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Early Switch From Intravenous to Oral Antibiotics in Hospitalized Patients With Bacteremic Community-Acquired Streptococcus pneumoniae Pneumonia
Julio A. Ramirez, MD;
Jose Bordon, MD
Arch Intern Med. 2001;161:848-850.
ABSTRACT
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Background The identification of Streptococcus pneumoniae
bacteremia in hospitalized patients with community-acquired pneumonia is considered
by some investigators to be an exclusion criterion for early switch from intravenous
to oral therapy.
Objective To determine whether the switch from intravenous to oral therapy in
such patients, once the patient reaches clinical stability, is associated
with poor clinical outcome.
Methods The medical records of 400 patients with community-acquired pneumonia
hospitalized at the Veterans Affairs Medical Center of Louisville (Louisville,
Ky) were reviewed to identify patients with bacteremic S pneumoniae. Four criteria were used to define when a patient reached
clinical stability and should be considered a candidate for switch therapy:
(1) cough and shortness of breath are improving, (2) patient is afebrile for
at least 8 hours, (3) white blood cell count is normalizing, and (4) oral
intake and gastrointestinal tract absorption are adequate.
Results A total of 36 bacteremic patients were identified. No clinical failures
occurred in 18 patients who reached clinical stability and were switched to
oral therapy or in 7 patients who reached clinical stability and continued
intravenous therapy. Clinical failures (5 deaths) occurred in the group of
11 patients who did not reach clinical stability.
Conclusion Once a hospitalized patient with community-acquired pneumonia reaches
clinical stability, it is safe to switch from intravenous to oral antibiotics
even if bacteremia caused by S pneumoniae was initially
documented.
INTRODUCTION
THE AMERICAN Thoracic Society in 1993 suggested that, in hospitalized
patients with community-acquired pneumonia (CAP), the initial intravenous
therapy may be switched to oral therapy (switch therapy) once the patient
shows evidence of early clinical improvement.1
Since then, several clinical trials have documented that performing switch
therapy once the patient reaches clinical stability is associated with good
clinical outcome, adequate patient satisfaction, and decreased length of hospital
stay.2-6
Blood cultures positive for Streptococcus pneumoniae in hospitalized patients with CAP have been identified as a prognostic
factor that is significantly associated with mortality.7
Since bacteremia is associated with poor outcome, physicians are frequently
reluctant to consider switch therapy in patients with bacteremic CAP. Although
the identification of bacteremia is considered by some investigators to be
an exclusion criterion for early switch from intravenous to oral therapy,8 we have not used bacteremia as an exclusion criterion
for switch therapy.2, 4, 6
Streptococcus pneumoniae is the most common
pathogen causing bacteremia in hospitalized patients with CAP. Bacteremia
caused by S pneumoniae has been documented in up
to 26% of hospitalized patients with CAP.9
Since controversy exists regarding the early use of oral therapy in these
patients, we decided to review our experience with the treatment of hospitalized
patients with bacteremic S pneumoniae.
Our objectives were (1) to define, in hospitalized patients with CAP
and S pneumoniae bacteremia, whether the switch from
intravenous to oral therapy is associated with poor clinical outcome and (2)
to compare the population of bacteremic patients with a general population
of hospitalized patients with CAP to define whether there is a difference
in the percentage of patients who reach clinical stability and the time required
for the patients to reach clinical stability.
PATIENTS AND METHODS
The medical records of 400 patients hospitalized with CAP at the Veterans
Affairs Medical Center of Louisville (Louisville, Ky) were reviewed to identify
patients with S pneumoniae–positive blood cultures.
Many of these patients had participated in previous clinical trials to evaluate
clinical outcome after switch therapy. Diagnostic criteria for CAP were followed
as previously published.2, 4, 6
The following 4 criteria were used to define when a patient has reached
clinical stability and should be considered a candidate for switch therapy:
(1) cough and shortness of breath are improving, (2) the patient has been
afebrile (temperature, <37.8°C) for at least 8 hours, (3) white blood
cell count is normalizing, and (4) oral intake and gastrointestinal tract
absorption are adequate. A patient who was able to take food by mouth without
evidence of diarrhea or malnutrition was considered to have adequate oral
intake and gastrointestinal tract absorption.
The clinical course was defined as clinical improvement in patients who met switch therapy criteria during the first 7 days
of hospitalization. The clinical course was defined as lack of improvement in patients who did not meet criteria for switch
therapy during the first 7 days of hospitalization.
All patients were treated initially with a regimen of intravenous antibiotics
that was in compliance with published guidelines.1
Cephalosporins were the most commonly used intravenous and oral antibiotics
(eg, ceftriaxone sodium, cefuroxime sodium). Antibiotic therapy was defined
as switch therapy when the patient was switched from
intravenous to oral antibiotics during the first 7 days of hospitalization.
The antibiotic therapy was classified as intravenous therapy when the patient was treated only with intravenous antibiotics during
the first 7 days of hospitalization.
According to the clinical course (improvement vs lack of improvement)
and antibiotic therapy (switch therapy vs intravenous therapy), the patients
were classified in 3 groups. Group A consisted of patients with clinical improvement
treated with switch therapy. These patients were switched from intravenous
to oral antibiotics once they met switch therapy criteria. Group B included
patients with clinical improvement treated with intravenous therapy only.
These patients were candidates for switch therapy during the initial 7 days
of intravenous therapy, but the primary physician decided not to use oral
therapy because of the presence of bacteremia. Group C consisted of patients
with lack of clinical improvement treated with intravenous therapy. These
patients did not meet criteria for switch therapy and were treated with intravenous
antibiotics only.
The severity of CAP at the time of hospital admission was evaluated
in patients in groups A, B, and C by determination of risk for mortality at
30 days,10 the Acute Physiology and Chronic
Health Evaluation II score,11 and the number
of factors for complicated courses.1
The clinical outcome was defined as cured in
patients with resolution or improvement of CAP during last follow-up and failure in patients who died as a consequence of CAP or
a complication related to CAP.
The percentage of patients who reached clinical stability and the time
to reach clinical stability were calculated for the population of bacteremic
patients. These data were compared with the data from a recently published
study of 200 consecutive hospitalized patients with CAP.6
A Cox proportional hazard analysis was performed on the time to reach clinical
stability data, testing the effect of the variable group.
RESULTS
From the total of 400 hospitalized patients with CAP, 36 patients were
identified with blood cultures positive for S pneumoniae at hospital admission. All isolates were susceptible to penicillin
and erythromycin. No atypical pathogens were identified in the 36 study patients.
Of the 36 bacteremic patients, 18 were in group A, 7 in group B, and 11 in
group C. The average risk class at time of hospitalization was 3.6 for group
A, 3.3 for group B, and 4.2 for group C. The average Acute Physiology and
Chronic Health Evaluation II score was 12.9 for group A, 11.6 for group B,
and 17.5 for group C. The average number of risk factors for complicated course
was 8.4 for group A, 7.3 for group B, and 10.4 for group C. The average patient
age was 58 years for group A, 58 years for group B, and 61 years for group
C. The clinical outcome of these 36 patients in groups A, B, and C is given
in Table 1.
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Clinical Outcome of Hospitalized Patients With Bacteremic Community-Acquired Streptococcus pneumoniae Pneumonia
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Of the bacteremic patients, 25 (69%) were candidates for switch therapy,
with a mean time to switch of 3.5 days. In the general population, 87% were
candidates for switch therapy, with a mean time to switch of 2.9 days. The
comparison of the bacteremic population with the general CAP population in
regard to the time to reach clinical stability is shown in Figure 1. The groups were different (P
= .03), with the patients in the general population having a 60% greater risk
of reaching early clinical stability.
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Percentage of the population reaching clinical stability by mean
time to reach stability in 36 bacteremic patients (squares) compared with
200 hospitalized patients with community-acquired pneumonia (triangles).
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COMMENT
The result of this study indicates that, in hospitalized patients with
CAP, it is safe to switch from intravenous to oral therapy as soon as the
patient reaches clinical stability, even if bacteremia caused by S pneumoniae was initially documented. The study showed that patients
with bacteremia are less likely to reach clinical stability and become candidates
for switch therapy than are a general population of hospitalized patients
with CAP. We also documented that, in bacteremic patients, the time to reach
clinical stability is significantly longer than in nonbacteremic patients.
The delay in reaching clinical stability in the bacteremic population cannot
be explained as secondary to poor antibiotic selection, because all patients
were initially treated with appropriate therapy against S pneumoniae. A clinical implication of this finding is that, in patients
with bacteremia, a lack of clinical response by day 3 of therapy may not represent
treatment failure but a delayed response to intravenous therapy.
The fact that patients with bacteremia have a delayed clinical response
to therapy should be considered during the design of antibiotic trials when
2 treatment arms are compared in relation to time to clinical stability and
switch therapy. If the outcome of the clinical trial is time to switch therapy,
the presence of bacteremia will act as a confounding variable.
When the data of this investigation are analyzed, it should be kept
in mind that this study has several limitations because of the retrospective
design and the small number of patients with bacteremia. Once patients reached
clinical stability, the decision to continue intravenous therapy vs switch
therapy was nonrandomized, and physicians may have decided to continue intravenous
therapy in patients with more severe disease. In our evaluation of severity
of disease, we were not able to see any difference in risk class, Acute Physiology
and Chronic Health Evaluation II score, or number of risk factors for complicated
course for the patients who reached clinical stability and were switched to
oral therapy vs the patients who reached clinical stability and continued
to receive intravenous therapy. The retrospective analysis of the cases seems
to indicate that the only reason for some physicians to continue intravenous
therapy in patients who reached clinical stability was the presence of positive
blood cultures at the time of hospitalization.
Although all isolates in this study were fully susceptible to penicillin,
with minimum inhibitory concentrations below 0.12 µg/mL, we do not consider
the identification of resistance to penicillin a contraindication for switch
therapy. After a recent report from the Centers for Disease Control and Prevention,
in our institution we redefined susceptibility for S pneumoniae when implicated as a cause of CAP. Streptococcus
pneumoniae is now considered penicillin resistant when the penicillin
minimum inhibitory concentration is 4 µg/mL or greater.12
Once treatment is switched from intravenous to oral antibiotics, it is not
necessary to keep the patient in the hospital to evaluate clinical response
to oral therapy.13 In the patients switched
to oral antibiotics in this study, there was no clinical suspicion of a secondary
focus of infection, such as endocarditis, meningitis, osteomyelitis, purulent
pericarditis, or septic arthritis. Since the switch from intravenous to oral
therapy is contraindicated in patients with S pneumoniae meningitis or endocarditis, these 2 complications should not be present
when switch therapy is instituted in patients with CAP and S pneumoniae bacteremia.
In summary, our data indicate that, in hospitalized patients with CAP
without clinical indication of meningitis or endocarditis, the presence of S pneumoniae bacteremia at the time of hospital admission
is not a contraindication for switching a clinically stable patient from intravenous
to oral therapy.
AUTHOR INFORMATION
Accepted for publication October 23, 2000.
Corresponding author: Julio A. Ramirez, MD, Division of Infectious
Diseases, Department of Medicine, University of Louisville, Louisville, KY
40292 (e-mail: j.ramirez{at}louisville.edu).
From the Division of Infectious Diseases, Department of Medicine, University
of Louisville School of Medicine, Louisville, Ky.
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