Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (42)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brown, R. B.
Right arrow Articles by Kunkel, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brown, R. B.
Right arrow Articles by Kunkel, M.
(Chest. 2003;123:1503-1511.)
© 2003 American College of Chest Physicians

Impact of Initial Antibiotic Choice on Clinical Outcomes in Community-Acquired Pneumonia*

Analysis of a Hospital Claims-Made Database

Richard B. Brown, MD, FCCP; Paul Iannini, MD; Peter Gross, MD and Mark Kunkel, MD

* From the Baystate Medical Center (Dr. Brown), Springfield, MA; the Danbury Hospital (Dr. Iannini), Danbury CT; the Hackensack University Medical Center (Dr. Gross), Hackensack, NJ; and Roche Laboratories (Dr. Kunkel), Nutley, NJ.

Correspondence to: Richard B. Brown, MD, FCCP, Chief, Infectious Disease Division, Baystate Medical Center, Springfield, MA 01199; e-mail: richard.brown{at}bhs.org


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: Much controversy exists regarding the initial choice of antibiotics and selected outcomes for patients with community-acquired pneumonia (CAP).

Methods: The investigators analyzed a hospital claims-made database to assess the impact of initial antibiotic choice on 30-day mortality, total hospital costs, and hospital length of stay (LOS). Fine risk groups allowed for stratification for variations in the severity of illness. Patients were divided into five monotherapy groups (ie, ceftriaxone, "other" cephalosporins, fluoroquinolones, macrolides, or penicillins) and four groups that received dual therapy (ie, the agents listed above, except macrolides) plus macrolides. Patients also were stratified by age (ie, > 65 years of age and < 65 years of age). Severely ill patients were excluded.

Results: Overall, 44,814 persons met the criteria for inclusion. Among monotherapy patients, those who received macrolides had the least mortality but were the least ill. Patients who received dual therapy generally had shorter LOSs, lower total hospital charges, and decreased mortality compared with those who received monotherapy. Differences among dual-therapy regimens regarding outcomes studies were noted. Patients who were < 65 years of age had lower mortality rates, shorter LOSs, and lower hospital charges than did the more elderly patients. Within this group, those who received dual therapy had better outcomes than those who received monotherapy.

Conclusions: We confirmed the value of dual therapy employing macrolides as a second agent in decreasing mortality from CAP, and we provided similar data regarding shorter LOSs and lower hospital charges. This appears to hold for a younger population. Differences among dual-therapy regimens (all employing macrolides) appear to exist and may be clinically relevant.

Key Words: antibiotics • community-acquired • cost-effectiveness • pneumonia


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Antibiotic therapy for community-acquired pneumonia (CAP) has received a great deal of attention over the past decade because of its substantial mortality, morbidity, and costs.1 2 3 Annual treatment in the elderly alone is associated with expenditures of approximately $9 billion.4 Both length of stay (LOS) and costs per case for the elderly are greater than those for younger individuals with this infection.5 6 However, the mortality rate of younger hospitalized cohorts vs that of older hospitalized cohorts is poorly understood. Other relevant issues are the emergence of resistance of common pathogens and the role of newer anti-microbial agents.7 8 9 10 Recommendations have been published11 12 13 14 regarding the need for hospitalization, the choice of antibiotics, the duration of therapy, and the determination of timing of hospital discharge, albeit with some differences.

Our study focused on the initial antibiotic choice for CAP in hospitalized patients. A number of investigations have verified the apparent benefit of selected antibiotic regimens, generally containing agents that are active against atypical organisms.15 16 Similar combinations also may have enhanced benefits for patients with severe pneumococcal pneumonia.17 Comparative antibiotic studies, however, have been conducted infrequently. Information obtained through hospital claims databases that deal with very large populations may be able to provide further insights about appropriate antimicrobial agent choices for CAP. Historically, analyses of this type of database have been flawed by the inability to stratify risk. Newer databases, however, can allow for severity adjustment. The current study analyzed a large hospital claims-made database of CAP to determine whether the initial antimicrobial agent choice impacted on selected clinical outcomes. These outcomes included the 30-day mortality rate, the hospital LOS, and the cost of hospitalization.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Hospital claims data were obtained from Pharmetrics Inc. Data were supplied from the HBSI EXPLORE database (Solucient, LLC; Evanston, IL). This database is composed of > 185 health-care organizations reflecting a wide diversity in size, geography, and services. The data, which include > 250 data elements for each patient record, include but are not limited to the full diagnosis, procedures performed, and transaction doses given, details by day of stay, diagnosis-related groups, physician identifiers, and estimated reimbursement. This organization captures data from hospital claims by discharge diagnosis and integrates them with pharmaceutical claims information. Materials compiled from the participating institutions from July 1, 1997, to June 30, 1999, were analyzed. Patients who were > 18 years of age with CAP diagnoses (ie, International Classification of Diseases, ninth revision, codes 480–487.0) were identified. Individuals were excluded if they initially required an ICU stay, had HIV infection, required mechanical ventilation during any portion of hospitalization, had incomplete antibiotic therapy data, or had been hospitalized with CAP within the previous 30 days. Additional reasons for exclusion from the study were patients noted to have < 24 h of hospitalization, and those within risk group E (see below).16 Data such as hospital costs were directly extracted from the database rather than derived.

Demographic data such as age, sex, and race were recorded. Patients were assigned risk scores according to criteria developed and validated by Fine and colleagues.18 19 Individuals were assigned point scores that ranged in aggregate from -2 to +11 based on the presence of the following factors: neoplasia; abnormal vital signs; pleurisy; age > 64 years; altered mental status; and high-risk pneumonia (ie, pneumonia associated with Staphylococcus aureus or enteric Gram-negative bacilli). The five risk categories were defined as follows: <0, class A; 0, class B; 1 to 4, class C; 5 to 7, class D; and >= 8, class E. The more extensive scoring system of Fine et al20 (ie, pneumonia severity index) was not employed because the additional clinical data necessary for this system were not available in the database that we used. The following dependent variables were measured: (1) mean length of hospitalization; (2) mean cost of hospitalization (based on charges extracted directly from the database); and (3) 30-day mortality rate.

Patients were divided into treatment cohorts based on the initial antibiotic therapy received for each episode of CAP. For the purposes of this investigation, analyses were restricted to antibiotic cohorts as follows: monotherapy with (1) ceftriaxone, (2) macrolides, (3) "other" cephalosporins, (4) fluorinated quinolones, or (5) penicillins; and dual therapy with the four classes listed above (except macrolides) plus a macrolide as the second agent. Separate analyses were performed for patients who were > 65 years of age vs those who were < 65 years of age. Ceftriaxone was specifically selected for investigation because of its broad acceptance as a cephalosporin of choice in the treatment of CAP, because of its inclusion in major practice guidelines11 12 13 14 and publications demonstrating efficacy with other regimens,14 21 22 23 and because it was the predominant cephalosporin found in this database (see below).

Associations between the risk group and either LOS or treatment charges were examined employing the Kruskal-Wallis test and two-way contrasts. Associations between risk group and mortality rates were examined by using {chi}2 test and the modified Bonferroni procedure. Mean risk scores were compared among different treatment cohorts using one-way analysis of variance and Tukey honestly significant difference tests.24 Differences in LOSs among different treatment cohorts were analyzed using Kruskal-Wallis tests and two-way contrasts.25 The methodology employed to address potential biases stemming from differences in risk scores among treatment cohorts involved patient stratification into respective risk groups and were compared across the cohorts within each category.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The database identified 188,627 patients with the diagnosis of CAP who had been admitted to the hospital during the 2-year study period. Reasons for exclusions and study cohorts are summarized in Figure 1 . Regarding excluded patients, >60% had incomplete antibiotic treatment information, and therefore no treatment characterization was possible. The remainder had received a wide variety of single-agent and multiple-agent combination therapies. The most commonly prescribed of these were vancomycin (686 prescriptions), fluconazole (551 prescriptions), and trimethoprim/sulfamethoxazole (367 prescriptions). Although > 9,000 patients were in risk group E, the antibiotic usage patterns and the availability of antibiotic data were sufficiently diffuse to render further analysis impossible. A total of 25,996 persons received one of the five classes of study antibiotics as monotherapy, while an additional 18,818 patients received macrolide agents plus one of the other four classes. These patients (44,814 patients) formed the basis for further analyses. Approximately 79% of these diagnoses were contained in International Classification of Diseases, ninth revision, code 486 (ie, pneumonia, organism unspecified). The three next most commonly noted diagnoses were pneumococcal pneumonia (4%), pneumonia due to other Gram-negative bacteria (2.4%), and bronchopneumonia, organism unspecified (2.1%). The data for the excluded patients were not similarly analyzed. Virtually all fluoroquinolone use consisted of either ciprofloxacin or ofloxacin. Aside from ceftriaxone, the most common cephalosporins employed were as follows: cefuroxime (3,923 patients); cefotaxime (1,672 patients); ceftazidime (1,152 patients); ceftizoxime (957patients); and cefazolin (727 patients). The predominant penicillins used for treatment were as follows: ampicillin/sulbactam (1,545 patients); ticarcillin/clavulanate (821 patients); piperacillin/tazobactam (713 patients); and ampicillin or amoxicillin (255 patients).



View larger version (15K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Reasons for exclusions and the initial patient cohorts. yo = years old.

 
Tables 1 and 2 , respectively, depict nonstratified demographic and outcome data for the monotherapy and dual-therapy cohorts. Regarding patients in the monotherapy cohort, those given macrolides were younger, were more likely to be in lower risk groups, and demonstrated the lowest mortality (p < 0.001). Patients who received ceftriaxone had the lowest hospital charges and the shortest LOS (p < 0.005). For the dual-therapy cohort, patients who received ceftriaxone plus a macrolide had the shortest LOSs and lowest total hospital charges (p < 0.001), with comparable mortality rates of < 3%. The use of fluoroquinolones or penicillins as monotherapy or as part of dual therapy with macrolides was associated with the highest total hospital charges and the longest LOSs.


View this table:
[in this window]
[in a new window]

  		Table 1. Demographics and Outcome Data for the Monotherapy Cohort*

 

View this table:
[in this window]
[in a new window]

  		Table 2. Demographics and Outcome Data for Dual-Therapy Cohort*

 
Table 3 depicts nonstratified outcomes comparing dual-therapy with monotherapy groups. Mortality was decreased among all dual-therapy groups when compared with monotherapy groups (p < .05) and was < 3% for all of the dual therapies that were investigated, compared to 5 to 8% for those receiving monotherapy. For patients who received ceftriaxone plus a macrolide, both LOS and total hospital charges were similarly decreased (p < .0001). No statistically significant decreases in LOS or total hospital charges were seen within the dual-therapy groups receiving fluoroquinolones or penicillins.


View this table:
[in this window]
[in a new window]

  		Table 3. Outcomes of Overall Patients, Monotherapy vs Dual Therapies

 
Table 4 and Table 4A depicts outcome data stratified by risk group for both the monotherapy and dual-therapy cohorts. With the exception of the use of fluoroquinolone agents, patients within risk groups C and D had statistically decreased mortality when receiving dual-therapy regimens. Similarly among the sickest patients studied, dual therapy with fluoroquinolone agents appeared to offer the least advantage regarding LOS and total hospital charges.


View this table:
[in this window]
[in a new window]

  		Table 4. Outcomes Stratified by Risk Group

 

View this table:
[in this window]
[in a new window]

  		Table 4A. Continued

 
Table 5 provides dual-therapy and monotherapy outcomes data for elderly vs younger patients. A total of 14,759 individuals (approximately 33%) were < 65 years old. A total of 151 patients who were < 65 years old (1%) died, with approximately two thirds of those in the monotherapy category. Mortality rates among younger patients were substantially lower than for those the elderly and were always < 2.5% for each monotherapy group. Dual therapy for younger patients further reduced mortality within each antibiotic group (p < 0.005), except for the group receiving fluoroquinolones in which the already low rate may not have been further reduced. For younger patients receiving dual therapy with ceftriaxone plus a macrolide, both LOS and total hospital charges were statistically reduced when compared to monotherapy with ceftriaxone alone. Regarding elderly patients, mortality rates were approximately twofold to threefold higher than those in the younger cohort. In general, dual therapies resulted in improved outcomes with the exception of those including fluoroquinolone agents.


View this table:
[in this window]
[in a new window]

  		Table 5. Comparison of Outcomes Stratified by Age

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The choice of antibiotics for CAP has become increasingly complicated because of increased antibiotic resistance among likely pathogens, the larger numbers of antibiotic choices, and the repeated observation that many patients with CAP receive empiric therapy because the presence of a specific pathogen has not been demonstrated.2 3 11 12 13 14 Antibiotic choice may be further confounded because an unknown number of cases may be associated with multiple pathogens in varying combinations.26 27 Some studies appear to demonstrate improved outcomes when empiric therapy combines treatment for both typical and atypical organisms, and often includes a macrolide agent.15 16 17 The reasons for enhanced outcomes may include an enhanced spectrum of coverage, "synergy" against specific pathogens, or modulation of the inflammatory effects of pneumonia.17 Such a treatment strategy appears to decrease LOS and/or 30-day mortality rate. The most recently published guidelines13 14 for the management of CAP reinforce the use of such an antibiotic strategy for persons of all ages who are hospitalized either on general medical wards or in critical care units. In addition, the evolving resistance of Streptococcus pneumoniae to macrolide and azilide agents may render these agents ineffective as monotherapy in some instances, despite excellent activity against most other pathogens.7 28 29

Analysis of outcomes must denote not only which ones are studied, but should also address those that may be interrelated. As an example, decreased hospital LOS and total hospital expenses could occur because of increased early hospital mortality (thus "shortening" LOS and "decreasing" costs). The current investigation analyzed a large hospital claims-made database, identified > 44,000 patients with CAP who met the study criteria for antimicrobial therapy, and studied three major outcomes. Several important limitations exist. First, a claims-made database limits the information available and may result in substantial numbers of excluded patients. As examples, no information was available to document the dose and duration of antibiotic therapy, and, beyond coding, there is no documentation available about the adequacy of diagnosis. Similarly, we have only limited information about pathogens and could not develop data that could have tied outcome to the adequacy of coverage. Additionally, we have no control over the antimicrobial agents that were chosen, and we recognize that several of the compounds studied were orally administered and may not have similar bioavailability as parenteral products (eg, selected cephalosporin agents). Dose variation could explain why "other cephalosporins" (of which cefotaxime comprised a substantial percentage) differed in some respects from outcomes noted with ceftriaxone (where dosing is likely to be more standardized). Other than this unsubstantiated possibility, we have no reason to suspect that outcomes with ceftriaxone would differ from those with cefotaxime. Second, the newer fluoroquinolone agents, which include levofloxacin, moxifloxacin, and gatifloxacin, were poorly represented in the study cohort, and thus results employing these newer agents may provide different results. However, recent data appear to demonstrate failure and even mortality with at least one of these newer agents.30 Third, no data were available to denote the potential role of antibiotics that were taken prior to hospital admission. Fourth, we did not assess the sickest patient populations, such as those in critical care units and those in risk group E, because of too few patients and a great deal of heterogeneity in treatment within that group. Severity of illness is one of the factors that helps to dictate antibiotic treatment choice13 14 31 and may have contributed additionally to selection bias. We employed risk stratification to help control for bias related to preexisting comorbidities. By employing the risk stratification of Fine and colleagues,18 19 issues related to innate differences in populations based on severity of illness should be obviated to a large extent.

Despite the noted limitations, several important results were observed. First, we believe that this study is the first to evaluate outcomes in a large number of younger patients. Approximately one third of the individuals studied were < 65 years old, and outcomes denoted shortened LOS, lower mortality, and lower total hospital charges when compared to an elderly cohort of patients. Additionally, dual therapy in the younger population reduced mortality in most groups compared to those who received monotherapy. These data corroborate those found in a small population of patients in which both LOS and total hospital charges were approximately 40% lower in patients who were < 60 years old.32 However, the impact of antibiotic therapy was not studied.

Second, dual-therapy regimens generally resulted in shorter LOSs, lower total hospital charges, and lower rates of mortality across all risk groups when compared to the comparable agent without a macrolide, and this was especially apparent in the sicker classes of patients (ie, those in risk groups C and D). These results confirm those of other studies,15 16 17 although not all outcomes were studied in each investigation. With the dual-therapy cohorts as studied, ceftriaxone plus a macrolide agent appeared to offer the best package of outcomes studied (ie, short LOSs, low total hospital charges, and no association with significant increases in mortality rates). This is in keeping with published recommendations for antibiotic use in patients with CAP.11 12 13 14 We would expect similar outcomes in regimens of properly dosed cefotaxime plus a macrolide agent. Penicillins generally performed less favorably, which is in keeping with other published data.16 The current study provides ongoing documentation of the value of dual therapies for the treatment of CAP. Younger patients have better outcomes than elderly patients, and dual therapy offers outcome advantages in this group as well.


   Acknowledgements
 
The authors acknowledge the advice and initial participation of Mark Kunkel, MD, for the initial database acquisition, and the statistical support provided by Pharmetrics, Inc.


   Footnotes
 
Abbreviations: CAP = community-acquired pneumonia; LOS = length of stay

Presented in part at the annual meeting of the Infectious Disease Society of America, October 25 to 28, 2001, San Francisco, CA.

This research was supported by a grant from Roche Laboratories, Nutley, NJ. Drs. Brown, Iannini, and Gross have received honoraria from Roche Laboratories, for medical lectures. Dr. Kunkel was a Roche Pharmaceuticals employee at the time of the study.

Received for publication July 9, 2002. Accepted for publication November 21, 2002.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Fine, MJ, Smith, MA, Carson, CA, et al (1996) Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis. JAMA 275,134-141[Abstract]
  2. Fang, GD, Fine, M, Orloff, J, et al New and emerging etiologies for community-acquired pneumonia with implications for therapy. Medicine 1990;69,307-316[Medline]
  3. Marrie, TJ, Durant, H, Yates, L Community-acquired pneumonia requiring hospitalization: 5-year prospective study. Rev Infect Dis 1989;4,586-599
  4. Lave, JR, Lin, CJ, Hughes-Cronwick, P, et al The cost of treating patients with community-acquired pneumonia. Semin Respir Crit Care Med 1999;20,189-197
  5. Koivula, I, Sten, M, Makela, PH Prognosis after community-acquired pneumonia in the elderly. Arch Intern Med 1999;159,1550-1555[Abstract/Free Full Text]
  6. Marrie, TJ Community-acquired pneumonia in the elderly. Clin Infect Dis 2000;31,1066-1078[CrossRef][ISI][Medline]
  7. Lonks, JR, Garau, J, Gomez, L, et al Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Clin Infect Dis 2002;35,556-564[CrossRef][ISI][Medline]
  8. Chen, DK, McGeer, A, de Azavedo, JC, et al Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N Engl J Med 1999;341,233-239[Abstract/Free Full Text]
  9. Thornsberry, C, Sahm, DF, Kelly, LJ, et al Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States: results for the TRUST surveillance program, 1999–2000. Clin Infect Dis 2002;34(suppl),S4-S16
  10. Gay, K, Baughman, W, Miller, Y, et al The emergence of Streptococcus pneumoniae resistant to macrolide antimicrobial agents: a 6-year population-based assessment. J Infect Dis 2000;182,1417-1424[CrossRef][ISI][Medline]
  11. American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Am J Respir Crit Care Med 2001;163,1730-1754[Free Full Text]
  12. Heffelfinger, JS, Dowell, SF, Jorgensen, JH, et al Management of community-acquired pneumonia in the era of penicillin resistance. Arch Intern Med 2000;160,399-408
  13. Bartlett, JG, Dowell, SF, Mandell, LA, et al Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis 2000;31,347-382[CrossRef][Medline]
  14. Mandell, LA, Marrie, TJ, Grossman, RF, et al Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin Infect Dis 2000;31,383-421[CrossRef][Medline]
  15. Stahl, JE, Barza, M, DesJardin, J, et al Effect of macrolides as part of initial antibiotic therapy on length of stay in patients hospitalized with community-acquired pneumonia. Arch Intern Med 1999;159,2576-2580[Abstract/Free Full Text]
  16. Gleason, PP, Meehan, TP, Fine, MJU, et al Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia. Arch Intern Med 1999;159,2562-2572[Abstract/Free Full Text]
  17. Waterer, GW, Somes, GW, Wunderink, RG Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med 2001;161,1837-1842[Abstract/Free Full Text]
  18. Fine, MJ, Singer, DE, Hanusa, BH, et al Validation of a pneumonia prognostic index using the MedisGroups comparative hospital database. Am J Med 1993;94,153-159[CrossRef][ISI][Medline]
  19. Fine, MJ, Smith, DN, Singer, DE Hospitalization decision in patients with community-acquired pneumonia: a prospective study. Am J Med 1990;89,713-722[CrossRef][ISI][Medline]
  20. Fine, MJ, Auble, TE, Yealy, DM, et al A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997;336,243-250[Abstract/Free Full Text]
  21. Dietrich, ES, Joseph, U, Vogel, F, et al Cost-effectiveness of ceftriaxone 1 gram vs. second-generation cephalosporins in the treatment of pneumonia in general medical wards in Germany. Infection 1999;27,148-154[Medline]
  22. deKlerk, GJ, van Steijn, JH, Lobatto, S, et al A randomised multicentre study of ceftriaxone versus standard therapy in the treatment of lower respiratory tract infections. Int J Antimicrob Agents 1999;12,121-127[Medline]
  23. Dudas, V, Hopefl, A, Jacobs, R, et al Antimicrobial selection for hospitalized patients with presumed community-acquired pneumonia: a survey of nonteaching US community hospitals. Ann Pharmacother 2000;34,446-452[Abstract]
  24. Jaccard, J, Becker, MA Statistics for the behavioral sciences. 3rd ed. 1997 Brooks/Cole. Pacific Grove, CA:
  25. Hollander, M, Wolfe, D Nonparametric statistical methods. 1973 Wiley & Co. New York, NY:
  26. Brown, RB, Sands, ML, Morris, AB Community-acquired pneumonia caused by mixed aerobic pathogens. Infect Dis Clin Pract 1993;2,32-39
  27. Tan, MJ, Tan, JS, File, TM Legionnaires disease with bacteremic coinfection. Clin Infect Dis 2002;35,533-539[CrossRef][ISI][Medline]
  28. Kelley, MA, Weber, DJ, Gilligan, P, et al Breakthrough pneumococcal bacteremia in patients being treated with azithromycin and clarithromycin. Clin Infect Dis 2000;31,1008-1011[CrossRef][ISI][Medline]
  29. Gay, K, Baughman, W, Miller, Y, et al The emergence of Streptococcus pneumoniae resistant to macrolide antimicrobial agents: a 6-year population-based assessment. J Infect Dis 2000;182,1417-1424[CrossRef][ISI][Medline]
  30. Davidson, R, Cavalcanti, R, Brunton, JL, et al Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 2002;346,747-750[Free Full Text]
  31. Dowell, SF The best treatment for pneumonia: new clues, but no definitive answers [editorial]. Arch Intern Med 1999;159,2511-2512[Free Full Text]
  32. Fedullo, AJ, Swinburne, AJ Relationship of patient age to clinical features and outcome for in-hospital treatment of pneumonia. J Gerontol 1985;40,29-33[Medline]



This article has been cited by other articles:


Home page
 ChestHome page
K. Z. Vardakas, M. E. Falagas, and M. L. Metersky
Interpretation of the Findings of a Cohort Study of Bacteremic Patients With Community-Acquired Pneumonia
Chest, November 1, 2007; 132(5): 1715 - 1716.
[Full Text] [PDF]

Home page
 ChestHome page
N. C. Dean, K. A. Bateman, S. M. Donnelly, M. P. Silver, G. L. Snow, and D. Hale
Improved clinical outcomes with utilization of a community-acquired pneumonia guideline.
Chest, September 1, 2006; 130(3): 794 - 799.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. S. Niederman, C. Feldman, and G. A. Richards
Combining information from prognostic scoring tools for CAP: an American view on how to get the best of all worlds.
Eur. Respir. J., January 1, 2006; 27(1): 9 - 11.
[Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
G. W. Amsden
Anti-inflammatory effects of macrolides--an underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions?
J. Antimicrob. Chemother., January 1, 2005; 55(1): 10 - 21.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
L. M. Baddour, V. L. Yu, K. P. Klugman, C. Feldman, A. Ortqvist, J. Rello, A. J. Morris, C. M. Luna, D. R. Snydman, W. C. Ko, et al.
Combination Antibiotic Therapy Lowers Mortality among Severely Ill Patients with Pneumococcal Bacteremia
Am. J. Respir. Crit. Care Med., August 15, 2004; 170(4): 440 - 444.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
G. L. Colice, M. A. Morley, C. Asche, and H. G. Birnbaum
Treatment Costs of Community-Acquired Pneumonia in an Employed Population
Chest, June 1, 2004; 125(6): 2140 - 2145.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. H. Powers and C. K. Cooper
Evaluating Combination Therapy in Community-Acquired Pneumonia
Chest, January 1, 2004; 125(1): 353 - 353.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (42)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brown, R. B.
Right arrow Articles by Kunkel, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brown, R. B.
Right arrow Articles by Kunkel, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS