The Curious Intersection of HIV and Staphylococcus aureus with a Focus on MRSA Franklin D. Lowy, MD Columbia University College of Physicians & Surgeons New York, NY
Topics to Be Covered Background Some basics Epidemiology of MRSA infections HIV and Staphylococcus aureus S. aureus/mrsa infections in HIV-infected individuals Temporal trends and epidemiology Risks for infection Clinical presentations of MRSA infections in HIVinfected subjects Types of infections Treatment of cutaneous and invasive infections Prevention of recurrent infections
Background Some basics
Sir Alexander Ogston - 1882 Micrococcus, which, when limited in its extent and activity, causes acute suppurative inflammation (phlegmon), produces, when more extensive and intense in its action on the human system, the most virulent forms of septicæmia and pyæmia...
Gram stain of S. aureus
Epidemiology of S. aureus Colonization and Infection Nasal colonization occurs in 20%-40% of normals There is an increased risk of infection in those who are colonized usually with the colonizing strain Colonization is increased in patients with HIV/AIDS, kidney or skin disease, diabetes, IDU, or those requiring longterm care Eradication of colonization is sometimes effective in reducing the incidence of S. aureus infections Wertheim et al., Lancet ID 2005
S. aureus and MRSA Timeline 1950 1960 1970 1980 1990 2000 Outbreaks of Phage 80/81 Infections Epidemic spread of MRSA worldwide Introduction Methicillin '59 Vancomycin 1 st USA Outbreak 2 nd wave of MRSA spread worldwide CA-MRSA Western Australia 1 st VISA Japan '97 CA-MRSA USA USA400 to USA300 1 st VRSA '02 USA 1 st MRSA '61 NB: MSSA continues to account for > 50% of S. aureus infections
Four Pediatric Deaths from Community-acquired Methicillin-Resistant S. aureus Minnesota and North Dakota, 1997-1999 MRSA is an emerging community pathogen among patients without established risk factors for MRSA infection (eg, recent hospitalization, recent surgery, residence in a long-term-care facility, or injecting-drug use). MMWR 48:707, 1999
MRSA Prevalence As a Cause of Skin/Soft Tissue Infections in Adult Emergency Department Patients 7/13 (54%) MRSA 59% 98% PVL+ 97% USA300 72% 300-0114 11/28 (39%) 3/20 (15%) 32/58 (55%) 24/47 (51%) 18/30 (60%) 25/42 (60%) 43/58 (74%) 23/32 (72%) 17/25 (68%) MSSA 17% 42% PVL+ 31% USA300 46/69 (67%) Moran et al., NEJM 2006
Community-Associated Sports participants MRSA Outbreaks Inmates in correctional facilities Military recruits Children in daycare Native Americans, Alaskan Natives, Pacific Islanders Men who have sex with men Hurricane evacuees in shelters Tattoo recipients Rural crystal methamphetamine users
Risk factors for CA-MRSA Infections: the 5 C s of CA-MRSA Contact Crowding Contaminated items Compromised skin integrity Cleanliness
S. AUREUS/MRSA INFECTIONS IN HIV-INFECTED INDIVIDUALS
MRSA Colonization/Infection in HIV-infected vs Non-HIV-Infected Increased colonization compared with non-hiv infected Increased number of body sites colonized Increased number of infections (including invasive ones) Increased diversity of infections Worse outcome especially for those with AIDS Increased number of community-associated MRSA infections Greater risk of recurrent infections No difference in clinical presentation of these infections between HIV+ and HIV- people Shadyab, Crum-Cianflone, HIV Med 2012 Cole, Popovich Curr HIV/AIDS Rep 2013
Temporal Trends in S. aureus Infections 1980s 1990s Among HIV-Infected Multiple studies reported S. aureus was the most frequently identified bacterial pathogen Endocarditis patients also affected by HIV status higher mortality in those with reduced CD4+ cell count (degree of immunosuppression) Many of the MRSA infections were healthcare associated 2000 Present Introduction of ART associated with reports of reduced numbers of bacteremias Closer linkage with community-associated MRSA infections developing Different risk factors with higher rates in selected populations: IDUs, MSMs Bacteremic infections remained higher HIV-infected than non-hiv infected Tumbarello et al., J Infect 1995; JAC 2002 Senthilkumar et al., CID 2001; Tacconelli et al., JID 1998 Hidron et al., AIDS 2011; Larsen et al., HIV Med 2011
Risks for MRSA Colonization and Infection Among the HIV-Infected Environmental factors Geographic location (ie, zip codes, public housing) Homelessness History of incarceration Increased contact with healthcare facilities Use of crack houses Weinke et al., EJCMID 1992 Miller et al., CID 2007 Popovich et al., CID 2013
Factors Associated with S. aureus Colonization Among HIV-Infected Urban population-based study In Chicago s Cook County study found a 6-fold increase in MRSA colonization in the area with large numbers of HIV-infected Started in high risk zip codes eg, areas of poverty, history of prior incarceration Alternative housing such as shelters Increased in prevalence on resampling 2000-2003 2004-2007 Relative risk of CA-MRSA vs MSSA SSTI Popovich et al., CID 2010
Risks for MRSA Colonization and Infection Host factors HIV/AIDS status Among the HIV-Infected Low viral load and/or low CD4+ cell count sometimes predictive of increased risk Potential protective effect of HAART Deficiency of Th17 T-cell subset may contribute to increased risk of infection Medical comorbidities (eg, diabetes, renal disease) Colonization or prior infection with MRSA Prior antibiotic exposure Nguyen et al. AIM 1999 Melles et al., Microbe Infect 2008
Risks for MRSA Colonization and Infection Behavioral factors Among the HIV-Infected Injection and non-injection-drug use Sexual practices (eg, multiple sexual partners, anonymous sex, history of STDs) Activities (eg, sports, social networks, occupation, children in day care) Szumowski et al., CID 2009 Crum-Cianflone et al., Medicine 2011
Risks for MRSA Colonization and Infection Among the HIV-Infected MRSA (especially CA-MRSA) related factors Methicillin (and other antimicrobial) resistance Arginine catabolic mobile element Panton Valentine Leukocidin Phenol-soluble modulins Alpha toxin
CLINICAL PRESENTATIONS OF MRSA INFECTIONS IN HIV-INFECTED SUBJECTS
Common (and Uncommon) Presentations of CA-MRSA in both HIV and non-hiv Infected Local pyogenic infections folliculitis, furuncles, carbuncles, mastitis, cellulitis Has been seen in association with toxic shock syndrome Systemic infections septicemia, endocarditis necrotizing fasciitis, pneumonia, osteomyelitis, pyomyositis Often life-threatening
Cutaneous CA-MRSA Infections A 25 year-old, HIV-infected male with recent history of crystal meth use and attending group-sex parties. For the past 6 months, he has had recurrent CA-MRSA cutaneous infections that have initially responded to therapy, only to relapse shortly after therapy is discontinued.
CA-MRSA - Necrotizing Pneumonia A 37-year-old male with AIDS, CD4 of 4, VL >100,000 presented with fever, chills, shortness of breath. History of influenza 1 week earlier. Blood and sputum cultures positive for CA-MRSA. WBC count 22,900. Started on vancomycin, changed to linezolid, rifampin. After failure to show significant improvement IVIG therapy after 3 days. Eventual slow clinical improvement
Management of MRSA Infections Hospitalize those suspected of having serious infections and, following cultures, initiate empiric therapy For skin/soft tissue infections (SSTI) incision and drainage is critical. Culture all collections Empiric antimicrobial therapy may be necessary for some SSTIs Consider the size, number and location of the lesion(s) Consider comorbidities of patient Cover wounds No data to suggest molecular typing or toxin-testing should guide management http://content.nejm.org/cgi/video_dl/357/19/e20/ NEJM Videos
Oral Antimicrobial Agents Available to Treat MRSA Infections Antibiotic Trimethoprim - sulfamethoxazole Clindamycin Tetracyclines doxycycline minocycline Linezolid Tedizolid Dose 1-2 DS tabs bid 600 mg q6-8h 100 mg q12h 600 mg q12h 200 mg daily Liu et al. CID 2011 Med Letter 2014 Cadena et al., AAC 2011
Oral Antimicrobial Treatment of CA- MRSA Infections Some Caveats NB: Need to be familiar with the antibiotic susceptibility profile of the CA-MRSA in your neighborhood Clindamycin Potential for inducible resistance, relatively higher risk of C. difficile-associated disease TMP/SMX Recent studies have reduced concern regarding lack of efficacy against Group A streptococcus causing cellulitis TMP/SMX single strength, rather than double strength, appears to be sufficient to treat these infections Tetracyclines Not recommended for children < 8 years old Linezolid Expensive, toxicity with long-term use Quinolones High prevalence of resistance as well as the potential for rapid development of resistance not recommended for MRSA infections
Parenteral Antimicrobial Therapy of MRSA Infections Antibiotic Vancomycin Daptomycin Linezolid Ceftaroline Tedizolid Telavancin Dalbavancin Oritavancin Parenteral Dose 15-20 mg/kg Q8-12h 4-8 mg/kg daily 600 mg BID 600 mg Q12h 200 IV daily (for SSTI) 10 mg/kg daily 1 gm IV day 1; 500 mg IV day 8 (for SSTI) 1200 mg IV (for SSTI) Liu et al., CID 2011 Med Letter 2014 Cadena et al., AAC 2011
Parenteral Antimicrobial Treatment of CA-MRSA Infections Some Caveats CA-MRSA isolates have increasingly become more antibioticresistant Vancomycin MICs have increased in many areas and may contribute to a poorer outcome In addition, VISA strains are a continuing concern Daptomycin cannot be used for pulmonary infections The combination of daptomycin and a b-lactam can restore daptomycin efficacy (when MIC increased) The newer agents (eg, daptomycin, oritavancin, tedizolid) have not yet been adequately studied for invasive infections
Recurrent CA-MRSA Infections Recurrences are relatively common especially among HIV-infected Factors associated with recurrences include: repeat exposure to infected and/or colonized persons Daycare, prison, sexual activity, sports teams Persistent colonization with high-risk activity such as body shaving Issue of oropharyngeal carriage Decolonization Nasal mupirocin + chlorhexidine showers Oral rifampin and doxycycline Bleach baths (1 tsp/gallon or 1 2 cup per adult bath) given for 15 min twice weekly for 3 months Environmental cleaning Simor, Clin Infect Dis 2007
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