnoses are not mutually exclusive.
*Not mutually exclusive.
Table II. Sites of invasive Staphylococcus aureus infection in children admitted to University Hospital in Syracuse, 1996 to 2006 Diagnosis*
MSSA n (%)
MRSA n (%)
S aureus n (%)
Bacteremia Bone/joint/muscle Abscess* Meningitis Lung/pneumonia Endo/pericarditis Catheter-related infection Cellulitis Other Total†
80 (41) 60 (31) 9 (5) 5 (3) 8 (4) 6 (3) 12 (6) 8 (4) 6 (3) 194 (100)
6 (13) 2 (13) 5 (31) 2 (13) 0 (0) 0 (0) 0 (0) 1 (6) 0 (0) 16 (100)
86 (41) 62 (29) 14 (7) 7 (3) 8 (4) 6 (3) 12 (6) 9 (4) 6 (3) 210 (100)
*All 4 patients with cutaneous abscesses had an associated diagnosis of bacteremia. Other abscesses included in the study include abdominal abscess (3), pharyngeal abscess (2), cerebellar abscess (1), paraspinal abscess (2), and liver abscess (2). †Patients could have >1 diagnosis (eg, bloodstream infection and osteomyelitis).
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