Please see full prescribing information available in this kit.

Please see full prescribing information available in this kit.

MRSA INFECTIONS: A LOCAL PROBLEM

ECHEZONA EZEANOLUE, MD, MPH, FAAP

ASSISTANT PROFESSOR OF PEDIATRICSDIRECTOR, PEDIATRIC & ADOLESCENT HIV SERVICES

UNIVERSITY OF NEVADA SCHOOL OF MEDICINE

2Please see full prescribing information available in this kit.

CASE STUDY 1

7-month-old female presents with a quarter size circular rash (figure 1) following 4 days of fever

On evaluation, she was afebrile and apart from the rash, the rest of her physical examination was normal

Started on clindamycin for suspected CA-MRSA skin infection


CASE STUDY 2

10 year old female presents to the emergency room with a 2 days history of fever, left ankle swelling and pain. She complained of twisting her left ankle 1 day prior to onset of symptom

On physical examination, she had a temperature of 102˚F and her extremities revealed diffuse left ankle swelling, moderate tenderness and inability to bear weight

Radiological evaluation of her ankle revealed no fractures, marked ankle effusion with necrotic bone. Peripheral white count was 12,000/mm3 with 13% bands. C-reactive protein was 35mg/dl

She was admitted and empirically started on intravenous ceftriaxone and nafcillin for suspected osteomyelitis


CASE STUDY 3

26 month-month-old female admitted with pneumonia complicated by empyema

She underwent decortication procedure and treated with vancomycin and ceftriaxone for six weeks and discharged

Readmitted with respiratory distress 2 weeks later and found to have empyema. She had a bronchoscopy, chest tube insertion and pleura fluid sent for culture. Started on vancomycin and ceftriaxone

Patient continues to have fever with persistent pleura effusion. Pleura cultures grew MRSA

5Please see full prescribing information available in this kit.Haddadin AS et al. Postgrad Med J. 2002;78:385-392.

Diekema DJ et al. Clin Infect Dis. 2001;32(suppl 2):S114-S132. Deresinski S. Clin Infect Dis. 2005;40:562-573.Zetola N et al. Lancet Infect Dis. 2005;5:275-286.

Nosocomial Infections and Resistance

2 million nosocomial infections per year in US hospitals

60% involve antibiotic-resistant bacteria– Staphylococcus aureus is the most common overall bacterial cause of

infection involving bloodstream, respiratory tract, and skin/soft tissue, according to the SENTRY Antimicrobial Surveillance Program

– Strains of S aureus that have acquired resistance to β-lactam antibiotics, most commonly through inheritance of the mecA resistance gene, are known as methicillin-resistant S aureus (MRSA)

– MRSA accounts for 29% to 35% of all clinical isolates of S aureus in US and European hospitals

Estimated excess costs related to antibiotic resistance approach $30 billion per year in US hospitals


2003 TSN Data Query Results:MRSA Rates Vary by Geographic Region

Pacific39.5%

Mountain47.1%

W.N. Central46.4%

W.S. Central54.5%

E.N. Central44.1%

E.S. Central58.3%

New England40.8%

Mid Atlantic 42.1%

S. Atlantic53.3%

TSN. Available at: http://www.susceptibilitycentral.com/TSN-Overview.asp. Accessed 6/4/05.

TSN=The Surveillance Network.


Physiology and Resistance Mechanisms of S aureus

WTA=wall teichoic acid; PVL=Panton-Valentine leukocidin; CHIP=chemotaxis inhibitory protein.

S aureus is an adaptive and successful human pathogen, with the ability to elaborate a range of virulence factors and toxins

Resistance to methicillin first appeared in 1961, attributed to inheritance of a mecA gene found on the mobile staphylococcal cassette chromosome mec (SCCmec)

Genetic analysis suggests that mecA has been transferred to S aureus over 20 times, resulting in 5 major lineages

Transfer of the mecA gene into S aureusstrains already well adapted to survival inhospital or community setting has given riseto 2 major MRSA categories:

– Health careassociate MRSA – Communityacquired MRSA

Zetola N et al. Lancet Infect Dis. 2005;5:275-286.Deresinski S. Clin Infect Dis. 2005;40:562-573. Foster TJ. J Clin Invest. 2004;114:1693-1696.


An Emerging Resistance Problem with S aureus

VISA - vancomycin-intermediate S aureus (vancomycin MIC >8-16 µg/mL) has emerged in MRSA strains in the US, Japan, UK, France, etc. Because many of these strains are also resistant to teicoplanin, they are also known as glycopeptide intermediate S aureus (GISA)

VRSA – vancomycin-resistant S aureus (vancomycin MIC ≥32 µg/mL). Four cases of VRSA (associated with vanA genes) have occurred in the US

Following a report from the CDC, the FDA issued a letter to testing labswarning that 2 methods used for automated susceptibility testing can miss rising vancomycin MIC.

Haddadin et al. Postgrad Med J. 2002;78:385-392.CDC. Morb Mortal Wkly Rep. 2004;53:322-323.Rudrik JT. Michigan Dept of Community Health. March 3, 2005.FDA Web site. Available at http://www.fda.gov/cdrh/oivd/letters/062904-vrsa1.html, accessed August 25, 2005.

MIC=minimal inhibitory concentration.


Settings Where MRSA Is Encountered

Multidrug resistant (MDR), including:– Clindamycin– Gentamicin– Fluoroquinolone

Usually PVL negative

Associated with nosocomial pneumonia (NP) and skin, surgical site, and bloodstream infections

Can typically be treated with common oral antibiotics. Usually only resistant to:

– Penicillin, oxacillin– Erythromycin, fluoroquinolones

Usually PVL positive and other toxin and virulence factors may be present

Associated with necrotizing skin, pulmonary, and bloodstream infections

Health CareAssociated MRSAHealth CareAssociated MRSA CommunityAcquired MRSACommunityAcquired MRSA

Naimi TS et al. JAMA. 2003;290:2976-2984.Deresinski S. Clin Infect Dis. 2005;40:562-573.Zetola N et al. Lancet Infect Dis. 2005;5:275-286.


Health CareAssociated and CommunityAcquired MRSA Rates Are Highly Correlated

0 10 20 30 40 50 60 70 80

Health CareAssociated MRSA (%)

80

70

60

50

40

30

20

10

0

Co

mm

un

ity-

Acq

uir

ed M

RS

A (

%)

Each point represents a single institution

R=.698; P<.001

Adapted from TSN® Database-USA. January 1-December 31, 2003.


Community–Acquired MRSA

In contrast to the rise in nosocomial MRSA from 1990 to the present (attributed to traditional risk factors in health care facilities), growing awareness of community-acquired MRSA has occurred through published reports of MRSA outbreaks over the past 2 decades, including skin and pneumonia outbreaks for which traditional risk factors were not identified.

Necrotizing pneumonia,United States and EuropeNecrotizing pneumonia,

United States and Europe

1980

Outbreak in Detroit, Mich• 2/3 of patients were IVDUOutbreak in Detroit, Mich

• 2/3 of patients were IVDU

Mid 1990s

Children• w/o identifiable risk factors

Children• w/o identifiable risk factors

Late 1990s

1998 - Athletes/sports teams 1999 - Native Americans

1998 - Athletes/sports teams 1999 - Native Americans

2000

Prison and jail populations Prison and jail populations

2003

IVDU=intravenous drug users.

Groom AV et al. JAMA. 2001;286:1201-1205. Herold BC et al. JAMA. 1998;279:593-598. CDC. Morb Mortal Wkly Rep. 2001;50:919-922.

Naimi TS et al. JAMA. 2003;290:2976-2984.Zetola N et al. Lancet Infect Dis. 2005;5:275-286.Levine DP et al. Ann Intern Med. 1982;97:330-338. CDC. Morb Mortal Wkly Rep. 2003;52:793-795.

Gillet Y et al. Lancet. 2002;359:753-759. CDC. Morb Mortal Wkly Rep. 1999;48:707-710.


The Burden of MRSA

Increased hospitalization– MRSA infections increase the median length of hospital stay for nosocomial

infections (median: 12 days for MRSA versus 4 days for methicillin-susceptible S aureus [MSSA]) and surgical site infections (SSIs) (median: 23 days for MRSA versus 14 days for MSSA)

Increased cost– MRSA infections increase per-patient hospital costs in New York City

hospitals by approximately $2500 to $3700 (expressed in 1995 dollars) compared with MSSA

– Direct hospital cost from nosocomial MRSA bacteremia is 2.8 times greater than that for MSSA bacteremia

– MRSA SSIs increase median hospital cost by approximately $40,000 compared with MSSA infections

Increased mortality– Nosocomial MRSA infections are associated with higher mortality compared

with MSSA (21% versus 8%)– MRSA SSIs are associated with a higher 90-day mortality rate (20.7% for

MRSA versus 6.7% MSSA)

Abramson MA, Sexton DJ. Infect Control Hosp Epidemiol. 1999;20:408-411. Engemann JJ et al. Clin Infect Dis. 2003;36:592-598.Rubin RJ et al. Emerg Infect Dis. 1999;5:9-17.


Clinical and Economic Outcomes and MRSA SSIs

Data for 479 patients were analyzed to assess the impact of MRSA on outcomes for patients with SSIs

MRSA infected SSI was associated with a >12-fold increase in the 90-day postoperative mortality rate

Patients with MRSA had longer durations of hospitalization

Median Hospital Charges

Engemann JJ et al. Clin Infect Dis. 2003;36:592-598.

20,000

40,000

60,000

80,000

100,000

Ho

sp

ital

Ch

arg

es (

do

llar

s)

0

No Infection MSSA MRSA

P<.001

P<.001

P<.001


MRSA Infections by Organ System and Setting

Results From a Prospective Cohort Study of Patients With MRSA Infections Identified in 12 Minnesota Laboratories, January 1

Through December 31, 2000

Results From a Prospective Cohort Study of Patients With MRSA Infections Identified in 12 Minnesota Laboratories, January 1

Through December 31, 2000

Health CareAssociated MRSAHealth CareAssociated MRSA CommunityAcquired MRSACommunityAcquired MRSA

Skin soft tissue74%

Other8%Bloodstream

4%

Urinary tract1%

Respiratory6%

Otitis media externa

7%

Skin soft tissue36%

Other12%

Bloodstream9%

Urinary tract20%

Respiratory22%

Otitis media externa

1%

Naimi TS et al. JAMA. 2003;290:2976-2984.


Nonsurgical superficial infections– Cellulitis– Impetiginous lesions

Uncomplicated

Classification of SSSIs: Uncomplicated

Cellulitis

Impetigo

FDA. Available at: http://www.fda.gov/cder/guidance/2566dft.pdf. Accessed June 14, 2005.Health-related pictures and definitions. Available at: http://health-pictures.com/cellulitis-pictures.htm. Accessed August 19, 2005.DermNet NZ. Available at: http://dermnetnz.org/bacterial/impetigo.html. Accessed August 19, 2005.


Uncomplicated

Classification of SSSIs: Uncomplicated

Nonsurgical superficial infections– Cellulitis– Impetiginous lesions

Surgical superficial infections– Furuncles– Simple abscesses

Treatment usually requires antibiotics and/or simple incision and drainage

Furuncles

Simple AbscessesFDA. Available at: http://www.fda.gov/cder/guidance/2566dft.pdf. Accessed June 14, 2005.OneSkin.com. Available at: http://dermatology.netfirms.com/SkinA2Z/F/Furuncles.html. Accessed August 19, 2005.Otolaryngolgy Houston. Available at: http://ghorayeb.com/NECKABSCESS.html. Accessed June 14, 2005.


Classification of SSSIs: Complicated

Complicated

Deep soft tissue infections

Infected ulcers

Infected burns

Major abscesses

May require extensive surgical debridement and reconstruction

Significant underlying disease state, which complicates response to treatment

Infected Burns

Infected Ulcer

FDA. Available at: http://www.fda.gov/cder/guidance/2566dft.pdf. Accessed June 14, 2005.Burn Surgery. Available at: http://burnsurgery.com/modules/burnwound%201/index.htm. Accessed August 3, 2005.AFIDS. Available at: http://afids.org/case8a.htm. Accessed August 3, 2005.


Are Antibiotics Necessary in the Management of Uncomplicated Skin and Subcutaneous Abscesses?

Double-blind prospective randomized trial

– 50 patients– All underwent outpatient

incision and drainage of cutaneous abscesses

Randomized to– Cephradine

• 27 patients

– Placebo• 23 patients

Ninety-six percent of the patients in each group were improved clinically after 7 days

Llera JL et al. Ann Emerg Med. 1985;14:15-19.

Cli

nic

al I

mp

rove

men

t (%

)0

20

40

60

80

100

Cephradine Placebo

Treatment Group

96 96


Indications for Antibiotics in the Management of SSSI Abscesses

Antibiotics not necessary for majority of patients

– Surgical drainage and wound care is key to effective management

Systemic signs of infection– Fever– Elevated WBC

– Left shift on differential count– Septic shock

Cellulitis or phlegmon

Immunocompromised patient

Certain foreign bodies– ie, Marlex mesh

Baddour LM. Skin abscess. UpToDate® [serial online]. April 6, 2005;13.2.


Which Antibiotics Should Be Used in the Management of SSSIs?

Therapy may be geared toward expected pathogens, guided by:

– Specific social history– Pre-existing medical condition– Drug allergies– Antecedent trauma

– Gram-stain of discharge or exudate– Local bacterial resistance patterns of the institution

Fung HB et al. Drugs. 2003;63:1459-1480.


DRUG TREATMENT OF UNCOMPLICATED CA-MRSA

Clindamycin

Trimethoprim/sulfamethoxazole

Rifampin


Current FDA-Approved Drug Treatmentsfor Health Care- Associated MRSA

Linezolid (IV, PO) Vancomycin (IV)

Linezolid (IV, PO) Vancomycin (IV) Daptomycin (IV) Tigecycline (IV)

cSSSI=complicated skin and skin structure infection.

NPNP cSSSIcSSSI


LOCAL SUSCEPTIBILITY PATTERN: UMC

DRUG SENSITIVE RESISTANT INTERMIDIATE

BACTRIM 86 14 0

CLINDAMYCIN 49.8 49.7 0.5

ERYTHROMYCIN 4.5 92.9 2.6

LINEZOLID 100 0 0

RIFAMPIN 97.5 2.4 0.1

VANCOMYCIN 99.2 0.8 0


LOCAL SUSCEPTIBILITY PATTERN: SUNRISE HOSPITAL

DRUG SENSITIVE (%) RESISTANT (%)

BACTRIM 98 2

CLINDAMYCIN 69 31

ERYTHROMYCIN 10 90

LINEZOLID 100 0

RIFAMPIN 95 5

VANCOMYCIN 100 0


CASE STUDY 1: ECTHYMA GANGRENOSUM

7-month-old female presents with a quarter size circular rash (figure 1) following 4 days of fever

Started on clindamycin for 10 days without improvement. She was referred to infectious diseases

She had a temperature of 101°F otherwise playful. Skin rash was atypical. She was admitted

Complete blood count, blood and wound cultures were obtained. Started on Intravenous piperacillin/tazobactam

She had severe neutropenia. Culture revealed pseudomonas aeruginosa

31Please see full prescribing information available in this kit.Craven DE et al. Infect Dis Clin North Am. 2004;18:939-962.

Singh N et al. Am J Respir Crit Care Med. 2000;162:505-511.Lodise TP et al. Cin Infect Dis. 2003;36:1418-1423.Kollef MH et al. Chest. 1999;115:462-474.

Benefits of Early, Appropriate Therapy

Cumulative evidence from multiple studies has demonstrated that early, appropriate therapy is associated with:

Shorter duration of antibiotic therapy– Short-course therapy is only an option when the right antibiotic is

used from the start

Decreased length of ICU or hospital stay

Lower total cost

Decreased mortality– Appropriate antimicrobial therapy reduces infection-related and

all-cause mortality

32Please see full prescribing information available in this kit.Mangili A et al. Clin Infect Dis. 2005;40:1058-1060.

Meka VG et al. Clin Infect Dis. 2004;39:1010-1015.

Importance of Short-Course Therapy

Short-course therapy lowers the risk of developing resistance and superinfections:– Vancomycin

• Vancomycin failure is associated with small shifts in MIC into the 1 µg/mL to 2 µg/mL range, associated in part with the presence of a polymorphism in the accessory gene regulator locus

• Vancomycin failure can be anticipated for glycopeptide-resistant S aureus strains

– Daptomycin• Daptomycin-resistant MRSA has been reported already

– Linezolid• Cases of linezolid-resistant S aureus have been reported, typically

associated with single nucleotide changes in 23S ribosomal RNA• Linezolid inhibits bacterial protein synthesis through a mechanism of action

different from that of the other antibacterial agents; therefore, cross-resistance between linezolid and other classes of antibiotics is unlikely


Controlling MRSA in the Hospital

Rigorous infection control policies– Surveillance of ICU infections to identify and quantify endemic

MDR pathogens – Strict adherence to barrier precautions (gown and glove) for infected or

colonized patients

Hand hygiene– Antiseptic-containing preparation before and after all patient contacts – Monitor compliance

Antibiotic stewardship– Avoid inappropriate or excessive antibiotic prophylaxis or therapy

Craven DE et al. Infect Dis Clin North Am. 2004;18:939-962.

Infection control and prevention in health care settings encompass several nonpharmacologic options, including, but not limited to:

Infection control and prevention in health care settings encompass several nonpharmacologic options, including, but not limited to:


Local regulations

A child diagnosed with infected, untreated skin patches, skin rashes, (excluding diaper rash), lasting more than one (1) day or weeping or bleeding skin lesions that have not been treated by a Licensed Medical Practitioner, is not permitted to attend daycare until written documentation from a health care professional is received stating that the child’s condition is not infectious/communicable/contagious.

https://owa.unr.edu/exchweb/bin/redir.asp?URL=http://www.cchd.org/download/environmental_health/child_care_regs82202.pdf

https://owa.unr.edu/exchweb/bin/redir.asp?URL=http://www.cchd.org/download/disease_factsheets/ca-mrsa_patient_facts_05.pdf

https://owa.unr.edu/exchweb/bin/redir.asp?URL=http://www.cchd.org/download/environmental_health/child_care_regs82202.pdf


Education Programs Reduce the Incidence of VAP in a Regional Health Care System

Ep

iso

des

per

1,0

00 V

enti

lato

r D

ays

Adapted from Babcock HM et al. Chest. 2004;125:2224-2231.

Pre-intervention period (1999)

Post-intervention period (1/01 to 6/02)

An education initiative for prevention of VAP was directed to respiratory care practitioners andICU nurses and began on Jan 1, 2000. VAP rates before and after the intervention were compared for each institution. The overall reduction in VAP episodes per 1,000 ventilator days was 45.8%.

0

2

4

6

8

10

12

AdultAcademic

Center

CommunityHospital 2

CommunityHospital 1

PediatricTeaching Hospital

P<.001

P=.003

P<.001 NS

4.9

10.5

7.9

4.9 5.17

2.03

8.17.9


MRSA SSTI Infection Rates Rising in the ED of a County-Owned Hospital

Prevalence of MRSA SSTI evaluated from August 2001 to March 2004 in a county hospital that services a largely uninsured low-income population with an annual census around 43,000 visits

MRSA was isolated from 44/96 (46%) of enrolled patients with single wound infections

– 8 were treated as out-patients, 36 were admitted

No clinical or epidemiologic features were predictive of MRSA infections

Moran EG et al. Emerg Infect Dis. 2005;11:928-930.

Other pathogens included: 15 MSSA, 19 Streptococcus spp, 4 coagulase-negative staphylococci, 2 diphtheroids, 2 Citrobacter spp, 2 Escherichia coli, 1 Enterococcus

29%(14/49)

Aug 2001 – Dec 2002

64%(30/47)

Jan 2003 – Mar 2004

16 Months

15 Months

The proportion of infections yielding MRSA increased as the study

progressed

Please see full prescribing information available in this kit.

THANK YOU

QUESTIONS AND DISCUSSION?

Please see full prescribing information available in this kit.

Documents

mrsa infections

ankle effusion

mrsa rates

case study

diffuse left ankle

year old female

nosocomial infections

days of fever