CA-MRSA AND COPD: ADVICE FOR THE CLINICIAN
| COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (CA-MRSA)—Paul G.
Auwaerter, MD, Associate Professor of Medicine and Clinical Director, Division of Infectious Diseases, Johns Hopkins
University School of Medicine, Baltimore, MD
|
| Impetigo: typically seen in children (occasionally adults); usually associated with poor hygiene; lesions weeping, crusted,
honey-colored; fever and systemic symptoms rare; usually occurs on face, sometimes on thorax; more commonly
caused by Staphylococcus aureus than by streptococci
|
 | Treatment: oral antibiotics not needed; bathing and improved hygiene usually sufficient; topical antibiotics can sterilize
area if necessary; since S aureus now major cause, penicillin alone no longer effective
|
| Erysipelas: superficial cellulitis characterized by brilliant, fiery-red appearance; usually affects face (adults) and limbs
(children and adults); almost always caused by group A streptococci; lesions warm and sharply demarcated from unaffected
skin; can spread quickly; penicillin usually effective (except in rare cases caused by S aureus)
|
| Cellulitis: seen most in seriously ill patients; deeper skin infection, with warm, red, diffuse lesions that usually move
proximally; skin may be taut; may spread quickly, especially if caused by group A β-hemolytic streptococci, which,
with S aureus, are most common pathogens
|
| Treatment: elevate extremities above heart (associated with faster resolution and less edema and discomfort); in recent
study, it took 36 hr for infection to stop spreading, even with parenteral antibiotics (in 25% of cases, 3 days before
spreading stopped); try oral therapy at home for few days before considering hospital admission
|
| Recurrent cellulitis: “cellulitis begets cellulitis”; must address host factors (eg, lymphedema) that predispose site to skin
inflammation and infection; cellulitis itself may cause changes and microscopic scarring in venous and lymphatic circulation
that promote recurrent infections; group A streptococci most commonly identified organism, although Staphylococcus
also possible (blood cultures rarely positive); underlying condition must be treated (support garments
for lymphedema; management of tinea pedis or onychomycosis, especially in diabetics; therapy for dry, cracked skin
or psoriasis); in rare cases, prophylaxis with daily doses of clindamycin or amoxicillin may be necessary for 6 to 12
mo if infection persists; consultation with infectious disease specialist may be necessary; high-risk patients include
postmastectomy patients or people who have undergone surgery to lower extremities
|
| Conditions often mistaken for cellulitis: include contact dermatitis; insect or spider bites; thrombophlebitis; cutaneous
drug reactions; and erythema nodosum
|
| Lymphangitis: erythematous streaks along lymphatic channels; usual culprit is group A streptococci (rare cases caused
by herpes simplex virus); treat as for cellulitis
|
| Folliculitis: perhaps most common superficial skin infection; often occurs in heavy-set people; more prevalent in warm
weather, due to sweating; patients may have more skin bacteria; most likely to occur in moist environments like armpits
or groin; consists of small pustules that form around hair follicle; almost always caused by S aureus, although “whirlpool
folliculitis” usually caused by Pseudomonas; Candida common nosocomial cause; other organisms responsible in HIV-
positive people; topical antibiotics and warm compresses recommended; should resolve within 5 to 10 days; consider oral
antibiotics for aggressive cases
|
| Furuncles and carbuncles (boils): furuncles usually measure <1 cm; often red, may be indurated, may form head;
carbuncle consists ofgroup of furuncles or large furuncle; usually develop in moist areas or proximal extremities; larger
lesions often associated with systemic symptoms like fever or malaise; pathogen usually S aureus; treat with incision and
drainage if well organized, antibiotics if lesion poorly organized or surrounded by cellulitis
|
| Nasal colonization: nares harbor staphylococci, which are easily transferred to skin; much evidence associates nasal
colonization with increased risk for infection; topical mupirocin can decrease nasal colonization significantly; however,
patients with recurrent infections present challenge
|
| Case: 46-yr-old physician experiencing fourth episode of boils; cultures positive for MRSA; decolonization recommended;
20% to 40% of American adults colonized by S aureus at any given time (incidence among health care workers
slightly higher); prophylactic decolonization with mupirocin ineffective, except among people undergoing renal dialysis;
mupirocin therapy lasts 5 days; another strategy is to wash skin with chlorhexidene or hexachlorophene (apply all
over body, including hair and eyebrows, leave on 5-10 min, then rinse, every other day for 1-2 wk, then scale back to
once or twice weekly); systemic antibiotics do not enter nares as efficiently as topical products; case patient returned
with fifth outbreak, admitting he had stopped using scrub few months earlier; patient instructed to scrub bathroom with
10% bleach solution on 2 consecutive days and to wash towels and bed linens in very hot water; after sixth bout, patient
mentioned he was hockey player and used old hockey gear from college; problem resolved after patient destroyed
gear (boils limited to hockey season)
|
| Staphylococcus aureus: secretes coagulase, virulence factor that inhibits phagocytosis
|
| CA-MRSA: first seen in children; defined as MRSA occurring in people who have had no interaction with health care
system; prevalence increased rapidly in urban areas in 1990s; distinguished from health care–acquired MRSA by its
predilection for soft tissue (cellulitis and abscesses); health care–associated MRSA usually afflicts sick, hospitalized
patients with intravenous (IV) lines and causes bacteremia; median age 70 yr; CA-MRSA more common in children
and young adults (median age 30 yr); has been associated with nonwhite descent and low income; especially problematic
among IV drug users, incarcerated persons, and sports teams; also occurs among homeless people and in
daycare centers; however, age only risk factor that distinguishes CA-MRSA from health care–acquired MRSA; can
be extremely virulent when it invades deep tissues
|
| Difference between CA-MRSA and health care–associated MRSA: CA-MRSA cannot carry resistance alleles to other
antibiotics; has Panton Valentine leukocidin (PVL) protein, marker for enhanced virulence; organisms with PVL
protein have enhanced cytokine activity and often associated with toxins that mobilize immune system; can cause
necrotizing pneumonia and severe skin and soft tissue infections; health care–acquired MRSA resistant to many
antibiotics, while CA-MRSA susceptible to many antibiotics other than methicillin (can be treated with trimethoprim
–sulfamethoxazole, doxycycline, or minocycline; some strains also sensitive to fluoroquinolones or clindamycin,
unlike healthcare–acquired MRSA)
|
| Clindamycin resistance: highly likely in CA-MRSA if strain erythromycin resistant; seen in ≈50% of CA-MRSA
strains; have laboratory perform D-test before reporting clindamycin susceptibility
|
| Treatment: traditionally includes oxacillin, nafcillin, cephalexin, and dicloxacillin, or vancomycin for hospitalized
penicllin-allergic patients; ambulatory patients who undergo incision and drainage do better than those who do not,
regardless of antibiotic used; consider decolonization for persistent cases; for outpatients with S aureus infection,
prescribe trimethoprim–sulfamethoxazole or tetracycline; evaluate clinical response within 1 to 2 days; if patient
does not improve within 2 to 3 days, consider incision and drainage and MRSA coverage; if patient requires hospitalization,
treat with vancomycin (assume organism MRSA); 20% to 40% of group A streptococci now resistant to
trimethoprim–sulfamethoxazole and tetracyclines; so treat cellulitis patients with clindamycin or cephalexin-nafcillin
to cover Streptococcus
|
| Suggested treatment for people with MRSA: vancomycin choice for severe cases; traditional therapies for ambulatory
patients; culture abscesses and change antibiotics if necessary
|
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)—Gerard W. Frank, MD, PhD, Associate Clinical Professor
of Medicine, the David Geffen School of Medicine at the University of California, Los Angeles
|
| Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition: airflow limitation that is not
fully reversible; could apply to asthma, chronic bronchitis, emphysema, and cystic fibrosis, but asthma technically not
COPD
|
| Reasons why asthma not COPD: asthma patients almost never smoke, while almost all COPD patients have smoked;
asthma evokes eosinophil response, while COPD evokes primarily neutrophil response; asthma affects bronchial smooth
muscle, which occurs only in medium to large airways, but COPD begins in small airways (<2 mm in diameter)
|
| Tobacco and COPD: 14% of white smokers and 3% of white nonsmokers have airflow limitation, so most smokers do
not develop COPD; rates slightly lower among black smokers and much lower among Asian smokers, suggesting genetic
differences in susceptibility
|
| Missed diagnoses: in recent survey of 192 primary care physicians presented with hypothetical scenario of cough and
dyspnea in smoker, diagnosis missed in 42% of male patients and 58% of female patients; pulmonary function tests ordered
in only 22% of cases; objective documentation of airflow limitation important in these patients
|
| Immunology of COPD: alveolar macrophages initiate inflammatory response to irritants, eg, smoke, and secrete factors
that recruit neutrophils, which can injure lungs; cytotoxic lymphocytes suppress protease inhibitors, so proteases
also damage lungs; forced expiratory volume in first second (FEV1 ) correlates inversely with number of inflammatory
cells harvested on bronchoscopy; alveolar macrophages enter alveolar epithelial lining, activating more neutrophils
and cytotoxic lymphocytes
|
| Inflammatory mediators: neutrophil-derived serine proteases known to produce emphysema in animals; matrix metalloproteinases
(collagenase and gelatinase; levels increased in emphysema) dissolve normal lung tissue; neutrophils also
release cathepsins, which also mediate inflammation and have systemic as well as local lung effects; along with proteases,
they destroy the alveolar wall (emphysema) and cause mucus hypersecretion (chronic bronchitis)
|
| Pathophysiology of COPD: alveoli lose their normal tethering effects on small airways, making them “floppy”; lumens
of airways then fill with hypersecreted mucus; inflammation produces thickening of airway wall, resulting in narrower
lumen and increased airway resistance
|
| COPD exacerbation: increase in neutrophils, eosinophils, and interleukins seen on bronchoscopy; increased nitric oxide
in exhaled breath, reflecting pulmonary inflammation; viruses prominent exacerbating agents, although bacteria play
larger role in severe cases; “unholy trinity” consists of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus
pneumoniae
|
| Medical management of COPD: antibiotics—empiric use associated with small but significant benefit; no benefit
from prophylactic antibiotics; bronchodilators— β2 -agents produce only 10% improvement in FEV1 , ie, less effective
than in asthma treatment; long-acting agents (eg, salmeterol) have proven benefit in managing COPD, although questions
about side effects and risk-benefit ratio remain; some evidence that these products decrease bacterial adherence to airway
epithelium; anticholinergics—more effective in COPD than in asthma (reverse vagal tone of bronchial smooth muscle;
implies vagal tone more prominent in COPD than in asthma); combination therapy—convenient but no more effective
than each agent given separately; reasonable regimen salmeterol-fluticasone combination (Advair), 2 puffs bid, ipratropium
(alone or in combination with albuterol [Combivent]), 2 puffs qid, and albuterol, 2 puffs as needed; albuterol best
rescue agent because it has fastest onset; tiotropium (Spiriva)—long-acting congener of ipratropium
|
| Theophylline: proven bronchodilator; reports of toxicity associated more with aminophylline; some evidence that it
strengthens diaphragm; efficacy enhanced when combined with long-acting β2 -agent
|
| Steroids: not as critical for COPD therapy as for asthma therapy (do not suppress neutrophil inflammation); long-term inhaled
steroids do not affect course of COPD; however, systemic steroids associated with better outcomes and reduced
need for hospitalization following exacerbations
|
| Nutrition: eating increases work of breathing in COPD; discourages patients from maintaining strength through eating; in
patients with emphysema, cathepsins associated with cachexia; some evidence suggests that megestrol may increase
caloric intake and stimulate ventilation among patients with COPD
|
| Lung volume reduction surgery: emphysema associated with increased lung compliance and decreased lung elastic recoil
during exhalation; volume reduction thought to restore driving force for exhalation (elastic recoil); however, in National
Emphysema Treatment Trial, severely ill patients (FEV1 <20%) had significantly worse 30-day mortality; best candidates patients
with upper lobe disease and poor preoperative performance
|
| Other treatment modalities: noninvasive positive pressure ventilation—spares many inpatients need for intubation
and mechanical ventilation; lung transplantation—for emphysema, provides symptomatic relief, but no survival
benefit; oxygen—offers clear survival benefit; pulmonary rehabilitation—improves exercise tolerance and perceived
quality of life, but confers no survival benefit and does not improve lung function; gets family involved and provides support
|
Educational Objectives
| The goal of this program is to review current knowledge of community-acquired methicillin-resistant Staphylococcus aureus
(CA-MRSA) infections and chronic obstructive pulmonary disease (COPD). After hearing and assimilating this program,
the listener will be able to:
|
| 1. Identify the main risk factor for CA-MRSA.
|
| 2. List some of the infections caused by CA-MRSA.
|
| 3. Describe the management and prevention of the most common CA-MRSA infections.
|
| 4. State the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of COPD.
|
| 5. Discuss the best approach to managing patients with COPD.
|
Discussed on this Program
Aminophylline (theophylline ethylenediamine) [Phyllocontin, Truphylline]
Amoxicillin [Amoxil, Amoxil Pediatric Drops, Trimox, Trimox Pediatric Drops]
Bacitracin [AK-Tracin, Altracin, Baciguent, Baci-IM]
Cefazolin sodium [Ancef, Zolicef]
Cephalexin [Biocef, Keflex]
Clindamycin (several preparations and trade names)
Daptomycin [Cubicin]
Dicloxacillin sodium
Doxycycline (several trade names)
Erythromycin [Akne-Mycin, A/T/S, Emgel, Eryderm 2%, Erygel, Ery Pads, Ilotycin]
Fluticasone propionate/salmeterol [Advair Diskus]
Formoterol fumarate [Foradil Aerolizer]
Ipratropium bromide and albuterol sulfate [Combivent, DuoNeb]
Linezolid [Zyvox]
Megestrol acetate [Megace, Megace ES]
Minocycline HCl (minomycin) [Arestin, Dynacin, Minocin, Minocin IV]
Mupirocin (pseudomonic acid A) [Bactroban, Bactroban Cream, Bactroban Nasal]
Nafcillin sodium
Oxacillin sodium
Polymyxin B sulfate(several trade names)
Quinine sulfate
Quinupristin/dalfopristin [Synercid]
Rifampin (rifampicin) [Rifadin, Rimactane]
Sulfamethoxazole [Gantanol]
Theophylline (several preparations and trade names)
Tiotropium bromide [Spiriva]
Trimethoprim–sulfamethoxazole (co-trimoxazole; TMP–SMZ) (several preparations and trade names)
Vancomycin [Vancocin, Vancoled]
Vanicream (ointment/lotion base)
Suggested Reading
Bellamy D et al: International Primary Care Respiratory Group (IPCRG) Guidelines: management of chronic obstructive
pulmonary disease (COPD). Prim Care Respir J 15:48, 2006; Chen SF: Staphylococcus aureus decolonization. Pediatr
Infect Dis J 24:79, 2005; Coia JE et al: Guidelines for the control and prevention of methicillin-resistant Staphylococcus
aureus (MRSA) in healthcare facilities. J Hosp Infect 63 Suppl 1:S1, 2006; Costa D et al: Influence of noninvasive
ventilation by BiPAP on exercise tolerance and respiratory muscle strength in chronic obstructive pulmonary disease patients
(COPD). Rev Lat Am Enfermagem 14:378, 2006; Currie GP, Lipworth BJ: Pharmacological management—
inhaled treatment. BMJ 332:1439, 2006; Donald M et al: Emergency department managemenet of home intravenous antibiotic
therapy for cellulitis. Emerg Med J 22:715, 2005; Johannessen A et al: Incidence of GOLD-defined chronic
obstructive pulmonary disease in a general adult population. Int J Tuberc Lung Dis 9:926, 2005; Malhotra S, Man SF,
Sin DD: Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs 11:275,
2006; Miravitlles M et al: Patient’s perception of exacerbations of COPD—the PERCEIVE study. Respir Med August
26, 2006 [Epub ahead of print]; O’Donnell RA et al: Relationship between peripheral airway dysfunction, airway obstruction,
and neutrophilic inflammation in COPD. Thorax 59:837, 2004; Pleasants RA: Review of the guidelines and
the literature in the treatment of acute bronchospasm in chronic obstructive pulmonary disease. Pharmacotherapy
26:156S, 2006; Ram FS et al: Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database
Syst Rev April 19, (2):CD004403, 2006; Wakhlu A et al: Conservative management of necrotizing fascitis in children.
J Pediatr Surg 41:1144, 2006; Ware JH: The National Emphysema Treatment Trial—how strong is the evidence?
N Engl J Med 348:2055, 2003; Wortheim HF et al: Effect of mupirocin treatment on nasal, pharyngeal, and perineal
carriage of Staphylococcus aureus in healthy adults. Antimicrob Agents Chemother 49:1465, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Auwaerter is on the advisory boards of Schering-Plough and Ortho-McNeil.
Dr. Auwaerter spoke on July 31, 2006, at the Infectious Diseases Update, held in Baltimore, MD, and sponsored by
the Johns Hopkins University School of Medicine. Dr. Frank was recorded on June 8, 2006, at the UCLA Family
Practice Refresher Course, held in Beverly Hills, CA, and sponsored by the David Geffen School of Medicine of the
University of Califonia at Los Angeles and the UCLA Department of Family Medicine. The Audio-Digest Foundation
thanks the speakers and the sponsors for their cooperation in the production of this program.
|
