Staphylococcus aureus Devlynne S. Ondusko, MD,* Dawn Nolt, MD, MPH † *Department of Pediatrics and † Division of Pediatric Infectious Diseases, Doernbecher Children’s Hospital, Oregon Health & Science University, Portland, OR Practice Gap Staphylococcus aureus can cause numerous disease processes, and management varies with pathology and severity. It is important for the general pediatrician to identify factors that increase a patient’s risk of developing S aureus infection to ensure appropriate treatment. Objectives After completing this article, readers should be able to: 1. Understand the epidemiology of common Staphylococcus aureus diseases. 2. Recognize risk factors that increase patient susceptibility to S aureus infections. 3. Understand the difference in clinical presentations and pathogenesis between S aureus infection and toxin-mediated illness. 4. Understand the importance of bacterial cultures, antibiotic susceptibilities, and local community prevalence of methicillin and clindamycin resistance. 5. Identify which antibiotics are appropriate for empirical treatment of methicillin-sensitive and methicillin-resistant S aureus. 6. Understand the level of evidential support regarding decolonization practices and when such practices are recommended. Abstract Staphylococcus aureus is a bacterium that can cause a variety of illnesses through suppurative or nonsuppurative (toxin-mediated) means. S aureus is a common cause of skin and skin structure infections as well as osteoarticular infections in the pediatric population. S aureus is also identified in cases of septicemia, infective endocarditis, pneumonia, ocular infections, and central nervous system infections. To design appropriate empirical therapy, pediatricians should be knowledgeable about the resistance patterns of S aureus in their communities, including methicillin and clindamycin resistance. This article reviews the microbiology, colonization and transmission, and antibiotic resistance of and clinical diseases caused by S aureus. AUTHOR DISCLOSURE Drs Ondusko and Nolt have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/ investigative use of a commercial product/ device. ABBREVIATIONS BLRBL b-lactamase–resistant b-lactam CA-MRSA community-acquired methicillin-resistant Staphylococcus aureus CNS central nervous system IE infective endocarditis IV intravenous MIC minimum inhibitory concentration MRSA methicillin-resistant Staphylococcus aureus MSSA methicillin-sensitive Staphylococcus aureus PBP penicillin-binding protein SSSS staphylococcal scalded skin syndrome SSSI skin and skin structure infection TMP-SMX trimethoprim-sulfamethoxazole TSS toxic shock syndrome VISA vancomycin-intermediate Staphylococcus aureus VRSA vancomycin-resistant Staphylococcus aureus Vol. 39 No. 6 JUNE 2018 287 by guest on January 1, 2019 http://pedsinreview.aappublications.org/ Downloaded from by guest on January 1, 2019 http://pedsinreview.aappublications.org/ Downloaded from by guest on January 1, 2019 http://pedsinreview.aappublications.org/ Downloaded from
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Staphylococcus aureusDevlynne S. Ondusko, MD,* Dawn Nolt, MD, MPH†
*Department of Pediatrics and †Division of Pediatric Infectious Diseases, Doernbecher Children’s Hospital,
Oregon Health & Science University, Portland, OR
Practice Gap
Staphylococcus aureus can cause numerous disease processes, and
management varies with pathology and severity. It is important for the
general pediatrician to identify factors that increase a patient’s risk of
developing S aureus infection to ensure appropriate treatment.
Objectives After completing this article, readers should be able to:
1. Understand the epidemiology of common Staphylococcus aureus diseases.
2. Recognize risk factors that increase patient susceptibility to S aureus
infections.
3. Understand the difference in clinical presentations and pathogenesis
between S aureus infection and toxin-mediated illness.
4. Understand the importance of bacterial cultures, antibiotic
susceptibilities, and local community prevalence of methicillin and
clindamycin resistance.
5. Identify which antibiotics are appropriate for empirical treatment of
methicillin-sensitive and methicillin-resistant S aureus.
6. Understand the level of evidential support regarding decolonization
practices and when such practices are recommended.
Abstract
Staphylococcus aureus is a bacterium that can cause a variety of illnesses
through suppurative or nonsuppurative (toxin-mediated) means. S aureus is
a common cause of skin and skin structure infections as well as osteoarticular
infections in the pediatric population. S aureus is also identified in cases of
septicemia, infective endocarditis, pneumonia, ocular infections, and central
nervous system infections. To design appropriate empirical therapy,
pediatricians should be knowledgeable about the resistance patterns of S
aureus in their communities, includingmethicillin and clindamycin resistance.
This article reviews the microbiology, colonization and transmission, and
antibiotic resistance of and clinical diseases caused by S aureus.
AUTHOR DISCLOSURE Drs Ondusko andNolt have disclosed no financial relationshipsrelevant to this article. This commentary doesnot contain a discussion of an unapproved/investigative use of a commercial product/device.
ABBREVIATIONS
BLRBL b-lactamase–resistant b-lactam
CA-MRSA community-acquired
methicillin-resistant
Staphylococcus aureus
CNS central nervous system
IE infective endocarditis
IV intravenous
MIC minimum inhibitory
concentration
MRSA methicillin-resistant
Staphylococcus aureus
MSSA methicillin-sensitive
Staphylococcus aureus
PBP penicillin-binding protein
SSSS staphylococcal scalded skin
syndrome
SSSI skin and skin structure infection
TMP-SMX trimethoprim-sulfamethoxazole
TSS toxic shock syndrome
VISA vancomycin-intermediate
Staphylococcus aureus
VRSA vancomycin-resistant
Staphylococcus aureus
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unknown Direct inoculation BLRBL Vancomycin,clindamycin,linezolid, doxycycline,TMP-SMX
7 days or guided byresponse totreatment
Bacteremia 1.54–1.95 per 1,000pediatrichospitalizations
Foreign body,respiratory,osteoarticular, or SSSIhematogenousspread of infection
BLRBL þ vancomycin Minimum 14 d afterfirst negativeblood culture
Infectiveendocarditis
0.41–0.43 per 100,000children (S aureus24%–36%)
Heart defect, foreignbody, intravenousdrug use
BLRBL þ vancomycin –gentamicin –rifampin
2–8 wk after firstnegative bloodculture
CNS infection 5%–6% of bacterialmeningitis; w23% ofVP shunt infections
Direct inoculation,foreign body, midlinespinal defect
Nafcillin/oxacillin þvancomycin
2 wk for meningitis;4–8 wk forintracranialabscess
Pneumonia 1% of CAP requiringhospitalization; 6%–32% of necrotizingpneumonia
Inhalation,hematogenousseeding
BLRBL Vancomycin,clindamycin,b
linezolid
7 d or guided byresponse totreatment
Osteoarticularinfection
7.1 per 100,000 children(overall, not specificto S aureus)
Hematogenous, directinoculation,contiguous spread
BLRBL Vancomycin,c
clindamycin,b
linezolid
3–4 wk for septicarthritis; 4–6 wkfor osteomyelitis
Ocular infections 12.1% ofophthalmologicinfections are causedby MRSA
Direct inoculation,contiguous and/orhematogenousspread
BLRBL Vancomycin,clindamycin,b
linezolid
2 wk
BLRBL¼b-lactamase–resistant b-lactam, CAP¼community-acquired pneumonia, CNS¼central nervous system, MRSA¼methicillin-resistantStaphylococcus aureus, MSSA¼methicillin-sensitive Staphylococcus aureus, SSSI¼skin and skin structure infection, TMP-SMX¼trimethoprim-sulfamethoxazole; VP¼ventriculoperitoneal.aMild SSSIs include impetigo, localized folliculitis, and superficial secondary bacterial infection.bClindamycin may be considered if a high percentage of S aureus isolates in the community are susceptible to clindamycin.cVancomycin is included in the empirical treatment if community rates of MRSA are greater than 10%.
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tages of clindamycin include excellent tissue penetration
(bone, abscess) and the high bioavailability of the oral drug.
However, clindamycin is a bacteriostatic drug against S
aureus and may not have activity against all isolates of
MSSA or MRSA. These 2 reasons should be recalled if the
TABLE 2. Antibiotics Used for Staphylococcus aureus in the PediatricPopulation
ANTIBIOTIC MECHANISM OF ACTION ADMINISTRATION DOSING MAXIMUM
Nafcillin Inhibition of bacterial cell wall synthesis by bindingof PBPs
IV 200 mg/kg per day divided every 6 h 2g/dose, 12 g/d
Oxacillin Inhibition of bacterial cell wall synthesis by bindingof PBPs
IV 200 mg/kg per day divided every 6 h 2g/dose, 12 g/d
Cefazolin Inhibition of bacterial cell wall synthesis by bindingof PBPs
IV 75–150mg/kg per day divided every 8 h 6 g/d
Cephalexin Inhibition of bacterial cell wall synthesis by bindingof PBPs
PO 50–100mg/kper daydividedevery 6–8h 4 g/d
Vancomycin Inhibition of bacterial cell wall synthesis by bindingof D-alanyl-D-alanine
IV 15–20 mg/kg per dose every 6 ha 2 g/d
Clindamycin Inhibition of bacterial protein synthesis by binding50S ribosome to inhibit transpeptidation
IV or PO 40 mg/kg per day divided every 6–8 h IV: 4.8 g/dPO: 1.8 g/d
Linezolid Inhibition of bacterial protein synthesis by binding50S ribosome to inhibit the initiation process
IV or PO Age<12 y: 10mg/kg per dose every 8 h 600 mg/doseAge ‡ 12 y: 600 mg every 12 h
Doxycycline Inhibit bacterial protein synthesis by binding30S ribosomal subunit preventing tRNA frombinding
IV or PO 2.2 mg/kg per day divided every 12 h 200 mg/d
TMP-SMX Inhibition of bacterial DNA synthesis by blockageof metabolic pathways
IV or PO 6–12 mg TMP/kg per day dividedevery 12 h
160 mgTMP/dose
IV¼intravenous, PBP¼penicillin-binding protein, PO¼oral, TMP-SMX¼trimethoprim-sulfamethoxazole.aVancomycin dosing and goal trough level depend on the age of the patient, severity of infection, and renal insufficiency.
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Outside of surgical site infection prevention, most decol-
onization regimens include household members. As noted
previously, household exposures (ie, close contacts) may
play a role in colonization. (54) Therefore, decolonization
of household contacts may alter the colonization pattern in
the index case, which could result in a successful and
sustained reduction of SSSIs. (54)
References for this article are at http://pedsinreview.aappubli-
cations.org/content/39/6/287.
Summary• Based on observational and epidemiologic studies,approximately one-third of the population is colonizedwith Staphylococcus aureus, and colonization of theindividual and/or household members is a risk factor forS aureus infection.
• From evidence-based guidelines, empirical treatment for non–life-threatening infections suspected to be from S aureus shouldinclude methicillin-sensitive S aureus (MSSA) treatment, ideally ab-lactamase–resistant b-lactam (BLRBL). Methicillin-resistant Saureus (MRSA) treatment may be included (either with a seconddrug or more often as clindamycin monotherapy) in geographicareas with high rates of community-acquired MRSA.
• From published clinical guidelines and expert opinion, empiricaltreatment for life-threatening and invasive S aureus infectionsshould cover both MSSA and MRSA. This includes a parenteralBLRBL (for MSSA) and vancomycin (for MRSA) while awaitingculture results and susceptibilities.
• From evidence-based guidelines, the treatment of staphylococcalscalded skin syndrome includes parenteral antibiotics and fluidand electrolyte management.
• Evidence-based guidelines recommend that the treatment oftoxic shock syndrome due to S aureus includes drainage of thenidus of infection, antibiotics targeted to inhibiting bacterial cellwall synthesis (such as nafcillin/oxacillin or vancomycin), andinhibiting protein synthesis (such as clindamycin).
• On the basis of Cochrane review and expert opinion,decolonization practices have little evidential support. Thesepractices may be used if the patient experiences recurrent skinand skin structure infections despite optimization of handhygiene and wound care. If decolonization is recommended, allmembers in the household should also undergo this process.
To view teaching slides that accompany this article,
visit http://pedsinreview.aappublications.org/
content/39/6/287.supplemental.
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PIR QuizThere are two ways to access the journal CME quizzes:
1. Individual CME quizzes are available via a handy blue CME link under the article title in the Table of Contents of any issue.
2. To access all CME articles, click “Journal CME” from Gateway’s orange mainmenu or go directly to: http://www.aappublications.
org/content/journal-cme.
3. To learn how to claim MOC points, go to: http://www.aappublications.org/content/moc-credit.
REQUIREMENTS: Learnerscan take Pediatrics in Reviewquizzes and claim creditonline only at: http://pedsinreview.org.
To successfully complete2018 Pediatrics in Reviewarticles for AMA PRACategory 1 CreditTM, learnersmustdemonstrate aminimumperformance level of 60% orhigher on this assessment.If you score less than 60%on the assessment, youwill be given additionalopportunities to answerquestions until an overall 60%or greater score is achieved.
This journal-based CMEactivity is available throughDec. 31, 2020, however, creditwill be recorded in the year inwhich the learner completesthe quiz.
2018 Pediatrics in Review nowis approved for a total of 30Maintenance of Certification(MOC) Part 2 credits by theAmerican Board of Pediatricsthrough the AAP MOCPortfolio Program. Completethe first 10 issues or a total of30 quizzes of journal CMEcredits, achieve a 60% passingscore on each, and startclaiming MOC credits as earlyas October 2018. To learn howto claim MOC points, go to:http://www.aappublications.org/content/moc-credit.
1. A previously healthy 3-year-old boy is brought to the office due to a painful lesion on hisright thigh. He has not had fever and is eating well. Mom states that the area started tohave whitish drainage this morning. His father has a history of recurrent methicillin-resistant Staphylococcus aureus (MRSA) skin infections. There is a 3-cm erythematous areaof his right thigh that has purulent drainage. A culture is obtained that grows MRSA.Which of the following is the mechanism of resistance to methicillin and other b-lactamantibiotics?
A. Alteration of penicillin-binding protein.B. b-Lactamase production.C. Decreased antibiotic membrane permeability.D. Efflux mechanism.E. Modification of the ribosomal antibiotic target.
2. A previously healthy 9-month-old girl is admitted to the hospital due to cellulitis of her leftbuttock that is not improved after 2 days of treatment with cephalexin. She is fussy butconsolable. Her temperature is 102.4°F (39.1°C). There is a 12�15-cm tender area oferythema and induration of her right buttock with central fluctuance. Incision anddrainage is performed and sent for culture. The hospital antibiogram notes that 36% ofS aureus isolates were resistant to clindamycin. Which of the following is the mostappropriate initial antibiotic treatment regimen?
A. Ampicillin-sulbactam.B. Ceftriaxone.C. Nafcillin.D. Trimethoprim-sulfamethoxazole (TMP-SMX).E. Vancomycin.
3. A 20-month-old boy is admitted to the hospital due to a 3-day history of fever. He startedlimping 4 days ago and now will not bear weight on his left leg. He has also developedswelling around his left knee. A magnetic resonance image of the left leg bone showsmarrow edema of the left distal femur and a subperiosteal fluid collection. The latestantibiogram released by the hospital lists a 26% incidence of MRSA isolated fromthe community. A blood culture is obtained, and he is started on intravenous (IV)vancomycin and ceftriaxone. He is taken to the operating room for incision and drainage.The blood culture and subperiosteal abscess culture grow S aureus susceptible tooxacillin (methicillin susceptible), vancomycin, linezolid, tetracycline, and TMP-SMX. Hehas no known drug allergies. Transition to which of the following IV antibiotics is mostappropriate?
A. Ampicillin.B. Doxycyline.C. Linezolid.D. Nafcillin.E. TMP-SMX.
4. By day 7 of hospitalization the same 20-month-old boy as in question 3 is significantlyimproved. He has been afebrile for 48 hours and is starting to bear weight on his left leg.A repeated blood culture has no growth after 72 hours. He is discharged on oralcephalexin.
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Which is the most appropriate total duration of antimicrobial therapy if he continues toclinically improve with normalization of his ESR?
A. Fourteen days.B. Six weeks.C. Ten days.D. Twelve weeks.E. Twenty-one days.
5. A 14-year-old girl with a history of recurrent acute sinusitis is admitted to the PICU afterpresenting to the emergency department with a 2-day history of fever and diffusemyalgia.Her most recent menstrual period ended 6 days ago. Over the past day she has had 2episodes of vomiting and 5 watery stools. She has also developed a rash. In the emergencydepartment her temperature was 102.2°F (39°C), heart rate was 112 beats/min, respiratoryrate was 28 breaths/min, blood pressure was 96/60 mm Hg, and oxygen saturation was97%. She was given 2 boluses of IV normal saline and is currently receiving a third bolus.She also received IV vancomycin and IV ceftriaxone. Her blood pressure, after 2 fluidboluses, currently is 111/70 mm Hg, and her heart rate is 84 beats/min. She is tiredappearing but can answer questions appropriately. She has conjunctival injection and adiffuse macular erythroderma. Her capillary refill time is 2 seconds. The remainder of herexamination findings are normal. Laboratory tests show awhite blood cell count of 15,200/mL(15.2�109/L), hemoglobin level of 12.4 g/dL (124 g/L), platelet count of 85 � 103/mL (85 �109/L), aspartate aminotransferase level of 106 U/L (1.8 mkat/L), creatine phosphokinaselevel of 232 U/L (3.9 mkat/L), blood urea nitrogen level of 15 mg/dL (5.4 mmol/L), andcreatinine level of 0.8 mg/dL (70.7 mmol/L). Blood culture is pending. Which of thefollowing is the most appropriate next step in management?
A. Computed tomographic scan of the abdomen and pelvis.B. Fresh frozen plasma transfusion.C. IV clindamycin.D. IV doxycycline.E. IV phenylephrine.
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DOI: 10.1542/pir.2017-02242018;39;287Pediatrics in Review
Devlynne S. Ondusko and Dawn NoltStaphylococcus aureus
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health maintenance, acute care, and emergency depart-
ment visits. This would help highlight and perhaps rein-
force in the consciousness of adolescents the importance
of this issue. Parents serve as role models, and because
adolescents will often emulate their parents’ behaviors,
addressing this issue to parents is also needed. Although
studies show that adolescents recognize the dangers
with TWD, they still report participating in the behavior.
As with other injury prevention strategies, it seems that
a focus on why abstaining from TWD is beneficial is a
more powerful approach than the focus on harm. For
some adolescents, compulsive texting may be a behavioral
addiction and may need to be addressed. Other innovative
strategies that need further evaluation include peer to peer
education, school-based interventions, messages on social
media, and capabilities to directly observe behaviors while
driving.
– Janet R. Serwint, MDAssociate Editor, In Brief
CME Quiz ClarificationAn astute reader noted a need for clarification in the CME quiz for the May 2017 review “Screening for Poverty and
Poverty-Related Social Determinants of Health” (Berman RS, Patel MR, Belamarich PF, Gross RS. Pediatric Rev. 2018;
39(5):235-246, DOI: 10.1542/pir.2017-0123). The child featured in the question 5 stem has been changed from a 1-year-
old-boy to a 7-year-old boy to more closely coincide with the answer options presented. The online version of the quiz
has been updated, and a clarification notice has been posted with the online version of the article. The journal appreciates
the clarification.
CME Quiz CorrectionAn error appeared in the print version of the CME quiz for the June 2018 review “Staphylococcus aureus” (Ondusko DS,
Nolt D. Pediatr Rev. 2018;39(6):287-298, DOI: 10.1542/pir.2017-0224). In question 5, the platelet count should read
“85 x 103mL (85 x 109/L).” The online version of the quiz is correct, and a correction notice has been posted with the
online version of the article. The journal regrets the error.
374 Pediatrics in Review
DOI: 10.1542/pir.2017-02242018;39;287Pediatrics in Review
Devlynne S. Ondusko and Dawn NoltStaphylococcus aureus
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