BRIEF REPORT

Risk Factors for Drug-resistant Streptococcus

pneumoniae and Antibiotic Prescribing
Practices in Outpatient Community-acquired
Pneumonia
Timothy C. Jenkins, MD, Joy Sakai, MD, Bryan C. Knepper, MPH, MSc, Claire J. Swartwood, PharmD,
Jason S. Haukoos, MD, MSc, Jeremy A. Long, MD, MPH, Connie S. Price, MD, and William J. Burman, MD

Abstract
Objectives: Due to antimicrobial resistance in Streptococcus pneumoniae, national guidelines recommend a respiratory fluoroquinolone or combination antimicrobial therapy for outpatient treatment of
community-acquired pneumonia (CAP) associated with risk factors for drug-resistant S. pneumoniae
(DRSP). The objectives of this study were to assess the prevalence of these risk factors and antibiotic
prescribing practices in cases of outpatient CAP treated in the acute care setting.
Methods: This was a retrospective cohort study of adult outpatients treated for CAP in the emergency
department (ED) or urgent care center of an urban, academic medical center from May 1, 2009, through
October 31, 2009, and comparison of antibiotic therapy in cases with and without DRSP risk factors.
Results: Of 175 patients, 90 (51%) had at least one DRSP risk factor, most commonly asthma (n = 28,
16%), alcohol abuse (n = 24, 14%), diabetes mellitus (n = 18, 10%), chronic obstructive pulmonary disease
(n = 16, 9%), age > 65 years (n = 16, 9%), and use of antibiotics within 3 months (15, 9%). Antibiotic prescriptions were similar among cases with and without DRSP risk factors: a macrolide (62% vs. 59%,
respectively, p = 0.65), doxycycline (27% vs. 28%, p = 0.82), or a respiratory fluoroquinolone (9% vs. 9%,
p = 0.90). Concordance with national guideline treatment recommendations was significantly lower in
cases with DRSP risk factors (9% vs. 87%, p < 0.0001).
Conclusions: DRSP risk factors were present in approximately half of outpatient CAP cases treated in
the acute care setting; however, guideline-concordant antibiotic therapy was infrequent. Strict adherence to current guidelines would substantially increase use of fluoroquinolones or combination therapy.
Whether the potential risks associated with these broad-spectrum regimens are justified by improved
clinical outcomes requires further study.
ACADEMIC EMERGENCY MEDICINE 2012; 19:703706 2012 by the Society for Academic Emergency
Medicine

he treatment of community-acquired pneumonia

(CAP) in the ambulatory care setting has been
complicated by the development of antimicrobial

resistance in Streptococcus pneumoniae.1 In 2007, the

Infectious Diseases Society of America (IDSA) and the
American Thoracic Society (ATS) published a consensus

From the Department of Medicine (TCJ, JAL, CSP, WJB), the Division of Infectious Diseases (TJC, CSP, WJB), the Department of
Patient Safety and Quality (BCK), the Department of Pharmacy (CJS), and the Department of Emergency Medicine (JSH), Denver
Health Medical Center, Denver, CO; the Department of Medicine (TCJ, JS, JAL, CSP, WJB), the Division of Infectious Diseases
(TCJ, CSP, WJB), the Department of Pharmacy (CJS), and the Department of Emergency Medicine (JSH), University of Colorado
Denver, Aurora, CO; and the Department of Epidemiology, Colorado School of Public Health (JSH), Aurora, CO.
Received September 27, 2011; revision received November 30, 2011; accepted January 2, 2012.
Presented at the 21st Annual Scientific Meeting of the Society for Healthcare Epidemiology of America, Dallas, TX, April 2011.
This work was supported by the Department of Patient Safety and Quality, Denver Health Medical Center. Dr. Haukoos was supported by an Independent Scientist Award (K02 HS017526) from the Agency of Healthcare Research and Quality. The authors have
no potential conflicts of interest to disclose.
Supervising Editor: Sandy Bogucki, MD, PhD.
Address for correspondence and reprints: Timothy C. Jenkins, MD; e-mail: timothy.jenkins@dhha.org.

2012 by the Society for Academic Emergency Medicine

doi: 10.1111/j.1553-2712.2012.01365.x

ISSN 1069-6563
PII ISSN 1069-6563583

703

704

guideline on the management of CAP, stratifying antibiotic recommendations for outpatient treatment based on
the presence or absence of risk factors for drug-resistant
S. pneumoniae (DRSP) such as recent antibiotic use and
chronic medical conditions.2 For patients with DRSP risk
factors, a respiratory fluoroquinolone or combination
therapy with a beta-lactam plus macrolide is recommended. For previously healthy patients without risk for
DRSP, a macrolide or doxycycline is suggested.
Overuse of fluoroquinolones and the emergence of
fluoroquinolone resistance in S. pneumoniae and a
number of other important pathogens have highlighted
the need to reexamine the role of these agents for
infections where effective alternatives are available.3,4
Although randomized trials have demonstrated the efficacy of fluoroquinolones for outpatient CAP,5,6 whether
use of these agents leads to improved outcomes compared with more narrow-spectrum antibiotics is not
known. Furthermore, to the best of our knowledge, the
prevalence of risk factors for DRSP, and thus the potential burden of fluoroquinolone therapy for outpatient
pneumonia treated according to IDSA ATS guidance,
has not been previously examined. The objectives of
this study were to assess the prevalence of the risk factors for DRSP infection set forth in the IDSA ATS
guideline and to describe antibiotic prescribing practices in outpatients with CAP treated in the acute care
setting.
METHODS
Study Design
We performed a retrospective cohort study of adults
at least 18 years old treated for pneumonia in the
emergency department (ED) or urgent care center from
May 1, 2009, through October 31, 2009. The study was
approved by the Colorado Multiple Institutional Review
Board.
Study Setting and Population
Denver Health is a vertically integrated public safety
net institution. Patients can access care at multiple sites,
including a 477-bed hospital, ED, urgent care center,
and outpatient clinics. The ED and adult urgent care
center have annual censuses of approximately 48,000
and 33,000 cases per year, respectively. There was not
an institutional guideline for outpatient CAP available
during the study period.
Study Protocol
We used International Classification of Diseases, 9th
Revision, Clinical Modification (ICD-9-CM) codes to
screen for possible cases. A provider diagnosis of pneumonia in the medical record (obtained by chart review)
was required for study inclusion. Cases were excluded
for being on antibiotic therapy at the time of the initial
visit, hospitalization, leaving without treatment, pregnancy, or prisoner status. Medical records were
reviewed for clinical data and antibiotic therapy by a
single abstractor (JS) using a standardized data collection instrument. Pilot review of 50 cases not included in
the final data set was performed to increase consistency
in the abstraction process.

Jenkins et al.

DRSP RISK FACTORS IN OUTPATIENT CAP

All cases with a provider diagnosis of pneumonia in

the medical record were included for analysis; however,
objective criteria of CAP were considered to be at least
two signs or symptoms and radiographic evidence of
pneumonia.2 Based on the clinical factors listed in the
IDSA ATS guideline, we defined risk for DRSP infection as the presence of any of the following conditions
documented in the medical record: use of antibiotics
within 3 months, age greater than 65 years, diabetes
mellitus, chronic obstructive pulmonary disease, asthma
or other chronic lung disease, coronary artery disease,
congestive heart failure, dialysis dependence, human
immunodeficiency virus infection, alcohol abuse, cirrhosis, malignancy, or use of an immunosuppressive medication.2 IDSA ATS guideline-concordant therapy was
defined as prescription of a respiratory fluoroquinolone
or a beta-lactam plus macrolide in cases with at least
one DRSP risk factor and a macrolide or doxycycline in
cases without DRSP risk factors. The CRB-65 severity
of illness score7 was calculated for each case.
Data Analysis
Descriptive statistics were used to summarize DRSP
risk factors and other clinical data, antibiotic selection,
and concordance with IDSA ATS treatment recommendations. Differences in variables between cases with
and without DRSP risk factors were assessed using the
Pearson chi-square, Fishers exact, or Wilcoxon ranksum test where appropriate. These analyses were performed for the total cohort (all cases with a provider
diagnosis of pneumonia) and for the subset of cases
meeting objective criteria for pneumonia. For all analyses, a p < 0.05 denotes statistical significance, with no
adjustment for the multiple comparisons. The familywise Type I error rate was 0.37. We used SAS Version
9.2 (SAS Institute, Cary, NC) for data analysis.
RESULTS
A total of 206 cases with a provider diagnosis of pneumonia in the medical record were identified. Thirty-one
cases were excluded, leaving 175 cases included in the
analysis (Figure 1). At least one DRSP risk factor was
present in 90 (51%) cases. Common risk factors
included asthma (28 of 175, 16%), alcohol abuse (24,
14%), diabetes mellitus (18, 10%), chronic obstructive
pulmonary disease (16, 9%), age greater than 65 years
(16, 9%), and use of antibiotics within 3 months (15,
9%). Of the 115 cases meeting objective criteria for
pneumonia, the prevalence of DRSP risk factors was
similar (58, 50%).
Patients with DRSP risk factors were older (median =
47 years vs. 37 years, p < 0.0001) and more likely to be
current smokers (46% vs. 39%, p = 0.04) or injection
drug users (9% vs. 1%, p = 0.04), take proton pump
inhibitors (19% vs. 4%, p = 0.002), and have had prior
pneumonia (16% vs. 5%, p = 0.02). CRB-65 scores were
0 or 1 in 173 (99%) cases and were higher in those with
DRSP risk factors (p = 0.03).
Antibiotic prescriptions at the initial visit were similar
among cases with and without DRSP risk factors: a macrolide (62% vs. 59%, respectively, p = 0.65), doxycycline
(27% vs. 28%, p = 0.82), or a respiratory fluoroquinolone

ACADEMIC EMERGENCY MEDICINE June 2012, Vol. 19, No. 6

Excluded:
27 on antibiotic therapy at the time of initial visit
2 left without treatment
1 hospitalized
1 pregnant

www.aemj.org

705

206 cases with a provider diagnosis

of pneumonia in the medical record

175 cases included for review

DRSP risk factor present

n = 90 (51%)
28 asthma
5 other chronic lung disease
24 alcohol abuse
2 cirrhosis
18 diabetes mellitus
2 HIV infection
16 age >65 years
1 malignancy
16 COPD
1 immunosuppressing medication
15 antibiotic use within 3 months
0 dialysis-dependence
13 CAD or CHF

115 met objective criteria for pneumonia

58 (50%) with DRSP risk factor
57 (50%) no DRSP risk factor

No DRSP risk factor

n = 85 (49%)

p<.0001

82 (91%) antibiotic therapy discordant with

IDSA/ATS guidance
56 macrolide
24 doxycycline
1 beta-lactam
1 non-respiratory fluoroquinolone

8 (9%) antibiotic therapy

concordant with IDSA/ATS
guidance
8 respiratory
fluoroquinolone

74 (87%) antibiotic
therapy concordant
with IDSA/ATS guidance
50 macrolide
24 doxycycline

11 (13%) antibiotic therapy

discordant with IDSA/ATS
guidance
8 respiratory fluoroquinolone
3 beta-lactam

Figure 1. Risk factors for DRSP infection and antibiotic prescribing practices in relation to national guideline recommendations.
More than one DRSP risk factor may have been present for individual cases. CAD = coronary artery disease; CHF = congestive heart
failure; COPD = chronic obstructive pulmonary disease; DRSP = drug-resistant S. pneumoniae. IDSA ATS = Infectious Diseases
Society of America American Thoracic Society.

(9% vs. 9%, p = 0.90; Figure 1). Prescribing patterns

were highly similar when the analysis was limited to
cases meeting objective criteria for pneumonia (data
not shown). Concordance with IDSA ATS antibiotic
recommendations was significantly lower in cases
involving DRSP risk factors, both for the total cohort
(9% vs. 87%, p < 0.0001) and for the 115 cases meeting
objective criteria for pneumonia (9% vs. 88%,
p < 0.0001).
DISCUSSION
In this cohort of outpatients treated for CAP in the
acute care setting, at least one risk factor for DRSP was
present in approximately half of cases. Concordance
with IDSA ATS guidance to use a respiratory fluoroquinolone or combination therapy in such cases was low
(9%). In general, the presence or absence of DRSP risk
factors appears to have had little effect on antibiotic
selection.
A number of studies have identified clinical factors
associated with antimicrobial resistance in S. pneumoniae.810 To our knowledge, this is the first study to
evaluate the prevalence of a group of risk factors for
DRSP infection, as set forth in the IDSA ATS guideline,2 in a cohort of outpatients with CAP. We found
that about half were associated with at least one DRSP
risk factor, both in the total cohort and when limiting
the analysis to cases meeting objective criteria for
pneumonia. This finding is of significance in that it
demonstrates the breadth of the IDSA ATS definition
and the resultant potential burden of broad-spectrum
antibiotic use (fluoroquinolone or combination therapy)
in such cases. The authors of the IDSA ATS guideline
acknowledge the uncertainty of the clinical relevance of
DRSP risk factors and state few well-controlled studies

have examined the impact of in vitro resistance on clinical outcomes of CAP.2 Despite this, the suggestion to
use a respiratory fluoroquinolone or combination therapy was classified as a strong recommendation with
Level I evidence.
We demonstrated very low adherence to IDSA ATS
treatment recommendations in the group with DRSP
factors; a respiratory fluoroquinolone was prescribed in
fewer than 10% of cases, while combination therapy
with a beta-lactam plus macrolide was never prescribed. It follows logically that strict adherence to the
IDSA ATS guideline recommendations would have substantially increased use of these broad-spectrum regimens. Fluoroquinolone resistance in Gram-negative
organisms is becoming increasingly problematic,4 and
fluoroquinolone use can lead to Clostridium difficile
infection11 and delay the diagnosis of tuberculosis.12
Furthermore,
combination
antimicrobial
therapy
increases the risk of adverse drug events compared
with monotherapy. Given these potential risks, we
believe that further research is needed to validate the
IDSA ATS treatment recommendations for cases with
DRSP risk factors. Clinical trials are warranted to evaluate whether fluoroquinolones or combination therapy
improve outcomes compared with narrower-spectrum
antibiotics and to more specifically define subsets of
patients who may benefit from such therapy.
LIMITATIONS
This study was performed at a single institution; the
prevalence of DRSP risk factors and antibiotic prescribing practices may not be generalizable. Second, in contrast to inpatient CAP, microbiologic confirmation of
pneumonia treated as an outpatient is rarely achieved;
therefore, we were not able to limit this study to cases

706

with documented S. pneumoniae infection. Moreover,

inclusion of all cases with a provider diagnosis of pneumonia without requirement for objective clinical and
radiographic evidence likely led to misclassification of
some cases. We chose this inclusion criterion because
the study was focused on provider antibiotic selection
when pneumonia was diagnosed, providing a more
real-world assessment of antibiotic use for this condition. Furthermore, the results were similar when limiting the analyses to cases meeting an objective
definition of CAP.
CONCLUSIONS
Risk factors for drug-resistant S. pneumoniae infection,
as defined in the Infectious Diseases Society of America
and the American Thoracic Society guideline, are very
common in outpatients treated for community-acquired
pneumonia. Although adherence to treatment recommendations for such cases was low in our institution,
whether the potential risks associated with guidelineconcordant treatment regimens are justified by
improved clinical outcomes is an important question
that requires further study.
References
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resistance among Streptococcus pneumoniae in the
United States: have we begun to turn the corner on
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2. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America American Thoracic Society consensus guidelines on the
management of community-acquired pneumonia in
adults. Clin Infect Dis. 2007; 44(Suppl 2):S2772.
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DRSP RISK FACTORS IN OUTPATIENT CAP

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