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Scott A. Flanders, MD1 BACKGROUND: Limited data exist on the effectiveness of ceftriaxone plus doxycy-
Vicky Dudas, PharmD2 cline in the treatment of patients hospitalized with community-acquired pneumo-
Kathleen Kerr, BA3 nia (CAP).
Charles E. McCulloch, PhD4 METHODS: We performed a retrospective cohort study of all adults hospitalized for
Ralph Gonzales, MD, MSPH3,4,5 pneumonia between January 1999 and July 2001 at an academic medical center.
Outcomes were compared for patients with CAP treated with ceftriaxone plus
1
Department of Medicine, University of Michigan, doxycycline versus other appropriate initial empiric antibiotic therapies. Outcomes
Ann Arbor, Michigan were adjusted with the use of a propensity score to account for differences in
2
Department of Clinical Pharmacy, School of patient characteristics and illness severity between groups.
Pharmacy, University of California, San Francisco, RESULTS: A total of 216 patients were treated with ceftriaxone plus doxycycline
San Francisco, California and 125 received other appropriate initial empiric antibiotic therapies. After ad-
3
Department of Medicine, University of California, justment, use of ceftriaxone plus doxycycline was associated with reduced inpa-
San Francisco, San Francisco, California tient mortality (OR 0.26, 95% CI: 0.08 0.81) and 30-day mortality (OR 0.37,
4 95% CI: 0.17 0.81), but not with length of stay or readmission rates. Analysis of a
Department of Epidemiology and Biostatistics,
University of California, San Francisco, San Fran- subset of the sample that excluded patients admitted from nursing homes, patients
cisco, California admitted to the ICU, and patients diagnosed with aspiration also showed reduced
5 inpatient mortality with the use of ceftriaxone plus doxycycline.
Division of General Internal Medicine, University
of California, San Francisco, San Francisco, Cali- CONCLUSIONS: The use of ceftriaxone plus doxycycline as an initial empiric therapy
fornia for patients hospitalized with CAP appears safe and effective, and its potential
superiority should be evaluated prospectively. Journal of Hospital Medicine 2006;
1:712. 2006 Society of Hospital Medicine.
METHODS Outcomes
Study Population TSI data were used to identify length of stay, death
A retrospective cohort study of all adults (age 18 during the index hospitalization, and return to the
years) discharged from the inpatient general med- emergency department or readmission within 30
icine service of Moftt-Long Hospital at the Univer- days of discharge. The National Death Index was
sity of California, San Francisco, was conducted used to identify all deaths that occurred after hos-
from January 1999 through July 2001. Eligibility cri- pital discharge. The 30-day mortality data included
teria included a principal discharge diagnosis of deaths occurring during the index hospitalization
CAP and a chest radiograph demonstrating an in- and in the 30 days after the index hospitalization
ltrate within 48 hours of admission. Exclusion cri- discharge.
teria included infection with the human immuno-
deciency virus, history of organ transplantation or Statistical Analysis
use of immunosuppressive therapy (including For the purposes of this analysis we compared pa-
prednisone 15 mg/day), cystic brosis, postob- tients treated with ceftriaxone plus doxycycline to
structive pneumonia, active tuberculosis, recent patients treated with other appropriate therapy. To
hospitalization (within 10 days), or admission for examine demographic and clinical differences be-
comfort care. The study protocol and procedures tween the two groups, statistical tests of compari-
were reviewed and approved by the UCSF Commit- son were performed using chi-square tests for the
tee for Human Research. dichotomous variables and t tests for the numeric
variables, all of which were normally distributed
Data Collection (after log transformation in the case of length of
Medical record review by trained research assis- stay).
tants blinded to the research question was used to To adjust for clinical variables that might con-
gather demographic data, comorbid illnesses, phys- tribute to differences in outcomes between the two
ical examination ndings on initial presentation, groups, we used backward stepwise logistic regres-
and laboratory or radiographic results on initial sion analysis to construct a propensity score15 for
Inpatient
Mortality 2.3% 14.4% 0.26 (0.080.81)
30-day
mortality 6.0% 20.0% 0.37 (0.170.81)
Length of stay
(median
days) 3.0 4.0 0.09 (0.250.06)a
30-day
readmission 10.7% 12.0% 0.87 (0.421.81)
Propensity score adjustment was based on the variables diagnosis of congestive heart failure, admission to the intensive care unit, and presence of comorbid illness
a
Estimated difference for the natural log of length of stay.
TABLE 3
Association between Ceftriaxone plus Doxycycline Therapy and Clinical Outcomes after Excluding Patients Admitted from Nursing Homes,
Diagnosed with Aspiration, or Admitted to the ICU
Abbreviations: ICU, intensive care unit; PSI, pneumonia severe index; LOS, length of stay. Propensity score adjustment was based on the variables age and comorbid illness.
a
Signicant difference between groups (P .02).
b
Estimated difference for the natural log of length of stay.
sion rates between the treatment groups were not ceftriaxone plus doxycycline in this subset also was
signicant (Table 2). associated with reduced odds of inpatient mortality
(OR 0.17, 95% CI: 0.04 0.77). The odds of 30-day
Subset Analysis mortality also were reduced but not signicantly, as
To address issues related to selection bias, we per- the condence interval included 1.0 (OR 0.43,
formed an analysis of a subset of the patients after 95% CI: 0.14 1.31). There were no differences be-
excluding those admitted from a nursing home, tween groups in length of stay or in 30-day read-
diagnosed with aspiration, or admitted to the ICU, mission rate.
for whom ceftriaxone plus doxycycline would not
be considered recommended (or rst-line) ther- DISCUSSION
apy. The two resulting groups were similar, except In our hospital setting, the use of ceftriaxone plus
there were fewer patients with comorbid illness in doxycycline as the initial empiric antibiotic therapy
the ceftriaxone plus doxycycline group (34% vs. for patients hospitalized with community-acquired
50%, P .015). The propensity score was rederived pneumonia was associated with signicantly lower
for this subset and used for adjustment. Unadjusted inpatient and 30-day mortality, even after adjusting
and adjusted outcomes are shown in Table 3. Use of for clinical differences between groups. We did not