Methicillin Resistant Staphylococcus aureus

Catherine D. Bacheller, MDInfectious Diseases

Medical Director, Infection Prevention and Control KMCAssistant Professor of Medicine, WSU

Staphylococcus aureus: History of Acquired Resistance

1945 1955 1965 1975 1985 1995

methicillin resistant

Multi-Drug Resistance

mupirocin resistant

glycopeptideintermediate

resistantpenicillinresistant

Mechanisms of MRSA Antibiotic Resistance

Mayer et al. Principles and Practice of Infectious Diseases. 1995;

Eliopoulos. Infectious Diseases. 1992.

• Activated B-lactamase• Reduced PBP capacity• Chromosomal mecA gene

Altered PBP

Low affinity for B-lactams

Causes resistance to all beta lactam antibiotics

Nosocomial Bloodstream Infections

Fungi (8%)

Edmond MB et al. Clin Infect Dis, 1999; 29: 239-244

Gram Negative (27%)

Gram Positive (64%)

Nosocomial Bloodstream Pathogens

Coagulase Negative Staphylococcus (32%)

Staphylococcus aureus (16%)

Enterococci (11%)

Candida (8%)

ViridansStreptococci (1%)

All Gram Negative (21%)

Other (11%)

Edmond MB et al. Clin Infect Dis, 1999; 29: 239-244

A Multi-Center Economic Analysis of MRSA Bacteremia

MSSA(n=148)

13.1 7.2 24% 19.5k

MRSA(n=148)

15.8 13.9* 34%† 23.1k

Welch KE, et al. 39th ICAAC. 1999, abstract

LOS ICU LOS Mortality Cost (Days) (Days) ($)

*P = 0.03; †P = 0.07

6-Month Impact of Resistance on LOS and Hospital Costs

Nosocomial Infections

with MRSA

Panlilio et al. Infect Control Hosp Epidemiol. 1992.

6060

Staphylococcus aureusICU Nosocomial Infections

05

101520253035404550

1987 1989 1991 1993 1995 1997

Per

cen

t R

esis

tan

t% Sens Vanc only % MRSA

Lowy, NEJM 1998; 339:520-32

The issue about trying to contain MRSA is also very much about:

1. Cost to the hospital in vancomycin use (to treat MRSA infections and for empiric treatment in units where MRSA is endemic)

2. Microbial cost - potential for VRSA, emergence or selection of VRE and other vancomycin-resistant organisms.

promed@usa.healthnet.org Subject: PROMED: Infection Control: MRSA (3) Date: Thu, 6 Jun 1996 17:43:27 -0400

S aureus Is Most Common Bacterial Pathogen Isolated From SSTIs of Hospitalized Patients

Adapted from Doern GV et al. Diagn Microbiol Infect Dis. 1999;34:67.

• Other organisms (320/1,562) represented 20.5% of the total bacteria recovered

The Pathogenic Potential of S. aureus(associated sites)

SKIN AND WOUND INFECTIONSImpetigoEcthymaFolliculitisFurunculosisCarbunclesCellulitisAbscessParonychiaSurgical sites infectionsBurn infectionsHidradentitis supprativascalded skin syndrome

BONEOsteomylelitis

HEARTEndocarditisMyocarditis

LUNGPneumonia

JOINTSSeptic arthritis

BLOODSepticemiaBacteremia

INTESTINAL TRACTFood poisoning

EYEEndophthalmitis

VAGINAToxic shock syndrome

Staphylococcal Virulence Factors

TOXINS-toxin-toxin-toxinEnterotoxins A-JExfoliative toxin A and BPanton-Valentine toxinToxic Shock Syndrome

Toxin

ENZYMES-lactamaseCatalaseCoagulaseCystein proteaseV8 proteaseMetalloprotease/aureolysinStaphopain

LipaseNucleaseThermonucleasePI-phospholipase CStaphylokinaseHyaluronidaseLipase/esteraseSerine-like proteins

SURFACE PROTEINSClumping factor A/BCollagen binding proteinFibrinogen-binding proteinFibronectin-binding proteinLactoferrin-binding proteinProtein ALaminin binding protein

Extracellular matrix-binding proteinVitronectin-binding proteinElastin-binding proteinBone sialoprotein-binding proteinSerine-aspartate repeat protein

S. aureus is an adaptable opportunist -commensal to pathogenic -different sets of virulence factors may be important in different diseases

Staphylococcal Infections

Preventing Spread of MRSA Outbreak Among Hospitalized Patients

• Timely ID of epidemic strain• Culture surveillance of patients and staff• Barrier precautions• Staff carriers to non-clinical duties• HANDWASHING !!!!!!!!!• Discharge of patients infected with epidemic

strain• Flagging infected patients records

National Clean Hands Week at Kettering Hospital September 18-24, 2005

Elimination of nasal carriage of methicillin-resistant Staphylococcus aureus with mupirocin during a hospital outbreak.

During a hospital outbreak of methicillin-resistant S. aureus (MRSA), involving more than 200 patients, 40 patients and 32 hospital staff who were stable nasal carriers of MRSA received topical application of 2% mupirocin, formulated in a white soft paraffin and lanolin ointment, to their anterior nares for five days. ...

… The elimination of nasal MRSA by mupirocin, and the introduction of isolation facilities, were associated with the control of the outbreak.

Hill RL; Duckworth GJ; Casewell MW J Antimicrob Chemother 1988;22:377 - 84.

promed@usa.healthnet.org Subject: PROMED: Infection Control: MRSA (3) Date: Thu, 6 Jun 1996 17:43:27 -0400

My personal impression is that there is probably a critical limit of MRSA prevalence beyond which control measures are largely futile (I hope to be proved wrong, perhaps by a case-control study of wards with and without control measures), and that control measures are most beneficial in hospitals which have a near-zero rate of MRSA.

MRSA: No Longer Limited toNosocomial Infections in the USA

Moreno et al. Clin Infect Dis. 1995.

Methicillin Resistant Staphylococciby Treatment Setting

0102030405060708090

100

ICU Non-ICU Outpatient

% resistant isolates

S. aureus

Coagulase-NegativeStaphylococci

Fridkin SK et al. Clin Infect Dis 1999; 29: 245-252

Here comes community-acquired MRSA…

MMWR, 48(32); 707-710. Aug 20, 1999

Methicillin-resistant Staphylococcus aureus

CA MRSA

CA MRSA

CA-MSRA in the Wisconsin News (Milwaukee Journal-Sentinel)

“He got an extreme case. It got into his joint, then his bone, then spilled into his blood, causing him to become septic,” said the father, adding that “the pain is tremendous.”

Subject: Tibia - MRSA osteomyelitis Vanderbilt University Date: Wed, 24 Dec 2003 06:11:14 -0600

Characteristics of CA-MRSA

• Community-acquired MRSA differs from HA-MRSA in that CA-MRSA is not multidrug-resistant and can usually be treated with clindamycin, trimethoprim/sulfamethoxazole, minocycline, or linezolid.

• Both organisms carry the staphylococcal cassette chromosome mecA (SCCmecA)

gene that encodes resistance to the ß-lactams

Emerging Infectious Diseases • Vol. 9, No. 8, August 2003

We assessed whether any common genetic markers existed among 117 CA-MRSA isolates from the United States, France, Switzerland, Australia, New Zealand, and Western Samoa by performing polymerase chain reaction for 24 virulence factors and the methicillin resistance determinant.

Although the selective advantage conferred by the combination of genetic traits (i.e., PVL locus and SSCmec IV in an agr3 background) is not clear, the spread of a limited number of clones in each continent suggests that these CA-MRSA strains are particularly suited to be successful community-based pathogens.

Limited number of clones found

Involvement of Panton-Valentine Leukocidin Producing Staphylococcus aureus in

Primary Skin Infections and Pneumonia.1. Panton-Valentine leukocidin (PVL) is a cytotoxin that causes

leukocyte destruction and tissue necrosis. It is produced by fewer than 5% of Staphylococcus aureus strains.

2. A collection of 172 S. aureus strains were screened for PVL genes by polymerase chain reaction amplification.

3. PVL genes were detected in 93% of strains associated with furunculosis and in 85% of those associated with severe necrotic hemorrhagic pneumonia (all community-acquired). They were detected in 55% of cellulitis strains, 50% of cutaneous abscess strains, 23% of osteomyelitis strains, and 13% of finger-pulp infection strains.

4. PVL genes were not detected in strains responsible for other infections, such as infective endocarditis, mediastinitis, hospital-acquired pneumonia, urinary tract infection, and enterocolitis, or in those associated with toxic-shock syndrome. It thus appears that PVL is mainly associated with necrotic lesions involving the skin or mucosa.

Gerard Lina, et al. Clinical Infectious Diseases    1999;29:1128-1132..

Pneumonia

CA MRSA Inpatient Therapy

Bacteremia• Vancomycin 1gm q 12hr (target trough 10-20)• Daptomycin 6mg/kg q 24hr• Quinupristin-dalfopristin 7.5mg/kg q 8hr via CVP

Ventilator Associated Pneumonia• Linezolid 600mg q 12hr (?superior)• Vancomycin 1gm q 12hr• (DO NOT USE Daptomycin)

CA MRSA Outpatient Therapy

I & D of abscess and Culture of fluid

Oral antibiotics for 2 weeks:• Clindamycin 300mg q 6hr (inducible resistance)• TMP/SMZ DS q 12hr (not active in pus)

?plus Rifampin 300mg q 12hr• Minocycline or Doxycycline 100mg q 12hr• Linezolid 600mg q 12hr ($$$$)

If recurrent infection, repeat above plus: Nasal & Nails: Mupirocin BID x 5days

Skin: Chlorhexidine (CHG) bath daily

Methicillin-resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management.

... MRSA colonization precedes infection. A major reservoir is the anterior nares. MRSA is usually introduced into an institution by a colonized or infected patient or health care worker. The principal mode of transmission is via the transiently colonized hands of hospital personnel...

Mulligan ME; Murray-Leisure KA; Ribner BS; Standiford HC; John JF; Korvick JA; Kauffman CA; Yu VL. Am J Med 1993;94:313

Handwashing is the single most important means of preventing

the spread of infections