BUGS AND DRUGS
| ANTIBIOTIC UPDATE —Paul D. Holtom, MD, Associate Professor of Medicine and Orthopedics, Keck School of
Medicine at the University of Southern California, Los Angeles
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| Improving current antibiotic therapies: goals—decrease adverse effects; decrease frequency of dosing and increase
compliance; overcome problem of resistance; profitability by pharmaceutical companies; challenges—
choosing optimal antibiotic; lack of controlled comparative studies; high cost; reservation of new antibiotics for
certain patients to prevent development of resistance
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| Antibiotic resistance: development caused by overuse of antibiotics in health care; 160 million prescriptions per
year written for outpatient antibiotics (50% given for inappropriate reasons [eg, common cold, viral respiratory
tract infections]); antibiotics in agriculture—>50% of antibiotics in United States used in agriculture for prophylaxis
or growth promotion in poultry and cattle feed; associated with development of resistance
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| Streptococcus pneumoniae: concerns about increase in penicillin-resistant S pneumoniae (overall resistance rate
35%); rate of ceftriaxone (Rocephin) resistance low for respiratory tract infection; resistance rates of fluoroquinolones
(eg, levofloxacin, moxifloxacin) low
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 | Macrolides: high rates of resistance (≈25%) with azithromycin (Zithromax) and clarithromycin (Biaxin); small
amount of data show giving azithromycin or clarithromycin to patient with macrolide-resistant organism may
lead to failure; no good correlation between respiratory tract infections and resistance and failure; telithromycin
(Ketek)—active against S pneumoniae (including resistant organisms); indicated for respiratory tract infections;
given orally once daily; slightly higher cost; adverse events include visual disturbances (eg, blurred vision, diplopia)
primarily in women <40 yr of age; fatal cases of telithromycin-associated hepatitis reported
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| Fluoroquinolones: gatifloxacin (Tequin) withdrawn from market; newer dosing—levofloxacin, 750 mg for 5 days
for mild to severe community-acquired pneumonia; using higher dose for shorter period may decrease development
of resistance and adverse effects; gemifloxacin (Factive)—indicated for respiratory tract infections, community-acquired
pneumonia, acute bacterial exacerbations of chronic bronchitis; high incidence of rash in
women with longer use (5 to 7 days recommended); incidence of rash lower in older men; more active against S
pneumoniae than moxifloxacin or levofloxacin, but no clinical evidence about improved outcomes
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| Staphylococcus aureus: 63% of S aureus infections methicillin-resistant S aureus (MRSA) in intensive care units
(ICU) in 2004; limited resources for treatment; major outbreaks of community-acquired MRSA seen; risk factors
include homelessness or marginal housing, intravenous (IV) drug use, and incarceration; efficacy, dosing, and toxicity
about vancomycin under discussion; IV quinupristin/dalfopristin (Synercid) rarely used because of toxicity;
linezolid—available IV and orally for oxacillin-resistant S aureus (ORSA); active against gram-positive organisms
and somewhat active against anaerobes; not active against gram-negative organisms; indicated for hospital-acquired
pneumonias (eg, S aureus or MRSA), complicated skin and skin structure infections, and diabetic foot infections;
expensive; weak monoamine oxidase (MAO) inhibitor (serotonin syndrome reported, particularly with use of
selective serotonin reuptake inhibitors [SSRIs]); associated with bone marrow suppression (usually with longer duration
of therapy; no strong clinical evidence about benefits of concomitant use of vitamin B6 ); monitor complete
blood count (CBC) weekly; nerve toxicity (eg, peripheral neuropathy, optic neuritis with blindness; effects irreversible)
with use >28 days; mitochondrial toxicity; daptomycin—given IV; unique mechanism of action contributes
to lower rate of resistance; indicated for skin and skin structure infections, MRSA bacteremia, and right-sided
endocarditis; active against S pneumoniae and S aureus, but binds to surfactant in lungs rather than to organisms
(“useless in treatment of pneumonia”); tigecycline—similar to tetracyclic agent; inhibits protein synthesis; bacteriostatic
against most organisms; highly active against gram-positive organisms (including MRSA); active against
gram-negative organisms (including multidrug-resistant Acinetobacter); activity against Pseudomonas aeruginosa
limited; active against anaerobes; given IV; approved for complicated skin and skin structure infections and complicated
intra-abdominal infections; ongoing trials for drug-resistant organisms and hospital- and community-acquired
pneumonias; dalbavancin—related to vancomycin; inhibits cell wall synthesis; active against organisms
sensitive to vancomycin and some vancomycin-resistant organisms; infusion can be given once weekly for 14 days;
well-tolerated and highly effective
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| Resistance in the future: increasing; MRSA epidemic continuing; community-associated MRSA increasing
(more virulent and resistant than current S aureus); resistance of S pneumoniae and gram-negative organisms increasing;
fluoroquinolone resistance in Escherichia coli; development of new antibiotics—challenges include small
number of new drugs, IV only, and active primarily against MRSA; no drugs in immediate pipeline with activity
against multidrug-resistant gram-negative organisms; new treatment strategies—higher doses, shorter courses; few
data about course of antibiotics currently used; optimal doses questionable; emergence of new pathogens—recent
pathogens include severe acute respiratory syndrome (SARS), West Nile virus, and H5N1 avian influenza virus
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| INFECTIONS IN THE ELDERLY —Dean C. Norman, MD, Professor of Medicine and Geriatric Medicine, David
Geffen School of Medicine at the University of California, Los Angeles, and Chief of Staff, Veterans Affairs Healthcare
Systems, Los Angeles
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| Settings and infections: community—respiratory tract infections; pneumonia; urinary tract infections (UTI); intra-
abdominal infections; endocarditis, osteomyelitis, and meningitis less common; acute care facility—aspiration
pneumonia; UTI related to catheter use; septic phlebitis; pressure ulcer; syndromes confused with infection (eg, fever
caused by drugs); long-term care facility—epidemics of respiratory tract infections (including influenza, respiratory
syncytial virus, pneumonia); UTI; soft tissue infections; gastroenteritis; screen for tuberculosis; incidence of
infection in nursing homes, 1 infection per resident per year
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| Infections in young patients compared to elderly patients: community-acquired pneumonia—caused by few
pathogens in young patients; many pathogens can be responsible in elderly patients; UTI—in young adults, usually
caused by E coli and affects mostly women; in elderly patients, multiple pathogens possible and more infections seen
in men
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| Factors for high morbidity and mortality: low reserve capacity; changes in host resistance; impact of comorbidities;
greater hospitalization rates and number of procedures in elderly; greater medication use; delays in diagnosis
and treatment; slower response to antimicrobial therapy
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| Changes that affect defenses to infection: thinning of skin; diminished cough reflex; genitourinary (GU) tract
changes; comorbidities; polypharmacy; do not use long-acting sedative hypnotic drugs; functional impairment (eg,
loss of mobility); implantable devices; T cell function—proliferation, cytotoxicity, interleukin 2 production, delayed-type
hypersensitivity reactions, and naive cells decrease with increased age; with aging, response to T-cell–
dependent antigens (ie, reduced antibody response to influenza and tetanus vaccines) decreases; B cell function,
macrophage function, neutrophil function, complement system, and natural killer cell function not significantly affected
by aging
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| Clinical aspects of infection: delirium; lethargy; anorexia; falls; bacteremia—patients may be afebrile; tachypnea;
confusion; pneumonia—patients may be afebrile with no chest pain; fever—older individuals at least 1ºF
colder after age 75 yr (ie, body temperature may be elevated from baseline with significant fever, but still remain
<101ºF); fever defined as persistent elevation of body temperature of ≥2ºF; oral temperature ≥99ºF on repeated
measurement; infections can be typical, but 33% of time classic presentations nonspecific or absent; fever and leukocytosis
(particularly left shift) highly specific for infection in older patients; fever not sensitive for infection
(20%-30% of time patients do not have fever)
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| Antibiotics: consider renal clearance; divalent cations markedly reduce absorption of quinolones (“if you’re using
antacids with quinolones, you’re not doing much for your patient”); toxicity—nephrotoxicity and ototoxicity with
aminoglycosides; drug fever with trimethoprim–sulfamethoxazole; hepatotoxicity with isonicotinic acid hydrazide
(INH); CNS toxicity with amantadine or rimantadine; toxicity with β-lactam drugs; seizures with improper dosing
of carbapenems; thrombocytopenia and anemia with linezolid; impact of Clostridium difficile with clindamycin
(particularly in nursing homes); increased hyper- and hypoglycemia reported in nursing homes with gatifloxacin
(no longer used in diabetic patients)
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| Aminoglycosides: use judiciously for shortest time; replace with less toxic drug; single daily dosing more economic,
but does not improve efficacy or reduce toxicity; not recommended for routine use, but may be useful in patients in
septic shock, in ICU, or with multiple drug-resistant pathogens
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| Pneumonia: ≈900,000 community-acquired pneumonia cases in elderly per year (40% hospitalized); bacteremia
more likely; nosocomial pneumonia rates and mortality higher in elderly; length of stay in hospital longer; study
concluded that ≈50% of elderly hospitalized for community-acquired pneumonia die within 1 yr; pneumonia leading
cause of infection requiring transfer to hospital from long-term care facility; pathogens—in community, 40%
to 60% of cases S pneumoniae; mixed infections, gram-negative bacilli, and Haemophilus influenza possible; in
long-term care facility, mixed infections and gram-negative bacilli (tend to be sensitive organisms [eg, Klebsiella])
more likely; in hospital, mixed infections, S pneumoniae, gram-negative bacilli, anaerobes, and MRSA common;
study of patients in ICU on ventilator found S pneumoniae associated with chronic obstructive pulmonary disease
(COPD), Legionella more likely in community-acquired pneumonia in older populations, and gram-negative bacilli
associated with diabetes
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| Penicillin resistance: in 1995 to 1998, penicillin resistance increased in white and black individuals; penicillin and
ampicillin ineffective empiric therapy for pneumonia
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| Laboratory studies: blood cultures; expectorated sputum; O2 saturation; CBC; renal function testing; in some
geographic locations (eg, Philadelphia, London, Pittsburgh) routine Legionella antigen testing
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| Supportive therapy: respiratory support; nutritional support; fluid and electrolyte management; treat underlying
diseases; avoid antipyretics, narcotics, and sedatives; encouraging early mobility shown to reduce length of hospital
stay by 1.1 days; respiratory fluoroquinolone first-line therapy for patients >50 yr of age (particularly with history
of antimicrobial therapy; macrolide or doxycycline can be used if patient not on previous antibiotics); IV
therapy in hospital; use broader spectrum antimicrobial therapy in patients in ICU with hospital-acquired pneumonia;
in long-term care facilities, discuss with patient and patient’s family needs and wishes (eg, transfer to hospital
for treatment in case of infection); patients in nursing homes that do not allow parenteral therapy can be treated
with amoxicillin–clavulanate or respiratory fluoroquinolones (eg, ceftriaxone [can be given once daily]; effective);
oral linezolid can be used for MRSA; O2 assessment recommended, but effects not significant; antibiotics used
within 4 to 8 hr shown to lower 30-day mortality; blood cultures before antimicrobial therapy shown to lower mortality
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| Prevention: influenza vaccine (individuals >50 yr of age should be vaccinated); revaccination for pneumococcal
vaccine—not as efficacious as influenza vaccine, but may be cost-effective; give second dose of vaccine to patients
who received vaccine >5 yr ago and <65 yr of age at time of vaccination; may be considered after 6 yr in
high-risk patients; no improvement with multiple vaccinations
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| MRSA shift: infections seen in pediatrics and younger adults; infections seen in older patients due to transfer to
acute care hospitals and community; community-associated MRSA infections—usually involve skin and soft tissues;
patients often present saying, “I had a spider bite and it became infected”; resistance to fluoroquinolones and
oxacillin; retention of sensitivity with trimethoprim–sulfamethoxazole, doxycycline, and rifampin; infections
mostly in younger individuals; outbreaks seen in daycare centers, American Indian communities, military, gay populations,
and prisoners; recommendations—if community-associated MRSA not suspected, use cephalexin (Keflex);
if suspected, use trimethoprim–sulfamethoxazole (2 tablets of double-strength po bid; rifampin may be
added); community-associated MRSA likely to become more common in older patients within 1 to 2 yr
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Educational Objectives
| The goal of this program is to educate the listener about antibiotic therapy and infections in the elderly. After hearing
and assimilating this program, the participant will be better able to:
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| 1. Discuss the problem of antibiotic resistance.
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| 2. Select appropriate antibiotics based on efficacy and side-effect profiles.
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| 3. Identify infection in elderly patients.
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| 4. Choose effective therapy for patients with infection.
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| 5. Counsel elderly patients and family members about infection and prevention.
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Discussed on This Program
Amantadine HCl [Symmetrel]
Amoxicillin and potassium clavulanate (co-amoxiclav) [Augmentin, Augmentin ES-600, Augmentin XR]
Ampicillin [Principen]
Azithromycin [Zithromax, Zmax]
Ceftriaxone sodium [Rocephin]
Cephalexin [Biocef, Keflex]
Clarithromycin [Biaxin, Biaxin XL]
Clindamycin [several trade names]
Dalbavancin
Daptomycin [Cubicin]
Doxycycline [several trade names]
Gatifloxacin [Tequin, Zymar]
Gemifloxacin mesylate [Factive]
Influenza virus vaccine [Fluarix, FluMist, Fluvirin, Fluzone]
Isoniazid (isonicotinic acid hydrazide; INH) [Nydrazid]
Levofloxacin [Levaquin, Quixin]
Linezolid [Zyvox]
Moxifloxacin HCl [Avelox, Avelox I.V., Vigamox]
Penicillin G [Bicillin C-R, Bicillin C-R 900/300, Bicillin L-A, Permapen, Pfizerpen, Wycillin]
Penicillin V (phenoxymethyl penicillin) [Penicillin VK, Veetids]
Pneumococcal 7-valent conjugate vaccine (diphtheria CRM197 protein) [Prevnar]
Pneumococcal vaccine, polyvalent [Pneumovax 23]
Quinupristin/dalfopristin [Synercid]
Rifampin (rifampicin) [Rifadin, Rimactane]
Rimantadine HCl [Flumadine]
Telithromycin [Ketek]
Tigecycline [Tygacil]
Trimethoprim–sulfamethoxazole (co-trimoxazole; TMP–SMZ) [several trade names]
Vancomycin [Vancocin, Vancoled]
Suggested Reading
Buckwalter M et al: Population pharmacokinetic analysis of dalbavancin, a novel lipoglycopeptide. J Clin Pharmacol
45:1279, 2005; El-Solh AA et al: Etiology of severe pneumonia in the very elderly. Am J Respir Crit Care
Med 163:645, 2001; Fowler VG Jr et al: Daptomycin versus standard therapy for bacteremia and endocarditis
caused by Staphylococcus aureus. N Engl J Med 355:653, 2006; Fridkin SK et al: Methicillin-resistant Staphylococcus
aureus disease in three communities. N Engl J Med 352:1436, 2005; Guay DR: Amantadine and rimantadine
prophylaxis of influenza A in nursing homes. A tolerability perspective. Drugs Aging 5:8, 1994; Jauregui LE et al:
Randomized, double-blind comparison of once-weekly dalbavancin versus twice-daily linezolid therapy for the treatment
of complicated skin and skin structure infections. Clin Infect Dis 41:1407, 2005; Kaplan V et al: Pneumonia:
still the old man's friend? Arch Intern Med 163:317, 2003; Meehan TP et al: Quality of care, process, and outcomes
in elderly patients with pneumonia. JAMA 278:2080, 1997; Mullins CD et al: Cost-effectiveness analysis of
linezolid compared with vancomycin for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus
aureus. Clin Ther 28:1184, 2006; Mundy LM et al: Early mobilization of patients hospitalized with
community-acquired pneumonia. Chest 124:883, 2003; Mylotte JM: Nursing home-acquired pneumonia: update on
treatment options. Drugs Aging 23:377, 2006; Raad I et al: Efficacy and safety of weekly dalbavancin therapy for
catheter-related bloodstream infection caused by gram-positive pathogens. Clin Infect Dis 40:374, 2005; Van Wart
SA et al: Population pharmacokinetics of tigecycline in patients with complicated intra-abdominal or skin and skin
structure infections. Antimicrob Agents Chemother 50:3701, 2006; Wenisch C et al: A holistic approach to MRSA
eradication in critically ill patients with MRSA pneumonia. Infection 34:148, 2006; Wenzel RP et al: Managing
antibiotic resistance. N Engl J Med 343:1961, 2000; Wise R et al: Antimicrobial resistance. Is a major threat to public
health. BMJ 317:609, 1998.
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. The following
has been disclosed: Dr. Holtom has received honoraria and/or research support and/or is on the Speakers’ Bureaus for
Cubist Pharmaceuticals Inc., Merck & Co. Inc., Ortho-McNeil Pharmaceutical, Pfizer, and Wyeth.
Dr. Holtom spoke in Los Angeles, CA, on October 21, 2006, at Current Issues in Infectious Disease, presented by the
Keck School of Medicine at the University of Southern California, Los Angeles. Dr. Norman was recorded in Beverly
Hills, CA, at the 33rd UCLA Family Practice Refresher Course, presented June 5-9, 2006, by the David Geffen
School of Medicine at the University of California, Los Angeles. The Audio-Digest Foundation thanks the speakers
and the sponsors for their cooperation in the production of this program.
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