SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Limitations
  7. Conclusions
  8. References

ACADEMIC EMERGENCY MEDICINE 2012; 19:703–706 © 2012 by the Society for Academic Emergency Medicine

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.

The 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 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

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Limitations
  7. Conclusions
  8. References

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.

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, Fisher’s exact, or Wilcoxon rank-sum 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

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Limitations
  7. Conclusions
  8. References

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%).

image

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.

Download figure to PowerPoint

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 (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

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Limitations
  7. Conclusions
  8. References

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.8–10 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

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Limitations
  7. Conclusions
  8. References

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 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

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Limitations
  7. Conclusions
  8. References

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 guideline-concordant treatment regimens are justified by improved clinical outcomes is an important question that requires further study.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Limitations
  7. Conclusions
  8. References
  • 1
    Doern GV, Richter SS, Miller A, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain antimicrobial classes? Clin Infect Dis. 2005; 41:13948.
  • 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.
  • 3
    Ambrose PG, Bast D, Doern GV, et al. Fluoroquinolone-resistant Streptococcus pneumoniae, an emerging but unrecognized public health concern: is it time to resight the goalposts? Clin Infect Dis. 2004; 39:15546.
  • 4
    Lautenbach E, Strom BL, Nachamkin I, et al. Longitudinal trends in fluoroquinolone resistance among Enterobacteriaceae isolates from inpatients and outpatients, 1989-2000: differences in the emergence and epidemiology of resistance across organisms. Clin Infect Dis. 2004; 38:65562.
  • 5
    Leophonte P, File T, Feldman C. Gemifloxacin once daily for 7 days compared to amoxicillin/clavulanic acid thrice daily for 10 days for the treatment of community-acquired pneumonia of suspected pneumococcal origin. Respir Med. 2004; 98:70820.
  • 6
    Gotfried MH, Dattani D, Riffer E, et al. A controlled, double-blind, multicenter study comparing clarithromycin extended-release tablets and levofloxacin tablets in the treatment of community-acquired pneumonia. Clin Ther. 2002; 24:73651.
  • 7
    Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003; 58:37782.
  • 8
    Yu VL, Chiou CC, Feldman C, et al. An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis. 2003; 37:2307.
  • 9
    Vanderkooi OG, Low DE, Green K, Powis JE, McGeer A. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin Infect Dis. 2005; 40:128897.
  • 10
    Nava JM, Bella F, Garau J, et al. Predictive factors for invasive disease due to penicillin-resistant Streptococcus pneumoniae: a population-based study. Clin Infect Dis. 1994; 19:88490.
  • 11
    Pepin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005; 41:125460.
  • 12
    Grupper M, Potasman I. Fluoroquinolones in community-acquired pneumonia when tuberculosis is around: an instructive case. Am J Med Sci. 2008; 335:1414.