MRSA:MRSA:Beyond Butt BoilsBeyond Butt Boils
Jeffrey S. Bennett, M.D.Jeffrey S. Bennett, M.D.Assistant Professor of Pediatrics/Infectious Assistant Professor of Pediatrics/Infectious
DiseaseDiseaseDirector, Section of Inpatient PediatricsDirector, Section of Inpatient Pediatrics
University of KentuckyUniversity of Kentucky
Educational GoalsEducational Goals History of current MRSA epidemicHistory of current MRSA epidemic Describe CA-MRSA, resistance patterns, Describe CA-MRSA, resistance patterns,
and virulence factorsand virulence factors Antimicrobial SelectionAntimicrobial Selection Review invasive and toxin mediated Review invasive and toxin mediated
MRSA diseases and their initial MRSA diseases and their initial treatmenttreatment
Managing the epidemic – media Managing the epidemic – media relations and talking pointsrelations and talking points
DisclosuresDisclosures Dr. Bennett has no relevant financial Dr. Bennett has no relevant financial
relationships with the relationships with the manufacturer(s) of any commercial manufacturer(s) of any commercial product(s) and/or provider of product(s) and/or provider of commercial services discussed in this commercial services discussed in this CME activity, and does not intend to CME activity, and does not intend to discuss an unapproved/investigative discuss an unapproved/investigative use of a commercial product/device use of a commercial product/device in this presentationin this presentation
Epidemic!!Epidemic!!
““Ripped from the Ripped from the Headlines”Headlines”
Jan 13, 2005 ABC News:Jan 13, 2005 ABC News:'Superbug' MRSA Worries Doctors, Athletes Drug-Resistant 'Superbug' MRSA Worries Doctors, Athletes Drug-Resistant
Germ Found in Locker Rooms; Can Kill Within DaysGerm Found in Locker Rooms; Can Kill Within Days October 17, 2007 Dallas Morning News:October 17, 2007 Dallas Morning News:
U.S. deaths from staph 'superbug' may surpass AIDS U.S. deaths from staph 'superbug' may surpass AIDS deathsdeaths
October 19, 2007 Chicago Tribune:October 19, 2007 Chicago Tribune:Superbug alert at high school; Infection struck 2 football Superbug alert at high school; Infection struck 2 football
playersplayers October 23, 2007 Wall Street Journal:October 23, 2007 Wall Street Journal:
Putting Superbugs on the DefensivePutting Superbugs on the Defensive October 28, 2007 China View News:October 28, 2007 China View News:
U.S. county to close all schools amid "superbug" fears (Pike U.S. county to close all schools amid "superbug" fears (Pike County, Kentucky)County, Kentucky)
Staphylococcus aureusStaphylococcus aureus BasicsBasics
Gram’s stain characteristics: spherical, Gram Gram’s stain characteristics: spherical, Gram positive cocci in pairs and groups/clusterspositive cocci in pairs and groups/clusters
Colonize anterior nares, skin of humans and Colonize anterior nares, skin of humans and warm-blooded animals (40% of normal warm-blooded animals (40% of normal population, 50-90% of health care workers); population, 50-90% of health care workers); throat colonization increasingly recognized as throat colonization increasingly recognized as a potentially important reservoira potentially important reservoir
Produce a large array of Virulence FactorsProduce a large array of Virulence Factors Cause a broad spectrum of human diseaseCause a broad spectrum of human disease Spread most commonly by skin-to-skin contactSpread most commonly by skin-to-skin contact Able to survive for extended periods on Able to survive for extended periods on
clothing, surfaces, other fomitesclothing, surfaces, other fomites
CA-MRSA BasicsCA-MRSA Basics CA-MRSA are genetically distinct from CA-MRSA are genetically distinct from
hospital-associated strains of MRSA (HA-hospital-associated strains of MRSA (HA-MRSA)MRSA)
Major virulence factor 1: antibiotic Major virulence factor 1: antibiotic resistanceresistance mec-Amec-A gene: decreased penicillin binding gene: decreased penicillin binding
protein affinity (PBP 2a), ß-lactam resistanceprotein affinity (PBP 2a), ß-lactam resistance ermerm gene: ribosomal subunit methylation, gene: ribosomal subunit methylation,
macrolide/lincosamide/streptogramin resistancemacrolide/lincosamide/streptogramin resistance Major virulence factor 2: Panton-Valentine Major virulence factor 2: Panton-Valentine
Leukocidin (PVL)Leukocidin (PVL) Creates lytic pores in WBC membranes, leads to Creates lytic pores in WBC membranes, leads to
focal tissue necrosis and rapid abscess (boil) focal tissue necrosis and rapid abscess (boil) formationformation
CA-MRSA vs. HA-MRSA*:CA-MRSA vs. HA-MRSA*:Same Exterior, but Very Same Exterior, but Very
Different Under the HoodDifferent Under the Hood Infection TypesInfection Types: CA-MRSA more often associated with : CA-MRSA more often associated with
skin and soft tissue infection (75%) vs. HA-MRSA (37%)skin and soft tissue infection (75%) vs. HA-MRSA (37%) Age DistributionAge Distribution: CA-MRSA found to be much more : CA-MRSA found to be much more
common in younger individuals (median age 23 years) common in younger individuals (median age 23 years) vs. HA-MRSA (median age 68 years)vs. HA-MRSA (median age 68 years)
Pulse-Field Gel Electrophoresis TypingPulse-Field Gel Electrophoresis Typing: CA-MRSA : CA-MRSA belong to very different PFGE clonal groups compared belong to very different PFGE clonal groups compared to HA-MRSA (genetically different)to HA-MRSA (genetically different)
Exotoxin Gene ProfilesExotoxin Gene Profiles: CA-MRSA commonly carry : CA-MRSA commonly carry genes for Panton-Valentine leukocidin (PVL), while HA-genes for Panton-Valentine leukocidin (PVL), while HA-MRSA do notMRSA do not
Antibiotic Susceptibility ProfilesAntibiotic Susceptibility Profiles: CA-MRSA are more : CA-MRSA are more likely to be susceptible to a broader range of antibiotics likely to be susceptible to a broader range of antibiotics than are HA-MRSAthan are HA-MRSA
**CA-MRSA: Community-Associated MRSACA-MRSA: Community-Associated MRSA**HA-MRSA: Healthcare-Associated MRSAHA-MRSA: Healthcare-Associated MRSA Naimi TS, et al. Naimi TS, et al. JAMAJAMA Dec 10, 2003;290: Dec 10, 2003;290:
2976-29842976-2984
Historical Resistance Historical Resistance TimelineTimeline
1941: introduction of penicillin1941: introduction of penicillin 1944: first reports of penicillin-resistant 1944: first reports of penicillin-resistant S. S.
aureusaureus 1956: discovery of Vancomycin1956: discovery of Vancomycin 1960: introduction of penicillinase-resistant 1960: introduction of penicillinase-resistant
drugs such as Methicillindrugs such as Methicillin 1975: first reports of nosocomial methicillin-1975: first reports of nosocomial methicillin-
resistant resistant S. aureusS. aureus (MRSA) (MRSA) 1983: reports of community-acquired MRSA in 1983: reports of community-acquired MRSA in
children from Ohio, Nebraska, Missouri, Hawaii, children from Ohio, Nebraska, Missouri, Hawaii, New Zealand (majority Clindamycin susceptible)New Zealand (majority Clindamycin susceptible)
Resistance Timeline: Resistance Timeline: MRSAMRSA
1996: first report of Vancomycin intermediate 1996: first report of Vancomycin intermediate resistant resistant S. aureusS. aureus (VISA) from Japan (VISA) from Japan
1998 JAMA: 70% of cases of 1998 JAMA: 70% of cases of S. aureusS. aureus disease in a disease in a Chicago pediatric hospital are community-Chicago pediatric hospital are community-acquired MRSA (CA-MRSA, most susc. to clinda, acquired MRSA (CA-MRSA, most susc. to clinda, TMP/SMX)TMP/SMX)
1999 MMWR: 4 cases of serious, invasive CA-1999 MMWR: 4 cases of serious, invasive CA-MRSA in children (majority susc. to clindamycin, MRSA in children (majority susc. to clindamycin, TMP/SMX.)TMP/SMX.)
2002 PIDJ: 67% of cases of 2002 PIDJ: 67% of cases of S. aureusS. aureus disease in disease in children in Texas Children’s Hospital, Houston, children in Texas Children’s Hospital, Houston, are CA-MRSAare CA-MRSA
2010 Infect Control Hosp Epidemiol: 73% of 2010 Infect Control Hosp Epidemiol: 73% of hospital-acquired MRSA at Texas Children’s are hospital-acquired MRSA at Texas Children’s are CA-MRSA isolates! CA-MRSA isolates!
Percent of methicillin-resistant Percent of methicillin-resistant Staphylococcus aureus casesStaphylococcus aureus cases
classified as community-associated, 2000–classified as community-associated, 2000–2005*2005*
*n = total number of community-associated methicillin-resistant Staphylococcus aureus cases per year
Como-Sabetti K, Harriman KH, Buck JM, et al. Public Health Reports. May-June 2009; 124: 427-35
Percent of community-associated methicillin-resistant Percent of community-associated methicillin-resistant Staphylococcus aureusStaphylococcus aureus
isolates by pulsed-field type and inducible clindamycin isolates by pulsed-field type and inducible clindamycin resistance by year, 2000–2005resistance by year, 2000–2005
Como-Sabetti K, Harriman KH, Buck JM, et al. Public Health Reports. May-June 2009; 124: 427-35
ICR 5 inducible clindamycin resistance
MRSA Infections at 25 Children’s Hospitals, MRSA Infections at 25 Children’s Hospitals, 1999-20081999-2008
Herigan JC, Hersh AL, Gerber JS, et al. Pediatr 2010; 125:e1294-e1300
S. aureus S. aureus at University of at University of KentuckyKentucky
Data from Clinical Microbiology Lab, Chandler Medical Center, University of Kentucky
(n=1000) (n=1219) (n=1374) (n=1326) (n=1558) (n=1772) (n=2084) (n=2240) (n=2253)
Percent
Interpretation of Interpretation of Microbiology Lab Microbiology Lab
Susceptibility ReportsSusceptibility ReportsTypical Susceptibility Report for CA-Typical Susceptibility Report for CA-
MRSA:MRSA: OxacillinOxacillinRR TetracyclineTetracycline SS GentamicinGentamicin SS CiprofloxacinCiprofloxacinSS VancomycinVancomycin SS Trimethoprim- SulfamethoxazoleTrimethoprim- Sulfamethoxazole SS ErythromycinErythromycin RR ClindamycinClindamycin SS
Clindamycin D-TestClindamycin D-Test
Erythromycin Erythromycin resistantresistantClindamycin Clindamycin inducibly resistant inducibly resistant (MLS(MLSBB))
Erythromycin Erythromycin resistantresistantClindamycin Clindamycin susceptiblesusceptible(eflux mechanism)(eflux mechanism)
Antimicrobial susceptibility and inducible clindamycin Antimicrobial susceptibility and inducible clindamycin resistance trends of CA-MRSA isolates, Minnesota Dept resistance trends of CA-MRSA isolates, Minnesota Dept
of Health, 2000–2005of Health, 2000–2005
2000 2000 2001 2001 2002 2002 2003 2003 2004 2004 20052005 Chi-squareChi-square(n=106)(n=106) (n=145)(n=145) (n=200)(n=200) (n=279) (n=279) (n=434) (n=434) (n=301) (n=301) for trendfor trend
Characteristic Characteristic Percent Percent Percent Percent Percent Percent Percent Percent Percent Percent Percent Percent (p-value)(p-value)Erythromycin Erythromycin 45 45 43 43 40 40 28 28 22 22 1313 92.8 ( 92.8 (p<0.01)p<0.01)Ciprofloxacin Ciprofloxacin 8080 77 77 78 78 68 68 68 68 59 59 26.9 (26.9 (p<0.01)p<0.01)Clindamycinc Clindamycinc 83 83 8383 86 86 8 8 86 86 88 88 NSNSGentamicin Gentamicin 94 94 97 97 98 98 9999 99 99 99 99 21.9 (21.9 (p<0.01)p<0.01)Tetracycline Tetracycline 9393 94 94 91 91 91 91 94 94 92 92 NSNSRifampin Rifampin 97 97 100 100 9999 99 99 99 99 100 100 NSNSTrimethoprim-Trimethoprim-
sulfamethoxazole sulfamethoxazole 95 95 100 100 99 99 100 100 100 100 99 99 14.6 (14.6 (p<0.01)p<0.01)Vancomycin Vancomycin 100 100 100 100 100 100 100 100 100 100 100 100 NSNSER-CS ER-CS 30 30 35 35 44 44 56 56 64 64 75 75 118.4 (118.4 (p<0.01)p<0.01)ICRICR 93 93 82 82 50 50 36 36 16 16 14 14 155.9 (155.9 (p<0.01)p<0.01)Clindamycin total Clindamycin total 58 58 56 56 64 64 64 64 76 76 77 77 38.0 (38.0 (p<0.01)p<0.01)
CA-MRSA = community-associated methicillin-resistant CA-MRSA = community-associated methicillin-resistant Staphylococcus aureusStaphylococcus aureusNS = not significantNS = not significantER-CS = erythromycin resistant/clindamycin susceptibleER-CS = erythromycin resistant/clindamycin susceptibleICR = inducible clindamycin resistanceICR = inducible clindamycin resistance
Como-Sabetti K, Harriman KH, Buck JM, et al. Public Health Reports. May-June 2009; 124: 427-35
Antimicrobial Management of Antimicrobial Management of Staphylococcus Staphylococcus aureus aureus infections in US Children’s Hospitals, infections in US Children’s Hospitals,
1999-20081999-2008Herigan JC, Hersh AL, Gerber JS, et al. Herigan JC, Hersh AL, Gerber JS, et al. Pediatr Pediatr 2010; 125:e1294-2010; 125:e1294-
e1300e1300
Is Current Standard Dosing of Is Current Standard Dosing of Vancomycin Adequate? Vancomycin Adequate?
Standard dose: 40mg/kg/day ÷ q6-8hStandard dose: 40mg/kg/day ÷ q6-8h AUC/MIC >400 associated with optimal AUC/MIC >400 associated with optimal
outcomes in adults (no pediatric study)outcomes in adults (no pediatric study) CA-MRSACA-MRSA MIC typically <0.5-2 mg/LMIC typically <0.5-2 mg/L Current dosing may be inadequate to Current dosing may be inadequate to
achieve therapeutic levels in children for achieve therapeutic levels in children for MRSA with MIC ≥ 1 MRSA with MIC ≥ 1 Jimenez-Truque N, et al. Pediatr Infect Dis J 2010;29:368-
70.Frymoyer A, et al. Pediatr Infect Dis J 2009;28: 398-402.
Vanc dosing: Lets go to Vanc dosing: Lets go to Monte Carlo!Monte Carlo!
A Monte Carlo simulation models known biological variance, replicating A Monte Carlo simulation models known biological variance, replicating real-world conditions over thousands of simulated encountersreal-world conditions over thousands of simulated encounters i.e. Probability of achieving optimal serum concentrations can be i.e. Probability of achieving optimal serum concentrations can be
modeled across a range of vancomycin doses against MRSA with modeled across a range of vancomycin doses against MRSA with different MIC’sdifferent MIC’s
Nifty, huh?!Nifty, huh?!
Frymoyer A, Hersh AL, Coralic Z, Benet LZ, Guglielmo BJ. Clin Ther. 2010;32:534-42
Evaluating the Empiric Dose of Vancomycin in Evaluating the Empiric Dose of Vancomycin in Pediatric PatientsPediatric Patients
McCabe T, Davis GA, Iocono J, Nelson C, Kuhn RJ. (University of McCabe T, Davis GA, Iocono J, Nelson C, Kuhn RJ. (University of Kentucky College of Pharmacy; Kentucky College of Pharmacy; Pending Submission)Pending Submission)
Age
(years)
Empiric Vancomycin Dose
(mg/kg/day)
<2 95
2-12 88
12-18 75
Retrospective chart review Jan 08Retrospective chart review Jan 08 to Mar 09to Mar 09Age 1m – 18yAge 1m – 18yDx: Abscess, Osteomyelitis, andDx: Abscess, Osteomyelitis, and Neutropenic FeverNeutropenic FeverGoal Trough: 15-20 mg/LGoal Trough: 15-20 mg/L
239 charts reviewed; 63 patients239 charts reviewed; 63 patients included in analysisincluded in analysisNo supratherapeutic levels or No supratherapeutic levels or renalrenal impairment were notedimpairment were notedCalculated: k(hrCalculated: k(hr-1-1), Vd (L/kg), t½ ), Vd (L/kg), t½ (hrs) (hrs)
•Standard empiric doses of Standard empiric doses of •<40mg/kg/day divided q8h<40mg/kg/day divided q8h•40-60mg/kg/day divided q8h or q6h40-60mg/kg/day divided q8h or q6h•60-84mg/kg/day divided q6h60-84mg/kg/day divided q6h
Table 4 Proposed Recommendations for Empiric Vancomycin Dosing in Pediatrics*
* Assuming normal renal function and fluid status
Time–kill curves of orally available Time–kill curves of orally available antimicrobials against MRSA.antimicrobials against MRSA.
Error bars represent – 1 standard deviation. RIF= rifampicin;SXT=trimethoprim/sulfamethoxazole.
Kaka AS, Rueda AM, Shelburne III SA. J Antimicrob Chemother 2006; 58: 680–683
Staphylococcus aureusStaphylococcus aureus Virulence FactorsVirulence Factors
Surface Proteins that promote colonization of host Surface Proteins that promote colonization of host tissues and attachment to host cells: fibronectintissues and attachment to host cells: fibronectin
Surface Factors that inhibit engulfment by phagocytes: Surface Factors that inhibit engulfment by phagocytes: polysaccharide capsule, protein A (binds IgG, disrupting polysaccharide capsule, protein A (binds IgG, disrupting phagocytosis)phagocytosis)
Invasins that promote bacterial spread within tissues: Invasins that promote bacterial spread within tissues: leukocidin (leukocidin (Panton-Valentine Leukocidin/PVLPanton-Valentine Leukocidin/PVL), ), kinases, hyaluronidasekinases, hyaluronidase
Biochemical Properties enhancing survival in Biochemical Properties enhancing survival in phagocytes: carotenoids, catalase productionphagocytes: carotenoids, catalase production
Immunological Disguises: Protein A, coagulase, clotting Immunological Disguises: Protein A, coagulase, clotting factorfactor
Membrane-Damaging Toxins that lyse eukaryotic cell Membrane-Damaging Toxins that lyse eukaryotic cell membranes: hemolysins, leukotoxin, leukocidin (PVL)membranes: hemolysins, leukotoxin, leukocidin (PVL)
Exotoxins that damage host tissues and provoke Exotoxins that damage host tissues and provoke disease: Alpha Toxin, Enterotoxins A-G, disease: Alpha Toxin, Enterotoxins A-G, Toxic Shock Toxic Shock Syndrome ToxinSyndrome Toxin (TSST-1), Exfoliative Toxin (TSST-1), Exfoliative Toxin
Inherent and Acquired Antibiotic ResistanceInherent and Acquired Antibiotic Resistance
Panton-Valentine Panton-Valentine Leukocidin (PVL)Leukocidin (PVL)
A Major CA-MRSA A Major CA-MRSA Virulence FactorVirulence Factor PVL-producing CA-MRSA are highly-PVL-producing CA-MRSA are highly-
associated with certain types of infectionsassociated with certain types of infections CellulitisCellulitis AbscessesAbscesses Complicated osteomyelitisComplicated osteomyelitis Necrotizing pneumonia and empyemaNecrotizing pneumonia and empyema
PVL is not commonly produced by HA-PVL is not commonly produced by HA-MRSAMRSA May be found in MSSAMay be found in MSSA
CA-MRSA: Clinical CA-MRSA: Clinical ManifestationsManifestations
PneumoniaPneumonia Pneumonia common in Pneumonia common in S. aureus S. aureus infectionsinfections
10-20% rate with invasive infection10-20% rate with invasive infection Many are due to predisposing virus (e.g. Many are due to predisposing virus (e.g.
influenza)influenza) 2/3 of 2/3 of S. aureus S. aureus pneumonias demonstrate pneumonias demonstrate
empyema; necrotizing pneumonia w/o empyema; necrotizing pneumonia w/o empyema also happensempyema also happens
Pneumonia may be due to septic emboli Pneumonia may be due to septic emboli from other source (osteomyelitis, from other source (osteomyelitis, endocarditis) – nodular pneumoniaendocarditis) – nodular pneumonia
PVL-Positive CA-MRSA and PVL-Positive CA-MRSA and Necrotizing PneumoniaNecrotizing Pneumonia
Young, previously healthy patient populationYoung, previously healthy patient population 45% < 1yr45% < 1yr
Flu-like prodromal illnessFlu-like prodromal illness; seems benign; seems benign!! Rapid progression to severe pneumonia and a Rapid progression to severe pneumonia and a
sepsis syndrome (mortality ~40% within 48 hrs.)sepsis syndrome (mortality ~40% within 48 hrs.) Radiographic appearance: necrotizing Radiographic appearance: necrotizing
pneumonia with cavitary lesions or pneumonia with cavitary lesions or pneumatocelespneumatoceles, often with pleural effusion, , often with pleural effusion, empyemaempyema, and/or pneumothorax , and/or pneumothorax (pyopneumothorax)(pyopneumothorax)
Therapeutic implication: consideration of Therapeutic implication: consideration of Clindamycin/Linezolid to inhibit protein (toxin) Clindamycin/Linezolid to inhibit protein (toxin) synthesis, shut off inflammatory cascadesynthesis, shut off inflammatory cascade
Necrotizing PneumoniaNecrotizing Pneumonia
Staphylococcal Staphylococcal PneumoniaPneumonia Early index of suspicionEarly index of suspicion
Dx by culture of surgical specimen or Dx by culture of surgical specimen or tracheal aspiratetracheal aspirate
VancomycinVancomycin initial drug of choice initial drug of choice Clinda for uncomplicated cases if local clinda Clinda for uncomplicated cases if local clinda
resistance is <10-15% resistance is <10-15% Vancomycin trough of 15-20mcg/ml suggestedVancomycin trough of 15-20mcg/ml suggested Linezolid shows promise as alternative agentLinezolid shows promise as alternative agent
Early VATS/drainage of empyema may Early VATS/drainage of empyema may reduce LOS and shorten recoveryreduce LOS and shorten recovery
Pulmonary AbscessPulmonary Abscess Isolated pulmonary Isolated pulmonary
abscess may occur w/o abscess may occur w/o clinical sepsisclinical sepsis
Primary or secondaryPrimary or secondary Fever, cough, CP, Fever, cough, CP,
malaise, wt loss malaise, wt loss May be managed with May be managed with
antibiotics alone if no antibiotics alone if no empyema (Clindamycin)empyema (Clindamycin)
EndocarditisEndocarditis Fever, malaise, new murmur, splenomegaly, Fever, malaise, new murmur, splenomegaly,
positive blood cultures (usually multiple) positive blood cultures (usually multiple) Echo aids in diagnosis (Modified Duke Criteria)Echo aids in diagnosis (Modified Duke Criteria) Embolic phenomena less common in young Embolic phenomena less common in young
children (petechiae, Janeway lesions)children (petechiae, Janeway lesions) Septic shock may be evident early or may not Septic shock may be evident early or may not
develop at all; can by quite indolent (index of develop at all; can by quite indolent (index of suspicion)suspicion)
Typically, vancomycin +/- gentamicin is Typically, vancomycin +/- gentamicin is empiric treatment; vancomycin trough empiric treatment; vancomycin trough
Osteomyelitis and Septic Osteomyelitis and Septic ArthritisArthritis
S. aureus S. aureus is leading cause in all age groupsis leading cause in all age groups Presents with nonspecific inflammatory Presents with nonspecific inflammatory
symptoms, irritability, and painsymptoms, irritability, and pain Septic hip: surgical emergencySeptic hip: surgical emergency Empiric antibiotics often can be safely Empiric antibiotics often can be safely
delayed until aspiration/culture if done delayed until aspiration/culture if done within 12 hourswithin 12 hours
MRI is best imaging modality for acute MRI is best imaging modality for acute infectioninfection
Osteomyelitis: Sites of Osteomyelitis: Sites of InvolvementInvolvement
Ulna 3%
Humerus12%
Pelvis 9%
Femur 27%
Fibula 5%
Tibia 22%
Hands/Feet 13%
Radius 4%
Septic Joint: Sites of Septic Joint: Sites of InfectionInfection
5%
25%
41%
13%
10%
1050 cases of pyogenic arthritis; Principles and Practice of Pediatric Infectious Disease; 2003; p. 475
Osteo and Septic Joint: Osteo and Septic Joint: ManagmentManagment
Empiric coverage of MRSA appropriateEmpiric coverage of MRSA appropriate Preferably after sampling/culture from sitePreferably after sampling/culture from site Clindamycin preferred if <10-15% local resistanceClindamycin preferred if <10-15% local resistance Vancomycin trough 15-20mcg/ml is recommended Vancomycin trough 15-20mcg/ml is recommended
by some expertsby some experts Non-operative management of osteomyelitisNon-operative management of osteomyelitis
No abscess on MRINo abscess on MRI Improving clinically with treatment over first weekImproving clinically with treatment over first week Repeat imaging, consider surgery if worsening or no Repeat imaging, consider surgery if worsening or no
improvementimprovement
Staph Scalded Skin Staph Scalded Skin Syndrome (SSSS)Syndrome (SSSS)
SSSSSSSS Mediated by exfoliative Mediated by exfoliative
toxins (ETA, ETB)toxins (ETA, ETB) Fever, widely spread, Fever, widely spread,
tender erythematender erythema Quickly form bullaeQuickly form bullae Nikolsky signNikolsky sign
On path, skin separates at On path, skin separates at granular layer in the granular layer in the epidermisepidermis
Treatment: Supportive care Treatment: Supportive care and antibiotic (oral or i.v.) and antibiotic (oral or i.v.) to reduce staph burdento reduce staph burden
Staph Scalded Skin Staph Scalded Skin SyndromeSyndrome
Staph Toxic Shock Staph Toxic Shock Syndrome (TSS)Syndrome (TSS)
TSSTSS Caused by Caused by TSST-1TSST-1, Staph , Staph
Enterotoxins B & C (Enterotoxins B & C (SEBSEB, , SECSEC)) Syndrome: Fever, erythroderma, Syndrome: Fever, erythroderma,
hypotension, and multisystem hypotension, and multisystem organ dysfunction (at least 3)organ dysfunction (at least 3)
Initial GI symptoms, malaise, Initial GI symptoms, malaise, and dizziness associated with and dizziness associated with seemingly benign infection or seemingly benign infection or post-oppost-op
TSSTSS TSST-1 inhibits local inflammatory TSST-1 inhibits local inflammatory
mediator releasemediator release Local infection appears surprisingly normalLocal infection appears surprisingly normal Identifying source site may be delayedIdentifying source site may be delayed
Eye and mouth: hyperemia, Eye and mouth: hyperemia, strawberry tonguestrawberry tongue
Blood culture rarely positiveBlood culture rarely positive Organ failure, ARDS in first few days; Organ failure, ARDS in first few days;
3% mortality3% mortality DDx: RMSF, Leptospirosis, other DDx: RMSF, Leptospirosis, other
bacterial sepsisbacterial sepsis
TSS: ManagementTSS: Management High index of suspicion (phone triage)High index of suspicion (phone triage) Identify and drain/remove source ASAPIdentify and drain/remove source ASAP 2 peripheral i.v.’s or CVL, intravascular 2 peripheral i.v.’s or CVL, intravascular
resuscitationresuscitation Empiric antibiotics: Empiric antibiotics: VancomycinVancomycin plus plus
ClindamycinClindamycin Intensive care; consider IVIG if not responding to Intensive care; consider IVIG if not responding to
abxabx Desquamation 1-2 weeks later is a hallmark of Desquamation 1-2 weeks later is a hallmark of
TSSTSS
Severe Sepsis SyndromeSevere Sepsis Syndrome Clinically similar to TSS, but fails to meet Clinically similar to TSS, but fails to meet
criteriacriteria S. aureus S. aureus isolated from clinical siteisolated from clinical site HypotensionHypotension ARDS/respiratory failureARDS/respiratory failure at least one other organ system involvedat least one other organ system involved
Historically disease of frail, Historically disease of frail, immunocompromisedimmunocompromised
Increasing in healthy children today; MSSA Increasing in healthy children today; MSSA and MRSA and MRSA
Mortality rate 60%!!Mortality rate 60%!!
Necrotizing Necrotizing FasciitisFasciitis
Purpura Purpura FulminansFulminans
Management of CA-MRSA Management of CA-MRSA InfectionsInfections
General RuleGeneral Rule: choice of empiric therapy : choice of empiric therapy should be tempered by the severity of the should be tempered by the severity of the infection and clinical status of the patient. infection and clinical status of the patient. Infectious Disease specialty consultation may Infectious Disease specialty consultation may be valuable in guiding diagnosis and treatment.be valuable in guiding diagnosis and treatment.
If a patient with a suspected Staphylococcal If a patient with a suspected Staphylococcal infection is being treated a ß-lactam antibiotic infection is being treated a ß-lactam antibiotic (e.g. nafcillin, cefazolin) and is not responding (e.g. nafcillin, cefazolin) and is not responding within 24-48 hours of initiation of therapy, the within 24-48 hours of initiation of therapy, the clinician must consider the possibility of MRSA clinician must consider the possibility of MRSA as the etiology.as the etiology.
Management of Active Management of Active Infection Caused by CA-Infection Caused by CA-
MRSAMRSA Incise, Drain and Culture whenever possibleIncise, Drain and Culture whenever possible Optimal management is based on the severity Optimal management is based on the severity
of illness of the patient you are seeing:of illness of the patient you are seeing: Hospitalization and parenteral antibiotic therapy Hospitalization and parenteral antibiotic therapy
forfor: systemic toxicity, bone and joint infections, : systemic toxicity, bone and joint infections, cellulitis that involves a large area and/or is cellulitis that involves a large area and/or is rapidly spreading, extensive and/or deep-seated rapidly spreading, extensive and/or deep-seated cutaneous abscesses not amenable to office cutaneous abscesses not amenable to office drainage, septic shock, necrotizing pneumonia, drainage, septic shock, necrotizing pneumonia, bacteremia, etc.bacteremia, etc.
Outpatient management and oral antibiotics forOutpatient management and oral antibiotics for: : simple, limited-area cellulitis or impetiginous simple, limited-area cellulitis or impetiginous lesions, superficial cutaneous abscesses, etc.lesions, superficial cutaneous abscesses, etc.
Management of Active Management of Active Infection Caused by CA-Infection Caused by CA-
MRSAMRSAEmpiric antibiotic therapy*:Empiric antibiotic therapy*: Outpatient: trimethoprim-Outpatient: trimethoprim-
sulfamethoxazole (TMP-SMZ), sulfamethoxazole (TMP-SMZ), clindamycin, tetracycline (>8 yrs), clindamycin, tetracycline (>8 yrs), linezolid (Zyvox)linezolid (Zyvox)
Inpatient: vancomycin, clindamycin, Inpatient: vancomycin, clindamycin, linezolid, TMP-SMZ, combination therapy linezolid, TMP-SMZ, combination therapy (e.g. vancomycin-clindamycin)(e.g. vancomycin-clindamycin)
The future?: tygecycline (Tygacil), The future?: tygecycline (Tygacil), daptomycin (Cubicin), anti-MRSA daptomycin (Cubicin), anti-MRSA cephalosporins (Ceftobiprole medocaril, cephalosporins (Ceftobiprole medocaril, others in development)others in development)
*Locate and drain all purulent foci*Locate and drain all purulent foci
ConclusionsConclusions CA-MRSA infection in children is epidemic and CA-MRSA infection in children is epidemic and
severe infections are now more frequently seensevere infections are now more frequently seen Accurate interpretation of susceptibility data is Accurate interpretation of susceptibility data is
an important element in the management of an important element in the management of CA-MRSA infection, including empiric dosingCA-MRSA infection, including empiric dosing
Early identification of CA-MRSA infection, Early identification of CA-MRSA infection, incision and drainage when appropriate, and incision and drainage when appropriate, and initiation of appropriate empiric antibiotic initiation of appropriate empiric antibiotic therapy are the mainstays of treatmenttherapy are the mainstays of treatment
For More InformationFor More InformationCDC Overview of Community-Associated MRSA: CDC Overview of Community-Associated MRSA:
http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html
CDC CA-MRSA Fact Sheets for the Public: CDC CA-MRSA Fact Sheets for the Public: http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca_public.html
CDC Questions and Answers about MRSA in CDC Questions and Answers about MRSA in Schools: Schools: http://www.cdc.gov/Features/MRSAinSchools/
