Emerging Infectious Disease (EID) involving Respiratory Tract

1
Emerging Infectious Disease (EID) involving
Respiratory Tract

• Sanit Reungrongrat, MD
• Pediatrics Department, Faculty of Medicine,
  Chiang Mai University

2
Underlying causes for EID

• Generalized social changes
• worldwide urbanization, IV drug abuse, changing
  sexual practice
• Demographic changes
• human mobility and refugee population
• Medical care
• blood transfusion, organ transplant, re-used
  syringes for antibiotic injections, contamination
  vaccines and antibiotic resistance

Kuiken T, et al. Curr Opin Biotech 200314641
3
Underlying causes for EID

• Economic and commercial trends
• intensive food production, extended irrigation,
  liberalized trading pattern
• Climatic changes
• global warming and regional changes
• Ecosystem disturbance
• deforestation, eutrophication of waterways,
  reduction in predators of disease vector organisms

Kuiken T, et al. Curr Opin Biotech 200314641
4
Human Metapneumovirus(hMPV)
5
hMPV

• Is a pathogen that emerged as a result of
  increased and tenacious diagnostic efforts rather
  than through expansion of it range or
  transmission to a new host species
• First identified in 2001 by van den Hoogen BC, et
  al. (Nat Med 20017719)
• Isolated from 28 young children, stored
  nasopharyngeal aspiration (NPA) with RTI over 20
  years in Netherlands
• New member of Metapneumovirus genus,
  Paramyxoviridae family

6
Classification of Viral Pathogens of
Paramyxoviridae Family
McIntosh K, McAdam AJ. N Engl J Med 2004350431
7
Genomic Structure of hMPV

• 13,350 nucleotides
• Negative-sense, nonsegmented RNA
• Pneumovirinae subfamily are distinguished from
  Paramyxovirinae subfamily by
• Distantly related amino acid sequences
• Significant related to F (fusion) and L
  (polymerase) proteins
• Pneumovirinae encode more mRNA (8-10 vs. 6-7),
  and proteins (NS1, NS2, M2-1,M2-2) which not
  found in Paramyxovirinae
• Metapneumovirus lack NS1, NS2 and have different
  positioning of the genes between M, and L

• Pneumoviruses 3'-NS1-NS2-N-P-M-SH-G-F-M2-L-5'
• Metapneumoviruses 3'-N-P-M-F-M2-SH-G-L-5'

Domachowske JB, et al. Clin Microbiol Newsletter
20032517
8
Electron Micrograph of hMPV

• Pleomorphic
• Average size 100-600 nm
• Nucleocapsids rarely observed
• Envelope projections of 13-17 nm

Nat Med 20017719
9
Indirect Immunofluorescence

• IDF with polyclonal antibodies to hMPV

Richards A, et al Nephrol Dial Transplant
2005202848-50
10
Virus Isolation, Cell Culture and Growth
Characteristics of hMPV

• Identified by RAP-PCR
• Is semi-quantitative reverse transcriptase
  PCR-based technique (RT-PCR) that is used to
  compare the entire pool of transcripts
• Real-time PCR is rapid (lt2hr)
• Culture by tertiary monkey kidney cells (tMK),
  LLC-MK2, Vero cell lines
• hMPV grows very slowly (10-14 days) observe by
  cytopathic effect (CPE)
• hMPV replication is trypsin dependent

CPE morphologic characteristics of monolayer
change as virions replicate inside the cells
Nat Med 20017719
11
Phylogeny of hMPV

• Indicator for the relationship between the newly
  identified virus isolates and members of
  Pneumovirinae
• Phylogenetic trees were constructed based on the
  N, P, M and F ORFs of these viruses

12
Heterogeneity of hMPV

• Phylogenetic tree analysis of sequence1
• Divided in two genotypes A and B
• Both genotypes can be divided in two subgroups
  A1, A2, B1, B2
• The F protein revealed 95 amino acid sequence
  identity between virus genotype A and B
• the G protein shared only 30 identity
• Virus neutralization assays with
  genotype-specific antibody demonstrated 12- to
  gt100-fold difference between genotype A and B
• Genotype A has clinical severity than genotype B2

F gene
G gene

1. Van den Hoogen BG, et al. Pediatr Infect Dis J
   200423S25.
2. Vicente D, et al. Clin Infect Dis 200642e111.

13
Seroprevalence of hMPV
Immunofluorescence assays Immunofluorescence assays Immunofluorescence assays Virus neutralization assays Virus neutralization assays Virus neutralization assays
Age (yrs) n tested n positive () n tested n positive () titer
0.5-1 20 5 (25) 12 3 (25) 16-32
1-2 20 11 (55) 13 4 (31) 16-32
2-5 20 14 (70) 8 3 (38) 16-512
5-10 20 20 (100) 4 4 (100) 32-256
10-20 20 20 (100) 4 3 (75) 32-128
gt20 20 20 (100) 4 3 (75) 32-128
8-99 72 72 (100) 11 11 (100) 16-128
Sero-archeological analysis using sera
collection in 1958

1. Serologic studies showed circulating antibodies
   to the virus in virtually all children age 5
   years or older
2. On the basic antibody prevalence, hMPV has
   circulate in the human populations at least 45
   years and more likely longer

Nat Med 20017719
14
Several epidemiologic studies of hMPV in most
parts of the world
36 studies 2.2-30
15
N601, agelt2yr
N488,01-7.7, 02-19, 03-2.2, 2.7HIV-infected
infant
N10,025, 4mo-79yr, mean 8.2yr, median 1.37yr,
92 lt5yr
N97, agelt5yr
N381, agelt15yr, median age 15 mo
N515
N166
N144
N247
N126
N587, agelt18yr
N116
N236,mean age 22 mo (9-38 mo)
16
N516, agelt5yr
N116, age 3mo-16yr
N63, agelt2yr
N214, mean age 10.1 mo
N374
N132, age 3mo-16yr
N236, median age 12 mo
N90, agelt2yr
N1,505, agelt15yr
N1,331, agelt15yr
N589, agelt5yr
N711, all age
17
N440, agelt5yr
N211, agelt1yr
N749, agelt2yr
N208, agelt3yr
N445, age 2mo-93yr)
N38
N1,294, all age
N2,384 detect AOM 50
N248
N296
N668, agelt5yr
18
Epidemiology of hMPV

• In the community 2.2 - 5
• In hospitalized children 5 - 10
• Age lt18 years 2.8 - 17.9
• Age lt5 years 5.5 - 13
• Age lt3 years 4.1 - 6
• Age lt2 years 11 - 25
• Age lt1 year 16.2

19
Age and Seasonal Distribution of hMPV (All
Age)(Osterhaus A, Fouchier R. Lancet
2003361890. (N115)
Number of patient
Age range (years)
Month
Netherland
20
Age distribution of hMPV-positive children (Age
lt5 yrs) (Esper F, et al JID 20041891338. N668)
54 cases (8.1)
No of patients
Months
USA
21
Age distribution of hMPV-positive children (Age
lt3 yrs) (Boivin G, et al Emerg Infect Dis
20039634. N208)
12 cases (6)
No of patients
Months
Canada
22
Epidemiology of hMPV

• Year of study vary by year or location
  periodic epidemics
• North America study more frequent in 2001 than
  2000 (7 vs.1.5)
• Italian study more frequent in 2002 and 2000
  than 2001 (43, 37 vs.7)
• African study more frequent in 2002 than 2001
  and 2003 (19 vs. 7.7, 2.2)
• Seasonality
• Temperate region late winter to spring
• Subtropics region late spring to summer (HK)

23
Seasonal incidence of hMPV. Queensland Australia,
2001-2004 (Sloots TP, et al. Emerg Infect Dis
2006121263)
N10,025, All ages
Su, summer (Dec-Feb) Au, autumn (Mar-May) W,
winter (Jun-Aug) Sp, spring (Sep-Nov)
24
Epidemiology of hMPV

• Asymptomatic infection is rare
• Incubation period 4-6 days, duration of symptoms
  before seeking medical usually lt7 days, viral
  shedding 1-2 weeks
• Peak age 6-12 months, male predomonant
• 30-85 of hospitalized children have underlying
  disease
• prematurity, chronic lung disease congenital
  heart disease, cancer, HIV-infected, asthma,
  renal failure, GERD

25
Epidemiology of hMPV

• Coinfection (5-17) with virus or bacteria, most
  common is RSV
• Others are influenza, parainfluenza, adenovirus,
  CMV, rhinovirus, SARS, S pneumoniae, M
  pneumoniae, C pneumoniae, H influenzae, K
  pneumoniae, E coli
• Cocirculation of different hMPV genotypes in one
  year

26
Rates, by year, of each genetypes of hMPV Data
are from 1982 to 2001 in the Vanderbilt Vaccine
Clinic
Williams JV, et al. JID 2006193387
27
Distribution of hMPV subtype in Queenland,
Australia, 2001-2004
Year Total samples tested hMPV subtypes hMPV subtypes hMPV subtypes hMPV subtypes
Year Total samples tested A1 A2 B1 B2
2001 59 58 24 8 10
2002 122 20 51 12 17
2003 189 10 36 30 24
2004 270 1 23 59 17

• Clinical records 74.4 admitted, LOS median, 3
  days mean 6.5 day, predominant SS, cough,
  rhinorrhea, crackles, fever (N273 cases)
• Classification severity mild 46.8, moderate
  42.5, severe 10.7

Sloots TP. Et al. Emerg Infect Dis 2006121263
28
Comparison of hMPV and RSV (1)

• Overall, hMPV is less commonly isolated from
  respiratory specimens than RSV
• RSV appears more common than hMPV in infants lt6
  months
• Similar to RSV, majority of hMPV cases occur in
  young (lt5 yrs) and elderly (gt65 yrs)
• hMPV peaks later (April), where as RSV peaks
  earlier (December-February)
• hMPV and RSV have similar clinical presentation
  in children and elderly
• In 1 study (Greensill J, et al. Emerg Infect Dis
  20039372), hMPV/RSV coinfection was detected in
  70

29
Comparison of hMPV and RSV (2)

• While both hMPV and RSV can provokes severe
  infections, disease severity and hospitalization
  appears more common with RSV
• Compared the clinical symptoms hMPV with
  age-matched RSV infected children RSV-infected
  found more dyspnea, hypoxemia and feeding
  difficulties
• Two studies in hospitalized patients show that
  hMPV did not need PICU, contrast to some of RSV
  and Influenza-infected patients1,2
• Pneumonia was more often associated with RSV

1. Viazou S, et al. J Clin Microbiol
2003413043. 2. Boivin G, et al. Emerg Infect
Dis 20039634.
30
Age distribution of hMPV and RSV (Age
lt2yrs)(Garcia-Garcia ML, et al. Arch Dis Child
200691290. N749
hMPV 64 cases (14) RSV 376 cases (76)
31
Monthly Distribution of hMPV and RSV (Age
lt1yr)(Ordas J, et al. J Clin Microbiol
20062739. N211)
hMPV 18 cases (16.2) RSV 96 cases (45.5)
32
Clinical Manifestation of hMPV (1)

• Fever 57 - 100
• Cough 63 - 100
• Rhinorrhea 46 - 92
• Sore throat 50 - 59.5
• Hoarseness 1 - 6
• Lacrimation 25
• Conjunctivitis 5 - 7
• Influenza-like illness 50 - 53
• Common cold 7 - 52
• Otitis media 12 - 51
• Diarrhea 6 - 37.5
• Vomiting 10 - 48.5
• Febrile seizure 16
• Truncal rash 10 - 19
• Feeding difficulties 36 - 65

33
Clinical Manifestation of hMPV (2)

• Hypoxia 24 - 47
• Wheeze 0 - 83
• Dyspnea 28 - 83
• Retractions 60 - 92
• Hyperventilation 42
• Cyanosis 4 - 8
• Rhinitis 27 - 80
• Rhinopharyngitis 5
• Pharyngitis 13 - 39
• Laryngitis 5
• Tachycardia 23 - 57
• Pneumonia 8 - 73
• Bronchiolitis 10 - 67
• Asthma exacerbation 14 - 22
• Bronchitis 0 - 60

34
Clinical Manifestation of hMPV (3)

• Croup 18
• Asthma 14
• Irritability 43
• Apnea 2 - 6
• Noisy breathing 14
• Tachypnea 67
• Rhonchi 20
• Crackles (rales) 8 - 100
• Sneezing 45.5
• Dry mouth 23
• Enlarged liver 6
• Headache 30
• Anorexia 45
• Drowsiness 85
• Lethargy 26

35
Lab Investigation

• Lymphopenia (lt1,500 cumm) 29
• Neutropenia (lt1,00 cumm) 6.5
• Elevated transaminase 3.3
• WBC (cumm) 5,930 - 16,500
• LDH (IU/L) 269 - 649
• CRP (mg/dL) 0.76 - 2.54

36
CXR

• Abnormal CXR 28 - 87
• Infiltrates 66
• Air trapping 19
• Atelectasis 40
• Other peribronchial cuffing, pulmonary edema,
  cardiomegaly, lobar pneumonia (coinfection with
  bacteria), pleural thickening

37
CXR Obtained in a 6-Month-Old Infant with hMPV
Bronchiolitis
Hyperinflation and diffuse perihilar infiltrates
Willaims JV, et al N Engl J Med 2004350443-450
38
Pathology of hMPV

• Pathology specimens of hMPV-positive
• Exam by light and electron microscopy
• BAL
• BAL showed
• Epithelial degenerative changes and eosinophilic
  cytoplasmic inclusions within epithelial cells,
  multinucleated giant cell, histocytosis

Red cytoplasmic inclusion
Degenerative epithelial cells
Multi nucleated giant cell
Vargas SO, et al. Pediatr Dev Pathol 20047478
39
Pathology of hMPV

• Lung biopsy showed
• Lipoid pneumonia
• Chronic airway inflammation
• Intraalveolar foamy
• Cholesteral clefts
• Hemosiderin-laden macrophages

Vargas SO, et al. Pediatr Dev Pathol 20047478
40
Management

• Supportive care and managing airway obstruction
• Antiviral therapy
• Prevention

41
Supportive Care

• Administer humidified oxygen
• Nasal suctioning to clear upper airway
• Monitor for apnea, hypoxia and impending
  respiratory failure
• Normalize body temperature
• Rehydrate with oral or intravenous fluids
• Monitor hydration status

42
Managing Airway Obstruction and Antiviral Therapy

• Bronchodilators
• Corticosteroids
• Ribavirin
• Intravenous immunoglobulin

43
Effect of Ribavirin and Glucocoticoid Treatment
in Mouse Model of hMPV infection

• A. Mean viral titers in lungs of hMPV-infected
  mice (BALB/c). On day 5 postinfection
• B. Lung inflammation in hMPV-infected mice
  evaluation with mean histopathological scores

Hamelin ME, et al Antimicrob Agents Chemother
200650774
44
Data of Management

• Oxygen administration 24.3 - 34.3
• Bronchodilator 30 - 32.4
• Corticosteroids 8.1 - 17
• Antibiotics 22.2 - 94
• Mechanical ventilation 2
• PICU 2
• Duration of fever 4 (2-7) days
• Duration of hospitalization 4 (3-7) days
• School absence, median (range) 10 (3-15) days

1. Wang SM, et al Clin Microbiol Infect
2006121221, 2. Foulongne V, et al. Pediatr
Infect Dis J 200625354, 3. Takao S, et al. Jpn
J Infect Dis 200356127, 4. Wolf DG, et al.
Pediatr Infect Dis J 200625320
45
Clinical and Socioeconomic Impact Among Household
Contacts

• Disease similar to infected child () 16 (12.5)
• Additional medical visits () 16 (12.5)
• Antipyretic prescriptions () 14 (10.9)
• Antibiotic prescriptions () 6 (4.7)
• Lost working days, median (range) 4 (2-10)
• Lost of school days, median (range) 4 (3-15)

Bosis S, et al. J med Virol 200575101.
46
Prevention

• Effort to reduce spread include
• Limiting contact with infected patients
• Removal from day care and group setting
• Proper hygiene frequent hand washing
• Disinfecting surface exposed to infectious
  secretions
• Cohorting hospitalized patients
• Vaccination
• Immunoprophylaxis

47
Community-Acquired MRSA(CA-MRSA)
48
CA-MRSA Definition

• CDC diagnosis made in the community setting or
  by culture positive for MRSA within 48 hrs after
  admission to hospital
• It is known that patients may be colonized with
  HA-MRSA for year before developing infection
• Nosocomial outbreak of CA-MRSA have been reports
  (MMWR Mar 31, 200655329)

http//www.cdc.gov/ncidod/hip/ARESIST/mrsa_comm_fa
q.htm
49
CA-MRSA Definition

• Molecular marker (Lyon) for definition
• The Panton-Valentine leukocidin (PVL) genes
• SCC mec IV
• Molecular methods
• Pulsed-field gel electrophoresis (PFGE)
• Multilocus sequence typing (MLST)
• PCR-based method CA-MRSA clones ST1 (USA
  400), ST8 (USA 300)

Vandenesch F et al. Emerg Infect Dis 20039978
50
CA-MRSA History

• S aureus is gram-positive coccid bacterium,
  originally susceptible to penicillin
• 1940s Penicillinase-producing strains appear
• 1959 Methicillin introduced
• 1961 MRSA emerged as nosocomial pathogen, first
  at UK
• Early 1990s CA-MRSA infections reported

51
Methicillin Resistance

• Altered penicillin-binding proteins (PBP2a) that
  had markly reduced affinity for all beta-lactam
  antibiotics
• PBP2a is encoded by the mecA gene which carried
  on the mobile DNA element (the staphylococcal
  cassette chromosome mec (SCCmec)

• The other important component of SCCmec
• The chromosome cassette recombinase (ccr) genes
  encodes for proteins that enable precise
  intregation into and excision from specific site
  of S. aureus chromosome (attBscc)

Foster TJ. J Clin Invest 20041141693
52
Methicillin Resistance

• SCCmec have 5 subtypes, varying in size from 20
  kilobase pairs (kb) to 68 kb
• Type I hospital origin
• Type II hospital origin, additional antibiotic
  resistance genes
• Type III hospital origin, additional antibiotic
  resistance genes
• Type IV community origin associated with
  frequent PVL gene
• Type V community origin
• SCCmec type IV
• does not carry multiple antibiotic resistance
  genes
• usually resistant only to methicillin, other
  beta-lactam antibiotic (cephalosporins,
  carbapenems) and erythromycin
• susceptible to TMP-SMX, clindamycin,
  tetracycline, ciprofloxacin, gentamicin, rifampin

53
Virulence Factors
SCCmec Resistant to methicillin
Collagen-adhesin protein Adherence to host cell EF,NP,arthritis,osteomyelitis
Bacteriocin of SA (bsa) interspecies EF
Superantigen -Enterotoxin -Staph enterotoxin A,B,C,G,H Activation of T cells EF, NP, TSS-like illness
-Staph exotoxin T Possible against immunity
Pore-forming toxins -PVL (LukSPVLukFPV) -LukELukD LukELukDv ?-hemolysin Necrosis, edema Destruction of intestinal microvilli Necrosis Necrosis, vascular leak, shock EF,NP Postantibiotic diarrhea EF EF, NP, Bullous impetigo
Exfloliative toxin A,B
EFepidermic furunculosis, NPnecrotizing
pneumonia, TSStoxic shock syndrome
54
PVL

• An extracellular bicomponent toxin that targets
  and induces leukocyte death with release of
  cytokines and intracellular proteases by creating
  pores in the cell membrane
• PVL genes are present in the majority of CA-MRSA
  isolated
• Associated skin and soft tissue infection
  (furunculosis, abscesses) or more rarely
  necrotizing pneumonia

• Agarose gel electrophoresis
• demonstrative PVL
• Lane 1 molecular weight marker
• Lane 2 positive PVL control strain of S aureus
• Lane 3 negative PVL control strain of S aureus
• Lane 4 negative clinical isolate of S aureus
• Lane 5 patient isolate of S aureus demonstrating
  a positive PCR product representing PVL

55
Burden of MRSA

• Increased hospitalization (3 times)
• MRSA infections increase the median length of
  hospital stay for nosocomial infections (median
  12 days for MRSA vs. 4 days for MSSA)
• Increased cost (3 times)
• MRSA infections increase per-patient hospital
  compared with MSSA (US48,824 vs. US14,141)
• Increased mortality (3 times)
• Nosocomial MRSA infections are associated with
  higher mortality compared with MSSA (21 vs. 8)

Abramson MA, Sexton DJ. Infect Control Hosp
Epidemiol 199920408, Engemann JJ et al. Clin
Infect Dis 200336592, Rubin RJ et al. Emerg
Infect Dis 199959
56
CA-MRSA Epidemiology

• The first report in children (Herold BC, et al.)
• Prevalence of CA-MRSA without risk factors
  increased from 10/10,000 in 1988-90 to 259/10,000
  in 1993-5 (8 cases and 35 cases)
• Cellulitis (55), abscess (27), pneumonia
  (13.5)
• CA-MRSA outbreaks have been reported throughout
  the world
• USA, Canada, Brazil, Uruguay, Belgium, Denmark,
  France, Germany, Greece, Holland, Latvia, Norway
  Sweden, Switzerland, UK, Taiwan, Korea, HK,
  Australia, Newzeland

Harold BC, et al. JAMA 1998279(8)593
57
Result of PCR to detect mecA gene and PFGE of
whole cell DNA
Mstandard lane, Ccontrol lane containing a MSSA
isolate
Harold BC, et al. JAMA 1998279(8)593
58
CA-MRSA Epidemiology

• Four pediatric deaths from CA-MRSA Minnesota
  and North Dakota, 1997-99 (MMWR, Aug 20
  199948707)
• Case reports
• 7-year-old black girl with high fever and Rt
  groin pain, she underwent surgical drainage for
  Rt hip infection and treated with cefazolin. On
  3rd day antimicrobial was changed to vancomycin
  when cultures of blood and joint fluid grew MRSA.
  Her course was complicated by ARDS, pneumonia and
  empyema. She died from pulmonary hemorrhage
  after 5-weeks of hospitalization

59

• Case reports (cont.)
• 16-month-old girl with shock, high fever,
  seizure, diffuse petechial rash. She was treated
  with ceftriaxone but developed respiratory
  failure and cardiac arrest and died within 2
  hours
• 13-year-old girl with fever, hemoptysis and
  respiratory distress. CXR revealed LLL
  infiltrate and pleural effusion. She was treated
  with cefriaxone and nafcillin. Within 5 hours of
  arriving at hospital, she become hypotensive and
  was intubated and treated with vancomycin and
  cefotaxime. She died on the 7th hospital day
  from cerebral edema and MOFS
• 12-month-old boy with bronchiolitis, vomiting,
  and dehydration. He had high fever and petechial
  rash. On 2nd hospital day he has large Rt
  pleural effusion and treated with vancomycin,
  cefuroxime and ICD. He developed respiratory
  failure and hypotension the following day and
  died

60
CA-MRSA Epidemiology

• Number of S aureus isolate/year (14-year study,
  OPD IPD in Driscoll Childrens Hospital) was
  relative stable in 1991-2000 (range, 214-330)
  before precipitously increasing from 402 in 2001
  to 820 in 2003
• Mainly is MRSA (19 in 2001 to 62.4 in 2003)

Purcell K, et al. Arch Pediatr Adolesc Med
2005159980
61
CA-MRSA Epidemiology

• 1,002 MRSA cases were CA-MRSA 982 cases (92.6)
• Mean age was 7.9 years and 51.3 were male
• Number of MRSA case/year was 43 cases in 2000 to
  467 cases in 2003, this increase was solely by
  rise in number of CA-MRSA infection

Purcell K, et al. Arch Pediatr Adolesc Med
2005159980
62
CA-MRSA Risk Factors

• Children
• Overcrowed facilities prisoners, militrary
  recruits
• Closed contact sports football, wrestling,
  fencing
• Low socioecomomic status, lack of sanitation
• Intravenous drugs abusers (IVDA)
• Native Americans, Aboriginal groups etc.
• Man who have sex with man

63
CA-MRSA Clinical Manifestations

• Skin and Soft tissue infections (70-90)
• Cellulitis, Folliculitis, Furunculosis,
  Abscesses, Impetigo, Wound Infection
• Invasive Infections (10-30)
• Bacteremia, Toxic Shock Syndrome
• Musculoskeletal Infections
• Osteomyelitis, Septic arthritis, Bursitis,
  Pyomyositis, Fasciitis
• Pneumonia, Empyema (30-50)
• Others Lymphadenitis, Endocarditis, etc.

Kaplan S. Semin Pediatr Infect Dis 200617113
64
CA-MRSA Pneumonia

• Clinical findings are no different with other
  organisms such as S pneumoniae
• Duration of hospitalization was longer than
  CA-MSSA (mean, 19 vs.14 days)
• Children with primary pneumonia are younger than
  secondary pneumonia from infections at other
  sites (mean, 3.5 vs. 9.9 years)
• CA-MRSA have been associated with necrotizing
  pneumonia, esp. coinfected with virus (influenza
  or parainfluenza)

Kaplan S. Semin Pediatr Infect Dis
200617113 Gonzalez BE, et al. Clin Infect Dis
200541583
65
CA-MRSA Pneumonia
Necrotizing pneumonia 1. patchy areas of
hemorrhage 2. extensive intraalveolar
hemorrhage admixed with neutrophil
infiltrates 3. karyorrhectic debris
Necrotizing tracheobronchitis 1. sloughing of
bronchial mucosa 2. extensive necrosis of
subepithelial connective tissue 3. necrotic debris
Gonzalez BE, et al. Clin Infect Dis 200541583
66
CA-MRSA Treatment

• Hospitalized, non-life-treatening invasive or
  noninvasive infections and without toxic
  appearance
• IV Clindamycin (ID, if abscess is present)
• Criticallly ill with life-treatening invasive
  infections
• IV Vancomycin or IV Clindamycin
• IV Clindamycin Gentamicin

alternative regimen Vancomycin Cloxacillin,
Vancomycin 3rd Cephalosporin suggestion to use
Vancomycin in life-treatening until known
negative D-test
67
CA-MRSA Clindamycin

• In patients with bacteremia, complicated
  pneumonia and musculoskeletal infections
• Dose 40 mg/kg/day IV
• Duration median, 20 days (range, 10-56 days)
• Complication relatively rare Clostridium
  difficile enteritis, loose stools or diarrhea is
  most common, rash
• Inducible resistance to clindamycin detected by
  double-disk diffusion test (D-test)

Martinez-Aguilar G, et al. Pediatr Infect Dis J
200322593
68
D-Test

• If the results show a blunted shape or D
  clindamycin resistance is presence and presumed
  to be due to inducible MLSB-resistance phenotype
  (macrolide-lincosamide-streptogramin B)
• Inducible clindamycin resistance (erm-mediated)
• No induction (msrA-mediated erythromycin
  resistance)

24 hrs, Temp 35 oC
Positive
Negative
69
Conclusions

• Available evidence suggests that CA-MRSA is an
  emerging problem in pediatrics
• Clinicians should be aware that therapy with
  beta-lactam antimicrobials can no longer be
  relied on as the sole empiric therapy for severe
  illness patients whose infections may be CA-MRSA
• What is the CA-MRSA situation in Thailand?