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 2003;14:641

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 2003;14:641

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 2001;7:719)
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
Pneumovirinae
Metapneumovirus
Human
Metapneumonvirus
McIntosh K, McAdam AJ. N Engl J Med 2004;350:431

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 2003;25:17

8. Electron Micrograph of hMPV
Pleomorphic
Average size nm
Nucleocapsids rarely observed
Envelope projections of nm
Nat Med 2001;7:719

9. Indirect Immunofluorescence
IDF with polyclonal antibodies to hMPV
Richards A, et al Nephrol Dial Transplant 2005;20:

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 (<2hr)
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 2001;7:719

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 >100-fold difference between genotype A and B
Genotype A has clinical severity than genotype B2
F gene
G gene
Van den Hoogen BG, et al. Pediatr Infect Dis J 2004;23:S25.
Vicente D, et al. Clin Infect Dis 2006;42:e111.

13. Seroprevalence of hMPV
Immunofluorescence assays
Virus neutralization assays
Age (yrs)
n tested
n positive (%)
titer
0.5-1 20
5 (25) 12
3 (25)
16-32
1-2
11 (55) 13
4 (31)
2-5
14 (70) 8
3 (38)
16-512
5-10
20 (100) 4
4 (100)
32-256
10-20
3 (75)
32-128
>20
8-99* 72
72 (100) 11
11 (100)
16-128
*Sero-archeological analysis using sera collection in 1958
Serologic studies showed circulating antibodies to the virus in virtually all children age 5 years or older
On the basic antibody prevalence, hMPV has circulate in the human populations at least 45 years and more likely longer
Nat Med 2001;7:719

14. Several epidemiologic studies of hMPV in most parts of the world

15. N=601, age<2yr
N=488,01-7.7%, 02-19%, %, 2.7%;HIV-infected infant
N=10,025, 4mo-79yr, mean 8.2yr, median 1.37yr, 92% <5yr
N=97, age<5yr
N=381, age<15yr, median age 15 mo
N=515
N=166
N=144
N=247
N=126
N=587, age<18yr
N=116
N=236,mean age 22 mo (9-38 mo)

16. N=516, age<5yr
N=116, age 3mo-16yr
N=63, age<2yr
N=214, mean age 10.1 mo
N=374
N=132, age 3mo-16yr
N=236, median age 12 mo
N=90, age<2yr
N=1,505, age<15yr
N=1,331, age<15yr
N=589, age<5yr
N=711, all age

17. N=440, age<5yr
N=211, age<1yr
N=749, age<2yr
N=208, age<3yr
N=445, age 2mo-93yr)
N=38
N=1,294, all age
N=2,384; detect AOM 50%
N=248
N=296
N=668, age<5yr

18. Epidemiology of hMPV In the community ~2.2% - 5%
In hospitalized children ~5% - 10%
Age <18 years: 2.8% %
Age <5 years: 5.5% - 13%
Age <3 years: 4.1% - 6%
Age <2 years: 11% - 25%
Age <1 year: 16.2%

19. Age and Seasonal Distribution of hMPV (All Age) (Osterhaus A, Fouchier R. Lancet 2003;361:890. (N=115)
Number of patient
Age range (years)
Month
Netherland

20. Age distribution of hMPV-positive children (Age <5 yrs) (Esper F, et al JID 2004;189:1338. N=668)
54 cases (8.1%)
No of patients
Months
USA

21. Age distribution of hMPV-positive children (Age <3 yrs) (Boivin G, et al Emerg Infect Dis 2003;9:634. N=208)
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
Seasonal incidence of hMPV. Queensland Australia, (Sloots TP, et al. Emerg Infect Dis 2006;12:1263)
N=10,025, 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 <7 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 2006;193:387

27. Distribution of hMPV subtype in Queenland, Australia, 2001-2004
Year
Total samples tested
hMPV subtypes A1 A2 B1 B2
2001 59 58 24 8 10
2002
122 20 51 12 17
2003
189 36 30
2004
270 1 23
Clinical records: 74.4% admitted, LOS median, 3 days; mean 6.5 day, predominant S&S, cough, rhinorrhea, crackles, fever (N=273 cases)
Classification severity: mild 46.8%, moderate 42.5%, severe 10.7%
Sloots TP. Et al. Emerg Infect Dis 2006;12:1263

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 <6 months
Similar to RSV, majority of hMPV cases occur in young (<5 yrs) and elderly (>65 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 2003;9:372), 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 2003;41:3043.
2. Boivin G, et al. Emerg Infect Dis 2003;9:634.

30. Age distribution of hMPV and RSV (Age <2yrs) (Garcia-Garcia ML, et al. Arch Dis Child 2006;91:290. N=749
hMPV 64 cases (14%)
RSV 376 cases (76%)

31. Monthly Distribution of hMPV and RSV (Age <1yr) (Ordas J, et al
Monthly Distribution of hMPV and RSV (Age <1yr) (Ordas J, et al. J Clin Microbiol 2006:2739. N=211)
hMPV 18 cases (16.2%)
RSV 96 cases (45.5%)

32. Clinical Manifestation of hMPV (1)
Fever %
Cough %
Rhinorrhea %
Sore throat %
Hoarseness %
Lacrimation 25%
Conjunctivitis %
Influenza-like illness %
Common cold %
Otitis media %
Diarrhea %
Vomiting %
Febrile seizure 16%
Truncal rash %
Feeding difficulties %

33. Clinical Manifestation of hMPV (2)
Hypoxia %
Wheeze %
Dyspnea %
Retractions %
Hyperventilation 42%
Cyanosis %
Rhinitis %
Rhinopharyngitis 5%
Pharyngitis %
Laryngitis 5%
Tachycardia %
Pneumonia %
Bronchiolitis %
Asthma exacerbation %
Bronchitis %

34. Clinical Manifestation of hMPV (3)
Croup 18%
Asthma 14%
Irritability 43%
Apnea %
Noisy breathing 14%
Tachypnea 67%
Rhonchi 20%
Crackles (rales) %
Sneezing %
Dry mouth 23%
Enlarged liver 6%
Headache 30%
Anorexia 45%
Drowsiness 85%
Lethargy 26%

35. Lab Investigation Lymphopenia (<1,500 cumm) 29%
Neutropenia (<1,00 cumm) 6.5%
Elevated transaminase 3.3%
WBC (cumm) 5, ,500
LDH (IU/L)
CRP (mg/dL)

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 2004;350:

38. Pathology of hMPV Pathology specimens of hMPV-positive BAL showed
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 2004;7:478

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 2004;7:478

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 2006;50:774

44. Data of Management Oxygen administration 24.3 - 34.3%
Bronchodilator %
Corticosteroids %
Antibiotics %
Mechanical ventilation 2%
PICU 2%
Duration of fever: (2-7) days
Duration of hospitalization: (3-7) days
School absence, median (range): 10 (3-15) days
1. Wang SM, et al Clin Microbiol Infect 2006;12:1221, 2. Foulongne V, et al. Pediatr Infect Dis J 2006;25:354, 3. Takao S, et al. Jpn J Infect Dis 2003;56:127, 4. Wolf DG, et al. Pediatr Infect Dis J 2006;25:320

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 (%) (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 2005;75:101.

46. Prevention Effort to reduce spread include: Vaccination
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, 2006;55:329)

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 2003;9:978

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 2004;114:1693

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 (LukSPV+LukFPV)
-LukE+LukD
LukE+LukDv
-hemolysin
Necrosis, edema
Destruction of intestinal microvilli
Necrosis
Necrosis, vascular leak, shock
EF,NP
Postantibiotic diarrhea
EF, NP, Bullous impetigo
Exfloliative toxin A,B
EF=epidermic furunculosis, NP=necrotizing pneumonia, TSS=toxic shock syndrome

54. Agarose gel electrophoresis
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 (US$48,824 vs. US$14,141)
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 1999;20:408, Engemann JJ et al.
Clin Infect Dis 2003;36:592, Rubin RJ et al. Emerg Infect Dis 1999;5:9

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 to 259/10,000 in (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 1998;279(8):593

57. Result of PCR to detect mecA gene and PFGE of whole cell DNA
M=standard lane, C=control lane containing a MSSA isolate
Harold BC, et al. JAMA 1998;279(8):593

58. CA-MRSA: Epidemiology
Four pediatric deaths from CA-MRSA – Minnesota and North Dakota, (MMWR, Aug :48;707)
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 Children’s Hospital) was relative stable in (range, ) 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 2005;159:980

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 2005;159:980

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 2006;17:113

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 2006;17:113
Gonzalez BE, et al. Clin Infect Dis 2005;41:583

65. Necrotizing tracheobronchitis: Necrotizing pneumonia:
CA-MRSA: Pneumonia
Necrotizing tracheobronchitis:
1. sloughing of bronchial mucosa
2. extensive necrosis of
subepithelial connective tissue
3. necrotic debris
Necrotizing pneumonia:
1. patchy areas of hemorrhage
2. extensive intraalveolar
hemorrhage admixed with
neutrophil infiltrates
3. karyorrhectic debris
Gonzalez BE, et al. Clin Infect Dis 2005;41:583

66. CA-MRSA: Treatment
Hospitalized, non-life-treatening invasive or noninvasive infections and without toxic appearance
IV Clindamycin + (I&D, 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, 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 2003;22:593

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?