INFECTIOUS DISEASE
From the 34th Annual Family Practice Refresher Course, sponsored by the David Geffen School of Medicine at the
University of California, Los Angeles
| VACCINE-PREVENTABLE DISEASES —David A. Pegues, MD, Professor of Clinical Medicine, and Program Director,
Infectious Diseases, David Geffen School of Medicine at the University of California, Los Angeles
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| Pertussis: everyone potentially at risk (even if previously vaccinated); most common bacterial cause and least well controlled
vaccine-preventable illness; characteristics—incubation period 1 wk to 10 days; onset typically insidious; upper
respiratory infection-type or catarrhal phase lasts ≈7 to 10 days; in minority of adults, followed by paroxysmal-cough
phase that may persist ≤1.5 mo, with resolution of cough after additional 1 to 2 wk; fever uncommon or minimal; disease
usually milder in adults (many patients minimally symptomatic; diagnosis problematic); culture difficult and not commonly
done; polymerase chain reaction (PCR) assays available, but culture likely negative by time patient presents for
medical care; serology used (detects IgM, IgA, and IgG antibodies); need high clinical index of suspicion to test (bacteriologic,
microbiologic with PCR, or serologic); overall attributable mortality rate low (but no deaths acceptable, since disease
preventable); acellular pertussis vaccine—widely used in pediatric formulation since 1996; adult vaccine—tetanus
toxoid, reduced diphtheria toxoid, and acelluar pertussis, adsorbed (Tdap); licensed in 2005; Adacel only vaccine appropriate
in individuals 11 to 54 yr of age; Boostrix available for adolescents and children (not licensed for those >19 yr of
age); updated Advisory Committee on Immunization Practices (ACIP) recommendation—October 2006; anyone 19 to 64
yr of age (or anyone >64 yr of age who expects frequent contact with children) should receive single dose of Tdap to replace
next routine tetanus and diphtheria (Td) booster for immunization (typical immunization schedule every 10 yr for
Td; Tdap may be administered sooner, particularly for health care workers; recommended that as few as 2 yr can pass between
last Td and first Tdap vaccination); other eligible individuals include those (regardless of age) who have close contact
with infants or children <12 yr of age, and women considering pregnancy (because of risk for in utero and
postpartum transmission)
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| Mumps: recommendation (updated in 1988) that 2 doses of measles, mumps, and rubella virus (MMR) vaccine be given
as routine part of pediatric vaccination schedule; second dose of MMR—protective; limited studies (due to low prevalence
of mumps in last few decades); some studies suggest attack rate decreased 5-fold due to 2-dose strategy; recent unpublished
study estimated >90% protective efficacy; updated ACIP recommendations—low-risk adults and children 1 to
4 yr of age should receive single dose of mumps vaccine; necessary to administer second dose to children before entering
school, students considering or pursuing postsecondary education, and workers in health care facilities; health care workers
should routinely receive 2 doses of vaccine (includes single dose of vaccine in outbreak setting for individuals previously
thought immune [born before 1957]); second dose administered between ages 1 to 4 yr before beginning school or
for low-risk adults outside of health care professions if outbreak occurs
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| Influenza: greatest burden of illness in those >50 or <5 yr of age; efficacy of vaccine—like many vaccines, works best
for those who need it least (eg, in healthy individuals <65 yr of age, vaccine 90% effective in preventing influenza-like
illness); only 30% to 40% effective in older individuals, but causes 50% to 60% reduction in need for hospitalization and
80% reduction in complications; priority to vaccinate health care workers, due to risk of transmission to high-risk individuals
in ambulatory or in-patient setting; vaccination has potential for improving and maintaining normal function of
institutions during flu season; regulatory overlay—beginning in 2007, Joint Commission on Accreditation of Healthcare
Organizations (JCAHO) mandated that all health care workers be offered influenza vaccination (those who do not accept
must sign mandatory paper or electronic declination form); routine over-the-counter (OTC) antiviral drugs for treating influenza
(particularly in Far East) resulted in dramatic increase of influenza A strains resistant to amantadine and rimantadine
(no longer used routinely for prophylaxis in outbreak or for treatment)
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| Varicella zoster: by 40 yr of age, 99.5% of Americans exposed to, and at risk for, recurrent zoster infection (“shingles” or
dermatomal zoster); burden of illness (ie, incidence) increases in linear (rather than exponential) fashion after 50 yr of age;
incidence of postherpetic neuralgia increases after 60 yr of age; lifetime probability of developing zoster infection at 85 yr of
age, 50%; purpose of vaccine to prevent infection and decrease severity of postinfectious complications; ACIP
recommendation—everyone ≥60 yr of age should receive vaccine, regardless of whether previously infected; in general, if
previously infected (particularly if >60 yr of age), low probability of second episode
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| SERIOUS BACTERIAL ORGANISMS —Dr. Pegues
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| Methicillin-resistant Staphylococcus aureus (MRSA): methicillin resistance most common phenotype of S aureus
among inpatient and outpatient staphylococcal isolates; various virulence genes and antibiotic-modifying enzymes (eg,
β-lactamase); usually encodes multidrug resistance (not just to dicloxacillin, oxacillin, and cephalexin but to other antistaphylococcal
antibiotics when health care-associated strain present); community-acquired MRSA (CA-MRSA)—
typically retains susceptibility to many OTC antiinfectives; although clindamycin resistance seen in community-acquired
strains, most typical epidemic strains retain clindamycin susceptibility; although CA-MRSA ciprofloxacin-susceptible,
fluoroquinolones not necessarily good choice for treatment because of rapid emergence of resistance during therapy;
health care-associated strains—responsible for necrotizing pneumonia, catheter-associated bloodstream infections, and
other device-associated infections; CA-MRSA—perhaps (but not entirely) due to presence of virulence gene (Panton-
Valentine leukocidin [PVL] and other toxins), has risk for causing necrotizing pneumonia and secondary bacteremia; has
smaller plasmid-encoded resistance determinant, making it highly transmissible; causes virulent skin and skin structure
infections; dominant clone—responsible for >90% of infections in United States, although several unique strains of CA-
MRSA present; USA300 clone; susceptible in vitro to clindamycin, erythromycin, doxycycline, and trimethoprim–sulfamethoxazole
(TMP–SMZ); speaker expecting resistance to emerge soon; spreads through intact skin and survives on variety
of environmental surfaces; grows more rapidly in vitro; survives for up to 24 hr; survives in fomites; data show CA-
MRSA overwhelmingly associated with skin and skin structure infections and uncommonly associated with infections
typically seen with health care-associated MRSA; study showed S aureus responsible for 75% of skin and skin structure
infections presenting to emergency departments (EDs); study showed MRSA found in 59% of S aureus isolates (of those
MRSA isolates, 97% USA300); take-home message—>50% of all skin and skin structure infections in urban EDs
caused by USA300; concerning that in 50% of cases, antibiotic given empirically, despite clinical presentation suggestive
of CA-MRSA; 57% of time, antibiotic discordant; emerging problem, with little data from randomized clinical trials; for
abscess <3 cm in diameter, study showed that in pediatric patients, incision and drainage alone often adequate to resolve
infection; if oral therapy indicated (eg, presence of comorbid condition or surrounding cellulitis), select monotherapy
without systemic toxicity (twice-daily drugs, eg, TMP–SMZ, doxycycline, usually convenient); for moderate infections
(patient systemically ill with fever or significant comorbidities), assess need for surgical management and whether as inpatient
or outpatient; combination therapy generally used; rifampin potent antistaphylococcal drug but has many drug-
drug interactions (use with caution); most typically used therapy TMP–SMZ with or without doxycycline or rifampin; for
severe infections, recommend hospitalization with prompt surgical consultation for drainage or debridement; typically,
vancomycin administered (maintain at peak level), then when patient clinically improved, transitioned to mono- or dual
therapy with oral agent; prevention—educate patient about ways of preventing transmission to others in household and
preventing recurrence of infection; eg, hand hygiene, hand washing and showering with liquid antimicrobial soap, avoiding
sharing personal care items, hot-laundering towels, wash cloths, and undergarments; in spite of hygiene measures, if
recurrent infections occur, appropriate to consider decolonization of CA-MRSA; for health care-associated MRSA, topical
mupirocin (with or without oral rifampin) for 5 days for removal from anterior nares (where bacteria reside) proven
moderately successful in suppressing nasal colonization; commonly, patients with CA-MRSA have active skin lesions
but negative nasal culture; decolonize CA-MRSA where located (skin); in addition to antimicrobial soap, consider using
skin antiseptic (eg, chlorhexidine [Hibiclens], undiluted [≤1-2 times weekly] or as wash [once daily])
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| Resistant microorganisms: Escherichia coli—in United States, 20% TMP–SMZ-resistant, 40% ampicillin-resistant,
and 8% quinolone-resistant; in nonelderly patients and those with adequate renal function, nitrofurantoin effective; doxycycline
exhibits potent activity against E coli; first- or second-generation cephalosporins more potent for treating E coli than
TMP–SMZ or ciprofloxacin; for serious infections, parenteral agent (carbapenem or aminoglycoside) recommended;
Clostridium difficile—hypertoxin-producing strain; causes outbreaks; mutations cause production of excess toxin (15 to 20
times more toxin produced constantly by epidemic strain); high level of resistance to fluoroquinolones; oral metronidazole
treatment of choice for mild disease; consider oral vancomycin (highly effective; dose 125 mg qid) in elderly, particularly
when acquired in intensive care unit (ICU) and/or associated with profuse diarrhea and marked leukemoid reaction; take
barrier precautions due to high transmissibility; use antimicrobial hand soaps; other drugs (eg, nitazoxanide) as effective as
vancomycin and considered for patients with treatment failure; for patients with refractory disease, refer to gastroenterologist
for other treatment
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| INFECTIOUS DISEASE IN OLDER PATIENTS —Dean C. Norman, MD, Professor of Medicine and Geriatrics, David
Geffen School of Medicine at the University of California, Los Angeles
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| General age-related considerations: infections setting-dependent (eg, in nursing home, ≈1 infection/patient per year);
difference in pathogens—in younger individuals, Streptococcus pneumoniae, Mycoplasma, and Chlamydia key causes of
community-acquired pneumonia (CAP); in elderly, variety of pathogens; in young adults with urinary tract infections (mostly
women), E coli most predominant pathogen, while in elderly (men and women), variety of pathogens (obtaining cultures before
antibiotic therapy recommended); higher morbidity and mortality—low reserve capacity; change in host resistance;
chronic illness or comorbidity; more likely to be hospitalized (risk for nosocomial infections); polypharmacy (adverse drug reactions
more likely); delayed diagnosis and treatment due to atypical presentations; more likely to undergo procedures and
have complications; delayed treatment response; changes in host defenses with age—skin thinner (more easily bruised); diminished
cough reflex; comorbidities more common; polypharmacy (avoid sedative hypnotic drugs in elderly if possible);
functional impairments (eg, loss of mobility); invasive or implantable devices
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| Effects of aging on immune system: decrease in T lymphocyte proliferation (major effect), cytotoxicity, interleukin
2 production, and delayed-type hypersensitivity reaction, and increase in memory cells; affects B-cell and antibody response;
less antibody response to T-cell vaccines (tetanus, influenza, and pneumococcal)
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| Clinical presentation of infection: ≥1 presenting sign(s), eg, delirium, lethargy, anorexia, falls, autonomic dysfunction,
focal neurologic signs; bacteremia may be afebrile and present instead with tachypnea, confusion, and hypotension;
pneumonia may be afebrile, and cough and sputum production may be absent; lack of febrile response—baseline temperatures
of elderly lower by 1°; oral temperature of 99°F on repeated measurement significant (particularly when baseline
96°F); presentations typical, nonspecific, or absent; fever highly specific and usually indicates serious bacterial or viral infection;
fever not sensitive marker for infection; ≈20% to 30% of infected elderly afebrile; diagnosis of fever of unknown
origin common
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| Antibiotics: renal clearance only notable pharmacologic difference; study—physicians routinely overestimated renal function
in elderly (eg, dosing errors 65% for aminoglycosides and 33% for cephalosporins); drug-drug interactions—divalent
cations (eg, antacids) markedly affect quinolone absorption; toxicity due to antibiotics—nephro- and ototoxicity; blood
dyscracias and rash with TMP–SMZ; hepatotoxicity with isoniazid (INH); central nervous system toxicity with amantadine
and rimantadine; diarrhea, drug fever, interstitial nephritis, and rash with β-lactam drugs; seizures with carbapenems; thromobocytopenia
and anemia with linezolid; C difficile colitis and diarrhea with clindamycin; hyper- and hypoglycemia with
fluoroquinolones; aminoglycosides—age may or may not be risk factor for toxicity; duration of exposure, elevated trough
levels, and intrinsic renal disease risk factors; use judiciously for shortest time possible; after results of culture known, replace
with less toxic drug if possible; once-daily dosing cost-effective; necessary to monitor levels if on multidose regimen
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| Pneumonia: each year, 1 in 20 individuals >85 yr of age develops pneumonia; more likely bacteremic, compared to
younger individuals with same pathogen; rate of nosocomial pneumonia per day higher in elderly, with higher mortality
rate; pneumonia leading cause of infection requiring transfer to hospital and accounts for 4.3% of elderly patients hospitalized;
in-hospital mortality rate 17%; in hospitalized patients, 40% of those >65 yr of age colonized with S aureus or
gram-negative bacilli (100% in ICU); older individuals rapidly colonized as they require higher levels of care; organisms
seen in CAP (vs nursing home- or hospital-acquired pneumonia)—gram-negative bacilli seen even in CAP; nursing
home-acquired pneumonia usually sensitive gram-negative bacilli; gram-negative bacilli and anaerobes key organisms in
acute care hospital pneumonia (severe aspiration pneumonia); recent data suggest that dental plaque in older individuals
with periodontitis plays role in high colonization rates with gram-negative bacilli and S aureus; Legionella more likely to
occur in community than in nursing home; among patients transferred directly to ICU from nursing home, large percentage
infected with gram-negative bacilli (although sensitive to antimicrobial therapy); resistance to S pneumoniae—
penicillin no longer useful empiric drug for treatment; atypical presentation common in elderly; work-up—blood culture
(5%-15% positive), O2 saturation, and arterial blood gases; also complete blood cell count, renal function, and electrolytes;
de-escalation therapy—for hospitalized patients with severe nosocomial pneumonia, start with broad-spectrum
antimicrobials; narrow down to less costly, more specific agents when culture results known; if patient clinically stable,
switch to oral antimicrobial therapy and discharge (ensure adequate support at home); helpful to have advanced directives
when patient sent to nursing home; study showed that clinical pathways significantly reduce hospitalizations; giving
antibiotics within 8 hr reduces mortality (new recommendation, within 4 hr of presentation); blood cultures lower odds of
mortality; prevention of ventilator-associated pneumonia—hand washing between patients; elevate head of bed; prophylaxis
for deep venous thrombosis; proton pump inhibitor
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| Vaccination: necessary; influenza vaccination—does not prevent symptomatic influenza but prevents development of severe
complications; avian influenza—vaccine approved and stockpiled for government workers; mildly protective; revaccinations
for Streptococcus—routine revaccinations not recommended
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Suggested Reading
Bloomfield SF: Community-acquired MRSA. Lancet 368:1328, 2006. Bouza E et al: Antimicrobial therapy of
Clostridium difficile-associated diarrhea. Med Clin North Am 90:1141, 2006; Burns IT et al: Immunization barriers and
solutions. J Fam Pract 54:S58, 2005; Collignon P et al: Fluoroquinolone-resistant Escherichia coli: food for thought. J
Infect Dis 194:8, 2006; Epub 2006 May 31. Eaton L: C difficile cases rising, but MRSA rates falling. BMJ 335:177,
2007; El Solh AA et al: Clinical and hemostatic responses to treatment in ventilator-associated pneumonia: role of bacterial
pathogens. Crit Care Med 35:490, 2007; Hawkes M et al: Community-associated MRSA: superbug at our doorstep.
CMAJ 176:54, 2007; Hidayat LK et al: High-dose vancomycin therapy for methicillin-resistant Staphylococcus
aureus infections: efficacy and toxicity. Arch Intern Med 166:2138, 2006; Kimmel SR et al: Addressing immunization
barriers, benefits, and risks. J Fam Pract 56:S61, 2007; Leffler D et al: Gastric acid-suppressive agents and risk of
Clostridium difficile-associated disease. JAMA 295:2599, 2006; Smith NM et al: Influenza vaccination for elderly people
and their care workers. Lancet 368:1752, 2006; Teffer Ayalew et al: The "age" factor in adult medicine. Mayo Clin
Proc 78:913, 2003; Tenover FC: Mechanisms of antimicrobial resistance in bacteria. Am J Med 119:S3, 2006; Voyich
JM et al: Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant
Staphylococcus aureus disease? J Infect Dis 194:1761, 2006; Epub 2006 Nov 2. Woolery WA et al: Fever of unknown
origin: keys to determining the etiology in older patients. Geriatrics 59:41, 2004; Zimmerman RK et al: Routine vaccines
across the life span, 2005. J Fam Pract 54:S9, 2005; Zimmerman RK et al: Vaccines for persons at high risk,
2007. J Fam Pract 56:S38, 2007.
Educational Objectives
| The goal of this program is to reduce the incidence of vaccine-preventable illnesses and improve the management of serious
infections due to multidrug-resistant organisms in the elderly. After hearing and assimilating this program, the clinician will
be better able to:
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 | 1. Apply the latest recommendations by the Advisory Committee on Immunization Practices for vaccine-preventable
illnesses.
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| 2. Recommend measures for prevention of transmission of methicillin-resistant Staphylococcus aureus in the household.
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| 3. Prescribe appropriate drugs for multidrug-resistant organisms.
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| 4. Discuss how infections differ in presentation in the elderly, compared to young adults.
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| 5. Describe age-related changes that contribute to higher morbidity and mortality rates from infections in the elderly.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty 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. Pegues is on the Speakers’ Bureaus of
Merck & Co, Inc, Pfizer Inc, Schering-Plough, and Astellas Pharma Inc.
Acknowledgements
Drs. Pegues and Norman were recorded at the 34th Annual UCLA Family Practice Refresher Course, held May 29 to June
2, 2007, in Los Angeles, CA, and sponsored by the David Geffen School of Medicine at the University of California, Los
Angeles. The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation in the production of this
program.
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