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Geriatric

Pharmacy Review Module 10: Pharmacotherapy for Infec<ous Diseases

Accreditation Information

ASCP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This home study web activity has been assigned 4 credit hours. ACPE UPN: 0203-0000-10-093-H01-P Release Date: 6/14/2010 Expiration Date: 6/15/2013

To receive continuing education credit for this course, participants must complete an on-line evaluation form and pass the online assessment with a score of 70% or better. If you do not receive a minimum score of 70% or better on the assessment, you are permitted 4 retakes. After passing the assessment, you can print and track your continuing education statements of credit online.

Geriatric Pharmacy Review courses have not yet been approved for Florida consultant pharmacy continuing education.

Copyright 2011 American Society of Consultant Pharmacists

Content Expert

Current Content Experts: Michael A. Dietrich, PharmD, BCPS Associate Professor of Pharmacy Practice Midwestern University College of Pharmacy David P. Elliot, PharmD Department of Clinical Pharmacy West Virginia University

Legacy Content Expert: David Guay, PharmD, FCP, FCCP, FASCP College of Pharmacy University of Minnesota

Copyright 2011 American Society of Consultant Pharmacists

Faculty Disclosures

Michael Dietrich discloses the following relationship: Speaker Bureau: Cubist, Wyeth, OMP, Elan, Schering Grant: Cubist

David P. Elliot, PharmD has no relevant financial relationships to disclose.

David Guay discloses the following relationships: Speaker Bureau: Boehringer Ingelheim Consultant & Writer: Abbott Labs

Copyright 2011 American Society of Consultant Pharmacists

Pneumonia in the Elderly


Learning Objectives:

By the end of this Review Concept you should be able to: State the prevalence and mortality associated with nosocomial pneumonia. Describe the pathogens responsible for both community acquired and nosocomial pneumonia. List risk factors for pneumonia in the elderly. Describe common signs and symptoms presented by patients with pneumonia. Cite lab tests and lab values that assist in the differential diagnosis of pneumonia. Describe pharmacologic treatment strategies for stable and unstable patients with pneumonia. Describe prophylactic treatment for patients at high risk for pneumonia

Describe indications, administration, effectiveness, and allergic reactions to vaccines used to immunize patients against influenza a and B, and pneumococcus.

Copyright 2011 American Society of Consultant Pharmacists

Pneumonia: Prevalence and Mortality


Prevalence 15% of acute care facility infections 10% of long-term care facility infections Mortality The most lethal nosocomial infection Infection of the lower respiratory tract is the fifth leading disease-related cause of death
Source:Hazzard, et al

Pneumonia has long been recognized as a special problem for the elderly. At times being looked upon as a favorable way to end suffering. Pneumonia is a well-recognized problem in both acute and long-term care facilities, and it accounts for ten to fifteen percent of all nosocomial infections. It is also the most lethal nosocomial infection. For the purposes of this review, nosocomial infections refers to those infections acquired in the hospital with the understanding that the lines of distinction are beginning to blur as more traditionally nosocomial infections are now appearing in the community by the American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) in their joint guidelines regarding the diagnosis and management of healthcare associated pneumonia (HCAP).

Copyright 2011 American Society of Consultant Pharmacists

Bacteriology of Community-Acquired Pneumonia (CAP)

Epidemiology Healthy pa*ent Pa*ent with COPD Immunocompromised pa*ent (ETOH, cancer, immunosuppressants, cor*costeroids) Aspira*ng pa*ent Post-inuenza pa*ent

Pathogen Streptococcus pneumoniae, Chlamydophilia pneumoniae, Mycoplasma pneumoniae S. pneumoniae, Haemophilus. inuenzae, Moraxella catarrhalis Legionella spp., Klebsiella spp., Staphylococcus aureus, anaerobes, S. pneumoniae, H. inuenzae, M. tuberculosis Anaerobes (Peptococcus, Peptostreptococcus spp.), S. Pneumoniae S. pneumoniae, S. aureus, H. inuenzae

A wide variety of microorganisms can cause community-acquired pneumonia in the elderly. In healthy patients, for example, the most common pathogens are Streptococcus pneumoniae, Chlamydophilia pneumoniae, and Mycoplasma pneumoniae. Patients with chronic obstructive pulmonary disease are especially susceptible to Streptococcus pneumoniae and Haemophilus influenzae, while immunosuppressed patients are susceptible to these and other pathogens. Aspiration can lead to infection by oral anaerobes such as Peptococcus and Peptostreptococcus species.

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Bacteriology of Nosocomial Pneumonia Agents of CAP plus


Pseudomonas aeruginosa Staphylococcus aureus (MRSA > MSSA) Klebsiella pneumoniae Enterobacter species Escherichia coli Proteus species Serratia marcescens

Nosocomial pneumonia can also be caused by a variety of microorganisms, including Pseudomonas, Klebsiella, E. coli and Staphylococcus aureus. Remember that Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, and Chlamydophilia and Mycoplasma pneumoniae are also important pathogens in nosocomial infections.

Copyright 2011 American Society of Consultant Pharmacists

Risk Factors for Pneumonia in the Elderly


Influenza Affects 10% of elderly population Elderly are 4 times more likely to be infected Elderly account for 75-80% of influenza deaths Risk Factors for Bacterial Pneumonia COPD Chronic bronchitis Severe hypoxia Pulmonary edema Acidosis Alcohol intoxication Conditions which promote aspiration (e.g., sedatives, neurological disease, bedridden patients) Gram-negative bacilli in the oropharaynx Viral pneumonia Azotemia Smoking Malnutrition Use of acid suppressive therapies
Photomicrograph of H. influenzae bacteria Linda M Stannard, University of Cape Town, http://www.uct.ac.za/depts/mmi/stannard/emimages.html

Copyright 2011 American Society of Consultant Pharmacists

Risk Factors for Pneumonia in the Elderly


Numerous risk factors predispose the elderly to bacterial pneumonia. The most important single risk factor is viral influenza, which attacks individuals over seventy with four times the frequency as compared to individuals under age forty. Other risk factors include chronic obstructive lung disease and chronic bronchitis, alcohol intoxication, and conditions that promote aspiration. Another risk factor, colonization of the oropharaynx with Gram-negative bacilli, is a common phenomenon in long-term care facilities and acute care hospitals. There is substantial controversy over the use of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2-RA) and the increased risk of bacterial pneumonia.

Copyright 2011 American Society of Consultant Pharmacists

Clinical Presentation

Common Signs & Symptoms Mild fever Mental status changes, lethargy, confusion Anorexia Tachypnea and tachycardia CHF or COPD exacerbation Less Common High spiking temperature Productive cough with purulent sputum Pleuritic chest pain

Elderly patients with pneumonia typically present with mild fever and mental status changes. Lethargy and confusion are common. Patients may exhibit abnormally high respiration (>24 breaths per minute) and heart rates. These signs are considered the most sensitive signs in the elderly patient. Conditions such as congestive heart failure or chronic obstructive lung disorders are frequently exacerbated by pneumonia. Less commonly seen are high spiking temperature, purulent sputum, and pleuritic chest pain.

Copyright 2011 American Society of Consultant Pharmacists

Diagnosis of Pneumonia
Sputum: > 25 neutrophils, < 10 epithelial cells/HPF Chest X-ray: Positive after rehydration

Diagnosis of pneumonia relies on good sputum samples, which are difficult for elderly patients to produce even after chest physiotherapy, nebulizer treatment, and nasotracheal suctioning. To be useful, sputum should show a neutrophil count above twenty-five, with epithelial cells below ten per high power field. A good sputum specimen should be gramstained, a rapid diagnostic test that separates organisms into gram-positives and gram-negatives. Knowing this information may help in choosing initial therapy. The specimen should also be cultured (organism will be know in in 24 hours and sensitivities will be known in 48 hours.) The chest x-ray, which is often the sole diagnostic test available, should be positive after rehydration.

CT scan of patient with pneumonia With permission from J. Stahl, Radiologische Klinik, Abt. Radiodiagnostik, Homburg/Saar, Germany The Virtual Radiological Case Collection

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Pneumonia Based on Pathogen

Pathogen S. pneumoniae Penicillin susceptible (MIC < 2) S. pneumoniae Highly Penicillin resistant (MIC >= 2) H. influenzae M. catarrhalis Anaerobes S. aureus Enterobacteriaceae Pseudomonas aeruginosa Legionella spp. Mycoplasma pneumoniae Chlamydophilia pneumoniae

Preferred Antimicrobial Penicillin G, amoxicillin Agents based on susceptibility testing including cefotaxime, ceftriaxone, levofloxacin, moxifloxacin, gemifloxacin, vancomycin 2nd or 3rd generation cephalosporin, doxycycline, -lactam/-lactamase inhibitor, azithromycin, TMP/SMX 2nd or 3rd generation cephalosporin, TMP/SMX, macrolide, -lactam/-lactamase inhibitor clindamycin, -lactam/-lactamase inhibitor nafcillin/oxacillin + rifampin or gentamicin, vancomycin (if MRSA), linezolid 3rd generation cephalosporin + aminoglycoside aminoglycoside or antipseudomonal fluoroquinolone + antipseudomonal -lactam macrolide rifampin, fluoroquinolone doxycycline, macrolide, fluoroquinolone doxycycline, macrolide, fluoroquinolone

Source: Mandall LA, Bartlett, JG, Dowell SF, File, TM, Musher DM, Whitney C. (2003). IDSA update of practice guideline for the management of community-acquired pneumonia in immunocompetent adults. Clinical Infectious Diseases, 37, 1405-33.

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Pneumonia Based on Pathogen


Treatment of pneumonia should be started as early as possible in the disease process. Studies have shown that treatment delays exceeding eight hours may contribute to increased mortality. Current Center for Safe Medical Practices (CMS) requirements include antibiotic administration within 4 hours of presentation. Therapy is usually empiric, but if known, antimicrobial therapy is directed toward the specific pathogen.

According to guidelines provided by the Infectious Diseases Society of America, parenteral penicillin or oral amoxicillin are preferred for susceptible strains of pneumococci, while ceftriaxone/cefotaxime, vancomycin or fluoroquinolones are recommended for highly resistant strains. For anaerobic bacterial infections, clinical drug trials show that clindamycin is superior to IV penicillin. Mycoplasma or Chlamydophilia pneumoniae is best treated by macrolides, doxycycline, or fluoroquinolones.

Copyright 2011 American Society of Consultant Pharmacists

Empiric Outpatient Treatment of Patients with Community Acquired Pneumonia (includes Nursing Facility Residents)

Drugs of Choice: Macrolides - clarithromycin (Biaxin) or azithromycin (Zithromax) Fluoroquinolones levofloxacin (Levaquin), moxifloxacin (Avelox), gemifloxacin (Factive) Doxycycline (Vibramycin)

Audio Transcript In elderly patients, treatment of pneumonia tends to be empiric. In the absence of an etiologic diagnosis, other factors such as severity of illness, clinical features, and concomitant medications play a major role in selecting appropriate therapy. Patients who are stable and do not require hospitalization typically benefit from antimicrobials such as macrolides, fluoroquinolones, or doxycycline. Macrolides are effective against atypical pathogens and community acquired strains of staphylococcus, but may produce gastrointestinal side effects. Respiratory fluoroquinolones are effective against a variety of microorganisms. Doxycycline is usually administered once daily, and is more effective against atypical organisms such as Mycoplasma pneumoniae, Chlamydophilia pneumoniae, and Legionella. If the NF resident is unable to swallow in the short-term or is moderately- to severely-ill and has a "Do Not Hospitalize" order, ceftriaxone IM (reconstituted with 1% lidocaine to reduce injection pain) can be used for 1-3 days until the resident is able to take oral medications, elevated temperature (if present) has fallen, and symptoms are responding to therapy. At this point, one of the oral agents listed previously can be started.

Copyright 2011 American Society of Consultant Pharmacists

Empiric Treatment of Patients Hospitalized with Community Acquired Pneumonia

Drugs of Choice: -lactam (cefotaxime or ceftriaxone) + macrolide (clarithromycin or azithromycin) -lactam/ -lactamase inhibitor + macrolide Fluoroquinolone - levofloxacin, moxifloxacin, gemifloxacin If in ICU, erythromycin, azithromycin, or a fluoroquinolone + cefotaxime or ceftriaxone, or a -lactam--lactamase inhibitor combination

Patients hospitalized with community acquired pneumonia should receive a beta-lactam with macrolide, or a fluoroquinolone alone. If the patient is in the intensive care unit, a macrolide or fluoroquinolone with a cephalosporin or beta-lactam/beta-lactamase inhibitor is the preferred combination. For most cases of bacterial pneumonia, ten days of treatment is sufficient. Newer evidence supports that Levofloxacin 750mg IV/PO daily (adjust for renal dysfunction) may be used for five days.

Copyright 2011 American Society of Consultant Pharmacists

Empiric Treatment of Patients with Hospital-Acquired Pneumonia (HAP)


HAP or VAP in patients with no known risk factors for MDR pathogens, early onset, any severity Ceftriaxone or Levofloxacin or Moxifloxacin or ciprofloxacin* or Ampicillin / sulbactam or Ertapenem HAP or VAP with known risk factors for MDR pathogens, early onset and any severity Antipseudomonal cephalosporin or carbapenem or -lactam/ -lactamase inhibitor PLUS Aminoglycoside or antipseudomonal fluoroquinolone PLUS Vancomycin or linezolid

The organisms associated with early onset HCAP are similar to those found in CAP. These include S. pneumoniae, H. Influenzae, MSSA and antibiotic sensitive Gram-negative bacilli. If MDR S. pneumoniae is suspected or prevalent, do not use ciprofloxacin. The risk of atypical organisms is diminished and routine additional coverage is not warranted. The therapy for early onset HAP can be achieved using ceftriaxone, a fluoroquinolone, -lactam/ -lactamase inhibitor or ertapenem. In patients with known risk factors for MDR pathogens it is essential to empirically cover P. aeruginosa, MRSA, K. pneumoniae (ESBL +), Acinetobacter spp. and potentially Legionella. This requires a three agent, broad spectrum regimen containing two antipseudomonal agents and one with activity against MRSA.

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Influenza A Respiratory Tract Infection


Amantadine (Symmetrel) 100 mg bid beginning within 48 hours of onset of symptoms and continued to 24-48 hours beyond disappearance of symptoms; dosage adjustment depends on degree of renal insufficiency ADRs: dizziness, depression, confusion, falls, sleep disturbances, seizures Rimantadine (Flumadine) 100 mg bid for 7 days beginning within 48 hours of onset of symptoms; decrease dose in elderly and renal/hepatic impairment (CrCl <10ml/min) ADRs: dizziness, depression, confusion, falls, sleep disturbances, seizures Oseltamivir phosphate (Tamiflu) 75 mg bid for 5 days beginning within 48 hours of onset of symptoms; dose decreased to 75 mg qd for Clcr < 30 ml/min ADRs: nausea, vomiting, diarrhea, bronchitis, vertigo Zanamivir (Relenza) inhaler- 2 inhalations (10 mg total) twice daily for 5 days beginning within 48 hours of onset of symptoms ADRs: dizziness, cough, nausea, bronchospasm

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Influenza A Respiratory Tract Infection

Doses for Renal Insufficiency Amantadine 100 mg po bid CLcr 30 to 50 mL/min CLcr 15 to 29 mL/min CLcr < 15 mL/min or hemodialysis 200 mg first day, then 100 mg daily 200 mg first day, then 100 mg every other day 200 mg weekly

Rimantadine 100 mg po bid CLcr < 10 mL/min 100 mg po qd

Oseltamivir CLcr < 30mL/min CLcr < 10mL/min 75 mg po qd for treatment, 75 mg po qod or 30 mg qd for prophylaxis not recommended

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Influenza A Respiratory Tract Infection


One hundred milligrams of amantadine or rimantadine taken twice a day has been found to be effective in treating patients with Influenza A respiratory tract infections. Adverse reactions include dizziness, depression, confusion, sleep disturbances, and seizures. The amantadine dosage must be adjusted for any level of renal dysfunction. Fewer side effects have been noted with rimantadine, which is administered with amantadine for patients with end-stage renal disease. The rimantadine dosage may need to be reduced in cases with end-stage renal failure. Treatment should begin within forty-eight hours of onset, and continued until forty-eight hours after symptoms subside, usually within seven to ten days. Oseltamivir phosphate was introduced in late 1999 and is administered twice daily for 5 days. Dosage adjustment should occur in renal insufficiency to 75 mg once daily. The most common side effects are GI related. Taking the drug with meals can significantly ameliorate these side effects. Another Influenza A treatment alternative introduced in 1999, zanamivir, is administered in an inhaler form using the Diskhaler. Zanamivir is dosed 2 inhalations twice daily, and side effects commonly include nausea, dizziness, cough, and bronchospasm in patients with asthma or COPD. Older patients may find the Diskhaler difficult to use. Both of these newer agents should be started within 48 hours of onset of influenza symptoms.

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Influenza B Respiratory Tract Infection

Oseltamivir phosphate (Tamiflu) 75 mg bid for 5 days beginning within 48 hours of onset of symptoms; dose decreased to 75mg qd for Clcr < 30 ml/min ADRs: nausea, vomiting, diarrhea, bronchitis, vertigo Zanamivir (Relenza) inhaler- 2 inhalations (10 mg total) twice daily for 5 days beginning within 48 hours of onset of symptoms ADRs: dizziness, cough, nausea, bronchospasm

Oseltamivir phosphate was introduced in late 1999 and is administered twice daily for 5 days. Dosage adjustment should occur in renal insufficiency to 75 mg once daily. The most common side effects are GI related. Taking the drug with meals can significantly ameliorate these side effects. Another Influenza A treatment alternative introduced in 1999, zanamivir, is administered in an inhaler form using the Diskhaler. Zanamivir is dosed 2 inhalations twice daily, and side effects commonly include nausea, dizziness, cough, and bronchospasm in patients with asthma or COPD. Older patients may find the Diskhaler difficult to use. Both of these newer agents should be started within 48 hours of onset of influenza symptoms. Amantadine an rimantadine have no activity against Influenza B and should not be used to treat patients with Influenza B respiratory tract infections.

Copyright 2011 American Society of Consultant Pharmacists

Prophylactic Treatment for Influenza A

Amantadine or rimantadine 100 mg qd x 14-21 days (or until about 5 days after last case has emerged in an outbreak)

In long-term care facilities, prophylaxis is often recommended for patients exposed to outbreaks of influenzal RTI. One hundred milligrams of amantidine or rimantadine should be taken daily for two to three weeks, or until about five days after the last case has emerged in the facility. Keep in mind that his type of prophylactic treatment is effective only with influenza A.

Copyright 2011 American Society of Consultant Pharmacists

Prophylactic Treatment for Influenza B

Oseltamivir phosphate (Tamiflu) 75 mg qd; dose decreased to 75mg qod for Clcr < 30 ml/min Zanamivir (Relenza) inhaler- 2 inhalations (10 mg total) qd To continue for 14-21 days (or about 5 days after last case has emerged in an outbreak)

For prophylaxis of Influenza B, oseltamivir phosphate 75 mg once daily or every other day if the creatinine clearance is less than 30 milliliters per minute or zanamivir two inhalations once daily can be used for two to three weeks or around five days after the last case has emerged in the facility. For facility-wide prophylaxis, oseltamivir is much easier to use tha zanamivir. For viruses other than Influenza A or Influenza B, infection control measures are the only viable option.

Copyright 2011 American Society of Consultant Pharmacists

Influenza Vaccine
Indications: may be given to anyone who wishes to reduce the chance of becoming infected strongly recommended for persons at great risk of influenza-related complications (e.g. persons > 65 years of age; residents of nursing homes and other chronic-care facilities; persons with chronic pulmonary, cardiovascular, or metabolic disease, renal dysfunction, hemoglobinopathies, or immunosuppression; children > 6 months receiving long-term aspirin therapy; women who will be in 2nd or 3rd trimester of pregnancy during flu season) also strongly recommended for health care workers and others in close contact with high-risk people (e.g. employees of long-term care facilities, caregivers, household members living with high-risk people) Contraindications: hypersensitivity to eggs Administration: 0.5 mL IM in deltoid every Fall (Oct 15 to Nov. 15); onset of seroconversion in 2 weeks, lasts 3-4 months Adverse Drug Reactions: 10-30% mild soreness for 1-2 days < 1% have flu-like illness with onset in 6 hours, lasting 2 days Effectiveness: 30-40% in elderly; reduces pneumonia, hospitalization and death by up to 81%

Copyright 2011 American Society of Consultant Pharmacists

Influenza Vaccine

Because of its importance as a risk factor for pneumonia and frequently lethal complications such as primary influenzal pneumonia, any person over sixty-five years old should be vaccinated for influenza A and B. The vaccine, which contains two influenza type A antigens and one influenza Type B antigen, is administered every Fall. A small percentage of patients will experience mild soreness or even flu-like symptoms for a day or two. The vaccine should not be administered to patients who show an immediate hypersensitivity to eggs. The vaccine is effective in preventing elderly patients from acquiring influenza infection thirty to forty percent of the time, and even more effective in preventing influenza-related deaths, complications, and hospitalizations.

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Pneumococcal Vaccine

Indications: Patients > 65 years; LTC facility residents; patients with solid tumors or hematological malignancies, HIV seropositive, chronic cardiovascular or pulmonary disease, diabetes, alcohol abuse, cirrhosis, asplenia, chronic renal failure, nephrotic syndrome; transplant recipients and immunosuppressed patients; patients using immunosuppressants, including systemic corticosteroids Administration: 0.5 mL IM/SC X 1 Repeat in 5 years if initial dose given before age 65 and person is now over age 65 or person has risk factors such as liver or kidney dysfunction, malignancies,immunosuppression is on dialysis, has asplenia. Adverse Drug Reactions: 10-50% have local reaction lasting 5-10 days 2% have fever > 100 F lasting > 1 day Effectiveness: 46% of elderly > 85 years Patients can also be vaccinated against the Strep. Pneumoniae, or pneumococcus, which causes lobar pneumonia. Of the approximately eighty serolotypes orstrains that have been identified, the vaccine contains antigens for twenty-three, which account for eighty-percent of bloodstream isolates. The vaccination is repeated in five years if the initial dose was administered before the age of sixty-five and the person is now over the age of 65, or if the patient has risk factors such as malignancies, liver or kidney dysfunction, or immunosuppression. Ten to fifty percent of vaccinees have a local allergic reaction to the drug that lasts five to ten days. Two percent have fever lasting one day. The vaccine is effective in forty-six percent of patients over the age of eighty-five years old.
Copyright 2011 American Society of Consultant Pharmacists

Resources

For additional information, see: American Thoracic Society (2001).Guidelines for the management of adults with community-acquired pneumonia. American Journal of Respiratory Critical Care Medicine, 164, 1730-1754. Department of Health and Human Services.(2002).Prevention and control of influenza.Recommendations of the Immunization Practices Advisory Committee.Mortality and Morbidity Weekly Report, 51 (RR-3), 1-31. Department of Health and Human Services.(1997).Prevention of pneumococcal disease.Recommendations of the Immunization Practices Advisory Committee.Mortality and Morbidity Weekly Report, 46 (RR-8), 1-24. Guidelines for the management of adults with HAP< VAP and health-care associated pneumoniae. American Thoracic Socierty, Am J Respir Crit Care Med 205 171:388. Fein, AM.(1999).Pneumonia in the elderly: overview of diagnostic and therapeutic approaches. Clinical Infectious Diseases, 28, 726-729. Guay, D. R.(2001).Therapeutics in the elderly, 3rd ed.Chapter 21, pp 569-598. Macfarlane, J. (1999).Lower respiratory tract infection and pneumonia in the community.Seminars in Respiratory Infections, 14(2), 151-162. Mandell, L. A., Bartlett, J. G., Dowell, S. F., & File, T. M, Jr. (2003).Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clinical Infectious Diseases, 37, 1405-1433.

Copyright 2011 American Society of Consultant Pharmacists

Resources
Marrie, T.J. (2002).Pneumonia in the long-term-care facility.Infection Control & Hospital Epidemiology, 23(3), 159-164. Marrie, T.J. (2000).Community-acquired pneumonia in the elderly.Clinical Infectious Diseases, 31(4), 1066-1078. Piedra, P. A.(1995).Influenza-virus pneumonia: pathogenesis, treatment, and prevention. Seminars in Respiratory Infection, 10(4), 216-223. Sethi, S. (2002).Bacterial pneumonia.Managing a deadly complication of influenza in older adults with comorbid disease.Geriatrics, 57(3), 56-61. Torres, A., El-Ebiary, M., Riquelme, R., Ruiz, M., Celis, R. (1999).Community-acquired pneumonia in the elderly.Seminars in Respiratory Infections, 14(2), 173-183. Websites: American Thoracic Society Infectious Diseases Society of America Pneumonia in the elderly byJoseph M. Mylotte, MD, CIC

Copyright 2011 American Society of Consultant Pharmacists

Tuberculosis in the Elderly

Learning Objectives:

By the end of this Review Concept you should be able to: Characterize the typical etiology, transmission, and pathogenesis of tuberculosis. List risk factors that predispose elderly patients to tuberculosis. Describe common clinical manifestations associated with tuberculosis. Cite laboratory tests and findings that assist in the diagnosis of tuberculosis. Describe initial, subsequent, and prophylactictreatment for elderly patients with TB.

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Pathogenesis of TB
Pathogen: Mycobacterium tuberculosis Transmission: droplets of respiratory secretions aerosolized by coughing, sneezing, etc.; can spread throughout facility Site of Infection: apex of the lung, usually Pathogenic Mechanism: Mostly reactivation TB, due to loss of T-cell mediated immunity

Tuberculosis warrants serious consideration in respiratory infections in elderly patients because of its frequency, its tendency to appear in individuals not previously suspected of the infection, and its communicability. Fortunately, it is one of the most easily treated serious infectious diseases that is likely to occur in the elderly. Mycobacterium tuberculosis is transmitted in the form of droplet nuclei andusually settles in the apex of one or both lungs, where high oxygen tensions facilitate its growth. Most cases of TB are the result of a reactivation of dormant bacilli acquired in the early 1900s, when hygiene was poorer. This reactivation occurs as a result of loss of T-cell mediated immunity. The increasing prevalence of nursing facility staff from countries where the disease is endemic (i.e. reasonably common) is another reason for concern. Such individuals can transmit the disease to other staff or previously non-infected residents.
Copyright 2011 American Society of Consultant Pharmacists

Major Risk Factors Associated with TB Infection


diabetes mellitus (DM) end stage renal disease (ESRD) alcoholism cancer immunosuppression systemic corticosteroid use

Multisystem disorders such as diabetes, cancer, and alcoholism increase susceptibility to tuberculosis. Immunosuppression and use of systemic corticosteroids are also major risk factors.

Copyright 2011 American Society of Consultant Pharmacists

Signs and Symptoms of TB


Common weight loss weakness cough dyspnea low grade temperature Less Common night sweats Hemoptysis

The clinical manifestations of tuberculosis may be subtle. Patients with TB usually present with weight loss, weakness, cough and dyspnea. A low-grade temperature is not uncommon. More rarely seen are night sweats and hemoptysis. You should always consider tuberculosis with patients who are not aspirators, but nevertheless have repeated respiratory tract infections that do not get better despite adequate therapy.

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Diagnosis of TB
Chest X-ray: solitary nodule in upper lobe, +/- hilar adenopathy Culture: sputum acid-fast bacillus (AFB) x 3 mornings, urine and gastric fluids PPD: positive on day 2 with induration > 10 mm; if negative, repeat in 1 week (two-step)

A diagnosis of TB is established through several laboratory tests. Chest x-rays usually show a solitary nodule in the upper lobe, with or without hilar adenopathy. Sputum culture shows acid-fast bacilli. Collect three consecutive morning sputums to maximize yield. Purified protein derivative (PPD) or Mantoux skin test is usually positive on day two, with induration greater than 10 millimeters. If the first PPD is negative, the test should be repeated in one week. This is because a booster effect is sometimes seen in elderly patients, who tend to have a high rate of anergy (i.e. nonresponse to skin testing with antigens). Long-term care facility residents who are suspected of having TB should be hospitalized immediately in negative pressure rooms to reduce the spread of the pathogen.

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Initial Treatment of TB
Agents: Isoniazid (INH) Rifampin (Rifadin) Pyrazinamide (PZA) Ethambutol (ETH) For Patients at Low Risk for Resistance: INH 300 mg qd + Rif 600 mg qd x 1-2 months -> INH 900 mg + Rif 600 mg twice a week to complete 9 months OR INH 300 mg qd + Rif 600 mg qd + PZA 15-30 mg/kg/day x 2 mos. -> INH 900 mg + Rif 600 mg twice a week x 4 months For Patients at Unknown or High Risk for Resistance: INH 300 mg qd + Rif 600 mg qd + PZA 15-30 mg/kg/day + ETH 15-25 mg/kg/day or Streptomycin 15 mg/kg/day until sensitivity test results available.

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Initial Treatment of TB

With strains of unknown or high risk of resistance, four agents should be considered in the initial treatment of patients with tuberculosis. These agents include isoniazid plus rifampin plus pyrazinamide plus ethambutol or streptomycin. This regimen is especially recommended if a staff member from a country where TB is endemic is the presumed source. In these countries, resistance rates are high due to the easy availability of antitubercular drugs. Therapeutic regimens designed for patients with low risk for resistance are effective with most elderly patients, since they acquired their TB in the preantibiotic era. Typical regimens include three hundred milligrams of isoniazid and six hundred milligrams of rifampin daily, for one to two months, followed by reduced frequency of isoniazid and rifampin administration for another seven to eight months. An alternative regimen includes fifteen to thirty milligrams per kilogram of pyrazinamide daily for the first two months followed by a shorter duration of isoniazid and rifampin twice a week. Regimens can be changed once sensitivity test results are available.

Copyright 2011 American Society of Consultant Pharmacists

Initial Treatment of TB

Monitor: liver function tests (LFTs), serum Cr, CBC, platelets, uric acid, visual acuity Observe: INH: hepatotoxicity, peripheral neuropathy, cholestatic jaundice RIF: acute interstitial nephritis and cholestatic jaundice ETH: optical neuritis, GI distress PZA: hepatotoxicity, gout

Most patients report side effects with TB medications. For example, isoniazid can cause peripheral neuropathy due to pyridoxine deficiency. Isoniazid and rifampin can cause cholestatic jaundice. Ethambutol is known to cause optic neuritis and nausea, and pyrazinamide is known to cause gout. During treatment, patients should be monitored for liver function, serum creatinine, complete blood count, platelets, and uric acid.

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Subsequent Treatment of TB

Pyridoxine 25-50 mg QD with INH If resistant to INH or RIF, substitute 2 agents to which the organism is sensitive for 18 mos. Continue to monitor LFTs, serum Cr, CBC, platelets, and uric acid

Twenty-five to fifty milligrams daily of pyridoxine should be added to Isoniazid treatment to prevent pyridoxine deficiency. Although resistance to Isoniazid or Rifampin is rare in long term care residents, you should be prepared to substitute two agents to which the organism is sensitive and continue treatment for eighteen months. Adding only a single agent to which the organism is sensitive will encourage the rapid development of resistance.

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Prophylactic Treatment of TB
Indications: New PPD conversion = 10 mm in last 2 years Positive PPD with additional risk factors such as: recent contact with infectious TB patient (=5mm) fibrotic changes on CXR (=5mm) o HIV, hematological and RES diseases (=10mm) o diabetes mellitus (=10mm) chronic malabsorption or renal failure (=10mm) prolonged systemic corticosteroid use or other immunosuppression low body weight (=10mm) head and neck cancers (=10mm) Prophylaxis: INH 300 mg po q.d. + pyridoxine 25-50 mg q.d. X 6-12 mos. Short-Course Prophylactic Treatment of TB Rifampin 10mg/kg daily for 4 months Avoid if patient has preexisting liver disease, OR if history of liver injury (=5mm)

due to INH

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Prophylactic Treatment of TB
If a new PPD conversion is greater than ten millimeters within the last two years, or if the patient has a positive PPD and additional risk factors, treat with three hundred milligrams of oral isoniazid and twenty-five to fifty milligrams of pyridoxine daily for six to twelve months. Although the INH prophylaxis regimen is preferred, rifampin alone for 4 months can be used if the patient cannot tolerate INH. Avoid rifampin alone if there is preexisting liver disease or a history of liver injury due to INH. The rifampin + pyrazinamide short-course prophylactic regimens (daily administration for 2 months or twice weekly for 2-3 months) are no longer acceptable alternatives due to the high risk of fatal hepatotoxicity, even with q2week liver function testing.

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Rifabutin
A rifamycin like rifampin but differs in side effect and drug interaction profiles Generally should use only in HIV-seropositive patients Dosing: depends on concurrent antiretrovirals being used* decrease dose 50% when CrCl below 30 mL/min Treatment: 150, 300, or 450-600 mg qd Or 150, 300, or 600 mg 2-3 times weekly Prophylaxis:generally not recommended AE:rash, GI, bone marrow suppression, uveitis, rarely hepatic * Dept. of Health and Human Services (2000). Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Morbidity Mortality Weekly Report, 49(9), 185-189.

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Rifabutin
Rifabutin, like rifampin, is a rifamycin but differs from rifampin in its adverse event and drug interaction profiles. In the treatment of TB, it should generally only be used in HIV-seropositive individuals. The dose of rifabutin (whether daily or twice/thrice weekly) is variable, depending on the concurrent antiretrovirals being used (details in MMWR ref.). In the rare cases where it is used in non-HIV-seropositive individuals, dosing is 5 mg/kg (max. 300 mg) daily or twice/thrice weekly. Like rifampin, it should rarely be used for prophylaxis of TB. Dose reduction is necessary in severe renal impairment. Rifabutin has fewer drug interactions than rifampin but these can still be significant. Although rifabutin shares the rash and GI side effects of rifampin, it is rarely hepatotoxic but does have unique ocular. (uveitis) and bone marrow suppressant (neutropenia, thrombocytopenia) side effects. The latter two are more common when enzyme-inhibiting drugs (eg. azole antifungals, clarithromycin, certain antiretrovirals) are being used concurrently.

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Resources
For additional information, see: Davies PD (1996).Tuberculosis in the elderly.Epidemiology and optimal management.Drugs & Aging. 8(6):436-44. Department of Health and Human Services (2002).Targeted tuberculin testing and treatment of latent tuberculosis.American Thoracic Society/CDC Statement Committee.Morbid Mortal Weekly Report, 49 (RR-6), 1-54. Hocking TL & Choi C (1997) .Tuberculosis:a strategy to detect and treat new and reactivated infections.Geriatrics, 52 (3):52-4, 60-3. Packham S (2001). Tuberculosis in the elderly.Gerontology, 47(4):175-9. Peloquin, CA (2002).Tuberculosis. (Chapter 110, pp. 1917-1937).In DiPiro J. T., et al. (Eds.). Pharmacotherapy: A pathophysiologic approach.McGraw-Hill, New York. Dept. of Health and Human Services (2000).Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors.Morbidity Mortality Weekly Report, 49(9), 185-189. Anonymous (2003).American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America.Treatment of tuberculosis.American Review of Respiratory and Critical Care Medicine, 167, 603-662. Tuberculosis.Net New Jersey Medical School National Tuberculosis Center WMHT Educational Telecommunications, The Peoples Plague Online
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Viral Hepatitis in the Elderly


Learning Objectives:

By the end of this Review Concept you should be able to: Differentiate the principal types of hepatitis based on etiology and mode of transmission. Describe incidence, clinical manifestations, prevention and treatment associated with Hepatitis A. Describe incidence, clinical manifestations, prevention and treatment associated with Hepatitis B. Identify serologic markers used to evaluate the severity, progression, and effectiveness of treatment for Hepatitis B. Describe incidence, clinical manifestations, prevention and treatment associated with Hepatitis C. Name diagnostic tests used to evaluate the severity, progression, and effectiveness of treatment for Hepatitis C.

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Types of Hepatitis and Associated Etiology

drug-induced hepatitis autoimmune hepatitis bacterial hepatitis fungal and parasitic hepatitis viral hepatitis type A: eating of food contaminated by fecal contact type B: spread via blood contact type C: spread via blood contact type D: co-infects with hepatitis B type E: eating of food contaminated by fecal contact (rare in the U.S.)

Hepatitis, an inflammatory disease that results in the destruction of liver tissue, can be caused by a variety of viral, bacterial, fungal, immunologic and chemical assaults. Although many viruses can be involved, there are five which are of major importance, transmitted through different routes. The most common mode of transmission of hepatitis C in the elderly is receipt of contaminated blood transfusions prior to 1990. While infrequent in the elderly population, viral hepatitis can present a serious problem for the older patient. Hepatitis B can cause severe acute hepatitis, or quickly evolve into fulminant liver failure. A large number of hepatitis B and C patients develop a chronic, subacute form of the disease without obvious symptoms. However, elderly patients with chronic Hepatitis B are more likely to have an acute fulminant course.

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Hepatitis A: Etiology, Transmission and Incidence

Etiology: picornavirus family (RNA) Transmission: consumption of food contaminated by fecal contact Incidence: 35,000 non-hospital cases & 13,000 hospital cases per year 152 deaths per year 76% non-hospital cases & 88% hospital cases > 14 years

Hepatitis A or infectious hepatitis is familiar to travelers to third world countries. It is a cytopathic disease, caused by an organism of the picornavirus family. It is estimated that nearly forty-eight thousand people are infected with hepatitis A every year, accounting for thirteen thousand hospital admissions in the U.S.. Over seventy-percent of these individuals are over fourteen years old. Evidence of hepatitis A is commonly seen in the elderly because they acquired the infection in the early years of this century, when hygienic conditions were relatively poor.

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Hepatitis A: Clinical Picture


Incubation Period: 2-4 weeks Onset: Abrupt Signs & Symptoms: fever abdominal pain fatigue and malaise nausea and vomiting diarrhea

The onset of hepatitis A is abrupt following a two to four week incubation period. Patients with hepatitis A complain of fever, abdominal pain, malaise, fatigue, nausea and vomiting, and diarrhea. They may present with jaundice and pruritus. Symptoms usually disappear within two to four weeks after onset. There is no chronic carrier state or sequelae with hepatitis A as compared to hepatitis B and C.

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Hepatitis A: Control Measures

Post-exposure prophylaxis:0.02ml/kg ISG x 1 dose IM if within 14 days of exposure Preexposure Immunization: Recommended for following high risk groups: international travelers military members of groups with high endemicity rates such as Native Alaskans and Americans, IV drug abusers, and developmentally challenged Seroconversion: 88% measurable anti-hepatitis antibodies within 2 weeks 99% measurable anti-hepatitis antibodies within 4 weeks

For nonimmune persons (i.e. they have no antibodies to HAV [anti-HAV]), post-exposure passive immunotherapy with 0.02 ml/kg of immune serum globulin IM will prevent infection if administered within 14 days of exposure. Vaccination provides the best defense against hepatitis A. Vaccination is recommended for travelers and military personnel, as well as members of high risk groups such as Alaskans and Native Americans, IV drug abusers, and the developmentally challenged. In eighty-eight percent of healthy patients, anti-HAV are measurable within two weeks after immunization, and ninety-nine percent have measurable anti-HAV within four weeks of immunization.

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Hepatitis A Vaccines

Hepatitis A Vaccines Hepatitis A vaccine, inactivated (Havrix) 1440 EIA units (1 mL) IM, initial and 6-12 months later Vaqta 50 units (1 mL) IM, initial and 6-12 months later Twinrix - HAV and HBV

Two vaccines are currently available to provide the best protection against hepatitis A:Havrix available from Smith Kline Beecham, and Vaqta, available through Merck.For older adults, the recommended dosages are fourteen hundred forty units of HAVRIX or fifty units of VAQTA.A booster dose of either drug may be given any time between six to twelve months after the primary dose.Twinrix, a combination vaccine against Hepatitis types A and B, available from GlaxoSmithKline is administered on the 0, 1, and 6 month schedule of hepatitis B vaccine (see below).

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Hepatitis B: Etiology, Transmission and Incidence


Etiology: complex virus consisting of three parts, one of which contains infectious DNA Transmission: direct contact with bodily fluids Incidence: 1,000,000 chronic cases in the U.S. 200,000-300,000 new acute cases per year 10,000-15,000 new chronic cases per year

Hepatitis B or serum hepatitis is a chronic problem for at least one million people in this country. There are at least two hundred thousand new acute cases and ten thousand new chronic cases per year. Hepatitis B is complex virus containing three distinct parts. The inner capsule of one of these parts, the Dane particle, contains the DNA that ultimately infects the host and activates his or herimmune system. Liver cells are destroyed in the antigen (virus) antibody reaction as innocent bystanders. Transmission is much like HIV, through direct contact with infected bodily fluids.

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Hepatitis B: Clinical Picture

Incubation Period: 45-180 days Onset: Insidious Early Signs & Symptoms: fatigue and loss of appetite fever joint pain and general achiness pruritus Later Signs and Symptoms: nausea and vomiting foul breath and bitter taste in the mouth dark brown urine and pale-colored bowel movements jaundice pain just below the ribs on the right side

Following an incubation period of forty five to one hundred eighty days, the onset of hepatitis B is insidious. Symptoms of hepatitis B may appear as long as four weeks to six months after infection, and typically include loss of appetite, fever, general aches, and fatigue. Patients may also experience pruritus and joint pain. As the infection progresses, patients present with nausea and vomiting, jaundice, and discoloration of urine.
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Hepatitis B: Complications Due to Liver Damage

cirrhosis end stage liver disease hepatocellularcarcinoma

Many people who develop the chronic form of the disease have only vague symptoms, even though the virus may be damaging their livers. Symptoms of advanced liver damage secondary to chronic hepatitis and cirrhosis include pain on the left side of the upper abdomen due to an enlarged spleen, swelling of the stomach and legs, and reddening of the palms. Patients bruise easily and bleed from the esophagus or stomach. They may also go on to develop liver failure. Chronic hepatitis B infection also predisposes to the development of a rare primary cancer of the liver which is poorly responsive to treatment called hepatocellular carcinoma.

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Hepatitis B Serologic Markers

Marker HBsAg IgM An*-HBc HBeAg An*-HBe An*-HBc An*-HBs

Characteris7cs rst to appear; disappears with clinical improvement; when seen with IgM an*-HBc, indicates acute infec*on; persistence beyond 6 months. indicates chronic infec*on indicates acute infec*on; helps dis*nguish An*-HBc acute and chronic infec*on; undetectable aMer 6 months.; with HBsAg, indicates acute infec*on indicates infec*vity; detectable in acute or chronic infec*ons; persistence beyond 10 wks indicates chronic liver disease is likely an*body for HBeAg, usually indicates benign outcome indicates current or previous infec*on indicates recovery or immunity; detectable aMer HBsAg disappears and recovery is complete; appears aMer inocula*on with HBV vaccine

Serologic markers are used to characterize the clinical stage of hepatitis B. Hepatitis B surface antigen is the first marker to appear, and it disappears with clinical improvement. Subsequent markers can be used to distinguish acute from chronic infection, the likelihood of the disease becoming chronic, progression to recovery, and response to hepatitis B vaccination.

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Hepatitis B Vaccine and Post-Exposure Prophylactic Treatment


Administration: Deltoid IM injection at 0, 1, 6 months OR 0, 1, 2, 12 months. Adverse Drug Reactions: 10-50% have local reaction lasting 5-10 days 2% have fever > 100F lasting > 1 day Effectiveness: 46% of elderly > 85 years Post-exposure Prophylaxis: hepatitis B vaccine and/or Hepatitis B Immune

Pre-exposure prophylaxis to hepatitis B is recommended during childhood. The vaccine is administered at zero, one and six months, or zero, one, two, and twelve months. If response is poor, up to three boosters may be administered. Post-exposure hepatitis B prophylaxis consists of hepatitis B vaccine and/or hepatitis B immunoglobulin.

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Hepatitis B: Goals of Treatment


Suppression of viral replication through: clearance of HBV DNA from serum clearance of HbeAg from + detection of anti-Hbe in serum Improvement of liver function Normalization of serum aminotransferase levels Decreased necrotic inflammatory activity Prevention of cirrhosis and hepatocellular carcinoma, improvement of survival

Treatment of hepatitis B focuses on the suppression of viral replication, either by clearance of hepatitis B DNA from serum, or clearance of hepatitis B e antigen and/or detection of antibodies hepatitis B e antigen. Clearance of hepatitis B e antigen appears to be the single best predictor of survival in infected patients. If liver function is compromised, normal serum aminotransferase levels are a target of therapy.

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Hepatitis B: Pharmacotherapy
Administration: Interferon-alpha2b SC 5million units qd or 10 million units 3 x week or lamivudine 100 mg po qd (if HIV -) or 150mg bid (if HIV +) or adefovir dipivoxil 10mg po qd Effectiveness: successful in 30%-40% of chronic cases Adverse Drug Reactions: Interferon fever, headache, myalgias, arthralgias are common psychiatric side - effects (depression, psychosis, irritability) induces or aggravates autoimmune diseases (esp. thyroid) reversible bone marrow suppression Lamivudine: well-tolerated Adefovir: nephrotoxicity Interferon alpha2b is the mainstay of treatment of hepatitis B in the United States. The drug suppresses viral replication by inhibiting viral protein synthesis and stimulating cell-mediated response. Five million units daily to ten million units administered three times a week has proved successful in treating thirty to forty percent of patients with chronic infection. Side effects include fever, chills, headache, myalgias, dizziness, reversible bone marrow suppression, psychiatric disorder and autoimmune disorders. Pre-treatment of acetaminophen may reduce some of the side effects of interferon. Two oral nucleotides, lamivudine (Epivir, Epivir-HB) and adefovir dipivoxil (Hepsera), are approved for treatment of HBV in the US. They are much better tolerated than interferon.Dose adjustment of both is needed for reduced renal function.
Copyright 2011 American Society of Consultant Pharmacists

Hepatitis C: Etiology, Transmission and Incidence


Etiology: flavivirus infection Transmission: parenteral contact with bodily fluids (transfusions, intravenous drug abuser) Incidence: 40-60% of chronic viral hepatitis, 80% of post-transfusion hepatitis 28,000 new cases each year leading cause of liver cirrhosis, carcinoma in developed countries, causing 8,000-10,000 deaths per year more common in people with pre-existing immunosuppression; found in 1-2% of American blood donors; 3% of chronic hemodialysis patients

Hepatitis C, formerly known as non-A, non-B hepatitis, is caused by a flavivirus transmitted mainly by parenteral contact with infected bodily fluids. Hepatitis C accounts for forty to sixty percent of chronic viral hepatitis, and eighty percent of post-transfusion hepatitis in this country. Although the number of new cases has dropped dramatically over the last decade due to rigorous blood screening, Hepatitis C is still found in one to two percent of blood donors. Hepatitis C-related liver damage is responsible for eight to ten thousand deaths per year and is the number one cause of cirrhosis and carcinoma of the liver in developed countries.

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Hepatitis C: Risk Factors


pre-existing immunosuppression high-risk sexual activity IV drug abuse alcohol abuse HIV

Hepatitis C is more common in individuals with pre-existing immunosuppression. It is found in three percent of chronic hemodialysis patients. Other risk factors include high-risk sexual activity, IV drug and alcohol abuse, and HIV.

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Hepatitis C: Clinical Picture

Incubation Period: 4-20 weeks (60-80% become chronic carriers) Onset: varies chronic hepatitis, 18.4 years cirrhosis, 20.6 years hepatocellular carcinoma, 28.3 years Signs & Symptoms: 70% are asymptomatic; GI disturbances and jaundice are the most common symptoms

The incubation period of hepatitis C ranges from four to twenty weeks and sixty to eighty percent of cases go on to a chronic carrier state. In thirty to forty percent of cases, the signs and symptoms are typical for acute hepatitis infection: nonspecific gastrointestinal problems, followed by jaundice, for anywhere between two and twelve weeks. However, up to seventy percent of patients are asymptomatic. Ninety percent will develop a chronic infection, with delayed onset of hepatic complications.

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Hepatitis C: Diagnosis

Antibody Detection: Enzyme immunoassay (EIA.2) Recombinant immunoblot assay (RIBA.2) to supplement or confirm HCV-RNA Detection: polymerase chain reaction (PCR) branched chain DNA (b-DNA) Disease Severity: liver function tests (LFTs) liver biopsy

Diagnosis of hepatitis C relies on the use of serologic testing. Enzyme immunoassay and recombinant immunoblot assay are used to determine the presence of hepatitis C antibodies. Hepatitis C RNA is measured using polymerase chain reaction and branched chain DNA assays. Liver biopsy is considered the gold standard for determining the severity of the infection and the rate of progression.

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Hepatitis C Prevention

Prevention: thorough screening of blood products modification of high-risk behaviors use of universal precautions

Currently, there are no vaccines for hepatitis C. Preventative measures include thorough screening of blood products, modification of high-risk behaviors, and use of universal precautions.

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Hepatitis C Treatment

Interferon alfacon 1:9mcg sc three times a week Interferon alpha 2a or 2b: 3 million units sc three times a week Peg-interferon alpha-2a: 180mcg sc once a week Peg-interferon alpha-2b: 1.5 mcg/kg once a week Ribavirin:500-600mg po bid Standard-of-care is pegylated interferon + ribavirin (never use ribavirin alone) Ribavirin causes dose-related anemia

Interferon monotherapy results in very low sustained response rates for HCV. Currently, the standard-of-care is a combination of an interferon plus ribavirin. Never use ribavirin alone, viral resistance develops rapidly. Following HCV RNA levels is the best method for evaluating treatment effectiveness.

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Resources
For additional information, see Ahmed A., Keeffe EB.(1999).Treatment strategies for chronic hepatitis C:update since the 1997 National Institutes of Health Consensus Development Conference.Journal of Gastroenterology & Hepatology. 14 Suppl:S12-8. Guay, D. R.(1999).Hepatitis C. Formulary.34:132-4, 137-40, 143. Hayashi J. Kashiwagi S.(1997).Hepatitis C virus infection in the elderly.Epidemiology, prophylaxis and optimal treatment.Drugs & Aging.11(4):296-308. James OF.1997.Parenchymal liver disease in the elderly. Gut. 41(4):430-2. Jansen PL. (2002).Liver disease in the elderly.Best Practice & Research in Clinical Gastroenterology.16(1):149-58. Marcus El. Tur-Kaspa R.(1997).Viral hepatitis in older adults.Journal of the American Geriatrics Society.45(6):755-63. Merle P., Trepo C., Zoulim F.(2001).Current management strategies for hepatitis B in the elderly.Drugs & Aging.18(10): 725-35. Michielsen P., Brenard R., Reynaert H. (2002).Treatment of hepatitis C:impact on the virus, quality of life and the natural history. Acta Gastroenterologica Belgica. 65(2):90-4. Regev A., Schiff ER.(2001).Liver disease in the elderly.Gastroentoenterology Clinics of North America. 30(2):547-63,xxi.

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Resources
Rivkina A., Rybalov S. (2002). Chronic hepatitis B:current and future treatment options.Pharmacotherapy. 22(6):721-37. HepNet Health on the Net, Hepatitis B Virus (HBV) Overview

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Urinary Tract Infections


Learning Objectives:

By the end of this Review Concept you should be able to:

Describe the incidence of urinary tract infections in the elderly. Identify bacteriologic agents that typically cause community-acquired and nosocomial UTI. Cite risk factors for UTI in elderly men and women. Describe possible variations and complications of urinary tract infection. List common clinical manifestations and laboratory findings for patients with UTI. Describe pharmacological treatment options for complicated and uncomplicated UTI. Describe treatment options for cystitis, pyelonephritis or urosepsis, and bacterial prostatitis. Discuss the approach to the elderly patient with asymptomatic bacturiuria. Describe the effectiveness of pharmacologic agents used in the prophylaxis of UTI.

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Epidemiology
Asymptomatic bacturiuria 30-50% of females in Long Term Care (LTC) facilities 20-30% of males in Long Term Care (LTC) facilities increased frequency with catheterization

Urinary tract infections are the most common infections in elderly institutionalized populations. Asymptomatic bacteriuria (i.e. bacteria in the urine without symptoms or evidence of tissue damage) occurs in thirty to fifty percent of elderly women and twenty to thirty percent of elderly men in long-term care facilities. Long-term catheterization increases this incidence to one hundred percent. It is important to diagnose active infections early, since UTIs are the most frequent cause of sepsis in the elderly.

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Bacteriology
Nosocomial Escherichia coli(40%) Proteus spp., Providencia stuartii, Morganella spp. (12%) Pseudomonas aeruginosa (11%) Enterococcus spp. Community-acquired Escherichia coli(majority) Proteus spp. Klebsiella spp.

In the hospital or long-term care setting, urinary tract infections are most commonly caused by E. coli, with a smaller percentage of cases caused by Proteus, Providencia and Morganella species. Pseudomonas account for eleven percent of UTIs. The number of cases attributable to Enterococci appears to be increasing. In the community at large, most urinary tract infections are caused by E. coli, Proteus and Klebsiella. Ninety percent of women have infections due to enteric gram-negative bacilli, mainly from E. coli. Forty percent of complicated and catheter-related UTIs are also due to E. coli. In contrast, up to 55% of UTIs in men are due to gram-positive organisms. Frequently, UTIs are due to two or more pathogens in the elderly, even in the absence of catheterization. Do not automatically disregard urine culture reports with multiple pathogens as being due to contamination or poor collection technique.

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Risk Factors for Urinary Tract Infection

In Elderly Women increased vaginal pH decreased perineal hygiene In Elderly Men: prostatic enlargement and urinary obstruction decline in prostatic antibacterial factor and zinc increased alkalinity of prostatic fluid

Elderly patients are predisposed to urinary tract infections by numerous risk factors. In postmenopausal women, increased vaginal pH alters endogenous flora, enabling colonization by gram negative rods (Enterobacteriaceae). In addition, adequate perineal hygiene may be more difficult due decreased mobility or decreased dexterity caused by arthritis, leading to urethral contamination. In elderly men, prostatic enlargement can lead to urinary obstruction and retention, providing a medium for bacterial growth. Prostatic antibacterial factor declines with age, as does zinc, a bactericidal trace element normally found in prostatic fluid. In older men, prostatic fluid becomes more alkaline, further predisposing them to UTIs.

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Other Risk Factors for Urinary Tract Infection

functional impairment history of stroke dementia incontinence of bowel and bladder diabetes mellitus bladder catheterization

Other risk factors associated with urinary tract infection include dementia, incontinence, and diabetes. Catheterization is a major risk factor--approximately eighty percent of UTIs in hospitalized patients are caused by catheterization or instrumentation. Catheter-related urinary tract infections are frequently polymicrobial. The longer the catheter remains in place, the higher the risk of bacteriuria, which is usually caused by the patient's own colonic flora. All patients catheterized for longer than thirty days will become bacteriuric.

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Urinary Tract Infections

pyelonephritis cystitis uncomplicated or complicated urosepsis bacterial prostatitis acute or chronic

Pyelonephritis occurs when the kidney is involved; the patient is usually seriously ill with fever and a high white blood cell count. Infection of the bladder or cystitis may be uncomplicated if no other structures are involved. Complicated infections, by definition, occur in patients with abnormalities of the urinary tract, catheters, urinary obstruction, or azotemia. Urosepsis is bloodstream infection originating from the urinary tract. Bacterial prostatitis is a common precursor of urinary tract infection. Chronic bacterial prostatitis should be considered in any male patient presenting with multiple UTIs.

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Signs and Symptoms of Urinary Tract Infection


Common: dysuria increased frequency and urgency of urination Less Common: mental status changes, e.g., malaise, lethargy decreased appetite and anorexia GI disturbances, e.g., nausea & vomiting, abdominal pain incontinence or nocturia respiratory distress With Pyeloneprhitis or Urosepsis: fever and chills back pain hypotension, tachycardia (urosepsis) Although dysuria is a common complaint, elderly patients often do not present with classic symptoms of urinary tract infection. Instead, they may present with mental status changes, decreased appetite, abdominal pain, nausea and vomiting, new onset of incontinence or nocturia, or even respiratory distress. In long-term care settings, diagnosis is sometimes difficult because patients are cognitively impaired and unable to complain of symptoms. Proper diagnosis is often delayed until the patient presents with fever and is more severely ill. Such signs and symptoms are more characteristic of pyelonephritis or urosepsis.
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Lab Findings
Urinalysis (UA): nitrite positive (selected organisms) WBC present and leukocyte esterase positive pH maybe elevated with Proteus or Providencia casts may be present with pyelonephritis Microbiology: Absolute colony-forming unit count is not as significant as presence of symptoms

The results of urinalysis are the same for elderly patients as for younger patients. A positive nitrite test is observed if the patient has certain nitrate-producing bacteria. White blood cells are present and leukocyte esterase is elevated. Urine pH may be elevated if Proteus or Providencia species is the causative organism (these organisms contain urease which converts to urea to ammonia which raises urine pH). An alkaline urine pH predisposes to infection (struvite) stones in the urinary tract. Casts may be present if the patient has pyelonephritis. Absolute colony-forming unit count is not as significant as is the presence of symptoms. Patients can have a UTI when the colony count is as low as 102 CFU/mL.

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Asymptomatic Bacteriuria

avoid treatment in majority only treat if patient to undergo an invasive genitourologic procedure (e.g. cystoscopy, TURP)or implantation of a prosthetic device or urinary tract is obstructed (esp. males)

In general, asymptomatic bacteruria should not be treated. Although transient clearing of bacteruria may occur, treatment can expose the patient to increased reinfection rates, antimicrobial resistance, adverse drug reactions and unnecessary cost. There is no convincing evidence that treating asymptomatic bacteruria in elderly patients reduces the risk of symptomatic infections or of organ damage.

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Treatment of Uncomplicated UTIs

Empiric Antibiotic Selection Consider local resistance patterns Usual first-line therapy amoxicillin (Amoxil), po 250 mg q8h TMP/SMX (Septra), po 160/800 mg q12h Alternate selections in areas of antimicrobial resistance amoxicillin 250-500 mg and 125 mg clavulanic acid q8h Quinolones Duration of therapy: 7-10 days

Resistance patterns of urinary pathogens vary according to geographic location and care setting. Consequently, it is important to be aware of local patterns of antimicrobial sensitivities. For acute, uncomplicated urinary tract infections, oral amoxicillin or trimethoprim/ sulfamethoxazole should be considered first-line drugs for empiric therapy. They are effective and inexpensive, and have relatively little toxicity. For patients with impaired renal function, the dose of trimethoprim/sulfamethoxazole should not be cut in half as recommended for systemic infections. Trimethoprim/sulfamethoxazole is unique in this regard as it needs adequate serum levels to push the components into the urine, thus the recommendation to not dose-adjust in renal failure. In settings of known resistance to first-line drugs, commonly used alternatives are amoxicillin with clavulanic acid and quinolones.

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Treatment of Upper Urinary Tract Infections


Community-Acquired: Hospitalized with enterococcus - ampicillin or ureido penicillin (e.g., azlocillin (Azlin), mezlocillin (Mezlin), piperacillin (Pipracil)) Hospitalized with GNR (gram negative rod) infection - 3rd generation cephalosporin, ureidopenicillin, TMP/ SMX, aminoglycoside, aztreonam (Azactam) Outpatient - TMP/SMX, quinolone Nosocomial: Ceftazidime and ureidopenicillin +/- aminoglycoside or aztreonam or quinolone or TMP/SMX, then tailored to cultures and sensitivity results

Antimicrobial therapy for urinary tract infections are based on the most likely causative organism until culture and sensitivity results are available. Concurrent diseases and drug therapy, drug allergies, and cost also play a role. Empiric guidelines for hospital treatment of community-acquired upper urinary tract infections include the administration of ureidopenicillins and third generation cephalosporins. Trimethoprim/sulfamethoxazole is also recommended. For nosocomial upper urinary tract infections, ceftazidime plus ureidopenicillin with or without aminoglycoside or aztreonam is recommended initially.

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Treatment of Complicated Cystitis


Community-acquired: Hospitalized - IV ampicillin 1 gm q6h + gentamicin or ureidopenicillin +/- 3rd gen. cephalosporin or aztreonam or quinolone or TMP/SMX Outpatient - po TMP/SMX, trimethoprim (Trimpex), quinolone Nosocomial: Hospitalized cephalosporin or aztreonam or quinolone or TMP/SMX Outpatient - poquinolone

When hospitalization is required, treatment of complicated cystitis should begin with two drug therapy consisting of IV ampicillin plus gentamicin or a ureidopenicillin, with or without third generation cephalosporin, aztreonam, a fluoroquinolone or trimethoprim/sulfamethoxazole. More often, community acquired cystitis is treated as an outpatient condition with oral trimethoprim/sulfamethoxazole, trimethoprim, or a quinolone. Patients should be switched from parenteral to oral medication only after the patient has been afebrile for at least twenty four hours and begins resolving signs and symptoms. For nosocomial cystitis, IV ceftazidime or ureidopenicillin is preferred, followed by an oral quinolone. Treatment of cystitis usually lasts seven to ten days for women, and ten to fourteen days for men.

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Treatment of Pyelonephritis or Urosepsis


Hospitalized - cephalosporin or aztreonam or quinolone or TMP/SMX Outpatient - po only 24 hours after patient has been afebrile and signs and symptoms begin resolving Duration of therapy: At least 14 days

Initial treatment for pyelonephritis or urosepsis is similar to that for hospital treatment of complicated communityacquired cystitis. IV ampicillin plus gentamicin or ureidopenicillin with or without a third generation cephalosporin or aztreonam or quinolone or trimethoprim/sulfamethoxazole (two drug therapy). The choice of oral medication depends on the pathogen and sensitivities, and should be given only after the patient has been afebrile for at least twenty four hours. Length of therapy is at least fourteen days.

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Bacterial Prostatitis


Acute Prostatitis: Hospitalized - IV ampicillin 1 gm q6h + gentamicin or ureidopenicillin +/- 3rd gen. cephalosporin or aztreonam or quinolone or TMP/SMX Outpatient - po only 48 hours after patient has been afebrile, then for 30 days Chronic Prostatitis: po quinolone full dose for =4 weeks

Acute prostatitis is treated with IV ampicillin plus gentamicin ora ureidopenicillin with/without a 3rd generation cephalosporin or aztreonam or quinolone or trimethoprim/sulfamethoxazole for at least forty eight hours. Although not technically a urinary tract infection, prostatitis is often seen in male patients with chronic UTI. Patients with acute prostatitis present with the familiar signs and symptoms of fever, chills, and dysuria, as well as an extremely tender prostate. The organism usually responsible is E. coli or Klebsiella. Acute prostatitis is treated with IV ampicillin plus gentamicin or a ureidopenicillin, cephalosporin, quinolone, or trimethoprim/sulfamethoxazole for at least forty eight hours. Oral therapy begins after the patient is afebrile and lasts for thirty days. Chronic prostatitis is evidenced by repeat UTIs usually with the same organism (with same antibiogram!). Infection can be localized to the prostate using the Meares & Stamey or Nickel protocols, although these are difficult procedures to do in older men. It is usually treated with full dose quinolone for a minimum of four weeks. Trimethoprim is a second line agent in chronic prostatitis. In patients who cannot be cured, chronic suppressive therapy with daily or thrice weekly ofloxacin (100mg) or ciprofloxacin (250mg) or TMP/SMX (1 SS tablet) or nitrofurantoin (100mg) may be used to eliminate symptoms.

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Prophylactic Treatment for Repeated UTIs


Medications: TMP/SMX HS, SS 3x week (M-W-F) trimethoprim (Trimpex) 400 mg qhs nitrofurantoin (Furalan) 40 mg qhs Cranberry juice Estrogen therapy Doses for Renal Insufficiency Nitrofurantoin (Furalan) 50 mg qhs CLcr < 50 mL/min: avoid use Not recommended Methenamine + vitamin C Treatment or preventive therapy for asymptomatic bacteriuria is not indicated. Likewise, the use of antimicrobial prophylaxis for patients with indwelling urinary catheters should be discouraged. Prophylactic treatment may be considered for any female patient presenting with two or more symptomatic urinary tract infections over a six month period or three or more infections per year. Prophylactic options include trimethoprim/sulfamethoxazole, trimethoprim, and nitrofurantoin. One of the major problems with long-term nitrofurantoin therapy is the risk of potentially-irreversible peripheral neuropathy and pulmonary fibrosis. In addition to the agents just described, cranberry juice may also provide some prophylactic benefit. The use of other cranberry products such as cranberry concentrate tablets have not been studied. Topical estrogen therapy is often prescribed for post-menopausal women with recurrent UTI because it increases colonization of vaginal lactobacilli and suppresses the colonization of pathogenic Enterobacteriaceae. However, its effectiveness has been questioned. For patients in long-term care facilities, intermittent catheterization should be substituted for chronic catheterization, if possible. There are insufficient efficacy data to recommend the use of methenamine plus vitamin C as a prophylactic option. An acidic urine environment is necessary for conversion to formaldehyde. Vitamin C is an ineffective urinary acidifier (no matter the dose) and the only effective urinary acidifier, ammonium chloride, induces a concurrent systemic acidosis as well. Urinary acidification increases the risk of urinary tract stone disease and systemic acidosis accelerates osteoporosis.
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Resources
For additional information, see: Eykyn SJ.(1998).Urinary tract infections in the elderly.British Journal of Urology, 82 Suppl 1,79-84. Hamilton-Miller JM. (1999).Issues in urinary tract infections in the elderly.World Journal of Urology, 17(6),396-401. Jacobs LG.(1996). Fungal urinary tract infections in the elderly:treatment guidelines.Drugs & Aging, 8(2),89-96. Keys TF.(2000).When should asymptomatic bacteriuria in the elderly be treated?Cleveland Clinic Journal of Medicine, 67(7),466-7. McCue JD.(2000).Complicated UTI.Effective treatment in the long-term care setting.Geriatrics, 55(9),48, 51-2, 55-8 passim. Nicolle LE. (2001).Urinary tract infections in long-term-care facilities.Infection Control & Hospital Epidemiology, 22(3), 167-75. Nicolle LE. (1997).Asymptomatic bacteriuria in the elderly.Urinary tract infections in long-term-care facilities.Infectious Disease Clinics of North America, 11(3),647-662. ODonnell JA., Hofmann MT.(2002) Urinary tract infection.How to manage nursing home patients with or without chronic catheterization.Geriatrics, 57(5),45, 49-52, 55-6 passim. Reid G., Nicolle LE.(1999).Asymptomatic bacteriuria in spinal cord patients and the elderly.Urologic Clinics of North America, 26(4),789-95.

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Resources
Shortliffe LM, McCue JD.(2002).Urinary tract infection at the age extremes: pediatrics and geriatrics.American Journal of Medicine, 113 Suppl 1A,55S-66S. Staleton A. Stamm WE. (1997).Prevention of urinary tract infection.Infectious Disease Clinics of North America, 11(3), 719-33. Wood CA., Abrutyn E.(1996) Optimal treatment of urinary tract infections in elderly patients.Drugs & Aging, 9(5),352-62. Yoshikawa TT., Nicolle LE., Norman DC.(1996). Management of complicated urinary tract infection in older patients.Journal of the American Geriatrics Society, 44(10),1235-41. Saint S, Kaufman SR, Rogers MA, Baker PD, Ossenkop K, Lipsky BA. Condom versus indwelling urinary catheters: a randomized trial. J Am Geriatr Soc. 2006 Jul;54(7):1055-61. Uehara S, Monden K, Nomoto K, Seno Y, Kariyama R, Kumon H. A pilot study evaluating the safety and effectiveness of Lactobacillus vaginal suppositories in patients with recurrent urinary tract infection. Int J Antimicrob Agents. 2006 Aug;28 Suppl 1:S30-4. Regal RE, Pham CQ, Bostwick TR. Urinary tract infections in extended care facilities: preventive management strategies. Consult Pharm. 2006 May;21(5):400-9. McMurdo ME, Bissett LY, Price RJ, Phillips G, Crombie IK. Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial. Age Ageing. 2005 May;34(3): 256-61. MedlinePlus: Urinary Tract Infections
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Skin, Bone and Joint Infections


Learning Objectives:

By the end of this Review Concept you should be able to:

Cite common skin infections that afflict the elderly. Describe the etiology of diabetic and non-diabetic skin infections. List risk factors for diabetic skin infections. Describe pharmacological treatment for diabetic and non-diabetic skin infections. Describe the clinical features, risk factors, and signs/symptoms associated with herpes zoster. Describe pharmacologic treatment of herpes zoster. Describe the etiology, transmission and clinical features associated with scabies. Describe pharmacologic treatment of scabies. Describe common clinical manifestations and treatment options for bone and joint infections.

Copyright 2011 American Society of Consultant Pharmacists

Infections of the Skin

Tinea (dermatophytes) Candidiasis (Candida albicans) Bacterial infections (diabetic and non-diabetic) Herpes zoster Scabies

Numerous age-related changes in the dermis, epidermis and subcutaneous layers of the skin make the elderly especially susceptible to skin and soft tissue infections. Tinea infections, which are caused by a class of fungi called dermatophytes, are very common in the elderly, as are yeast infections caused by Candida albicans. Although they do not necessarily occur with greater frequency in older adults, bacterial infections often present different clinical features when they afflict the elderly and they can be associated with sepsis and death.

Copyright 2011 American Society of Consultant Pharmacists

Tinea (dermatophytes)
Organisms Trichophyton, Epidermophyton, Microsporum genera (fungi) Involvement Skin (non-hair bearing and hair-bearing) and nails Diagnosis Clinical - verify via culture or KOH prep Treatment Topical agents, except nail, beard, scalp infections Oral agents - imidazoles, terbinafine vs. griseofulvin span>Tinea versicolor - selenium sulfide, zine pyrithione

Copyright 2011 American Society of Consultant Pharmacists

Tinea (dermatophytes)

Tinea or dermatophyte infections are due to three genera of fungi: Trichophyton, Epidermophyton, Microsporum. Involved areas include non-hair-bearing skin (tinea corporis), hair-bearing skin (tinea barbae [beard], tinea capitis [scalp], tinea cruris [perineum]), and finger and toenails (onychomycosis). A related condition, tinea versicolor, is caused by Pityrosporum ovale. Diagnosis is made usually on clinical grounds but can be verified by culture or potassium hydroxide preparation using skin scrapings or nail fragments. Skin infections usually respond to a 1-2 week course of topical imidazoles, terbinafine, naftifine, butenafine, or ciclopirox. Onychomycosis responds poorly to topical agents, including ciclopirox lacquer. Oral agents (imidazoles, terbinafine, griseofulvin) are indicated in onychomycosis, infections not responding to topical therapy, and tinea barbae/capitis. In onychomycosis, up to 1 year of therapy may be necessary (i.e. until infected nail has grown out) unless an imidazole or terbinafine is used. Oral imidazoles or terbinafine are preferable to griseofulvin due to shorter therapy courses and superior efficacy/ tolerability. Treatment of nail infections solely for cosmetic purposes should be discouraged as these agents are costly, have potential side effects, and interact with many other medications. Tinea versicolor usually responds well to topical selenium sulfide or zinc pyrithione. Environmental control involves eliminating the source of the infection (disinfect inanimate surfaces, check companion animals).

Copyright 2011 American Society of Consultant Pharmacists

Candidiasis
Organisms Vast majority due to C. albicans Involvement Esp. warm, moist skin areas (skin folds) Nail infections are rare Oral cavity Diagnosis Clinical - verify via culture Treatment Topicals are D.O.C. (imidazoles, ciclopirox vs. nystatin) Role of topical corticosteroids Drying agents Oral cavity nystatin swish and swallow vs. imidazoles

Copyright 2011 American Society of Consultant Pharmacists

Candidiasis
Most Candida infections of the skin, nails, and oral cavity are due to C. albicans. Candidal skin infections occur preferentially in warm, moist areas such as skin folds (intertriginous) under the breasts or in the perineum. Candida infections are usually more inflammatory than tinea infections and show a pronounced erythema, usually with small satellite papules/pustules surrounding the erythematous area. Diagnosis is usually made on clinical grounds but can be verified by culture. Skin infections usually respond well to topical treatment (imidazoles, ciclopirox are preferred over nystatin due to shorter therapy courses and superior efficacy). Concurrent use of a topical corticosteroid for the first few days to reduce inflammation can be considered but be cautious about the use of potent agents in areas of thin skin such as the perineum due to the risk of local side effects. Affected areas should be kept dry but avoid using cornstarch as it is a foodstuff for the organism. Treatment of oral candidosis involves environmental control (disinfection of dental appliances such as dentures), elimination of risk factors (reevaluate need for systemic corticosteroids, rinse mouth after use of inhaled corticosteroids), and use of an antifungal (imidazoles are preferred over nystatin due to shorter treatment courses and superior efficacy/tolerability).

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Bacteriology of Skin Infections


Non-diabetic: Group A streptococcus (S. pyogenes) Staphylococcus aureus Other streptococci (groups B, C, F, G) Diabetic: Gram positives S. aureus, Streptococcus spp., Enterococcus spp. Gram negatives Proteus spp., E. coli Anaerobes Bacteroides fragilis, Peptococcus spp, Peptostreptococcus spp.

Bacterial skin infections are often associated with diabetes. While non-diabetic infections are usually caused by group A strep, other strep, or staphylococci, diabetes-related skin infections tend to be polymicrobic with an average of 4 or 5 organisms, including anaerobes. Acute diabetic foot infections are predominantly Gram-positive cocci (i.e. S. aureus); however chronic wound are more likely to be polymicrobial. Rates of MRSA, especially community associated MRSA (CA-MRSA) are on the rise. Patients with diabetes do more poorly when infected with MRSA than their non-diabetic matches. Patients with diabetes are at increased risk for multi-drug resistant pathogens due to prior antibiotic use and more frequent hospitalizations.

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Risk Factors for Diabetic Skin Infections

Neuropathy Ischemia Immune defects Patient disabilities Reduced vision, limited mobility, previous amputations

Several conditions predispose the diabetic patient to bacterial skin infections. They include sensory neuropathy, angiopathy, ischemia, immune defects and patient disabilities.

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Treatment of Non-diabetic Skin Infections


Medications MSSA and other Gram-positive organisms Anti-staph penicillin (e.g.: oxacillin, nafcillin) 1st generation cephalosporin (e.g. Cefazolin, cephalexin) Erythromycin Clindamycin Fluoroquinolones (e.g.: levofloxacin, moxifloxacin, gemifloxacin) MRSA and CA-MRSA Vancomycin (only if MRSA) SMZ/TMP (superficial CA-MRSA) Linezolid Daptomycin Tetracycline (e.g.: tigecycline, minocycline) Duration: 10 14 days

Treatment of non-diabetic skin infections is usually based on the use of an anti-staph penicillin or first-generation cephalosporin. Vancomycin is prescribed only if the patient has methicillin-resistant Staphylococcus aureus (MRSA). In light of the growing problem of community associated MRSA (CA-MRSA), older agents such as SMZ/TMP, clindamycin, or minocycline and the newer agents such as linezolid, daptomycin or tigecycline may be used. Data on the place in therapy of the newer agents is emerging.
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Treatment of Diabetic Skin Infections


Indications: Depends on severity Medications Cefotetan (currently unavailable) or cefoxitin Ampicillin/sulbactam (Unasyn ) Ticarcillin/clavulanate (Timentin) Piperacillin/tazobactam (Zosyn ) Imipenem/cilastatin (Imipenem) or meropenem (Merrem)or Ertapenem (Invanz) Clindamycin or metronidazole + gentamicin or fluoroquinolone Duration: 10 14 days, or longer

The choice of IV or oral therapy for the treatment of diabetic skin infections depends on the severity of the infection. For more sever infections and those requiring IV administration the 2nd generation cephamycins; cefotetan (currently unavailable) or cefoxitin are often used, as well as ampicillin/sulbactam, piperacillin/tazobactam or ticarcillin / clavulanate. The combination of clindamycin or metronidazole (anaerobic coverage) with gentamicin or fluoroquinolone (ciprofloxacin or levofloxacin) may also be prescribed. The later combination offers an oral alternative Treatment usually lasts between ten and fourteen days, or until the ulcer looks better. Patients with diabetes frequently have osteomyelitis in a contiguous bone, which requires a prolongation of therapy and potentially surgery.

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Septic Arthritis (Joint Infection)


Clinical Presentation: Monoarticular pain Fever Joint swelling Decreased mobility Elevated erythrocyte sedimentation rate (ESR) Treatment: oxacillin, cefazolin, or vancomycin (if MRSA) for 2 3 weeks

Joint infections that afflict the aged are usually caused by staphylococci. Patients with staphylococcal arthritis present with monoarticular pain, fever, joint swelling, and decreased mobility. The erythrocyte sedimentation rate (an acute phase reactant) is usually elevated. Patients with staph-related joint infections are best treated with oxacillin or cefazolin for two to three weeks. Vancomycin or a newer anti-MRSA agent may be prescribed for patients who have MRSA. Erythromycin is not considered adequate in such cases. If the infection occurs in a joint with a prosthetic device, more often the device must be removed to effect cure.

Copyright 2011 American Society of Consultant Pharmacists

Bone Infections (Osteomyelitis)

Bacteriology: Hematogenous = S. aureus Contiguous = site dependant Treatment: same agents as for skin infection, but for at least 4 6 weeks

Bone infections can also be caused by multiple pathogens. If the infection is hematogenous (i.e. spread via the bloodstream), staphylococci are the most likely culprits. If the infection is contiguous (from an adjacent tissue infection site), the specific pathogen involved will depend on the affected site, whether it is a diabetic skin lesion, sinusitis, or traumatic injury. Generally speaking, treatment of bone infections relies on the same broad range of agents used to treat skin infections. For contiguous infections, surgical debridement is often required. Duration of treatment is usually longer, at least four to six weeks.

Copyright 2011 American Society of Consultant Pharmacists

Herpes Zoster: Clinical Picture

Bacteriology: reactivation of latent varicella (chicken pox) Pathogenesis: vesicular eruption along one or more dermatomes Clinical Signs & Symptoms: acute --> chronic pain in 50% of patients over age 50

Herpes zoster, commonly known as shingles, is a skin infection that can cause serious long-term sequelae in the elderly. It is caused by the reactivation of latent varicella virus in one or more dorsal ganglia, leading to a vesicular eruption along one or more dermatomes. For over half of all patients over fifty, the long-term result is chronic pain known as post-herpetic neuralgia.

Copyright 2011 American Society of Consultant Pharmacists

Risk Factors for Herpes Zoster

Age-related immunosuppression Systemic corticosteroid use Psychological stress (e.g., bereavement) Malignancies and local irradiation Trauma Surgery HIV/AIDS

Patients who are most susceptible to herpes zoster are those whose cellular immunity has been compromised by age or other factors such as cancer, corticosteroid use, or psychological stress. It is an opportunistic infection frequently recognized as an early clinical sign of AIDS in HIV-infected patients.

Copyright 2011 American Society of Consultant Pharmacists

Signs and Symptoms of Herpes Zoster

Malaise Fever Burning Itching Sharp pain

Prior to the development of skin lesions, the patient with an active herpes zoster infection may experience a prodrome of malaise, fever, burning, itching or sharp pain. The key to differential diagnosis is identification of the specific dermatome involved, as vesicles never cross the midline of the body.

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Herpes Zoster


Within 72 hrs of lesion breakout: Acyclovir (Zovirax) 800 mg po 5x/day (adjusted based on renal function) for 7 10 days Famcyclovir (Famvir) 500 mg tid for 7 10 days Valacyclovir (Valtrex) 1000 mg tid for 7 10 days Dose for Renal Insufficiency Acyclovir for 7 10 days: Clcr 10 to 25 Clcr < 10 Famicyclovir for 7 10 days: Clcr 40 to 59 Clcr 20 to 39 Clcr < 20 500 mg q12h 500 mg q24h> unknown 800 mg q8h 800 mg q12h

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Herpes Zoster

Treatment of herpes zoster focuses on prompt healing of rash, alleviation of acute pain and prevention of post-herpetic neuralgia and other complications. The treatments of choice are acyclovir, famcyclovir, and valacyclovir. Dosages should be adjusted for renal function. To be effective, treatment must begin within seventy-two hours of the appearance of lesions. Although these agents can prevent dissemination of infection, loss of eyesight from ocular zoster and modify the acute pain, they have no effect on post-herpetic neuralgia.

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Etiology and Transmission of Scabies


Etiology: Sarcoptes scabiei (itch mite) Transmission: close personal contact Sites of infestation: digital web spaces, volar wrist, antecubital fossa, axillae, areolae, umbilicus, lower abdomen, genitals and buttocks

Although technically an infestation rather than an infection, scabies is an underestimated problem among the elderly, especially those in long-term care facilities. Transmitted by close personal contact, the disease is caused by the itch mite Sarcoptes scabei. Common sites for infestation include the digital web spaces and volar wrist, antecubital fossa, axillae, lower abdomen, genitals and buttocks.

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Clinical Presentation of Scabies

Onset: 2-4 weeks after infestation Signs & Symptoms Pruritus Lesions with excoriated papules Burrows may be visible Diagnosis: scraping of mite, eggs, feces within lesions (by dermatologist)

Patients with scabies begin showing signs and symptoms two to four weeks after the female mite burrows under the skin to lay its eggs. These signs and symptoms include: pruritus, with visible lesions or burrows, and excoriated papules. Definitive diagnosis is made through microscopic demonstration of the mite, eggs, or feces within lesional scrapings, preferably done by a dermatologist.

Copyright 2011 American Society of Consultant Pharmacists

Treatment of Scabies

Administration: Apply permethrin 5% to entire body and rinse after 8 hours or single oral dose of ivermectin 200 250 mcg/kg, and then repeat in 2 weeks If crusted scabies: Apply permethrin 5% to body and head and rinse after 8 hours PLUS ivermectin 200 250 mcg/kg x 1 dose po every one to two weeks, for a total of 2 or 3 doses Repeat permethrin treatment excluding head on day 7 Re-examine after 1 and 3 weeks

Treat all other potential close contacts, including staff and patients families, within 24 hours. Permethrin five percent has become the treatment of choice for scabies, replacing lindane, crotamiton, and benzyl benzoate. In addition to increased mite resistance to these agents, lindane is known to cause neurotoxicity and benzyl benzoate frequently causes dermatitis. Permethrin should always be applied to both the body and head in elders as up to 1/3 have mite infestation above the neck. All other patients and employees who have had close contact with the patient should be treated along with their families within twenty-four hours. Bedding and clothing should also be treated by either washing in very hot water, or placing the items into an airtight plastic bag for 3 days if the items are not hot water washable. Both of these methods cause the mites to die.

Copyright 2011 American Society of Consultant Pharmacists

Resources
For additional information: Brodell RT., Elewski B.(1997).Superficial fungal infections. Errors to avoid in diagnosis and treatment.Postgraduate Medicine. 101(4):279-87. Elgart ML.(2002).Skin infections and infestations in geriatric patients.Clinics in Geriatric Medicine.18(1):89-101.Gupta AK.(2000).Onychomycosis in the elderly.Drugs & Aging. 16(6):397-407. Hedderwick S., Kauffman CA.(1997).Opportunistic fungal infections: superficial and systemic candidiasis. Geriatrics. 52 (10):50-4, 59. IDSA Guidelines for the diagnosis and management of skin and soft-tissue infections (2005). Clinical infectious Diseases 41: 1373. IDSA Guidelines for the diagnosis and treatment of diabetic foot infections (2004). Clinical Infectious Diseases; 39:885-910. Laube S, Farrell AM.(2002).Bacterial skin infections in the elderly:diagnosis and treatment.Drugs & Aging.19(5):331-42. Lertzman BH., Gaspari AA.(1996).Drug treatment of skin and soft tissue infections in elderly long-term care residents.Drugs & Aging.9(2):109-21. O'Donnell JA.Hofmann MT.(2001).Skin and soft tissues. Management of four common infections in the nursing home patient. Geriatrics.56(10):33-8, 41.

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Resources
Electronic Textbook of Dermatology Dermatology Image Atlas - Johns Hopkins World Ortho Electronic Textbook Infections of Bones and Joints

Copyright 2011 American Society of Consultant Pharmacists

Drug Resistance in the Elderly


Learning Objectives:

By the end of this Review Concept you should be able to:

Describe the current scope of the problem presented by antimicrobial drug resistance. Cite common infectious organisms that are resistant to antimicrobial therapy. Describe the health costs associated with antimicrobial drug resistance. Describe current and proposed methods for the treatment and control of methicillin-resistant and glycopeptideintermediate Staphylococcus aureus (MRSA and GISA). Describe pathogenic variations, epidemiology, and risk factors for vancomycin-resistant enterococcus (VRE). Describe current strategies for detecting, treating, and controlling the spread of VRE. Describe current therapeutic limitations and drugs of choice for the treatment of infections involving Pseudomonas aeruginosa, Enterobacter cloacae, Stenotrophomonas maltophilia, Streptococcus pneumoniae, and other organisms.

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Multi-Drug Resistant Organisms


Causing Nosocomial Infections: Staphylococcus aureus Enterococcus spp. Klebsiella spp. Enterobacter spp. Escherichia coli Pseudomonas spp. Acinetobacter spp. Causing Community-Acquired Infections: Pneumococcus (Streptococcus pneumoniae) S. aureus (community associated methicillin resistant S. aureus) Gonococcus spp. Mycobacterium tuberculosis Group A streptococci E. coli

Despite the best efforts of scientists and clinicians, the problem of multi-drug resistance continues to increase. Major resistant organisms causing nosocomial infections include Staphylococcus aureus, Enterococcus sp., Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, and more recently Acinetobacter species. Multi-drug resistant bacteria causing community acquired infections include the S. pneumoniae, CA-MRSA, Gonococci sp., Mycobacterium tuberculosis, group A streptococci, and E. coli.
Copyright 2011 American Society of Consultant Pharmacists

Costs of Antimicrobial Resistance

Antimicrobial resistance has been implicated in deaths caused by Enterococci in the hospital setting, and by tuberculosis both in the hospital and the community. In addition to increased risk of complications and mortality, the length of stay and additional costs of treating diseases caused by resistant strains of some organisms has at least doubled in recent years. Elderly patients in nursing homes are at especially high risk for resistance-related problems due to clonal spread and frequent antibiotic use.

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Control of Methicillin-Resistant Staphylococcus aureus (MRSA)

One of the most persistent problems in antimicrobial resistance is that posed by methicillin-resistant Staphylococcus aureus. Since total eradication of the organism is not possible, transmission must be minimized through thorough hand washing and the use of universal precautions.

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Treatment of Infections Due to Glycopeptide Intermediate Staphylococcus Aureus (GISA)


High doses of vancomycin (concentration > minimum inhibitory concentration (MIC)) Quinupristin / Dalfopristin (Synercid) Linezolid (Zyvox) Daptomycin (Cubicin) Tigecycline (Tygacil)

A new strain of vancomycin-non-susceptible staph, known as glycopeptide-intermediate Staphylococcus aureus, or G-IS-A, is beginning to frustrate treatment efforts. Potential therapies for GISA infections include higher doses of vancomycin, and alternative agents such as daptomycin, quinupristin / dalfopristin, linezolid or tigecycline.

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Community Associated Methicillin Resistant S. aureus (CA-MRSA)

Increasing rates throughout the nation Frequent cause of skin and soft tissue infections Many report spider bites Resistance to all beta-lactam antibiotics Many non beta-lactam antibiotic retain activity

Another new strain of S. aureus is emerging a leading cause of skin and soft tissue infections in the community. Community associated MRSA is often reported as a spider bite by patients. The strains frequently produce a toxin that causes pus formation and swelling. The strain is resistant to all beta-lactam antibiotics but retains susceptibility to many older non-beta-lactam agents such as vancomycin, trimethoprim/sulfa (TMP/SMX), tetracycline and clindamycin. Newer agents as previously discussed may also play role in the management of this increasing problem.

Copyright 2011 American Society of Consultant Pharmacists

Control of MRSA and GISA Outbreaks


Hand washing (both) Use of universal precautions (both) De-colonizing with 2-drug combinations (MRSA ONLY) i.e.:TMP/SMX + rifampin OR minocycline + rifampin Topical mupirocin also an option (MRSA ONLY)

Outbreaks of methicillin-resistant staph are managed through combined de-colonization with trimethoprim/ sulfamethoxazole, rifampin, minocycline, and/or mupirocin. Such treatment is not only costly, it also carries the risk of side effects while possibly inducing resistance as well. Decolonization is not possible with GISA.

Copyright 2011 American Society of Consultant Pharmacists

Vancomycin-resistant Enterococcus (VRE)


Van A: Inducible high level of resistance to vancomycin (MIC > 32 mg/L) and teicoplanin (not available in U.S) Transferable via plasmid/transposon Van B: Inducible but variable level of resistance to vancomycin; susceptible to teicoplanin Transferable (chromosomal) Van C: Intrinsic low-level resistance to vancomycin (MIC 8-16 mg/L), susceptible to teicoplanin Non-transferable Van A, B and C may be associated with therapeutic failure of vancomycin and the elimination of the synergism of vancomycin + aminoglycosides

Enterococcal resistance is another serious problem in the health care setting. Vancomycin-resistant strains have always included rare human pathogens such as Lactobacillus, Leuconostoc, and Pediococcus species. There appears to be at least three types of vancomycin resistance among enterococci. All result from the elaboration of key enzymes and resulting modification of the vancomycin-binding site in the enterococcal cell wall. Vancomycin-resistant enterococci are often co-resistant with penicillins, aminoglycosides, and many other antibiotics.

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Epidemiology of VRE
First seen in France, 1986; origin unknown Most are faecium or faecalis Very geographic Spreads via animals, sewage (community) and via beds, bedpans, rectal thermometers, urine containers, BP cuffs, etc. (hospital) Colonizes for prolonged period of time within facility and between facility spread

Vancomycin-resistant enterococci were first detected in France in 1986. Its origin is unknown. Most V-R-E are faecium or faecalis. Incidents of V-R-E are also geographically isolated, with high rates in some areas and with low rates or nonexistence in others. The organism can spread through the community via animals and sewage, and in the clinical setting through contaminated bedpans, rectal thermometers, blood pressure cuffs and other hospital equipment. Prolonged colonization in stool and perhaps skin facilitates spread of the organisms within and between health care facilities. The environment is a very important source of infection and complicates infection control strategies.

Copyright 2011 American Society of Consultant Pharmacists

Risk Factors for VRE

Prolonged hospitalization Invasive devices and procedures Immunosuppression (rejection, AIDS) Prior use of antibiotics Intraabdominal surgery Selective gut decontamination Renal insufficiency ICU residence Severe underlying disease Proximity to colonized or infected patient or caregiver Elderly Neutropenia Enteral feedings

Risk factors for infection by vancomycin-resistant enterococci include: prolonged hospitalization, invasive devices and procedures, and immunosuppression. Renal and organ transplant units in the United States and other countries have been sites of V-R-E outbreaks. Other risk factors include prior use of antibiotics, especially vancomycin and cephalosporins.

Copyright 2011 American Society of Consultant Pharmacists

Detection of VRE
Testing: Must test all enterococci for vancomycin, gentamicin/ streptomycin resistance Most reliable tests are E-tests and agar disk diffusion using new breakpoints

All enterococci must now be tested for vancomycin and gentamicin / streptomycin resistance. Detection is based on the use of the E-test and agar disk diffusion tests using new breakpoints. It is important to keep in mind that some automated systems may rely on old breakpoints that fail to identify low-level resistance.

Copyright 2011 American Society of Consultant Pharmacists

Treatment of VRE
Potential Pharmacotherapies: First Line Quinupristin/dalfopristin (Synercid) Linezolid (Zyvox) Daptomycin (Cubicin) Second Line Doxycycline Tigecycline (Tygacil) High-dose ampicillin or ampicillin/sulbactam (Unasyn) Nitrofurantoin (UTI only) Chloramphenicol (Chloromycetin) Investigational Oritavancin Dalbavancin (Vibramycin) Daptomycin, linezolid, and quinupristin/ dalfopristin (latter only for E. faecium, not faecalis) are approved for the treatment of VRE infections. Other possible treatments include doxycycline, tigecycline, nitrofurantoin, chloramphenicol, and highdose ampicillin (with or without sulbactam), alone or in combination. Additional control measures include environmental disinfection, use of dedicated equipment to prevent spread, universal and barrier precautions, and use of private rooms or cohorting colonized / infected patients together. Additional Precautions: Environmental disinfection Removal of foreign devices from room / patient Use of dedicated equipment Strict barrier precautions (private room or cohort patients together) Universal precautions

Copyright 2011 American Society of Consultant Pharmacists

Pseudomonas aeruginosa

Resistant to: many therapies, frequently including aminoglycosides and fluoroquinolones Recommended strategy: Combination therapy

As serious as these vancomycin-resistant strains of staphylococi and enterococci are, the problem of antimicrobial resistance is by no means limited to these organisms. Resistance has occurred with every available antibiotic therapy for Pseudomonas aeruginosa. The greatest problem is the recent emergence of aminoglycoside and fluoroquinolone resistance. For this reason, therapy should be based on results of sensitivity testing and combination therapy is strongly recommended, at least for pulmonary infections. Empirical therapy should include a combination of antipseudomonal agents from two different antimicrobial classes. Local susceptibility (antibiogram) and patient specific data should be used in the selection of the optimum regimen.

Copyright 2011 American Society of Consultant Pharmacists

Enterobacter Species

Resistant to: cephalosporins (inducible) Drug(s) of choice: TMP/SMX (Septra) Carbapenems Imipenem / cilastatin (Primaxin) Meropenem (Merrem) Ertapenem (Invanz) Aminoglycosides

With respect to the treatment of Enterobacter species, cephalosporins may appear effective in sensitivity testing, but resistance is quickly induced. Combination therapy is critical for severe infections.

Copyright 2011 American Society of Consultant Pharmacists

Stenotrophomonas maltophilia

Resistant to: Most therapies Drugs of choice: TMP/SMX (Septra) Clavulanate (Ticarcillin/clavulanate) Chloramphenicol (Chloromycetin)

Stenotrophomonas maltophilia (Xanthomonas) has always been very resistant to therapy. This organism is increasing in frequency due to the introduction and use of the carbapenems (eg., imipenem), to which it is often resistant. Drugs of choice include trimethoprim/sulfamethoxazole, the clavulanate component of ticarcillin/clavulanate and chloramphenicol.

Copyright 2011 American Society of Consultant Pharmacists

Streptococcus Pneumoniae
Resistant to: penicillin (> 35% of patients) Recommended strategy: alternative, non-penicillin therapy Drugs of choice: Ceftriaxone (Rocephin) or Cefotaxime (Claforan) Vancomycin (Vancocin) (with ceftriaxone in meningitis only) Selected respiratory fluoroquinolones Macrolides (increasing resistance)

Alterations in penicillin binding proteins have caused penicillin resistance to increase to over thirty-five percent in Streptococcus pneumoniae infected patients in the U.S. Although effective, vancomycin should be used only in meningeal infections. Drugs of choice include ceftriaxone, cefotaxime, and the respiratory fluoroquinolones such as levofloxacin, moxifloxacin or gemifloxacin. Macrolides have been used extensively over the past decade and resistance rates have nearly matched those of the penicillin. Although in vitro resistance may not predict clinical outcome, caution should be used when selecting agents with known high rates of resistance. The newer ketolide, telithromycin demonstrates very high susceptibilities; however recent questions over hepatic safety may limit routine use.
Copyright 2011 American Society of Consultant Pharmacists

Other Treatments Compromised by Antibiotic Resistance

TB: isoniazid --> isoniazid + rifampin, + pyrazinamide + ethambutol HIV: 1/2 protease inhibitors + 2 nucleoside reverse transcriptase inhibitors Or 1 non-nucleoside RTI + 2 RTIs

Other treatments compromised by antibiotic resistance include isoniazid, which has mandated combination therapy for tuberculosis. Up to four drugs are being used for initial treatment in certain geographic areas and with certain ethnic groups. HIV patients now require at least triple antibiotic therapy to overcome the therapeutic limitations posed by the antimicrobial resistance of HIV.

Copyright 2011 American Society of Consultant Pharmacists

Resources
For additional information, see: Bonomo RA.(2000).Multiple antibiotic resistant bacteria in long-term-care facilities:An emerging problem in the practice of infectious diseases.Clinical Infectious Diseases,31(6),1414 1422. Bradley SF.(1997). Methicillin-resistant Staphylococcus aureus in nursing homes.Epidemiology, prevention, and management.Drugs & Aging, 10(3),185 198. Bonomo RA.Resistant pathogens in respiratory tract infections in older people.Journal of the American Geriatrics Society, 50(7 Suppl),S236 241. Linares, J.(2001).The VISA/GISA problem:therapeutic implications.Clinical Microbiology & Infection, 7 Suppl 4,8 15. Linden PK (2002).Treatment options for vancomycin resistant enterococcal infections.Drugs,62, 425-441. Nicolle LE.(2002).Resistant pathogens in urinary tract infections.Journal of the American Geriatrics Society, 50(7 Suppl),S230 235. Nicolle LE, Strausbaugh LJ, Garibaldi RA.(1996).Infections and antibiotic resistance in nursing homes.Clinical Microbiology Reviews,9(1),1 17. Norman DC. (2002).Management of antibiotic-resistant bacteria.Journal of the American Geriatrics Society,50(7 Suppl),S242 246. CDC National Center for Infectious Disease WHO Network for Antimicrobial Resistance
Copyright 2011 American Society of Consultant Pharmacists