INFECTIOUS DISEASE
From the 27th Annual Infectious Disease and Antibiotic Therapy Conference, sponsored by the Orlando Regional
Healthcare System
| COMMUNITY-ACQUIRED PNEUMONIA —John T. Sinnott, MD, Associate Dean, International Affairs; Clinical Director,
Signature Program in Allergy, Immunology, and Infectious Disease; Cullison Professor of Medicine, Surgery, Obstetrics/Gynecology,
and Mental Health; and Director, Division of Tropical Diseases, Department of Internal Medicine,
University of South Florida College of Medicine, Tampa
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| Pneumococcal pneumonia: typical presentation single hard-shaking chill, pleuritic chest pain, and rust-colored sputum;
typical presentation not often seen; usually prodrome where patient sick ≈1 wk before developing pneumococcal
disease; many of these patients coinfected; first 10 cases in mid-1990s (when quinolones used instead of penicillin) led to
shorter hospital stays and better survival rates; actually treating coinfecting atypical organism (eg, Mycoplasma, Legionella
, Chlamydia); typical pneumonia—illness limited to lung; causes include Haemophilus influenzae with
chronic obstructive pulmonary disease, Klebsiella with alcoholism, and pneumococcus; atypical causative organisms include
influenza virus and pneumoviruses (called respiratory syncytial virus [RSV] in children);
metapneumoviruses—causative organism in ≈5% of pneumonias in adults; isolated in Holland; older mindset about
bacteria still present; traditionally use culture to identify causative organism, but not necessarily true; using DNA probes
and polymerase chain reaction (PCR), different pathogens found; culture not best way to identify pathogen; molecular diagnostics
evolving as new method; at present, identifying pathogen clinical
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| Case 1: woman, 55 yr of age, tennis player, presents with right-sided pleuritic chest pain, rust-colored sputum, and temperature
of 102°F; respiratory rate 18 bpm; vital signs good, blood pressure (BP) 135/80 mm Hg; diagnosis classic pneumococcal
disease; whether other organisms involved depends on history; if patient fine until 1 hr ago, clearly
pneumococcal; if patient gives history of cold for 2 wk with runny nose, consider atypical organisms; if patient gives history
of headache, think Mycoplasma; patients usually treated with quinolone or azithromycin (Zithromax) and followed
as outpatients; issue of which quinolone to use; speaker uses one with least interactions (levofloxacin [eg, Levaquin])
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| Case 2: man, 25 yr of age, medical student, has headache and paroxysmal cough that keeps him awake at night; treated
with amoxicillin for 1 wk but continues to do poorly; nurse obtains x-ray (physician unaware); temperature 99°F, respiratory
rate 16 bpm, and pulse rate 100 beats/min; diagnosis Mycoplasma pneumonia; previously thought more common in
college-aged patients, but PCR discovering more cases in elderly (usually from exposure to sick grandchildren);
immunity—mediated by IgM and lasts only 2 to 3 yr; associated with aplastic anemia and transverse myelitis (may involve
white matter of brain and Mycoplasma encephalitis); associated diseases not common; remember, in central nervous
system (CNS) inflammatory diseases, pathogen found only 20% of time; also associated with Stevens-Johnson
syndrome (which is associated with nonsteroidal anti-inflammatory drugs [NSAIDs], famotidine, penicillin, and other
drugs, but perhaps real cause Mycoplasma, and drugs incidental factor); bullous myringitis—occurs in 5% of adults
and 50% of children; tracheitis—causes cough; diagnosis made if, when patient’s head turned to one side and trachea
pressed, paroxysmal cough induced; only 2 causative pathogens known (Mycoplasma and influenza virus [fever, cough,
and backache common, with headache less frequent]); study by Johnson compared cough preparations with opiates;
cough stopped by blunting J receptors with opiates; avoid NSAIDs (can exacerbate cough) and angiotensin-converting
enzyme inhibitors (ACEIs)
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| Chlamydophila (formerly Chlamydia) pneumoniae: small organisms that exist as elementary bodies; highly inflammatory
agent (symptoms persist even after treatment); need to decrease inflammatory response to organism; persistent
Chlamydophila infection found in some asthma patients; consider C pneumoniae if patient relapses after therapy; initiate
second course of antibiotics (usually quinolone) and anti-inflammatory agents; second course given for 14 days to
ensure all spores killed; multiple cases of Reiter syndrome in nonsexually active patients with C pneumoniae; 25% of
patients with Reiter syndrome disabled within 5 yr
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| Legionella: common on cruise ships; water natural habitat; most people have fair degree of immunity; pneumonia, confusion,
diarrhea, and hyponatremia seen with full-fledged disease (however, 95% of patients have more minor syndrome)
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| Case 3: pregnant woman, 22 yr of age, mother of 2, living on air force base; cough and temperature of 103°F; both children
also have cough; respiratory rate 36 bpm and BP 100/60 mm Hg; white blood cell (WBC) count 2000/mm3 with 35%
bands; diagnosis primary influenza pneumonia; in general, only 0.5% of patients have full-blown pneumonia when first
get influenza; if they do, mortality 50%; primary influenza defined as fever, cough, backache, and temperature >102°F;
abrupt onset; after 7 days, secondary pneumonia (bacterial) appears; possible causative organisms include atypical bacteria,
Staphylococcus, and pneumococcus; complicating agent in avian influenza methicillin-resistant Staphylococcus aureus
(MRSA); in United States, only 50% of staphylococcal infections MRSA (>80% in Asia); mortality due to
pneumonia from bird flu significantly attributable to MRSA; no deaths from bird flu if patient already on statin drug
(anti-inflammatory and pneumoprotective); can use oseltamivir (Tamiflu) and amantadine (Symmetrel) together (different
mechanisms of action)
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| 1918 Spanish influenza: every strain of influenza virus that has affected humans since Spanish flu descendant of this
strain; now at risk of being displaced by H5N1 (avian influenza); difference between 1918 and now—then, world population
1.8 billion, today, 6.6 billion; then, mode of transportation ships and trains, today, jet airplanes; then, time to circle
globe 4 mo, today, 4 days; have vaccines (but none against avian flu) and antiviral drugs; conclusions—in
community-acquired pneumonia, never certain but often dealing with 2 pathogens and need to cover both; pandemic inevitable
and need to prepare
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| NEWER DRUGS FOR TREATING SKIN INFECTIONS —Ellis S. Caplan, MD, Clinical Associate Professor of Medicine,
University of Maryland Medical Center, Baltimore
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| Skin infections: acute wound infections secondary to trauma, bite, surgical site, cellulitis, erysipelas, and diabetic foot;
chronic wound infections (eg, abscesses, ischemic ulcers, venous stasis ulcers, decubitus ulcers)
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| Methicillin-resistant S aureus: recent study of patients who came to emergency department (ED) showed 75% of skin
infections staphylococcal; 57% had MRSA; same organism in all MRSA (called USA 300), identified by pulsed-field
determination (same toxins); MRSA in community different from that in hospital; MRSA in hospital increased significantly;
MRSA worse than methicillin-susceptible S aureus (MSSA); has higher mortality (>20% vs 7%); risk
factors—antibiotic use in past year; long-term care or nursing home residence; exposure to athletic or correctional facilities;
immunocompromised patients; military training; poor hand hygiene; crowded living conditions; antibiotic exposure
(third-generation cephalosporins and fluoroquinolones)
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 | Community-acquired (CA)-MRSA: causes skin or soft-tissue infections, necrotizing pneumonia, necrotizing fasciitis,
rapidly fatal septicemia, endocarditis, and osteomyelitis; produces Panton-Valentine leukocidin (PVL); in one study,
PVL present in 98% of patients with MRSA and in ≈30% with MSSA; patients present with multiple boils, recurrent
boils, and boils associated with high-grade fever; unlike organisms in hospital setting, usually sensitive to clindamcyin,
trimethoprim-sulfamethoxazole (TMP-SMZ), linezolid, minocycline, and tetracycline; 57% of patients who presented
to ED for MRSA put on wrong drug (non-MRSA drug, most often ampicillin); no difference seen between patients put
on wrong drug and patients put on right drug, emphasizing importance of surgical debridement; same drugs available
for MSSA, except ceftriaxone and levofloxacin (do not cover MRSA)
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| Linezolid for antimicrobial therapy
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| Characteristics: first oxazolidinone approved for clinical use; inhibitor of protein synthesis initiation (mechanism different
from other antibiotics); only gram-positive spectrum; cross resistance unlikely; some resistance reported but not yet
major problem; oral bioavailability (first oral drug that can treat MRSA in hospital); ingestion of food has no significant
effect; volume of distribution 40 to 50 L; intravenous (IV), tablets, and oral suspension formulations; distributes
readily into tissues; 31% protein binding; leading side effects (diarrhea and headache) relatively benign
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| Warnings: causes myelosuppression, including anemia, leukopenia, pancytopenia, and thrombocytopenia; complete
blood cell count (CBC) should be monitored weekly; discontinue in patients who develop or have worsening myelosuppression;
not approved for >28 days of therapy; at 14 days of therapy, platelet abnormalities sometimes seen
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| Precautions: lactic acidosis (including fatal) reported, with patients experiencing repeated episodes of nausea and vomiting;
not studied in patients with uncontrolled hypertension; no clinical trials for regimen lasting >28 days; peripheral
and optic neuropathy reported with >28-day regimen
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| Drug interactions: reversible nonselective inhibitor of monoamine oxidase; potential for interaction with adrenergic and
serotonergic agents, particularly those in cough syrups and in over-the-counter preparations; significant pressor response
in those whose dietary intake of tyramine >100 mg (particularly from ripe cheese)
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| Dosing: not necessary to adjust dose for advanced age, sex, mild-to-moderate renal insufficiency, or hepatic insufficiency;
renal insufficiency—30% of oral and IV doses eliminated during 3-hr dialysis, so subsequent dosing required;
accumulation of primary metabolites also observed (clinical significance unknown); IV administration easy but
cannot be mixed with amphotericin, chlorpromazine, diazepam, pentamidine, erythromycin, phenytoin (Dilantin), or
TMP-SMZ; chemical incompatibility with ceftriaxone
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| Daptomycin: IV formulation only; given once daily; gram-positive spectrum; not indicated for treatment of pneumonia
(inactivated by surfactant in lungs); effective in right-sided endocarditis with multiple abscesses; 90% of organisms
sensitive (eg, Enterococcus faecalis [vancomycin-resistant], Enterococcus faecium, Staphylococcus epidermidis,
Staphylococcus haemolyticus, S aureus)
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| Pharmacodynamics: bactericidal, with rapid concentration-dependent killing; originally formulated for bid dosing but
side effects significant; key predictors for efficacy peak exposures and total exposure; 5- or 10-hr postantibiotic effect
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| Possible negative effects: side effects—musculoskeletal; most common adverse effects constipation (6.2%) and IV site
reaction (5.8%); safety profile—similar to comparator (vancomycin); creatine kinase (CK) elevations occur at rates
similar to comparator (2.8% vs 1.8%), with no difference in musculoskeletal side effects; muscle effects—generally
mild (muscle pain and weakness); severe CK elevation >4 times upper limit of normal (ULN); onset typically >7 days;
resolves when drug discontinued; does not cause muscle necrosis; CK elevation lasts for 10 days; observed in <0.2% of
patients given once-daily dose of 4 mg/kg; monitor patients for muscle pain; monitor CK weekly; discontinue if CK
>10 times ULN (uncommon); drug interactions—in clinical trials, no interaction with aztreonam, warfarin, simvastatin,
or probenecid; caution with tobramcyin (no significant interaction at 2 mg/kg, but no data for higher doses); limited
clinical experience with anticoagulation with warfarin (should be watched closely)
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| Dosage: for skin infections, 4 mg/kg (IV infusion over 30 min) once daily; repeat q24h (not necessary to repeat in liver
and renal failure); duration of treatment 7 to 14 days for skin and skin structure infections (longer for more serious infections);
in renal failure, if creatinine clearance <30 mL/min, give q48h; speaker usually gives regular dose for first 3
days, then reduced when patient on dialysis, with another dose given after dialysis; not necessary to adjust dose for elderly,
obese patients, and those with mild-to-moderate hepatic impairment (no inhibition of cytochrome P [CYP]450 system);
not yet tested in children and those with severe hepatic insufficiency
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| Drug therapy for complicated skin infections: gram-negative rods usually involved; include decubitus ulcers and
diabetic foot lesions; causative organisms include Escherichia coli, Klebsiella, Pseudomonas, and Enterobacter; E
coli becoming more resistant; amoxicillin and potassium clavulanate (co-amoxiclav)—limited activity against Enterobacter
and Serratia; not tested against Acinetobacter (ampicillin and sulbactam [Unasyn] effective);
minocycline—effective for Serratia
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| Moxifloxacin: better anaerobic activity than other quinolones; administration—given once daily; consider in mixed infection;
not necessary to adjust for renal disease; cannot be used for urinary tract infections; not necessary to monitor
glucose; dose 400 mg IV or oral; as efficacious as piperacillin/tazobactam; no activity against MRSA; safety
considerations—contraindicated in persons with hypersensitivity to quinolones; anaphylactic reactions seen; causes
minor QT prolongation and should be avoided in patients on Class IA (eg, quinidine, procainamide) or Class III (eg,
amiodarone, sotalol) antiarrhythmic agents; as with all quinolones, can cause CNS side effects
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| Tigecycline: expanded activity against resistant gram-positive and gram-negative organisms (due to minocycline side
chain, which expands its broad spectrum in vitro); active against MRSA, Streptococcus, E faecalis, and E faecium;
efficacy against MRSA and MSSA equivalent to other drugs; excellent gram-positive and anaerobic activity; gram-
negative activity for Klebsiella, Enterobacter, Serratia, and Acinetobacter (not approved for use, but used by
speaker); does not cover Pseudomonas; effective against resistant organisms, including extended-spectrum β-lactamase
(ESBL)-producing ones and E coli; derivative of tetracycline (glycylcycline)
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| Metabolism and dosing: eliminated unchanged, primarily by biliary and fecal route (59%); does not affect activity of
CYP450 isoforms; low potential for drug interactions; not metabolized by and does not inhibit or induce CYP450 ;
33% excreted in urine; dosage—initial dose 100 mg, then 50 mg q12h; not tested in children <18 yr of age; pharmacokinetics
not altered by age, sex, or race; no dosage adjustment necessary in renal impairment; not dialyzable; in
severe hepatic insufficiency, initial dose 100 mg followed by 25 mg q12h; most common side effects in studies nausea
and vomiting (mild; not clinically observed by speaker); equal to vancomycin and aztreonam for skin infections
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| Safety considerations: pregnancy category D; safety and efficacy not established in children and lactating women;
pseudomembranous colitis reported with nearly all antibiotics; concurrent use with oral contraceptives renders oral
contraceptives less effective; causes permanent tooth discoloration; should not be administered simultaneously through
same Y-site with amphotericin B, chlorpromazine, methylprednisolone, and voriconazole (causes precipitation); approved
for skin and abdominal infections
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Suggested Reading
Cunha BA: Oral antibiotic therapy of serious systemic infections. Med Clin North Am 90:1197, 2006; de Roux A et
al: Impact of alcohol abuse in the etiology and severity of community-acquired pneumonia. Chest 129:1219, 2006; Ebell
MH: Outpatient vs. inpatient treatment of community-acquired pneumonia. Am Fam Physician 73:1425, 2006;
Eliopoulos GM: Current and new antimicrobial agents. Am Heart J 147:587, 2004; Ewig S: Against misleading predictions
for severe community-acquired pneumonia. Am J Respir Crit Care Med 175:289; author reply 289, 2007; Goossens
H et al: Community acquired pneumonia in primary care. BMJ 332:1045, 2006; Greig J et al: More on
pneumonia: treatment of MRSA in community acquired pneumonia. BMJ 332:1334, 2006; Grundmann H et al: Emergence
and resurgence of methicillin-resistant Staphylococcus aureus as a public-health threat. Lancet 368:874, 2006; Jetton
L: Therapy for methicillin-resistant Staphylococcus aureus. N Engl J Med 355:2154; author reply 2155, 2006; John
CC et al: Therapies and vaccines for emerging bacterial infections: learning from methicillin-resistant Staphylococcus
aureus. Pediatr Clin North Am 53:699, 2006; Kalorin CM et al: Community associated methicillin resistant Staphylococcus
aureus causing Fournier's gangrene and genital infections. J Urol 177:967, 2007; Khardori N: Antibiotics--past,
present, and future. Med Clin North Am 90:1049, 2006; Lutfiyya MN et al: Diagnosis and treatment of community-acquired
pneumonia. Am Fam Physician 73:442, 2006; Mandell LA et al: Medication options for the treatment of CAP.
Am Fam Physician 74:1479, 2006; Mills GD et al: Severe community acquired pneumonia. BMJ 333:1181, 2006; Moran
GJ et al: Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med
355:666, 2006; Peeters MJ et al: Clinical characteristics of linezolid-resistant Staphylococcus aureus infections. Am J
Med Sci 330:102, 2005; Stralin K et al: Staphylococcus aureus in community-acquired pneumonia. Chest 130:623,
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; Wesson KM et al: Linezolid, quinupristin/
dalfopristin, and daptomycin in dermatology. Dis Mon 50:395, 2004.
Educational Objectives
| The goal of this program is to improve the management of community-acquired pneumonia and skin infections. After
hearing and assimilating this program, the clinician will be better able to:
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| 1. Differentiate pneumonias caused by different organisms.
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| 2. Discuss the differences between the 1918 Spanish influenza pandemic and a present-day pandemic.
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| 3. Review the risk factors for methicillin-resistant Staphylococcus aureus.
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| 4. Prescribe the appropriate antibiotic for skin and skin structure infections.
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| 5. Recognize the adverse events associated with the newer antibiotics.
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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. Caplan is a consultant and a member of the
Speakers’ Bureau for Wyeth Pharmaceuticals.
Acknowledgements
Drs. Sinnott and Caplan were recorded at the 27th Annual Infectious Disease and Antibiotic Therapy Conference, held
December 1-3, 2006, in Orlando, FL, and sponsored by the Orlando (Florida) Regional Healthcare System. The Audio-Digest
Foundation thanks the speakers and the sponsor for their cooperation in the production of this program.
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