MANAGEMENT OF MRSA MANAGEMENT OF MRSA PNEUMONIPNEUMONI

MUHAMMAD ILYAS MUHAMMAD ILYAS

PULMONARY DIVISION DEPARTEMENT OF INTERNAL MEDICINE PULMONARY DIVISION DEPARTEMENT OF INTERNAL MEDICINE DEPARTMENT OF PULMONARY AND RESPIRATORY MEDICINEDEPARTMENT OF PULMONARY AND RESPIRATORY MEDICINE

FACULTY OF MEDICINE HASANUDDIN UNIVERSITYFACULTY OF MEDICINE HASANUDDIN UNIVERSITYDR. WAHIDIN SUDIROHUSODO HOSPITALDR. WAHIDIN SUDIROHUSODO HOSPITAL

Methicillin Resistant Methicillin Resistant Staphylococcus aureus Staphylococcus aureus (MRSA): strain are resistant to methicillin and (MRSA): strain are resistant to methicillin and other beta-lactam antibioticsother beta-lactam antibiotics

Heterogeneous, epidemic strainsHeterogeneous, epidemic strains 20-40% of HAP and VAP20-40% of HAP and VAP HCAP, HAP and VAP HCAP, HAP and VAP HA MRSA HA MRSA In 1961 In 1961 hospital associated hospital associated In mid-1990 In mid-1990 infections in healthy individuals infections in healthy individuals

in communityin community Now Now world-wide world-wide

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INTRODUCTION

PATHOGENESISPATHOGENESIS Inhalation aspiration Hematogenous direct

pneumonia

Defence Mechanism of Lung

Comorbid :

DM CKD

HIV COPD pneumooniosis

Predisposition :

influenzae alkoholism Poor nutrition

debiliti

ColonizationColonizationAnterior nares, skin (hands, axillae, Anterior nares, skin (hands, axillae, perineum) and open woundperineum) and open wound

TransmissionTransmissionContaminated hand or Contaminated hand or environmental surfacesenvironmental surfaces

HA-MRSA hands to healthcare workersHA-MRSA hands to healthcare workers CA-MRSA direct contact with colonized or CA-MRSA direct contact with colonized or

infected individualsinfected individuals

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MRSAMRSA

Infections of MRSAInfections of MRSA

Skin and soft tissue infectionsSkin and soft tissue infections Bacteremia and infective endocarditisBacteremia and infective endocarditis PneumoniaPneumonia Bone and joint infectionsBone and joint infections CNS infectionCNS infection

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Microorganisms with Drug Microorganisms with Drug Resistance That are Major Resistance That are Major

Problems in HospitalsProblems in HospitalsGram-positive Organism Gram-negative Organism

MRSA ESBL (Klebsiella species, E.coli, Enterobacter species)

MRSA (HRV) VRSA Enterobacter speciesVRE Pseudomonas aeruginosa

Acinetobacter baumaniiNote: HRV, heterogeneous resistance to vancomycin

Levy SB; CID 2001:33 (Suppl 3)6

IMPACTIMPACTOutcomeOutcome High mortalityHigh mortality Higher co-morbiditiesHigher co-morbidities Longer hospital stayLonger hospital stay Higher healthcare costsHigher healthcare costs

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Methicillin-resistant Methicillin-resistant Staphylococcus aureus (MRSA)Staphylococcus aureus (MRSA)

Produce a penicillin-binding protein Produce a penicillin-binding protein

reduced affinity for β-lactam antibiotics reduced affinity for β-lactam antibiotics encoded by mec A gene encoded by mec A gene carried by one of carried by one of the family of four mobile genetic elementsthe family of four mobile genetic elements

Strains with mec A Strains with mec A resistant to all resistant to all commercially available β-lactam and other commercially available β-lactam and other staphylococcal drugs staphylococcal drugs

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Mechanism of resistanceMechanism of resistance β-lactam with the use of penicillin β-lactam with the use of penicillin S.aureusS.aureus

began to develop resistance via chromosomal began to develop resistance via chromosomal and plasmid mediated β-lactamaseand plasmid mediated β-lactamase

The enzyme cleaves the β-lactamase ringThe enzyme cleaves the β-lactamase ring In 1959, methicillin, a semi synthetic, β-In 1959, methicillin, a semi synthetic, β-

lactamase resistant penicillin was introduce lactamase resistant penicillin was introduce By the early 1960, MRSA had appearedBy the early 1960, MRSA had appeared Resistance is mediated by the mec A gene, Resistance is mediated by the mec A gene,

which is a part of the mobile genomic which is a part of the mobile genomic element staphylococcal chromosome cassette element staphylococcal chromosome cassette (SCC mec) (SCC mec)

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MecA gene expression produced MecA gene expression produced an altered penicillin binding an altered penicillin binding protein (PBP 2a)protein (PBP 2a)

They bind to protein responsible They bind to protein responsible for bacterial cell wall synthesis for bacterial cell wall synthesis by transpeptidation (peptidase by transpeptidation (peptidase enzymes, aka penicillin binding enzymes, aka penicillin binding protein)protein)

If the PBP alter If the PBP alter antibiotic can antibiotic can not inhibit cell wall formation not inhibit cell wall formation resistantresistant

There are 4 type of SCC mec, There are 4 type of SCC mec, each with varying array of drug each with varying array of drug resistanceresistance

SCC mec II – III SCC mec II – III hospital MRSA hospital MRSA strain strain

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Types of MRSATypes of MRSAHA-MRSA CA-MRSA

Onset 48 h hospitalization < 12 mo healthcare

exposure

No healthcare exposure

Risk factor Prolonged hospitalization, antibiotic use, ICU, HD, colonization, IVDU, HIV, MSM

No risk factor, young, healthy, outbreak in child care, military, person

Infection Severe invasive SS II (35%), bacteremia, pneumonia

SSTI (predominant-75%), non-necrotizing pneumonia, DM, UTI, sepsis

Resistant gene (Sccmec)

Type II Type IV or V

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Factors Independently Associated With Factors Independently Associated With MRSA Infection MRSA Infection

Previous hospitalization (within the Previous hospitalization (within the last last 12 months)12 months)

Longer LOS before infectionLonger LOS before infection SurgerySurgery Enteral feedingsEnteral feedings Levofloxacin useLevofloxacin use Macrolide use Macrolide use

Graffunder EM et al. J Antimicrob Chemother. 2002;49:999-1005. 12

Appropriate clinical sample Appropriate clinical sample sputum, blood, pus, pleural fluid, sputum, blood, pus, pleural fluid, bronchoalveolar lavagebronchoalveolar lavage

Culture and resistant Culture and resistant Strain Strain PCR PCR

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DIAGNOSISDIAGNOSIS

ManagementManagementFor hospitalized patients with For hospitalized patients with severe CAP, defined by any one severe CAP, defined by any one of following of following A requirement for ICUA requirement for ICU Necrotizing or cavitary infiltratesNecrotizing or cavitary infiltrates Empyema Empyema

Pending sputum and/or blood culture result (A-III)

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Vancomycin IV, 15-20 mg/Kg/dose every 8-Vancomycin IV, 15-20 mg/Kg/dose every 8-12 hours (A-II) 12 hours (A-II) oror

Linezolid 600 mg PO/IV twice daily (A-II) Linezolid 600 mg PO/IV twice daily (A-II) oror Clindamycin 600 mg PO/IV three times daily Clindamycin 600 mg PO/IV three times daily

(B-III)(B-III) Duration 7-21 days Duration 7-21 days depending on the depending on the

extent of infectionextent of infection If patient with MRSA pneumonia If patient with MRSA pneumonia

complicated with empyema complicated with empyema drainage drainage

Treatment CA/HA-MRSATreatment CA/HA-MRSA

Clinical practice guideline. ID 2011:52 91 February)15

GUIDELINES FOR HAP, VAP or HCAP

HAP, VAP or HCAP Suspected (All Disease Severity)

Risk Factors for MDR Pathogens causing HAP, VAP, HCAP :

• Antimicrobial therapy in preceding 90 days• Current hospitalization of 5 days or more• High frequency of antibiotic resistance in the community or in the specific hospital unit• Presence of risk factors for HCAP• Immunosuppressive disease and/or therapy suggesting

NO YESLimited Spectrum AB

TherapyBroad Spectrum AB

Therapy

MRSA risk factors are present and high incidence locally

Vancomycin or LinezolidGuidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare associated Pneumonia (ATS & IDSA 2005)16

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MRSA pneumonia MRSA pneumonia mortality and mortality and morbiditymorbidity

HA – CA MRSAHA – CA MRSA Recognize risk factor for MRSARecognize risk factor for MRSA Drug of choice Drug of choice vancomycin , vancomycin ,

linezolidlinezolid

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SUMMARYSUMMARY

PANTAI LOSARI MAKASSAR