INFECTIOUS DISEASE: MRSA/INFLUENZA
From Orlando Regional Healthcare’s Internal Medicine Conference: The Year in Review
| COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (CA-
MRSA)—Jose A. Vazquez, MD, Professor of Medicine, Wayne State University School of Medicine, and
Senior Staff, Henry Ford Hospital, Detroit, MI
|
| Antimicrobial resistance: CA-MRSA now significant problem for internists; potential mortality
|
 | Coagulase-negative Staphylococcus aureus: invasive pathogen; produces endocarditis in older adults in
community
|
| Vancomycin-resistant enterococcus: 30% to 35% prevalence in large teaching institutions
|
| Hospital-acquired MRSA (HA-MRSA): differs from CA-MRSA in virulence, drug susceptibility, and
diseases produced
|
| Vancomycin-resistant S aureus (VRSA): currently 7 cases worldwide (5 from southeast Michigan area)
|
| S aureus: frequent cause of skin and soft tissue infections; in diabetic foot infections, cellulitis alone
monobacterial infection (S aureus or Streptococcus); responsible for 18% to 20% of blood infections in
hospital (>80% of intravenous [IV] line infections)
|
| Progression of MRSA: prevalence 60% to 70% of S aureus infections by 2005, 80% to 90% in Detroit since
late 1980s; as result of hospitalization of infected patients, CA-MRSA now causing nosocomial skin and
soft tissue infections and disseminated syndromes; types of MRSA—types I-III, HA-MRSA; types IV-V,
CA-MRSA; differ in drug susceptibility; also differentiated by Panton-Valentine leukocidin (PVL) gene
that codes for virulence factors
|
| “Vancomycin creep”: increase in minimal inhibitory concentration (MIC) of vancomycin; now 16 to 18 µg/
mL; as result, vancomycin may not be effective in some MRSA infections; vancomycin-intermediate S
aureus (VISA) now termed GISA (glycopeptide-intermediate S aureus); MIC of VRSA up to 64 µg/mL
|
| Heteroresistant S aureus (HR-SA): subpopulations (up to ≈10%) of GISA (depends on colony used for
susceptibility testing); MIC usually <4 µg/mL
|
| Emergence of MRSA: 1960, first isolate; 1998-1999, first described in sports teams and American Indians;
2000-2001, appears in prisons and jails; since 2003-2004, producing disease throughout
|
| Characteristics of CA-MRSA: now called USA300 clone; contains PVL gene for cytotoxin that causes destruction
in skin and soft tissue as well as white blood cells in area; rarely found in nasal cavity, but
common in axilla and groin; treated with drugs often used in community, eg, some tetracyclines, quinolones,
trimethoprim-sulfamethoxazole (TMP-SMZ); associated with necrotizing and recurrent skin infections;
community-acquired pneumonia from MRSA beginning to emerge; overall prevalence ≈36%
in United States (50%-70% in California; 15%-20% in Midwest)
|
| How HA-MRSA differs from CA-MRSA: multidrug resistant; often resistant to clindamycin, gentamicin,
and fluoroquinolones; PVL gene rarely present; associated with pneumonia and surgical site and
bloodstream infections
|
| Risk factors: recent hospitalization or recent antibiotic use confer highest risk; recent surgery; exposure to
infected person (contagion common); chronic illness; imprisonment; hospitalization—within previous ≤6
mo, risk 3.5 times higher, within 6 to 12 mo, ≈2.2 times higher; for nursing home residents, risk ≈2 times
higher; study of hospitalized patients—≈400 with skin and soft tissue infections from S aureus; 72%
MRSA; ≈90% admitted with CA-MRSA (99% USA300 clone with PVL gene)
|
| Manifestations: necrotizing disease; disseminated carbuncles and furuncles (often do not respond to therapy
or recur when therapy withdrawn); suspect in patient not responding to antibiotic in 24 to 48 hr;
presentations—resembles spider bite (necrotic center); necrotizing fasciitis (can advance from carbuncle
to fasciitis in 24-48 hr); diagnostic point—susceptibility to clindamycin indicates CA-MRSA; susceptibility
of HA-MRSA only 21%
|
| Management recommendations: no guidelines currently
|
| Mild infections:incision and drainage of carbuncles and furuncles, followed by chlorhexidine washes
(once daily for ≈7 days); antibiotic options—clindamycin (450 mg q8h; capsules 150 mg, requiring patient
to take 9 daily; problems of compliance; inducible resistance); doxycycline (100 mg bid;
speaker’s first choice); TMP-SMZ (2 double-strength tablets bid; potential for sulfonamide allergy);
doxycycline may be more effective; evaluate further—have patient return to office in 48 to 72 hr; if response
inadequate, reevaluate therapy
|
| More serious infections: outpatient—linezolid (Zyvox; 600 mg bid); resistance absent; inpatient—
vancomycin (15 mg/kg q12h); linezolid (600 mg bid or IV); daptomycin (4 mg/kg)
|
| Benefits of early therapy: shorter duration; decreased hospital stay; lower cost; decreased morbidity; appropriate
therapy reduces infection-related and all-cause mortality; start early if CA-MRSA suspected
|
| INFLUENZA: OLD DISEASE, NEW CHALLENGES —Jonathan A. McCullers, MD, Assistant Professor
of Medicine, Department of Molecular Sciences, University of Tennessee College of Medicine, and
Associate Member, Department of Infectious Diseases, St. Jude Children’s Hospital, Memphis, TN
|
| Clinical features: sudden onset; incubation period typically 2 to 3 days; infectious period varies by age;
adults shed virus for ≈1 day before symptoms appear, highlighting importance of vaccinating health care
workers; shedding continues ≤45 days after onset
|
| Impact on individual: 7 to 15 days of illness; 5 to 6 days of restricted activity; 3 to 4 days of reduced capacity;
3 days of missed work or school
|
| At risk for complications: very young or elderly; most of mortality in patients >65 yr of age; patients with
chronic medical conditions—pulmonary, renal, metabolic, and cardiovascular disease (except hypertension);
neurologic or neuromuscular disorders; hemoglobinopathies; immunosuppression (eg, HIV infection,
cancer chemotherapy, high-dose steroids); others—pregnant women, everyone >50 yr of age,
and residents of long-term care facilities
|
| Preventing hospitalization: rationale for focusing on high-risk categories
|
| Vaccination recommendations: from Advisory Committee on Immunization Practices (ACIP) of Centers
for Disease Control and Prevention (CDC)
|
| Anyone who wants to avoid getting influenza
|
| Anyone at high risk for complications and hospitalization
|
| Pregnant women or women who expect to become pregnant during influenza season
|
| Children <5 yr of age (vectors for spread of disease)
|
| Anyone who can transmit influenza to those at high risk, eg, elderly, health care workers, household contacts
of children <5 yr of age (eg, parents, older siblings, nannies)
|
| Problem with approach: influenza remains sixth or seventh leading cause of death in United States; solution
may be universal vaccination, beginning with children
|
| Antiviral therapy: 2 major proteins on viral surface; hemagglutinin (HA; allows virus to enter cell; target of
antibodies); neuraminidase (NA; cleaves sialic acid, allowing virus to leave cell); also M2 ion channel
|
| Neuraminidase inhibitors: oseltamivir (Tamiflu); zanamivir (Relenza); block neuraminidase and prevent
viral budding and spread through respiratory tract; may prevent secondary bacterial pneumonia and
otitis media; should be given early in infection
|
| M2-inhibitors: amantadine; rimantadine; block M2 ion channel; prevent viral uncoating; resistance
present—in >90% of all influenza viruses in United States during last 2 yr; central nervous system side
effects and pharmacokinetic issues also limit utility; ≈70% of avian influenza viruses naturally resistant
|
| Antigenic shift and drift: drift—minor changes within viral subtype; occurs annually, necessitating changes
in vaccine; may cause epidemic; shift—major change produces new subtype; may cause pandemic
|
| Influenza vaccines: 2 currently approved in United States
|
| Trivalent inactivated vaccine (TIV): delivered by intramuscular injection; standard “flu shot”; introduced
in 1960s; contains killed virus grown in eggs; results in IgG antibodies to virus; recommended
for everyone >6 mo of age
|
| Live-attenuated influenza vaccine (LAIV): delivered by nasal spray; introduced in 2003; presents to immune
system as would wild-type virus; cold-adapted and temperature sensitive; in addition to IgG immunity,
may induce T-cell-based immunity and mucosal IgA antibodies (intercept and neutralize virus
at mucosal barrier); replicates efficiently at 25°C (nasopharyngeal temperature); grows poorly at 37° to
39°C (core body temperature in lungs); restrictions—LAIV recommended for healthy persons 5 to 49
yr of age; both vaccines grown in chicken eggs, so contraindicated in people allergic to eggs
|
| Vaccination of health care workers: every major medical group recommends giving free of charge at place
of work; overall vaccination rate ranges from 34% in 1997 to 42% in 2005 (“we do a terrible job putting
our patients at risk”); CDC said LAIV acceptable (does not transmit among adults)
|
Suggested Reading
Atmar RL et al: A dose-response evaluation of inactivate influenza vaccine given intranasally and intramuscularly
to healthy young adults. Vaccine 25:5367, 2007; Carleton HA et al: Community-adapted methicillin-resistant
Staphylococcus aureus (MRSA): population dynamics of an expanding community
reservoir of MRSA. J Infect Dis 190:1730, 2004; Charlebois ED et al: Origins of community strains of methicillin-resistant
Staphylococcus aureus. Clin Infect Dis 39:47, 2004; Gold HS et al: Antimicrobial-drug resistance.
N Engl J Med 335:1445, 1996; King MD et al: Emergence of community-acquired methicillin-
resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections.
Ann Intern Med 144:309, 2006; McCullers JA: Antiviral therapy of influenza. Expert Opin Investig
Drugs 14:305, 2005; McCullers JA: Evolution, benefits, and shortcomings of vaccine management. J
Manag Care Pharm 13:S2, 2007; McCullers JA: Insights into the interaction between influenza virus and
pneumococcus. Clin Microbiol Rev 19:571, 2006; McCullers JA: The clinical need for new antiviral drugs
directed against influenza virus. J Infect Dis 193:751, 2006; Naimi TS et al: Comparison of community- and
health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 290:2976, 2003; Pan ES
et al: Population dynamics of nasal strains of methicillin-resistant Staphylococcus aureus--and their relation
to community-associated disease activity. J Infect Dis 192:811, 2005.
Educational Objectives
| The goal of this program is to improve prevention and treatment of community-acquired methicillin-
resistant Staphylococcus aureus (CA-MRSA) and influenza. After hearing and assimilating this program, the
clinician will be better able to:
|
| 1. Diagnose CA-MRSA.
|
| 2. Identify the different manifestations of MRSA.
|
| 3. Manage patients infected with CA-MRSA.
|
| 4. Initiate antiviral therapy in patients infected with influenza.
|
| 5. Describe the evolution of influenza and the annual adjustment in vaccine, and administer vaccination
to patients at risk for hospitalization resulting from influenza, as well as anyone who wants to avoid
influenza infection.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of
interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and
not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Vazquez—Pfizer,
Enzon, Asteen, Merck (honoraria; consultant; grants); Dr. McCullers—Aventis-Pasteur (Speakers Bureau); GlaxoSmithKline,
MedImmune (Speakers Bureau; consultant). The planning committee reported nothing to disclose.
Acknowledgements
Drs. Vazquez and McCullers were recorded at Internal Medicine Conference: The Year in Review sponsored by Orlando
Regional Healthcare, July 16-20, 2007, in Lake Buena Vista, FL. The Audio-Digest Foundation thanks the speakers and the
sponsor for their cooperation in the production of this program.
|
