CAP Case Studies

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Supplement issue

Case Studies of Lower Respiratory Tract Infections:Community-Acquired PneumoniaThomas M. File, Jr., MD, MSc Department of Internal Medicine and Infectious Disease Section, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio, USA; and Infectious Disease Service and Division of HIV Research, Summa Health System, Akron, Ohio, USA

ABSTRACT

Community-acquired pneumonia (CAP) is a common and potentially serious illness with signicant humanand economic costs to society. The recent collaborative statement from the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) represents the most up-to-date evidence-based

guidelines from North America, incorporating important advances in the management of patients withCAP. The cases presented in this review highlight many of the recent recommendations from theIDSA/ATS guidelines. 2010 Elsevier Inc. All rights reserved. The American Journal of Medicine (2010) 123, S4S15

KEYWORDS: Community-acquired infection; Fluoroquinolone; Methicillin-resistant Staphylococcus aureus ; Respi-ratory disorders; Tuberculosis

Community-acquired pneumonia (CAP) is a common andpotentially serious illness, particularly in elderly patientsand those with signicant comorbidities. 1-3 In the UnitedStates, CAP is the most frequent cause of death due to

infectious disease and is the eighth leading cause of deathoverall. 4,5 The mortality rate of patients treated on an out-patient basis is 1%; the rate for those who require admis-sion to the hospital averages 12%, but it approaches 40% forpatients with severe CAP who require admission to theintensive care unit (ICU). 1 The annual estimated incidenceof CAP requiring hospitalization is 267 individuals per100,000 population and 1,014 individuals 65 years of age. 6 More cases occur during the winter months. Theestimated economic cost in the United States exceeds $12billion a year. 7

In light of the impact of CAP, numerous professional

societies have developed guidelines for management of these infections. 8 The primary purposes of these guidelinesare to optimize care and, ultimately, improve outcome of patients. The most recent evidence-based guidelines fromNorth America are the collaborative statement from the

Infectious Diseases Society of America (IDSA) and theAmerican Thoracic Society (ATS), which incorporates im-portant advances in the management of patients with CAP. 8

The cases presented in this review highlight many of the

recent recommendations from the IDSA/ATS guidelines.

CASE 1

PresentationA 66-year-old man presented to his primary care practitionerwith a headache, fever, and cough for the previous 3 days, andrecent bouts of confusion.

History and Physical Examination

The patient had smoked cigarettes (approximately 1 pack per day) since age 17, had had type 2 diabetes mellitus for15 years, and had coronary artery bypass surgery 12 yearsago. He was treated with a macrolide (azithromycin) forsinusitis 8 weeks before presentation. Vital signs were asfollows: temperature, 100.8F (38.2C); pulse, 110 beats perminute, respiratory rate, 28 breaths per minute. Auscultationof his lungs revealed rhonchi in the right lower lobe. Ablood test showed leukocytosis (white blood cell [WBC]count 20,000 per mm 3 (20 109 /L), and his blood glucoselevel was 180 mg/dL (1 mg/dL 0.0555 mmol/L).

Statement of author disclosure: Please see the Author Disclosuressection at the end of this article.

Requests for reprints should be addressed to Thomas M. File, Jr., MD,MSc, Infectious Disease Service and Division of HIV Research, SummaHealth System, 75 Arch Street, Suite 506, Akron, Ohio, 44304.

E-mail address: [email protected] .

0002-9343/$ -see front matter 2010 Elsevier Inc. All rights reserved.doi:10.1016/j.amjmed.2010.02.002
mailto:[email protected]:[email protected]:[email protected]


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Comment. A patient presenting to a practitioners ofcewith cough (either productive or nonproductive), pleuriticchest pain, shortness of breath, temperature 38C, andcrackles on auscultation shows the classic signs and symp-toms of CAP. As seen with this patient, mental statuschanges may complement respiratory manifestations of thedisease; gastrointestinal symptoms (e.g., nausea, vomiting,diarrhea) also may be present. Leukocytosis (WBC countbetween 15,000/mm 3 and 30,000/mm 3 ) with a leftwardshift is the major blood test abnormality observed in patientswith CAP. No clear constellation of symptoms and signs hasbeen observed to universally and accurately predict thepatient with pneumonia. A demonstrative inltrate by im-aging techniques and/or supporting microbiologic data alsoare necessary.

Diagnostic TestingThe presence of a right lower lobe inltrate was detected ona plain chest radiograph ( Figure 1 ). Although this patientsclinical picture does suggest CAP, clinical symptoms andsigns alone are not specic for the denitive diagnosis,especially in elderly patients. A chest imaging study isrequired for an accurate diagnosis. 8 The presence of a newinltrate on a chest radiograph is considered the gold

standard when clinical features are supportive, as in thispatient. Radiologists are unable to reliably differentiate be-

tween bacterial and nonbacterial pneumonia based on ra-diographic appearance.

DiagnosisThe patient was diagnosed with CAP.

Determination of Site of CareThe patient was determined to have a class III PneumoniaSeverity Index (PSI) classication and a CURB-65 (confu-sion; urea 7 mmol/L; respiratory rate 30/min; low sys-tolic [ 90 mm Hg] or diastolic [ 60 mm Hg] blood pres-sure; age 65 years) score of 2a classication associated

with a mortality rate of 8% to 9%. The patient was admittedto a local hospital for care.

Comment. After establishment of the diagnosis, the nextmanagement decision is to determine the site of care. Thisdetermination has an impact on the intensity of diagnostictesting and options for empirical antimicrobial therapy. Ad-vantages of outpatient therapy include preference by mostpatients (if considered safe), association with faster conva-lescence of illness, avoidance of potential nosocomial com-plications, and decreased cost. The general consensus in themedical care community is that the majority of patients with

CAP can indeed be treated safely as outpatients. However,selected patients (like the patient in this case study) should

Figure 1 Plain chest radiograph showing presence of right lower lobe inltrate.

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be hospitalized based on their risk for poor outcome, whichmay be mitigated by close observation, respiratory support,intravenous antibiotics, and management of comorbid ill-ness. Deciding on whether to hospitalize a patient is basedon such tools as the Pneumonia Prediction Rule and theCURB-65 Rule. 9-11 The Pneumonia Prediction Rule utilizesa combination of demographic variables, comorbidities,

physical observations, and laboratory and radiographic vari-ables to assign patients to 1 of 5 classes. 9 The classes aredemarcated by distinct risks of mortality and consequentrecommendations regarding site of care as shown in Table 1 ;scoring to determine class is shown in Table 2 .10

Our current patient merits a class III status (PSI score 86points [age 66 years confusion 20]) with a risk of mor-tality of 5%, and is suggested for brief hospital observa-tion. Although the Pneumonia Prediction Rule is effectivein determining mortality risk, it is not user-friendly in theclinical setting, because it includes laboratory results thatmay not be available when a disposition decision must be

made. The CURB-65 Rule is more useful at the bedside,because it uses a much less rigorous process in its clinicaldeterminationmeasurements include confusion, urea con-centration, respiratory rate, blood pressure, and age. Thepatient with CAP in this case study scored a 2 (age 65years confusion), which also merits hospitalization. De-spite its simplicity, however, the CURB-65 may be consid-ered impractical because both a blood sample and labora-tory analysis of blood urea often are required. As a result,the CRB-65 was devised; it eliminates the blood urea de-termination but is otherwise identical to the CURB-65 and,therefore, is optimally designed for the ofce setting (see

Figure 2 and Figure 3). The performance of CRB-65 wasshown to be comparable to C URB-65 and PSI in a study byCapelastegui and colleagues. 12 Thus, once the diagnosis isestablished, the PSI or CURB-65 (or CRB-65) scores cansupport an initial site-of-care decision (i.e., hospital versusoutpatient).

Diagnostic Testing for EtiologyA blood culture, sputum Gram stain, and urinary antigentest were performed. In recent guidelines most tests areconsidered optional, but I advocate performing blood cul-tures, sputum Gram stain and culture, and urinary antigen

tests for Streptococcus pneumoniae and Legionella speciesfor patients requiring admission to the hospital. However,obtaining these tests should never delay administration of an-timicrobial therapy because timely administration is critical forgood outcome. Positive blood cultures are observed in approx-imately 11% of high-risk patients with CAP, although false-positive blood cultures can lead to prolong ed hospital stayswith signicantly greater use of vancomycin. 8,13

It may be difcult to obtain a good sputum sample, andvalidity of the Gram stain may be inuenced by such factorsas specimen collection, transport time to the microbiologylaboratory, rapidity of sample processing, satisfactory use of

cytologic criteria, absence of prior antibiotic therapy, andexperience of the interpreter; however, when stringent cri-

teria are applied, specicity for pneumococcal pneumoniacan approach 90%. 8,14 Epidemiologic trends should be con-sidered in deciding to perform additional diagnostic tests forless usual CAP pathogens, such as fungus or Mycobacteriaspecies.

The urinary antigen test for S pneumoniae is 50% to80% sensitive and 90% specic in adults. 8 In a pro-spective study of 269 patients with CAP and no identi-able pathogen, S pneumoniae urinary antigen was de-tected in 69 (27.5%) of those patients. 15 The additional

information on etiology may help narrow down choicesof antibiotic therapy.

Table 1 Pneumonia prediction rule

Total Points Class Mortality (%) How to Treat

I 0.1 Outpatient70 II 0.6 Outpatient

71-90 III 0.9-2.8 Brief hospital observation91-130 IV 8.2-9.3 Inpatient

130 V 27.0-29.2 Inpatient ICUICU intensive care unit. Adapted from N Engl J Med.10

Table 2 Point scoring system for assignment to risk classesII, III, IV, and V

Characteristic Points Assigned

Demographic FactorAge

Men Age (yr)

Women Age (yr) 10Nursing home resident 10Coexisting illnesses

Neoplastic disease 30Liver disease 20Congestive heart failure 10Cerebrovascular disease 10Renal disease 10

Physical examination ndingsAltered mental status 20Respiratory rate 30/min 20Systolic blood pressure 90 mm Hg 20Temperature 35C or 40C 15

Pulse 125 beats/min 10Laboratory and radiographic ndings

Arterial pH 7.35 30Blood urea nitrogen 30 mg/dL

(11 mmol/L)20

Sodium 130 mmol/L 20Glucose 250 mg/dL (14 mmol/L) 10Hematocrit 30% 10Partial pressure of arterial oxygen

60 mm Hg10

Pleural effusion 10

Adapted from N Engl J Med.10

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TreatmentThe patient was administered levooxacin 750 mg oncedaily for 5 days. The patient was stabilized by the second

day of therapy and was switched from intravenous to oraltherapy.

For the majority of patients, an etiologic pathogenicagent will not be identied owing to the lack of rapiddiagnostic methods. Consequently, an empirical approach toinitial therapy is typically based on the likelihood that a keypathogen is responsible. For this patient (hospitalized, non-ICU) the most common pathogens include S pneumoniae , Mycoplasma pneumoniae , Chlamydia pneumoniae , Hae-mophilus inuenzae , or Legionella species.

Empirical treatment of CAP is nearly universal becausepathogen identication, when possible, is generally not

available when a treatment decision needs to be made, andthe presenting clinical features are not specic enough toreliably predict the etiology of CAP. The recommendedtreatment option for an inpatient on the general ward iseither combination therapy with a -lactam, such as cefo-taxime, ceftriaxone, ertapenem, or ampicillin-sulbactam,plus azithromycin, or monotherapy with a respiratory uo -roquinolone (levooxacin, moxioxacin, gemioxacin). 8

Because the patient previously had been treated with amacrolide, levooxacin 750 mg once daily was adminis-tered. 16 A switch from intravenous to oral treatment isrecommended once the patient is stable, typically by the

second or third day of treatment in most cases even if S pneumoniae bacteremia is present. A treatment duration of

5 days is often adequate for either an outpatient or generalward patient with CAP, assuming the patient is doing wellat 48 to 72 hours and in the absence of an unusual pathogen.

When deciding on initial therapy, the clinician shouldalways ask the patient whether she or he has receivedantimicrobials within the last 3 months, because this is animportant risk factor for antimicrobial resistance. In suchcases, empirical therapy with a different antibiotic class ispreferred.

OutcomeThe patients fever was reduced within 3 days of therapy.His cough and fatigue remained for several weeks. Despitean initial good response from antimicrobial therapy with

resolution of fever and acute morbidity, it is very commonfor patients to experience prolonged cough and malaise. Toincrease their understanding of their illness and expectedclinical course, patients should be informed that symptomscan last for a prolonged period.

Although this patient was treated successfully, up to 15%of patients may not respond appropriately to initial antibi-otic treatment. The most common causes of treatment fail-ure are lack of or delayed response by the host despiteappropriate antibiotics or infection with an organism that isnot covered by the initial antibiotic regimen. Other causes of treatment failure include a resistant pathogen, an unusual

pathogen, a suppurative complication (e.g., empyema), orobstruction. It should be noted that a chest radiograph can

Figure 2 CRB-65 versus CURB-65 and Pneumonia Severity Index (PSI). CURB-65 confusion;urea 7 mmol/L; respiratory rate 30/min; low systolic ( 90 mm Hg) or diastolic ( 60 mmHg) blood pressure; age 65 years; CRB-65 confusion; respiratory rate 30/min; low systolic( 90 mm Hg) or diastolic ( 60 mm Hg) blood pressure; age 65 years. (Adapted from Eur Respir J .12 )



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remain abnormal for weeks (even in the presence of suc-cessful treatment).

CASE 2

PresentationA 79-year-old woman presented to her primary care prac-titioner with progressive weight loss, malaise, and a non-

productive cough that had developed over the past 3 weeks.

HistoryThe patient had several comorbid conditions, including obe-sity, type 2 diabetes, and hypertension. The last time sherecalled having a persistent cough (although less severe thanwhat she was now experiencing) was 10 years prior, whenshe had been administered an angiotensin-converting en-zyme (ACE) inhibitor to control her hypertension; the ACEinhibitor was discontinued and she remained on a dailyregimen of an angiotensin receptor blocker with a diuretic.Her greatest complaint in recent visits had been deteriorat-

ing vision related to macular degeneration. She had a stiltedgait secondary to a hip fracture repair experienced 5 years

ago. Her history also included a nonmalignant breast massthat had been biopsied approximately 10 years ago. She hada remote smoking history of approximately 2 packs of cigarettes per day, but she had quit in her late 40s.

Physical ExaminationPhysical examination revealed a fever (100.5F [38.1C]),elevated blood pressure 140/90 mm Hg, and a loss of 3 lb

(1.35 kg) since her last visit 4 months prior. The patient hadshortness of breath and, upon auscultation of her lungs, raleswere heard bilaterally. Blood analysis showed hemoglobinof 11.4 g/dL (114 g/L), WBC of 9.48 109 /L, and a plateletcount of 349 109 /L. A chest radiograph performed in theofce was interpreted as showing chronic brotic changesand probable small patchy inltrates.

TreatmentThe patient was treated with an oral uoroquinolone for 5days and was scheduled for a return to the ofce at the endof therapy. In such cases as this patient with several comor-

bidities, empirical antibiotic therapy for an outpatient withCAP includes a respiratory uoroquinolone. These agents

Figure 3 Calculation of CURB-65 (confusion; urea 7 mmol/L; respiratory rate30/min; low systolic [ 90 mm Hg] or diastolic [ 60 mm Hg] blood pressure; age65 years). DBP diastolic blood pressure; ICU intensive care unit; SBP systolic

blood pressure. (For urea 7 mmol/L 20 mg/dL.) (Reprinted with permission fromThorax .11 )



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are widely chosen as empirical therapy for CAP owing totheir broad-spectrum activity, high bioavailability, and con-venient dosing schedules.

Posttreatment AssessmentThe patient felt improved at the conclusion of therapy andcanceled her follow-up appointment. The ofce receptionistplaced her call through to the physician assistant, to whomthe patient reported that her cough had dissipated somewhat

and that she no longer had a fever.

Return VisitThe patient returned to the ofce 2 months later concernedthat she had been coughing up blood over the previous 2days. In addition to hemoptysis, the patient revealed thatsince her previous visit she had continued to feel malaise,was continuing to lose weight, and had been experiencingnight sweats. The primary care physician suspected tuber-culosis (TB) (the patient now recalled that a family memberhad once been diagnosed with TB) and had the patienttransferred immediately for isolation in a local hospital.

A repeat chest radiograph revealed progressive bilateralbronodular diseases with a miliary pattern (see Figure 4).

The hospitalist ordered a sputum culture and the culture wassubsequently positive for Mycobacterium tuberculosis .

DiagnosisThe patient was diagnosed with TB. Although TB is fre-quently overlooked as a cause of CAP, it is responsible forapproximately 0.3% of cases in the United States. 17 This isfar removed from the prevalence seen in the epicenter of thehuman immunodeciency virus (HIV) pandemic in sub-Saharan Africa. An indication of TB as a common cause of CAP is illustrated by a prospective study of 266 patientsadmitted with a diagnosis of CAP in a hospital in Durban,South Africa, between May 2000 and July 2001a high-prevalence HIV setting. A microbiologic diagnosis of 169patients (64%) showed 44 with TB, 31 with Pneumocystis jirovecii pneumonia, and 35 with bacterial pneumonia. 18

A retrospective review of patients with active TB showshow pulmonary TB was unsuspected in a 515-bed, univer-sity-afliated, community teaching hospital located in Ak-ron, Ohio. In patients with cultures for M tuberculosis (1983to 1987), of 31 cases with active disease (admitted to 9different services), TB was not suspected in 13 (42%). The

patients with unsuspected TB were older, had a delay inisolation (1 vs. 6 days; P 0.002), had a longer hospital-ization (16 vs. 11 days; P 0.02), and showed a highermortality rate (46% vs. 11%; P 0.07). Interestingly, mostwere admitted with a diagnosis of CAP as well as carcinomaof the lung and congestive heart failure, among the admit-ting diagnoses; of note, these patients did not belong topopulations traditionally thought to be at risk. In the 13patients with unsuspected TB, the chest radiograph ndingswere as follows: upper lobe inltrate and/or cavitation (n6), lower lobe inltrate (n 2), bilateral diffuse inltrate(n 2), pulmonary nodule (n 1), pleural effusion (n 1),

and bilateral apical scarring (n 1).19Table 3 17 shows when to suspect TB as a cause of CAP,

Figure 4 Chest radiograph showing progressive bilateral bronodular diseases.

Table 3 When to suspect tuberculosis as a cause of community-acquired pneumonia

Patients from endemic areas Chest x-ray: upper lobe inltrate, cavitation, miliary pattern Hemoptysis or 1 mo of any of the following: cough, fever,

malaise, weakness, night sweats, or signicant weight loss Nursing home patients, homeless, prison dweller, alcoholism Human immunodeciency virus Exposure to tuberculosis

Adapted from Respir Care Clin North Am.17



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and Figure 5 shows worldwide endemic areas for TB. Toavoid misdiagnosing TB as CAP, it is recommended that thefollowing patients be considered suspect for TB: (1) patientswith a chest radiograph showing upper lobe inltrate, cav-itation, and a miliary pattern; (2) patients with hemoptysis

or 1 month of any cough, fever, malaise, weakness, nightsweats, or signicant weight loss; (3) patients failing orrelapsing after empirical therapy; and (4) any patient withHIV, regardless of CD4 count, with a known history of positive tuberculin skin test, previou s TB, or recent expo-sure to TB, who presents with CAP. 17

Fluoroquinolones should not be used as rst-line therapyto treat CAP in areas of endemic TB or in the other condi-tions listed in Table 2 . These drugs are likely to both mask active TB and se lect for quinolone resistance in the infect-ing mycobacteria. 20 Thus, clinicians should be aware of risk factors associated with TB pneumonia and avoid using a

uoroquinolone empirically in these patients owing to therisk of promoting uoroquinolone resistance.

As observed in the present case, several studies havedemonstrated delays in the treatment of TB in patientstreated empirically with uoroquinolones. 21-25 In a retro-spective study of 33 patients with culture-conrmed TB atJohns Hopkins Hospital in Baltimore, Maryland, 16 (48 %)patients received uoroquinolones for presumed CAP. 26

The median time between presentation to the hospital andinitiation of TB treatment was 21 days in those patientstreated with uoroquinolones compared with 5 days in thosepatients who did not receive uoroquinolone therapy ( P

0.04). This delay in treatment may be ascribed to partialsymptom resolution, as observed in the present case. Al-

though the patient in this case recovered fully, empiricaltreatment with uoroquinolones with the consequent delayin treatment has been associated with poorer outcomes ascomp are d with patients who do not receive uoroquino-lones. 21 Monotherapy with an empirical uoroquinolone

in patients with suspected CAP who have TB may beassociated with an initial partial response, but it is fol-lowed by gradual worsening of symptoms leading topoorer outcomes.

In a study by Ginsburg and colleagues, 27 2 of 55 M tuberculosis isolates were found to have decreased suscep-tibility to uoroquinolones, compared with 0 of 36 isolatesfrom nonuoroquinolone-treated patients. However, thiswas in a relatively small sample and more recent studieshave questioned whether empirical treatment with uoro-quinolone s is a concern in terms of increased M tuber culosisresistance. 28 For example, Huang and coworkers 29 found

that uoroquinolone resistance was restricted to multidrugresistant (MDR) strains and was a consequence of treatingpatients with MDR TB strains rather than empirical use inthe community setting. In a study of 420 M tuberculosisisolates from January 2004 to December 2005 in endemicareas of Taiwan, it was found that neither previous use of uoroquinolones nor duration of uoroquinolone exposurewas correlated with uoroquinolone susceptibility of theisolates. 30

Low and colleagues 28 propose that increasing empiricaluse of uoroquinolones to treat CAP may not necessarilylead to increased numbers of resistant M tuberculosis clones

in the future. This supposition is based on the use of uo-roquinolones in combination therapy and by the use of

Figure 5 Cases of tuberculosis per 100,000 population (2000). (Courtesy of University of California at Santa Cruz.)



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