Treatment of Nursing Home– Acquired Pneumonia KYLE MILLS, PharmD, BCPS, and A. CHRISTIE NELSON, PharmD University of Wyoming School of Pharmacy, Laramie, Wyoming BRADFORD T. WINSLOW, MD, FAAFP, Swedish Family Medicine Residency Program, Littleton, Colorado KATHRYN LEE SPRINGER, MD, Greater Denver Infectious Diseases, Denver, Colorado Pneumonia is an important cause of morbidity and mortality in nursing home residents, with 30-day mortality rates ranging from 10 to 30 percent. Streptococcus pneumoniae is the most common cause of nursing home–acquired pneu- monia, although Staphylococcus aureus and gram-negative organisms may be more common in severe cases. Antibiotic therapy for nursing home–acquired pneumonia should target a broad range of organisms, and drug-resistant microbes should be considered when making treatment decisions. In the nursing home setting, treatment should consist of an antipneumococcal fluoroquinolone alone or either a high-dose beta-lactam/beta-lactamase inhibitor or a second- or third-generation cephalosporin, in combination with azithromycin. Treatment of hospitalized patients with nursing home–acquired pneumonia requires broad-spectrum antibiotics with coverage of many gram-negative and gram-positive organisms, including methicillin-resistant S. aureus. Appropriate dosing of antibiotics for nursing home–acquired pneumonia is important to optimize effectiveness and avoid adverse effects. Because many nursing home residents take multiple medications, it is important to consider possible drug interactions. (Am Fam Physician. 2009;79(11):976-982. Copyright 2009 American Academy of Family Physicians.)
▲ See related editorial on page 938.
Pneumonia is the second most com- infection with multidrug-resistant patho-
mon cause of infection in nursing gens include antibiotic therapy within home residents, and is associated the preceding 90 days, a high incidence of with notable morbidity and mortal-
antibiotic resistance in the community or
ity.1 Attributable 30-day mortality rates range facility, chronic hemodialysis, and immu-from 10 to 30 percent.2-4 Prompt diagnosis nosuppression.7 One study found that recent and management are therefore essential. antibiotic use and the inability to perform This article reviews the clinical management activities of daily living were independently of nursing home–acquired pneumonia, with associated with antibiotic-resistant nurs-an emphasis on antimicrobial therapy.
ing home–acquired pneumonia requir-ing intensive care unit (ICU) admission or
Nursing home–acquired pneumonia is usu-
Nursing home–acquired pneumonia can
ally bacterial in origin, although the specific also be caused by viral infection (Table 15-12). microbiologic cause is often not identified.5-12 Influenza and respiratory syncytial virus Common bacterial etiologies are listed in (RSV) are important causes of respiratory Table 1.5-12 Streptococcus pneumoniae is the illness and mortality in nursing home resi-most common causative agent. However, dents.13,14 Physicians should suspect viral eti-in severe cases of nursing home–acquired ologies from late fall through early spring, pneumonia requiring hospitalization and and whenever outbreaks of respiratory infec-mechanical ventilation, the rates of infec-
tion occur. Influenza predisposes patients
tion with Staphylococcus aureus and enteric to a secondary bacterial pneumonia.15 In gram-negative organisms appear to exceed a population-based analysis involving 381 those of S. pneumoniae.5
nursing homes over a period of four years,
These organisms can be associated with investigators found that each year influenza
antimicrobial resistance, especially in infection was associated with approximately the nursing home setting. Risk factors for 28 hospitalizations; 147 courses of antibiotics;
976 American Family Physician Volume 79, Number 11 ◆ June 1, 2009
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use of one individual user of the Web site. All other rights reserved. Contact copyrig[email protected] for copyright questions and/or permission requests. Nursing Home–Acquired Pneumonia SORT: KEY RECOMMENDATIONS FOR PRACTICE
Physicians should suspect infection with resistant organisms in nursing home patients who received
antibiotics within the previous 90 days; when there is a high incidence of antibiotic resistance in the community or facility; and in patients who receive chronic dialysis, are immunosuppressed, or have difficulty performing activities of daily living.
Nursing home–acquired pneumonia should be suspected in patients with new or progressive
infiltrate plus a new-onset fever, leukocytosis, purulent sputum, or hypoxia.
Nonhospitalized nursing home patients requiring treatment for pneumonia should be treated with an
antipneumococcal fluoroquinolone, or either a high-dose beta-lactam/beta-lactamase inhibitor or a second- or third-generation cephalosporin, in combination with azithromycin (Zithromax).
Empiric coverage of methicil in-resistant Staphylococcus aureus and double coverage of Pseudomonal
pneumonia should be prescribed for patients requiring intensive care unit admission. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp. org/afpsort.xml.
and 15 deaths per 1,000 residents with heart or lung dis-
more, presence of crackles, or absence of wheezes on aus-
ease, diabetes mellitus, or immunosuppression. Similarly, cultation.18 The 2005 American Thoracic Society/Infec-RSV accounted for approximately 15 hospitalizations, tious Diseases Society of America (ATS/IDSA) guideline 76 courses of antibiotics, and 17 deaths per 1,000 resi-
recommends that the clinical diagnosis of health care–
dents with similar conditions.13 A recent report described associated pneumonia, including nursing home–human metapneumovirus as the cause of an outbreak of acquired pneumonia, be based on a new or progressive respiratory infections, including pneumonia, in a Cana-
infiltrate on chest radiography plus clinical findings con-
sistent with pneumonia (i.e., new-onset fever [tempera-ture greater than 100.4° F (38° C)], leukocytosis, purulent
The clinical manifestations of pneumonia in older adults
The 2005 ATS/IDSA guideline also recommends that
may be subtle. In one study, investigators found that per-
lower respiratory tract samples be obtained from nurs-
sons 65 years and older are less likely to complain of fever, ing home residents hospitalized with nursing home–chills, myalgia, and pleuritic chest pain than younger per-
acquired pneumonia, particularly from those who are
sons.17 One prospective study revealed that 80 percent of intubated, to guide treatment.7 Although respiratory nursing home residents with pneumonia exhibit three or cultures from nonintubated patients, and from those fewer respiratory signs or symptoms, but 92 percent have managed in the nursing home, could be considered, it is at least one identifiable respiratory manifestation, such important to note that these are infrequently obtained, as cough, respiratory rate of 30 breaths per minute or tend to produce a low yield of pathogenic microorgan-
isms, and are commonly contaminated with oropharyn-geal microflora, making interpretation difficult.19,20
Table 1. Common Etiologies of Nursing
Blood cultures are infrequently positive in patients with
pneumonia, but may be considered in those who require intensive care. Rapid antigen tests of respiratory secre-
tions, such as nasal washings, nasopharyngeal swabs, or throat swabs, can assist with the diagnosis of influenza
and RSV during the appropriate seasons.21 Urinary anti-
gen testing for S. pneumoniae and Legionella pneumoph-ila serotype 1 may be considered, although most studies
examining its use have been performed in patients with
community-acquired pneumonia (CAP).22-26 One limita-
tion of urinary antigen testing is the lack of information
about antibiotic susceptibility. Therefore, a sputum Gram
stain and culture should be considered if patients are able
Information from references 5 through 12.
to generate a useful sample and the results can be obtained in time to influence therapeutic decision-making.21
June 1, 2009 ◆ Volume 79, Number 11American Family Physician 977 Nursing Home–Acquired Pneumonia Evaluation of Suspected Aspiration Pneumonia
Signs and symptoms of lower respiratory tract infection
In many nursing home residents with
History of gastric content aspiration (definite or suspected)?
pneumonia, a diagnosis of aspiration pneu-monitis or aspiration pneumonia should be considered. Aspiration pneumonitis is an
inflammatory syndrome that does not typi-
cally require antibiotic therapy,27 whereas aspiration pneumonia is an infection for which antibiotic therapy should be initiated. Risk factors for these conditions include a
history of stroke, dementia, gastroesopha-geal reflux disease, and tube-feeding require-
ments. Pathogens isolated from nursing home
patients with severe aspiration pneumonia have included enteric gram-negative bacte-
ria, S. aureus, and anaerobes.6 The results of
a recent prospective cohort study validated
a new algorithm for diagnosis of aspiration pneumonitis versus aspiration pneumonia
Treatment IN THE NURSING HOME SETTING Figure 1. Algorithm for the evaluation of suspected aspiration
There is little evidence to suggest the clinical pneumonia.
superiority of one antibiotic over another for Adapted with permission from Mylotte JM, Goodnough S, Gould M. Pneumonia versus
nursing home–acquired pneumonia, par-
aspiration pneumonitis in nursing home residents: prospective application of a clinical algo-
ticularly in the nursing home setting. Previ-
rithm. J Am Geriatr Soc. 2005;53(5):756.
ous guidelines have recommended antibiotic therapy based primarily on microbiologic data.7,29,30
apy after three days of parenteral therapy. Successful
The 2005 ATS/IDSA guideline for the treatment of response was documented in 78 percent of patients
health care–associated pneumonia does not specifically treated with cefepime and 66 percent of patients treated address treatment of nursing home–acquired pneumo-
with ceftriaxone (P = not significant).32 Each year, the
nia in the nursing home setting.7 Guidelines based on Centers for Disease Control and Prevention (CDC) limited data and expert opinion recommend the use of recommendations for influenza treatment should be an antipneumococcal fluoroquinolone (e.g., levofloxa-
consulted for updates on recent resistance patterns and
cin [Levaquin] or moxifloxacin [Avelox]) alone or either treatment or prevention recommendations. a high-dose beta-lactam/beta-lactamase inhibitor (e.g.,
When a viral etiology of nursing home–acquired
amoxicillin/clavulanate [Augmentin]) or a second- or pneumonia is diagnosed and there is low suspicion of third-generation cephalosporin (e.g., cefuroxime [Cef-
secondary bacterial infection, antibiotics often can be
tin], cefpodoxime [Vantin], ceftriaxone [Rocephin]), discontinued. However, it should be noted that older in combination with azithromycin (Zithromax). Oral patients with influenza are at high risk of bacterial therapy is preferred over parenteral therapy in mild to superinfection. Oseltamivir (Tamiflu) and zanamivir moderate cases.29,30 Intramuscular cephalosporins also (Relenza) are approved for the treatment of influenza may be used.1,31
A and B in adults, but therapy should begin within two
A randomized, double-blind trial compared the safety days of symptom onset to confer the most benefit, and
and effectiveness of once-daily intramuscular injections increasing resistance to oseltamivir has recently been of cefepime (Maxipime) and ceftriaxone for nursing reported.33 These agents may lessen the severity of influ-home–acquired pneumonia treated within the nurs-
enza manifestations and may reduce the incidence of
ing home. Sixty-nine residents 60 years and older with post-influenza bacterial pneumonia.34radiographically-confirmed pneumonia and creatinine
Influenza vaccination is recommended for the preven-
clearances of less than 60 mL per minute were included tion of influenza in nursing home residents, but does not in the study. Most patients were switched to oral ther-
provide complete protection.34 Similarly, pneumococcal
978 American Family Physician Volume 79, Number 11 ◆ June 1, 2009Nursing Home–Acquired Pneumonia Table 2. Initial Intravenous, Adult Doses of Antibiotics for Empiric Therapy of Hospital- Acquired Pneumonia, Including Ventilator- Associated Pneumonia, and Healthcare–
vaccination is recommended for all nursing home
Associated Pneumonia in Patients with
patients in accordance with the latest CDC guidelines for
Late-Onset Disease or Risk Factors for
the prevention of pneumococcal pneumonia.35 Oseltami-
vir should be used prophylactically when an outbreak of influenza A or B occurs within a nursing home.34 There
are no data to support specific treatments for RSV and
human metapneumovirus in nursing home residents.36
IN HOSPITALIZED PATIENTS
Intravenous antimicrobial therapy should be initiated
for nursing home patients hospitalized with pneumonia,
with empiric coverage of methicillin-resistant S. aureus
(MRSA) and Pseudomonas aeruginosa. Antibiotic cover-
age of atypical organisms is controversial, and there are
no data to support such therapy. If an etiologic agent
is identified, antibiotic therapy should be narrowed to
minimize antibiotic resistance, toxicity, and cost. Hos-
pitalized patients are more likely to have drug-resis-
tant and highly pathogenic organisms.5-7,11 Antibiotics
administered in the past 90 days generally should not be
prescribed again, because the risk of infection with resis-
Nursing home residency is a major risk factor for MRSA
colonization, which can lead to subsequent infection. Rates of MRSA from six nursing homes and one skilled-
*—Dosages are based on normal renal and hepatic function.
nursing facility in the United States ranged from 24 to
†—Trough levels for gentamicin and tobramycin should be less than 1 µg/ml, and for amikacin they should be less than 4–5 µg/ml.
77 percent.38-40 Vancomycin (Vancocin; given intrave-
‡—Trough levels for vancomycin should be 15–20 µg/ml.
nously) and linezolid (Zyvox; given orally or intrave-
Reprinted with permission from American Thoracic Society; Infec-
nously) are recommended for the treatment of MRSA
tious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-
Risk factors for pneumonia caused by P. aeruginosa associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):402.
were identified in a study of 559 cases of CAP, including 45 cases of nursing home–acquired pneumonia. They include hospitalization within the previous 30 days or
For hospitalized patients with nursing home–acquired
pulmonary comorbid illness (e.g., chronic obstructive pneumonia, the 2005 ATS/IDSA guideline7 recom-pulmonary disease, asthma, chronic bronchitis, bron-
mends a combination antibiotic therapy consisting of
chiectasis, interstitial lung disease).42 When choosing the following: antipseudomonal agents, the physician should refer to
• An antipseudomonal cephalosporin, an antipseu-
local pseudomonal susceptibility patterns.
domonal carbapenem, or an extended-spectrum beta-
One prospective, randomized trial compared the effec-
tiveness of cefepime, with or without metronidazole (Fla-
gyl), versus ertapenem (Invanz) for hospital- or skilled
• An antipseudomonal fluoroquinolone or an amino-
facility–acquired pneumonia in nonventilated, non-ICU glycoside patients.43 The addition of vancomycin was permitted for
patients with suspected MRSA infection. Enterobacteria-
• An anti-MRSA agent (vancomycin or linezolid). ceae, S. pneumoniae, and S. aureus comprised 19.5, 12.9,
The broad empiric therapy includes coverage of MRSA
and 11.6 percent of the pathogens recovered, respectively. and double-coverage of P. aeruginosa. Specific antibiot-Forty percent of the S. aureus isolates were methicillin-
ics and recommended dosages are provided in (Table 2).7
resistant. Outcomes were similar; 87.3 percent of patients These recommendations are based on microbiologic data who received ertapenem and 86.0 percent of patients who from patients with severe pneumonia. Treatment should received cefepime improved.
be tailored to the local microbiology, resistance patterns,
June 1, 2009 ◆ Volume 79, Number 11American Family Physician 979 Nursing Home–Acquired Pneumonia
and specific patient risk factors.7 Aminoglycoside use cilastatin (Primaxin), which can cause seizures, should increased mortality in a retrospective review.44 If chosen be avoided in older patients with renal impairment. as therapy, aminoglycosides should be used with caution
Vancomycin dosing should be optimized to maintain
in patients with impaired renal function. Tigecycline trough concentrations in the range of 15 to 20 mcg per (Tygacil) and doripenem (Doribax) are newer antibiot-
mL.7 However, a retrospective review of patients with
ics being investigated in the treatment of health care– MRSA pneumonia did not demonstrate any correlation associated pneumonia, but they are not approved by the between serum vancomycin trough concentrations and U.S. Food and Drug Administration for this indication. mortality.51These medications may play a role in the treatment of hospitalized patients with nursing home–acquired pneu-
ADVERSE EFFECTS OF ANTIMICROBIAL AGENTS IN OLDER ADULTS
Adverse drug events are more likely to occur in older
adults than in other patients.50 The safest and most effec-
TIMING AND DURATION OF ANTIBIOTIC THERAPY
tive medication should be prescribed in an appropriate
The timing of initiation of antibiotic therapy in hospital-
dose for the shortest duration possible to adequately treat
ized patients with nursing home–acquired pneumonia the infection. In a study of nursing home patients, use of may be an important predictor of outcome.45 Therapy antibiotics was associated with preventable adverse drug given within four hours of admission was associated reactions (Table 3 50).52 with decreased length of stay and decreased mortality in one retrospective study, and is an important outcome DRUG INTERACTIONS WITH ANTIMICROBIAL AGENTS IN OLDER ADULTS
measure for the Centers for Medicare and Medicaid Ser-vices.45,46 However, other studies have not demonstrated Increasing age is associated with an increasing number a survival benefit or a more rapid clinical response.47,48 of medications used on a daily or weekly basis.53 Up to The 2007 IDSA/ATS guideline recommends initiation of 67 percent of nursing home patients will experience an antibiotic therapy for CAP within the emergency depart-
adverse drug reaction during a six- to 12-month stay, and
ment or as soon as possible after the diagnosis is made, use of more than eight medications is associated with rather than within a specified time period.21 Although no studies have specifically measured outcomes for nurs-ing home patients, similar recommendations apply to
Table 3. Adverse Effects of Antibiotics in Older Patients
The IDSA/ATS guideline recommends a seven-
to eight-day duration of therapy for health care–
associated pneumonia that has been treated with appro-
priate empiric antibiotics, has clinically improved, and
that is not caused by nonfermenting gram-negative bac-
Diarrhea, Clostridium difficile–associated
disease, drug-related fever, interstitial nephritis, rash, thrombocytopenia,
DOSING OF ANTIBIOTICS IN THE NURSING HOME PATIENT
Critically ill patients often have altered pharmacoki-
Diarrhea, C. difficile–associated disease
netics and pharmacodynamics, and antibiotics must be
dosed more aggressively than in other patients.49 Empiric
antibiotics in critically ill patients with nursing home–
acquired pneumonia should be dosed as outlined in
Table 2.7 As renal function declines with age, proper dos-
ing of antibiotic agents must be ensured to avoid adverse
effects.50 The Cockcroft-Gault equation is commonly
used to estimate creatinine clearance; manufacturers
generally use this equation to estimate creatinine clear-
Adapted with permission from Faulkner CM, Cox HL, Wil iamson JC.
ance when making recommendations about drug dosing
Unique aspects of antimicrobial use in older adults. Clin Infect Dis.
in patients with renal insufficiency. Aminoglycosides,
which can cause nephro- and ototoxicity, and imipenem/
980 American Family Physician Volume 79, Number 11 ◆ June 1, 2009Nursing Home–Acquired Pneumonia Table 4. Selected Drug Interactions of Common Antibiotics
Loop diuretics, nonsteroidal anti-inflammatory drugs,
Aluminum, magnesium, iron, zinc, calcium, sucralfate
Serotonergic agents (selective serotonin reuptake
inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, tramadol [Ultram])
Adapted with permission from Faulkner CM, Cox HL, Wil iamson JC. Unique aspects of antimicrobial use in older adults. Clin Infect Dis. 2005;40(7):1001.
increased rates of adverse drug reactions.54 Because of Hitchcock Medical Center in Lebanon, N.H., and a fellowship in infectious the large number of medications prescribed in nursing diseases at the University of Colorado Health Sciences Center, Denver. home patients, the potential for drug interactions is very Address correspondence to Kyle Mills, PharmD, BCPS, Swedish Medical high. Table 4 lists some common drug interactions with Center, 501 E. Hampden Ave., #3260, Englewood, CO 80113 (e-mail: which prescribers should be familiar.50 Most antibiotics [email protected]). Reprints are not available from the authors. alter the anticoagulant effects of warfarin (Coumadin), Author disclosure: Nothing to disclose. primarily by increasing these effects. All patients concur- rently taking antibiotics and warfarin should have their REFERENCES International Normalized Ratio monitored closely dur-
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[published correction appears in MMWR Morb Mortal Wkly Rep. 2006;55(29):800]. MMWR Recomm Rep. 2006;55(RR-10):1-42. 982 American Family Physician Volume 79, Number 11 ◆ June 1, 2009
Sara Lee Plain 4 oz Par Baked Variety Pack Bagels Units Unit Gross Net Cs Case Case Detailed Product Description (Slices, Units/Bag, Length Width Hght Case Pallet 14 Digit GTIN Cube Ti /Hi Sara Lee 4 oz P/B Bagel Variety Pack (5 Plain, 5 Cinn Dot Item Number : Kosher Symbol: Product Approx Dimensions: Thawed Shelf Life : Frozen Shelf Life ( Months
Woensdag 27-11-’96 Peter heeft last gehad van darmkrampen. Na het ontbijt begonnen we te pakken. De man van de tafellakens kwam langs. Wim ging onze terugreis bevesigen. Om 10u zouden we bericht I.v.m. ons terugreis krijgen. Ik vroeg Manney om de boodschapper om 2 kokosnoten : een in de bast en een andere zonder omhulsel te gaan kopen. We gaven Arun nog een pakje mignonetten en gaven fooien aan