MALICIOUS MICROBES: GOOD NEWS/BAD NEWS
| UPPER RESPIRATORY TRACT INFECTIONS —George C. Mejicano, MD, Associate Professor of Medicine and Assistant
Dean for Continuing Medical Education, University of Wisconsin Medical School, Madison
|
Sinusitis
| Acute sinusitis: secondary infection of paranasal sinuses; viral respiratory tract infection (RTI) results in abscess, potentially
leading to bacterial superinfection that must be treated; common cold—viral rhinosinusitis; 87% of patients with
common colds have evidence of sinus cavity disease on computed tomography (CT); up to 2 in 100 progress to bacterial
infection; maxillary sinus most often affected
|
| Normal sinus cycle: ostium open; secreted mucus normal in amount and composition and stays fluid (very important);
mucus contains secretory IgA that helps prevent infection; secretions absorb soluble pollutants and particulate matter;
bacteria swept up by mucociliary escalator; flow prevents local mucosal damage
|
| Sinus cycle leading to sinusitis: ostium closed; mucosal congestion mostly due to viral rhinitis; anatomic obstruction
also blocks flow and drainage; secretions stagnate and thicken; pH changes lead to gas metabolism changes, damaging
mucosa and ciliary escalator; host milieu creates culture medium for bacterial superinfection; retained secretions cause
more tissue inflammation in cavity; further thickening develops into acute bacterial sinus infection
|
| Predisposing factors: impaired mucociliary function caused by—viral RTI; cold dry air; chemicals (particularly in
cigarette smoke) and drugs; cystic fibrosis; congenital ciliary dysmotility; obstruction of sinus ostia—deviated septum;
allergic rhinitis; food allergies; rhinitis medicamentosa (oxymetazoline [Afrin] abuse; use of topical decongestants for >3
days causes rebound effect); increased risk for microbial invasion—immune defects (eg, antibody deficiencies, AIDS,
diabetes, Wegener’s granulomatosis); iatrogenic factors (eg, intubation); patient factors (eg, intranasal cocaine use)
|
| Organisms: viruses—rhinovirus, influenza, parainfluenza; bacteria—predominantly Streptococcus pneumoniae, Haemophilus
influenzae, Moraxella catarrhalis (cause three fourths of bacterial infections); use antibiotic that treats all 3
organisms; antibacterial resistance (various mechanisms); fungi—allergic fungal sinusitis may play role; nosocomial
infections—eg, gram-negative organisms; occasionally Staphylococcus aureus
|
| Clinical diagnosis: study data show sedimentation rate and C-reactive protein (CRP) provide good sensitivity and reasonable
specificity; evidence-based predictive features (Williams et al, 1993)—maxillary toothache best indicator; purulent
secretion by examination or history, poor response to decongestants, and abnormal sinus transillumination also
helpful; headache, eye pain, and sinus congestion not helpful; number of predictors determines probability of disease (eg,
with 3 predictors, 63% chance of having sinusitis); 1997 Canadian Sinusitis Symposium—if <2 clinical features
present, sinusitis ruled out; if 4 or 5 features present, sinusitis present (use antibiotics); if 2 to 3 features present, consider
x-rays; sinus transilluminaton—good predictive test developed by Gwaltney; in darkened room, place very bright light
(eg, Welch-Allyn) on infraorbital rim and look at roof of mouth; if sinus normal, unlikely to have secretions; if opacification
seen, secretions present 100% of time; “double sickening” sign—worsening symptoms after period of initial improvement;
bacterial infection set up by preceding viral infection; 4 best signs and symptoms—endorsed by American
College of Physicians (ACP), American Academy of Family Physicians (AAFP), Infectious Diseases Society of American
(IDSA), and Centers for Disease Control and Prevention (CDC); purulent nasal discharge, maxillary tooth pain or facial
pain (particularly unilateral), tenderness along maxillary sinus, double sickening effect; radiology—single view sufficient,
but correlation only 50%; air-fluid level more reliable than thickening; x-rays rarely needed; CT imaging—cheaper,
faster; problem that scans may be too sensitive, ie, patient asymptomatic but fluid seen in sinuses; CT indicated for surgical
candidates, when extensions or complications present, or when patient unresponsive to standard therapy; cultures—
worthless due to contamination; endoscopic collection “decent,” but contamination present; sinus aspiration—gold standard;
indications include septic or immunocompromised patient, nosocomial infection, poor response to therapy, presence
of 1 of 5 complications of bacterial sinusitis (ie, meningitis, brain abscess, periorbital cellulitis, osteomyelitits, cavernous sinus
thrombosis)
|
| Management: rule out dental source and complications; surgical management to correct anatomic abnormalities (eg, ostial
blockage) and promote drainage; consider hospitalization for acutely ill or immunocompromised patient; caution required
with frontal sinus because of thinness of cribriform plate and possibility of brain abscess; Potts puffy tumor (subperiosteal
abscess of frontal bone) may be medical emergency
|
| Treatment: steam and saline prevent nasal crusting and liquefy secretions; decongestants (topical and systemic) increase
ostial diameter; topical agents have rebound effect; pseudoephedrine causes vasoconstriction (use with caution in pregnant
women); topical steroids have role if allergic component present; mucoevacuants (eg, guaifenesin); antibiotics—
placebo effect >40%; simple drugs work, especially β-lactams; amoxicillin still first choice; antibiotics reduce clinical
failures by half; amoxicillin and sulfonamides equal to other drugs; recommended duration of therapy 10 to 14 days; evidence
that 3 days may be sufficient; ACP, CDC, IDSA, AAFP principles—most are viral; difficult to distinguish bacterial
from viral infection; radiography not recommended for routine cases; usually resolves by itself; 2005 Wisconsin
Antibiotics Resistance Network recommendations—1) for mild symptoms, just watch; 2) for mild disease not improving
and no recent history of antibiotic use, prescribe amoxicillin or doxycycline, macrolide if evidence of resistance; 3)
for patient with severe disease or recent antibiotic use, prescribe amoxicillin–clavulanate, cefuroxime, or similar cephalosporin;
if patient allergic to penicillin, use fluoroquinolone or telithromycin; for most drugs, treat 10 days, 5 days for
telithromycin; chronic sinusitis—many infections or symptoms >12 wk; frequently not infectious disease (think allergy)
|
Pharyngitis
| Causes: group A streptococci and group C streptococci cause 45% to 50%; also metapneumovirus and mycoplasma; difficult
to recognize solely clinically, requires tests; hints— cough, myalgias (influenza); conjunctivitis (adenovirus); enlarged
retrocervical nodes, splenomegaly (Epstein-Barr virus); rash, lymphadenopathy in armpits (primary HIV);
vesicles, ulcers (herpes simplex); pseudomembrane (diphtheria); hoarseness (viral laryngitis)
|
| Streptococcal pharyngitis: typical features—acute onset; pharyngeal erythema, exudates, anterior cervical nodes; features
not diagnostic; scarlet fever—rash characteristic in group A; 50% of cases in school-age children due to group A;
10% of cases in adults >30 yr of age; “pinpoint” sandpapery rash; desquamation of hands and soles; diagnosis—throat
culture gold standard; rapid antigen test very good, but if negative, get culture; if either positive, treat; complications—
acute rheumatic fever, poststreptococcal glomerulonephritis, scarlet fever, abscess, epiglottitis; management—treat if
suspicion high, but confirm case; treatment within 9 days of symptom onset can prevent acute rheumatic fever; symptoms
improve in 3 days, even when not treated, slightly quicker when treated; patients noninfectious within 24 hr of starting
antibiotics; treatment—penicillin (500 mg bid in adults; 250 mg bid in children); benzathine penicillin injection for patients
who cannot tolerate pills; erythromycin in penicillin allergy; once-daily therapy (amoxicillin 750 mg) being
pushed; follow-up —work up contacts only if they have history of rheumatic fever or have persistent recurrent pharyngitis;
follow-up cultures for patients only if symptoms persist, history of rheumatic fever or outbreak situation; recurrent
group A streptococcus—due to β-lactamases produced by other organisms; use clindamycin or amoxicillin–clavulanate
|
| EMERGING VIRAL ILLNESSES: PREVENTION AND MANAGEMENT —R. Jeffery Kohlwes, MD, MPH, Associate
Professor of Medicine, University of California, San Francisco, School of Medicine, and Director, San Francisco Veterans
Affairs Medical Center Primary Care in Internal Medicine Program
|
West Nile Virus
| Cell cycle: Culex mosquito bites crows, leading to hyperinfection syndrome (West Nile [WN] virus concentrated in mosquito
and becomes increasingly infectious to humans, horses, and other hosts)
|
| Natural history: mosquito bite injects salivary virus into bloodstream; person develops viremia; after 3 to 14 days incubation,
symptoms manifest; attack rate 20%, ie, 80% of people asymptomatic; 20% develop WN fever, nonspecific viral syndrome
not associated with severe sequelae; <1% develop severe form (neuroinvasive); <50% seek care; lasts 3 to 10
days, then disappears; URI symptoms rare; flu-like syndrome (myalgias, fever); chronic fatigue syndrome now being
seen in patients initially infected in New York
|
| Diagnosis: requires high level of suspicion; neuroinvasive disease—changes in mental status, focal weakness; 60% of
patients present with meningoencephalitis; basilar inflammatory process with leakage of gadolinium on magnetic resonance
imaging (MRI), consistent with edema; patients older, or immunocompromised, or have other medical problems
(eg, cancer, HIV); within 48 hr of bite, develop fever, headache, myalgias; worsening of symptoms (eg, flaccid paralysis,
Parkinsonian tremor or gait, bulbar palsy); younger patients present with aseptic meningitis; represent 40% of patients
with neuroinvasive WN; have better prognosis; lumbar puncture reveals cerebrospinal fluid (CSF) pleocytosis (nonspecific
finding); normal glucose, elevated protein, lymphocytic predom-inance, but some reports of neutrophilic predominance;
supportive care based on severity; neurologically altered patients and those unable to care for themselves require
hospitalization
|
| Who gets tested? someone with neurologic findings or febrile illness >7 days in endemic area; reportable disease; tracking
in California assesses efficacy of control measures; test—IgM antibody-capture enzyme-linked immunosorbent assay
(ELISA); sensitivity on CSF sample lower, so also send polymerase chain reaction (PCR) test; people with antibodies to
St. Louis encephalitis or dengue fever may have false-positive results on WN test; sensitivity has improved, specificity
“terrific”; refer to CDC’s WN city and states website
|
| Treatment: supportive care; trials of high-dose ribavirin and interferon have not shown improved neurologic outcome
|
| Prevention: standing water problematic; change water frequently in birdbaths and introduce bacteria that eat mosquito larvae;
repair ripped screens; N, N-diethyl-m-toluamide (DEET)-containing insect repellants (10%-50% in adults, 10%-
20% in children); for healthy children, WN virus similar to chickenpox; better to get it when young (lifelong immunity)
|
Avian Influenza
| Types: C—not worrisome; B—causes less severe illness; A—(bird flu) worrisome; causes most potentially severe illness,
epidemics, and pandemics; changes yearly, reinfecting population
|
| Ongoing infection cycle: 2 influenza surface proteins—neuraminidase (N) cleaves neuramic acid (major component of
respiratory mucin) and allows release of virus to respiratory tree; hemagglutinin (H) binds to sialic acid residues on respiratory
lining, allowing opsonization of virus into cell; protein changes enable virus to change yearly
|
| Three major influenza subtypes infecting humans: H1N1, H1N2, H3N2; (in birds, 16 variations of H and 9 of N);
bird flu recognized as H5N1; humans antigenically naive to H5 (acts as new infection); antigenic drift—causes minor
epidemics from year to year; minor changes in viral ribonucleic acid (RNA) cause minor changes to hemagglutinin; antigenic
shift—causes severe pandemics every 10 to 40 yr; human influenza virus reassorts with duck, swine, ferret
influenza virus, causing novel changes in H and N; periodicity—novel virus in human population causes pandemic; antibodies
rise slowly; this virus remains dominant H and N type, with some antigenic drift; after 10 to 40 yr, another pandemic
occurs due to antigenic shift
|
| Statistics: complication rate—people >65 yr of age develop secondary bacterial pneumonia and may die; typically get
sicker, then better, then get worse at 7 to 10 days; develop Haemophilus influenzae or pneumococcal pneumonia;
speaker’s projection—if patients got H5N1, pandemic would develop; based on 25% attack rate and 5% mortality rate,
125 deaths per 10,000 population; occurs at all ages; infects lungs, causing necrotizing, hemorrhagic, (primarily viral)
pneumonia
|
| Ability to move from birds to humans: risk factors—antigenically naive population; mixing of migratory and domestic
fowl; poverty; limited public health resources; ducks asymptomatic carriers; high-risk factors—exposure to ill poultry;
handling fighting roosters; infected ducks; playing with poultry; eating undercooked poultry
|
| Clinical findings: severe manifestation hemorrhagic necrotizing pneumonia; incubation 2 to 8 days; high fever; diarrhea
common and virus in stool; URI symptoms rare; unable to get enough virus on nasopharyngeal swab (use oropharyngeal);
encephalitis reported; high mortality in young; lobar pneumonia to acute respiratory distress syndrome
|
| Diagnosis: viral culture or PCR; oropharyngeal swab; Rapid flu tests poor; suspect in—travelers returning from endemic
countries with undiagnosed febrile illness and their contacts; people with undiagnosed febrile illness who handle poultry
or other birds from endemic area
|
| Medical response: hospitalization and isolation prevents up to 50% of secondary cases; contact tracing, treatment, and
isolation; medical therapy—amantadine and rimantadine do not work; no reason to think zanamivir will not work; oral oseltamivir
treatment of choice; requires early treatment (<48 hr); also works prophylactically
|
Educational Objectives
| The purpose of this program is to provide the listener with information on the nature and management of infectious diseases.
After hearing and assimilating this program, the clinician will be better able to:
|
 | 1. List the predisposing conditions leading to sinusitis.
|
| 2. Review the clinical diagnosis and treatment of sinusitis.
|
| 3. Discuss the causes and treatment of pharyngitis.
|
| 4. Describe the infection cycle of West Nile virus.
|
| 5. Summarize the clinical findings and treatment of avian influenza.
|
Discussed on This Program
Amantadine HCl [Symmetrel]
Amoxicillin [Amoxil, Amoxil Pediatric Drops, Trimox, Trimox Pediatric Drops ]
Amoxicillin and potassium clavulanate (co-amoxiclav) [Augmentin, Augmentin ES-600, Augmentin XR]
Cefuroxime [Ceftin, Kefurox, Zinacef]
Clindamycin [Cleocin, Cleocin Pediatric Cleocin Phosphate, Cleocin T, Clindagel, ClindaMax, ClindaMax Lotion,
Clindesse, Clindets]
Doxycycline (several trade names)
Erythromycin (several trade names and formulations)
Guaifenesin (several trade names)
Interferon alfa-2b recombinant and ribavirin combination [Rebetron]
Oseltamivir phosphate [Tamiflu]
Oxymetazoline HCl (several trade names)
Penicillin G [Bicillin C-R, Bicillin C-R 900/300, Bicillin L-A, Permapen, Pfizerpen, Wycillin]
Penicillin V (phenoxymethyl penicillin)
Penicillin VK, Veetids]
Pseudoephedrine HCl (d-isoephedrine HCl) [several trade names]
Rimantadine HCl [Flumadine]
Telithromycin [Ketek]
Zanamivir [Relenza]
Suggested Reading
Banks DJ et al: The fundamental contribution of phages to GAS evolution, genome diversification and strain emergence.
Trends Microbiol 10:515, 2002; Batzloff MR et al: Vaccine development for group A streptococcus infections and associated
disease. Curr Drug Targets 5:57, 2004; Beasley DW: Recent advances in the molecular biology of west nile virus.
Curr Mol Med 5:835, 2005; Brook I et al: Microbiology of acute exacerbation of chronic sinusitis. Ann Otol Rhinol
Laryngol 114:573, 2005; Brook I, Hausfeld JN: Recovery of interfering bacteria in the nasopharynx following antimicrobial
therapy of acute maxillary sinusitis with telithromycin or amoxicillin-clavulanate. Antimicrob Agents Chemother
49:4793, 2005; Chan-Tack KM, Forrest GL: West nile virus meningoencephalitis and acute flaccid paralysis after infliximab
treatment. J Rheumatol 33:191, 2006; Chatterjee P: Hong Kong battens down the hatches. Lancet 366:2073,
2005; Dubin MG et al: Concordance of middle meatal swab and maxillary sinus aspirate in acute and chronic sinusitis: a
meta-analysis. Am J Rhinol 19:462, 2005; Esposito S et al: Aetiology of acute pharyngitis: the role of atypical bacteria. J
Med Microbiol 53:645, 2004; Jin XW, Mossad SB: Avian influenza: an emerging pandemic threat. Cleve Clin J Med
72:1129, 2005; Louie JK et al: Characterization of viral agents causing acute respiratory infection in a San Francisco University
Medical Center Clinic during the influenza season. Clin Infect Dis 15:822, 2005; Mossad SB: Influenza 2005-
2006: vaccine supplies adequate, but bird flu looms. Cleve Clin J Med 72:1041, 2005; Poole et al: A trial of high-dose,
short-course levofloxacin for the treatment of acute bacterial sinusitis. Otolaryngol Head Neck Surg 134:10, 2006; Ramanathan
MP et al: Expression and evolutionary analysis of West Nile virus (Merion strain). J Neurovirol 11:544,
2005; Russell CJ, Webster RG: The genesis of a pandemic influenza virus. Cell 123:368, 2005; Sibbald B: Pandemic
preparedness: begin at the source. CMAJ 173:1309, 2005;Trends Microbiol 10:515, 2002; Tyler KL: West nile virus infection.
Rev Neurol Dis 1:83, 2004; Webster RG et al: The spread of the H5N1 bird flu epidemic in Asia in 2004. Arch
Virol Suppl 19:117, 2005; Williams KN, Bishai WR: Clarithromycin extended-release in community-acquired respiratory
tract infections. Expert Opin Pharmacother 6:2867, 2005; Wright ED, Frenkiel SL: Infectious adult rhinosinusitis:
etiology, diagnosis, and management principles. J Otolaryngol 34:S7, 200.
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, Dr. Mejicano
has disclosed that he is a consultant for Merck Frosst.
Dr. Mejicano addressed the 2005 Update in Infectious Diseases, held December 8-10, 2005, in Madison, WI, and
sponsored by the University of Wisconsin Medical School. Dr. Kohlwes addressed the 20th Annual Primary Care
Medicine: Principles and Practice, held October 19-21, 2005, in San Francisco, CA, sponsored by the University of
California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks the speakers, University of Wisconsin
Medical School, and the University of California, San Francisco, School of Medicine, for their cooperation in
the production of this program.
|
