Jayashree Ravishankar, MD Medical Director, STAR Health Center New York/ New Jersey AETC & SUNY Downstate Medical Center & Simona Bratu, MD SUNY Downstate Medical Center 5/12/06 Community Acquired Methicillin Resistant Staphylococcus aureus in HIV-Infected Patients: An Emerging Pathogen

Case: History 43 yo male w/ no past medical Hx presents with 3 days of scrotal edema, perirectal discharge, fever, chills 43 yo male w/ no past medical Hx presents with 3 days of scrotal edema, perirectal discharge, fever, chills States “one day I had a small pimple on my penis, the next day the whole area just exploded” States “one day I had a small pimple on my penis, the next day the whole area just exploded” No allergies, no travel Hx No allergies, no travel Hx +Hx unprotected sex w/both men and women +Hx unprotected sex w/both men and women +Hx recent wt loss (about 30 lbs in 4 mo) +Hx recent wt loss (about 30 lbs in 4 mo)

Case: Physical Examination On admission febrile to 103°, other vital signs normal On admission febrile to 103°, other vital signs normal Gen: thin male, looks younger than stated age Gen: thin male, looks younger than stated age HEENT: PERRLA, oropharynx clear HEENT: PERRLA, oropharynx clear Heart: RRR No M/R/G Heart: RRR No M/R/G Lungs: clear bilaterally Lungs: clear bilaterally Abd: normal sounds, soft, no HSM. Tender R inguinal mass, warm, fluctuant Abd: normal sounds, soft, no HSM. Tender R inguinal mass, warm, fluctuant GU: extensive scrotal/perirectal abscess GU: extensive scrotal/perirectal abscess

Case: Laboratory Test Results WBC: 28,560, 88% PMNs WBC: 28,560, 88% PMNs Hb/Ht: 12.7/40 Hb/Ht: 12.7/40 Platelet: 336 Platelet: 336 BUN/Cr: 14/1.0 BUN/Cr: 14/1.0

MRSA skin and soft tissue infection, penis and scrotum

Case: Cultures Perirectal abscess culture x 2: community- acquired (CA)-MRSA Perirectal abscess culture x 2: community- acquired (CA)-MRSA sensitive to clindamycin, gentamicin, rifampin, tetracycline, bactrim, vancomycin sensitive to clindamycin, gentamicin, rifampin, tetracycline, bactrim, vancomycin Scrotal abscess culture: CA-MRSA Scrotal abscess culture: CA-MRSA Inguinal aspirate: CA-MRSA Inguinal aspirate: CA-MRSA HIV Ab+, CD4=240 cells/mm³ HIV Ab+, CD4=240 cells/mm³ All blood cultures negative All blood cultures negative

History Shortly after penicillin was introduced in 1940s, PCN-resistant S aureus emerged Shortly after penicillin was introduced in 1940s, PCN-resistant S aureus emerged Methicillin was introduced in 1961, MRSA was reported 1 yr later Methicillin was introduced in 1961, MRSA was reported 1 yr later MRSA now accounts for >50% of S aureus isolates from ICUs in the U.S. MRSA now accounts for >50% of S aureus isolates from ICUs in the U.S.

Emergence of Community- Acquired Methicillin Resistant Staphylococcus aureus (CA MRSA) Earliest reports of outbreaks of CA- MRSA in the aboriginal communities in Western Australia. Earliest reports of outbreaks of CA- MRSA in the aboriginal communities in Western Australia. CA-MRSA reported in 1982 among IVDU in Detroit, Michigan. CA-MRSA reported in 1982 among IVDU in Detroit, Michigan. MRSA is increasingly acquired in the community (rather than in medical settings) MRSA is increasingly acquired in the community (rather than in medical settings)

What constitutes CA-MRSA? 1.Lack of multidrug resistant phenotype 2.Presence of exotoxin virulence factors like Panton-Valentine leukocidin 3.Type IV SCC (staphylococcal chromosome cassette) 4.Molecular distinction from nosocomial strains

Phenotype and Molecular Characteristics of CA-MRSA Multiple toxins, including super antigens Multiple toxins, including super antigens Panton-Valentine leukocidin (PVL) is a cytotoxin which causes leukocyte destruction Panton-Valentine leukocidin (PVL) is a cytotoxin which causes leukocyte destruction Responsible for necrotic skin lesions and severe necrotizing pneumonia Responsible for necrotic skin lesions and severe necrotizing pneumonia

Representative Antimicrobial Susceptibilities (%) of CA- and Hospital-Acquired (HA)-MRSA ANTIMICROBIAL AGENT % Susceptible CAHA Oxacillin00 Cipro7916 Clinda8321 Erythro449 Gent9480 Rifampin9694 Tetracycline9292 TMP-SMX9590 Vancomycin100100

Populations at risk Children Children Soldiers Soldiers Prisoners Prisoners Homeless people Homeless people IVDU IVDU MSM MSM

Risk Factors for CA-MRSA among HIV+ MSM Nolan E.Lee :Risk Factors for Community-Associated Methicillin-Resistant Staphylococcus aureus Skin Infections among HIV-Positive Men Who Have Sex with Men. CID 2005;40:1529–34

The Five “C”s of Transmission Crowding Crowding Cleanliness Cleanliness Contaminated surfaces Contaminated surfaces Contact Contact Compromised skin Compromised skin

Clinical Syndromes Skin and soft tissue infections (SSTI) Skin and soft tissue infections (SSTI) Furunculosis Furunculosis Cutaneous skin abscesses Cutaneous skin abscesses Deep seated abscesses Deep seated abscesses Community acquired pneumonia Community acquired pneumonia Bacteremia Bacteremia Osteomyelitis Osteomyelitis

Approach to Suspected Staphylococcal Infections Consider MRSA in suspected S.aureus infections in the community setting Consider MRSA in suspected S.aureus infections in the community setting Maintain a low threshold for obtaining cultures to document MRSA Maintain a low threshold for obtaining cultures to document MRSA Recommend surgical drainage of infections when feasible Recommend surgical drainage of infections when feasible

Adequate drainage of purulent collections = the cornerstone of therapy

Initial Therapeutic Decision Assess disease severity Assess disease severity Assess the need for parenteral therapy Assess the need for parenteral therapy Consider local susceptibility patterns Consider local susceptibility patterns

Follow Up on the Results of Susceptibility Testing!!! Susceptibility patterns vary from region to region Susceptibility patterns vary from region to region

Treatment of Seriously Ill Patients with Skin and Soft Tissue Infections Vancomycin is still the preferred antibiotic. Vancomycin is still the preferred antibiotic. In case of intolerance to vancomycin or failure, alternative therapy: In case of intolerance to vancomycin or failure, alternative therapy: Linezolid Linezolid Quinupristin-dalfopristin Quinupristin-dalfopristin Daptomycin Daptomycin

Treatment of Seriously Ill Patients with Pneumonia Vancomycin Vancomycin Linezolid (alternative therapy if intolerance to or failure of vancomycin) Linezolid (alternative therapy if intolerance to or failure of vancomycin) Do not use daptomycin for pneumonia Do not use daptomycin for pneumonia

Treatment of Seriously Ill Patients with Bacteremia Vancomycin Vancomycin Alternative therapy: Alternative therapy: Daptomycin Daptomycin Linezolid Linezolid Quinupristin-dalfopristin Quinupristin-dalfopristin

Outpatient Therapy for CA-MRSA Skin and Soft Tissue Infections Limited information on the value of antibiotics in the treatment of SSTIs Isolates are generally susceptible to the following oral antibiotics: clindamycin, TMP-SMX, tetracyclines, linezolid The efficacy of adding a second drug such as rifampin is uncertain. Beware of interaction of rifampin with protease inhibitors

Clindamycin Active against many CA-MRSA strains Active against many CA-MRSA strains Toxin-inhibiting properties Toxin-inhibiting properties Concerns: Concerns: - inducible resistance - risk of Clostridium difficile colitis

Inducible Clindamycin Resistance (MLSBi Phenotype) MRSA strains that are susceptible to clindamycin but resistant to erythromycin MRSA strains that are susceptible to clindamycin but resistant to erythromycin Due to the presence of erythromycin ribosomal methylase gene (erm) Due to the presence of erythromycin ribosomal methylase gene (erm)

Positive D-test = MLSBi Phenotype It is called D test as the shape of the zone of clearance around clindamycin is shaped like a ‘D’ It is called D test as the shape of the zone of clearance around clindamycin is shaped like a ‘D’ D-test is recommended on all S.aureus isolates reported as resistant to erythromycin and susceptible to clindamycin D-test is recommended on all S.aureus isolates reported as resistant to erythromycin and susceptible to clindamycin

Clinical Implications of Inducible Clindamycin Resistance MLSBi phenotype precludes the use of clindamycin for severe infections MLSBi phenotype precludes the use of clindamycin for severe infections For uncomplicated infections (cellulitis) due to MLSBi CA-MRSA the efficacy of clindamycin is unclear For uncomplicated infections (cellulitis) due to MLSBi CA-MRSA the efficacy of clindamycin is unclear

Trimethoprim-sulfamethoxazole (TMP-SMX, Bactrim, Septra) Many CA-MRSA isolates remain susceptible to TMP-SMX Many CA-MRSA isolates remain susceptible to TMP-SMX Good oral bioavailability Good oral bioavailability Bactericidal against S aureus Bactericidal against S aureus Dose: 10 mg/kg/day (TMP component) in divided doses twice daily Dose: 10 mg/kg/day (TMP component) in divided doses twice daily

TMP-SMX Limitations Side effects: rash and allergic reactions, bone marrow suppression with higher doses and prolonged use, electrolyte disturbances Side effects: rash and allergic reactions, bone marrow suppression with higher doses and prolonged use, electrolyte disturbances Not a good choice for empiric therapy, because of frequent resistance in Streptococcus pyogenes (group A streptococci) Not a good choice for empiric therapy, because of frequent resistance in Streptococcus pyogenes (group A streptococci)

Doxycycline/Minocycline: Caution!!! Limited clinical data Limited clinical data Might be an alternative treatment for patients with SSTIs due to MRSA, in selected cases Might be an alternative treatment for patients with SSTIs due to MRSA, in selected cases

Preventing Staphylococcal Skin Lesions Encourage good hygiene; scrupulous hand washing Discourage sharing of personal items such as towels Establish appropriate cleaning procedures and schedules for clothes and equipment Cover wounds Decolonization? Vaccination?

Acknowledgement Amy Wecker, MD Amy Wecker, MD Frank Lowy, MD Frank Lowy, MD

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