FORMIDABLE INFECTIONS
From the 27th Annual University of California, San Francisco, School of Medicine Symposium on Advances in
Infectious Diseases
| TUBERCULOSIS: DIAGNOSIS AND TREATMENT OF LATENT INFECTION —Robert M. Jasmer, MD, Assistant
Professor of Medicine, University of California, San Francisco, School of Medicine
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| Tuberculosis (TB) screening: indicated in at-risk population; if negative—treatment usually not indicated; history of
contact with infectious case mandates treatment until individual proven negative for latent TB infection (LTBI); if LTBI
present, skin test converts 8 to 12 wk after exposure; chest x-ray—mandatory when TB test positive; if normal, treatment
may be necessary for LTBI; if abnormal, look for active TB; sources of TB infection—contact with infectious
case; exposure to people from TB-endemic countries or medically underserved/low-income population groups; employment
in health care or correctional facilities; medical risk factors for progression to active TB—HIV infection; abnormal
chest x-ray compatible with past TB; positive skin test; age <5 yr; skin-test conversion
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| Evaluation: chest x-ray—calcified granuloma (does not indicate increased risk; sputum analysis unnecessary); parenchymal
scarring (manifestation of increased risk; 1 in 10 patients have active TB on sputum culture); screening mandated
by—medical conditions (immunosuppression; malignancy; injection drug use; alcoholism; diabetes; malnutrition;
renal failure; silicosis); use of immunosuppressive agents, eg, steroids, tumor necrosis factor-α (TNF-α) drugs, including
etanercept (Enbrel), infliximab, or adalimumab
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| Frequency of screening: depends on exposure; San Francisco General Hospital mandates—annual testing for general
employees; testing every 6 mo for people working in TB clinic or emergency department, eg, performing bronchoscopy
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| TB skin test (TST), ie, purified protein derivative (PPD) test: look for delayed hypersensitivity reaction; false-
positive evaluations associated with recent bacillus Calmette Guérin (BCG; Mycobacterium bovis) vaccination or presence
of nontuberculous mycobacteria; cutoff reaction sizes—≥5 mm for patients with high-risk conditions, (eg, HIV,
immunocompromised state, recent contact with TB, abnormal x-ray generating suspicion of active TB); ≥10 mm for
health care workers, people living in high-risk congregate facilities, drug users, foreign-born individuals from high-risk
countries, and people with medical risk factors; ≥15 mm for lower-risk groups; PPD test limitations—boosting; difficulty
interpreting results; need for patients to return to clinic in couple of days; high patient dropout rate; risk for false-
positive readings
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| Blood tests: in vitro equivalent of PPD skin test; evaluate whole blood; test multiple antigens; avoid problems with boosting;
Enzyme Linked ImmunoSpot (ELISPOT) TB test—not approved by Food and Drug Administration (FDA)
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| QuantiFERON-TB Gold (QFT-Gold) test: FDA approved for detection of LTBI; avoids arbitrariness of PPD test;
uses antigens specific (but not 100%) for Mycobacterium tuberculosis, ie, ESAT-6 and CFP-10 (not present in BCG;
present in other mycobacteria not often seen in United States); differentiates between TB, nontuberculous mycobacteria
(NTM), and BCG; Centers for Disease Control and Prevention (CDC) recommends using QFT-Gold test in all circumstances
where TST currently used, including—screening; surveillance of health care workers; data suggest—
QFT-Gold more sensitive and specific than TST; antigen “cocktails” retain high sensitivity; QFT-Gold test will eventually
replace PPD and can reduce overtreatment
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| Treatment of LTBI: American Thoracic Society (ATS) and CDC guidelines for treating LTBI—divide patients
into HIV-positive and HIV-negative populations; 9 mo of isoniazid (INH) preferred for all patients with LTBI; 4 mo of
rifampin next best option; role of rifampin/pyrazinamide therapy limited by hepatotoxicity; do not have age cutoff for administering
treatment (management currently focuses on high-risk groups, ie, beneficial effects of treatment outweigh risk
for treatment-associated toxicity); sputum analysis—recommended in patients with fibrotic lesions (10% incidence of
positive cultures); reliance on symptomatology alone causes diagnostic problems (≤30% of subjects do not cough)
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| Empiric approach to patient with LTBI: requires clinical judgment; if suspicion high for active TB—administer
4-drug regimen, ie, INH, rifampin, ethambutol, and pyrazinamide; repeat sputum evaluation at 2 mo; if sputum culture
negative, obtain second x-ray; culture-negative TB—base clinical diagnosis on response to empiric therapy; if repeated
x-ray shows improvement and patient feels better, administer additional 4 mo of INH and rifampin (drop ethambutol and
pyrazinamide); inactive TB—characterized by negative initial culture, unchanged x-ray, absence of symptoms; additional
treatment unnecessary; with low suspicion of active disease—if culture negative and x-ray unchanged, patient
has inactive TB; administer 4 mo of rifampin plus INH, or 9 mo of INH
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| Approach to special cases of LTBI: intermittent dosing (must be directly observed); contact with INH-resistant
TB—mandates 4 to 6 mo of rifampin; children and immunocompromised individuals may require longer duration of
therapy; patients—receiving protease inhibitors should be switched from rifampin to rifabutin; who cannot tolerate INH
should be switched to rifampin
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| Patient monitoring: baseline laboratory testing—unnecessary; monitor liver enzyme levels in patients with HIV infection,
pregnant women, women who have recently delivered, and individuals with history of liver disease or alcoholism;
monthly evaluation necessary to—monitor drug compliance; detect symptoms of hepatitis
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| Drugs: risk for INH-induced hepatitis low; rifampin—use limited by risk for silicosis and drug interactions; rifampin
and pyrazinamide—first-line for active TB; risk greater for hepatotoxicity than INH with rifampin and pyrazinamide
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| PNEUMONIA: COMMUNITY-ACQUIRED DISEASE —Lisa G. Winston, MD, Assistant Clinical Professor of Medicine,
University of California, San Francisco, School of Medicine; Hospital Epidemiologist, San Francisco General Hospital
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| Acute pneumonia: associated with ≥2 new symptoms—fever or hypothermia; rigor and/or diaphoresis; sputum production
or color change; symptoms generating initial concern—cough; chest pain; dyspnea; additional clues—new
infiltrate on chest x-ray and/or abnormal chest examination; no hospitalization or residence in nursing facility in 14 days
before symptom onset; point—increase in age-adjusted death rates related to increase in population with comorbid predisposing
conditions; transmission—microaspiration of organisms colonizing nasopharynx; direct inhalation of aerosolized
pathogens; bacteremic spread (relatively uncommon); factors contributing to development of pneumonia—
defects in host defenses; virulence of organism; size of inoculum
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| Chest radiograph: helps avoid overtreatment with antibiotics, differentiate pneumonia from other suspected conditions,
identify specific etiology or coexisting conditions, and triage patient
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| Microbiologic investigation: Gram stain of sputum—useless unless sputum sample contains <10 squamous cells and
>25 polymorphonuclear leukocytes per low-power field; helpful when single organism present in large numbers; useful in
hospitalized patients; useless when sample obtained after antibiotic therapy started; blood cultures—obtain before antibiotic
therapy; positive cultures clarify diagnosis; Legionella—urine antigen test (rapid and sensitive; detects only Legionella
pneumophila serogroup 1); culture using selective media takes longer; pneumococcal urinary antigen test—
simple and fast; poor sensitivity in adults; poor specificity in children; additional studies—influenza test when suspected;
serologic studies helpful epidemiologically, useless clinically; bronchoscopy—useful in patients with fulminant course unresponsive
to conventional therapy; better yield achievable on bronchoalveolar lavage
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| Concerns: clinical syndrome at presentation and chest x-ray findings not predictive of infecting organism; Staphylococcus
aureus—rare cause of community-acquired pneumonia (CAP); common cause of health care-associated pneumonia;
incidence may be increasing; consider when patients fail treatment; other factors—role of viruses underestimated; no
etiologic agent identified in 20% to 70% of cases
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| Streptococcus pneumoniae: causes two thirds of CAP of known etiology, fatal pneumonia, and bacteremic pneumonia;
risks—extremes of age; alcoholism; chronic obstructive pulmonary disease (COPD); smoking; nursing home residence;
influenza; injection drug use; obstructed airway; HIV
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| Drug-resistant S. pneumoniae: susceptibility based on level of β-lactam in cerebrospinal fluid (CSF); resistance classified
according to minimum inhibitory concentration (MIC)—susceptible (≤0.06 µg/mL); intermediate (0.1 to 1.0 µg/
mL); resistant (≥2 µg/mL); active β-lactams, ie, MIC ≤2 µg/mL—ceftriaxone; cefotaxime; cefepime; amoxicillin;
amoxicillin clavulanate; caveat—resistance to macrolides, tetracycline, and trimethoprim-sulfamethoxazole increases with
penicillin resistance; other drug resistance—macrolides and doxycycline (reliable for pneumococci susceptible to penicillin,
less reliable for those not susceptible); trimethoprim-sulfamethoxazole (unreliable for treating pneumococcus); fluoroquinolones
(susceptibility rate ≥98%; resistance increasing); pneumococci susceptible to vancomycin and linezolid
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| Legionella: severe disease suggested by—high fever; hyponatremia; elevated lactate dehydrogenase (LDH); altered
mental status; caveat—these findings may be more appropriate as markers for severe pneumonia rather than Legionella
; risk factors—age; smoking; immunocompromise (especially cell- mediated); travel; renal and liver diseases;
diabetes; malignancy; treatment—fluoroquinolone or azithromycin; other drugs used empirically, eg, tetracycline (effective,
but not used for confirmed or severe cases); azithromycin—extended half life reduces duration of treatment
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| Other organisms: H influenzae—causes 3% to 10% of CAP; risk increased by COPD and/or smoking; β-lactamase production
in ≈30% of H influenzae cases; Mycoplasma pneumoniae—common cause of respiratory infections and otitis media
in children and young adults; can cause epidemics in close quarters; patients present with sore throat, nausea, and
vomiting; hemolytic anemia or targetoid rash suggestive of Mycoplasma; treatment doxycycline, macrolide, or fluoroquinolone
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| Risk stratification: designed to avoid unnecessary hospitalization and reduce cost; Pneumonia Patient Outcomes Research
Team (PORT) score—identifies low-risk patients with CAP; stratifies CAP risk into 5 classes; assigns risk via
point system for classes II to IV; mortality <1% for classes I and II; does not take societal factors into account; HIV infection
excluded; pneumonia severity index calculator (available at http://pda.ahrq.gov/ clinic/psi/psicalc.asp) helps physician determine
score; clinical judgement supersedes PORT score; floor vs intensive care unit (ICU)—few criteria; high-risk factors
include fast respiratory rate, low diastolic blood pressure, high blood urea nitrogen (BUN) levels, confused mental
status, hypoxemia, and bilateral multilobar pneumonia on chest x-ray
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| ATS guidelines: factors generating concern for risk of—enteric gram-negative rods (nursing home residence; cardiopulmo
nary disease; multiple comorbidities; recent antibiotic therapy); drug-resistant pneumococcus (age >65 yr; use of
β-lactam antibiotics within previous ≤3 mo; alcoholism; immunosuppression; multiple comorbidities; exposure to child
in day care facility); Pseudomonas aeruginosa infection not usually covered in empiric therapy (structural lung disease;
treatment with >10 mg/day of prednisone; recent use of broad-spectrum antibiotics; malnutrition)
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| ATS guidelines for empiric therapy: group I (outpatients without cardiopulmonary disease or modifying risk
factors)—azithromycin or clarithromycin as first-line therapy, doxycycline as second-line alternative; group II (outpatients
with cardiopulmonary disease and/or other modifying factors)—to kill resistant pneumococci, administer β-
lactam with macrolide, or doxycycline; appropriately high doses of β-lactam kill pneumococci missed by macrolide or
doxycycline; indicated in people who received large doses of fluoroquinolones or who cannot take fluoroquinolones
(amoxicillin plus doxycycline inexpensive and well tolerated, but less convenient than antipneumococcal fluoroquinolone);
group III—inpatients with cardiopulmonary disease and/or modifying factors ( β-lactam antibiotic with macrolide or
doxycycline; IV antipneumococcal fluoroquinolone alone; antipneumococcal fluoroquinolones po work well [patient
must be capable of oral feeding and not consuming anything that binds to fluoroquinolone]); inpatients without cardiopulmonary
disease or modifying factors (guidelines recommend IV azithromycin alone; β-lactam plus doxycycline or antipneumococcal
fluoroquinolone [IV or po] provides better pneumococcal coverage); group IV (in ICU)—not at risk for
P. aeruginosa (cefotaxime or ceftriaxone + azithromycin [IV] or fluoroquinolone po); at risk for P aeruginosa (antipseudomonal
β-lactam plus ciprofloxacin [IV]; high-dose levofloxacin covers atypical infections); severely ill patient colonized
with resistant gram-negative organism (antipseudomonal β-lactam + aminoglycoside + azithromycin [IV] or
antipneumococcal fluoroquinolone [IV])
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| Centers for Medicare and Medicaid Services (CMS) guidelines for inpatients: not in ICU— β-lactam (IV
or IM) + macrolide (IV or po) or doxycycline (IV or po); quinolone alone (IV or PO); in ICU— β-lactam (IV) + macrolide
(IV) or quinolone (IV); patients with β-lactam allergy can receive quinolone (IV) +/- clindamycin (IV); at risk for
pseudomonas—antipseudomonal β-lactam (IV) + antipseudomonal quinolone (IV); antipseudomonal β-lactam (IV) +
aminoglycoside (IV) + antipneumococcal quinolone (IV) or macrolide (IV); patients with β-lactam allergy treated with
aztreonam + antipneumococcal quinolone +/- aminoglycoside
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| Additional points: telithromycin—use limited by risk for fulminant hepatic failure and interaction with statins; duration
of therapy—7 to 10 days for most patients (shorter with azithromycin or high-dose levofloxacin)
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| Oral therapy: reduces cost, hospitalization, and complications; usually initiated at ≤3 days of hospital admission; once
organism identified, use narrow-spectrum agent, eg, amoxicillin; empiric options include macrolide, doxycycline, or antipneumococcal
fluoroquinolone alone or combined with amoxicillin + macrolide or doxycycline
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Educational Objectives
| The goal of this program is to educate the listener about current concepts in the management of latent tuberculosis (TB) and
community-acquired pneumonia (CAP). After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Identify factors that increase risk of TB transmission.
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| 2. Discuss the role of the QuantiFERON-TB and enzyme-linked Immunospot (ELISPOT) blood tests in the diagnosis
of TB.
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| 3. Review current recommendations for managing latent TB.
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| 4. Implement appropriate radiographic and microbiologic techniques for diagnosing pneumonia.
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| 5. Assess current treatment guidelines for managing patients with CAP.
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Discussed on This Program
Adalimumab [Humira]
Amoxicillin (several trade names and preparations)
Amoxicillin and potassium clavulanate (co-amoxiclav) [Augmentin, Augmentin ES-600, Augmentin XR]
Azithromycin [Zithromax, Zmax]
Aztreonam [Azactam]
BCG vaccine [TICE BCG]
Cefepime HCl [Maxipime]
Cefotaxime sodium [Claforan]
Ceftriaxone sodium [Rocephin]
Ciprofloxacin [Ciloxan, Cipro, Cipro I.V., Cipro XR, Proquin XR]
Clarithromycin [Biaxin, Biaxin XL]
Clindamycin (several trade names and preparations)
Doxycycline (several trade names and preparations)
Etanercept [Enbrel]
Ethambutol HCl [Myambutol]
Imipenem-cilastatin [Primaxin I.M., Primaxin I.V.]
Infliximab [Remicade
Isoniazid (isonicotinic acid hydrazide; INH) [Nydrazid]
Levofloxacin [Levaquin, Quixin]
Linezolid [Zyvox]
Meropenem [Merrem IV]
Penicillin (several trade names and preparations)
Piperacillin sodium and tazobactam sodium [Zosyn]
Pneumococcal vaccine, polyvalent [Pneumovax 23]
Pyrazinamide [Zinamide]
Rifabutin [Mycobutin]
Rifampin (rifampicin) [Rifadin, Rimactane]
Rifapentine [Priftin]
Telithromycin [Ketek]
Tetracycline HCl [Sumycin 𣝢’, Sumycin 𣡜’, Sumycin Syrup]
Trimethoprim-sulfamethoxazole (co-trimoxazole; TMP-SMZ) [several trade names and preparations]
Vancomycin [Vancocin, Vancoled]
Suggested Reading
Blumberg HM et al: Update on the treatment of tuberculosis and latent tuberculosis infection. JAMA 294:182, 2005;
Bodi M et al: Antibiotic prescription for community-acquired pneumonia in the intensive care unit: impact of adherence
to Infectious Diseases Society of America guidelines on survival. Clin Infect Dis 41:1709, 2005; British Thoracic Society
Standards of Care Committee: BTS Guidelines for the management of community acquired pneumonia in
adults. Thorax 56:4:IV1-64, 2001; Carratala 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; File TM Jr: Clinical implications
and treatment of multiresistant Streptococcus pneumoniae pneumonia. Clin Microbiol Infect 12 Suppl 3:31, 2006;
Taylor Z et al: Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society,
CDC, and the Infectious Diseases Society of America. MMWR Recomm Rep 54:1161, 2005; Winston LG et al: Penicillin-nonsusceptible
Streptococcus pneumoniae at San Francisco General Hospital. Clin Infect Dis 29:580, 1999.
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. For this issue, the faculty reported
nothing to disclose.
Drs. Jasmer and Winston gave their scientific presentations at the 27th Annual Advances in Infectious Disease: New
Directions for Primary Care, presented April 26 to 28, 2006, in San Francisco, by the University of California, San
Francisco, School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation
in the production of this program.
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