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CLINICAL ARTICLES
Impact of Infectious Diseases Specialists and Microbiological Data on the
Appropriateness of Antimicrobial Therapy for Bacteremia
Baudouin Byl, Philippe Clevenbergh,* Frédérique Jacobs,
Marc J. Struelens, Francis Zech, Alain Kentos, and
Jean-Pierre Thys
From the Infectious Diseases Clinic and Microbiology Department,
Erasme Hospital, Free University of Brussels, Brussels; and Internal
Medicine Department, Saint-Luc Hospital, Catholic University of
Louvain, Louvain, Belgium
Antimicrobial therapy for 428 episodes of bacteremia in an 850-bed university hospital was
prospectively evaluated for 1 year to measure the impact of two factors— blood culture results and
the therapy chosen by infectious diseases specialists (IDSs)— on quality of treatment and outcome.
Initial shock, a simplified acute physiology score of >15, and inappropriateness of the empirical
treatment were independently associated with increased mortality. Empirical treatment was appropriate in 63% of the episodes. This proportion reached 78% for the episodes treated by IDSs,
compared with 54% for the others (P < .001). After availability of blood culture results, the
proportion of appropriate treatments increased to 94%, with 97% for IDS-treated patients and 89%
for other patients (P 5 .008). IDSs more frequently shifted to oral antibiotics and used fewer
broad-spectrum drugs. This study underlines the impact of blood culture results and of IDSs on the
prescription of appropriate treatment for bacteremia and on the better use of antimicrobial drugs.
Early clinical recognition of sepsis, rapid laboratory detection of the causative organisms, and prompt initiation of
appropriate antimicrobial therapy are all essential aspects of
the management of severe infections such as bacteremia.
When the pathogens and their susceptibilities are determined, streamlining and adapting antimicrobial regimens
are important to ensure optimal treatment and to limit the
untoward consequences of the misuse of antimicrobial
agents, particularly the selection of resistant microorganisms and excessive costs of treatments.
See editorial response by Tice on pages 67– 8.
In our hospital, a team of infectious diseases physicians acts
on an on-call basis in all wards, in close cooperation with the
microbiology laboratory, to advise on management of infectious diseases. The aim of this study was to evaluate the impact
of the infectious diseases specialists (IDSs) and the microbiology results on the quality of empirical and documented antimicrobial therapy in a prospective observational study of the
management and outcome of bacteremia. Bacteremia was se-
Received 6 April 1998; revised 29 September 1998.
*
Current affiliation: CHU Nice, Hôpital Archet, Nice, France.
Reprints or correspondence: Dr. Baudouin Byl, Infectious Diseases Clinic,
Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070
Brussels, Belgium ([email protected]).
Clinical Infectious Diseases 1999;29:60 – 6
© 1999 by the Infectious Diseases Society of America. All rights reserved.
1058 – 4838/99/2901– 0009$03.00
lected because a rapid microbiological diagnosis of this severe
infectious disease can be achieved and criteria for appropriate
antimicrobial therapy are relatively well established [1].
Patients and Methods
Patient population. The Erasme University Hospital (Université Libre de Bruxelles, Belgium) is an 850-bed tertiary care
institution that admits 27,000 patients annually, of whom
;12,000 undergo surgery. The local guidelines for management of infections, edited as a pocketbook by IDSs, are available to all hospital physicians. They are derived from standard
guidelines for empirical and documented treatment and adapted
to the suspected site of infection, place of acquisition, severity
of clinical presentation, and/or particular conditions such as
immunosuppression or drug allergy. The infectious disease
team consisted of three full-time IDSs and two fellows (P.C.
and A.K.) during our study. IDSs provided advice on an on-call
basis in all the departments of the hospital and also provided
unsolicited advice when notified by the microbiology laboratory about positive blood cultures or significant findings from
samples such as CSF or bronchoalveolar lavage.
All inpatients presenting with bacteremia during a 12-month
period (1 January to 31 December 1994) were included in the
study. The data were prospectively collected by the IDS team
for all the patients, from the day on which they began providing
care for them. Data concerning periods of observation before
IDS intervention were collected retrospectively by review of
the patients’ histories and medical charts, as were data for the
entire hospital courses of patients not treated by IDSs. If the
CID 1999;29 (July)
Role of Infectious Diseases Specialists in the Treatment of Bacteremia
presence or absence of a particular finding was not clearly
indicated in the patient’s chart, that patient was excluded from
analysis related to that variable. Therefore, the denominator
varied according to the number of cases in which information
on each item was available.
Blood cultures. Blood cultures were performed by collection of at least two 20-mL samples of venous blood, which
were inoculated in 10-mL aliquots into a BBL-Septichek Colombia bottle (Becton-Dickinson, Erembodegem, Belgium)
and a Castaneda brain-heart infusion bottle (Sanofi-Pasteur,
Marnes-la-Coquette, France), both biphasic blood culture media. All isolates were identified to the species level by standard
microbiological techniques. Antimicrobial susceptibility was
determined with use of primary colonies isolated from agar
slides of the biphasic culture media or, alternatively, an adjusted suspension of washed bacterial cells from the bloodbroth mixture. A rapid (4-hour) automated microdilution test
system (ATB system; bioMérieux, Marcy-l’Etoile, France) was
employed for Staphylococcus aureus and Enterobacteriaceae.
Other bacteria were tested by disk-diffusion techniques (Neosensitabs; Rosco, Taastrup, Denmark).
The susceptibility breakpoints were in accordance with the
guidelines of the National Committee for Clinical Laboratory
Standards. All positive blood culture results were reported
immediately, via phone and computer, by the microbiologist to
the caring physician and IDS, and were transmitted to the
patient database. A hierarchical system was used in reporting
the susceptibility results to limit the unjustified prescription of
broad-spectrum drugs.
Bacteremia. Each positive blood culture was evaluated to
determine whether it more likely represented true bacteremia or
contamination, on the basis of available clinical and microbiological data. In the interpretation of isolations of potential
pathogens arising from the skin microflora, such as coagulasenegative Staphylococcus or Corynebacterium species, at least
two positive blood cultures for the same microorganism (i.e.,
identical in terms of species and antimicrobial susceptibility
profile) were required before a diagnosis of bacteremia was
considered. An episode of bacteremia was defined by the first
positive blood culture or by a new positive culture .7 days
after the initial episode (or earlier if it was clinically obviously
related to a new episode of infection).
Origin and source of bacteremia. Bacteremia was considered to be community-acquired if the first positive blood culture specimen was taken within the first 48 hours of admission.
After this delay, the infection was considered nosocomial. The
source of bacteremia was considered clinically documented if
there were focal signs and symptoms, and it was considered
microbiologically documented when the same microorganism
was isolated from blood and the infected site. In the absence of
a recognized source, bacteremia was classified as primary.
Sepsis, septic shock, and death. Sepsis and septic shock
were defined as proposed by Bone et al. [2]. Death was attrib-
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uted to bacteremia if occurring within 7 days from the last
positive blood culture and if no other immediate cause of death
was evident.
Simplified Acute Physiology Score (SAPS). The SAPS [3]
was determined on the day when blood cultures were performed and was used to stratify the patients according to initial
severity of disease. For analysis of mortality, the patients were
grouped in five categories according to their SAPS.
Predisposing factors. The following factors were recorded: malignancies, liver cirrhosis, corticosteroid therapy (equivalent to .10 mg of prednisone per day for the previous 2
weeks), diabetes mellitus, granulocytopenia, AIDS, surgery
within the previous 28 days, endoscopic procedures, and a stay
in the intensive care unit in the previous 7 days.
Antibiotic therapy. Data were obtained concerning antibiotic therapy for the 28 days before the first positive blood
culture and until the patient was discharged or lost to followup. The antibiotic regimen was assessed at four time points:
when (1) empirical therapy began (at the time of the first blood
culture); (2) the gram stain findings for the blood culture isolate
became available; (3) susceptibility test results were available;
and (4) a switch was made from iv to oral antimicrobial
administration.
Criteria for appropriateness of therapy. Appropriate antimicrobial therapy was defined by the use of agents that had
been shown to be active in vitro against the infecting microorganisms, that were of clinically proven efficacy, and that
were given by the iv route at adequate doses. Changes in the
empirical therapeutic regimen were considered only if they
were made within 24 hours after performance of blood cultures. In the same way, only treatment adaptations that were
made within 24 hours of the report of gram stain or susceptibility test results were considered to be a consequence of these
results and were included in the analysis.
Compliance of the antimicrobial therapy with local guidelines. Antimicrobial therapy was evaluated according to the
clinical condition of the patient, the suspected source of infection, and the place of acquisition, and it was compared to the
recommended antimicrobial therapy in the local-guidelines
pocketbook. Treatment was classified as either in accordance
or not in accordance with these guidelines, on the basis of
previously described criteria [4 – 6].
Criteria for switching from iv to oral therapy. The following criteria, adapted from Ramirez [7], were used to consider
the possibility of switching to oral administration: the infection
was treatable by oral therapy (with the exclusion of meningitis,
endocarditis, and infection of surgically inserted iv catheters
left in situ); at least 3 days of iv treatment for gram-negative
bacteremia and 10 days of iv treatment for S. aureus bacteremia were administered; clinical response (e.g., disappearance
of fever or subjective and objective improvement of the clinical
condition) occurred during iv treatment; digestive absorption
was normal; and drugs that would be adequately absorbed
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Byl et al.
orally and would be active against the infecting microorganisms were available.
Statistical analysis. Univariate analysis was performed
with Epi Info software [8]. The difference in proportions was
tested with the x2 test or Fisher’s exact test as appropriate. The
difference in means was tested with the Wilcoxon signed-rank
test for pairs. All tests were two-tailed, and P values , .05
were considered significant. Independent predictors were identified by a multivariate logistic-regression analysis model including initially the variables found to be significantly associated with outcome (either death or appropriate treatment) by
univariate analysis.
Results
Demographic characteristics and clinical presentation of
bacteremic patients. During the study period, 428 episodes of
bacteremia involving 372 patients were identified. The mean
(6 SD) age was 58 (6 17) years, and 223 of the patients were
male. One hundred sixty-eight episodes (39%) were of
community-acquired bacteremia, and 260 (61%) were of
hospital-acquired bacteremia. Ninety-seven (23%) occurred
within 28 days after surgery, and 63 (15%) occurred during a
stay in the intensive care unit (ICU) or within 7 days after
discharge from the ICU. One-hundred eighty-five (43%) of the
428 episodes occurred during ongoing antimicrobial treatment
(111 patients) or within 28 days after completion of such
treatment (74 patients). One hundred fifty-two (59%) of 258
episodes of nosocomial bacteremia occurred during or following recent exposure to antimicrobial drugs, as compared with
only 33 (20%) of the 168 episodes of community-acquired
bacteremia (P , .001).
Two hundred twenty-eight episodes (53%) involved patients
presenting with one or more of the following underlying diseases or conditions: hematologic or solid tumor (118), corticosteroid therapy (74), liver cirrhosis (45), diabetes mellitus (40),
granulocytopenia (31), solid organ transplant (27), AIDS (15),
and end-stage renal failure (13). The sources of bacteremia
were identified as follows: iv devices in 92 episodes (23%),
urinary tract in 70 (16%), digestive tract in 66 (15%), respiratory tract in 36 (8.4%), soft tissues in 21 (4.9%), endocarditis
in 13 (3.0%), CNS in 11 (2.6%), bone and joint in 7 (1.6%),
and others in 13 (3.0%); bacteremia was considered primary in
99 (23%) of the cases.
Four hundred sixty-seven pathogens were isolated during the
428 episodes, as shown in table 1. Among cases due to
coagulase-negative Staphylococcus, the source of bacteremia
was confirmed microbiologically in 83% (by catheter cultures,
semiquantitative cultures, CSF cultures, etc.), and all the other
cases fulfilled the defined criteria. Thirty-five (8.2%) of the
episodes were polymicrobial.
Appropriateness of the empirical antimicrobial therapy.
On the day that blood culture was performed, 269 patients
(63%) received appropriate antimicrobial therapy, while 77
CID 1999;29 (July)
Table 1. Pathogens isolated in 393 episodes of community-acquired
and hospital-acquired monomicrobial bacteremia and fungemia.
No. (%) of episodes
Organism (no. of episodes)
Gram-positive bacteria (182)
Staphylococcus aureus (61)
Coagulase-negative staphylococci (70)
Enterococcus species (8)
Streptococcus pneumoniae (19)
Other (24)
Gram-negative bacteria (181)
Escherichia coli (94)
Klebsiella species (14)
Enterobacter species (21)
Pseudomonas aeruginosa (14)
Other (38)
Anaerobic bacteria (11)
Yeasts and fungi (19)
Candida albicans (12)
Other (7)
Community-acquired Nosocomial
(n 5 157)
(n 5 236)
20 (13)
17 (11)
3 (2)
15 (10)
15 (10)
41 (17)
53 (22)
5 (1)
4 (2)
9 (4)
52 (33)
4 (3)
1 (1)
4 (3)
15 (10)
6 (4)
42 (18)
10 (4)
20 (8)
10 (4)
23 (10)
5 (2)
3 (2)
2 (1)
9 (4)
5 (2)
(18%) received inappropriate treatment and 82 (19%) received
no antimicrobial treatment. Patients appropriately treated
showed a trend for higher SAPS than those for other patients
(9.4 6 5.5 and 8.2 6 4.4, respectively; P 5 .068).
The proportion of appropriately treated patients was not
statistically different among immunosuppressed vs. other patients (58% vs. 68%). By contrast, the appropriateness of the
treatment was significantly correlated to the nature of the
pathogen: empirical therapy for infection caused by grampositive cocci, gram-negative bacilli, and fungi was appropriate
in 59%, 69%, and 32% of the episodes, respectively
(P 5 .002). Nineteen (54%) of 35 polymicrobial episodes were
treated appropriately, as compared to 247 (63%) of 393 monomicrobial episodes (P 5 .41).
By univariate analysis, nosocomial infection and previous or
ongoing antimicrobial treatment were associated with increased risk of inappropriate treatment, while initial presentation with shock was associated with a lower risk of inappropriate treatment (table 2).
IDSs were involved in the empirical initial management of
bacteremia for 30% of the patients. When patients were stratified by source of infection, the proportion treated by either
IDSs or other physicians remained essentially unchanged, and
there was no category of infection in which the rate of appropriate treatment was lower for patients treated by IDSs than for
patients treated by other physicians. The median and range of
the SAPSs were identical for patients treated by IDSs and those
treated by other physicians. By contrast, the proportions of
patients with previous or ongoing antimicrobial treatment were
55% of IDS-treated patients and 38% of patients treated by
others (P 5 .0024). IDSs initiated a new treatment for 25% of
the bacteremic patients, while other physicians, providing ini-
CID 1999;29 (July)
Role of Infectious Diseases Specialists in the Treatment of Bacteremia
63
Table 2. Univariate analysis of factors predicting appropriateness of empirical therapy for bacteremia, on the day of sampling for blood
cultures.
No. (%) of appropriately treated patients/
no. of patients
Factor
Underlying condition
Nosocomial acquisition
Previous antimicrobial therapy
Ongoing antimicrobial therapy
Initial sepsis
Initial septic shock
Polymicrobial bacteremia
Yeasts or fungi
Managing physician
IDS, all episodes
IDS, community-acquired episodes
IDS, nosocomial episodes
NOTE.
Factor
present
Factor absent
OR for inappropriate
treatment (95% CI)
P value
141/260 (54)
106/185 (57)
57/111 (51)
204/320 (64)
36/47 (77)
19/35 (54)
6/19 (32)
125/168 (74)
163/241 (68)
209/317 (66)
53/92 (57)
222/370 (60)
247/393 (63)
260/409 (64)
2.45 (1.57–3.84)
1.56 (1.03–2.36)
1.83 (1.15–2.91)
0.77 (0.47–1.27)
0.46 (0.21–0.97)
1.42 (0.67–3.01)
3.78 (1.31–11.41)
,.0001
.037
.009
.342
.041
.413
.010
99/127 (78)
41/51 (80)
58/76 (76)
160/294 (54)
80/113 (71)
80/181 (44)
0.34 (0.20–0.56)
0.59 (0.24–1.40)
0.25 (0.13–0.47)
,.0001
.271
,.0001
IDS 5 infectious disease specialist.
Table 3. Proportion of patients initially treated by an IDS, according to the department of hospitalization, and appropriateness of the
empirical treatment, according to the treating physician.
Department
(no. of episodes)
Intensive care (68)
Internal medicine (63)
Gastroenterology (73)
Other unit (131)
Emergency (84)
Percentage of
patients
initially
treated by
IDS
28
24
51
27
24
No. (%) of appropriately treated
patients/no. of patients
IDS
Other
physician
P value
(x2)
14/19 (74)
13/15 (87)
28/37 (76)
25/36 (69)
16/20 (80)
19/49 (39)
22/48 (46)
15/36 (42)
47/95 (49)
49/64 (77)
.021
.013
.007
.064
1.000
NOTE. P values are for comparisons between appropriateness of treatment
by IDS, and other physicians.
tial care for 70% of the patients, prescribed a new treatment for
46% of the whole study population.
The proportion of appropriately treated patients was significantly higher for the group cared for by the IDSs than for those
cared for by other physicians (78% vs. 54%) (table 2). The
improved appropriateness of therapeutic choices made by IDSs
was particularly marked in cases of nosocomial bacteremia
(table 2). When coagulase-negative Staphylococcus was excluded from statistical analysis, the rate of appropriateness of
treatments by IDSs in comparison with those of other physicians became 77% vs. 57% (P , .001). When cases due to
coagulase-negative Staphylococcus were taken into account,
the proportion of appropriate IDS treatments compared with
those by other physicians was 81% vs. 42% (P , .001). The
proportions of appropriately treated patients according to the
hospital department and the treating physician are reported in
table 3.
A delay of 2 days was required before the proportion of appropriate treatments no longer differed significantly between categories of treating physicians (figure 1). By multivariate analysis, an
episode of community-acquired bacteremia, lack of recent or
ongoing antimicrobial therapy, blood pathogens other than yeasts,
and IDS as prescribing physician appeared to predict independently the appropriateness of empirical treatment.
Empirical management was in compliance with the local guidelines in 315 (74%) of the episodes. Among the noncompliant
managements, 69 involved the choice of a nonrecommended drug
or administration, and the last 39 episodes were empirically not
treated. Sixty-nine percent of compliant managements appeared
appropriate, vs. 44% of noncompliant managements (P , .001).
Relationship between appropriate empirical treatment and
mortality. The overall mortality was 20% (85 deaths in 428
episodes), and the infection-related mortality was estimated at
13% (57 episodes). The appropriateness of the empirical treatment was associated with a decrease in infection-related mortality for patients without initial shock (table 4). With adjustment for initial SAPS, the odds ratio for death among patients
with appropriate empirical treatment (vs. those treated inappropriately) was 0.47 (95% CI: 0.25– 0.87; P 5 .017). After
exclusion of patients who died within the first 24 hours after
blood cultures were performed, the risk of infection-related
death was significantly lower for patients with appropriate
empirical treatment than for inappropriately treated patients
(OR: 0.38; 95% CI: 0.17– 0.83; P 5 .013).
There was no significant difference in overall mortality (17%
vs. 20%) and infection-related mortality (11% vs. 15%) between patients treated by IDSs vs. those treated by other
physicians. By multivariate analysis, the predicting factors of
increased overall mortality included shock (OR: 12.8; 95% CI:
5.5–29.7; P , .0001), SAPS of .15 (OR: 4.4; 95% CI:
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Byl et al.
Figure 1. Proportion of bacteremic episodes appropriately treated
by infectious disease specialists (circles) and other physicians
(squares) over time. The difference between the two curves is statistically significant during the first 2 days (P , .05 [x2]).
1.9 –10.5; P 5 .0007), and appropriate empirical treatment
(OR: 0.45; 95% CI: 0.22– 0.92; P 5 .03). When included in
this multivariate analysis, the prescribing physician did not
affect mortality (OR: 0.97; 95% CI: 0.44 –2.1).
Relationship between microbial pathogen or source and
mortality. Bacteremia caused by the most frequently isolated
pathogens, including Escherichia coli, Pseudomonas aeruginosa, and S. aureus, was associated with a significant (9.7–
10.3-fold) increase in infection-related deaths over those
caused by coagulase-negative Staphylococcus, while Candida
was associated with a 35-fold greater mortality than that asso-
CID 1999;29 (July)
ciated with the latter microorganism. On the other hand, bacteremia originating from the respiratory tract, soft tissues, or
endocarditis and primary bacteremia resulted in a significant
(10.7–13.1-fold) increase in infection-related deaths in comparison with those due to catheter-related bacteremia.
Appropriateness of treatment, as determined on the basis of
blood culture results. The cumulative proportions of results
available after 24, 48, and 72 hours were 47%, 74%, and 86%,
respectively, of gram stain findings and 8%, 44%, and 72% of
susceptibility test findings. When the gram stain results were
obtained, 364 patients (85%) remained evaluable. Thirty-four
others (7.9%) had died (22 of them had received appropriate
treatment), of whom 31 died because of infection. The 34 other
patients were lost to follow-up or did not require further antimicrobial therapy. Report of the blood-isolate gram stain findings was associated with a substantial, statistically significant
increase in the proportion of patients receiving appropriate
therapy, from 63% to 94% (P , .001).
At this time, patients were significantly more often treated
appropriately by IDSs than by other physicians (table 5). Likewise, all patients treated by IDSs received an appropriate
treatment when the results of antimicrobial susceptibility were
available, whereas a few patients treated by other physicians
were still inappropriately treated.
Unjustified use of broad-spectrum drugs. Use of antimicrobial regimens with an excessively broad spectrum was determined
on the basis of local guidelines, with the nature and susceptibility
of the pathogen and clinical data taken into account. When gram
stain findings were available, broad-spectrum drugs were overused for 8 (3%) of 269 IDS-treated patients vs. 10 (9%) of 111
patients treated by other physicians (P 5 .024). The corresponding
proportions when susceptibilities were reported were 51 of 275
patients (19%) and 27 of 92 (29%), respectively (P 5 .041). A
large part (19 of 51 episodes) of IDSs’ overuse of broad-spectrum
drugs involved prescription of fluoroquinolones in a switch to oral
therapy; these were less commonly used by other physicians (3 of
27 episodes; P 5 .030).
Table 4. Overall and infection-related mortality among bacteremic patients with or without septic
shock, by appropriateness of empirical antimicrobial therapy.
Septic shock
on day of
blood culture
Absent
Present
Total no. (%) of deaths/total
deaths per treatment category
No. (%) of infection-related
deaths/total deaths per treatment
category
No. of
episodes
Appropriate
Inappropriate
Appropriate
370
47
24/222 (11)*
24/36 (67)‡
27/148 (18)
10/11 (91)
10/222 (4.5)†
23/36 (64)§
Inappropriate
18/148(12)
6/11 (55)
NOTE. P values are for univariate analysis by x2 test for comparisons between appropriate and inappropriate
treatment.
* P 5 .06.
†
P 5 .01.
‡
P 5 .15.
§
P 5 .73.
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Role of Infectious Diseases Specialists in the Treatment of Bacteremia
65
Table 5. Appropriateness of the treatment given at the time when blood-isolate gram stain and
antimicrobial susceptibility test results were available, according to the treating physician.
Laboratory test results
Gram stain
Antimicrobial susceptibility
No. of
evaluable
patients
All physicians
IDSs
Other physicians
P value (x2)
364
352
343 (94)
349 (99)
249/258 (97)
265/265 (100)
94/106 (89)
84/87 (97)
.008
.015
Proportion (% of total) of appropriate treatments by
NOTE. P values are for comparisons between appropriateness of IDSs’ and other physicians’ treatments.
Relationship between previous antimicrobial therapy and
susceptibility of pathogen to antibiotics. Compared to other
patients, patients who had received a b-lactam antibiotic in the
previous 28 days were infected with gram-negative bacilli with
a higher rate of resistance to amoxicillin– clavulanic acid (49%
vs. 14%; P , .01), ceftazidime (13% vs. 1%; P , .001), and
cotrimoxazole, (41% vs. 20%; P , .01). Likewise, blood
isolates from patients who had received ciprofloxacin and who
presented with infection due to gram-negative bacilli had increased rates of resistance to penicillins, imipenem, ciprofloxacin, and cotrimoxazole. Increased resistance was due to a shift
toward naturally more resistant bacterial species and to acquired resistance within strains of the same species. In addition,
previous exposure to antibiotics increased the risk of subsequent fungemia. This was true for 16 (8.6%) of 185 previously
treated patients vs. 3 (1.2%) of 241 untreated patients (OR:
7.51; 95% CI: 2.02–32.95; P , .001).
Switch from iv to oral treatment. Among 363 episodes
evaluable, an oral switch was deemed possible in 160 (44%)
and implemented in 114 of them (71%). Therapy was switched
to the oral route in 49 (78%) of the evaluable episodes of
urinary tract infections, 36 (66%) of digestive tract infections,
36 (21%) of primary or iv device infections, 17 (57%) of
respiratory tract infections, and 8 (47%) of soft-tissue infections. Of the episodes in which a switch was deemed possible,
IDSs were consulted in 98 (61%). They prescribed an oral
switch in 93 (95%) of these episodes. By contrast, when no IDS
was consulted, a switch was made in only 21 (34%) of 62
opportunities for using oral administration (P , .001).
Discussion
Appropriate empirical therapy for bacteremia in adults has
been reported for proportions of patients ranging from ,60%
to 85% [5, 9 –20]. However, when recent series evaluating only
antibiotics administered within the first 24 hours are considered, without exclusion of early deaths, the appropriateness of
empirical treatment of bacteremia ranges from 59% to 68% [5,
12, 14 –16, 18, 19], which appears similar to the rate of 63% in
the present study. Effective antimicrobial therapy administered
early during the course of bloodstream infection has been
demonstrated to improve survival rates [5, 9, 13, 17, 21].
This emphasizes the key role of empirical treatment given
before results of blood cultures are available, before all microbiological data are known, or even on a clinical basis alone. In
our study, the lack of appropriate treatment was most often due
to incorrect clinical evaluation of the risk factors for severe
infection, bacteremia, or infection with drug-resistant pathogens. Indeed, no indicator is available to accurately predict the
presence of bacteremia [22–27].
This investigation shows that physicians with special training in
the management of infectious diseases discriminate more accurately infected from uninfected patients and prescribe appropriate
empirical treatment more often and earlier than do nonspecialized
physicians. Our study underlines clearly that the problem is of
particular importance in the treatment of nosocomial bacteremia.
Reporting of the blood culture result increased considerably the
proportion of bacteremic patients who had appropriate treatment
prescribed by the IDSs or by other physicians.
This dramatic improvement in appropriate treatment on the
basis of microbiological data underlines the potential benefit of
applying rapid microbial detection and testing methods, as
previously shown [28, 29]. However, in other recent studies,
the value of blood culture results appeared more limited, with
8% to 20% of the patients still treated inappropriately or
receiving excessively broad-spectrum drugs after the susceptibility results were available [12–14, 17, 19, 20]. By contrast,
our study clearly points to the benefit of the intervention of
IDSs for bacteriologically documented infection. They effectively increased the appropriateness of the documented treatment, streamlined therapy, and prevented the unnecessary use
of broad-spectrum agents or parenteral administration. Others
have shown that active notification of positive blood culture
results can lead to alteration of therapy for as many as 50% of
patients, leading to more rational treatment, improved outcome, and reduction in cost [15, 16].
In a study by Nathwani et al., the impact of an unsolicited
systematic IDS consultation for bacteremia improved the appropriateness of antibiotic treatment at no extra cost, since the increased use of appropriate empirical treatment for about half of the
patients was counterbalanced by the streamlining of treatment to
include later use of less-expensive drugs in ;45% of courses [30].
Although data on the impact of IDSs on the outcome of
infection remain scarce, some investigators reported that IDSs
contribute to both a better use of antibiotic resources and better
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Byl et al.
management of infection by improvement in the employment
of diagnostic and therapeutic procedures [30 –32]. However,
evaluation of the IDSs’ impact on the care of hospitalized
infected patients is hampered by potential biases related to the
fact that the IDS consultation may be a marker of a more severe
infection, as suggested previously [33].
In conclusion, our study confirms that blood culture results
are essential in optimizing antimicrobial therapy for infections
accompanied with bacteremia, and it underlines the fact that
IDSs provide more appropriate empirical and documented
treatment of bacteremia than other physicians in our hospital.
This improved clinical performance was related to better assessment of both severity of infection and the probability of an
infection due to nosocomial or resistant pathogens. Moreover,
IDSs used antimicrobial agents more judiciously when susceptibility reports were available, particularly by reducing the use
of excessively broad-spectrum drugs and by shifting treatment
more frequently to the oral route.
These data emphasize the importance of close coordination
between the clinical laboratory, the IDSs, and other specialty
physicians in ensuring optimal care for severely infected patients. They also underscore the need to foster the education of
physicians in the field of antimicrobial therapy for and management of infections.
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