clinical policy: critical issues in the management of ...pneumonia can be divided into 4 categories...

INFECTIOUS DISEASE/CLINICAL POLICY

Clinical Policy: Critical Issues in the Management of AdultPatients Presenting to the Emergency Department With

Community-Acquired Pneumonia

From the American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Critical Issuesin the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Community-AcquiredPneumonia:

Devorah J. Nazarian, MD, ChairOrin L. Eddy, MDThomas W. Lukens, MD, PhDScott D. Weingart, MDWyatt W. Decker, MD

Members of the American College of Emergency Physicians Clinical Policies Committee (Oversight Committee):

Wyatt W. Decker, MD (Co-Chair 2006-2007, Chair 2007-2009)

Andy S. Jagoda, MD (Chair 2003-2006, Co-Chair 2006-2007)

Deborah B. Diercks, MDBarry M. Diner, MD (Methodologist)Jonathan A. Edlow, MDFrancis M. Fesmire, MDJohn T. Finnell, II, MD, MSc (Liaison for Emergency

Medical Informatics Section 2004-2006)Steven A. Godwin, MDSigrid A. Hahn, MDJohn M. Howell, MDJ. Stephen Huff, MDEric J. Lavonas, MDThomas W. Lukens, MD, PhDDonna L. Mason, RN, MS, CEN (ENA Representative

2004-2006)Edward Melnick, MD (EMRA Representative 2007-2008)Anthony M. Napoli, MD (EMRA Representative 2004-2006)

704 Annals of Emergency Medicine

Devorah Nazarian, MDAnnMarie Papa, RN, MSN, CEN, FAEN (ENA

Representative 2007-2009)Jim Richmann, RN, BS, MA(c), CEN (ENA Representative

2006-2007)Scott M. Silvers, MDEdward P. Sloan, MD, MPHMolly E. W. Thiessen, MD (EMRA Representative 2006-

2008)Robert L. Wears, MD, MS (Methodologist)Stephen J. Wolf, MDCherri D. Hobgood, MD (Board Liaison 2004-2006)David C. Seaberg, MD, CPE (Board Liaison 2006-2009)Rhonda R. Whitson, RHIA, Staff Liaison, Clinical Policies

Committee and Subcommittees

Approved by the ACEP Board of Directors, June 23, 2009

Supported by the Emergency Nurses Association, July21, 2009

Policy statements and clinical policies are the official policies of the American College of EmergencyPhysicians and, as such, are not subject to the same peer review process as articles appearing in the printjournal. Policy statements and clinical policies of ACEP do not necessarily reflect the policies and beliefsof Annals of Emergency Medicine and its editors.

0196-0644/$-see front matterCopyright © 2009 by the American College of Emergency Physicians.doi:10.1016/j.annemergmed.2009.07.002

Volume , . : November

Clinical Policy

[Ann Emerg Med. 2009;54:704-731.]

ABSTRACTThis clinical policy from the American College of Emergency

Physicians focuses on critical issues concerning the managementof adult patients presenting to the emergency department (ED)with community-acquired pneumonia. It is an update of the2001 clinical policy for the management and risk stratificationof adult patients presenting to the ED with community-acquired pneumonia. A subcommittee reviewed the currentliterature to derive evidence-based recommendations to helpanswer the following questions: (1) Are routine blood culturesindicated in patients admitted with community-acquiredpneumonia? (2) In adult patients with community-acquiredpneumonia without severe sepsis, is there a benefit in mortalityor morbidity from the administration of antibiotics within aspecific time course? The evidence was graded andrecommendations were given based on the strength of evidence.

INTRODUCTIONCommunity-acquired pneumonia (CAP) is a major health

problem in the United States. CAP is the seventh leading cause ofdeath in the United States, with 1.7 million hospital admissions peryear.1,2 The annual economic costs of CAP-related hospitalizationshave been estimated at $9 billion.3 Pneumonia carries an age-adjusted mortality rate up to 22%.1 Despite clinical advances,pneumonia mortality rates have not decreased significantly sincepenicillin became routinely available.4

Pneumonia can be divided into 4 categories based on the site ofacquisition of illness: CAP, hospital-acquired pneumonia (HAP),ventilator-associated pneumonia (VAP), and health care-associatedpneumonia (HCAP).5 CAP has recently been defined as an acutepulmonary infection in a patient who is not hospitalized or living ina long-term care facility 14 or more days before presentation anddoes not meet the criteria for HCAP.5 HAP is defined as a newinfection occurring 48 hours or longer after hospital admission.VAP is defined as pneumonia occurring 48 to 72 hours afterendotracheal intubation. HCAP encompasses many patientspreviously defined as having CAP. HCAP is defined as infectionoccurring within 90 days of a 2-day or longer hospitalization; in anursing home or long-term care residence; within 30 days ofreceiving intravenous antibacterial therapy, chemotherapy, orwound care or after a hospital or hemodialysis clinic visit; or in anypatient in contact with a multidrug-resistant pathogen.6 Anemerging body of evidence suggests that patients with HCAP moreclosely resemble patients with HAP and may require HAP-liketreatments.6-8

Given the significance of CAP, improving pneumonia care hasbecome a recent focus of many organizations such as The JointCommission and the Centers for Medicare & Medicaid Services(CMS). There are a number of core measures for patients admittedwith the diagnosis of pneumonia. Core measures that evaluate theemergency department (ED) care of CAP patients include blood
culture collection prior to first antibiotic administration (when ED

blood cultures are drawn), administration of initial antibioticswithin 6 hours of ED arrival (previously within 4 hours), andappropriate antibiotic selection.9

To comply with antibiotic quality measures and CMS andprivate payer pay for performance programs, some EDs havemoved toward treating possible CAP patients with antibioticsbefore the diagnosis is confirmed.10 In this age of increasingantibiotic resistance, this may have negative consequences inexcess of any putative benefit. Kanwar et al11 studied 2 cohortsof patients with the ED diagnosis of CAP, before and after theimplementation of antibiotic timing guidelines. To achieve anincrease in the number of patients with time to first antibioticdose less than 4 hours, an additional 17% of patients wereunnecessarily treated with antibiotics. Khalil et al12 performed aretrospective analysis of factors associated with the eventualdiagnosis of CAP in patients presenting to the ED. Of 1,948patients who presented with respiratory complaints, only 198eventually were diagnosed with CAP. If half of the patients inthis study received empiric antibiotics, at least 40% of thepatients would have received antibiotics unnecessarily,potentially increasing antibiotic resistance in the community. Inan online questionnaire, Pines et al10 found that 37% ofacademic EDs administer antibiotics before obtaining chestradiograph. In a retrospective chart review of patients admittedwith pneumonia, 22% of the patients presented in a mannerthat can result in delayed antibiotics delivery as a result ofdiagnostic uncertainty.13 The most recent iteration of the CMSguidelines includes provisions for diagnostic uncertainty whenassessing time to first antibiotic dose. With the current EDcrowding crisis, the feasibility of rapid antibiotic administrationcan be difficult.14-16

The disposition of patients with pneumonia is a majordecision for emergency physicians, with impact on patientoutcome. Prognostic tools such as the Pneumonia SeverityIndex (PSI) and severity-of-illness indexes such as the CURBand CURB-65 scores have been validated in several studies andcan be used to aid in admission decisions.17,18 The PSI stratifiespatients into 5 categories on the basis of mortality risk. It hasbeen suggested that patients in groups I and II be treated asoutpatients, those in group III be treated in an observation unitor with a short hospitalization, and those patients who fall intogroups IV and V be admitted for treatment.19 CURB-65 is aneasy-to-use severity-of-illness score that uses the followingfactors as indicators of increased mortality: Confusion, Urea,Respiratory rate, low Blood pressure, and age 65 or greater. Limet al20 suggested that patients with a CURB-65 score of 2 betreated as inpatients; those with a score of 3 or greater will oftenrequire an ICU.* These prognostic tools do not take intoaccount the psychosocial factors and other comorbidities that

*Confusion based on specific mental test or disorientation to person,place, or time, Urea �7 mmol/L (20 mg/dL), Respiratory Rate �30breaths/min, Blood pressure systolic �90 mm Hg or diastolic �60 mm
Hg, and age �65 years.
Annals of Emergency Medicine 705

Clinical Policy

may also play a role in the emergency physician’s determinationof the best site of treatment for patients with CAP.

Most patients admitted for CAP are first cared for in theED.21 This clinical policy critically evaluates the availableevidence about 2 often controversial critical issues in the care ofpatients admitted with the diagnosis of CAP.11,13,22-25 Thefocused critical questions addressed in this policy include thefollowing:1. Are routine blood cultures indicated in patients admitted

with CAP?2. In adult patients with CAP without severe sepsis, is there a

benefit in mortality and morbidity from the administrationof antibiotics within a specific time course?

METHODOLOGYThis clinical policy was created after careful review and

critical analysis of the medical literature. Multiple searches ofMEDLINE, MEDLINE In-Process, and the Cochrane databasewere performed. Specific key words/phrases used in the searchesare identified under each critical question. All searches werelimited to English-language sources, human studies, and adults.Additional articles were reviewed from the bibliography ofarticles cited and from published textbooks and review articles.Subcommittee members supplied articles from their own files,and more recent articles identified during the process were alsoincluded.

The reasons for developing clinical policies in emergencymedicine and the approaches used in their development havebeen enumerated.26 This policy is a product of the AmericanCollege of Emergency Physicians (ACEP) clinical policydevelopment process, including expert review, and is based onthe existing literature; when literature was not available,consensus of emergency physicians was used. Expert reviewcomments were received from individual emergency physiciansand from individual members of the American College of ChestPhysicians, the American College of Physicians, the InfectiousDiseases Society of America, the Institute for Clinical SystemsImprovement, the Society for Academic Emergency Medicine,and ACEP’s Section on Critical Care Medicine. Their responseswere used to further refine and enhance this policy; however,their responses do not imply endorsement of this clinical policy.Clinical policies are scheduled for revision every 3 years;however, interim reviews are conducted when technology or thepractice environment changes significantly.

All articles used in the formulation of this clinical policy weregraded by at least 2 subcommittee members for strength ofevidence and classified by the subcommittee members into 3classes of evidence on the basis of the design of the study, withdesign 1 representing the strongest evidence and design 3representing the weakest evidence for therapeutic, diagnostic,and prognostic clinical reports, respectively (Appendix A).Articles were then graded on 6 dimensions thought to be mostrelevant to the development of a clinical guideline: blindedversus nonblinded outcome assessment, blinded or randomized
allocation, direct or indirect outcome measures (reliability and

validity), biases (eg, selection, detection, transfer), externalvalidity (ie, generalizability), and sufficient sample size. Articlesreceived a final grade (Class I, II, III) on the basis of apredetermined formula, taking into account design and qualityof study (Appendix B). Articles with fatal flaws were given an“X” grade and not used in formulating recommendations in thispolicy. Evidence grading was done with respect to the specificdata being extracted and the specific critical question beingreviewed. Thus, the level of evidence for any one study may varyaccording to the question, and it is possible for a single article toreceive different levels of grading as different critical questionsare answered. Question-specific level of evidence grading may befound in the Evidentiary Table included at the end of thispolicy.

Clinical findings and strength of recommendations regardingpatient management were then made according to the followingcriteria:

Level A recommendations. Generally accepted principles forpatient management that reflect a high degree of clinicalcertainty (ie, based on strength of evidence Class I oroverwhelming evidence from strength of evidence Class IIstudies that directly address all of the issues).

Level B recommendations. Recommendations for patientmanagement that may identify a particular strategy or range ofmanagement strategies that reflect moderate clinical certainty(ie, based on strength of evidence Class II studies that directlyaddress the issue, decision analysis that directly addresses theissue, or strong consensus of strength of evidence Class IIIstudies).

Level C recommendations. Other strategies for patientmanagement that are based on preliminary, inconclusive, orconflicting evidence, or in the absence of any publishedliterature, based on panel consensus.

There are certain circumstances in which therecommendations stemming from a body of evidence shouldnot be rated as highly as the individual studies on which theyare based. Factors such as heterogeneity of results, uncertaintyabout effect magnitude and consequences, strength of priorbeliefs, and publication bias, among others, might lead to such adowngrading of recommendations.

This policy is not intended to be a complete manual on theevaluation and management of adult patients with CAP but rathera focused examination of critical issues that have particularrelevance to the current practice of emergency medicine.

It is the goal of the Clinical Policies Committee to providean evidence-based recommendation when the medical literatureprovides enough quality information to answer a criticalquestion. When the medical literature does not contain enoughquality information to answer a critical question, the membersof the Clinical Policies Committee believe that it is equallyimportant to alert emergency physicians to this fact.

Recommendations offered in this policy are not intended torepresent the only diagnostic and management options that theemergency physician should consider. ACEP clearly recognizes


Clinical Policy

the importance of the individual physician’s judgment. Rather,this guideline defines for the physician those strategies for whichmedical literature exists to provide support for answers to thecrucial questions addressed in this policy.

Scope of Application. This guideline is intended forphysicians working in hospital-based EDs.

Inclusion Criteria. This guideline is intended for patients18 years of age or older with signs and symptoms of CAP andradiographic evidence of pneumonia.

Exclusion Criteria. This guideline is not intended forpatients who are pregnant, or immunocompromised (includingpatients with HIV/AIDS, organ transplant, or recipients ofcorticosteroids, antineoplastic therapy, or otherimmunosuppressive agents), or have been hospitalized withinthe last 30 days.

CRITICAL QUESTIONS1. Are routine blood cultures indicated in patients

admitted with CAP?

Patient Management RecommendationsLevel A recommendations. None specified.Level B recommendations. Do not routinely obtain blood

cultures in patients admitted with CAP.Level C recommendations. Consider obtaining blood

cultures in higher-risk patients admitted with CAP (eg, severedisease, immunocompromise, significant comorbidities, or otherrisk factors for infection with resistant organisms).

Key words/phrases for literature searches: pneumonia,community-acquired pneumonia, blood cultures, microbiology,bacteremia, utility of blood cultures, timeline 1996 – May 20,2009.

The following have been identified as CMS core measures forpatients admitted with CAP: (1) the collection of blood culturesprior to antibiotic administration, when ED blood cultures aredrawn; (2) blood cultures performed within 24 hours prior to or24 hours after hospital arrival for patients who were transferredor admitted to the ICU within 24 hours of presentation to thehospital.9 The 2007 American Thoracic Society and InfectiousDiseases Society of America guidelines for the management ofpatients with CAP recommended pretreatment blood culturesfor those patients hospitalized with the following conditions:cavitary infiltrates, leukopenia, active alcohol abuse, chronicsevere liver disease, asplenia, positive test result forpneumococcal urinary antigen, pleural effusion, or thoseadmitted to the ICU. Blood cultures are optional for thosewithout the specifically listed conditions.27

Ideally, blood cultures identify a pathogen and its susceptibility,allowing antibiotic therapy to be customized for each patient.However, blood cultures are infrequently positive, and bloodculture results do not often lead to change in management. Avariety of Class II and III studies have reported the incidence ofpositive culture results in patients admitted with CAP. The yield
reported ranges from 0% in a series of 74 patients with nonsevere

CAP without significant comorbidities28 to 33% in 146 ICUpatients with CAP from Reunion Island.29 Typically, the range is1% to 16%.30-41

A number of Class II and III studies have investigated theimpact of blood cultures on antibiotic management in CAPpatients. Antibiotic therapy was changed based on blood cultureresults in 0% to 5% of patients cultured.31-33,38,39,42-44 Changein patient condition (either improvement or deterioration) wasmore likely to prompt antibiotic modification than results ofblood cultures.33,44,45 Few changes were made for coverage ofresistant organisms identified by blood cultures. The Class IIstudy by Campbell et al31 found that only 0.4% of bloodcultures drawn yielded an organism resistant to recommendedempiric antibiotics. Similarly, the Class II study by Kennedy etal39 noted 4 of 414 cultures drawn (1%) yielded resistantorganisms, resulting in 2 patients having their initial treatmentchanged (2 others had coverage altered to more effectiveantibiotics before culture results were known). One Class IIstudy45 and multiple Class III studies reporting changes inempiric therapy based on blood culture results demonstratesimilar findings. These studies, ranging in size from 86 to 517patients, reported organisms resistant to empiric therapy in 0%to 2.7% of patients that were cultured.32,33,38,42-46

There are few data about blood culture performance in CAPpatients and association with outcomes such as mortality, timeto clinical stability, and length of stay. In a Class II multicenterstudy, Dedier et al47 retrospectively examined 1,062 patientswith a primary admission diagnosis of pneumonia. They foundno difference in mortality or length of stay between patientswho had blood cultures and those who did not have bloodcultures before receiving antibiotics and no difference inmortality or length of stay between patients who had bloodcultures and those who did not have blood cultures within 24hours of admission. In the frequently cited Class III study byMeehan et al,48 investigators retrospectively examined a nationalstudy set of 1,343 Medicare patients with a discharge diagnosisof pneumonia. The authors concluded that blood culturecollection within 24 hours was associated with lower 30-daymortality; however, the odds ratio (OR) was 0.9, with aconfidence interval (CI) of 0.81 to 1.0 and a nonsignificant Pvalue of 0.07. This same study examined collection of bloodcultures before or after antibiotic administration and found nosignificant association with lower mortality if patients had bloodcultures collected before receiving antibiotics.

Blood culture results may be misleading and may causeunintended consequences. False-positive or contaminatedspecimens are common, and in some studies, rates of false-positive blood cultures approach those of true-positive.32,33,39-40,42

Treatment based on preliminary false-positive blood cultureresults may lead to unnecessary antibiotic coverage andincreased length of stay, pending final identification of theorganism. Metersky et al40 retrospectively analyzed 13,043Medicare patients with CAP and found 7% with true-positive
blood cultures and 5% false-positive blood cultures. Patients

Clinical Policy

with contaminated blood cultures had an average length of stayof 1 day longer than those who did not have contaminatedblood cultures (P�0.01). False-positive blood cultures are alsocostly. Bates et al49 reported that total hospital charges were$4,000 greater for patients with contaminated blood culturescompared with those with negative blood cultures.

Data suggest that blood cultures are more likely to provideresults leading to a change in management in select patients.Liver disease, hypotension, hypothermia or fever, tachycardia,uremia, hyponatremia, and leucopenia or leukocytosis have beenidentified as independent predictors of bacteremia.40

Immunocompromised patients and patients from nursinghomes or other long-term care facilities are more likely to haveunusual or resistant pathogens identified by bloodcultures.34,39,50 Patients with severe pneumonia may also benefitfrom blood culture tests.29,51 In a prospective Class III study of209 patients, Waterer and Wunderink38 found that bloodculture results led to change in antibiotics only in patients withPSI class IV and V disease, whereas patients in PSI class I to IIIhad no antibiotic changes based on blood culture results.

In summary, the routine use of blood cultures in all patientsadmitted with CAP has a low yield and rarely leads to change inmanagement or outcome for patients admitted with CAP. False-positive blood culture results may complicate the course for patientsadmitted with CAP. Therefore, blood cultures should be tailored tothe individual patient. Patients with severe pneumonia, who areimmunocompromised or have other significant comorbidities, maybenefit from having blood cultures drawn. Because antibioticadministration before blood culture testing decreases blood cultureyield, when blood cultures are necessary, they should be drawnbefore antibiotic administration.37,40,41

2. In adult patients with CAP without severe sepsis, isthere a benefit in mortality or morbidity from theadministration of antibiotics within a specific time course?

Patient Management RecommendationsLevel A recommendations. None specified.Level B recommendations. There is insufficient evidence to

establish a benefit in mortality or morbidity from antibioticsadministered in less than 4, 6, or 8 hours from ED arrival.

Level C recommendations. Administer antibiotics as soon asfeasible once the diagnosis of CAP is established; there isinsufficient evidence to establish a benefit in morbidity or mortalityfrom antibiotics administered within any specific time course.

Key words/phrases for literature searches: pneumonia,community-acquired pneumonia, time to treatment, rapidantibiotic delivery, morbidity, mortality, outcomes, length ofstay, quality of care, timeline 1988 – May 20, 2009.

The timely administration of antibiotics to infected patientsis good emergency medical practice. Before giving antibiotics, areasonable assurance of the diagnosis is essential to avoidmistreatment, medication overuse, and increased antibiotic

13,22,52
resistance.

In the most recent consensus guidelines on the managementof CAP in adults, the Infectious Diseases Society of Americaand the American Thoracic Society agreed that there is a paucityof data to support a specific time recommendation for theadministration of antibiotics in ED patients with CAP.27 Theirrecommendation states: for patients admitted through the ED, thefirst antibiotic dose should be administered while [the patient is]still in the ED.†

Four-Hour CutoffIn a frequently cited article, Houck et al53 analyzed whether

the time to first antibiotic dose might be associated withreductions in mortality and morbidity. In a retrospectivemulticenter, Class III study, Houck et al53 examined the chartsof 13,771 Medicare patients with a primary or secondaryInternational Classification of Diseases, Ninth Revision (ICD-9) diagnosis of pneumonia, who had not received out-of-hospital antibiotics. The patients analyzed were older than 65years, had not received out-of-hospital antibiotics, and hadradiographic evidence of pneumonia in the ED. This studyshowed an association between antibiotics administered within4 hours and a decreased 30-day mortality, with an OR of 0.85(95% CI 0.76 to 0.95). There was also a significant associationwith reduction of inhospital mortality and reduction of lengthof stay exceeding the 5-day median.

This study’s limitations include the following: more patientsin the group with time to first antibiotic dose less than 4 hoursreceived appropriate antibiotics, though this was included inmultivariate analysis.53 There was a post hoc determination ofthe 4-hour cutoff. Any of the cutoff times from 3 to 8 hourswere associated with similar 30-day mortality. The researcherschose the 4-hour cutoff, even though adjusted ORs of the 4-and 8-hour cutoffs were identical. They attempted to controlfor confounders through the performance of multivariateanalysis. Although the study controlled for many possibleconfounders, the possibility of missing others potentially biasesthe results, which may account for the fact that despite themultivariate analysis, patients who received antibiotics between0 and 2 hours did not have any significant mortality reduction.

Early administration of antibiotics is reliant on the earlydiagnosis of pneumonia. Patients whose disease is more difficult todiagnose because of atypical presentations may receive theirantibiotics later. If any of the factors that lead to the delayeddiagnosis are also associated with mortality, then the link betweenearly antibiotic administration and mortality may be spurious.Waterer et al54 examined these factors in a prospective Class IIstudy. The researchers performed an observational study of time tofirst antibiotic dose in patients older than 18 years and diagnosedwith CAP during their hospitalization. In univariate analysis, thisstudy confirmed the aforementioned association between time tofirst antibiotic dose less than 4 hours and mortality. However,when the data were examined for factors that can cause a delayed

†Infectious Diseases Society of America/American Thoracic Society
grading: moderate recommendation, level III evidence.

Clinical Policy

diagnosis of pneumonia, 3 factors emerged: altered mental status,the absence of hypoxia, and the absence of fever. When reanalyzedcontrolling for these factors, all of the mortality benefit associatedwith time to first antibiotic dose less than 4 hours disappeared.Altered mental status and the absence of fever remained associatedwith increased mortality after the multivariate analysis. This study’sresults indicate that for patients presenting with CAP and alteredmental status or the inability to mount a febrile response, it may bemore difficult to rapidly diagnose pneumonia, and they may be athigher risk for death.54 The study by Houck et al53 did notspecifically control for altered mental status or the presence of feverin the multivariate analysis.

In a prospective, observational Class II study, Silber et al55

examined the differences in time to clinical stability‡ in 409patients based on their door-to-antibiotic time. Three cohortswere analyzed: antibiotics in less than 4 hours, antibiotics in 4to 8 hours, and antibiotics in greater than 8 hours. There wereno statistically significant differences in time to clinical stabilitybetween the groups.

In another Class II study, Marrie and Wu56 implemented aCAP pathway for non-ICU patients at 6 Canadian hospitals.They prospectively analyzed the effects of time to first antibioticdose on inhospital mortality. Of the 3,043 patients included inanalysis, the mortality rate for time to first antibiotic dose lessthan 4 hours was 9.2% and the rate for time to first antibioticdose greater than 4 hours was 8.6%. If patients who receivedantibiotics before their arrival at the ED were removed (as in thestudy by Houck et al53), the mortality rate for time to firstantibiotic dose less than 4 hours was 8.3% and the mortalityrate for time to first antibiotic dose greater than 4 hours was8.1%, a nonsignificant difference.

Battleman et al57 performed a Class III, multicenter,retrospective analysis of 609 patients with a chart-codingdiagnosis of pneumonia. They examined the associationbetween time to first antibiotic dose and prolonged length ofstay (prolonged length of stay was defined as �9 days). They foundan association between shorter time to first antibiotic dose andfewer patients with prolonged length of stay. This finding was alsoobserved in patients who received their antibiotics in the ED ratherthan on the floor. This study excluded patients who died, and theactual data analysis of prolonged length of stay was not provided.Potential factors that may lead to a delayed diagnosis were notincluded in the analysis.

Six-Hour CutoffNo research has specifically examined a 6-hour cutoff for the

time to first antibiotic dose. This time period was part of thedata of the study by Houck et al53 mentioned above. This cutoffhad a significant association with reduced mortality (adjusted

‡Time to clinical stability is a composite measure of the first 24-hourperiod during which the patient has all of the following: systolic bloodpressure �90 mm Hg, pulse rate �100 beats/min, respiratory rate �24breaths/min, temperature �101°F, O2 saturation �90, and the ability to
eat.

OR 0.84; 95% CI 0.73 to 0.95); but the conclusions are limitedby all of the same factors present in the 4-hour cutoff.

Beyond 6 HoursAn 8-hour cutoff for time to first antibiotic dose has been

analyzed in a number of studies. A large, multicenter, retrospective,Class III study by Meehan et al48 demonstrated an associationbetween antibiotic administration within 8 hours of ED arrival andmortality (adjusted OR 0.85; 95% CI 0.75 to 0.96). This studyshares the same methodology as the analysis by Houck et al,53 andits conclusions are limited by many of the same issues. Patientswere included based on claims data, which may have led toselection bias. Confounding factors such as altered mental status,the absence of fever, and other clinical factors hindering diagnosiswere not included in the multivariate analysis.

The study by Marrie and Wu56 mentioned above alsoincluded data on time to first antibiotic dose less than 8 hourscompared with greater than 8 hours. There was no significantmortality difference between these 2 groups. Even when patientswho received antibiotics before arrival at the hospital wereremoved from the cohorts, no significant mortality benefitemerged for early antibiotic administration.§

Dedier et al47 retrospectively studied 1,062 CAP patientsfrom 38 hospitals. This Class III study examined the effect oftime to first antibiotic dose less than 8 hours on inpatientmortality, length of stay, and time to clinical stability. Therewere no significant associations with rapid antibioticadministration in any of these measures. There is insufficientevidence to establish a specific cutoff time for antibioticsadministration in patients who are diagnosed with CAP in theED. In the noncritically ill patient, it is prudent to administerantibiotics as soon as possible after a definitive diagnosis ismade.

Relevant industry relationships of subcommitteemembers: There were no relevant industry relationshipsdisclosed by the subcommittee members.

Relevant industry relationships are those relationshipswith companies associated with products or services thatsignificantly impact the specific aspect of disease addressedin the critical question.

Earn CME Credit: Continuing Medical Education is available forthis article at: http://www.ACEP.EMedHome.com.

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§P values of 0.81 were calculated from the study data with the SPSS 14.0
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http://www.ACEP.EMedHome.com

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26. Schriger DL, Cantrill SV, Greene CS. The origins, benefits, harms,and implications of emergency medicine clinical policies. AnnEmerg Med. 1993;22:597-602.

27. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious DiseasesSociety of America/American Thoracic Society consensusguidelines on the management of community-acquired pneumoniain adults. Clin Infect Dis. 2007;44:S27-S72.

28. Theerthakarai R, El-Halees W, Ismail M, et al. Nonvalue of theinitial microbiological studies in the management of nonseverecommunity-acquired pneumonia. Chest. 2001;119:181-184.

29. Paganin F, Lilienthal, F, Bourdin A, et al. Severe community-acquired pneumonia: assessment of microbial aetiology asmortality factor. Eur Respir J. 2004;24:779-785.

30. Beovic B, Bonac, B, Kese D, et al. Aetiology and clinicalpresentation of mild community-acquired bacterial pneumonia.Eur J Clin Microbiol Infect Dis. 2003;22:584-591.

31. Campbell SG, Marrie TJ, Anstey R, et al. The contribution of bloodcultures to the clinical management of adult patients admitted tothe hospital with community-acquired pneumonia: a prospectiveobservational study. Chest. 2003;123:1142-1150.

32. Chalasani NP, Valdecanas MA, Gopal AK, et al. Clinical utility ofblood cultures in adult patients with community-acquiredpneumonia without defined underlying risks. Chest. 1995;108:932-936.

33. Corbo J, Friedman B, Bijur P, et al. Limited usefulness of initialblood cultures in community acquired pneumonia. Emerg Med J.2004;21:446-448.

34. El-Solh AA, Sikka P, Ramadan F, et al. Etiology of severepneumonia in the very elderly. Am J Respir Crit Care Med. 2001;163:645-651.

35. Ewig S, Bauer T, Hasper E, et al. Value of routine microbialinvestigation in community-acquired pneumonia treated in atertiary care center. Respiration. 1996;63:164-169.

36. Fine MJ, Stone RA, Singer DE, et al. Processes and outcomes ofcare for patients with community-acquired pneumonia: resultsfrom the Pneumonia Patient Outcomes Research Team (PORT)cohort study. Arch Intern Med. 1999;159:970-980.

37. Glerant JC, Hellmuth D, Schmit JL, et al. Utility of blood culturesin community-acquired pneumonia requiring hospitalization:influence of antibiotic treatment before admission. Respir Med.1999;93:208-212.

38. Waterer GW, Wunderink RG. The influence of the severity ofcommunity-acquired pneumonia on the usefulness of bloodcultures. Respir Med. 2001;95:78-82.

39. Kennedy M, Bates DW, Wright SB, et al. Do emergencydepartment blood cultures change practice in patients withpneumonia? Ann Emerg Med. 2005;46:393-400.

40. Metersky ML, Ma A, Bratzler DW, et al. Predicting bacteremia inpatients with community-acquired pneumonia. Am J Respir CritCare Med. 2004;169:342-347.

41. van der Eerden MM, Vlaspolder F, de Graaff CS, et al. Value of
intensive diagnostic microbiological investigation in low- and high-

http://www.jointcommission.org/PerformanceMeasurement/PerformanceMeasurement/Current+NHQM+Manual.htm



Clinical Policy

risk patients with community-acquired pneumonia. Eur J ClinMicrobiol Infect Dis. 2005;24:241-249.

42. Ramanujam P, Rathlev NK. Blood cultures do not changemanagement in hospitalized patients with community-acquiredpneumonia. Acad Emerg Med. 2006;13:740-745.

43. Socan M, Marinic-Fiser N, Kraigher A, et al. Microbial aetiology ofcommunity-acquired pneumonia in hospitalized patients. EurJ Clin Microbiol Infect Dis. 1999;18:777-782.

44. Woodhead MA, Arrowsmith J, Chamberlain-Webber R, et al. Thevalue of routine microbial investigation in community-acquiredpneumonia. Respir Med. 1991;85:313-317.

45. Sanyal S, Smith PR, Saha AC, et al. Initial microbiologic studiesdid not affect outcome in adults hospitalized with community-acquired pneumonia. Am J Respir Crit Care Med. 1999;160:346-348.

46. Waterer GW, Jennings SG, Wunderink RG. The impact of bloodcultures on antibiotic therapy in pneumococcal pneumonia.Chest. 1999;116:1278-1281.

47. Dedier J, Singer DE, Chang Y, et al. Processes of care, illnessseverity, and outcomes in the management of community-acquired pneumonia at academic hospitals. Arch Intern Med.2001;161:2099-2104.

48. Meehan TP, Fine MJ, Krumholz HM, et al. Quality of care,process, and outcomes in elderly patients with pneumonia. JAMA.1997;278:2080-2084.

49. Bates DW, Goldman L, Lee TH. Contaminant blood cultures andresource utilization. The true consequences of false-positiveresults. JAMA. 1991;265:365-369.


50. Lujan M, Gallego M, Fontanals D, et al. Prospective observationalstudy of bacteremic pneumococcal pneumonia: effect of discordanttherapy on mortality. Crit Care Med. 2004;32:625-631.

51. Moine P, Vercken JB, Chevret S, et al. Severe community-acquired pneumonia. Etiology, epidemiology, and prognosisfactors. French Study Group for Community-Acquired Pneumoniain the Intensive Care Unit. Chest. 1994;105:1487-1495.

52. Houck PM. Antibiotics and pneumonia: is timing everything or justa cause of more problems? Chest. 2006;130:1-3.

53. Houck PM, Bratzler DW, Nsa W, et al. Timing of antibioticadministration and outcomes for Medicare patients hospitalizedwith community-acquired pneumonia. Arch Intern Med. 2004;164:637-644.

54. Waterer GW, Kessler LA, Wunderink RG. Delayed administrationof antibiotics and atypical presentation in community-acquiredpneumonia. Chest. 2006;130:11-15.

55. Silber SH, Garrett C, Singh R, et al. Early administration ofantibiotics does not shorten time to clinical stability in patientswith moderate-to-severe community-acquired pneumonia. Chest.2003;124:1798-1804.

56. Marrie TJ, Wu L. Factors influencing in-hospital mortality incommunity-acquired pneumonia: a prospective study ofpatients not initially admitted to the ICU. Chest. 2005;127:1260-1270.

57. Battleman DS, Callahan M, Thaler HT. Rapid antibiotic deliveryand appropriate antibiotic selection reduce length of hospital stayof patients with community-acquired pneumonia: link betweenquality of care and resource utilization. Arch Intern Med. 2002;162:682-688.


Evi

dent

iary

Tab

le.

Stud

y Y

ear

Des

ign

Inte

rven

tion(

s)/T

est(

s)/M

odal

ityO

utco

me

Mea

sure

/Cri

teri

on

Stan

dard

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Thee

rthak

arai

et

al28

2001

Pr

ospe

ctiv

e ob

serv

atio

nal

stud

y; 1

ho

spita

l in

Pate

rson

, NJ

Enro

lled

cons

ecut

ive

patie

nts w

ith

the

diag

nosi

s of C

AP

to a

sses

s the

va

lue

of th

e in

itial

mic

robi

olog

ical

st

udie

s, co

nsis

ting

of sp

utum

Gra

m’s

st

ain,

sput

um c

ultu

re, a

nd b

lood

cu

lture

, in

the

etio

logi

c di

agno

sis o

f C

AP

with

out c

omor

bidi

ty

212

patie

nts

scre

ened

,74

patie

nts

incl

uded

; age

s 22-

64

y; a

ll pa

tient

s had

: sp

utum

Gra

m’s

stai

n (a

ll m

ixed

flor

a),

sput

um c

ultu

re (4

pa

thog

ens 5

%),

bl

ood

cultu

res (

all

nega

tive)

No

posi

tive

bloo

d cu

lture

re

sults

in th

is lo

w-r

isk

popu

latio

n w

ith

nons

ever

e C

AP;

all

patie

nts h

ad im

prov

ed

sym

ptom

s by

48 h

and

be

cam

e af

ebril

e in

96

h;

no p

atie

nt re

quire

d a

chan

ge in

em

piric

an

tibio

tic c

over

age

inst

itute

d at

adm

issi

on

Smal

l sam

ple

size

; un

usua

lly lo

w y

ield

on

cultu

res;

no

base

line

patie

nt

com

paris

ons;

stud

y in

clud

ed

only

thos

e pa

tient

s abl

e to

pr

oduc

e va

lid sp

utum

sa

mpl

e, th

ey c

ould

diff

er

from

all

patie

nts w

ith C

AP;

po

ssib

le se

lect

ion

bias

; 21

(28%

) did

not

mee

t ATS

gu

idel

ine

crite

ria fo

r ad

mis

sion

; mul

tiple

ex

clus

ion

crite

ria,

esse

ntia

lly e

limin

atin

g al

l hi

gh-r

isk,

eld

erly

, and

sick

pa

tient

s

III

Paga

nin

et

al29

2004

Pr

ospe

ctiv

e ob

serv

atio

nal

stud

y 19

95-

2004

; dat

a fr

om 1

hos

pita

l on

a F

renc

h is

land

in th

e In

dian

Oce

an

Con

secu

tive

patie

nts a

dmitt

ed fr

om

the

ED to

ICU

for C

AP

from

9/1

995-

12/2

000;

stud

y ob

ject

ive:

to a

sses

s th

e et

iolo

gy a

nd p

rogn

ostic

fact

ors o

f C

AP

patie

nts a

dmitt

ed to

the

ICU

; ex

clus

ion

crite

ria: s

ever

e im

mun

osup

pres

sion

146

patie

nts,

34

excl

uded

as t

hey

did

not m

eet d

efin

ition

of

CA

P; 1

12 to

tal

incl

uded

; 94

(84%

) m

ale,

70

(62.

5%)

alco

holic

, 48

(43%

) di

ed; 5

5 pa

tient

s PSI

I-

II-I

II; 5

7 pa

tient

s PS

I IV

-V; a

ll ha

d at

le

ast 1

blo

od c

ultu

re;

37 (3

3%) p

ositi

ve

bloo

d cu

lture

; 23

S pn

eum

onia

e, 9

K

lebs

iella

, 2 c

ases

of

resi

stan

t S

pneu

mon

iae

Blo

od c

ultu

re m

ore

likel

y to

be

posi

tive

in si

cker

pa

tient

s, an

d po

sitiv

e bl

ood

cultu

re w

as a

n in

depe

nden

t ris

k fa

ctor

fo

r dea

th in

sick

er

patie

nts w

ith C

AP

(rel

ativ

e ris

k 2.

7; C

I 0.8

-8.

9; P

=0.0

002)

, als

o se

ptic

shoc

k, h

igh

SAPS

II

scor

e an

d in

fect

ion

with

Kle

bsie

lla

Stud

y se

tting

and

pop

ulat

ion

(Fre

nch

isla

nd in

the

Indi

an

Oce

an),

mos

tly m

ale,

m

ostly

alc

ohol

ic; n

ot

gene

raliz

able

, sel

ectio

n bi

as; l

ow le

vel o

f ant

ibio

tic

resi

stan

ce; 5

5 pa

tient

s PSI

I-II

-III

(why

wer

e th

ese

in th

e IC

U?)

III

Clinical Policy

712 Anna
ls of Emergency Medicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/Mod

ality

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Beo

vic

et a

l30

2003

Pr

ospe

ctiv

e;

mul

ticen

ter i

n Sl

oven

ia

Con

secu

tive

patie

nts w

ith C

AP

pres

entin

g to

7 st

udy

cent

ers l

ooki

ng

at e

tiolo

gy a

nd c

linic

al p

ictu

re o

f m

ild C

AP;

stud

y pa

tient

s wer

e bo

th

inpa

tient

and

out

patie

nts

116

patie

nts e

nrol

led,

11

3 in

clud

ed in

stud

y 10

9 ha

d co

mpl

ete

data

; 96/

109

(88%

) w

ere

PSI I

or I

I; 1

patie

nt h

ad a

pos

itive

bl

ood

cultu

re (S

pn

eum

onia

e);

etio

logy

est

ablis

hed

in 6

8 (6

2.4%

), 17

ty

pica

l, 42

aty

pica

l, 9

mix

ed

Aty

pica

l pat

hoge

ns p

lay

an im

porta

nt ro

le in

mild

C

AP;

ther

e w

as a

su

bsta

ntia

l sim

ilarit

y in

th

e cl

inic

al p

rese

ntat

ion

of p

neum

onia

cau

sed

by

diff

eren

t age

nts;

blo

od

cultu

res a

re v

ery

rare

ly

posi

tive

in m

ild C

AP

treat

ed w

ith o

ral

antib

iotic

s

Trea

tmen

t with

ora

l age

nts

was

incl

usio

n cr

iteria

; po

tent

ial s

elec

tion

bias

; ve

ry sm

all n

umbe

r of

patie

nts g

iven

that

en

rollm

ent i

nclu

ded

7 st

udy

cent

ers;

stud

y pa

tient

s wer

e bo

th in

patie

nt a

nd

outp

atie

nts;

inve

stig

ator

s do

not r

epor

t how

man

y w

ere

inpa

tient

s

III

Clinical Policy


Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/Mod

ality

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Cam

pbel

l et

al31

2003

Pr

ospe

ctiv

e;

mul

ticen

ter,

19 c

ente

rs in

C

anad

a

Patie

nts a

dmitt

ed w

ith C

AP

eith

er

rece

ivin

g ca

re p

er c

linic

al g

uide

line

or c

onve

ntio

nal m

anag

emen

t;

clin

ical

use

fuln

ess o

f blo

od c

ultu

re in

th

e m

anag

emen

t of p

atie

nts

hosp

italiz

ed w

ith C

AP

2,80

4 pa

tient

s en

rolle

d, 1

,061

ex

clud

ed; 7

16

inte

rven

tion

arm

; 1,

027

conv

entio

nal

arm

; 760

(74%

) bl

ood

cultu

res d

raw

n,

43 (5

.7%

) “s

igni

fican

t” p

ositi

ve

bloo

d cu

lture

; 3

patie

nts (

0.4%

, 3/

760)

cha

nged

to

broa

der s

pect

rum

as

indi

cate

d by

blo

od

cultu

re, 1

MSS

A, 1

PR

SP, 1

MR

SA;

6 ch

ange

d to

bro

ader

sp

ectru

m n

ot

indi

cate

d by

blo

od

cultu

re; 1

2 ch

ange

d to

nar

row

er/c

heap

er

as in

dica

ted

by b

lood

cu

lture

; 2 c

hang

ed to

na

rrow

er/c

heap

er n

ot

indi

cate

d by

blo

od

cultu

re; 1

7 co

ntin

ued

empi

ric th

erap

y de

spite

blo

od c

ultu

re

indi

catio

n to

step

do

wn;

blo

od c

ultu

re

resu

lts d

id n

ot

corr

elat

e w

ith P

SI

Ther

e w

as a

2%

cha

nce

(15/

760)

of h

avin

g a

chan

ge o

f the

rapy

di

rect

ed b

y bl

ood

cultu

re

resu

lts; i

n on

ly 0

.4%

was

th

is c

hang

e lik

ely

to h

ave

impr

oved

the

outc

ome

for

the

patie

nt; t

hose

with

po

sitiv

e bl

ood

cultu

re h

ad

a 39

% c

hanc

e of

hav

ing

ther

apy

chan

ged

due

to

bloo

d cu

lture

resu

lts, a

nd

a 42

% c

hanc

e of

hav

ing

ther

apy

cont

inue

d no

t in

dica

ted

by b

lood

cul

ture

re

sults

; rou

tine

bloo

d cu

lture

s rar

ely

cont

ribut

e si

gnifi

cant

ly to

the

clin

ical

man

agem

ent o

f C

AP

Dat

a pu

lled

from

stud

y on

us

e of

clin

ical

pat

hway

for

man

agin

g C

AP

— li

mits

in

tern

al v

alid

ity; l

arge

nu

mbe

r of p

atie

nts e

xclu

ded

— p

oten

tial s

elec

tion

bias

; in

terv

entio

n ar

m p

atie

nts

may

be

less

like

ly to

step

do

wn

or c

hang

e dr

ugs

beca

use

drug

is su

pplie

d;

in

terv

entio

n pa

tient

s mor

e lik

ely

to h

ave

bloo

d cu

lture

dr

awn

(58%

vs.

33%

);

limits

val

idity

; bas

elin

e ch

arac

teris

tics o

f pat

ient

s no

t com

pare

d; se

lect

ion

bias

; fal

se-p

ositi

ve

cont

amin

ants

not

cou

nted

or

disc

usse

d

II

Clinical Policy

714 Annals of
Emergency Medicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/Mod

ality

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Cha

lasa

ni e

t al

32

1995

R

etro

spec

tive;

si

ngle

in

stitu

tion

Cha

rt re

view

of a

dults

hos

pita

lized

w

ith C

AP

to d

eter

min

e th

e cl

inic

al

utili

ty o

f obt

aini

ng ro

utin

e bl

ood

cultu

re b

efor

e th

e ad

min

istra

tion

of

antib

iotic

s in

certa

in n

on-

imm

unos

uppr

esse

d pa

tient

s

1,25

0 pa

tient

s id

entif

ied

with

di

scha

rge

diag

nosi

s of

CA

P, 5

17 p

atie

nts

met

stud

y cr

iteria

; 6.

6% (3

4) tr

ue-

posi

tive

bloo

d cu

lture

, 4.8

% (2

5)

cont

amin

ated

blo

od

cultu

re; 5

6 pa

tient

s ha

d an

tibio

tics

chan

ged:

42

patie

nts

with

neg

ativ

e bl

ood

cultu

re a

nd 1

4 pa

tient

s with

pos

itive

bl

ood

cultu

re; 1

.4%

(7

of 5

17 p

atie

nts)

ha

d an

tibio

tic c

hang

e as

a re

sult

of b

lood

cu

lture

resu

lts, 6

na

rrow

ed, a

nd 1

br

oade

ned

to c

over

H

influ

enza

e

Blo

od c

ultu

res h

ave

limite

d cl

inic

al u

tility

and

qu

estio

nabl

e co

st-

effe

ctiv

enes

s; n

o pe

nici

llin

resi

stan

ce

note

d; ra

te o

f tru

e-

posi

tive

bloo

d cu

lture

si

mila

r to

rate

of

cont

amin

ated

blo

od

cultu

re

Ret

rosp

ectiv

e de

sign

; pa

tient

s ide

ntifi

ed b

y di

scha

rge

diag

nosi

s;

sele

ctio

n bi

as; l

ow ra

te o

f an

tibio

tic re

sist

ance

co

mpa

red

to c

urre

nt 2

007

rate

s; c

onta

min

ant

dete

rmin

ed b

y tre

atin

g ph

ysic

ian;

reas

on fo

r an

tibio

tic c

hang

e in

ferr

ed

for t

he c

hart,

not

nec

essa

rily

docu

men

ted

III

Clinical Policy


Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Cor

bo e

t al33

2004

R

etro

spec

tive;

si

ngle

in

stitu

tion

in

the

Bro

nx

In E

D p

atie

nts h

ospi

taliz

ed w

ith

CA

P, th

e hy

poth

esis

that

the

prop

ortio

n of

fals

e-po

sitiv

e bl

ood

cultu

res w

ould

exc

eed

the

prop

ortio

n of

true

pos

itive

s was

te

sted

; a se

cond

ary

aim

was

to

quan

tify

the

freq

uenc

y w

ith

whi

ch a

ntib

iotic

ther

apy

was

ch

ange

d ba

sed

on b

lood

cul

ture

re

sults

821

patie

nts a

dmitt

ed, 3

55

had

bloo

d cu

lture

s;20

%

posi

tive

bloo

d cu

lture

s (7

0/35

5), 3

3 tru

e-po

sitiv

e (9

%) a

nd 3

7 fa

lse-

posi

tive

(10%

); 23

8 pa

tient

s had

ch

ange

in a

ntib

iotic

s; 2

5 tru

e-po

sitiv

e ch

ange

d an

tibio

tics:

10

due

to

bloo

d cu

lture

s, 10

due

to

clin

ical

impr

ovem

ent,

1 du

e to

wor

seni

ng, 4

for

othe

r rea

sons

; 26

fals

e po

sitiv

e ch

ange

d an

tibio

tics:

6 d

ue to

blo

od

cultu

res,

187/

285

with

ne

gativ

e bl

ood

cultu

res

chan

ged

antib

iotic

s with

2

chan

ges d

ue to

blo

od

cultu

re re

sults

; ove

rall,

18

patie

nts (

5%) h

ad

antib

iotic

cha

nge

attri

bute

d to

blo

od

cultu

re: 1

0 tru

e-po

sitiv

e w

ith a

ntib

iotic

cha

nge

(7

narr

owed

, 3 b

road

ened

[n

ot b

ecau

se re

sist

ant])

, 6

fals

e po

sitiv

e w

ith

antib

iotic

cha

nge,

2 tr

ue-

nega

tive

with

ant

ibio

tic

chan

ge; 1

51 (4

3%) h

ad

antib

iotic

s cha

nged

due

to

clin

ical

impr

ovem

ent

and

23 (6

%) w

ith

antib

iotic

s cha

nged

due

to

clin

ical

det

erio

ratio

n

Rat

e of

con

tam

inat

ed

bloo

d cu

lture

s equ

aled

ra

te o

f tru

e-po

sitiv

e bl

ood

cultu

res;

clin

ical

co

nditi

on is

use

d m

uch

mor

e fr

eque

ntly

than

bl

ood

cultu

re to

cha

nge

antib

iotic

s; n

o or

gani

sm

was

iden

tifie

d by

blo

od

cultu

re th

at w

as re

sist

ant

to a

ntib

iotic

regi

men

or

igin

ally

cho

sen

Ret

rosp

ectiv

e de

sign

; un

derly

ing

cond

ition

s sta

ted

to b

e si

mila

r in

grou

ps b

ut

no ta

ble

prov

ided

; aut

hors

co

mm

ent t

hat l

engt

h of

stay

is

incr

ease

d w

hen

antib

iotic

co

vera

ge is

err

oneo

usly

br

oade

ned

to c

over

fals

e-

posi

tive

bloo

d cu

lture

re

sults

but

no

data

giv

en;

no d

ata

on m

orta

lity,

leng

th

of st

ay;P

SI n

ot re

porte

d

III

Clinical Policy

716 Annals o
f Emergency Medicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

El-S

olh

et

al34

2001

Pr

ospe

ctiv

e co

hort;

2

univ

ersi

ty

hosp

itals

in

New

Yor

k st

ate

Elde

rly p

atie

nts w

ith C

AP

adm

itted

to a

n IC

U w

hile

re

ceiv

ing

mec

hani

cal v

entil

atio

n st

udie

d to

det

erm

ine

the

prev

alen

ce o

f res

pira

tory

pa

thog

ens a

nd th

e ef

fect

of

com

orbi

dity

and

func

tiona

l st

atus

on

the

mic

robi

al e

tiolo

gy

of se

vere

pne

umon

ia in

the

very

el

derly

; nur

sing

hom

e, a

s wel

l as

CA

P pa

tient

s, in

clud

ed

136

patie

nts e

ligib

le, 1

04

patie

nts e

nrol

led,

57

from

ho

me,

47

from

nur

sing

ho

me;

in c

omm

unity

pa

tient

s the

mos

t com

mon

pa

thog

en w

as S

pn

eum

onia

e, le

gion

ella

; in

nur

sing

hom

e pa

tient

s th

e m

ost c

omm

on

path

ogen

was

S a

ureu

s(M

SSA

11,

MR

SA 3

); m

orta

lity

of 5

4.8%

not

di

ffer

ent b

etw

een

com

mun

ity v

s nur

sing

ho

me

patie

nts;

m

orta

lity

sign

ifica

ntly

hi

gher

in th

ose

who

re

ceiv

ed in

adeq

uate

an

timic

robi

al th

erap

y (3

9% v

s 4%

, P=0

.007

)

93 b

lood

cul

ture

s, 15

po

sitiv

e (1

6%),

mor

e po

sitiv

e fr

om n

ursi

ng

hom

e th

an h

ome

(10

vs 5

) bu

t not

stat

istic

ally

si

gnifi

cant

; eld

erly

nu

rsin

g ho

me

patie

nts

requ

iring

mec

hani

cal

vent

ilatio

n ar

e at

risk

for

path

ogen

s tha

t are

di

ffer

ent f

rom

the

usua

l C

AP

and

thos

e pa

thog

ens

are

pote

ntia

lly d

rug

resi

stan

t

Few

dat

a on

blo

od c

ultu

res;

ve

ry sp

ecifi

c, se

lect

po

pula

tion,

not

ge

nera

lizab

le; p

hysi

cian

ca

re n

ot st

anda

rdiz

ed

III

Ewig

et a

l3519

96

Ret

rosp

ectiv

e;

1 ho

spita

l in

Ger

man

y

CA

P pa

tient

s ref

erre

d to

a

terti

ary

care

cen

ter s

tudi

ed to

de

term

ine

the

diag

nost

ic y

ield

of

mic

robi

olog

ical

inve

stig

atio

ns

and

thei

r val

ue in

dire

ctin

g an

tibio

tic th

erap

y; re

latio

nshi

p be

twee

n m

icro

bial

resu

lts a

nd

asso

ciat

ion

with

pre

treat

men

t, se

verit

y of

dis

ease

, and

cha

nge

in a

ntib

iotic

s

93 e

piso

des i

n 92

pat

ient

s, 32

ICU

pat

ient

s 22

tran

sfer

s in

from

an

othe

r ins

titut

ion;

20

die

d; 7

4% (6

9) tr

eate

d w

ith a

t lea

st 1

ant

ibio

tic

befo

re a

dmis

sion

; 50

blo

od c

ultu

res d

one,

w

ith 7

pos

itive

(14%

); 52

sero

logy

with

12

defin

itive

pat

hoge

ns;

25 b

ronc

hosc

opy

with

1

defin

itive

pat

hoge

n;

56 sp

utum

cul

ture

—

excl

uded

to id

entif

y de

finiti

ve p

atho

gen

Res

ults

of m

icro

bial

in

vest

igat

ion

led

to

antib

iotic

cha

nge

in 9

ca

ses;

blo

od c

ultu

re

resu

lts le

d to

ant

ibio

tic

chan

ge in

0 c

ases

; de

finiti

ve p

atho

gen

iden

tifie

d in

8/3

2 (2

5%)

seve

re a

nd 1

1/51

(22%

) no

nsev

ere

CA

P; se

verit

y di

d no

t cor

rela

te w

ith

abili

ty to

iden

tify

path

ogen

—th

ey d

id n

ot

spec

ifica

lly a

ddre

ss b

lood

cu

lture

and

seve

rity

Smal

l stu

dy p

opul

atio

n gi

ven

data

from

8 y

; al

thou

gh n

o ba

selin

e pa

tient

ta

ble,

repo

rted

mix

is

atyp

ical

(mal

e:fe

mal

e 62

:30)

, als

o lo

ts o

f tra

nsfe

rs

in, m

uch

pote

ntia

l bia

s, ca

nnot

gen

eral

ize

to E

D

popu

latio

n; P

SI n

ot re

porte

d

III

Clinical Policy

Volume
, . : November Annals of Emergency Medicine 717

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/Mod

ality

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Fine

et a

l36

1999

Pr

ospe

ctiv

e ob

serv

atio

nal;

m

ultic

ente

r

Am

bula

tory

and

hos

pita

lized

CA

P pa

tient

s stu

died

for p

roce

ss-o

f-ca

re

bloo

d cu

lture

, oth

er la

bora

tory

and

m

icro

biol

ogic

test

ing,

leng

th o

f sta

y,

adm

it to

ICU

, mor

talit

y, ti

me

to

retu

rn to

usu

al a

ctiv

ities

12,5

00 p

oten

tial

case

s of C

AP

scre

ened

; 3,9

64

pote

ntia

l par

ticip

ants

; 2,

287

(57.

7%)

patie

nts e

nrol

led,

944

ou

tpat

ient

s, 1,

343

inpa

tient

s; 8

.5%

(77)

of

out

patie

nts h

ad

bloo

d cu

lture

bef

ore

antib

iotic

s, 2.

6% (2

) w

ere

posi

tive;

71.

2%

(951

) inp

atie

nts h

ad

bloo

d cu

lture

bef

ore

antib

iotic

s, 82

(8.6

%)

wer

e po

sitiv

e

Mos

t pat

ient

s with

pn

eum

onia

hav

e pn

eum

onia

of u

nkno

wn

etio

logy

, neg

ativ

e bl

ood

cultu

re; S

pne

umon

iae

and

H

influ

enza

e m

ost c

omm

on

path

ogen

s ide

ntifi

ed; b

lood

cu

lture

rec

omm

ende

d de

spite

low

yie

ld b

ecau

se

of th

e pr

ogno

stic

im

porta

nce

of b

acte

rem

ia

and

the

pote

ntia

l to

dire

ct

ther

apy

agai

nst a

spec

ific

path

ogen

Larg

e nu

mbe

r of e

ligib

le

patie

nts n

ot e

nrol

led;

en

rolle

d pa

tient

s wer

e yo

unge

r, m

ore

likel

y to

be

whi

te, m

ore

likel

y to

be

low

ris

k fo

r mor

talit

y; fe

w

outp

atie

nts h

ad b

lood

cu

lture

don

e; st

udy

did

not

dire

ctly

ass

ess t

he e

ffec

t of

rout

ine

mic

robi

olog

ic

test

ing

on m

edic

al o

utco

mes

III

Gle

rant

et

al37

1999

Pr

ospe

ctiv

e ob

serv

atio

nal;

1

hosp

ital i

n Fr

ance

Patie

nts h

ospi

taliz

ed fo

r mod

erat

e C

AP

(non

-IC

U) t

o co

mpa

re th

e ut

ility

and

cos

t ben

efits

of b

lood

cu

lture

in p

atie

nts w

ho h

ad o

r had

no

t rec

eive

d an

tibio

tic th

erap

y be

fore

ad

mis

sion

53 p

atie

nts;

all

had

bloo

d cu

lture

s;

30 n

o pr

evio

us

antib

iotic

, 23

had

prev

ious

ant

ibio

tic;

30 w

ithou

t pre

viou

s an

tibio

tics h

ad 7

4 bl

ood

cultu

res d

raw

n,

8 po

sitiv

e in

5

patie

nts;

23

with

pr

evio

us a

ntib

iotic

s ha

d 62

blo

od c

ultu

res

draw

n, 0

true

- po

sitiv

e, 2

co

ntam

inan

ts;

bact

erem

ia in

pat

ient

s w

ithou

t pre

viou

s an

tibio

tic 5

/30

vs

with

ant

ibio

tic 0

/23

P<0.

05; a

ll is

olat

ed

orga

nism

s wer

e su

scep

tible

to a

nti-

biot

ic in

itial

ly c

hose

n

Ther

e is

redu

ced

clin

ical

ut

ility

and

cos

t ben

efit

of

bloo

d cu

lture

s in

patie

nts

hosp

italiz

ed fo

r mod

erat

e C

AP

who

hav

e re

ceiv

ed a

n an

tibio

tic tr

eatm

ent b

efor

e

adm

issi

on; b

lood

cul

ture

s no

t lik

ely

to b

e po

sitiv

e in

m

oder

atel

y ill

hos

pita

lized

pa

tient

s pre

viou

sly

treat

ed

with

ant

ibio

tics

Aut

hors

do

not s

tate

how

m

any

CA

P pa

tient

s wer

e m

isse

d or

not

enr

olle

d;

smal

l stu

dy p

opul

atio

n;

auth

ors s

tate

coe

xist

ing

illne

sses

sim

ilar i

n pr

etre

ated

and

not

pre

treat

ed

grou

ps; h

owev

er, n

o ta

ble

or

stat

istic

s pro

vide

d to

show

ba

selin

e ch

arac

teris

tics o

f th

e 2

grou

ps; P

SI n

ot

repo

rted

III

Clinical Policy

718 Ann
als of Emergency Medicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Wat

erer

and

W

unde

rink38

2001

Pr

ospe

ctiv

e co

hort;

1

hosp

ital i

n M

emph

is

Pros

pect

ivel

y st

udie

d th

e yi

eld

and

effe

ct o

f blo

od

cultu

re in

pat

ient

s adm

itted

w

ith C

AP;

stud

ied

the

rela

tions

hip

betw

een

bloo

d cu

lture

yie

ld a

nd

corr

elat

ion

with

PSI

, as

wel

l as w

heth

er b

lood

cu

lture

resu

lts le

d to

a

chan

ge in

man

agem

ent;

hypo

thes

ized

that

blo

od

cultu

re w

ould

onl

y ha

ve a

si

gnifi

cant

eff

ect o

n pa

tient

m

anag

emen

t in

patie

nts i

n PS

I gra

des I

V a

nd V

; in

clud

ed o

nly

if su

bjec

ts

had

2 bl

ood

cultu

res b

efor

e

any

antib

iotic

; exc

lusi

on

crite

ria: n

onam

bula

tory

nu

rsin

g ho

me

patie

nts,

had

chem

othe

rapy

in p

ast 3

0 da

ys, h

ad p

revi

ous

hosp

italiz

atio

n in

pas

t 30

days

, AID

S,

imm

unos

uppr

essa

nt

ther

apy

Hig

her P

SI c

orre

late

d w

ith

high

er y

ield

from

blo

od c

ultu

re

P=0.

02

PSI #

+blo

od c

ultu

re

I – 1

(5.3

%)

II –

6 (1

0.2%

) II

I – 4

(10.

3%)

IV –

10

(26.

7%)

V –

8 (1

3.9%

); ch

ange

in m

anag

emen

t bas

ed

on b

lood

cul

ture

resu

lts; n

o di

ffer

ence

in m

orta

lity

in

patie

nts w

ith e

mpi

ric a

ntib

iotic

ch

ange

(16%

) vs t

hose

with

ch

ange

bas

ed o

n m

icro

biol

ogic

al re

sults

(25%

) (s

igni

fican

ce n

ot re

porte

d);

20 S

pne

umon

ia is

olat

ed,

3 ha

d M

IC>2

for p

enic

illin

, 11

resi

stan

t to

eryt

hrom

ycin

209

subj

ects

; all

had

bloo

d cu

lture

s;22

(10.

5%) d

ied,

38

(18.

2%) p

ositi

ve b

lood

cu

lture

, 9

(4%

) con

tam

inan

ts,

29 (1

3.9%

) tru

e-po

sitiv

e bl

ood

cultu

re,

12/2

9 ha

d ch

ange

in

man

agem

ent b

ased

on

bloo

d cu

lture

resu

lts: i

n 7

antib

iotic

ther

apy

was

in

tens

ified

, cha

nged

in 1

pa

tient

, and

dec

reas

ed in

5

patie

nts;

for P

SI I-

III,

11/1

17 h

ad p

ositi

ve b

lood

cu

lture

, 0 h

ad c

hang

e in

m

anag

emen

t bas

ed o

n bl

ood

cultu

re; f

or P

SI IV

-V

, 18/

92 h

ad p

ositi

ve

bloo

d cu

lture

, 12

had

chan

ge in

man

agem

ent

base

d on

blo

od c

ultu

re;

bloo

d cu

lture

isol

ate

resi

stan

t to

empi

ric

antib

iotic

in 1

cas

e; b

lood

cu

lture

resu

lts le

d to

a

chan

ge in

man

agem

ent

only

in si

cker

pat

ient

s with

PS

I IV

-V

.

Pros

pect

ive

coho

rt, n

ot c

lear

th

at th

is w

as c

onse

cutiv

e pa

tient

s; o

nly

incl

uded

pa

tient

s who

had

2 b

lood

cu

lture

s bef

ore

antib

iotic

s;

auth

ors d

o no

t rep

ort h

ow

man

y to

tal p

atie

nts w

ith

CA

P w

ere

adm

itted

and

did

no

t hav

e bl

ood

cultu

re; a

lso

auth

ors d

o no

t rep

ort

num

ber o

f pat

ient

s with

C

AP

not e

nrol

led;

pot

entia

l se

lect

ion

bias

; con

clus

ions

ab

out p

atie

nts w

ith p

ositi

ve

bloo

d cu

lture

are

lim

ited

by

the

smal

l num

ber o

f the

se

patie

nts,

n=29

; the

1 p

atie

nt

with

a b

lood

cul

ture

sh

owin

g a

resi

stan

t or

gani

sm le

adin

g to

a

chan

ge in

ant

ibio

tic d

ied

III

Clinical Policy

Volume , . :
November Annals of Emergency Medicine 719

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Ken

nedy

et

al39

2005

Pr

ospe

ctiv

e ob

serv

atio

nal;

1

hosp

ital i

n B

osto

n

Patie

nts a

dmitt

ed w

ith

bloo

d cu

lture

don

e an

d C

AP

diag

nose

d, a

nd th

e re

latio

nshi

p be

twee

n bl

ood

cultu

re re

sults

and

cha

nge

in e

mpi

ric th

erap

y in

blo

od

cultu

re–p

ositi

ve p

atie

nts

3,76

2 ED

pat

ient

s had

blo

od

cultu

res,

414

patie

nts

diag

nose

d w

ith p

neum

onia

; 7%

(29)

blo

od c

ultu

res t

rue-

po

sitiv

e, 3

60 b

lood

cul

ture

s ne

gativ

e; 6

% b

lood

cul

ture

s co

nsid

ered

con

tam

inat

ed;

3 pa

tient

s die

d be

fore

blo

od

cultu

re re

sults

; 15

patie

nts h

ad

ther

apy

alte

red

by b

lood

cu

lture

resu

lts: 1

1 na

rrow

ed, 4

br

oade

ned;

in 1

1 pa

tient

s the

th

erap

y un

chan

ged,

and

of

thes

e, 8

cou

ld h

ave

been

na

rrow

ed; 4

pat

ient

s had

blo

od

cultu

res p

ositi

ve fo

r org

anis

m

resi

stan

t to

empi

ric th

erap

y; 2

ha

d th

erap

y ch

ange

d to

bet

ter

antib

iotic

bef

ore

bloo

d cu

lture

re

sults

(bas

ed o

n cl

inic

al

cond

ition

); al

l 4 o

f the

se

patie

nts h

ad ri

sk fa

ctor

s for

re

sist

ant o

rgan

ism

s: 3

nur

sing

ho

me

resi

dent

s and

1 a

lcoh

olic

w

ith m

ultip

le c

omor

bidi

ties;

30 o

rgan

ism

s ide

ntifi

ed in

29

patie

nts;

12/

30 n

onsu

scep

tible

to

at l

east

1 a

ntib

iotic

; 9/3

0 no

nsus

cept

ible

to a

gent

s in

mor

e th

an 1

ant

ibio

tic c

lass

Blo

od c

ultu

res a

re lo

w

yiel

d an

d in

freq

uent

ly

chan

ge m

anag

emen

t; 3.

6%

of a

ll pa

tient

s had

blo

od

cultu

re; i

n bl

ood

cultu

re

posi

tive

patie

nts,

bloo

d cu

lture

lead

s to

chan

ge in

m

anag

emen

t in

52%

(1

5/29

); 10

0 bl

ood

cultu

res

wou

ld h

ave

to b

e do

ne in

C

AP

patie

nts t

o id

entif

y 1

patie

nt w

ith a

resi

stan

t or

gani

sm; a

ll pa

tient

s with

bl

ood

cultu

res p

ositi

ve fo

r re

sist

ant p

atho

gens

had

ris

k fa

ctor

s for

resi

stan

t or

gani

sms:

3 n

ursi

ng h

ome

resi

dent

s and

1 a

lcoh

olic

w

ith m

ultip

le

com

orbi

ditie

s; ra

te o

f tru

e-po

sitiv

e bl

ood

cultu

res

sim

ilar t

o ra

te o

f co

ntam

inat

ed b

lood

cu

lture

s

Ana

lysi

s of b

lood

cul

ture

- po

sitiv

e pa

tient

s as a

gro

up

is p

robl

emat

ic b

ecau

se th

ere

are

only

29

patie

nts;

lo

w ra

te o

f pen

icill

in

resi

stan

ce (2

0%);

ob

tain

ing

bloo

d cu

lture

was

pa

rt of

stud

y in

clus

ion

crite

ria; m

ay o

vere

stim

ate

bloo

d cu

lture

yie

ld;

stud

y di

d no

t inc

lude

pa

tient

s with

CA

P w

ho d

id

not h

ave

a bl

ood

cultu

re

done

: sel

ectio

n bi

as

II

Clinical Policy

720 Annals of Emerg
ency Medicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Met

ersk

y et

al

4020

04

Ret

rosp

ectiv

e;

mul

ticen

ter

natio

nal s

tudy

fr

om M

edic

are

clai

ms d

atab

ase

Rev

iew

of M

edic

are

Nat

iona

l Pne

umon

ia

Proj

ect/C

MS

QI p

rogr

am

data

base

to d

eter

min

e pr

edic

tors

of b

acte

rem

ia;

deci

sion

tool

mad

e an

d va

lidat

ed;

deriv

atio

n of

rule

: 4/

1998

-3/1

999;

va

lidat

ion

of ru

le:

7/20

00-3

/200

1

Der

ivat

ion

stud

y; 3

9,24

2 ca

ses

of p

neum

onia

,16,

327

excl

uded

—

no

bloo

d cu

lture

; 5,1

80

excl

uded

bas

ed o

n cr

iteria

and

4,

692

excl

uded

for m

issi

ng

data

; 13,

043

case

s rev

iew

ed:

7% (8

86) b

acte

rem

ia;

5% (6

43) c

onta

min

ated

blo

od

cultu

res;

mul

tivar

iate

ana

lysi

s sh

owed

incr

ease

d le

ngth

of

stay

due

to fa

lse-

posi

tive

bloo

d cu

lture

resu

lts; u

se o

f an

tibio

tics b

efor

e bl

ood

cultu

re

was

neg

ativ

ely

asso

ciat

ed w

ith

bact

erem

ia; i

ndep

ende

nt

pred

icto

rs o

f bac

tere

mia

: liv

er d

isea

se, s

ysto

lic B

P <9

0 m

m H

g; te

mpe

ratu

re <

35° o

r >4

0° C

; pul

se >

125

bea

ts/m

in;

bloo

d ur

ea n

itrog

en >

30

mg/

dL; s

odiu

m <

130

mm

ol/L

W

BC

<5,

000/

mm

3 or

>20,

000/

mm

3 ; age

, res

pira

tory

co

mpr

omis

e no

t ass

ocia

ted

with

bac

tere

mia

; val

idat

ion

stud

y: 1

2,77

1 pa

tient

s,7%

(9

54) b

acte

rem

ic; 8

49

bact

erem

ic p

atie

nts w

ould

be

iden

tifie

d by

dec

isio

n to

ol, 1

05

mis

sed;

583

(5%

) con

tam

inan

ts

Patie

nts w

ith c

onta

min

ated

bl

ood

cultu

res h

ad lo

nger

le

ngth

of s

tay

than

thos

e w

ho d

id n

ot P

<0.0

1;us

e of

an

tibio

tics b

efor

e bl

ood

cultu

re w

as n

egat

ivel

y as

soci

ated

with

bac

tere

mia

;de

cisi

on to

ol id

entif

ied

88%

-89%

of p

atie

nts w

ith

bact

erem

ia w

hile

redu

cing

38

% o

f blo

od c

ultu

res

done

;20%

mor

talit

y am

ong

patie

nts w

ith

bact

erem

ia w

ould

hav

e be

en m

isse

d by

dec

isio

n ru

le; P

SI n

ot si

gnifi

cant

ly

asso

ciat

ed w

ith b

acte

rem

ia

Patie

nts i

dent

ified

from

cl

aim

s dat

a w

ith

retro

spec

tive

revi

ew,

po

tent

ial s

elec

tion

bias

; pa

tient

s age

>65

y, p

oten

tial

for b

ias;

not

gen

eral

izab

le;

tool

is b

ette

r at d

etec

ting

pneu

moc

occa

l bac

tere

mia

th

an o

ther

pat

hoge

ns; o

nly

dete

cted

65%

of n

on-

pneu

moc

occa

l St

rept

ococ

cus s

p;

a pr

oble

m b

ecau

se o

ne g

oal

of b

lood

cul

ture

is to

id

entif

y un

usua

l org

anis

ms;

st

udy

not d

esig

ned

to

anal

yze

outc

ome;

rule

not

te

sted

pro

spec

tivel

y

II fo

r bl

ood

cultu

re

yiel

d;

III f

or

othe

r co

nclu

-si

ons

Clinical Policy

Volume , . : N
ovember Annals of Emergency Medicine 721

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

van

der

Eerd

en e

t al

41

2005

Pr

ospe

ctiv

e ob

serv

atio

nal;

1 la

rge

hosp

ital

in th

e N

ethe

rland

s

Eval

uate

d th

e di

agno

stic

yi

eld

of d

iffer

ent

mic

robi

olog

ical

test

s in

hosp

italiz

ed p

atie

nts w

ith

CA

P

262

patie

nts,

158

(60%

), pa

tient

s with

iden

tifie

d pa

thog

en, 4

0 (1

5%) p

ositi

ve

bloo

d cu

lture

s; n

o pe

nici

llin

or

mac

rolid

e re

sist

ant S

pn

eum

onia

e id

entif

ied;

pr

etre

atm

ent w

ith a

ntib

iotic

s le

d to

low

er b

lood

cul

ture

yi

eld:

5/6

6 (8

%) v

s 35/

188

(19%

), P=

0.03

; com

bina

tion

sput

um e

xam

inat

ion

with

G

ram

’s st

ain,

cul

ture

, and

pn

eum

ococ

cal a

ntig

en sh

owed

th

e hi

ghes

t dia

gnos

tic y

ield

(4

9%),

follo

wed

by

urin

ary

PCA

test

(20%

), fo

llow

ed b

y bl

ood

cultu

re (1

6%);

no

corr

elat

ion

betw

een

bloo

d cu

lture

yie

ld a

nd d

isea

se

seve

rity/

PSI

Inve

stig

atio

n of

sput

um

with

Gra

m’s

stai

n; c

ultu

re

and

pneu

moc

occa

l ant

igen

pr

ovid

ed th

e la

rges

t yie

ld

in d

eter

min

ing

the

etio

logy

of C

AP;

pr

etre

atm

ent w

ith

antib

iotic

s dec

reas

es b

lood

cu

lture

yie

ld

Tota

l num

ber o

f pat

ient

s ho

spita

lized

for p

neum

onia

an

d ho

w m

any

patie

nts w

ere

not e

nrol

led

and

not

repo

rted

— p

oten

tial

sele

ctio

n bi

as; s

ome

base

line

char

acte

ristic

s gi

ven

but n

o ta

ble

for

com

paris

on; l

ow a

ntib

iotic

re

sist

ance

rate

; not

ge

nera

lizab

le; n

o co

mm

ent

on e

ffec

t of b

lood

cu

lture

/mic

robi

olog

ic re

sults

on

mor

talit

y or

leng

th o

f st

ay, o

r cha

nge

in a

ntib

iotic

s

II fo

r bl

ood

cultu

re

yiel

d

Ram

anuj

am

and

Rat

hlev

42

2006

R

etro

spec

tive

obse

rvat

iona

l; si

ngle

hos

pita

l

Patie

nts a

dmitt

ed fr

om E

D

with

dia

gnos

is o

f CA

P in

w

hich

blo

od c

ultu

res w

ere

draw

n be

fore

ant

ibio

tics;

in

clud

ed IC

U p

atie

nts,

excl

uded

im

mun

osup

pres

sed,

re

cent

ly h

ospi

taliz

ed a

nd

nurs

ing

hom

e pa

tient

s;

all p

atie

nts w

ere

treat

ed

with

eith

er

ceftr

iaxo

ne+a

zith

rom

ycin

or

levo

floxa

cin

Num

ber o

f pos

itive

blo

od

cultu

res a

nd c

hang

es in

an

tibio

tics d

ue to

blo

od c

ultu

re

resu

lts; r

ecov

ery

of re

sist

ant

orga

nism

s and

if e

mpi

ric

antib

iotic

s are

suff

icie

nt fo

r pa

tient

s with

CA

P

532

ED p

atie

nts

hosp

italiz

ed w

ith C

AP;

28

9 pa

tient

s enr

olle

d;13

(4

.5%

) pat

ient

s had

true

- po

sitiv

e bl

ood

cultu

res,

13

had

fals

e-po

sitiv

e bl

ood

cultu

res;

org

anis

ms

isol

ated

wer

e se

nsiti

ve to

em

piric

ant

ibio

tics i

n al

l ca

ses;

no

patie

nt re

quire

d an

ant

ibio

tic c

hang

e du

e to

re

sist

ance

; 4 p

atie

nts h

ad

chan

ge in

ant

ibio

tics d

ue to

de

terio

ratio

n of

clin

ical

st

atus

Ret

rosp

ectiv

e de

sign

; sm

all s

tudy

pop

ulat

ion;

m

any

CA

P pa

tient

s did

not

ha

ve a

blo

od c

ultu

re —

po

ssib

le se

lect

ion

bias

; sm

all n

umbe

r of p

ositi

ve

bloo

d cu

lture

s with

no

resi

stan

t org

anis

ms,

diff

icul

t to

say

whe

ther

em

piric

an

tibio

tics a

re a

lway

s ap

prop

riate

III

Clinical Policy

722 Annals of
Emergency Medicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Soca

n et

al43

19

99

Pros

pect

ive;

1

hosp

ital i

n Sl

oven

ia

Adu

lt pa

tient

s >15

y o

f age

ad

mitt

ed w

ith p

neum

onia

(in

clud

ed n

ursi

ng h

ome

patie

nts)

to d

eter

min

e th

e m

icro

bial

etio

logy

of

pneu

mon

ia in

adu

lt pa

tient

s

211

patie

nts,

195

had

bloo

d cu

lture

s with

blo

od c

ultu

res

posi

tive

in 2

3 (1

2%);

em

piric

ther

apy

chan

ged

beca

use

of b

lood

cul

ture

resu

lts

in 2

(1%

of a

ll bl

ood

cultu

res

or 9

% o

f pos

itive

blo

od

cultu

res)

pat

ient

s

Blo

od c

ultu

re re

sults

do

not o

ften

lead

to c

hang

e in

th

erap

y in

this

setti

ng

Tota

l num

ber o

f pat

ient

s ho

spita

lized

for p

neum

onia

an

d nu

mbe

r not

enr

olle

d no

t re

porte

d; p

oten

tial s

elec

tion

bias

; unu

sual

ly lo

w ra

te o

f pn

eum

ococ

cal p

neum

onia

5.

7%, a

nd lo

w ra

te o

f an

tibio

tic re

sist

ance

; lim

its

gene

raliz

abili

ty; o

ne th

ird o

f pa

tient

s wer

e ta

king

an

tibio

tic b

efor

e ad

mis

sion

to

hos

pita

l

III

Woo

dhea

d et

al44

1991

Pr

ospe

ctiv

e;

2 B

ritis

h ho

spita

ls

How

mic

robi

olog

ical

in

vest

igat

ions

are

use

d in

an

uns

elec

ted

grou

p of

ad

ult p

atie

nts w

ith C

AP,

an

d ev

alua

te th

e us

eful

ness

of

the

resu

lts o

btai

ned

in

chan

ging

ant

ibio

tic

regi

men

; con

secu

tive

adul

ts

adm

itted

with

CA

P;

patie

nts i

dent

ified

pr

ospe

ctiv

ely,

cha

rts

revi

ewed

retro

spec

tivel

y;

excl

uded

: pat

ient

s ad

mitt

ed to

ger

iatri

c w

ard,

co

mm

unic

able

dis

ease

uni

t, m

alig

nanc

y,

imm

unos

uppr

essi

on

Cha

nge

in a

ntib

iotic

ther

apy

due

to m

icro

biol

ogic

al

iden

tific

atio

n of

pat

hoge

ns;

antib

iotic

cha

nges

occ

urre

d in

: 33

(31%

) pat

ient

s tot

al;

13/2

8 (4

6%) o

f pat

ient

s with

pa

thog

en id

entif

ied

(by

any

met

hod)

; 20/

78 (2

6%) o

f pa

tient

s with

out p

atho

gen

iden

tifie

d; 9

(8%

) pat

ient

s had

ch

ange

bec

ause

of r

esul

ts o

f m

icro

biol

ogic

al te

sts;

18

(17%

) ha

d ch

ange

bec

ause

of c

linic

al

cond

ition

122

patie

nts i

dent

ified

, 106

in

clud

ed; 2

8 (2

6%) h

ad

caus

ativ

e pa

thog

en

iden

tifie

d; 8

6 (8

1%) h

ad

bloo

d cu

lture

don

e, 9

(1

0%) p

ositi

ve; 4

(4%

) had

ch

ange

bec

ause

of b

lood

cu

lture

resu

lts; 2

(2%

) had

co

vera

ge b

road

ened

be

caus

e of

blo

od c

ultu

re

resu

lts; b

lood

cul

ture

s are

in

freq

uent

ly p

ositi

ve a

nd

rare

ly c

hang

e m

anag

emen

t

No

info

rmat

ion/

repo

rting

on

antib

iotic

resi

stan

ce,

ther

efor

e un

sure

whe

ther

st

udy

has e

xter

nal v

alid

ity;

olde

r dat

a fr

om B

ritai

n,

limits

gen

eral

izab

ility

; ab

solu

te n

umbe

r of p

atie

nts

with

ant

ibio

tic c

hang

es is

lo

w, d

iffic

ult t

o m

ake

conc

lusi

ons b

ased

on

33

patie

nts

III

Clinical Policy

Volume , . : No
vember Annals of Emergency Medicine 723

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Sany

al e

t al

45

1999

R

etro

spec

tive;

si

ngle

hos

pita

l

Rev

iew

of a

ll ad

ult p

atie

nts

with

CA

P di

scha

rged

in

1996

trea

ted

by 1

993

ATS

gu

idel

ines

to d

eter

min

e w

heth

er re

sults

of

mic

robi

olog

ic st

udie

s led

to

chan

ge in

ant

ibio

tics i

n pa

tient

s who

fail

to re

spon

d to

initi

al a

ntib

iotic

s (n

onre

spon

ders

); co

mpa

red

patie

nts w

ith se

vere

and

no

nsev

ere

CA

P

184

patie

nts,

94.6

% (1

74) h

ad

bloo

d cu

lture

s, 11

% (1

9/17

4)

bloo

d cu

lture

s pos

itive

; 116

ha

d sp

utum

ana

lysi

s, 34

%

(40/

116)

pos

itive

; no

diff

eren

ce in

rate

of p

ositi

ve

bloo

d cu

lture

bet

wee

n se

vere

C

AP

and

nons

ever

e C

AP

(11%

fo

r eac

h); 1

4% (2

5/18

4) d

id

not r

espo

nd to

initi

al

antib

iotic

s; 6

non

seve

re C

AP,

no

ne h

ad p

ositi

ve b

lood

cu

lture

, cha

nges

in a

ntib

iotic

s m

ade

empi

rical

ly; 1

9 se

vere

C

AP:

4 d

ied

<72

h, 1

3 ha

d po

sitiv

e m

icro

biol

ogic

stud

ies,

1 ha

d an

tibio

tic c

hang

e ba

sed

on b

lood

cul

ture

(gre

w

MR

SA);

11 p

atie

nts h

ad

mic

robi

olog

ic st

udie

s sen

sitiv

e to

initi

al a

ntib

iotic

s, bu

t an

tibio

tics w

ere

chan

ged

empi

rical

ly b

ecau

se o

f clin

ical

de

terio

ratio

n; p

atie

nts w

ith

bact

erem

ia h

ad g

reat

er

mor

talit

y th

an n

onba

cter

emic

pa

tient

s (21

% v

s 6.5

%,

P<0.

05)

Blo

od c

ultu

re c

hang

ed

man

agem

ent i

n 1

patie

nt,

0.5%

(1/1

74) o

f all

bloo

d cu

lture

s or 5

% (1

/19)

of

posi

tive

bloo

d cu

lture

s;

antib

iotic

s cha

nged

em

piric

ally

mor

e fr

eque

ntly

than

per

resu

lts

of m

icro

biol

ogic

stud

ies

(85%

vs 1

5%; n

o P

valu

e re

porte

d); i

n no

nres

pond

ers

ther

e w

as n

o di

ffer

ence

in

mor

talit

y be

twee

n th

ose

in

who

m a

ntib

iotic

s wer

e ch

ange

d em

piric

ally

and

th

ose

with

mic

robi

olog

ic

stud

y-gu

ided

cha

nges

Diff

icul

t to

com

e to

co

nclu

sion

abo

ut

nonr

espo

nder

s bec

ause

ac

tual

num

ber o

f no

nres

pond

ers (

25) i

s low

; re

trosp

ectiv

e de

sign

; pa

tient

s ide

ntifi

ed b

y di

scha

rge

diag

nosi

s;

low

leve

l of a

ntib

iotic

re

sist

ance

; all

S pn

eum

onia

e is

olat

ed b

y bl

ood

cultu

res

wer

e su

scep

tible

to

peni

cilli

n; a

ll pa

tient

s for

w

hom

mic

robi

olog

ic st

udie

s ch

ange

d m

anag

emen

t cam

e fr

om lo

ng-te

rm c

are

faci

lity

II fo

r bl

ood

cultu

re

yiel

d

Clinical Policy

724 Annals of Emerge
ncy Medicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Wat

erer

et

al46

19

99

Ret

rosp

ectiv

e;

1 ho

spita

l in

Mem

phis

To d

eter

min

e ho

w o

ften

phys

icia

ns c

hang

e m

anag

emen

t bas

ed o

n bl

ood

cultu

re re

sults

po

sitiv

e fo

r S p

neum

onia

; in

clud

ed p

atie

nts a

dmitt

ed

with

dia

gnos

is o

f CA

P,

bloo

d cu

lture

dra

wn

befo

re

antib

iotic

s and

at l

east

1

posi

tive

bloo

d cu

lture

for S

pn

eum

onia

; re

trosp

ectiv

e ch

art r

evie

w p

erfo

rmed

1,80

5 pa

tient

s with

CA

P;

118

patie

nts w

ith p

ositi

ve

bloo

d cu

lture

for S

pne

umon

ia;

105

char

ts a

vaila

ble;

74

patie

nts w

ith C

AP

and

bloo

d cu

lture

pos

itive

for S

pn

eum

onia

e in

clud

ed in

stud

y;

15 is

olat

es w

ere

peni

cilli

n re

sist

ant,

4 “h

igh

grad

e” (o

nly

one

with

MIC

=4);

4 is

olat

es

wer

e ce

phal

ospo

rin re

sist

ant,

1 hi

gh g

rade

; 51

patie

nts w

ithou

t pe

nici

llin

alle

rgy

grew

S

pneu

mon

iae

susc

eptib

le to

pe

nici

llin;

ant

ibio

tics w

ere

chan

ged

to p

enic

illin

in o

nly

11 o

f the

se (2

1.6%

)

Blo

od c

ultu

re c

hang

ed

man

agem

ent i

n 31

(42%

of

posi

tive

bloo

d cu

lture

); an

tibio

tic c

hang

ed in

2

(2.7

%) p

atie

nts b

ecau

se o

f re

sist

ance

; no

corr

elat

ion

betw

een

dise

ase

seve

rity

and

bloo

d cu

lture

po

sitiv

ity; p

hysi

cian

s ofte

n do

not

nar

row

ther

apy

as

indi

cate

d by

blo

od c

ultu

re

resu

lts

Ret

rosp

ectiv

e de

sign

; se

lect

pop

ulat

ion—

stud

y lo

oks a

t adm

itted

CA

P pa

tient

s with

blo

od c

ultu

res

posi

tive

for S

pne

umon

iae

only

; res

ista

nce

rate

low

and

le

vel o

f res

ista

nce

low

co

mpa

red

with

200

7 ra

tes o

f re

sist

ance

; aut

hors

do

not

repo

rt ho

w m

any

patie

nts

with

CA

P ha

d bl

ood

cultu

res d

one;

ther

efor

e ca

nnot

cal

cula

te b

lood

cu

lture

yie

ld; f

urth

erm

ore,

ca

nnot

cal

cula

te th

e ov

eral

l ut

ility

of b

lood

cul

ture

(of

the

tota

l num

ber o

f blo

od

cultu

res d

one,

wha

t pe

rcen

tage

led

to a

cha

nge

in m

anag

emen

t?)

III

Ded

ier e

t al

47

2001

R

etro

spec

tive

char

t rev

iew

; m

ultic

ente

r; 38

Uni

ted

Stat

es a

cade

mic

ho

spita

ls

CA

P pa

tient

s stu

died

to

dete

rmin

e re

latio

nshi

p be

twee

n pr

ompt

ac

hiev

emen

t of p

roce

ss o

f ca

re m

arke

rs (b

lood

cul

ture

w

ithin

24

hour

s of a

dmit,

bl

ood

cultu

re b

efor

e an

tibio

tic, a

ntib

iotic

with

in

8 h

of h

ospi

tal a

rriv

al,

oxyg

enat

ion

mea

sure

men

t w

ithin

24

h) a

nd o

utco

mes

(r

each

ing

clin

ical

stab

ility

w

ithin

48

h of

hos

pita

l ad

mis

sion

, dec

reas

ed

leng

th o

f sta

y an

d in

patie

nt

deat

hs)

1,45

7 pa

tient

s, 1,

062

elig

ible

; 89

% a

dmitt

ed th

roug

h ED

; 76

.2%

had

ant

ibio

tics w

ithin

8

h; 8

2.5%

blo

od c

ultu

res b

y 24

h;

72.

3% h

ad b

lood

cul

ture

s be

fore

ant

ibio

tics;

94.

5% h

ad

oxyg

en m

easu

red

by 2

4 h;

in

crea

sed

seve

rity

of il

lnes

s w

as a

ssoc

iate

d w

ith b

lood

cu

lture

per

form

ance

(P=0

.009

) an

d sh

orte

r tim

e to

ant

ibio

tics

(P=0

.04)

No

impr

ovem

ent i

n de

ath,

le

ngth

of s

tay

for p

atie

nts

with

blo

od c

ultu

re b

efor

e

antib

iotic

s or p

atie

nts w

ith

bloo

d cu

lture

s with

in 2

4 h;

no

con

sist

ent r

elat

ions

hip

betw

een

proc

ess-

of-c

are

mar

ker a

chie

vem

ent a

nd

impr

ovem

ent i

n th

e cl

inic

al

outc

omes

Ret

rosp

ectiv

e de

sign

; pa

tient

s ide

ntifi

ed b

y di

scha

rge

diag

nosi

s;

sele

ctio

n bi

as; m

edia

n nu

mbe

r of p

atie

nts f

rom

ea

ch h

ospi

tal 2

8, w

hich

se

ems l

ow; l

arge

num

ber o

f pa

tient

s exc

lude

d; h

igh

num

ber o

f low

-ris

k pa

tient

s in

the

stud

y po

pula

tion

(29%

PSI

I-II

); da

ta n

ot

give

n ex

plic

itly

for P

SI IV

-V

pat

ient

s; n

o pr

open

sity

m

atch

ing

perf

orm

ed d

espi

te

low

rate

of o

utco

me

II fo

r bl

ood

cultu

re;

III f

or

anti-

biot

ics

Clinical Policy

Volume ,
. : November Annals of Emergency Medicine 725

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Mee

han

et

al48

1997

R

etro

spec

tive;

m

ultic

ente

r na

tiona

l stu

dy

from

Med

icar

e cl

aim

s dat

abas

e

Rev

iew

of c

laim

s dat

a fr

om

Med

icar

e na

tiona

l cla

ims

hist

ory

file

and

patie

nt

char

ts to

ass

ess q

ualit

y of

ca

re fo

r Med

icar

e pa

tient

s ho

spita

lized

with

pn

eum

onia

and

to

dete

rmin

e w

heth

er p

roce

ss-

of-c

are

perf

orm

ance

is

asso

ciat

ed w

ith lo

wer

30-

day

mor

talit

y; 4

pro

cess

es

of c

are

inve

stig

ated

: bl

ood

cultu

res b

efor

e

antib

iotic

s, bl

ood

cultu

res

with

in 2

4 h,

tim

e to

an

tibio

tic a

dmin

istra

tion,

an

d ox

ygen

atio

n as

sess

men

t with

in 2

4 h

500

pote

ntia

l cas

es w

ere

sele

cted

rand

omly

from

eac

h st

ate,

DC

, and

Pue

rto R

ico;

26

,000

pot

entia

l cas

es, 1

4,06

9 ag

greg

ate

stud

y se

t;2,

500

subs

et o

f sam

pled

cas

es

crea

ted,

exc

lusi

on c

riter

ia

appl

ied

to c

reat

e 1,

343

natio

nal

stud

y se

t; m

ean

age

79.4

y;

23.4

% fr

om n

ursi

ng h

omes

; 58

.2%

had

at l

east

1

com

orbi

dity

; inh

ospi

tal

mor

talit

y 10

.3%

; 30-

day

mor

talit

y 15

.3%

; bl

ood

cultu

re c

olle

ctio

n w

ithin

24

h o

f adm

issi

on a

ssoc

iate

d w

ith lo

wer

30-

day

mor

talit

y:

OR

0.9

(95%

CI 0

.81-

1.0)

, P=

0.07

; blo

od c

ultu

re

colle

ctio

n be

fore

ant

ibio

tic

adm

inis

tratio

n w

as n

ot

sign

ifica

ntly

ass

ocia

ted

with

hi

gher

or l

ower

mor

talit

y O

R

0.92

(95%

CI 0

.82-

1.2)

, P=

0.10

Adm

inis

terin

g an

tibio

tics

with

in 8

h o

f hos

pita

l ar

rival

and

col

lect

ing

bloo

d cu

lture

s with

in 2

4 ho

urs

wer

e as

soci

ated

with

im

prov

ed su

rviv

al

Ret

rosp

ectiv

e re

view

of

clai

ms d

ata;

pot

entia

l se

lect

ion

bias

; stu

dy

popu

latio

n ol

der,

ofte

n fr

om

nurs

ing

hom

e, o

ften

with

co

mor

bidi

ties —

pat

ient

s m

ore

likel

y to

hav

e bl

ood

cultu

res a

nyw

ay; K

appa

for

abst

ract

ors a

s low

as 0

.48

for r

ecen

t che

mot

hera

py,

0.52

for m

enta

l sta

tus;

K

appa

for

blo

od c

ultu

re

0.83

with

in 2

4 h;

stud

y po

pula

tion

olde

r and

sick

er

than

gen

eral

ED

pat

ient

s;

conc

lusi

on th

at b

lood

cu

lture

don

e w

ithin

24

h is

as

soci

ated

with

redu

ced

mor

talit

y co

mes

from

dat

a w

ith P

=0.0

7, C

I inc

lude

s 1;

stat

istic

ally

sign

ifica

nt?

III

Clinical Policy

726 Annals of Emergency M
edicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Luja

n et

al50

20

04

Pros

pect

ive

obse

rvat

iona

l; 1

hosp

ital i

n B

arce

lona

Patie

nts a

ge >

18 y

ho

spita

lized

with

CA

P w

ith

bloo

d cu

lture

pos

itive

for S

pn

eum

onia

e to

eva

luat

e th

e ef

fect

of d

isco

rdan

t em

piric

al th

erap

y on

ou

tcom

e in

bac

tere

mic

pn

eum

ococ

cal C

AP;

ou

tcom

es e

xam

ined

in

clud

ed 2

8-da

y m

orta

lity,

us

e of

vas

oact

ive

med

icat

ions

, and

su

ppur

ativ

e co

mpl

icat

ions

100

cons

ecut

ive

patie

nts,

29

pneu

moc

occa

l iso

late

s sho

wed

so

me

resi

stan

ce to

pen

icill

in:

17 in

term

edia

te m

inim

um

inhi

bito

ry c

once

ntra

tions

(0

.12-

1 µg

/mL)

, 12

high

m

inim

um in

hibi

tory

co

ncen

tratio

ns (>

2 µg

/mL)

; 18

non

susc

eptib

le to

m

acro

lides

, 2 n

onsu

scep

tible

to

ceph

alos

porin

, 27

patie

nts

imm

unoc

ompr

omis

ed;

10 p

atie

nts h

ad d

isco

rdan

t th

erap

y, 5

0% (5

/10)

pat

ient

s w

ith d

isco

rdan

t the

rapy

die

d co

mpa

red

with

13/

90 (1

4%)

who

had

con

cord

ant t

hera

py;

estim

ated

exc

ess m

orta

lity

for

initi

al d

isco

rdan

t the

rapy

was

35

.6%

(95%

CI 3

.73-

67.4

); on

ly 3

of 9

pat

ient

s stil

l aliv

e w

hen

bloo

d cu

lture

de

mon

stra

ted

disc

orda

nt

ther

apy

actu

ally

had

ther

apy

chan

ged

to a

ppro

pria

te th

erap

y

Sign

ifica

nt a

ssoc

iatio

n be

twee

n di

scor

dant

ther

apy

and

high

er m

oral

ity in

ba

cter

emic

pat

ient

s with

pn

eum

ococ

cal C

AP;

nu

rsin

g ho

me

resi

denc

e an

d im

mun

ocom

prom

ised

pa

tient

s wer

e si

gnifi

cant

ly

asso

ciat

ed w

ith p

enic

illin

an

d m

acro

lide

resi

stan

ce

Dis

cord

ant p

ool i

nclu

ded

patie

nts w

ith in

term

edia

te

resi

stan

ce p

ossi

ble

skew

ing

resu

lts to

show

dis

cord

ant

ther

apy

caus

es le

ss h

arm

; ve

ry sm

all n

umbe

r of

patie

nts w

ith d

isco

rdan

t th

erap

y (1

0) le

ads t

o ve

ry

wid

e C

I; sp

ecifi

c gr

oup

of

patie

nts —

blo

od c

ultu

re

posi

tive

for S

pne

umon

ia;

6 pa

tient

s rec

eivi

ng

disc

orda

nt th

erap

y tre

ated

w

ith a

mox

icill

in-c

lavu

lana

te

as th

e in

itial

em

piric

an

tibio

tic, i

nclu

ding

2 w

ho

wer

e PS

I V; n

ot ty

pica

l of

empi

ric tr

eatm

ent f

or

hosp

italiz

ed p

atie

nts i

n th

e U

nite

d St

ates

; inc

lude

d im

mun

ocom

prom

ised

pa

tient

s — p

ossi

bly

bias

ing

to h

ighe

r mor

talit

y

III

Clinical Policy

Volume , . : Novemb
er Annals of Emergency Medicine 727

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Moi

ne e

t al

5119

94

Pros

pect

ive

obse

rvat

iona

l; m

ultic

ente

r; 15

Fr

ench

cen

ters

Con

secu

tive

patie

nts

hosp

italiz

ed w

ith se

vere

C

AP

in th

e IC

U to

de

term

ine

caus

ativ

e ag

ents

, th

e va

lue

of c

linic

al,

biol

ogic

, and

radi

olog

ic

feat

ures

in p

redi

ctin

g th

e et

iolo

gy, a

nd to

def

ine

prog

nost

ic fa

ctor

s in

patie

nts w

ith se

vere

CA

P

157

CA

P pa

tient

s, 25

ex

clud

ed; 1

32 st

udy

patie

nts:

98

mal

e, 3

4 fe

mal

e;

46 h

ad a

ntib

iotic

s bef

ore

ad

mis

sion

; 127

had

blo

od

cultu

res,

34 (2

7%) p

ositi

ve

bloo

d cu

lture

s, 22

S

pneu

mon

iae,

4 S

trep

toco

ccus

spec

ies,

1 Es

cher

ichi

a co

li, 5

K

lebs

iella

; 31

patie

nts h

ad

ther

apy

mod

ified

bas

ed o

n ba

cter

iolo

gic

resu

lts, 1

6 pa

tient

s with

uns

ucce

ssfu

l tre

atm

ent r

espo

nse

had

ther

apy

mod

ified

bas

ed o

n ba

cter

iolo

gic

resu

lts

(cha

nges

due

to b

lood

cul

ture

in

par

ticul

ar n

ot re

porte

d)

27%

bac

tere

mia

in th

is

popu

latio

n of

pat

ient

s with

se

vere

CA

P; b

lood

cul

ture

yi

eld

high

er in

sick

er

patie

nts;

bac

tere

mia

si

gnifi

cant

ly a

ssoc

iate

d w

ith d

eath

in th

is

popu

latio

n; d

eter

min

ing

the

etio

logy

did

not

im

prov

e su

rviv

al;

15/3

4 pa

tient

s with

po

sitiv

e bl

ood

cultu

re d

ied;

ba

cter

emia

sign

ifica

ntly

as

soci

ated

with

dea

th

(P=0

.004

)

Extre

me

mal

e pr

edom

inan

ce

98:3

4; a

lthou

gh 3

1 pa

tient

s ha

d th

erap

y m

odifi

ed b

ased

on

bac

terio

logi

c fin

ding

s, it

was

not

repo

rted

in h

ow

man

y bl

ood

cultu

re

spec

ifica

lly c

hang

ed

man

agem

ent

II

Hou

ck e

t al

5320

04

Mul

ticen

ter

retro

spec

tive

coho

rt

Enro

lled

18,2

09 p

atie

nts,

4,43

8 pa

tient

s exc

lude

d fo

r pr

etre

atm

ent a

ntib

iotic

s;

char

t rev

iew

of 1

3,77

1 pa

tient

s ≥6

5 y

with

ICD

-9

code

of p

neum

onia

from

m

ore

than

3,5

00 h

ospi

tals

w

ho d

id n

ot re

ceiv

e an

tibio

tics b

efor

e ar

rival

at

hosp

ital;

patie

nts g

athe

red

durin

g a

1-y

per

iod

base

d on

cla

ims d

ata

Inho

spita

l mor

talit

y, 3

0-da

y m

orta

lity,

and

leng

th o

f sta

y >

5 da

ys; a

s ass

ocia

ted

with

an

tibio

tic a

dmin

istra

tion

befo

re

or a

fter 4

h fr

om a

rriv

al

Afte

r per

form

ance

of

mul

tivar

iate

logi

stic

re

gres

sion

, ant

ibio

tic

adm

inis

tratio

n w

ithin

4 h

w

hen

com

pare

d to

>4

h yi

elde

d an

adj

uste

d O

R o

f 0.

85 (9

5% C

I 0.7

4-0.

98)

for i

nhos

pita

l mor

talit

y, a

n ad

just

ed O

R o

f 0.8

5 (9

5%

CI 0

.76-

0.95

) for

30-

day

mor

talit

y, a

nd a

n ad

just

ed

OR

of

0.9

(95%

CI 0

.83-

0.96

) for

leng

th o

f sta

y

grea

ter t

han

5 da

ys

4-h

cuto

ff w

as d

eter

min

ed

post

hoc

; 3- t

o 8-

h cu

toff

s ha

d ne

ar id

entic

al 3

0-da

y m

orta

lity

asso

ciat

ions

; th

ough

incl

uded

in th

e m

ultiv

aria

te a

naly

sis,

mor

e pa

tient

s in

the

antib

iotic

s <4

h gr

oup

rece

ived

ant

ibio

tic

regi

men

s dee

med

ap

prop

riate

; did

not

ana

lyze

fo

r alte

red

men

tal s

tatu

s;

enro

llmen

t bas

ed o

n cl

aim

s da

ta a

nd e

qual

num

bers

sa

mpl

ed p

er st

ate,

not

bas

ed

on st

ate

popu

latio

n; d

id n

ot

anal

yze

by in

divi

dual

ho

spita

l; ho

spita

ls th

at

diag

nose

mor

e ef

ficie

ntly

m

ay b

e as

soci

ated

with

be

tter o

vera

ll ca

re

III

Clinical Policy

728 Anna
ls of Emergency Medicine Volume , . : November

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Wat

erer

et

al54

20

06

Sing

le c

ente

r pr

ospe

ctiv

e co

hort

451

patie

nts s

plit

into

an

tibio

tic b

efor

e or

afte

r 4-

h gr

oups

; abo

ut 5

0% o

f pa

tient

s in

each

coh

ort

Ant

ibio

tics b

efor

e or

afte

r 4 h

as

ass

ocia

ted

with

mor

talit

y;

also

look

ed a

t ass

ocia

tions

with

se

verit

y, se

ptic

shoc

k, h

ypox

ia,

and

decr

ease

d m

enta

l sta

tus

On

univ

aria

te a

naly

sis,

antib

iotic

s >4

h a

fter

arriv

al w

as a

ssoc

iate

d w

ith

incr

ease

d ris

k of

dea

th, b

ut

whe

n m

ultiv

aria

te a

naly

sis

perf

orm

ed, n

o st

atis

tical

ly

sign

ifica

nt in

crea

sed

risk

of d

eath

bas

ed o

n an

tibio

tic

time;

alte

red

men

tal s

tate

as

soci

ated

with

an

adju

sted

O

R 3

.33

(95%

CI 1

.28-

8.77

) and

abs

ence

of f

ever

w

as a

ssoc

iate

d w

ith

adju

sted

OR

2.5

5 (9

5% C

I 1.

02-6

.37)

for m

orta

lity

Sing

le c

ente

r; sm

all n

umbe

r of

mor

talit

ies i

n ag

e >6

5 y

popu

latio

n; n

o m

entio

n is

m

ade

abou

t whe

ther

any

pa

tient

s rec

eive

d ou

t-of-

hosp

ital a

ntib

iotic

s

II

Silb

er e

t al55

20

03

Pros

pect

ive

obse

rvat

iona

l co

hort

409

patie

nts >

21 y

(tho

ugh

mos

t >65

y) w

ith m

oder

ate

to se

vere

pne

umon

ia (b

ased

on

PO

RT

scor

e) w

ere

plac

ed in

to 3

gro

ups b

ased

on

thei

r tim

e fr

om a

rriv

al to

an

tibio

tics (

grou

p 1

rece

ived

ant

ibio

tics i

n <4

h,

grou

p 2

from

4 to

8 h

, gr

oup

3 in

>8

h)

Tim

e to

clin

ical

stab

ility

— a

co

mpo

site

mea

sure

of t

he fi

rst

24 h

per

iod

that

the

patie

nt h

as

all o

f the

follo

win

g: S

BP

≥90

mm

Hg,

pul

se ra

te ≤

100

beat

s/m

in, r

espi

rato

ry ra

te ≤

24

brea

ths/

min

, tem

pera

ture

≤1

01°F

, O2 S

at ≥

90, a

nd th

e ab

ility

to e

at

No

stat

istic

ally

sign

ifica

nt

diff

eren

ces b

etw

een

the

grou

ps in

tim

e to

clin

ical

st

abili

ty

Excl

uded

pat

ient

s who

re

ceiv

ed in

appr

opria

te

antib

iotic

s; e

xclu

ded

patie

nts w

ho n

ever

reac

hed

clin

ical

stab

ility

; mod

erat

e sa

mpl

e si

ze m

ay h

ave

mis

sed

diff

eren

ces

II

Mar

rie a

nd

Wu56

20

05

Mul

ticen

ter,

pros

pect

ive

obse

rvat

iona

l tri

al

3,04

3 pa

tient

s, m

ean

age

70

y; e

xclu

ded

patie

nts:

ad

mitt

ed to

the

ICU

from

th

e ED

, asp

iratio

n pn

eum

oniti

s (1s

t y o

nly)

, tu

berc

ulos

is, c

ystic

fibr

osis

, pr

egna

nt, o

r tak

ing

im

mun

osup

pres

sive

dr

ugs/

CD

4 <2

50

Impl

emen

ted

a ca

re p

athw

ay;

track

ed m

any

inte

rven

tions

and

pr

ogno

stic

fact

ors i

nclu

ding

an

tibio

tics b

efor

e or

afte

r 4 h

No

sign

ifica

nt d

iffer

ence

in

mor

talit

y w

ith a

4 o

r 8 h

cu

toff

Onl

y pe

rfor

med

uni

varia

te

anal

ysis

on

the

time

to

antib

iotic

and

mor

talit

y as

soci

atio

ns; l

ack

of

mul

tivar

iate

ana

lysi

s of

conf

ound

ing

fact

ors

decr

ease

s clin

ical

util

ity o

f th

ese

resu

lts

II

Clinical Policy

Volume , .
: November Annals of Emergency Medicine 729

Evi

dent

iary

Tab

le (c

ontin

ued)

. St

udy

Yea

r D

esig

n In

terv

entio

n(s)

/Tes

t(s)

/M

odal

ity

Out

com

e M

easu

re/C

rite

rion

St

anda

rd

Res

ults

L

imita

tions

/Com

men

ts

Cla

ss

Bat

tlem

an e

t al

5720

02

Mul

ticen

ter

retro

spec

tive

coho

rt

609

patie

nts f

rom

7

hosp

itals

with

dia

gnos

is o

f pn

eum

onia

bas

ed o

n D

RG

co

ding

Prol

onge

d le

ngth

of s

tay

(d

efin

ed a

s ≥9

days

) as

asso

ciat

ed w

ith d

oor-

to-n

eedl

e tim

e an

d w

heth

er a

ntib

iotic

s w

ere

adm

inis

tere

d in

ED

or o

n flo

or

Dec

reas

ed n

umbe

r of

patie

nts w

ith p

rolo

nged

le

ngth

of s

tay

asso

ciat

ed

with

shor

ter d

oor-

to-n

eedl

e tim

es a

nd a

ntib

iotic

s ad

min

iste

red

in th

e ED

Excl

uded

mor

talit

ies f

rom

an

alys

is; d

ata

not s

how

n fo

r an

alys

is o

f doo

r-to

-nee

dle

time

III

ATS,

Am

eric

an T

hora

cic

Soci

ety;

BP,

blo

od p

ress

ure;

CAP

, com

mun

ity-a

cqui

red

pneu

mon

ia; C

I, co

nfid

ence

inte

rval

; CM

S, C

ente

rs fo

r Med

icar

e an

d M

edic

aid

Se

rvic

es; D

RG, D

iagn

osis

-Rel

ated

Gro

up; E

D, e

mer

genc

y de

partm

ent;

H, H

aem

ophi

lus;

h, h

our;

ICD

-9, I

nter

natio

nal C

lass

ifica

tion

of D

isea

ses,

Nin

th R

evis

ion;

IC

U, i

nten

sive

car

e un

it; M

IC, m

inim

um in

hibi

tory

con

cent

ratio

ns; M

RSA,

met

hici

llin-

resi

stan

t Sta

phyl

ococ

cus a

ureu

s; M

SSA,

met

hici

llin-

susc

eptib

le

Stap

hylo

cocc

us a

ureu

s; m

in, m

inut

e; O

2, ox

ygen

; OR,

odd

s rat

io; P

CA,

pne

umoc

occa

l ant

igen

; PO

RT, P

atie

nt O

utco

mes

Res

earc

h Te

am; P

RSP,

pen

icill

in

resi

stan

t Str

epto

cocc

us p

neum

onia

e; P

SI, p

neum

onia

seve

rity

inde

x; Q

I, qu

ality

impr

ovem

ent;

S,st

rept

ococ

cus;

SAP

S, si

mpl

ified

acu

te p

hysi

olog

y sc

ore;

Sat

, sa

tura

tion;

SBP

, sys

tolic

blo

od p

ress

ure;

vs,

vers

us; y

, yea

r; W

BC, w

hite

blo

od c

ell c

ount

.

Clinical Policy


Clinical Policy


Diagnosis‡

Prognosis§

cohort using a criterion standard Population prospective cohort

ve observational Retrospective cohortCase control

tonsensus, review)

Case seriesCase reportOther (eg, consensus, review)

lly.

Appendix A. Literature classification schema.*

Design/Class Therapy†

1 Randomized, controlled trial or meta-analysesof randomized trials

Prospective

2 Nonrandomized trial Retrospecti

3 Case seriesCase reportOther (eg, consensus, review)

Case seriesCase reporOther (eg, c

*Some designs (eg, surveys) will not fit this schema and should be assessed individua†Objective is to measure therapeutic efficacy comparing �2 interventions.‡Objective is to determine the sensitivity and specificity of diagnostic tests.§Objective is to predict outcome including mortality and morbidity.

Appendix B. Approach to downgrading strength of evidence.

Downgrading

Design/Class

1 2 3

None I II III1 level II III X2 levels III X XFatally flawed X X X


clinical policy: critical issues in the management of ...pneumonia can be divided into 4 categories...

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