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Early Switch and Early Discharge Strategies in Patients With Community-Acquired Pneumonia
A Meta-analysis
David C. Rhew, MD;
George S. Tu, MD;
Joshua Ofman, MD, MSHS;
James M. Henning, MS;
Margaret S. Richards, PhD;
Scott R. Weingarten, MD, MPH
Arch Intern Med. 2001;161:722-727.
ABSTRACT
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Background The effectiveness of early switch and early discharge strategies in
patients with community-acquired pneumonia remains unknown.
Methods We searched the MEDLINE, HEALTHSTAR, EMBASE, Cochrane Collaboration,
and Best Evidence databases from January 1, 1980, to March 31, 2000, for community-acquired
pneumonia studies that included specific switch criteria or recommendations
to switch on a particular day.
Results From 1794 titles identified, 121 articles were reviewed. We identified
10 prospective, interventional, community-acquired pneumonia–specific
studies that evaluated length of stay (LOS). Nine studies applied an early
switch from parenteral to oral antibiotic criteria. Six different criteria
for switching were applied in the 9 studies. Five of the studies that applied
early switch criteria also applied separate criteria for early discharge.
Six studies applied an early switch and early discharge strategy to an intervention
and control group, and 5 of these provided SD values for LOS. The mean change
in LOS was not significantly (P = .05) reduced in
studies of early switch and early discharge (-1.64 days; 95% confidence
interval, -3.30 to 0.02 days). However, when the 2 studies in which
the recommended LOS was longer than the control LOS were excluded from the
analysis, the mean change in LOS was reduced by 3 days (-3.04 days;
95% confidence interval, -4.90 to -1.19 days). Studies did not
reveal significant differences in clinical outcomes between the intervention
and control groups.
Conclusions There is considerable variability in early switch from parenteral to
oral antibiotic criteria for patients with community-acquired pneumonia. Early
switch and early discharge strategies may significantly and safely reduce
the mean LOS when the recommended LOS is shorter than the actual LOS.
INTRODUCTION
COMMUNITY-acquired pneumonia (CAP) is responsible for approximately
500 000 hospitalizations in the United States each year.1
The total annual cost of treating patients with CAP is approximately $9.7
billion, and the primary determinant of cost is length of stay (LOS) in the
hospital.2 The duration of parenteral antibiotic
therapy is often the primary factor affecting LOS for patients with CAP.3 In addition, economic pressures facing hospitals have
resulted in a shortened LOS and in increased interest in switching patients
from parenteral to oral antibiotics earlier than usual treatment and discharging
them from the hospital. Findings from the Pneumonia Patient Outcomes Research
Team suggest that while the mean LOS varies among hospitals, clinical outcomes
are no worse for patients with a shorter LOS compared with patients who are
hospitalized longer.4
Since duration of parenteral antibiotic therapy is often the primary
factor determining LOS in the hospital, strategies to achieve early switch
from parenteral to oral antibiotics and early discharge for patients with
CAP are implemented by various institutions in an attempt to improve the efficiency
of care. Several studies have evaluated early switch and early discharge strategies.
For example, a recent study by Ramirez et al3
demonstrated that up to 44% of hospitalized patients may be treated with early
switch and early discharge strategies, and that application of these strategies
nationwide could result in annual savings of approximately $400 million. However,
studies vary in their designs, criteria for switch and discharge, and results.
Furthermore, it remains unclear (1) when a patient can be switched or discharged,
(2) how effective early switch and early discharge strategies are in reducing
LOS, and (3) how these strategies affect patient outcomes. Hence, there is
a need to synthesize the existing data to provide practical guidance for clinicians.
Therefore, we conducted a meta-analysis of the medical literature to appraise
the impact of early switch and early discharge strategies in the management
of CAP. The goals of our study were to (1) evaluate the various criteria used
in studies for early switch to determine which have been shown to be safe
in scientific studies and (2) assess the impact of early switch and early
discharge strategies on clinical outcomes and LOS.
MATERIALS AND METHODS
We searched the MEDLINE, HEALTHSTAR, EMBASE, Cochrane Collaboration,
and Best Evidence databases for prospective trials, retrospective trials,
meta-analyses, and systematic reviews addressing early switch from parenteral
to oral antibiotics and early discharge in patients with CAP. The following
medical subject headings were searched: pneumonia, respiratory tract infections,
community-acquired infections, infection, guidelines, economics, meta-analysis,
prospective studies, randomized controlled trials, controlled clinical trials,
treatment outcome, treatment failure, hospitalization, antibiotics, patient
discharge, length of stay, quality of health care, outcome and process assessment
(health care), quality assurance (health care), and total quality management.
In addition, a literature search was performed based on the following title
words: switch, conversion, intravenous to oral, parenteral to oral, community-acquired,
pathway, guideline, quality, outcome, and discharge. A study was defined as
having an early switch and early discharge strategy
if it described a method or intervention designed to shorten LOS by recommending
early switch, early discharge, or both from the hospital. The search was limited
to English-language articles published between January 1, 1980, and March
31, 2000, human subjects, and clinical trials. Exclusion criteria applied
to articles included the following: (1) a less rigorous study design (a retrospective
or noninterventional study, review article [unless specifically addressing
early switch from parenteral to oral antibiotics, early discharge, or both];
a letter; an editorial; a case study; a decision analysis; a consensus statement;
a highlight from a conference; or an abstract); (2) a specific patient population
(not specific for CAP, outpatient, aged <18 years, infected with the human
immunodeficiency virus, has the acquired immunodeficiency virus syndrome,
underwent transplantation, or has cystic fibrosis); (3) a nonbacterial cause
(mycobacterial, fungal, or viral); (4) a nonclinical evaluation (in vitro
activity, pharmacological features, or cytokines); (5) the study primarily
addresses an issue not related to early switch from parenteral to oral antibiotics,
early discharge, or both (no LOS evaluation, cause, epidemiological features,
specific pathogen, admission decision, diagnosis or diagnostic workup, adverse
drug reactions, antibiotic resistance, complications, or prevention); or (6)
absence of criteria for switch, recommended day of switch, or recommended
minimum number of days of parenteral treatment.
After exclusion, the remaining articles were evaluated for switch criteria,
discharge criteria, and outcomes. Articles were eligible for switch criteria
evaluation if they described specific clinical requirements for switching
from parenteral to oral antibiotics. Articles were eligible for discharge
criteria evaluation if they were eligible for switch criteria evaluation and
described additional requirements for discharging the patient from the hospital.
When switch and discharge criteria overlapped within a study, criteria were
listed once as part of the switch criteria. Only studies that evaluated LOS
were eligible for the outcomes evaluation. Furthermore, studies that compared
parallel groups with different recommended days of parenteral and oral therapy
were included if the intervention that recommended the shortest time to starting
an oral antibiotic also involved a switch from parenteral to oral antibiotics
(ie, articles in which oral antibiotics were started on day 1 without a switch
were excluded). Outcomes studies were classified as being prospectively controlled
vs uncontrolled or having a historical control group. A study was considered
to be controlled if it fulfilled the following criteria: (1) the control group
was identified at the start of the study and (2) LOS was compared in 2 or
more groups. Finally, we reviewed the bibliographies of all selected articles
and surveyed local experts in infectious disease, pulmonary and critical care,
and health services research to identify additional studies.
QUALITY CONTROL
The process of selecting articles occurred in 3 predefined stages: (1)
title review, (2) abstract review, and (3) article review. Two reviewers (D.C.R.
and G.S.T.) independently selected titles, and an all-inclusive list of titles
was compiled. After the second and third stage of the review process, all
articles were independently reviewed, with interrater agreement assessed by 
value.
STATISTICAL METHODS
 2 Analysis demonstrated significant (P = .000000019) variability between differences in LOS between studies.
Therefore, to combine the difference in LOS for each study, we performed a
random-effects meta-analysis5 using a software
program (FAST* PRO6). P<.05
was considered statistically significant. Furthermore, values for
agreement were calculated using the methods described by Fleiss.7
RESULTS
Our initial search yielded 1794 titles, from which 266 abstracts were
reviewed. Most articles were excluded because they evaluated patients without
CAP or addressed a topic that was not related to early switch from parenteral
to oral antibiotics or early discharge. One hundred twenty-one articles were
then selected and reviewed. The values from the abstract and article
reviews were 0.80 and 0.65, respectively. We identified 10 studies3, 8-16
that applied early switch and early discharge criteria to a population of
patients with CAP in a prospective interventional trial (Figure 1).
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The article selection process. CAP indicates community-acquired pneumonia;
LOS, length of stay; IV, intravenous; and ICU, intensive care unit.
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CRITERIA FOR SWITCH
Nine studies3, 8-15
applied early switch criteria (reviewer , 1.0) (Table 1). The most common criteria were afebrile (100%), improvement
or resolution of respiratory signs and symptoms (89%), and able to take oral
antibiotics (67%). Afebrile—the only criterion
included in every study—was defined in several different ways: 4 studies
used the term afebrile or normal temperature,9, 12, 14-15
1 described a temperature of 100°F or less ( 37.8°C),13
1 described a temperature of 38°C or less,8
and 1 described a temperature less than 38°C or 100.4°F.10
Three studies by Ramirez and colleagues3, 9, 14
applied the same switch criteria; also, one study each by Rhew11
and Weingarten13 and colleagues applied the
same switch criteria. In total, 6 different criteria for switching were applied
in the 9 studies. Furthermore, a specific postswitch antibiotic was recommended
in 4 of the 9, a specific day for switching (median, day 3) in 5 of the 9,
and a specific day for discharge (median, day 4) in 4 of the 9 studies that
applied early switch criteria.
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Table 1. Criteria for Early Switch From Parenteral to Oral Antibiotics
for Patients With Community-Acquired Pneumonia*
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CRITERIA FOR DISCHARGE
Five of the studies3, 8, 11, 13-14
that applied early switch criteria also applied separate criteria for early
discharge (reviewer , 1.0) (Table
2). The most common criterion for early discharge was care of comorbid
conditions (eg, no unstable comorbid conditions or congestive heart failure).
There was an even greater lack of commonality among discharge criteria vs
switch criteria, with 4 different discharge criteria combinations applied
in the 5 studies.
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Table 2. Criteria for Early Discharge for Patients With Community-Acquired
Pneumonia*
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SWITCH ON SPECIFIC DAY OR MINIMUM PARENTERAL TREATMENT
Three CAP-specific prospective interventional studies11, 13, 16
recommended switching to an oral antibiotic on a specific day (Table 3). The median recommended day of switch was day 3 (range,
2-10 days). Five articles10-11,13, 15-16
recommended switching to an oral antibiotic after a minimum number of days
of parenteral therapy. The median recommended duration of parenteral antibiotics
was 3 days (range, 2-10 days).
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Table 3. Studies That Recommend Switching From a Parenteral to an Oral
Antibiotic on a Specific Day or After a Minimum Number of Days of Parenteral
Treatment for Patients With Community-Acquired Pneumonia
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OUTCOMES
All 10 CAP-specific prospective interventional studies3, 8-16
met inclusion criteria for outcomes evaluation. Eight studies8-11,13-16
provided mean age data for 2463 patients; the mean age in these studies was
61 years. However, although the study by Marrie and colleagues8
accounted for approximately 80% of the total number of patients, the comparison
groups in this study were sites instead of patients. Age data were not provided
for 1236 patients in 2 studies.3, 12
Six studies8, 10-11,13, 15-16
applied an early switch and early discharge strategy to an intervention and
control group (Table 4), and 5
of these studies8, 10-11,13, 16
provided SD values for LOS. The mean change in LOS was not significantly (P = .05) reduced based on the random-effects model (-1.64
days; 95% confidence interval, -3.30 to 0.02 days). The studies by Rhew11 and Weingarten13 and
colleagues recommended an intervention LOS that was longer than or equal to
the control LOS. When these 2 studies were excluded from the analysis, the
mean change in LOS was 3 days (-3.04 days; 95% confidence interval, -4.90
to -1.19 days) (Table 4).
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Table 4. Features of Prospective Interventional Controlled Trials
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The following clinical outcomes were compared between the intervention
and control groups: complications or therapeutic failures (4 studies8, 10, 13, 16),
mortality (3 studies8, 10, 13),
readmission (3 studies8, 11, 13),
health-related quality of life (3 studies8, 11, 13),
therapeutic success (2 studies10, 16),
patient satisfaction with care (2 studies11, 13),
intensive care unit admission (1 study8), any
adverse outcome (1 study8), and relapse (1
study10). Studies did not reveal significant
differences between the intervention and control groups for any of these clinical
outcomes. Characteristics of studies that may have confounded the LOS analysis
are detailed in Table 5. In general,
there did not appear to be a major confounding factor affecting the evaluation
of LOS, such as disproportionately high dropout rates in the intervention
groups, high mortality rates, or high readmission rates.
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Table 5. Characteristics of Prospective Interventional Controlled Trials
That May Confound Length-of-Stay Analysis*
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In addition, we identified 4 studies3, 9, 12, 14
(n = 985) that applied an early switch and early discharge intervention to
a population of patients with CAP and that had no control group or a historical
control group (Table 6). In the
3 uncontrolled studies,3, 9, 12
the comparison group consisted of patients who did not receive the intervention
despite being assigned at the start of the study to receive it. The other
study14 used a historical control group. Early
switch strategies were applied to 710 (72%) of the patients in these 4 studies
with a historical control or no control group. Where data were available,
the mean time to switch and the mean LOS in patients receiving the intervention
appeared to be less than the values observed for control patients.
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Table 6. Features of Prospective Uncontrolled or Historically Controlled
Studies*
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COMMENT
To our knowledge, this study represents the first meta-analysis of the
literature to evaluate early switch from parenteral to oral antibiotics and
early discharge strategies in patients with CAP. Our review demonstrates that
there is considerable variability in early switch and early discharge criteria
that promotes uncertainty regarding the interpretation of outcomes. Moreover,
the results of this meta-analysis demonstrate that, although implementing
early switch criteria is safe, effectiveness in reducing LOS is dependent
on proper assessment of baseline LOS.
Lengths of stay in the 6 prospectively controlled trials8, 10-11,13, 15-16
are quite variable (range, 3.5-11 days). This may suggest that the patients
in these trials are not similar and that pooled analysis should not have been
performed on these data. However, in the 5 trials8, 10-11,13, 16
in which meta-analysis is performed, all patients are diagnosed as having
CAP and the mean age is similar (range, 56-69.6 years). Two studies11, 13 enroll "low-risk" patients who do
not have an obvious reason for continued hospitalization on the third hospital
day, and these patients demonstrated a relatively short baseline mean LOS
(3.5 and 4.2 days, respectively) that is shorter than that recommended by
the guideline. When these 2 studies are excluded from the analysis, the mean
change in LOS is reduced by 3 days. The potential impact of including these
2 studies with low-risk patients in the meta-analysis, however, is that it
may have been more difficult to demonstrate a significant reduction in LOS
with the intervention, thus resulting in a more conservative estimate of the
effect of early switch and early discharge.
It is likely that other factors, such as secular trends and geography,
may have contributed to the variation in LOS between studies. Length of stay
has been declining over time; yet, for the study by Marrie and colleagues8 (the most recent study in this meta-analysis), the
mean LOSs in the intervention and control groups are 8.2 and 9.6 days, respectively.
These LOSs are twice the mean LOS in the studies by Rhew11
and Weingarten13 and colleagues. In our present
study, regional differences may also explain the variability in LOS. The study
by Marrie et al was conducted in Canada, whereas the other studies were conducted
in the United States. Moreover, the study by Marrie et al is 1 of 2 trials8, 12 applying early switch and early discharge
as one component of a clinical pathway. It is possible that the results in
these trials may not be reproducible when these criteria are extracted from
a pathway. On the other hand, the other components in the pathway do not specifically
focus on reducing LOS and are unlikely to have directly promoted an early
discharge.
Our findings are relevant to clinicians and future investigators in
several ways. First, although there is much variability in criteria, some
features of early switch and early discharge are applied commonly. For instance,
resolution of fever, improving respiratory signs and/or symptoms, and the
ability to take oral medications are common criteria for early switch, whereas
care of comorbid conditions is a common criterion for early discharge. Clinicians
should ensure that, at a minimum, these criteria be included as part of an
early switch and early discharge strategy. Second, these data demonstrate
that early switch and early discharge strategies may or may not reduce LOS.
A critical factor to the success of a strategy involves assessing whether
the baseline LOS is longer than that recommended by the guideline. Rhew11 and Weingarten13 and
colleagues attribute their reversed LOSs to changing practice patterns, and
comment that LOS should be assessed immediately before the implementation
of the guideline. Third, studies that evaluate the effect of early switch
and early discharge demonstrate considerable variability in their designs.
Nearly half of the trials are uncontrolled or use a historical control group.
These types of analyses potentiate the bias of comparison group patients having
longer LOSs because of temporal changes in practice patterns or other unmeasured
effects.
Having identified so much variation in the application of early switch
and early discharge criteria, we believe that there is a need for continued
research and for consensus on a standard minimum set. Despite this variability,
however, we believe that early switch and early discharge strategies may significantly
and safely reduce the mean LOS when the recommended LOS is shorter than the
actual LOS. Further prospectively controlled interventional studies with baseline
LOS assessments are needed to verify these findings.
AUTHOR INFORMATION
Accepted for publication September 21, 2000.
Presented in part at the International Society for Pharmacoeconomics
and Outcomes Research (ISPOR) Fifth Annual International Meeting, Washington,
DC, May 23, 2000.
We thank Victor Hasselblad, PhD, for his assistance with the statistical
analyses performed.
Corresponding author and reprints: David C. Rhew, MD, Zynx Health
Inc, 9100 Wilshire Blvd, Suite 655, East Tower, Beverly Hills, CA 90212 (e-mail: rhew{at}zynx.com).
From Zynx Health Inc, Cedars-Sinai Departments of Medicine and Health
Services Research, Beverly Hills, Calif (Drs Rhew, Tu, Ofman, and Weingarten);
the University of California, Los Angeles, UCLA School of Medicine (Drs Tu,
Ofman, and Weingarten); West Los Angeles Veterans Affairs Medical Center,
Los Angeles, Calif (Dr Rhew); and TAP Pharmaceutical Products Inc, Lake Forest,
Ill (Mr Henning and Dr Richards).
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