INFECTIOUS DISEASE UPDATE
From Primary Care Medicine: Principles and Practice, presented by the University of California, San Francisco, School of
Medicine
| VACCINES FOR ADULTS: WHAT’S NEW ?—Lisa Winston, MD, Assistant Clinical Professor of Medicine, Division of
Infectious Diseases, University of California, San Francisco, School of Medicine, Interim Vice Chief of Medical Service
and Hospital Epidemiologist, San Francisco General Hospital
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| Mumps vaccination for health care workers: change in vaccination recommendations due to recent large outbreak of
mumps in midwestern United States; outbreak involved strain of mumps thought to be covered by measles, mumps, rubella,
(MMR) vaccination; vaccinated persons at risk, particularly those who had only one dose of MMR; health care
workers born before 1957 should now consider getting one dose of MMR vaccine unless they have documented immunity,
defined as having had physician-diagnosed mumps or positive serology (workers in area of mumps outbreak should
get 2 doses); all those born during or after 1957 should get 2 doses of vaccine, unless they have documented preexisting
immunity
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| Pneumococcal polysaccharide vaccine (Pneumovax): 23-valent vaccine; does not appear to decrease pneumonia in older
adults but probably decreases mortality and pneumococcal bacteremia; indications—age >65 yr; most chronic cardiopulmonary
conditions; diabetes; liver or renal failure; splenectomy; immunosuppression; cochlear implants; certain native
populations; residents of long-term care facilities; revaccination—practice varies; Centers for Disease Control and Prevention
(CDC) recommendations on revaccination; little supporting data, but common practice
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| Meningococcal vaccine: Menomune—traditional vaccine; tetravalent (covers serogroups A, C, Y, and W-135); polysaccharide;
problems (poor response in patients <2 yr of age; short duration of protection; multiple doses may lead to immune
hyporesponsiveness with serotypes A and C; no effect on carriage; serogroup B not covered); Menactra—new
vaccine; also tetravalent (covers same serogroups as Menomune); protein conjugate; approved for patients 11 to 55 yr
of age; has longer-lasting antibody titers; good antibody response to revaccination; serogroup B still not covered; recommended
as routine for ages 11 to 18 yr (ideally given at age 11-12 yr; if not given then, patient can catch up at high
school or college entry); also recommended for military recruits, some travelers, patients with terminal complement
deficiencies or asplenia
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 | Questions about meningococcal vaccine: clinical efficacy undetermined; no current recommendations on revaccination;
unlikely to be cost-effective; possible link with Guillain-Barré syndrome (17 cases reported between June 2005 and
September 2006 within 6 wk of vaccination; slight increase above expected rate)
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| Pertussis vaccine: childhood vaccine—diphtheria-tetanus-acellular pertussis (DTaP; contains full doses of diphtheria and
tetanus toxoids, and acellular pertussis antigens; vaccines for adults and adolescents—tetanus-diphtheria (Td) and tetanus-diphtheria-acellular
pertussis (Tdap); contain tetanus toxoid and reduced dose of diphtheria toxoid, plus or minus reduced
dose of acellular pertussis antigens; pertussis—immunity (from vaccine or disease) wanes over time; ≈600,000
cases annually in United States in persons 19 to 64 yr of age
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| Recommendations: for adults 19 to 64 yr of age—give single dose of Tdap to replace routine Td vaccine given every 10
yr (if necessary, can be given at shorter interval from last tetanus-containing vaccine); recommended for adults who
will have contact with infants <12 mo of age; currently not recommended during pregnancy (should be given immediately
postpartum if not given previously); for adolescents—give Tdap instead of Td vaccine at routine 11- to 12-yr
visit; no current recommendations for Tdap booster; recommended for all health care workers with patient contact; not
licensed for patients >65 yr of age
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| Influenza vaccine: inactivated vaccine given by injection—always contains 2 influenza A strains and one influenza B
strain; few contraindications (only absolute contraindication anaphylactic reaction to chicken eggs; all others relative);
live attenuated influenza vaccine (LAIV)—intranasal; contains same strains as inactivated vaccine; attenuated,
heat-sensitive (does not replicate in lower airway), and cold-adapted (replicates in nose); approved for healthy
people 2 to 49 yr of age (including health care workers and contacts of most high-risk patients; should not be given
to those working with highly immunocompromised patients)
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| Influenza vaccine indications: adults ≥50 yr of age; children 6 mo to 5 yr of age; patients with chronic medical conditions;
residents of long-term care facilities; women pregnant during influenza season; health care workers; healthy persons with
high-risk contacts; anyone who wants to avoid having influenza
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| LAIV: contraindications—outside recommended age ranges; chronic medical conditions (including asthma); pregnancy;
history of Guillain-Barré syndrome; anaphylaxis to eggs; contact with highly immunosuppressed patients; side
effects—runny or stuffy nose common; efficacy—in children, LAIV very efficacious (may be more effective than inactivated
vaccine); 2006 study in New England Journal of Medicine (NEJM) looking at efficacy of vaccine in adults
found LAIV not as effective as inactivated vaccine, especially against influenza B
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| Varicella vaccine: Varivax—recommended for all adults without immunity; contraindications—pregnancy; most forms
of immunocompromise; given as 2 doses; Zostavax—varicella-zoster vaccine; efficacy (randomized trial of >38,000
adults in NEJM in June 2005 found vaccine reduced incidence of herpes zoster by >50% and postherpetic neuralgia by
>65%); fairly well tolerated (injection-site reactions common; other adverse effects uncommon); currently only provisional
recommendations from Advisory Committee on Immunization Practices (ACIP; recommends single dose of vaccine
for adults ≥60 yr of age, even with previous history of herpes zoster; contraindicated in immunocompromised
patients)
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| Human papillomavirus (HPV) vaccine: genital HPV most common sexually transmitted infection in United States;
quadrivalent HPV vaccine (Gardasil) licensed by Food and Drug Administration (FDA) in June 2006; contains major
capsid protein L1 from virus types 6, 11, 16, and 18 (types 16 and 18 associated with 70% of cervical cancers; types 6 and
11 associated with 90% of genital warts); FDA approval pending for bivalent vaccine (Cervarix) against virus types 16
and 18; efficacy—close to 100% in preventing short-term infection with HPV types included in vaccine (if patients not
previously infected); recommended for girls at 11- to 12-yr visit (greatest benefit before onset of sexual activity and infection
with HPV); catch-up vaccination recommended for females 13 to 26 yr of age not previously vaccinated; not
much evidence of protection against types of virus with which patients already infected at time of vaccination; 3-dose series
(at 0, 2, and 6 mo); expensive ($360 for series); ongoing controversies
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| UPDATE ON COMMUNITY ACQUIRED PNEUMONIA —Bradley A. Sharpe, MD, Assistant Clinical Professor, Division
of Hospital Medicine, Department of Medicine, University of California, San Francisco, School of Medicine
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| Background: 5million cases of community acquired pneumonia (CAP) annually (80% treated as outpatients); sixth leading
cause of death in United States (inpatient mortality ≤30%; outpatient mortality <1%; mortality highest in whites)
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| Clinical presentation: patients present with cough, shortness of breath, and sputum production
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| Etiology: not true that difference between typical and atypical pneumonia identifiable; best evidence suggests no history,
examination, laboratory test, or clinical or radiographic feature can predict causative organism; most experts now suggest
that pneumonia should be thought of in terms of severity of illness (ie, is patient only slightly ill and treatable as outpatient;
does he or she require admission but not to intensive care unit [ICU]; does patient need to be admitted to ICU); better
predictor of underlying microbiology than clinical features; in outpatients, tend to see mix of typical (eg,
Streptococcus pneumoniae, Haemophilus influenzae) and atypical (eg, Mycoplasma, Chlamydia)
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| Staphylococcus aureus pneumonia: most often caused by methicillin-sensitive S aureus (MSSA), but in past few years,
CDC has reported 25 cases of influenza-associated community-acquired methicillin-resistant S aureus (MRSA) infection;
all cases in young patients (median age 20 yr; many teenagers) and most (66%) did not have risk factors for MRSA
infection; thus, if young patient presents in any setting with rapidly progressive multilobar infiltrate, consider coverage
against MRSA during treatment
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| Diagnosis of CAP: practice guidelines state that diagnosis requires both clinical presentation (including physical examination
[PE]) and evidence of infiltrate on chest x-ray (CXR) or other imaging (patient history and PE not sensitive or specific
enough to make diagnosis alone; all patients with suspected pneumonia require CXR to confirm diagnosis); may still end up
treating patient for pneumonia without evidence of infiltrate on CXR, but consider other diagnoses (eg, pulmonary embolism,
chronic obstructive pulmonary disease [COPD] exacerbation)
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| Adjunctive diagnostic testing: blood cultures required in patient ill enough to be admitted (in some cases can provide specific
diagnosis so patient does not have to be treated empirically), but no evidence of benefit; not routinely indicated in management
of outpatients (positive in ≤10% of patients with CAP; unlikely to be positive in patient who can be seen and
treated in outpatient setting); sputum culture also not routinely required in management of outpatients
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| Future of diagnostic testing: pneumococcal urinary antigen—by-product of pneumococcus excreted in urine; fast test—
can be done in office; >90% specificity (but does not indicate whether organism drug-resistant or sensitive);
procalcitonin—precursor of calcitonin that does not have hormonal activity; inflammatory marker; studies show procalcitonin
greatly elevated in people with bacterial infections (test not yet available)
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| Decision to admit: once CAP diagnosed, deciding whether patient should be admitted or treated as outpatient extremely
important; reasons for not admitting patient—studies comparing persons admitted or treated as outpatients have found
that those treated in outpatient setting return to normal activities sooner and actually prefer to be treated as outpatients;
inpatient care 25 times more expensive; hospitals “not that safe”
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| Pneumonia severity index (PSI)/Pneumonia Outcomes Research Team (PORT) score: stratifies patients into 5 classes
of risk; over past 10 yr, used increasingly to help decide where patients diagnosed with CAP can safely be treated; expert
guidelines recommend—that prognostic model such as PSI/PORT score be used in every patient with CAP to help identify
possible candidates for outpatient treatment; that class I and II patients should definitely, and class III patients should probably,
be treated as outpatients; class IV should be admitted, and class V placed in ICU; limitations of PSI/PORT scoring
system—laboratory data required; hypoxia (counts for 10 points in scoring system but not binary decision, whereas most
pulmonologists say if O2 saturation <90%, patient should be admitted); coexisting comorbid conditions (often reason for admitting
patients with class I, II, and III disease); most useful in managing borderline patients (when unsure whether to admit)
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| Algorithm for admission decision: if patient hypoxic, has active coexisting condition, or unable to take oral medications, he
or she should be admitted (no need for scoring system); patients who score as PSI/PORT class IV or V require admission; if
patient class I, II, or III, ask whether other reasons he or she should not go home (eg, unstable social situation; frail condition;
general feeling patient needs to be in hospital); if no such mitigating factors, patient probably can go home on oral medication
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| Treatment principles: any empiric therapy must cover typical and atypical organisms; pneumococcus still leading cause
of CAP; in cases of pneumococcal pneumonia, important to determine whether underlying organism drug-susceptible or
drug-resistant strain of S pneumonia
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| Risk factors for drug-resistant S pneumoniae (DRSP): age >65 yr; any chronic disease; diabetes mellitus; alcoholism;
active malignancy; immunosuppression; antibiotics in last 3 mo
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| CAP treatment guideline recommendations: outpatient, healthy with no risk factors for DRSP—doxycycline or macrolide
(azithromycin, clarithromycin, or erythromycin); outpatient with risk factors for DRSP—monotherapy with oral
fluoroquinolone or oral β-lactam (amoxicillin or amoxicillin-potassium clavulanate [Augmentin]) plus doxycycline or
plus macrolide; University of California, San Francisco guidelines—for patients with no comorbidities and not recently
on antibiotics, doxycycline first choice; for patients with risk factors for DRSP, respiratory fluoroquinolone first choice
and β-lactam plus macrolide second choice; inpatient, non-ICU—fluoroquinolone or β-lactam plus macrolide (levofloxacin
or ceftriaxone and azithromycin); inpatient, ICU—intravenous (IV) β-lactam plus macrolide or fluoroquinolone;
any other antibiotics depend on patient’s pseudomonal risk factors
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| Duration of therapy: increasing evidence for shorter courses of therapy (studies have reported clinical success with 3-5 days of
azithromycin, 5 days of high-dose levofloxacin, and in Europe, with 3 days of amoxicillin outpatient therapy); new guidelines
state patients with CAP should be treated for minimum of 5 days
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| Prevention: Pneumovax—vaccine against S pneumoniae; covers 90% of serotypes that cause disease; does not prevent
pneumonia in high-risk patients and does not have mortality benefit, but probably does prevent invasive pneumococcal
disease, eg, bacteremia, empyema, meningitis; studies have found that while Pneumovax does not prevent persons from
getting pneumonia, disease not as severe in patients with vaccination; indicated for all patients >65 yr of age or with
chronic medical condition; influenza vaccine—effectively prevents influenza in older and younger patients (prevents
both hospitalization and pneumonia, and studies show mortality benefit in adult patients); smoking cessation
counseling—may also help prevent pneumonia and should be provided to all patients who smoke (some evidence that
current and passive smokers at increased risk of developing pneumonia); avoidance of proton pump inhibitors (PPIs)—
studies suggest that current PPI or histamine-2 (H2 )-blocker use increases risk for pneumonia; dose effect (more doses
patient takes, higher the risk)
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Suggested Reading
Ashkenazi S et al: Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine
in young children with recurrent respiratory tract infections Pediatr Infect Dis J 25:870, 2006; Atlas SJ et al: Safely
increasing the proportion of patients with community-acquired pneumonia treated as outpatients: an interventional trial.
Arch Intern Med 158:1350, 1998; Bilukha OO, Rosenstein N: Prevention and control of meningococcal disease. Recommendations
of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 54:1, 2005; Carratalà J
et al: Outpatient care compared with hospitalization for community-acquired pneumonia: a randomized trial in low-risk patients.
Ann Intern Med 142:165, 2005; Centers for Disease Control and Prevention (CDC): Update: Guillain-Barré syndrome
among recipients of Menactra meningococcal conjugate vaccine--United States, June 2005-September 2006.
MMWR Morb Mortal Wkly Rep 55(41):1120, 2006; Fine MJ et al: A prediction rule to identify low-risk patients with
community-acquired pneumonia. N Engl J Med 336:243, 1997; Fukuda K, Kieny MP: Different approaches to influenza
vaccination. N Engl J Med 355:2586, 2006; Garland SM et al: Quadrivalent vaccine against human papillomavirus to prevent
anogenital diseases. N Engl J Med 356:1928, 2007; Jackson LA et al: Effectiveness of pneumococcal polysaccharide
vaccine in older adults. N Engl J Med 348:1747, 2003; Kimberlin DW, Whitley RJ: Varicella-zoster vaccine for the prevention
of herpes zoster. N Engl J Med 356:1338, 2007; Koutsky LA et al: A controlled trial of a human paillomavirus
type 16 vaccine. N Engl J Med 347:1645, 2002; Li JZ et al: Efficacy of short-course antibiotic regimens for community-acquired
pneumonia: a meta-analysis. Am J Med 120:783, 2007; Mandell LA et al: Infectious Diseases Society of America/
American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect
Dis 44 Suppl 2:S27, 2007; Niederman MS: Recent advances in community-acquired pneumonia: inpatient and outpatient.
Chest 131:1205, 2007; Niederman MS et al: American Thoracic Society. Guidelines for the management of adults
with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J
Respir Crit Care Med 163:1730, 2001; Ohmit SE et al: Prevention of antigenically drifted influenza by inactivated and live
attenuated vaccines. N Engl J Med 355:2513, 2006; Oxman MN et al: A vaccine to prevent herpes zoster and postherpetic
neuralgia in older adults. N Engl J Med 352:2271, 2005; Prevention of pneumococcal disease: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR Recomm Rep 46:1, 1997; Sharpe BA, Flanders SA: Community-acquired
pneumonia: a practical approach to management for the hospitalist. J Hosp Med 1:177, 2006; Steinbrook
R: The potential of human papillomavirus vaccines. N Engl J Med 354:1109, 2006; Ward JI et al: Efficacy of an acellular
pertussis vaccine among adolescents and adults. N Engl J Med 353:1555, 2005.
Educational Objectives
| The goal of this program is to improve the prevention and treatment of infectious disease by providing updates on some of the
vaccines available for adults and adolescents and on the management of community acquired pneumonia (CAP). After hearing
and assimilating this program, the clinician will be better able to:
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| 1. Describe the vaccines available for protection against pneumococcal and meningococcal disease, influenza, varicella,
and human papillomavirus (including their components, efficacy, indications, and contraindications).
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| 2. Cite and follow current vaccination recommendations and guidelines.
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| 3. Employ the Pneumonia Severity index (PSI)/Pneumonia Outcomes Research Team (PORT) score to determine
whether a patient diagnosed with CAP requires admission.
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| 4. Initiate appropriate antibiotic treatment in the outpatient with CAP.
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| 5. Describe some of the preventive treatments and strategies for CAP and their benefits.
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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 faculty and planning committee reported
nothing to disclose.
Acknowledgements
Drs. Winston and Sharpe were recorded at Primary Care Medicine: Principles and Practice, held October 25-27, 2007, in
San Francisco, CA, and sponsored by the University of California, San Francisco, School of Medicine. The Audio-Digest
Foundation thanks Drs. Winston and Sharpe and the University of California, San Francisco, School of Medicine for their
cooperation in the production of this program.
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